Nitsbin ( ) I. Medicine 1st Edition - (Revised) - 1
Nitsbin ( ) I. Medicine 1st Edition - (Revised) - 1
Nitsbin ( ) I. Medicine 1st Edition - (Revised) - 1
Preface i
Copyright © 2015/2022
All rights reserved
Commemoration
This book is in memory of Dr. Habtamu Animaw,
who lost his life suddenly, due to unknown cause,
two months before his graduation, in paqume 03,
2012 E.C, while working his internship ward
activity, at University of Gondar Hospital.
May his soul Rest in peace.
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Nitsbin (ንጽቢን) Bedside oriented Internal medicine 1st edition
Preface ii
Comments here
❖ Email
[email protected]
❖ Telegram
https://t.me/Nitsbin21orit
1st edition
Nitsibin(ንጽቢን)
Internal medicine
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Nitsbin (ንጽቢን) Bedside oriented Internal medicine 1st edition
Preface iii
Preface
Nitsbin means ‘‘Book of art’’ in Geez language (ንጽቢን በልሳነ ግእዝ ‘‘የጥበብ መጽሐፍ’’
ማለት ነው ። ሐኪም ማለትም ሐከመ = ጥበበኛ ሆነ ፣ ብልሃተኛ ሆነ ከሚለው የግእዝ ግስ
ተገኝቷል ። ሐኪም ማለት ጥበበኛ ከሆነ፤ ሕክምና ማለት ደግሞ ጥበብ ይሆናልና ይህን ቃል
ወደድን). We also prefer this name because “Medicine is not only a Science; it is
also an art” as said by Paracelsus. So, Nitsbin means ‘‘book of medicine’’ indirectly.
The book is made on common Medical cases & approaches by Ethiopian Junior medical doctors (GP)
to be used as a quick reference & guide. The aim of Nitsbin is to enable & equip medical students
with the basic & necessary medical knowledge, skills & approaches to patients in a very short period
of time. We hope that, it will be important also for junior medical and health science practitioners.
Nitsbin is a modified form of my previous bedside note ‘‘Internal medicine long and short
case notes by Mulualem.G (ኦሪት)’’ which was prepared in 2010 E.C during my 4th year (C-I)
attachment. I was considering only for myself and it was in hand written form. But I found that most
of students need a short-revised note for Clinical case approach and it was necessary to revise the
hand written note in to short and precise book with the intension of collecting & comprising
common medical cases in one place for easy access for undergraduates and junior medical and
health science practitioners.
We recommend you to read Standard books first and use Nitsbin as revision. Otherwise depending
only on Nitsbin is strongly forbidden.
Nitsbin has two major parts; long cases (containing 14 chapters and case report sample) & short
cases (containing 11 chapters).
Long cases contain important information on how to approach patients. Like;
✓ Some basic Information for taking history (clinical features, cause and risk factors,
complications, DDx…)
✓ Pertinent physical examination findings
✓ Sample histories for each case
✓ Investigations to be done & what is expected from each investigation considering availability
in Ethiopia and cost effectiveness.
✓ Discussion about the case & management
✓ Case reporting format for bedside, round, exam and case discussion
Short cases mainly contain
✓ Exam oriented physical examination techniques and possible findings
✓ DDX, IX and management principles of common physical examination findings
✓ Common medical procedures with indication, contraindication, complication of a procedure,
principle of management and result analysis with YouTube video link for each procedure.
✓ Emergency and OPD cases
✓ Poisoning, Drug Overdose, and Envenomation
✓ CXR Interpretation
✓ Basics of ECG and ECG interpretation
✓ Basics about rational use of antibiotics
✓ Symptoms and signs in Amharic (የበሽታ ምልክቶች አማርኛ ትርጉም)
✓ Anatomical body parts in Amharic (የሰውነት አካል ክፍሎች አማርኛ ትርጉም)
✓ Common Laboratory Investigations with practical points and procedures (plus you tube
video link)
✓ Reference Intervals for Laboratory Tests
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Nitsbin (ንጽቢን) Bedside oriented Internal medicine 1st edition
Acknowledgment iv
Acknowledgment
I thank God first and most for everything that had been and that ever will be, it is
all by the will of God.
I would like to acknowledge Dr. Asmare Walle and Dr. Robel Dibaba (Co-Author’s)
for their contribution in the preparation of this Bedside oriented book. If it was not
for you, I know this book will never been real. Lastly with effortful contribution of co-
authors, we prepared Nitsbin as a ‘’Bedside oriented book’’ depending on our clinical
year attachment experiences.
I would also like to thank my juniors and classmates at UOG who was using my
hand note (orit Internal medicine long and short case notes) and providing me
constructive comments. They also initiated me to prepare the hand written form into
a short and precise revision book. So, this book come to reality.
Lastly, I would also like to acknowledge the cover page designer Mr. Tadele
Tesfaye (Phone number: +251 91 881 2871. Email: [email protected].
Telegram: https://t.me/Tadele_tesfaye )
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About the authors v
Author
Co-Author’s
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Acronyms & Abbreviations vi
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Table of contents ix
Table of contents
Contents page
Preface ................................................................................................................................................. iii
Acknowledgment ................................................................................................................................ iv
About the authors .............................................................................................................................. v
Acronyms & Abbreviations .............................................................................................................. vi
Table of contents .............................................................................................................................. ix
Part I; Long cases ............................................................................................................................. 1
Mysteries of best physician's about patient approach ............................................................ 2
Chapter 1; Heart failure (ልብ ድካም) ............................................................................................. 3
1.1 Heart Failure/HF/ .............................................................................................................. 18
1.1.1 Management of heart failure ................................................................................. 24
1.2 Acute Rheumatic Fever(ARF) & Rheumatic heart disease (RHD) .................... 34
1.3 Valvular heart disease (VHD) ....................................................................................... 49
1.4 Atherosclerotic cardiovascular diseases ..................................................................... 59
1.4.1 Ischemic heart disease (IHD) ............................................................................... 59
1.4.1.1 Acute coronary syndrome (ACS) ................................................................. 62
1.4.1.2 Chronic coronary syndrome........................................................................... 74
1.4.2 Peripheral Arterial Disease (Chronic Arterial Insufficiency) .......................... 77
1.4.3 Arterial occlusion (acute limb ischemia) ............................................................ 80
1.5 Hypertension (የደም ግፊት) and HHD .......................................................................... 81
1.5.1 Hypertensive crisis ........................................................................................................ 90
1.6 Infective endocarditis (IE)............................................................................................... 96
1.7 Arrhythmia ......................................................................................................................... 105
1. Tachyarrhythmias ............................................................................................................ 107
2. Bradycardia (Bradyarrhythmia) .................................................................................... 115
Cardiac arrest (የልብ ምት መቋረጥ) ..................................................................................... 116
Cardioversion and Defibrillation .......................................................................................... 119
1.8 Pericarditis ........................................................................................................................ 121
1.9 Cardiomyopathy (CMP) and myocarditis ................................................................. 128
1.10 Cardiogenic shock and Pulmonary edema ......................................................... 140
1.10. 1 Cardiogenic shock................................................................................................... 142
1.10.2 Pulmonary edema ..................................................................................................... 142
1.10.2.1 ARDS (Acute respiratory distress syndrome) ............................................ 147
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10.5.10 RPR (Rapid reagain card test for syphilis) .............................................. 1335
10.5.11 VDRL Slide Qualitative Test ......................................................................... 1336
10.5.12 ASO latex slide agglutination test ............................................................... 1337
10.6 Basic microbiological tests ..................................................................................... 1337
10.6.1 AFB........................................................................................................................... 1337
10.6.2 Gram stain .............................................................................................................. 1339
10.6.3 Culture & biochemical tests .............................................................................. 1342
Chapter 11; Reference Intervals for Laboratory Tests...................................................... 1351
Reading assignment .................................................................................................................... 1357
References (ዋቢ መጽሐፍት) ....................................................................................................... 1358
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Table of contents
Part I; Long
cases
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Mysteries of best physician's about patient approach
GOOD LUCK!!!
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Chapter 1; Heart failure (ልብ ድካም)
The cardinal symptoms of heart failure (HF) are fatigue and shortness of
breath.
Fatigue
o Although fatigue traditionally has been ascribed to the low cardiac output
in HF, it is likely that skeletal-muscle abnormalities and other noncardiac
comorbidities (e.g., anemia) also contribute to this symptom.
o Fatigue is a non-specific symptom: if the predominate symptom is
fatigue consider also Hypothyroidism, Adrenal insufficiency, CKD, CLD,
DM and after exclusion of organic causes: chronic fatigue syndrome.
Dyspnea or shortness of breath → Defined as difficult or labored breath
o In the early stages of HF, dyspnea is observed only during exertion;
however, as the disease progresses, dyspnea occurs with less
strenuous activity, and it ultimately may occur even at rest.
o The origin of dyspnea in HF is probably multifactorial.
o The most important mechanism is pulmonary congestion with
accumulation of interstitial or intra-alveolar fluid, which activates juxta
capillary J receptors, which in turn stimulate the rapid, shallow breathing
characteristic of cardiac dyspnea.
o Other factors that contribute to dyspnea on exertion include reductions
in pulmonary compliance, increased airway resistance, respiratory muscle
and/or diaphragm fatigue, and anemia.
o Dyspnea may become less frequent with the onset of right ventricular
(RV) failure and tricuspid regurgitation
Orthopnea
o Defined as dyspnea occurring in the recumbent position
o It is usually a later manifestation of HF than is exertional dyspnea.
o It results from redistribution of fluid from the splanchnic circulation and
lower extremities into the central circulation during recumbency, with a
resultant increase in pulmonary capillary pressure.
o Orthopnea generally is relieved by sitting upright or sleeping with
additional pillows.
o Although orthopnea is a relatively specific symptom of HF, it may occur
in patients with abdominal obesity or ascites and patients with
pulmonary disease whose lung mechanics favor an upright posture
Nocturnal cough 3
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Chapter 1; Heart failure (ልብ ድካም)
➢ Weight loss
o E.g. significant weight loss from 53 kg to 45 kg which is 15% of
his/her initial body weight or
o Unquantified but significant weight loss to the extent his/her closes
become loose (if s/he didn’t remember his/her initial body weight but
claim that S/he lose his/her body weight)
o Make sure that the patient is not in diuretics
➢ Chest pain → angina (common in old age → M ≥ 45 years, F ≥ 55 years)
o Retro sternal chest pain
o Squeezing type, heaviness, pressure/burning sensation
o Radiates to left shoulder or medial border of left arm (it can radiate
from jaw to umbilicus)
o Worsened by exertion and relieved by rest or taking nitroglycerine
(nitrates)
o Lasts for 2-5 minutes
o Levine sign +ve… pt make a fist and put his fist on chest to
characterize the smx
o Remark: nitroglycerine alleviate chest pain because of esophageal
spasm
➢ Wheezing…. Diffuse due to cardiac asthma
Preciptant factors
➢ HTN
➢ Endocarditis (IE)
➢ Arrhythmia (manifest with new onset palpitation and Irregularly irregular
pulse)
➢ Recurrent rheumatic fever and myocarditis
➢ Thyrotoxicosis and pregnancy
➢ Fever (for infection)
➢ Anemia
➢ Infarction
➢ Lung infection (e.g. pneumonia)
➢ Embolism (PE, DVT)
➢ Stress (Dietary i.e. Salt intake, Drug withdrawal, Psychological stress,
physical stress)
Complication of CHF
Sample hx of a pt’ from chilga with a DX of NYHA class IV, stage III CHF 2ry to
CRMVHD (MR, TR and AR) precipitated by CAP.
Chief compliant
HPI
This patient was last relatively healthy 3 months back, at which time she started
to experience a gradual onset of dyspnea while doing ordinary activities like going
to church which progressively increase in severity and she began to experience
shortness of breath at rest within one month. Associated with orthopnea of 3
pillows, PND and Palpitation.
One month before admission, she started to experience a gradual onset of dry
cough which later becomes position dependent productive nocturnal cough with
whitish and frothy, non-foul smelling, Non blood tingled, sputum of 3-4 Arabic
coffee cup per day which is aggregated when she assumes supine position but no
chest pain or fever.
Concomitantly she also experienced bilateral, painless leg swelling which starts
from foot and goes upwards to involve the whole leg within 2 weeks duration. The
swelling disappears in the morning and marked on sitting position or prolonged
standing.
She has also significant weight loss from 40 kg to 35 kg within 3 months which is
12.5% of her initial body weight.
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Chapter 1; Heart failure (ልብ ድካም)
Two weeks before admission she experienced chest pain, fever, fast breathing and
worsening of cough for which she visited a local health center at chillga where
she was given augmentin 625 mg, PO,TID for 7 days and azithromycin 500mg,
po, daily for 3 days (hx from referral paper) but no improvement. Later she was
referred to our hospital for better investigation and mgt.
Finally, she was admitted to our hospital carried on stretcher by her families
N.B these +ve and -ve statements may not be included in all
causes of CHF. So, modify based on your case
Chief compliant
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Chapter 1; Heart failure (ልብ ድካም)
HPI
This is a known cardiac pt for the past 5 years on enalapril to be taken 1 tablet
twice per day and Lasix (furosemide) to be taken half tablet two times per day,
on salt free diet and recommended to decrease alcohol intake and to avoid
smoking. He was on follow up every month here in our hospital. He discontinued
his medication 4 months back due to financial problem.
Associated with this he has also position dependent productive nocturnal cough of
whitish and frothy, non-foul smelling, Non blood tingled sputum of 1ACC/day which
is aggregated by lying supine position.
Readers are recommended to see CVS examination from short case of Nitsbin
(click here → 1.2 Cardiovascular System)
1 GA
✓ Patient may be Acute sick looking, chronic sick looking or acute sick
looking on chronic background depending on the underlying cause and
presence of complication
✓ May be in cardio-pulmonary distress (click and see 1.2 Cardiovascular
System examination)
✓ In mild or moderately severe HF, the patient appears to be in no distress
at rest except for feeling uncomfortable when lying flat for more than a few
minutes.
✓ In more severe HF, the patient must sit upright, may have labored
breathing, and may not be able to finish a sentence because of shortness
of breath.
2 Vital signs
✓ BP
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Chapter 1; Heart failure (ልብ ድካም)
3 HEENT
4 LGS
5 RS
o Result from the transudation of fluid from the intravascular space into
the alveoli.
o In patients with pulmonary edema, rales may be heard widely over
both lung fields and may be accompanied by expiratory wheezing
(cardiac asthma).
o When present in patients without concomitant lung disease, rales are
specific for HF.
o Importantly, rales are frequently absent in patients with chronic HF,
even when LV filling pressures are elevated, because of increased
lymphatic drainage of alveolar fluid.
✓ Pleural effusions
o Result from the elevation of pleural capillary pressure and the
resulting transudation of fluid into the pleural cavities.
o Since the pleural veins drain into both the systemic and the
pulmonary veins, pleural effusions occur most commonly with
biventricular failure.
o Although pleural effusions are often bilateral in HF, when they are
unilateral, they occur more frequently in the right pleural space
✓ Consolidation → if there is pneumonia as precipitant (BBS).
✓ Friction rub → Sign of pericarditis (unlike to plural origin not associated with
respiratory cycle).
6 CVS
Arterial examination
Venous examination
7 Abdominal examination
✓ Hepatomegaly
o It is an important sign in patients with HF. which is tender, smooth
and with blunted edge from cardiac congestion of liver
o may pulsate during systole if TR is present.
✓ Ascites → a late sign, occurs as a consequence of increased pressure in
the hepatic veins and the veins draining the peritoneum.
✓ Jaundice → also a late finding in HF, results from impairment of hepatic
function secondary to hepatic congestion and hepatocellular hypoxemia and
is associated with elevations of both direct and indirect bilirubin.
o Remark: severe hemolysis also results in jaundice: severe anemia
may be a cause or precipitant of HF
✓ Rarely tipped splenomegaly from IE
8 GUS
9 MSS
✓ Pallor → Anemia
✓ Cyanosis and cold extremities → suggest decreased CO
o Peripheral vasoconstriction leading to cool peripheral extremities and
cyanosis of the lips and nail beds is caused by excessive adrenergic
activity.
NB: Look for skin manifestation of IE
11 NS
DDX
For Dyspnea (SOB)* For GBS#
1. CHF 2ry to (see table about ‘’etiologies of HF’’ from the 1. CHF → symmetrical and
discussion part below) worsens in the evening and
a. RHD improves early in the
N.B VHD can result from RVHD,
b. HHD morning
IE or DVHD (for old age)
c. IHD 2. Constrictive pericarditis
d. CMP (usually isolated ascites)
e. Constrictive pericarditis (Pericardial disease) 3. CKD
f. CHD 4. Nephrotic syndrome → affects
g. Arrhythmia face first
h. IE 5. CLD
i. Severe anemia 6. Advanced Lymphoma (NHL)
j. Thyrotoxicosis 7. Disseminated TB or SLE to
2. Pulmonary TB pericardium (result in
3. Bronchial Asthma (severe persistent Asthma) Constrictive pericarditis),
4. Cor pulmonale pleura, Peritoneum…
a. COPD 8. Varicose veins and DVT →
b. Lung Abscess More of peripheral edema
c. Bronchiectasis 9. Vasodilating drugs (e.g. CCB’s)
d. ILD 10. ? Protein losing enteropathy
5. Lung ca
* In most patients who present with classic signs and symptoms of HF, the diagnosis is relatively
straightforward. However, even experienced clinicians have difficulty differentiating the dyspnea that
arises from cardiac and pulmonary causes. In this regard, Echo, CXR, biomarkers, pulmonary function
testing, may be useful.
* When HF develops in patients with a preserved EF, it may be difficult to determine the relative
contribution of HF to the dyspnea that occurs in chronic lung disease and/or obesity.
#
Ankle edema may arise secondary to varicose veins, obesity, renal disease, or gravitational effects.
Remark: If all workup for causes of ankle edema are normal consider idiopathic edema. 14
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Chapter 1; Heart failure (ልብ ድካም)
Ass’t example
NYHA class IV, stage C, CHF 2ry to CRMVHD (MR,
TR, AR) precipitated by CAP
IX
Discussion
Epidemiology
The overall prevalence of HF in the adult population in developed countries is
2%.
HF prevalence follows an exponential pattern, rising with age, and affects 6 -
10% of people aged >65.
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Chapter 1; Heart failure (ልብ ድካም)
Forms of CHF
1. HFrEF vs HFpEF
➢ See the notes above and table below (etiologies of heart failure)
2. Right sided versus left sided:
Difference between heart failure (HF) and congestive heart failure (CHF)
HF CHF
✓ dyspnea, orthopnea, PND, weakness and ✓ dyspnea, orthopnea and PND together with
decreased exercise tolerance peripheral edema, hepatomegaly, ascites
✓HF symptoms without sign and smx of ✓ HF symptoms together with sign and smx
congestion of congestion
☛ NO Sign of congested heart failure ☛ +ve Signs of congested heart failure →
✓There is Murmur of Valvular lesions refer CVS examination of Nitsbin (click
To guide and monitor management: K+, Na+, Cr, BUN, ALT, AST, serum albumin.
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Chapter 1; Heart failure (ልብ ድካም)
FIGURE 252-1 (Harrison 20th edition) Pathogenesis of heart failure with a depressed ejection
fraction. Heart failure begins after an index event produces an initial decline in the heart’s
pumping capacity. After this initial decline in pumping capacity, a variety of compensatory
mechanisms are activated, including the adrenergic nervous system, the renin-angiotensin-
aldosterone system, and the cytokine system. In the short term, these systems are able to
restore cardiovascular function to a normal homeostatic range with the result that the
patient remains asymptomatic. However, sustained activation of these systems leads to
secondary end-organ damage within the ventricle, with worsening left ventricular remodeling
and subsequent cardiac decompensation.
to the CNS also activate efferent sympathetic nervous system pathways that innervate the
heart, kidney, peripheral vasculature, and skeletal muscles. Sympathetic stimulation of the
kidney leads to the release of renin, with a resultant increase in the circulating levels of
angiotensin II and aldosterone. The activation of the renin-angiotensin-aldosterone system
promotes salt and water retention and leads to vasoconstriction of the peripheral
vasculature, myocyte hypertrophy, myocyte cell death, and myocardial fibrosis. Although
these neurohormonal mechanisms facilitate short term adaptation by maintaining blood
pressure, these same neurohormonal mechanisms result in end-organ changes in the heart
and the circulation, as well as to the excessive salt and water retention in advanced HF.
Principle of HF management
1. General measures
2. Treating congestion (Diuretics)
3. Correcting the precipitant factor
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Chapter 1; Heart failure (ልብ ድካም)
1. General measures
• Bed rest
• Elevate bed to Semi-upright position
• Salt restriction (< 2gm or decrease added salt)
• Fluid restriction (< 1.5 - 2 L/day) for hyponatremic patients
• Administer O2 if SaO2 < 90%.
• Activity and life style modifications:
✓ Small and frequent meals
✓ Restrictions on activities within the context of the specific
diagnosis & the patient's ability.
➢ Competitive & strenuous sports activities are usually
contraindicated
➢ reduce anxiety and emotional stress
✓ Weight loss for obese patients
✓ Cessation of smoking
✓ Avoid other CVD risk factors
✓ Send sample for Cr, BUN, K+ and Na+ initially and proceed with diuresis.
✓ For diuretic naive patients start furosemide 20 - 40 mg IV (if BP>90/60
mmHg) and double the dose every 2 - 4 hour until the urine output is >1
ml/kg/hr (40-70ml/hr) [max. 400-600mg/day or 200mg per dose].
➢ Response to IV dose occurs 2-4 hours later.
➢ For those already on oral furosemide, start with equal dose of IV
furosemide.
➢ Maintain the dose of furosemide which gave adequate response on
a TID basis.
✓ Start spironolactone 25 - 50 mg/day unless K+ > 5.0 meq/l or Cr > 1.6
mg/dl or GFR<30 ml/min (main reason of adding spironolactone is to
prevent hypokalemia due to furosemide).
➢ Initial dose is 25 mg po per day increased up to 100 mg BID
➢ Since hyperkalemia is a life-threatening side effect of spironolactone
it is contraindicated in patients with renal failure (k+ >5 mmol/l or
>2.5 mg/dl of CRr)
➢ Remark: In advanced HF spironolactone dose ≥ 50mg have been
found to be necessary to produce natriuresis. Studies shows with the
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Chapter 1; Heart failure (ልብ ድካም)
NB: Patients with deranged renal function and hypoalbuminemia require higher
doses of diuretics from the outset.
Patient improving
❖ Decrease the dose of diuretics every day depending on patient condition.
o goal is to use the lowest possible dose and frequency to keep
patient dry.
❖ Change IV furosemide to PO and observe the patient with ambulation for a
day or two.
❖ Remark: since PO absorption rate of Lasix is poor, use conversion rate IV
to PO Lasix at 1:2 (20mg IV = 40mg PO).
o Patients requiring higher dose of furosemide may require a double
dose.
Institute further management for the underlying heart disease (see specific
topic and comorbidities below)
❖ Digoxin, for class C or D HF and with reduced EF, 0.125 - 0.25 mg, PO,
daily for positive inotropy and rate control in patients with atrial fibrillation.
➢ Effects: - positive inotropic effect (increase myocardial contractility),
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Chapter 1; Heart failure (ልብ ድካም)
ACEI
o Enalapril 2.5 mg, PO, BID, titrated as tolerated to target dose of 10
mg, PO, BID (maximum: 20 mg/day).
Alternative;
o Lisinopril 2.5 to 5 mg, PO, daily; increase by no more than 10 mg
increments at intervals no less than 2 weeks to the highest tolerated
dose (maximum: 40 mg/day)
ARBs
o Candesartan 4 mg, PO, daily or alternatively 4 to 8 mg, PO, daily;
double the dose at 2-week intervals, as tolerated; target dose: 32
mg once daily
Alternative;
o Valsartan 40 mg, PO BID; titrate dose to 80 mg, and then to 160
mg BID, as tolerated; maximum dose: 320 mg/day.
Beta- blockers
o Metoprolol; Metoprolol tartrate is short acting form, which is
preferred as initial management (especially in pt’s with ACS).
Metoprolol succinate is long acting form
▪ Remark: Metoprolol succinate is superior treatment option
compared to Metoprolol tartrate in treatment of HTN, CHF and
Coronary heart disease.
▪ Metoprolol tartrate (Immediate release): 50 mg, PO, BID;
usual dosage range: 50 to 200 mg, PO, BID; may increase
dose at weekly intervals to desired effect (maximum: 400
mg/day).
▪ Metoprolol succinate (Extended release): 12.5 to 25 mg once
daily; may double dosage every 2 weeks as tolerated up to
target dose of 200 mg/day.
o Carvedilol
▪ Immediate release; 3.125 mg, PO, BID for 2 weeks; if this
dose is tolerated, may increase to 6.25 mg PO, BID. Double
the dose every 2 weeks to the highest dose tolerated by
patient (maximum 25mg)
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Chapter 1; Heart failure (ልብ ድካም)
Date time BP PR RR T0 Wt SO2 UOP Crepit Hepato JVP Edema Cr Na+ K+ Sign
ation megaly
Before Discharge
❖ Proper advice: salt consumption, activity, adherence to medications and follow up.
❖ Prescribe adequate medications and give requests for further planned outpatient investigations.
❖ Document medications with dose and further plans clearly on the discharge note.
❖ Early appointment preferably in one-week time to follow up clinic.
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Chapter 1; Heart failure (ልብ ድካም)
Assess Manage:
Steps in the management of Heart Failure with Reduced Left Ventricular Systolic
Function (HFrEF)
ARBs (ATII receptor blockers) ✓Candesartan 8-32 mg/day in 1-2 divided doses
☛ Alternative to ACEI (cough, Alternative
angioedema) but not a substitute ✓Valsartan 40 - 80 mg PO BID
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Chapter 1; Heart failure (ልብ ድካም)
☛ * for Chronic heart failure in rheumatic heart disease patients, click and see Valvular heart
disease (VHD)
☛ ACEI, ARBs, Beta- blockers and Aldosterone antagonists have survival benefits and anti-
remodeling effect
☛ Choice between drugs depends on underlying heart disease
☛ Avoid combination of drugs from same group or ACEI with ARBs and spironolactone
Prognosis
Despite recent advances in the management of HF, the development of
symptomatic HF still carries a poor prognosis.
30 - 40% of patients die within 1 year of diagnosis and 60 - 70% die
within 5 years, mainly from worsening HF or as a sudden event (probably
because of a ventricular arrhythmia).
Although it is difficult to predict prognosis in an individual, patients with
symptoms at rest (NYHA class IV) have a 30 - 70% annual mortality rate,
whereas patients with symptoms with moderate activity (NYHA class II)
have an annual mortality rate of 5 - 10%. Thus, functional status is an
important predictor of patient outcome
Epidemiology
Pathogenesis
Clinical features
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Chapter 1; Heart failure (ልብ ድካም)
Joint involvement
The most common form of joint involvement in ARF is arthritis (i.e.,
objective evidence of inflammation, with hot, swollen, red, and/or
tender joints, and involvement of more than one joint (i.e., polyarthritis)).
Polyarthritis is typically migratory, moving from one joint to
another over a period of hours.
ARF almost always affects the large joints, most commonly the knees,
ankles, hips, and elbows, and is asymmetric.
The pain is severe and usually disabling until anti-inflammatory medication
is commenced.
Less severe joint involvement is also relatively common and has
been recognized as a potential major manifestation in high-risk populations
in the most recent revision of the Jones criteria.
Arthralgia without objective joint inflammation usually affects large joints in
the same migratory pattern as polyarthritis.
In some populations, aseptic mono-arthritis may be a presenting feature of
ARF, which may, in turn, result from early commencement of anti-
inflammatory medication before the typical migratory pattern is established.
The joint manifestations of ARF are highly responsive to salicylates
and other NSAIDs.
o Indeed, joint involvement that persists for more than 1 or 2 days
after starting salicylates is unlikely to be due to ARF.
Chorea
Sydenham’s chorea commonly occurs in the absence of other
manifestations, follows a prolonged latent period after GAS
infection, and is found mainly in females.
The choreiform movements affect particularly the head (causing
characteristic darting movements of the tongue) and the upper limbs.
They may be generalized or restricted to one side of the body (hemi-
chorea).
In mild cases, chorea may be evident only on careful examination, whereas
in the most severe cases, the affected individuals are unable to perform
activities of daily living.
There is often associated emotional lability or obsessive-compulsive traits,
which may last longer than the choreiform movements (which usually
resolve within 6 weeks but sometimes may take up to 6 months).
Clinical maneuvers to elicit features of chorea include:
☛ Milkmaid's grip
☛ spooning and pronation of the hands during extension 37
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Chapter 1; Heart failure (ልብ ድካም)
Skin manifestations
Erythema marginatum
o The classic rash of ARF is erythema marginatum, which begins
as pink macules that clear centrally, leaving a serpiginous, spreading
edge.
o The rash is evanescent, appearing and disappearing before the
examiner’s eyes.
o It occurs usually on the trunk, sometimes on the limbs, but almost
never on the face.
Subcutaneous nodules
o occur as painless, small (0.5 - 2 cm), mobile lumps beneath the skin
overlying bony prominences, particularly of the hands, feet, elbows,
occiput, and occasionally the vertebrae.
o They are a delayed manifestation, appearing 2 - 3 weeks after the
onset of disease, last for just a few days up to 3 weeks, and are
commonly associated with carditis.
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Chapter 1; Heart failure (ልብ ድካም)
Other features
Fever occurs in most cases of ARF, although rarely in cases of pure
chorea.
o Although high-grade fever (≥39°C) is the rule, lower grade
temperature elevations are not uncommon.
Elevated acute-phase reactants are also present in most cases.
➢ With the exception of chorea and low-grade carditis, both of which may
become manifest many months later, evidence of a preceding GAS infection
is essential in making the diagnosis of ARF.
➢ Because most cases do not have a positive throat swab culture or rapid
antigen test, serologic evidence is usually needed.
o The most common serologic tests are the anti-streptolysin O (ASO)
and anti-DNase B (ADB) titers.
o For this group, there is a set of “low-risk” criteria; for all others,
there is a set of more sensitive criteria.
b
Subclinical carditis indicates echocardiographic valvulitis.
c
Polyarthralgia should only be considered as a major manifestation in moderate- to high-risk
populations after exclusion of other causes. As in past versions of the criteria, erythema marginatum
and Subcutaneous nodules are rarely “standalone” major criteria. Additionally, joint manifestations can
only be considered in either the major or minor categories but not both in the same patient.
d
CRP value must be greater than upper limit of normal for laboratory. Also, because ESR may evolve
during the course of ARF, peak ESR values should be used.
Abbreviations: ARF, acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte sedimentation
rate. GAS, Group A Streptococcal
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Chapter 1; Heart failure (ልብ ድካም)
N → Subcutaneous Nodules
E → Erythema marginatum
S → Sydenham Chorea
Management of ARF
➢ There is no treatment for ARF that has been proven to alter the
likelihood of developing, or the severity of RHD. With the exception of
treatment of heart failure, which may be life-saving in cases of severe
carditis, the treatment of ARF is symptomatic.
Non-pharmacologic
✓ Bed rest if the patient has severe rheumatic carditis or arthritis/arthralgia
only.
o Traditional recommendations for long-term bed rest, once the
cornerstone of management, are no longer widely practiced.
Instead, bed rest should be prescribed as needed while arthritis
and arthralgia are present and for patients with heart failure. Once
symptoms are well controlled, gradual mobilization can commence
as tolerated.
✓ Salt restriction if there is associated Heart Failure.
Pharmacologic
5 approaches
1. Antibiotic therapy
✓ All patients with ARF should receive antibiotics sufficient to treat the
precipitating group A streptococcal infection.
✓ Penicillin is the drug of choice and can be given orally
o Penicillin V, 500 mg [250 mg for children ≤27 kg] PO, BID, for
10 days or
o Amoxicillin, 50 mg/kg [maximum, 1 g] daily, for 10 days or
o benzathine penicillin G, 1.2 million units (600,000 units for
children ≤27 kg), IM, stat
✓ for more, refer tonsillopharyngitis management (click here → 3.7.2 Acute
tonsillopharyngitis (የቶንሲል በሽታ ፣ የአንቃር እና ጉሮሮ ብግነት))
Aspirin dose from UpToDate 2018. Pediatricians in Ethiopia recommend the UpToDate
1
5. Prevention
Primary prevention:
▪ Ideal: eliminating risk factors for GAS infection which are over crowdedness
and poor hygiene (the antibiotics discussed above)
▪ If sore throat is treated within 9 days of commencement ARF will be prevented
Secondary prevention
The mainstay of controlling ARF and RHD is secondary prevention.
Because patients with ARF are at dramatically higher risk than the general
population of developing a further episode of ARF after a group
A streptococcal infection, they should receive long-term penicillin
prophylaxis to prevent recurrences.
Long term antibiotic prophylaxis is required for those patients who have
sustained an episode of rheumatic fever (see the table below)
o First line
▪ A single IM injection of benzathine penicillin G (600,000 IU
for children ≤ 27kg and 1.2 million IU for those >27kg and
adults) every 4 weeks (i.e. monthly)
☛ It can be given every 3 weeks, to persons
considered to be at particularly high risk.
o Alternative
▪ penicillin V, 250 mg, PO, BID For 10 days, every month or
▪ amoxicillin 500 mg po TID for 10 days, every month
o For Penicillin-allergic patients
▪ Erythromycin, 250mg, P.O. BID for 10 days, every month
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Chapter 1; Heart failure (ልብ ድካም)
Follow UP
Weekly or every 2 weeks follow up of ESR and CRP (normalize within 4-
6 weeks)
Echo after 1 month to see the progression of carditis
Prognosis of ARF
ARC: acute rheumatic carditis; MS: mitral stenosis; MV: mitral valve; MR: mitral regurgitation.
Clinical features
People with RHD are often asymptomatic for many years before their valvular
disease progresses to cause cardiac failure.
While chronic RHD occurs only as a sequalae of ARF, the majority of patients
with RHD lack a history of past ARF, suggesting that the diagnosis of ARF is
frequently missed with the initial or recurrent insults being subclinical or not
detected.
RHD generally presents as valve disease, which may or may not be detected
by a murmur.
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Chapter 1; Heart failure (ልብ ድካም)
oFor individuals ≤20 years old, borderline disease of both the aortic
valve and Mitral Valve.
▪ Combined AR and MR, particularly in high-prevalence regions
and in the absence of CHD, is regarded as rheumatic.
o For individuals <35 years old, pathologic AR, and at least two
morphologic features of RHD of the aortic valve.
▪ Bicuspid aortic valve, dilated aortic root, and hypertension
must be excluded.
➢ Borderline RHD only applies to individuals ≤20 years old and is present if
one of the following criteria is present: (For patients with no history of ARF)
o At least two morphologic features of RHD of the MV without
pathologic MR or MS
o Pathologic MR
o Pathologic AR
➢ For patients with history of ARF
o Consider the diagnosis of RHD definite if there is a typical valvular
abnormality (as defined by one or more morphologic World Heart
Federation criteria of RHD (table below) or
o Evidence of World Heart Federation criteria for pathologic
regurgitation).
MV: mitral valve; AMVL: anterior mitral valve leaflet; AV: aortic valve; RHD: rheumatic heart disease.
¶: ≥3 mm for individuals aged ≤20 years; ≥4 mm for individuals aged 21 to 40 years; ≥5 mm for
individuals aged >40 years
Patients with rheumatic valve disease should undergo periodic clinical and
echocardiographic evaluation with frequency based upon the severity of
disease, as described for individual valve lesions In VHD below.
Standard indications for valve intervention apply with choice of procedure
(eg, mitral valve repair or replacement) based upon patient characteristics
and available treatment options.
As noted above, secondary prevention of rheumatic fever is recommended
in patients with history of ARF and/or RHD.
Annual influenza vaccination and meticulous dental hygiene with annual
check-ups are recommended for patients with RHD.
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Chapter 1; Heart failure (ልብ ድካም)
Causes
✓Acute
o IE
o Aortic dissection
o Trauma (Iatrogenic during a failed replacement surgery)
✓Chronic
o Primary valvular disease:
▪ Rheumatic fever (RHD)
▪ IE
▪ Congenital Bicuspid aortic valve
▪ SLE
▪ Syphilitic aortitis
▪ Ankylosing spondylitis.
▪ Myxomatous (prolapse)
o Aortic root disease: widening of the aortic annulus and separation of the
aortic leaflets are responsible for the AR. causes include;
✓ Aortic dissection
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Chapter 1; Heart failure (ልብ ድካም)
Clinical Features
Symptoms
Physical examination
Diagnosis
Serial monitoring
✓ Mild chronic AR- clinical evaluation yearly and routine echo every 2-3 years
✓ Moderate AR - echo every 1-2 years
✓ Severe AR - echo yearly
Treatment
✓ Start enalapril 2.5mg po/day and escalate or amlodipine 5-10mg po/day for
the following patients
☛ Symptomatic severe AR with LV dilation
☛ Asymptomatic severe AR with LVEF <50%
✓ Patients with congestion- refer to pulmonary edema and cardiogenic shock
management
✓ Severe AR with reduced LVEF- refer to the management of HFrEF
☛ N.B. avoid the use of beta blockers in patients with severe AR
✓ Endocarditis prophylaxis- not indicated
✓ Pregnancy – should be avoided in the following patients
➢ NYHA class III to IV symptoms
➢ LVEF <40%
➢ Marfan syndrome
✓ Indications for surgical interventions- patients who can afford and have the
following indications should undergo aortic valve replacement or repair
➢ Symptomatic severe chronic AR
➢ Asymptomatic severe chronic AR and LVEF <50%
➢ Severe chronic AR and severe LV dilatation- LVEDD >75mm or
LVESD >55mm
➢ Severe AR with coronary artery disease requiring bypass graft
surgery
2. TR (Tricuspid Regurgitation)
Causes
Primary (organic)
• Rheumatic fever/RHD
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Chapter 1; Heart failure (ልብ ድካም)
• IE
• Papillary muscle injury (post-MI)
• Myxomatous (tricuspid valve prolapse)
• Leaflet trauma
• Radiation
• Carcinoid heart disease
• Endomyocardial fibrosis
• Congenital Heart disease in children (Ebstein’s malformation of the
tricuspid valve)
Secondary (functional)
• More than 80% of TR cases encountered in clinical practice are
secondary (functional)
• RV and tricuspid annular dilatation due to multiple causes of RV
enlargement such as
o MI (i.e. remodeling post-RV MI)
o Cardiomyopathy
o Atrial fibrillation (AF)
o Longstanding pulmonary HTN
o Left-sided valve disease
Clinical Features
Symptoms
Signs
Diagnosis
ECG
• inferior Q-wave MI suggestive of a prior RV MI
• RVH
• RA enlargement
• AF
• a bizarre right bundle branch block-type pattern with preexcitation in
patients with Ebstein’s anomaly
CXR
• RA and RV enlargement, depending on the chronicity and severity of
TR
TTE (Trans thoracic echo) is usually definitive with demonstration of
• Diagnosis and assessment of TR
• RA dilation and RV volume overload
• Prolapsing, flail, scarred, or displaced/tethered tricuspid leaflets with
annular dilatation
• In patients with severe TR, the CO is usually markedly reduced
Treatment
Diuretics can be useful for patients with severe TR and signs of right heart
failure. Loop diuretics like furosemide are typically used
An aldosterone antagonist may be particularly helpful because many
patients have secondary hyperaldosteronism from marked hepatic
congestion.
If heart failure due to left ventricular systolic dysfunction is present,
standard therapy, including beta-blockers and ARB’s are recommended
Correction of pulmonary hypertension can result in improvement in
functional TR, so causes of pulmonary hypertension (such as HF, MS, and
chronic thromboembolic pulmonary disease) should be addressed
Indications for surgical intervention (Tricuspid valve surgery)
• For patients with severe TR who are undergoing left-sided valve
surgery
• For treatment of moderate TR in patients undergoing left-sided valve
surgery who have
o Tricuspid annular dilation (>40 mm)
o A history of right heart failure, or
o Pulmonary arterial hypertension.
• For treatment of severe, primary TR with right heart failure not
responsive to standard medical therapy
• Progressively declining RV systolic function.
3. MR (Mitral Regurgitation)
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Chapter 1; Heart failure (ልብ ድካም)
Causes
❖ Acute
o IE (most often S. aureus)
o Papillary muscle rupture (Post MI) or dysfunction (from ischemia)
o Chordae tendineae rupture
o Blunt trauma
❖ Chronic
o Primary MR - is due to primary abnormality of the valve apparatus. Common
etiologies include
▪ Rheumatic fever/RHD
▪ IE
▪ Mitral valve prolapse (MVP)
▪ Trauma
▪ Congenital (cleft, AV canal)
o Secondary (functional) MR- is due to LV dilatation resulting in annular
dilatation of the mitral valve. Common causes include
▪ IHD
▪ DCMP
▪ HCMP
▪ Chronic Atrial Fibrillation with Left Atrial enlargement and annular dilatation
o Mitral annular calcification
▪ may include elements of both primary and secondary MR as the disease
process may encroach on the leaflets, impair the normal sphincteric
function of the annulus, or both
Clinical Features
Symptoms
✓ Dyspnea on exertion, PND, orthopnea
✓ Palpitations
✓ Later LV failure like Pulmonary edema
Signs
✓ Active precordium with displaced PMI
✓ Apical systolic thrill
✓ S3 gallop
✓ Murmur of MR
Diagnosis
✓ CXR findings: Cardiomegaly, dilated LV, pulmonary edema.
✓ ECG: AFib
✓ Echocardiogram: MR; dilated LA and LV; decreased LV function.
☛ (Doppler and color flow studies) to diagnose the etiology & assess
the severity of MR
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Chapter 1; Heart failure (ልብ ድካም)
Treatment
➢ Depends on the presence or absence of symptoms.
Asymptomatic patients- need only close follow-up.
☛ If patients have associated hypertension, it should be
treated with enalapril or amlodipine
Symptomatic patients- need medical therapy
✓ Lasix 40mg po BID and escalate till the congestion is relieved
✓ Start enalapril 2.5mg po/day and escalate up to 20mg po/day or
maximally tolerated dose
✓ If LVEF < 40%- refer to the protocol for heart failure with reduced
ejection fraction
Atrial fibrillation- refer to AF management protocol
Anticoagulation- similar to patients with mitral stenosis
Endocarditis prophylaxis- not indicated unless prior IE
Prevention of rheumatic recurrence- similar to patients with rheumatic
MR
Indications for surgical intervention- patients who can afford and have
the following indications should be referred early to undergo mitral valve
repair or replacement
✓ Symptomatic severe MR
✓ Asymptomatic severe MR with one of the following factors
o LVEF<60% or LVESD >40mm
o New onset AF
o Pulmonary hypertension
Etiology
Clinical Features
Symptoms
Signs
➢ Murmur of MS.
➢ Irregularly irregular pulse
➢ With long-standing disease, will find signs of RVF (e.g., right ventricular
heave, raised JVP, hepatomegaly, ascites) and/or pulmonary HTN (loud
P2).
➢ Basal rales on the chest, acute pulmonary edema.
➢ All signs and symptoms will increase with exercise and during
pregnancy.
Diagnosis
Treatment
HF- Treatment should be instituted for Acute cases (like pulmonary edema and
cardiogenic shock), and symptomatic patients
For patients with symptoms of congestion- pulmonary or peripheral edema
✓ Start Lasix 40mg po BID and escalate every 2wks-1 month till
symptoms subside.
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Chapter 1; Heart failure (ልብ ድካም)
Indications for surgical intervention- patients who can afford and have the
following indications should be referred as early as possible to undergo PBMV
or valve replacement
✓ Moderate to severe MS with symptoms
✓ Asymptomatic patients with moderate to severe MS and either
pulmonary artery pressure at rest >50mmHg (can be measured with
Doppler echocardiography) or new onset AF
Clinical Features
Symptoms
▪ Patients remain asymptomatic till the valve area is ≤1 cm2.
▪ Classic symptoms include exertional angina, syncope (usually exertional),
dyspnea, and excessive fatigue.
▪ Heart failure symptoms, such as dyspnea on exertion, orthopnea, or
PND
Signs
▪ Active precordium with displaced PMI
▪ Murmur of AS
Diagnosis
✓ CXR findings: Calcific aortic valve, enlarged LV/LA (late)
✓ ECG findings: LVH, LA abnormality
✓ Echocardiography: Valve lesion, degree of stenosis, LVH
✓ Lipid profile
Severity- depends on aortic valve area (AVA)
☛ Mild AS → AVA 1.5-2 cm2
☛ Moderate AS → AVA 1.0-1.5 cm2
☛ Severe AS → AVA ≤ 1 cm2
☛ Aortic valve sclerosis- thickened aortic valve with AVA >2 cm2
Follow-up echocardiography should be done based on the severity of AS
Mild AS- every 3-5 years
Moderate AS- every 2 years
Severe AS - yearly
Treatment
Mainly indicated for symptomatic patients
In patients with severe AS (valve area <1 cm2), strenuous physical activity
and competitive sports should be avoided, even in the asymptomatic stage.
Avoid dehydration and hypovolemia
Reading assignment
Tricuspid stenosis (TS)
Pulmonic stenosis (PS)
Pulmonic Regurgitation (PR)
Multiple and Mixed VHD
Pathophysiology
Determinants of myocardial oxygen demand
✓ Heart rate
✓ Myocardial contractility, and
✓ Myocardial wall tension
Determinants of myocardial oxygen supply
✓ Inspired fraction of oxygen
✓ Pulmonary function
✓ Hemoglobin concentration and function
✓ Adequate level of coronary blood flow
☛ Any mismatch between the above factors could result in myocardial
ischemia/infarction
Causes
❖ Atherosclerosis
❖ Vasospasm (Prinz metal’s angina)
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Chapter 1; Heart failure (ልብ ድካም)
❖ Arterial thrombi
❖ Coronary emboli
❖ Aortitis
❖ Congenital anomalies- the origin of the left anterior descending coronary artery
from the pulmonary artery
❖ Severe anemia or the presence of carboxyhemoglobin
❖ Increased oxygen demand e.g. - LVH
❖ Two or more causes of ischemia often coexist in a patient e.g. - LVH due to
HTN and atherosclerosis
Coronary atherosclerosis
Asymptomatic
o Silent myocardial ischemia
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Chapter 1; Heart failure (ልብ ድካም)
CLASSIFICATION OF ACS
1. Unstable angina:
2. ST-segment elevation myocardial infarction (STEMI):
3. Non-ST-segment elevation myocardial infarction (NSTEMI):
Figure; Acute coronary syndromes. Following disruption of a vulnerable plaque, patients experience
ischemic discomfort resulting from a reduction of flow through the affected epicardial coronary artery.
The flow reduction may be caused by a completely occlusive thrombus (right) or sub totally occlusive
thrombus (left). Patients with ischemic discomfort may present with or without ST-segment elevation.
Of patients with ST-segment elevation, the majority (wide red arrow) ultimately develop a Q wave on
the ECG (Qw MI), while a minority (thin red arrow) do not develop Q wave and, in older literature,
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Chapter 1; Heart failure (ልብ ድካም)
were said to have sustained a non-Q-wave MI (NQMI). Patients who present without ST-segment
elevation are suffering from either unstable angina or a non-ST-segment elevation MI (NSTEMI)
(wide green arrows), a distinction that is ultimately made based on the presence or absence of a
serum cardiac biomarker such as CK-MB or a cardiac troponin detected in the blood. The majority of
patients presenting with NSTEMI do not develop a Q wave on the ECG; a minority develop a Qw
MI (thin green arrow).
Definitions of ACS
Pathophysiology
Diagnosis
❖ ECG
✓ ST-segment depression
✓ Transient ST-segment elevation
✓ T-wave inversion
❖ Cardiac biomarkers- elevated in NSTEMI
✓ Cardiac troponin- more specific and sensitive marker of myocardial
necrosis
✓ CKMB
❖ Echocardiography
✓ May show regional wall motion abnormalities
❖ Coronary angiography
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Chapter 1; Heart failure (ልብ ድካም)
Clinical Features
P/E
should raise the suspicion of ACS in these patients
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Chapter 1; Heart failure (ልብ ድካም)
Class I - no evidence of HF
Class II - findings consistent with mild to moderate HF (S3, lung rales less
than one-half way up the posterior lung fields, or jugular venous distension)
Class III - overt pulmonary edema (click and see 1.10.2 Pulmonary edema)
Class IV - Cardiogenic shock (pump failure) (click and see the respective topic)
Diagnosis of STEMI
Other IX
techniques
✓ CBC with platelet count
✓ PT, aPTT and INR
✓ Electrolytes
✓ BUN & Creatinine
✓ RBS
✓ Serum lipid profile
✓ Non specific indices of tissue necrosis and inflammation
COMPLICATIONS OF STEMI
Mechanical
➢ Rupture of the left ventricular free wall
➢ Rupture of IVS
➢ MR
➢ Left ventricular dysfunction
➢ LV aneurysm
➢ Pericarditis
Electrical complications
➢ Arrhythmias
Complications which can be as a result of both mechanical and electrical
disturbances
➢ Heart failure
➢ Cardiogenic shock
➢ Thromboembolism
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Management of ACS
Early referral to the high-level facility or urgent specialist consultation is
recommended
Non pharmacologic
Categorize patients based on the above evaluation (see the above table)
✓ Patients with high and intermediate likelihood of ACS should be
admitted to the medical ICU and managed according to ACS
management protocol
✓ Patients with low likelihood of ACS can be discharged from the ED
with advice to come early if they have similar chest pain
☛ Manage the possible cause of the current complaint
Hospital admission and strict bed rest with continuous cardiac monitoring
(ECG monitoring).
❖ Absolute bed rest for 12hrs
❖ Movement only around the bed after 48hrs
❖ Movement to toilet and less than ordinary activities after 72hrs
❖ Avoid strenuous activities for 2 weeks
Establish IV access and obtain blood for troponin, electrolytes, coagulation
profile, RFT.
NPO and fluid diet for the 1st 12hr’s
Give supplemental oxygen if patients are hypoxic (Spo2 <90 %).
Pharmacologic
of contraindications
▪ 5 µg/minute, increase by 5 µg/minute every 3 to 5 minutes to
20 µg/minute. If no response at 20 µg/minute, may increase
by 10 to 20 µg/minute every 3 to 5 minutes (maximum dose:
400 µg/minute)
✓ Enoxaparin
o Patients <75 years of age: Initial: 30 mg IV single bolus plus
1 mg/kg (maximum: 100 mg for the first 2 doses only) SC,
BID.
▪ The first SC dose should be administered with the IV
bolus. Maintenance: After first 2 doses, administer 1
mg/kg Sc, BID
o Patients ≥75 years of age: Initial: 0.75 mg/kg, SC, BID (Note:
No IV bolus is administered in this population); a maximum
dose of 75 mg is recommended for the first 2 doses.
▪ Maintenance: After first 2 doses, administer 0.75 mg/kg
SC, BID
✓ Alternative: UFH 5000 IU (60 IU/kg), IV loading followed by 250
IU/kg (17,500 IU), SC BID
☛ If infuser is available give maintenance dose 12U/Kg/hr IV
continuous infusion.
Other therapies
a. Statin
❖ High intensity statin therapy; for Age ≤ 75 years
✓ Atorvastatin 80 mg PO daily; if unable to tolerate,
may reduce dose to 40 mg once daily
✓ Alternative; rosuvastatin 20 to 40mg PO, daily
❖ Moderate-intensity statin therapy; for age > 75 years or not
a candidate for high intensity therapy
✓ Atorvastatin 10 to 20 mg PO daily
✓ Alternative;
o Rosuvastatin 20 to 40mg PO, daily or
o Simvastatin 20 to 40mg PO, daily
▪ Low intensity is used to decrease statin induced myopathy in
old age
of ST elevation, Q waves)
➢ Echocardiography: LV function, wall motion abnormality, LV thrombus
➢ Follow troponin levels
➢ Watch for mechanical and electrical complications (the most feared cxn
of ACS is arrythmia)
➢ Watch for bleeding in patients at high risk for bleeding
➢ Obesity
➢ Sedentary lifestyle (lack of physical activity)
➢ Stress
➢ Excess alcohol use
Clinical Features
Treatment of CCS
❖ Antiplatelet therapy
✓ ASA 75-100 mg PO daily
✓ Alternative: Clopidogrel 75 mg Po daily
❖ Beta blocker: chest pain, heart rate and blood pressure control
✓ Metoprolol succinate 50-200 mg PO daily
✓ Alternative: Bisoprolol 2.5-10 mg PO daily
❖ Statin: target LDL< 70 mg/dl, dose of statin titrated as per the response
✓ Atorvastatin 20-80 mg PO daily
✓ Alternative: Rosuvastatin 5-20 mg PO daily
❖ Angina management
✓ Betablockers: see above
✓ Calcium channel blockers
☛ Amlodipine 2.5-10 mg PO daily for those with hypertension
✓ Nitrates
☛ Nitroglycerine 0.4 mg sublingual tablets for acute relief
☛ Isosorbide dinitrate 2.5-20 mg PO single dose or divided
doses as needed
☛ Trimetazidine 35 mg Po daily
❖ Review risk factor, symptoms and indication for revascularization
❖ Refractory cases: Need Cardiologist evaluation
Coronary revascularization
Indications
✓ The presence of unstable phases of the disease
✓ Intractable symptoms despite medical therapy
✓ Severe ischemia or high-risk coronary anatomy
✓ Diabetes
✓ Impaired LV function
Revascularization should be employed in conjunction with but not replace
the continuing need to modify risk factors and assess medical therapy
Two options
✓ Percutaneous coronary intervention (PCI)
✓ Coronary artery bypass grafting (CABG)
Indications for early revascularization
✓ Recurrent angina at rest despite medical Rx
✓ Elevated troponin
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Risk factors
➢ Smoking is by far the most important risk factor
➢ Chronic Coronary Syndrome
➢ Dyslipidemia
➢ Hypertension
➢ Diabetes: prevalence is markedly increased in these patients
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Chapter 1; Heart failure (ልብ ድካም)
Clinical Features
Symptoms:
Signs:
Rutherford
Fontaine
➢ Stage 1 – No symptoms
➢ Stage 2 – Intermittent claudication subdivided into:
☛ Stage 2a – Without pain on resting, but with claudication at a
distance of greater than 650 feet (200 meters)
☛ Stage 2b – Without pain on resting, but with a claudication distance
of less than 650 feet (200 meters)
➢ Stage 3 – Nocturnal and/or resting pain
➢ Stage 4 – Necrosis (death of tissue) and/or gangrene in the limb
Diagnosis
Clinical suspicion based on symptoms, signs and risk factors
Ankle-to-brachial index (ABI): Ratio of the systolic BP at the ankle to the
systolic BP at the arm.
𝐒𝐁𝐏 𝐨𝐟 𝐚𝐧𝐤𝐥𝐞
☛ Normal 𝐀𝐁𝐈 = 𝐒𝐁𝐏 𝐎𝐅 𝐁𝐫𝐚𝐜𝐤𝐢𝐚𝐥 𝐚𝐫𝐭𝐞𝐫𝐲
= 𝟎. 𝟗 − 𝟏. 𝟑
☛ SBP of ankle measured by Doppler ultrasound guided BP
measurement. But, SBP of arm can be measured by
sphygmomanometer (by any BP cuff available in the ward)
☛ ABI < 0.9 is evidence for PAD, ABI >1.3 is due to no
compressible vessels (vessel wall calcification) and indicates
severe disease
☛ Claudication usually when ABI < 0.7
☛ Rest pain usually when ABI < 0.4
Doppler study of the peripheral vessels
Arteriography (contrast in vessels and radiographs)
o Gold standard for diagnosing and locating PAD
Treatment
Non pharmacologic
Conservative management for intermittent claudication.
➢ Smoking cessation (the importance of this cannot be
overemphasized). Smoking is linked to progression of
atherosclerosis and causes vasoconstriction (further decreasing
blood flow).
➢ Graduated exercise program: Walk to point of claudication, rest,
and then continue walking for another cycle.
➢ Foot care (especially important in diabetic patients).
➢ Avoid extremes of temperature (especially extreme cold).
Pharmacologic
➢ Atherosclerotic risk factor reduction (control of hyperlipidemia,
Hypertension, Diabetes):
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➢ Antiplatelets
o ASA 81-100 mg Po daily
o Alternative: Clopidogrel 75 mg Po daily
➢ Statin
o Atorvastatin 20 - 80 mg Po daily
o Alternative: Rosuvastatin 5-20 mg Po daily
Sources of emboli:
Heart (85%)
❖ Atrial fibrillation is the most common cause of embolus from the
heart
❖ Post-MI
❖ Post arterial procedure (i.e., coronary angiogram, peripheral
angiogram)
❖ Endocarditis
❖ Myxoma
Aneurysms
Atheromatous plaque
❖ Pain: acute onset. The patient can tell you precisely when and where
it happened. The pain is very severe, and the patient may have to sit
down or may fall to the ground.
❖ Pallor
❖ Polar (cold)
❖ Paralysis
❖ Paresthesia’s
❖ Pulselessness
Diagnosis
Treatment
Hypertension
✓ Have diabetes
✓ Have chronic kidney disease (CKD)
✓ Are obese
✓ Use tobacco
✓ Have a family history of heart attack or stroke
Diagnosing hypertension 82
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Diagnosis of hypertension
Previously Currently
In our setup we are still using the previous staging system for clinical purpose
Once diagnosis of hypertension is made: Look for end-organ damage based on:
➢ History: Smoking, excess salt intake, sedentary life, low fruit and vegetable
intake, excess alcohol consumption
➢ Cardiovascular Risk assessment; For all patients found to have raised BP, their
future 10-year cardiovascular risk should be assessed by using WHO CV risk
score (Refer WHO CV risk assessment manual). In a setting where serum
cholesterol and FBS can be determined use the laboratory-based risk
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Classification of HTN
2. Secondary HTN
Hypertension Treatment
❖ Patient who couldn’t achieve target blood pressure with life style
interventions.
❖ At initial presentation in those with:
o End-organ damage or high WHO cardiovascular risk (>20%)
o Hypertensive Crises
o Enalapril Initial: 5 mg, PO, daily (2.5 mg, PO, daily in patients
taking diuretics); titrate upward, usually at 1- to 2-week
intervals; usual dose range: 10 to 40 mg daily. Target dose:
20 mg daily in 1 or 2 divided doses. Maximum: 40 mg/day.
▪ Note: May add a diuretic if blood pressure cannot be
controlled with enalapril alone.
Or
o Captopril; Initial dose: 25 mg, PO, BID to TID (a lower initial
dose of 12.5 mg, PO, TID may also be considered; may
increase at 1- to 2-week intervals up to 50 mg PO TID;
maximum dose: 450 mg/day
▪ add thiazide diuretic, unless severe renal impairment
coexists then consider loop diuretic, before further
dosage increases or consider other treatment options
First line
✓ Hydrochlorothiazide 25mg/day
✓ Nifedipine (immediate release) 20-40mg/2-3 times /day
✓ Amlodipine/felodipine 2.5-10 mg once daily (escalate 2.5mg every week)
2 line
nd
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Precipitants:
➢ Progression of essential hypertension +/- medical noncompliance
➢ Progression of renovascular disease: AGN, preeclampsia
➢ Endocrine: pheochromocytoma
➢ Cerebral injury (low BP in acute stroke- with treatment)
☛ Patients with substantially elevated BP who lack acute HMOD are not
considered a hypertensive emergency and can typically be treated with
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Basic investigations:
Drug selection2:
✓ Hydralazine: 10-20mg, IV, q20-30 min for maximum of 3-4 doses; fall in BP
begins within 10 to 30 minutes and lasts 2 to 4 hours combined with one
of the following;
➢ Propranolol 20mg Po stat and evaluate: (i.e. if no contraindication for
propranolol/overt heart failure or severe COPD start with hydralazine)
▪ Patients with ACS and aortic dissection (avoid reflex
tachycardia)
92
2
Source; Cardiology handbook, university of Gondar hospital, management guidelines, 2014
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NB:
3
Reference; UpToDate, © 2018, version 2.0
93
4
Reference; UpToDate, © 2018, version 2.0
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Chapter 1; Heart failure (ልብ ድካም)
Follow-Up
❖ Beta blockers are not recommended as first-line therapy. If a heart attack has
been diagnosed within the previous three years, or there is atrial fibrillation or
heart failure, then a beta blocker should be added to the starting dose of
antihypertensive medication. Patients with angina may also benefit from
treatment with a beta blocker.
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Chapter 1; Heart failure (ልብ ድካም)
Image; LVH
Risk factors
Classifications
Further Classification
Acute endocarditis
subacute endocarditis
✓Most commonly caused by S. aureus ✓Caused by less virulent organisms, such
(highly virulent). as S. viridans and Enterococcus
✓Occurs on a normal heart valve.
✓Rapidly destructive, Metastatic foci
✓Occurs on damaged heart valves
✓Indolent nature
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✓If untreated, fatal in less than 6 weeks. ✓If untreated, takes much longer than 6
weeks to cause death
Clinical presentations
❖ History
1. Acute endocarditis is characterized by high grade fever with rapidly
progressive heart failure and metastatic infection. Common etiologies
include S.aureus, pneumococci, and enterococci
2. Subacute endocarditis- evolves during weeks to months with only
modest toxicity. It is commonly caused by viridians streptococci,
CONS, Enterococci, and HACEK group
❖ Common findings include
✓ Persistent fever
✓ Heart murmurs
✓ Otherwise-unexplained arterial emboli, and
✓ Cutaneous and mucocutaneous lesions, like petechiae, splinter
hemorrhages, janeway lesions, osler’s node, and Roth spots.
Splinter Hemorrhages
Janeway lesions
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Osler’s Nodes
More specific, painful and erythematous nodules, located on pulp of fingers and
toes, more common in subacute IE
Diagnosis
Minor Criteria
1. Predisposing condition (abnormal valve or abnormal risk of
bacteremia like IV drug abuse, GI/GU manipulation….)
2. Fever ≥38.0°C (100.4°F)
3. Vascular phenomena: Septic arterial or pulmonary emboli, mycotic
aneurysms, intracranial hemorrhage, conjunctival hemorrhages, Janeway
lesions5
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5 Janeway lesions are painless erythematous lesions on palms and soles.
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❖ Definite IE
✓ Clinical criteria
➢ 2 major criteria, or
➢ 1 major and 3 minor criteria, or
➢ 5 minor criteria
✓ Pathologic criteria
➢ Microorganism: (via culture or histology) in a
valvular vegetation, embolized vegetation, or
intracardiac abscess
➢ Pathological lesions: vegetation or intracardiac
abscess present, confirmed by histology showing
active endocarditis
❖ Possible IE
✓ 1 major criterion and 1 minor criterion or
✓ 3 minor criteria
❖ Rejected IE
✓ Firm alternative diagnosis for manifestations IE, or
✓ Sustained resolution of manifestations of endocarditis, with
antibiotic therapy for 4 days or less, or
✓ No pathological evidence of infective endocarditis at
surgery or autopsy
Organisms
Native valve endocarditis
➢ S. viridans is the most common organism in native valve
endocarditis.
➢ Other common organisms include:
− Staphylococcus species (S. aureus more commonly than S.
epidermidis) and Enterococci.
− Streptococcus bovis is associated with increased risk of
active colonic malignancy
− HACEK group of organisms: Haemophilus, Actinobacillus,
Cardiobacterium, Eikenella, and Kingella.
Treatment of IE
❖ PRINCIPLES OF TREATMENT
1) Parentral antibiotics
2) Only bactericidal antibiotics are effective and Bacteriologic result should
direct antibiotic selection
3) High dose & combination of antibiotics designed to give sustained
bactericidal serum concentration to penetrate vegetations!
4) Prolonged treatment to kill dormant bacteria clustered in vegetations! (4-6
wks)
5) 3 sets of blood cultures should be drawn prior to initiating antibiotic
therapy. start antibiotic treatment immediately after blood culture is
collected over 1 hour in Acute endocarditis or prosthetic valve
endocarditis.
✓ Culture positive
➢ Treat based on the isolated organism and susceptibility pattern
✓ Culture negative endocarditis
➢ SBE- ceftriaxone 2gm/day + gentamycin 3mg/kg for the first
2wks and continue with ceftriaxone only for the remaining wks
of therapy
➢ Acute endocarditis- continue vancomycin + gentamycin for 2
wks and then vancomycin only for the remaining wks of therapy
• Patients with proven or suspected enterococcal
endocarditis should receive combination of vancomycin
and gentamicin for the whole duration of therapy
• If vancomycin is not available or patient cannot afford,
use ceftriaxone 2gm/day with gentamycin
• In our setup we are using ceftriaxone and gentamycin
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If cultures are negative but there is high clinical suspicion, treat empirically
(See table below) until the organism can be isolated.
Anticoagulants and antiplatelets are not recommended to prevent or treat
embolic complications.
*Treatment should be modified based on culture and sensitivity results as well as clinical
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Chapter 1; Heart failure (ልብ ድካም)
Prophylaxis
1.7 Arrhythmia
Readers are recommended to click here and read → Chapter 6; Basics of
ECG and ECG interpretation before reading arrythmia.
1. Tachyarrhythmias
Treatment
Non pharmacologic
❖ Vagal maneuvers: maneuvers which increase vagal activity can terminate
episodes of PSVT. ECG and blood pressure monitoring is required during
the procedure.
☛ Carotid sinus massage: supine position with the neck extended. The
carotid sinus is located inferior to the angle of the jaw at the level
of the thyroid cartilage. Steady pressure is applied to one carotid
sinus for 5 to 10 seconds. If no response, repeat it in the
contralateral side after 1-2 minutes.
Note: Carotid massage should not be attempted in patients with carotid
bruit/stenosis or ischemic stroke. Both carotid sinuses should never be
massaged simultaneously.
☛ Valsalva maneuver: while in the supine position the patient is
instructed to exhale forcefully against a closed glottis with closed
mouth and nose for 10 seconds. Adequacy indicated by neck vein
distension, and increased tone in the abdominal wall muscles.
❖ Synchronized electrical Cardioversion: required rarely for hemodynamically
unstable patients. The energy needed is 150 to 200 joules for monophasic
defibrillators.
Pharmacologic
✓ Adenosine, I.V, very rapidly (over 1-2 seconds): Initial: 6mg; if not effective
within 1-2 minutes, 12mg may be given; may repeat 12mg bolus if needed.
Follow each dose with 20ml very rapid NS flush.
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Alternatives
✓ Metoprolol, IV, 2.5-5mg every 2-5 minutes (maximum total dose: 15mg over
a 10-15minute period). OR
✓ Verapamil, I.V, 2.5-5mg over 2 minutes; second dose of 5-10mg may be
given after 15-30 minutes; maximum total dose: 20-30mg OR
✓ Digoxin, 0.5 to 1mg IV over a period of 10 to 15 min followed by 0.25mg
every 2-4 hours with a total dose less than 1.5mg with in 24-hour period
Atrial fibrillation
Atrial flutter
Atrial flutter is characterized by regular rapid atrial rate of 260 - 300 beats
per minute, which usually results in a regular ventricular response in a 2:1
ratio resulting in a heart rate of 130 - 150 beats per minute.
The ventricular response can sometimes be in 3:1, 4:1, irregular or rarely
1:1 ratio.
The typical ECG finding is of saw-tooth appearance of the baseline mainly
on inferior leads (II, III, AVF) with rapid, regular and narrow QRS.
Treatment
Note: The management of atrial fibrillation and atrial flutter are the same.
Non pharmacologic
Pharmacologic
First line
✓ Metoprolol, 2.5 - 5mg, IV, over 3–5 min, to maximum total dose 15mg
over 10-15 minutes
Alternative
✓ Digoxin, 0.25mg, IV, q2h until 1 mg total (digoxin is the first line medicine
if atrial fibrillation is associated with severe left Ventricular dysfunction)
❖ The higher the score, the higher the annual stroke risk.
❖ For patients with CHA2DS2VASc score >1, anticoagulation is generally
indicated unless high bleeding risk
o Score 0 → No antithrombotic
o Score 1 → Anti-platelet or anticoagulation
o Score ≥ 2 → anticoagulation.
❖ Commonly used Antiplatelets include Aspirin (1st line) & clopidogrel (2nd
line). Commonly used anticoagulants include warfarin, UFH, LMWH
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Warfarin:
Treatment
Non pharmacologic
CPR should be provided to patients with sustained VT with cardiac arrest
(the victim is unresponsive, pulseless and not breathing).
O2 via face mask or nasal catheter.
Continuous ECG monitor.
Suction device and endotracheal intubation set should be ready.
Correct electrolyte disorders.
Reassure patients with non-sustained ventricular tachycardia.
Defibrillation:
➢ Sustained polymorphic VT, ventricular flutter, or ventricular fibrillation
Emergency defibrillation (without synchronization), with >200 Joules
(monophasic), increase the energy to the maximum if arrhythmia persists.
➢ Sustained monomorphic VT: synchronized with >200 Joules (monophasic).
Note:
Pharmacologic
First line:
✓ Amiodarone, IV
➢ Stable VT regimen:
☛ Step 1: 150mg over first 10 minutes (dilute in 100ml D5W)
☛ Step 2: 360mg over next 6 hours (dilute in 500ml D5W): 1
mg/minute
☛ Step 3: 540mg (dilute in 500 to 1000ml D5W) over next 18 hours:
0.5mg/minute
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✓ lidocaine, IV
➢ Both stable VT and Pulseless VT (cardiac arrest) regimen:
☛ Lidocaine, I.V, 1 - 1.5mg/kg; repeat with 0.5 - 0.75mg/kg every 5-10
minutes if no response. (maximum cumulative dose: 3mg/kg).
☛ Follow with continuous infusion of 1 - 4mg/minute
☛ Preparation for continuous infusion: 2g of lidocaine/250ml D5W
☛ Rate of infusion: 1mg/min = 7.5ml/hour, 2mg/min =15ml/hour, 3mg/min=
22.5ml/hr, 4mg/min= 30ml/min
Prevention of recurrence
Non-pharmacologic
➢ Standard treatment of the underlying cause is the main stay of treatment for
preventing recurrent VT. (e.g. treatment of acute coronary syndrome)
➢ Correct precipitating causes (e.g. hypoxia, hypo/hyperkalemia, acidosis,
pulmonary embolism).
➢ Discontinue arrhythmogenic medicines-digoxin, antiarrhythmic medicines.
Pharmacologic
First line
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2. Bradycardia (Bradyarrhythmia)
Treatment
❖ Look for reversible causes and act accordingly
[Sudden] cardiac arrest is the sudden cessation of cardiac activity so that the
victim becomes unresponsive, with no normal breathing and no signs of
circulation.
If corrective measures are not taken rapidly, this condition progresses to
sudden death.
Cardiac arrest should be used to signify an event as described above, that is
reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac
pacing.
Sudden cardiac death (SCD) should not be used to describe events that are
not fatal."
These events mostly occur in patients with structural heart disease (that may
not have been previously diagnosed), particularly coronary heart disease or
sustained ventricular tachycardia/ventricular fibrillation.
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Energy selection
o Select the appropriate energy for the specific arrhythmia
o Press the sync button if synchronization is required
Clear you and your team and deliver the shock
o Say “I am going to shock on three. One, two, three, shocking”
o Perform a visual check to make sure you have no contact with the
patient, the stretcher or other equipment
https://youtu.be/Dubih8EzBJQ
https://youtu.be/T7Zv9vLdWtE
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1.8 Pericarditis
Classification of pericarditis
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Chapter 1; Heart failure (ልብ ድካም)
A. Rheumatic fever
B. Collagen vascular disease (SLE, RA, ankylosing spondylitis, scleroderma,
granulomatosis with polyangiitis [Wegener’s])
C. Drug-induced (e.g., procainamide, hydralazine, phenytoin, isoniazid, minoxidil,
anticoagulants, methysergide)
D. Postcardiac injury
1. Post pericardiotomy
2. Posttraumatic
3. Post myocardial infarction (Dressler’s syndrome)
ACUTE PERICARDITIS
DIFFERENTIAL DIAGNOSIS
complexes.
✓ Stage 2: after several days, the ST segments return to normal
✓ Stage 3 :T waves become inverted
✓ Stage 4: ultimately, weeks or months after the onset of acute pericarditis,
the ECG returns to normal
Echo
• Presence of pericardial effusion and its hemodynamic effect
1. Pericardial Effusion
2. Cardiac Tamponade
3. Constrictive pericarditis (1%)
4. Recurrence (15-30% in idiopathic)
CLINICAL FEATURES
Occasionally, large, asymptomatic chronic effusions are discovered when
CXR is obtained for an unrelated reason
Pericardial pain
Dyspnea (in tamponade)
Tachycardia is the rule unless heart rate lowering drugs have been
administered, conduction system disease coexists, or a preterminal
bradycardic reflex has supervened
Apical impulse may not be palpable
ed cardiac dullness
Friction rub may disappear
Ewart’s sign (the base of the left lung may be compressed by pericardial
fluid and produce an area dullness and increased fremitus (and egophony)
beneath the angle of the left scapula)
Beck's triad → severe tamponade
• Hypotension
• Muffled heart sounds
• Elevated JVP
uncomfortable patient, with signs reflecting varying degrees of reduced
cardiac output and shock including tachypnea; diaphoresis; cool extremities;
peripheral cyanosis; depressed sensorium
Hypotension is usually present, although in early stages compensatory
mechanisms maintain the blood pressure
A paradoxical pulse
DIAGNOSTIC APPROACH
MANAGEMENT
❖ Treatement of the underlying disease
❖ Management of cardiac tamponade
➢ Fluid resucitation
➢ Fluid drainage: the choice between open drainage and
pericardiocentesis is based upon local preference and experience,
and upon individual patient considerations
2. CONSTRICTIVE PERICARDITIS
PATHOPHYSIOLOGY
Inability of the ventricles to fill because of the limitations imposed by the rigid,
thickened pericardium
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CLINICAL MANIFESTATION
DIFFERENTIAL DIAGNOSIS
Restrictive cardiomyopathy
Cardiac tamponade
Core pulmonale
Tricuspid stenosis
INVESTIGATIONS
❖ ECG:
➢ Low voltage of the QRS complexes
➢ Diffuse flattening or inversion of the T waves.
➢ Atrial fibrillation (in about 1/3 of patients)
❖ CXR: shows a normal or slightly enlarged heart; pericardial calcification is
most common in tuberculous pericarditis
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❖ ECHO
❖ CT/MRI scan
❖ Cardiac catheterization
A. Cardiomyopathy (CMP)
Classification
A. Etiologic classification
❖ Primary cardiomyopathies→ Predominantly involving the heart; Are further
subdivided in to
✓ Genetic
✓ Acquired
✓ Mixed
❖ Secondary cardiomyopathies → Accompanied by other organ system
involvement
B. Morphologic classification
✓ Based on echocardiographic and autopsy findings
➢ Dilated cardiomyopathy (DCMP)
➢ Restrictive cardiomyopathy (RCMP) and
➢ Hypertrophic cardiomyopathy (HCMP)
General presentation
Early symptoms often relate to exertional intolerance with SOB or fatigue
Progressive SOB
Nocturnal cough
Chest pain
Peripheral oedema and ascites
Arrhythmias
Embolic events
IX
ECG
CXR
ECHO (two-dimensional and Doppler)
Chemistry:
✓ Na, K, Ca, Mg, RBS/FBS, U/A, Creatinine and BUN, Albumin, total
protein, LFT, Lipid profile, TSH, Creatine kinase, Serum iron,
transferrin saturation,
Hematology:
✓ Hgb, CBC, ESR
➢ Lyme disease
➢ Toxoplasmosis
❖ Catheterization with coronary angiography in patients with angina who are
candidates for intervention
❖ Serologies for active rheumatologic disease
❖ Endomyocardial biopsy including sample for electron microscopy when
suspecting specific diagnosis with therapeutic implications
❖ Screening for sleep-disordered breathing
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Etiology
1. Idiopathic(primary)- 2/3rd of cases
2. Secondary:
❖ Post infectious (viral myocarditis/ coxsackie, adenovirus, HIV, hepatitis C/,
parasitic/ T. cruzi—Chagas’ disease, trypanosomiasis, toxoplasmosis/,
bacterial/ diphtheria/, spirochetal/ Borrelia burgdorferi—Lyme disease)/,
Rickettsial /Q fever/, Fungal /with systemic infection/)
❖ Toxic (alcohol, chemotherapeutics, heavy metals)
❖ Metabolic (nutritional deficiency, endocrinopathies/ Thyroid disease,
Pheochromocytoma, Diabetes/, electrolyte deficiencies/ Ca, Mg,
Phosphate/, obesity, hemochromatosis)
❖ Peripartum cardiomyopathy
❖ A reversible form of DCM may be found with alcohol abuse, pregnancy,
thyroid disease, cocaine use, and chronic uncontrolled tachycardia
❖ Develops within the 3rd trimester or within the first 6 months after delivery
❖ Risk factors
✓ Increased maternal age
✓ Increased parity
✓ Twin pregnancy
✓ Malnutrition
✓ Use of tocolytic therapy for premature labor
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✓ Preeclampsia
Treatment
✓ Abstinence from alcohol
✓ Diuretics and neurohormonal antagonists
INVESTIGATIONS
❖ CXR:
✓ Enlargement of the cardiac silhouette due to LV dilatation
✓ The lung fields may demonstrate pulmonary vascular redistribution
and interstitial or, in advanced cases, alveolar edema
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TREATEMENT OF DCMP
Prognosis of DCMP
2. HYPERTROPHIC CARDIOMYOPATHY(HCMP)
Variants of HCM
8 - 10% 15 - 20%
65 - 70%
PATHOPHYSIOLOGY OF HCM
INVESTIGATION
TREATEMENT OF HCM
❖ Since SCD often occurs during or just after physical exertion, competitive
sports and very strenuous activities should be proscribed
❖ Dehydration should be avoided, and diuretics used with caution in
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congested patients
❖ Beta- blockers drugs and verapamil
✓ decrease HR and increase the length of time for diastolic filling, as
well as to decrease the inotropic state
Amiodarone reduces frequency of arrythmias
❖ Diuretics, nitrates, dihydropyridine calcium blockers, vasodilators, and -
adrenergic agonists are best avoided, particularly in patients with known LV
outflow tract pressure gradients
❖ Alcohol ingestion may produce sufficient vasodilatation to exacerbate an
outflow pressure gradient
❖ Atrial fibrillation is poorly tolerated, and a strong effort should be made to
restore and then maintain sinus rhythm and slow rate
✓ Beta blockers
✓ Amiodarone
✓ Non-dihydropyridine calcium channel blockers
✓ Electrical cardioversion
❖ Surgical myotomy/myectomy and alcohol septal ablation can also reduce
obstruction and improve symptoms
❖ The insertion of an ICD should be considered in patients with a high-risk
profile for SCD
✓ Two or more risk factors for SCD
Causes
❖ Infiltrative disorders
✓ Amyloidosis
✓ Storage disorders
✓ Hemochromatosis
✓ Inherited metabolic defects
➢ Fabry’s disease
➢ Glycogen storage disease
❖ Fibrotic
✓ Radiation
✓ Scleroderma
✓ Endomyocardial
✓ Tropical endomyocardial fibrosis (EMF)
✓ Hyper eosinophilic syndrome (Loffler’s endocarditis)
✓ Carcinoid syndrome
CLINICAL FEATURES
Investigations
Treatment of RCMP
B. Myocarditis
❖ Myocarditis (inflammation of the heart) can result from multiple causes but is
most commonly attributed infective agents that can injure the myocardium
through direct invasion, production of cardiotoxic substances, or chronic
inflammation with or without persistent infection.
❖ Classified as
➢ Infectious and non-infectious myocarditis (The paradigm of noninfective
inflammatory myocarditis is cardiac transplant rejection)
➢ Acute, subacute and chronic myocarditis
❖ Infectious myocarditis has been reported with almost all types of infective
agents but is most commonly associated with viruses and the protozoan
trypanosoma cruzi
❖ Myocarditis is often associated with systemic inflammatory diseases, such as
polymyositis and dermatomyositis, which affect skeletal and cardiac muscle.
o Myopericarditis
o Arrhythmias
Pulmonary or systemic emboli
Investigation
➢ ECG
➢ Echo
➢ Cardiac troponins
➢ Creatine phosphokinase
➢ Cardiac MRI
➢ Endomyocardial biopsy- indications
o Presentation with ventricular tachyarrhythmias
o Suspicion of alternative diagnosis such as sarcoidosis and giant cell
myocarditis
➢ Circulating viral titers between acute and convalescent blood samples
Management
PE=Pulmonary Edema
PE:Pulmonaryedema CS=Cardiogenic
Factors leading to less rapid deterioration shock to rapid deterioration
Factors leading
✓ Non adherence to drugs/diet or under dosage ✓ Tachy/brady arrhythmia
✓ Infections (pneumonia, IE) ✓ Acute Coronary Syndrome (ACS)
✓ Anemia ✓ Acute pulmonary embolism
✓ Thyroid disorders ✓ Hypertensive crisis
✓ Pregnancy ✓ Cardiac tamponade
✓ Renal failure ✓ Aortic dissection
✓ Drugs (BB, CCB, NSAIDS)
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Pathophysiology
❖ Pulmonary edema is due to the movement of excess fluid into the alveoli
as a result of an alteration in one or more of Starling's forces.
❖ In cardiogenic pulmonary edema, a high pulmonary capillary pressure (as
estimated clinically from the pulmonary artery wedge pressure) is
responsible for the abnormal fluid movement. In contrast, noncardiogenic
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than elevated pulmonary capillary pressure are responsible for protein and
fluid accumulation in the alveoli
❖ Cardiogenic pulmonary edema is characterized by increased transudation of
protein-poor fluid into the pulmonary interstitium and alveolar spaces.
❖ The primary etiologic factor is a rapid and acute increase in left ventricular
filling pressures and left atrial pressure, usually associated with a reduction
in cardiac output.
Clinical features
▪ Acute pulmonary edema usually presents with the
o Rapid onset of dyspnea at rest
o Tachypnea
o Tachycardia, and
o Severe hypoxemia (SO2< 90%).
▪ Other features include;
o Cardiorespiratory distress
o High/normal BP
▪ Hypertension is due to release of endogenous
catecholamines.
o Relative dullness
o Decreased air entry
o Fine crepitations (Bilateral basal rales) and wheeze in the lung
▪ Crackles and wheezing due to alveolar flooding and airway
compression from peribronchial cuffing may be audible.
o Raised JVP
o S3 gallop
Diagnosis
➢ Chest X-ray → CXR finding of pulmonary edema
o Vascular redistribution: cephalization of the vessels (Diversion of
Blood vessel circulation towards the Apex)
o Interstitial edema, peribronchial cuffing, and Kerley B and A lines.
▪ Kerley B lines: seen at the peripheral lung; due to
thickened interlobular septa.
▪ Kerley A lines radiate outward from the hila and may
represent dilation of lymphatic channels.
o Alveolar edema
▪ Bilateral perihilar opacifications
▪ Bat wing/butterfly appearance when severe
▪ Pleural effusions and cardiomegaly are often present.
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Picture; A) Kerley B lines (black arrow); Tiny horizontal lines seen at the periphery of the
basal lung area, perpendicular to the pleura…represent fluid in the interlobular septa. B) PA
CXR: typical batwing distribution of air space disease
➢ Echo → may identify systolic and diastolic ventricular dysfunction and valvular
lesions.
➢ ECG → ST elevation and evolving Q waves are usually diagnostic of acute MI
and should prompt immediate institution of MI protocols and coronary artery
revascularization therapy.
➢ BNP → when substantially elevated, support heart failure as the etiology of
acute dyspnea with pulmonary edema.
❖ Physical Methods
o In no hypotensive patients, venous return can be reduced by use
of the sitting position with the legs dangling along the side of the
bed.
❖ Oxygen Therapy
o Early oxygenation and ventilation support are lifesaving
o Generally, the goal is O2 saturation of ≥92%, but very high saturation
(>98%) may be detrimental.
o Oxygen should be given in Sitting position
o If SO2< 90%, administer O2 by nasal canula at 4-6 l/min.
o If SO2 doesn’t improve in 10 min, administer high flow O2(10-12 l/min)
by face mask.
o If SO2 is still low, give ventilator support by CPAP in conscious
cooperative patients or intubate if patient cannot protect his /her
airways and put on MV with low PEEP.
o If SO2 is persistently higher than 90% and cardiorespiratory distress
improves with treatment, revert O2 administration to nasal canula and
progressively decrease O2 flow and discontinue
❖ Administer morphine 2-4 mg IV bolus every 2-4 hr.
❖ Furosemide 40mg IV for naïve (intravenous dose which is equal to their
previous oral dose for those already taking oral furosemide) and double
the dose every 1hr until adequate urine output AND crackles in the chest
start to decrease and maintain the dose of furosemide that gave
adequate response every 4hrs for the first 24 hr and decrease frequency
in subsequent days.
☛ Follow up of response and other management principles are similar to
management of other heart failure syndromes (click here → Management of
heart failure)
For patients not responding adequately to diuretics with systolic BP >110mmHg,
the following vasodilator therapies can be used:
o Sublingual nitroglycerin (0.4 mg × 3 every 5 min) is first-line therapy for
acute cardiogenic pulmonary edema.
o If pulmonary edema persists in the absence of hypotension, sublingual
may be followed by IV nitroglycerin.
o IV nitroglycerine infusion
▪ 10 to 20 µg/minute, with subsequent titration (eg, 10 to 20
µg/minute every 5 to 15 minutes) up to 200 µg/minute or
▪ 0.3 to 0.5 µg/kg/minute with titration (if SBP ≥90 mm Hg) in
increments of 20 µg/minute every 1 to 3 minutes up to 400
µg/minute.
▪ Patients who do not respond hemodynamically with doses of
~200 µg/minute should be considered non-responders
o If nitroglycerine not available, either of the following can be tried.
✓ Isosorbide dinitrate 10mg, PO, TID (8AM, 1PM and 6PM) escalated
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to 40mg PO TID or
✓ Captopril 6.25mg to 12.5 mg, PO, TID (target dose; 50mg TID) or
✓ enalapril 2.5 mg, PO, BID, titrated every 6hrs as tolerated to target
dose of 10 mg, PO, BID (maximum: 20 mg/day).
✓ Notice; ACE inhibitors reduce both afterload and preload and are
recommended for hypertensive patients.
More than 60 possible causes of ARDS have been identified and other potential
causes continue to emerge as adverse pulmonary reactions to new therapies are
observed
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CLINICAL FEATURES
Investigations
➢ Sepsis work up based on septic focus → CBC, ESR and CRP, U/A, S/E,
Culture, CXR
➢ CXR → The initial chest radiograph typically has bilateral alveolar infiltrates
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Diffuse alveolar damage (DAD) is the most common pathologic finding seen in
patients with ARDS.
1. “acute/exudative phase → Common findings during the first week include
eosinophilic hyaline membranes, intra-alveolar edema, congestion of the
capillaries, widening of the interstitium, and extensive thrombi caused by
localized coagulation abnormalities
2. Proliferative phase → Later findings include expansion of the interstitium
with loose, myxoid fibroblastic tissue, type 2 pneumocyte hyperplasia,
squamous metaplasia, thrombi, and vascular remodeling. Some patients
progress to a fibrotic stage, characterized by obliteration of normal lung
architecture, diffuse fibrosis, and cyst formation.
DIAGNOSTIC EVALUATION
with respect to which conditions should or should not be included under the
ARDS diagnostic umbrella.
➢ Generally included are disorders that are known to cause diffuse alveolar
damage and have the potential to resolve over time.
➢ Thus, viral or diffuse bacterial pneumonia and acute inhalational injuries are
included, whereas eosinophilic pneumonia and diffuse alveolar hemorrhage
associated with collagen vascular diseases are not.
➢ R/o Cardiogenic pulmonary edema
o It is the primary alternative that needs to be excluded because it is
common and can be clinically indistinguishable from ARDS.
o See clinical features from the table above (Distinguishing features of
Cardiogenic from Noncardiogenic Pulmonary Edema) → Absence of these
features helps distinguish ARDS from cardiogenic pulmonary edema
o Distinguishing cardiogenic pulmonary edema from ARDS can be aided by
measurement of a brain natriuretic peptide (BNP) level, echocardiography,
and, less often, right heart catheterization.
➢ Excluding other causes of hypoxemic respiratory failure
DIFFERENTIAL DIAGNOSIS
Management
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Figure; Algorithm for the initial management of ARDS. Clinical trials have provided
evidence-based therapeutic goals for a stepwise approach to the early mechanical
ventilation, oxygenation, and correction of acidosis and diuresis of critically ill patients with
ARDS.
FiO2, inspired O2 percentage; MAP, mean arterial pressure; PBW, predicted body weight;
RR, respiratory rate; SPO2, arterial oxyhemoglobin saturation measured by pulse oximetry.
Complications
➢ N.B the approach (Hx, P/E, IX, DDX…) we discussed here is considering Cor
pulmonale 2ry to COPD. If you have a patient with different diagnosis (e.g.
COPD only, Cor pulmonale 2ry to Post TB fibrosis…), you can modify this
approach.
Cor pulmonale
➢ The symptoms in chronic Cor pulmonale generally are related to the underlying
pulmonary disorder.
➢ In our set up, Cor pulmonale patients usually have longstanding COPD or TB
(e.g. Post TB fibrosis…) then they develop Cor pulmonale (isolated RSHF) smx
➢ They may present with
o Dyspnea or Exacerbation of SOB → the most common symptom
o Lower-extremity edema and even increased abdominal girth due to
ascites, even may progress to GBS (Generalized body swelling)
For example
➢ SOB Of 2 years duration associated with productive cough with sputum
production. The Patient diagnosed to have TB, Treated and improved. Currently
presented with exacerbation of SOB of two weeks duration and GBS of one-
week duration (characterize GBS in detail) but no orthopnea, PND or
palpitation (absence of these symptoms suggests isolated RSHF) (refer CHF of
Nitsibn for GBS characterization)
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Chapter 2; Cor pulmonale and Chronic lung disorders
➢ Wheezing
➢ Chest tightness (squeezing chest pain or chest discomfort which
exacerbated by exertion but no radiation)
➢ Recurrent respiratory infections (cough, runny nose, sore throat, fever…) →
risk factor for exacerbation
➢ GBS if they develop Cor pulmonale.
Exposure
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Chapter 2; Cor pulmonale and Chronic lung disorders
Host Factors
Complication of COPD
Sample history
Sample history of a patient from sanja woreda with the DX of cor pulmonale 2ry to
COPD
Chief compliant
Exacerbation of SOB of 01-week duration
HPI
For the past 20 years, this patient had a progressively increasing intermittent productive
cough with non-foul-smelling, non-blood tinged, sputum of 3-4 Arabic coffee cup per day
which later became increased up-to 10 Arabic coffee cup/day which is aggravated by
dust and increase in intensity and frequency at night.
Four years back she was having insidious onset of progressively increasing shortness of
breath. For this she visited sanja primary hospital where she was admitted and told to
have lung disease (unspecified) after CXR and blood examination was done and she
was on intra nasal oxygen and discharged after 2 weeks of hospital stay. For the same
compliant she had a total of 4 admissions.
Two weeks prior to her admission, she started to experience generalized body swelling
which starts from foot and goes upwards to involve the leg, abdomen and finally the face
associated with stabbing type of RUQ abdominal pain, loss of appetite and Unquantified
but significant weight loss to the extent her closes become loose but no Orthopnea,
PND, chest pain or palpitation.
Currently presented with exacerbation of shortness of breath while doing supra ordinary
activities like fetching water from long distance which later worsen to the extent of
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➢ She cooks 3x/day in muddy kitchen which has no windows. And she has dust
exposure throughout her life while cleaning the house and excreta of cattle’s.
She is and lives in a family size of 6. all are alive and healthy, they live in
iron corrugated house having 2 rooms, one windows and one door (all are
functional.), they have separate kitchen and toilet room (indoor air pollution)
➢ Her husband is a farmer, she is house wife, Claimed that, their income is
enough to support the family/if possible, quantify/ (socioeconomic status is RF,
to assess Work place dust exposure, such as factory workers, coal mining,
cotton textile industry)
➢ She experienced cough, rhinorrhea, fever and sore throat repeatedly where she
was treated at a local health center multiple times. (URTI are RF for
exacerbation of COPD or may happen as a complication of COPD)
➢ No hx of cigarette smoking or hemoptysis (smoking is RF for both COPD,
Emphysema and Lung ca → the last is DDX or CXN)
➢ No family hx of similar illness (genetic→ AAT deficiency)
➢ He/she usually eats injera made of ‘‘teff’’ and ‘‘machilla’’ and ‘’wott’’ made of
‘‘atter’’ and ‘‘dagusa’’ 3-4 times per day. Occasionally he/she eats meat during
holidays (nutrition)
➢ No hx of contact with a known TB patient or previous TB treatment (post TB
fibrosis as DDX)
➢ No self or family hx of DM, HTN or Asthma (RF and DDX)
➢ Screened for RVI 6 months back and found to be NR (RF)
➢ No hx of bone pain, herbicide exposure, epistaxis or bleeding from other body
sites (mediastinal lymphoma → DDX)
➢ No hx of drug intake other than those mentioned above (drugs as a cause of
cough e.g. amiodarone, methotrexate, hydralazine, ACE-I)
Finally, S/he was admitted to our hospital supported physically by his families
1. GA
Respiratory distress signs (e.g. use of accessory muscle of Respiration)
“tripod” position
Picture; “tripod position”; child is sitting up and leaning forward on outstretched hands, to
facilitate the actions of the sternocleidomastoid, scalene, and intercostal muscles which helps to
decrease respiratory distress (RD). This is a patient with epiglottitis who developed RD, we put here to have
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Knowhow of tripod position
Picture; Left) ‘’Tripod position’’ in patient with emphysema, Right) Patient with Chronic bronchitis
sitting comfortably. But this is not necessarily the Stereotype (the opposite form may be seen).
Low BMI, with significant weight loss → Due to inadequate oral intake
Previously the consideration was; Pink puffers (emphysema) tilt forward, blue
bloaters (chronic bronchitis) sit comfortably
o Nowadays, classifying patients as Pink puffers and blue bloaters is
obsolete, because most patients have features of both chronic
bronchitis and emphysema
2. Vital signs
✓ Febrile → if there is acute respiratory infection
✓ Desaturated patient (decreased O2 saturation)
3. HEENT
✓ Plethora (injected and hyperemic conjunctiva) → 2ry to polycythemia
✓ Anemia features → pale conjunctiva
✓ Central cyanosis
4. LGS
5. RS
✓ Inspection
Use of accessory muscles of respiration → predominantly in emphysema
Pursing of lips → close lips tightly during expiration (in emphysema)
Reduced tracheal length above the sternal notch
Tracheal tug → trachea descend during inspiration
Subcostal and intercostal retraction
Jugular vein distension during expiration
Barrel shaped chest → AP diameter of chest > lateral diameter due to
hyperinflation → cmn in emphysema
Central cyanosis → predominantly in chronic bronchitis
Hoover’s sign +ve → paradoxical inward movement of ribcage with
inspiration
✓ Palpation
Decreased chest expansion bilaterally → like restrictive lung disease
Tracheal tug
✓ Percussion
hyper resonant → cmn in emphysema
loss of cardiac and liver dullness → flattening of diaphragm
poor diaphragmatic excursion → enlarged liver volume
✓ auscultation
decreased Air entry bilaterally
vesicular breath sound with prolonged expiration
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➢ Central cyanosis
➢ Flapping tremor
➢ Bounding pulse
➢ CHF features (raised JVP, right ventricular heave, loud P2, hepatomegaly,
pedal edema)
6. CVS
✓ Distended neck vein from RSHF → N.B. Neck vein distension, liver
enlargement and peripheral oedema could be due to cor pulmonale or due
to severe hyperinflation.
✓ Parasternal heave from RV hypertrophy in pulmonary HTN
✓ Split of S2 which suggests corpulmonale
✓ Murmur of TR and PR
✓ Distant heart sound
7. Abdominal examination
✓ Easily palpable liver due to severe hyperinflation or due to congestion from
RSHF.
In the case of RSHF it is tender hepatomegaly. In severe
hyperinflation, liver may palpable due to pushing down effect from
diaphragm but, it doesn’t mean hepatomegaly. SO, Hepatomegaly
is after measuring TVLS.
8 GUS
9 MSS
✓ cyanosis
11 NS
➢ The most blatant findings are reflective of high right-sided filling pressures and
hypervolemia such as
Elevated JVP
Hepatomegaly
Pulsatile liver
Ascites, and especially lower-extremity edema.
➢ Cyanosis is a late finding in cor pulmonale
Signs of COPD can be summarized as the follows (Source → Harrison 20th edition)
➢ In the early stages of COPD, patients usually have an entirely normal physical
examination.
➢ Current smokers may have signs of active smoking, including;
An odor of smoke or
Nicotine staining of fingernails.
➢ Expiratory wheezing → In patients with more severe disease
➢ A barrel chest and enlarged lung volumes with poor diaphragmatic excursion
→ signs of hyperinflation
➢ Patients with severe airflow obstruction may also exhibit;
Use of accessory muscles of respiration
Sitting in the characteristic “tripod” position → to facilitate the actions of
the sternocleidomastoid, scalene, and intercostal muscles.
➢ Cyanosis, visible in the lips and nail beds.
➢ Cachexia, with significant weight loss, bitemporal wasting, and diffuse loss of
subcutaneous adipose tissue → may happen in Advanced disease
Associated with both inadequate oral intake and elevated levels of
inflammatory cytokines (TNF-α).
An independent poor prognostic factor in COPD.
➢ Hoover’s sign (Paradoxical inward movement of the rib cage with inspiration)
Seen In advanced disease
The result of alteration of the vector of diaphragmatic contraction on the
rib cage as a result of chronic hyperinflation.
➢ Signs of overt right heart failure, termed Cor pulmonale, are relatively
infrequent since the advent of supplemental oxygen therapy.
➢ Clubbing of the digits is not a sign of COPD
Its presence should alert the clinician to initiate an investigation for
causes of clubbing (the development of lung cancer is the most likely
explanation for newly developed clubbing).
➢ Although traditional teaching is that patients with predominant
emphysema, termed “pink puffers,” are thin and noncyanotic at rest
and have prominent use of accessory muscles, and patients with
chronic bronchitis are more likely to be heavy and cyanotic (“blue
bloaters”), current evidence demonstrates that most patients have elements of
both chronic bronchitis and emphysema and that the physical examination does
not reliably differentiate the two entities.
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DDX
1) COPD
Onset in mid-life; onset in early adulthood should prompt suspicion
for alpha-1 antitrypsin deficiency
Symptoms slowly progressive
Long smoking history, although can occur in nonsmokers
Dyspnea during exercise
Largely irreversible airflow limitation
2) Asthma
i.e. Severe and severe persistent form of asthma are DDX for COPD
It may be one of the variants of COPD
seasonal and there may be triggering agents
Symptoms vary from day to day, more at night/early morning
wheezing is predominant
Onset early in life (common in childhood, peak at 3 years)
Allergy, rhinitis, and/or eczema also present
+ve Family history of asthma
Largely reversible airflow limitation
3) Bronchiectasis
Cough and large volume of mucopurulent, tenacious, position dependent,
sputum last for months to years
There may be hemoptysis
Commonly associated with recurrent or persistent bacterial infection
Coarse crackles on auscultation, clubbing of digits
Chest radiograph/HRCT shows bronchial dilation, bronchial wall thickening
‘’Trump truck sign’’ and ‘’signet ring sign’’ in high resolution CT (HRCT)
→ continuous non tapering airway with bronchial dilatation and bronchial
wall thickening
▪ N.B HRCT is gold standard Ix for bronchiectasis
Obstructive spirometry finding
Bronchiectasis is 2ry to
▪ Acquired → TB (Post TB fibrosis is the commonest cause in our
setup), pneumonia, obstruction of the bronchial tree
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➢ CHF
➢ Constrictive pericarditis
➢ RCMP (Restrictive cardiomyopathy)
➢ Right ventricular infarction
➢ Atrial myxoma
➢ VSD (Ventricular septal defect)
Table; Aetiology of Chronic Cor Pulmonale (i.e Cor pulmonale 2ry to;)
ILD
Pt’s present with prolonged unexplained SOB, dry cough
Classified as
▪ Known/idiopathic
▪ Acute/subacute/chronic
▪ Granulomatous/inflammatory
There are so many disorders (>200) which classified under ILD because they have similar
C/F, radiologic feature and mgt. such as;
▪ Idiopathic interstitial pneumonias (idiopathic pulmonary fibrosis/IPF/)
o IPF is the commonest form of ILD
▪ Secondary interstitial diseases
▪ Sarcoidosis
Combined pulmonary fibrosis and emphysema
Others including Developmental lung disorders (e.g. Bronchopulmonary dysplasia in infants)
2. Disorders of Chronic (Alveolar) Hypoxia
Chest wall disorders
Kyphoscoliosis
Chronic exposure to high altitude
Neuromuscular respiratory failure
Alveolar hypoventilation syndromes
Central hypoventilation syndrome
3. Diseases of the Pulmonary Vasculature
Pulmonary arterial hypertension (PAH)
Chronic thromboembolic pulmonary hypertension (e.g. Massive PTE in acute cases or Chronic
PTE)
Mediastinal disorders affecting central pulmonary vasculature
Pulmonary tumour thrombotic microangiopathy
IX
Baseline IX
1) CXR
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image 1 image 2
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image 3 image 4
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How can we differentiate obstructive lung disease (e.g. COPD, Asthma) from
Restrictive lung disease (e.g. ILD) based on spirometry?
✓ In obstructive lung disease, FEV1 decreased but FVC is normal so
FEV1/FVC ratio decreased. In restrictive lung disease, FEV1 and
FVC decreased simultaneously so the FEV1/FVC ratio is normal.
Discussion
Pathophysiology
Treatment
Clinical features
➢ WHO classifies patients with PH into five groups based upon etiology. 176
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Group I → There are no effective primary therapies for most types of group I
PAH. As a result, advanced therapy is often needed
Without treatment PAH is invariably fatal.
While there is no cure for PAH, current pharmacologic therapies improve
morbidity, and in some cases, mortality.
Management options include;
▪ Prostacyclin and prostacyclin analogues and agonists
▪ NO (Nitric oxide) pathway enhancers
▪ Endothelin receptor antagonists (ERAs) and
▪ Combination of those agents
Group II → treatment of the underlying heart disease
Group III → treatment of the underlying cause of hypoxemia and correction of
the hypoxemia with supplemental oxygen.
Oxygen is the only modality with proven mortality benefit in some patients
with group III PH
Group IV → Anticoagulation is primary medical therapy for patients with group
IV PH
Surgical thromboendarterectomy is primary surgical therapy for selected
patients with thromboembolic obstruction of the proximal pulmonary
arteries
Group V → treatment of the underlying cause
➢ GOLD8 (Global Initiative for Chronic Obstructive Lung Disease), defines COPD
as:
"COPD is a common, preventable, and treatable disease that is characterized by persistent
respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities
usually caused by significant exposure to noxious particles or gases.’’
COPD includes;
Emphysema → an anatomically defined condition characterized by
destruction of the lung alveoli with air space enlargement
Chronic bronchitis → a clinically defined condition with chronic cough and
phlegm; and
Small airway disease → a condition in which small bronchioles are
narrowed and reduced in number.
Emphysema, chronic bronchitis, and small airway disease are present in
varying degrees in different COPD patients.
Patients with a history of cigarette smoking without chronic airflow obstruction
may have chronic bronchitis, emphysema, and dyspnea. Although these
patients are not included within the classic definition of COPD, they may have
similar disease processes.
The chronic airflow limitation that characterizes COPD is caused by a mixture
of small airways disease (e.g. obstructive bronchiolitis) and parenchymal
destruction (emphysema), the relative contributions of which vary from person
to person.
It is a chronic disease that is showing progressive upward trend in both
mortality and morbidity
COPD is the 3rd leading cause of death in the United States. And also,
almost 90% of COPD deaths occur in low- and middle-income countries, where
effective strategies for prevention and control are not always implemented or
accessible.
Different guidelines use other forms of terminology for COPD (chronic
obstructive pulmonary disease). All of them are the same entities, these are;
COLD (chronic obstructive lung disease)
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2021, GOLD, COPD diagnosis, management and prevention guideline; Free PDF File
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* For details of asthma, refer respiratory section from short case on Nitsbin (click here → Asthma (አስም) )
Chronic bronchitis
Emphysema:
Chronic obstructive asthma (Chronic asthma with airway remodeling and fixed
obstruction).
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Emphysema classification
Pathophysiology
Irreversible
➢ Fibrosis and narrowing of the airways
➢ Loss of elastic recoil due to alveolar destruction
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Reversible
➢ Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi
➢ Smooth muscle contraction in peripheral and central airways
➢ Dynamic hyperinflation during exercise
Natural history
Diagnosis of COPD
Presumptive Diagnosis
For details of Clinical features and Investigation → look at the approach part
above
Symptom severity is assessed using the CAT score or mMRC grade (CAT =
COPD Assessment Tool, mMRC = Modified Medical Research Council)
Lung function, in addition to the number of exacerbations and hospitalizations
for exacerbations in the previous 12 months, can be used to predict future
risk.
A history of 0 or 1 exacerbation in the past 12 months and GOLD I or II
spirometry level suggests a low future risk of exacerbations
≥ 2 exacerbations or a hospitalized exacerbation or GOLD III or IV
spirometry level suggest a high future risk.
These components are combined into four groups as shown the table:
*mMRC: modified Medical Research Council dyspnea scale → Provides a single number for
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➢ An 8-item COPD health status measure with Likert scale responses for questions about
cough, phlegm, chest tightness, dyspnea on one flight of stairs, limitation in home
activities, confidence in leaving the home, sleep and energy.
➢ Range of total score is 0 - 40.
C. Oxygen therapy:
➢ Indications for continuous long-term oxygen therapy (LTOT) for patients with
COPD → i.e. indication for home oxygen
Saturation of oxygen (SaO2) ≤ 88 % or PaO2 ≤ 55 mmHg (7.32 kPa)
confirmed twice over 3 weeks period
In the presence of Cor pulmonale; one of the following
▪ SaO2 ≤ 89 % or PaO2 ≤ 59 mmHg (7.85 kPa)
▪ Evidence of pulmonary hypertension (ECG evidence of P pulmonale)
▪ Polycythemia (Hematocrit > 55 %) or
▪ Clinical evidence of right heart failure (peripheral edema suggesting
CHF)
Specific situations
▪ SaO2 ≥ 90 % or PaO2 ≥60 mmHg (7.98 kPa) with lung disease and
other clinical needs such as sleep apnea with nocturnal desaturation
not corrected by CPAP.
▪ If the patient meets criteria at rest, O2 should also be prescribed
during sleep and exercise, and appropriately titrated.
▪ If the patient is normoxemic at rest but desaturates during exercise
(PaO2 ≤55 mmHg [7.32 kPa]), O2 is generally prescribed for use
during exercise. For patients who desaturate (PaO2 ≤55 mmHg [7.32
kPa]) during sleep, further evaluation with polysomnography may be
indicated to assess for sleep-disordered breathing.
N.B.
The Only three interventions have been demonstrated to improve survival of
patients with COPD are;
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☛ Smoking cessation
☛ Oxygen therapy in chronically hypoxemic patients, and
☛ Lung volume reduction surgery (LVRS) in selected patients with
emphysema.
Oxygen is a drug that should be given with correct dosing and based on
indication
Order example; ‘’put on Intranasal oxygen at a rate of 2 L/minute''
Relation between oxygen flow rate and the fraction of inspired oxygen(FiO2)
100%
90%
90% 86%
82%
78%
80% 74%
70%
70% 64% 66%
60%
60% 56%
52%
48%
50% 44%
40%
40% 36%
32%
28%
30% 24%
20%
10%
0%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Chart; Relation between oxygen flow rate in L/min (X-axis) and the fraction of inspired oxygen
(FiO2)/y-axis/. Each additional L/min in oxygen flow increases the FiO2 by about 4 % (i.e. 24%,
28%, 32%... the difference in between is 4%). For example, if you put the patient in 2L/min, S/he
will get 28% additional oxygen from the baseline SaO2(On the other way, if the initial SaO2 is 62
%, in order to make 90%, this patient will require additional 28 % oxygen which is 2L/min). If ≥
10L/min is required, use face mask instead of Intra nasal cannula.
D. Pulmonary rehabilitation:
E. Pharmacologic therapies;
These are used to reduced symptoms, reduce the frequency and severity of
exacerbations, and improve exercise tolerance and health status.
But, none of the existing medications for COPD has been shown to modify the
long-term decline in lung function that is the hallmark of this disease.
Therefore, pharmacotherapy for COPD is used to decrease symptoms and/or
complications.
Pharmacologic therapy options for COPD include;
Bronchodilators
Steroids (ICS or OCS) 188
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C. Combined ICS and bronchodilators → The FDC of an ICS and a LABA (e.g.
fluticasone with salmeterol, budesonide with formoterol)
Because there is no loose preparation of LABAs in the market, we
generally tend to use combination of LABA/ICS.
This combination improves lung function, reduces the frequency and
severity of exacerbations and improves quality of life especially in patients
with moderate to very severe COPD and exacerbations. These
advantages may be accompanied by an increased risk of pneumonia,
particularly in the elderly.
Use this combination especially when there is;
▪ History of hospitalization for exacerbation
▪ ≥ 2 exacerbations per year
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FIGURE 286-6 (Harrison 20th edition); Medication therapy for stable COPD. Recommended
pharmacologic treatment of stable COPD is based on respiratory symptoms and exacerbation
frequency.
➢ Lung Transplantation
COPD is currently the second leading indication for lung transplantation.
candidates for lung transplantation should have;
▪ very severe airflow limitation
▪ severe disability despite maximal medical therapy, and
▪ be free of significant comorbid conditions such as liver, renal, or
cardiac disease.
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Precipitating Causes
Patient Approach
DDX for COPD exacerbations → see Approach part of this chapter above
Investigation
Chest x-ray or chest CT scan.
▪ For patients with severe underlying COPD, who are in moderate
or severe distress, or those with focal findings
▪ Approximately 25% of x-rays in this clinical situation will be
abnormal, with the most frequent findings being pneumonia and
CHF.
Arterial blood-gas analysis
▪ For patients with advanced COPD, a history of hypercarbia, mental
status changes (confusion, sleepiness), or those in significant
distress.
▪ The presence of hypercarbia, defined as a PCO2 >45 mmHg, has
important implications for treatment (discussed below).
Pulmonary function test is not recommended
Most COPD patients in our country are undiagnosed, a few of them are told
they have ‘’bronchitis’’ without confirmatory spirometry and still fewer have
confirmed COPD.
Therefore, as discussed in patient approach part, COPD with acute
exacerbation should be considered in every patient presenting with a
recent worsening of his/her longstanding cough or dyspnea or sputum
color change (purulence).
Pharmacologic management
? Mucolytic Agents: a few patients with viscous sputum may benefit but
the widespread use cannot be recommended
? Antitussives: Cough, a troublesome symptom in COPD, has a protective
role. Regular use of antitussives contraindicated
1. Oxygen therapy
☛ Deliver a flow rate of <15L/min.
☛ Source of oxygen can be a cylinder (>99% pure oxygen) or oxygen
concentrator (90% oxygen,10% nitrogen).
☛ Titrated to achieve a SaO2 of 88-90% to avoid oxygen induced
hypercapnia.
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3. Corticosteroids
☛ Only used when having a significant exacerbation (moderate or severe
disease), as they may lead to development of pneumonia and sepsis
☛ Can be given orally (prednisolone 40mg) or IV (hydrocortisone or
methylprednisolone). Oral and IV routes are equally effective
☛ Recommended for 5-7 days only
4. Antibiotics
☛ Recommended for moderate to severe illness or when the sputum is
purulent.
☛ Patients experiencing COPD exacerbations with clinical signs of airway
infection (e.g., increased volume and change of color of sputum, and/or
fever) may benefit from antibiotic treatment.
☛ Antibiotics are usually given for 5-7days
☛ The specific antibiotic given should depend on the sensitivity pattern of
the hospital.
o Commonly Augmentin (Amoxicillin/clavulanic acid), cephalosporins,
quinolones or macrolides can be used.
☛ Sputum culture is generally not helpful except in few conditions which
may be associated with Gram negative infections like pseudomonas
aeruginosa. Such as
o Patient has recurrent exacerbation.
o Patient is on invasive mechanical ventilation.
2.2.2 Asthma
→ Refer under short case of Nitsbin (click here → Asthma (አስም))
Here, we will discuss about Bronchiectasis and lung abscess. For Empyema,
refer respiratory section from short case of Nitsbin (click here → Empyema and
Complicated Parapneumonic Effusions)
2.3.1 Bronchiectasis
Etiology
✓ Acquired (~74%)
▪ Infectious → A variety of infections can cause bronchiectasis by
destroying and damaging the bronchial walls and interfering with
ciliary action.
o Influenza, Adenovirus, Pertussis, Mycobacterium (M. TB, MAC)
o Post TB fibrosis is the commonest cause in Ethiopia
o Recurrent infections (airway obstruction, immunodeficiency,
allergic bronchopulmonary aspergillosis, mycobacterium)
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✓ Congenital:
▪ Cystic fibrosis, Primary ciliary dyskinesia (e.g., Kartagener
syndrome), Immunoglobulin deficiency (IgG, IgA...)
o Cystic fibrosis (CF) is the most common cause of
bronchiectasis (accounts for half of all cases) world wide
o Have diffuse pattern commonly occur in upper lobes.
➢ In many cases (25 - 50%), the etiology of bronchiectasis is not determined
(idiopathic).
Pathophysiology
Clinical Presentation:
Most cases, onset is in childhood but, symptoms generally appear in 2nd - 3rd
Decades
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B. CXR
Although chest radiographs lack sensitivity, the presence of “tram tracks”
indicating dilated airways is consistent with bronchiectasis.
CXR is abnormal in most cases, but findings are nonspecific. Suspicious,
but non diagnostic radiographic findings include linear atelectasis, dilated
and thickened airways and irregular peripheral opacities that may
represent mucopurulent plugs.
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Management of Bronchiectasis
2) Surgical management
Aspiration → The major risk factor for primary lung abscesses. Patients at
particular risk for aspiration include;
o Those with altered mental status
o Prior cerebrovascular or cardiovascular events
o Seizures
o Esophageal dysmotility or esophageal lesions (strictures or tumors)
o Gastric distention and/or GERD, especially those who spend substantial
time in the recumbent position
o Alcoholism
o Drug overdose
o Bulbar dysfunction
o Neuromuscular disease.
Clinical features
− Clinical manifestations may initially be similar to those of pneumonia, with
fevers, cough, sputum production, and chest pain
− Copious putrid or malodorous sputum is typical for anaerobic infection and
common in lung abscess.
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Differential diagnosis
1. CXR
➢ a thick-walled cavity with an air-fluid level
➢ pulmonary infiltrates with cavity confirm diagnosis in majority of patients.
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Image 1, Lung abscess; PA (A) and lateral (B) CXR show areas of consolidation and several air-fluid levels
within the right lower lobe. Less extensive consolidation is evident in the right middle lobe.
2. CT scan
➢ CT permits better anatomic definition than CXR and may provide earlier
evidence of cavitation.
➢ CT may also yield additional information regarding a possible underlying
cause of lung abscess, such as malignancy
➢ May help to distinguish a peripheral lung abscess from a pleural infection.
o This distinction has important implications for treatment because a
pleural space infection, such as an empyema, may require urgent
drainage.
➢ But in our setup CT is too costly for most patients and it is better to
diagnose clinically and with CXR findings
Image 2, Lung abscess; CT image of the above pt confirms the CXR findings and also demonstrates a few
centrilobular nodules in the right middle lobe (black arrow). The patient was a 50-year-old man with
pneumonia due to anaerobic organisms.
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Figure; Representative chest CT scans demonstrating development of lung abscesses. This patient was
immunocompromised by underlying lymphoma and developed severe Pseudomonas aeruginosa pneumonia, as
represented by a left lung infiltrate with concern for central regions of necrosis (panel A, black arrow). Two
weeks later, areas of cavitation with air-fluid levels were visible in this region and were consistent with the
development of lung abscesses (panel B, white arrow).
First line
Second line → duration for 4-8 weeks or longer until the abscess radiologically
resolves
➢ After treatment with intravenous antibiotics for the first 2-3 weeks or
until significant resolution of symptoms, patients can be treated with oral
antibiotics until the end of treatment.
➢ Augmentin (Amoxicillin + clavulanic acid), 625mg P.O TID is the preferred
agent.
➢ Clindamycin, 300mg P.O, QID9 is an alternative otherwise the choice may
be guided by the susceptibility data available.
Follow up
Surgical management
Indication;
Patients who do not respond to antibiotics and whose additional diagnostic
studies fail to identify an additional pathogen that can be treated
Treatment Options include;
Surgical resection and
Percutaneous drainage of the abscess → especially when the patient is a poor
surgical candidate.
9
This dose if from Harrison 20 th edition. 2021 national STG guideline for General hospitals of Ethiopia
recommend ‘’Clindamycin 600mg, PO, TID’’
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Prognosis
Mortality rates for secondary abscesses are generally higher—as high as 75%,
while rates for primary abscesses have been as low as 2%
Other poor prognostic factors include;
o Age of > 60 years
o The presence of aerobic bacteria
o Sepsis at presentation
o Symptom duration of >8 weeks, and
o Abscess size of >6 cm.
Prevention
PATHOGENESIS
➢ The ILDs are nonmalignant disorders and are not caused by identified
infectious agents.
➢ The precise pathway(s) leading from injury to fibrosis is not known.
Although there are multiple initiating agent(s) of injury, the
immunopathogenic responses of lung tissue are limited, and the
mechanisms of repair have common features.
➢ the two major histopathologic patterns are a granulomatous pattern and a
pattern in which inflammation and fibrosis predominate;
➢ Granulomatous Lung Disease
o This process is characterized by an accumulation of T lymphocytes,
macrophages, and epithelioid cells organized into discrete structures
(granulomas) in the lung parenchyma.
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the lung may overwhelm even intact reparative mechanisms and lead to
pulmonary fibrosis.
CLINICAL PRESENTATION
Duration of Illness;
➢ Acute presentation (days to weeks)
o although unusual, occurs with allergy (drugs, fungi, helminths), acute
interstitial pneumonia (AIP), eosinophilic pneumonia, and
hypersensitivity pneumonitis. These conditions may be confused with
atypical pneumonias because of diffuse alveolar opacities on chest x-
ray.
➢ Subacute presentation (weeks to months)
o may occur in all ILDs but is seen especially in sarcoidosis, drug-
induced ILDs, the alveolar hemorrhage syndromes, cryptogenic
organizing pneumonia (COP), and the acute immunologic pneumonia
that complicates systemic lupus erythematosus (SLE) or polymyositis.
➢ chronic presentation (months to years).
o In most ILDs, the symptoms and signs form a chronic presentation
o Examples include IPF, sarcoidosis, pulmonary Langerhans cell
histiocytosis (PLCH), pneumoconiosis, and CTDs.
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Age
➢ Most patients with sarcoidosis, ILD associated with CTD,
lymphangioleiomyomatosis (LAM), PLCH, and inherited forms of ILD (familial
IPF, Gaucher disease, Hermansky-Pudlak syndrome) present between the
ages of 20 and 40 years.
➢ Most patients with IPF are older than 60 years
Smoking History
➢ 2/3rd to 75% of patients with IPF and familial lung fibrosis have a history of
smoking.
➢ Patients with PLCH, respiratory bronchiolitis/desquamative interstitial
pneumonia (DIP), Goodpasture syndrome, respiratory bronchiolitis, and
pulmonary alveolar proteinosis are usually current or former smokers.
Symptoms
➢ Patients with ILD can present with a number of symptoms, and it is
important to ascertain the duration, severity, and progression of symptoms.
➢ Most of the symptoms are nonspecific, but some will help to narrow the
differential. In particular, patients should be asked about extrapulmonary
symptoms that might suggest a systemic disorder.
➢ Dyspnea
o Dyspnea is a common complaint of patients with cardiac or pulmonary
disease.
o In most instances, the patient has attributed the insidious onset of
breathlessness with exertion to aging, deconditioning, obesity, or a
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DIAGNOSIS
➢ LABORATORY TESTS
o The routine laboratory evaluation of suspected ILD typically includes
▪ LFT
▪ RFT
▪ CBC With differentials → to check for evidence of anemia,
polycythemia, leukocytosis, or eosinophilia
▪ Urinalysis.
o LDH → A raised LDH level is a nonspecific finding common to ILDs.
o Antinuclear antibodies and anti-immunoglobulin antibodies (rheumatoid
factors) → are identified in some patients, even in the absence of a
defined CTD.
o serum level of ACE → commonly Elevated in ILDs, especially
sarcoidosis.
o Serum precipitins confirm exposure when hypersensitivity pneumonitis
is suspected, although they are not diagnostic of the process.
o Antineutrophil cytoplasmic or anti-basement membrane antibodies are
useful if vasculitis is suspected.
IMAGING
➢ Chest radiography
o The most common radiographic abnormality on routine chest
radiograph is a reticular pattern; however, nodular or mixed patterns
(alveolar filling and increased interstitial markings) are not unusual.
o Subgroups of ILDs exhibit nodular opacities with a predilection for the
upper lung zones (sarcoidosis, PLCH, chronic hypersensitivity
pneumonitis, silicosis, berylliosis, RA [necrobiotic nodular form],
ankylosing spondylitis).
o Although the chest radiograph is useful in suggesting the presence of
interstitial lung disease (ILD), the correlation between the radiographic
pattern and the stage of disease (clinical or histopathologic) is
generally poor.
o Only the radiographic finding of honeycombing (small cystic spaces)
correlates with pathologic findings and, when present, portends a poor
prognosis.
o The chest radiograph is normal in as many as 10 percent of patients
with some forms of ILD, particularly those with hypersensitivity
pneumonitis.
➢ HRCT
o Should be obtained in almost all patients with diffuse pulmonary
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o
the decreased TLC.
The FEV1/FVC ratio is usually normal or increased.
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➢ When the results of the above evaluation do not allow the clinician to make
a confident diagnosis of a given type or stage of interstitial lung disease
(ILD), lung biopsy with multidisciplinary interpretation of the results may be
necessary.
➢ Indications
o atypical or progressive symptoms and signs (fever, weight loss,
hemoptysis, signs of vasculitis)
o atypical radiographic features
o unexplained extrapulmonary manifestations
o rapid clinical deterioration, or
o sudden change in radiographic appearance.
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Treatment of ILD
➢ Although the course of ILD is variable, progression is common and often
insidious. All treatable possibilities should be carefully considered.
➢ Because therapy does not reverse fibrosis, the major goals of treatment are
o permanent removal of the offending agent, when known, and
o early identification and aggressive suppression of the acute and
chronic inflammatory process, thereby reducing further lung damage.
➢ Hypoxemia (PaO2<55 mmHg) at rest and/or with exercise should be
managed with supplemental oxygen.
➢ Management of cor pulmonale may be required as the disease progresses.
➢ Pulmonary rehabilitation has been shown to improve the quality of life in
patients with ILD.
DRUG THERAPY
➢ Glucocorticoids
o They are the mainstay of therapy for suppression of the inflammation
present in ILD, but the success rate is low.
o there is no direct evidence that steroids improve survival in many of
the diseases for which they are commonly used.
o Glucocorticoid therapy is recommended for symptomatic ILD patients
with eosinophilic pneumonias, COP, CTD, sarcoidosis, hypersensitivity
pneumonitis, acute inorganic dust exposures, acute radiation
pneumonitis, DAH, and drug-induced ILD.
o In organic dust disease, glucocorticoids are recommended for both the
acute and chronic stages.
o The optimal dose and proper length of therapy with glucocorticoids in
the treatment of most ILDs are not known.
o A common starting dose is prednisone, 0.5 - 1 mg/kg, PO, daily for
4–12 weeks, at which time the patient is reevaluated.
▪ If the patient is stable or improved, the dose is tapered to 0.25–
0.5 mg/kg and is maintained at this level for an additional 4–12
weeks, depending on the course.
▪ Rapid tapering or a shortened course of glucocorticoid treatment
can result in recurrence.
▪ If the patient’s condition continues to decline on glucocorticoids, a
second agent (see below) often is added and the prednisone dose
is lowered to or maintained at 0.25 mg/kg per day.
o Cyclophosphamide, azathioprine (1 - 2 mg/kg/day), and mycophenolate
mofetil, with or without glucocorticoids for 8–12 weeks
▪ An objective response usually requires at least to occur.
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➢ SOB
✓ Progressive in onset
✓ Common if there is pleural effusion from disseminated TB
➢ Chest pain (pleuritic chest pain) /54%/ → also from pleural effusion and
characterized by
✓ Sudden, sharp, stabbing, localized pain
✓ Aggravated by deep breathing, coughing, sneezing, laughing
etc
✓ Relieved by assuming to the same side of the effusion
o N.B pain relieved by leaning forward in pericarditis
✓ May radiate to shoulder or back
✓ Associated with rapid and shallow breathing, SOB, dry cough
Risk factors
Determinants of transmission
▪ Duration of contact with TB pt
▪ Shared environment of contact (e.g poorly ventilated house)
▪ Similar illness in the family, living in the same house or
dormitory, camp, refuge place
▪ Geographical location → TB is common in 3rd world countries
RF for developing disease after infection
▪ Cigarette smoking
▪ Comorbidities → RVI (RVI increase risk of acquiring TB, 20-37
times greater lifetime risk than HIV negative), DM, CKD…
▪ Recent infection (< 1 year)
▪ Fibrotic lung disease
▪ Malnutrition and immunocompromisation
LOC → increase risk of Aspiration
Industrial chemical exposure
Complication of TB
Sample history
Chief compliant
HPI
This patient was last relatively healthy 03 weeks back at which time she
started to experience a gradual onset of initially dry cough which Comes day
and night without aggravating and relieving factor. Later becomes non position
dependent productive cough with Mucoid, non-position dependent, Non blood
tingled, non-foul-smelling sputum of half to 1 Arabic coffee cup per day which
Increase in frequency and amount progressively. Associated with this she also
experienced low grade, intermittent fever, profuse night sweat to the extent her
under wear becomes soaked and unquantified but significant weight loss to the
extent her clothes become loose but no SOB or chest pain.
10 years back, her husband was diagnosed with Pulmonary TB. Diagnosis was
made with sputum examination and CXR at addis zemen primary hospital. He
discontinued the medication due to unknown reason and died (contact hx is strong
RF)
Currently she is not married and lives in family size of 4. She has 3 boys and
one daughter. All are above 5 years old, alive and healthy. (family screening,
especially those under five years old, is one of principle of management)
Lives in well ventilated iron corrugated house having 2 windows and
one door, all are functional, with separate kitchen. (poorly ventilated house
accelerates TB transmission and RF for COPD → DDX)
She was screened for RVI 04 months back and found to be NR (RVI
increase risk of acquiring TB 37x than seronegative persons)
No hx of Cigarette smoking, or hemoptysis (cigarette is RF for developing disease after
TB infection, and RF for Lung ca → DDX)
No hx of abnormal body movement, LOC or tracheal intubation (aspiration →
RF)
No hx of DM, HTN or Asthma (comorbidities → RF)
No hx of swelling over the neck, axilla or groin (LN TB or scrofula → CXN)
No hx of Flank pain, dysuria, urgency, frequency or hematuria (Genito urinary
TB /stricture, pyelonephritis, sterile pyuria…. Infertility and menstrual abnormality in females/ → cxn)
No hx of bone pain, joint pain or swelling (bone TB → CXN)
No hx of tinnitus, blurring of vision, light headedness or easy fatigability
(anaemia 2ry to bone marrow suppression _ bone TB → CXN)
No hx of headache, fever or neck stiffness (TB meningitis → CXN)
No hx of back pain, body weakness or back bone deformity
which result in paraplegia → CXN)
(gibbus formation
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Chapter 3; TB/Tuberculosis/ (የሳንባ ነቀርሳ ፣ ቲቢ)
2 Vital signs
3 HEENT
4 LGS
5 RS
➢ Clubbing
➢ Signs of pleural effusion
➢ Rales, rhonchi, amphoric breath sound
➢ Apical consolidation signs
➢ Localized wheeze → TB bronchitis, LAP obstructing the bronchus
6 CVS
7 Abdominal examination
9 MSS
10 IS
11 NS
For Cor pulmonale, COPD, Bronchiectasis, Lung abscess and ILD refer
chapter 2 (click here → Chapter 2; Cor pulmonale and Chronic lung disorders
Chapter 2; )
8) Lung ca
usually have +ve family hx of lung ca, common in smokers and
present with bloody sputum.
refer under long case of nitsbin (click here → Chapter 4; Lung
9) SLE
cancer (የሳንባ ካንሰር)) 224
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F: M ratio is 9:1
Involves lung, pleura (pleural effusion), pericardium (leg edema)
refer under short case of nitsbin (click here →Systemic lupus
erythematosus (SLE) (lupus))
10) MAC (mycobacterium avium complex)
11) FUNGAL infections
12) GERD
13) VL
14) Brucellosis
✓ Extremely rare
✓ associated with animal abortus exposure
✓ caused by brucella abortus
✓ have similar clinical picture as TB and difficult to differentiate
IX
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2. Sputum examination
Sputum examination includes
o AFB microscopy
o Culture → gold standard, minimum of 10-100 bacilli per ml
are required for growth, unlike AFB microscopy which needs
approximately 10,000 bacilli per ml for detection of bacteria
o Gene expert → TB dx, RMP sensitivity
o Gram stain → to screen bacterial superinfection
o PCR if available
AFB microscopy
o The detection of acid-fast bacilli (AFB) on microscopic
examination of stained sputum smears is the most rapid and
inexpensive TB diagnostic tool.
o A serious of at least 3 single specimens should be collected
in 8 to 24 hours interval (with at least one specimen obtained
early in the morning) which should be submitted to the
laboratory for AFB smear and mycobacterial culture, although
the diagnosis often can be made with 2 specimens
▪ Spot - morning - spot examination (currently we are
using spot - spot examination only)
o If pt present with dry cough, use induced sputum with BAL or
hypertonic saline method
o Sputum AFB smears are relatively less sensitive (45 - 80%)
than nucleic acid amplification (NAA) or culture; approximately
10,000 bacilli per mL are needed for detection of bacteria in
AFB smear using light microscopy.
MYCOBACTERIAL CULTURE
o +ve in 80% of active TB
o Gold standard, minimum of 10-100 bacilli per ml are required
for growth
o 6 - 8 weeks may be required before growth is detected for
conventional media and 1-3wks for Liquid media
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N.B
❖ Smear +ve TB
2 +ve sputum examination or
1 +ve sputum examination and one of the following
o 1 culture +ve examination or
o Typical CXR finding or
o RVI pt
❖ Smear -ve TB
Culture +ve but doesn’t fulfil the above criteria and unresponsive
to broad spectrum antibiotics
✓ For smear -ve patients
▪ Repeat smear and request CXR
▪ If all IX including CXR do not suggest TB, prescribe
antibiotics for two weeks
❖ Follow up sputum examination (Look at management part below)
➢ Sputum examination for all new smear +ve pt’s should be repeated at
2nd, 5th, and 6th months
➢ Sputum examination for previously treated patient should be done at 3rd,
5th and 8th months
3. Pleural fluid analysis → for pleural involvement; refer under short cases of
nitsbin (click here → pleural fluid analysis)
Determinations of ADA and IFN-γ levels in pleural fluid may be
useful adjunctive tests in the diagnosis of pleural TB (Tuberculous
pleural effusion is a value >40 U/L).
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C. Baseline investigation
6. CBC
NcNc anaemia
Thrombocytopenia 2ry to Rifampicin treatment
7. ESR → elevated (supportive for diagnosis)
8. U/A → U/A done as baseline, urine culture may be done for dx
Sterile pyuria (i.e. culture -ve pus in urine)
Urine culture may be +ve for genitourinary TB
9. RFT → as a Pre-treatment Evaluation
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TB lymphadenitis
▪ FNAC, LN Biopsy, AFB, Tissue culture (50%+ve)
▪ From enlarged LN
▪ N.B Biopsy also can be taken from pleura and solid lesions
TB peritonitis
▪ Abdominal U/S
▪ Peritoneal TAP
Musculo skeletal tuberculosis (TB)
▪ X-ray of the involved part
▪ Synovial fluid aspiration or synovial biopsy and analysis if there is
Joint swelling
• findings of Synovial fluid analysis are usually nonspecific
▪ Microscopy and culture of infected material
• Tissue may be obtained by needle aspiration and/or biopsy;
CT guidance is useful in regions where available.
▪ CT or MRI reveals the characteristic lesion.
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Chapter 3; TB/Tuberculosis/ (የሳንባ ነቀርሳ ፣ ቲቢ)
Discussion
3.1 Pulmonary TB
E. EPIDEMIOLOGY
MICROBIOLOGY
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Transmission of M. tuberculosis
CLINICAL MANIFESTATION
Case of tuberculosis:
Refers to a patient in whom TB has been bacteriologically Confirmed or
diagnosed by a clinician decision.
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Chapter 3; TB/Tuberculosis/ (የሳንባ ነቀርሳ ፣ ቲቢ)
1. TB LYMPHADENITIS
3. Tuberculous empyema
Tuberculous empyema may result in severe pleural fibrosis and restrictive lung
disease.
Removal of the thickened visceral pleura (decortication) is occasionally
necessary to improve lung function.
4. TB of CNS
➢ TB meningitis and intracranial tuberculoma are the two most common forms.
4.1 TB MENINGITIS
Diagnosis
4.2 TUBERCULOMA
5. GI TB
7. Genitourinary TB Genitourinary TB
8. SKELETAL TB
➢ Most commonly affects the lower thoracic and upper lumbar region; disease
involving the cervical and upper thoracic region is less common.
➢ Infection generally begins with inflammation of the anterior aspect of the
intervertebral joints; typically, it spreads behind the anterior ligament to involve
the adjacent vertebral body. Once two adjacent vertebrae are involved,
infection enters the adjoining intervertebral disc space.
➢ This tends to occur later in Pott's disease than in bacterial vertebral
osteomyelitis and may have the radiographic appearance of relative disc
sparing.
➢ Eventually, the avascular disc tissue dies; there is vertebral narrowing and
subsequent vertebral collapse. Gibbus deformity, a form of structural kyphosis,
distorts spinal canal anatomy. The spinal cord is then at risk of compression,
resulting in paraplegia.
➢ Spread may occur into the soft paravertebral tissue to form a so-called “cold
abscess” (soft tissue mass). It’s formation of at the site is common.
➢ Noncontiguous spinal disease (eg, disease at more than one level) is
uncommon, although in one South African series it was described in 16 of 98
cases.
➢ The most common symptom is local pain, which increases in severity over
weeks to months, sometimes in association with muscle spasm and rigidity.
The muscle spasm can extend beyond the diseased area. In some cases, a
characteristic erect posture and "aldermanic" gait may be observed in which
the patient walks with short, deliberate steps to avoid jarring of the spine.
Constitutional symptoms such as fever and weight loss are present in less
than 40 percent of cases.
➢ The diagnosis of musculoskeletal TB is established by microscopy and culture
of infected material. Tissue may be obtained by needle aspiration and/or biopsy;
computed tomography (CT) guidance is useful in regions where available.
➢ CT or MRI reveals the characteristic lesion
➢ The diagnosis of tuberculous arthritis can be established by synovial biopsy.
Synovial fluid may be examined, but findings are usually nonspecific; the white
cell count can be high or low, with preponderance of either neutrophils or
lymphocytes.
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9. TB PERICARDITIS
➢ Tuberculous pericarditis occurs in approximately 1 to 2 % of patients with
pulmonary tuberculosis (TB).
➢ Develops frequently in HIV-infected patients
➢ Case fatality rates are as high as 40%
➢ Direct extension from adjacent mediastinal or hilar lymph nodes, hematogenous
spread.
➢ Four pathological stages of tuberculous pericarditis have been described:
Fibrinous exudation with polymorphonuclear leukocytosis, abundant
mycobacteria, and early granuloma formation with loose organization of
macrophages and T cells
Serosanguineous effusion with lymphocytic exudate and high protein
concentration; tubercle bacilli present in low concentrations
Absorption of effusion with granulomatous caseation and pericardial
thickening with subsequent fibrosis
Constrictive scarring; fibrosing visceral and parietal pericardium contracts
on the cardiac chambers and may become calcified, leading to
constrictive pericarditis, which impedes diastolic filling.
Clinical features
➢ The onset may be subacute, although an acute presentation
➢ Dyspnea, fever, dull retrosternal pain, and a pericardial friction rub, is possible.
(Cough -94%, Dyspnea - 88%, Chest pain (often pleuritic) - 76%, Night sweats
- 56%, Orthopnea - 53%, Weight loss - 48%)
➢ An effusion eventually develops in many cases; cardiovascular symptoms and
signs of cardiac tamponade may ultimately appear.
Investigation
➢ Echo, CT, or MRI shows effusion and thickness across the pericardial space.
➢ Pericardiocentesis under echocardiographic guidance; exudative fluid, with a
high count of predominantly lymphocytes and monocytes; hemorrhagic effusion
is common.
➢ Direct smear examination is very rarely positive.
➢ Culture - +ve in up to 2/3rd of cases, pericardial biopsy has a higher yield.
Complications:
➢ Chronic constrictive pericarditis, tamponade calcification, which may be visible
on a chest radiograph.
➢ The approach to antituberculosis therapy for treatment of tuberculous
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Miliary tuberculosis
NB; The term "miliary" was coined in 1700 by John Jacobus Manget, who likened
the appearance of the involved lung to millet seeds, with its surface covered with
small, firm white nodules. some authors use disseminated TB interchangeably with
miliary TB. however, miliary TB in fact refers more specifically to disseminated TB
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Picture; miliary TB
3.4 Management of TB
Principles of TB Treatment
➢ To decrease TB transmission
➢ Before you put patients on anti-TB drugs, gather baseline information on: how
diagnosis of TB has been made, check for confirmatory Bacteriologic
information, determine the site of involvement, offer HIV test, assess risk for
drug resistance and co-morbid conditions like pregnancy, renal or liver disease
...
Table: First line TB treatment adult and pediatric dosing chart using body weight bands
Adult and pediatric ≥25 kg weight Pediatrics
Patient Regimen and dose in two phases Daily dose Regimen and dose in two phases
weight Intensive: 2(RHZE); Continuation: (mg/kg weight) Intensive: 2(RHZ) (E) Continuation: 4(RH)
band (kg) 4(RH);
RHZ; 75/50/150 E; 100 RH; 75/50 mg
RHZE RH; 150/75 mg mg
;150/75/400/275 mg
mg
20-29 1 ½ 1 ½ 4-7kg 1 1 1
30-39 2 2 8-11kg 2 2 2
40-54 3 3 12-15kg 3 3 3
≥55 4 4 16-24kg 4 4 4
25+kg Adult dosages recommended
Note: all TB patients on treatment need daily Pyridoxine 50mg tablet supplement.
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➢ Amikacin (Am)
➢ Capreomycin (Cm)
➢ Cycloserine (Cs)
➢ Ethionamide (Eto)
➢ Kanamycin (Km)
➢ Levofloxacin (Lfx)
➢ para-Aminosalicylic acid (PAS)
➢ Streptomycin (S) → 1st line in some clinical conditions
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If not possible to consult, then avoid Streptomycin & Ethambutol; therefore, the
recommended regimen is 2RHZ/4RH.
Pericardial tuberculosis
For patients with pericardial tuberculosis, the same regimen (as pulmonary) of
anti-TB treatment is recommended (need expert opinion in diagnosis and
treatment).
Corticosteroids are recommended as adjunctive therapy for 11 weeks during
the first period of anti-tuberculosis therapy with tapering as shown in the table
below.
Tuberculous meningitis
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Chapter 3; TB/Tuberculosis/ (የሳንባ ነቀርሳ ፣ ቲቢ)
Fig. Flow Chart for Sputum AFB Follow-up for bacteriologically confirmed previously
treated PTB Patients
N.B
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Chapter 3; TB/Tuberculosis/ (የሳንባ ነቀርሳ ፣ ቲቢ)
Epidemiology
A number of environmental and lifestyle factors have been associated with the
subsequent development of lung cancer, of which cigarette smoking is the
most important.
Smoking
☛ The primary risk factor for the development of lung cancer is cigarette
smoking, which is estimated to account for approximately 90 % of all
lung cancers.
☛ The risk of developing lung cancer for a current smoker of one pack
per day for 40 years is approximately 20 times that of someone who
has never smoked.
☛ Factors that increase the risk of developing lung cancer in smokers
include the extent of smoking and exposure to other carcinogenic
factors, such as asbestos.
☛ Carcinogens and tumor promoters in
✓ Pack year=dose X length, (RR-13X,1.5X)
✓ Sex - women more susceptible
✓ Quitting/prevent starting
☛ Decreases with cessation of smoking but may never return to the
nonsmoker level.
Genetic factors
☛ Genetic factors can affect both the risk for and prognosis from lung
cancer.
☛ Although the genetic basis of lung cancer is still being elucidated,
there is a clearly established familial risk (most patients have +ve
family hx of lung ca).
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Chapter 4; Lung cancer (የሳንባ ካንሰር)
☛ can increase the risk of a second primary lung cancer in patients who
have been treated for other malignancies.
Environmental toxins
☛ These include exposure to second-hand smoke, asbestos, radon,
metals (arsenic, chromium, and nickel), ionizing radiation, and
polycyclic aromatic hydrocarbons.
Pulmonary fibrosis
☛ The risk for lung cancer is increased approximately sevenfold in
patients with pulmonary fibrosis. This increased risk appears to be
independent of smoking.
HIV infection
☛ The incidence of lung cancer among individuals infected with HIV is
increased compared with that seen in uninfected controls.
Alcohol
Dietary factors
☛ various dietary factors (antioxidants, cruciferous vegetables, and
phytoestrogens) may reduce the risk of lung cancer, but the role of
these factors is not well established.
☛ As an example, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention
Study actually showed an increase in lung cancer among smokers with
dietary supplementation of beta-carotene.
Pathology
2. Adenocarcinoma
4. Carcinoid Tumor
Summary on pathology
➢ Adenocarcinoma + nonsmoker → consider another primary site
➢ Central mass and endobronchial smx → squamous/small cell ca
➢ Peripheral nodule/mass with pleural → adenocarcinoma/large cell ca
➢ Squamous and large cell → cavitate 10-20%
➢ Bronchoalveolar ca → from peripheral airways-radiologically single mass,
diffuse, multinodular, fluffy infiltrates
Clinical manifestations
Staging
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Chapter 4; Lung cancer (የሳንባ ካንሰር)
Diagnosis
Goals — The major goals of the initial evaluation of a patient with suspected
lung cancer are to assess the following:
o Clinical extent and stage of disease
o Optimal target site and modality for the first tissue biopsy
o Specific histological subtype
o Presence of comorbidities, secondary complications, and paraneoplastic
syndromes that influence treatment options and outcome
o Patient values and preferences that influence diagnostic and therapeutic
choice
The preferred approach uses imaging as a road map and invasive biopsy as a
tool to confirm both the histopathological diagnosis and the stage of disease.
When feasible, diagnosis and staging should be established concurrently by
targeting for invasive biopsy the abnormality that would yield the most
advanced stage. However, some patients will require multiple imaging
studies and/or invasive procedures for tissue sampling.
No single diagnostic algorithm sufficiently addresses the complexity and
variation in disease patterns of lung cancer.
Clinical suspicion;
o The majority of patients who present with clinical signs or symptoms
due to lung cancer have advanced disease.
o The most common presenting manifestations are the following:
▪ Cough (50 to 75%)
▪ Hemoptysis (25 to 50%)
▪ Dyspnea (25 %)
▪ Chest pain (20 %)
o Lung cancer should always be suspected in a current or former smoker
with new onset of cough or hemoptysis.
o Both non-small cell lung cancer (NSCLC) and small cell lung cancer
(SCLC) can present with similar symptoms, and few clinical features
reliably distinguish them from each other.
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Chapter 4; Lung cancer (የሳንባ ካንሰር)
this setting, an MRI of the brain may be performed for the early
detection of brain metastases so that early treatment can be
administered before development of neurologic deficits or seizures
o In patients with clinical stage I/II disease who are candidates for curative
resection, there is consensus that routine brain imaging with MRI
is not indicated.
lab investigations; perform the following laboratory studies when chest imaging
is suspicious for lung cancer:
o CBC
o Electrolytes
o Liver enzymes
o LFT
o RFT
pathology;
o A diagnosis of lung cancer should not be made without definitive
pathology.
o At a minimum, this involves selecting a biopsy site and obtaining an
adequate sample for microscopic examination.
o Cytologic specimens can be obtained from the following sites;
▪ Lung → Sputum, transthoracic needle aspirates, and bronchoscopic
washings, brushings, or needle aspirates
▪ Lymph node → Transthoracic, transbronchial, and transesophageal
aspirates
▪ Distant metastasis → Pleural fluid, needle aspirates of metastatic
tissue.
o Core or biopsy tissue can be obtained from the following:
▪ Lung → Endobronchial biopsy (forceps), transbronchial biopsy
(forceps or needle), transthoracic (needle) biopsy, surgical biopsy
▪ Lymph node → Bronchoscopic and transthoracic needle core
biopsy, surgical biopsy.
▪ Distant metastasis – Core needle aspirates of metastatic tissue
(eg liver, bone, adrenal).
Management of Lung ca
1. NSCLC
2. SCLC;
Chemotherapy;
o LIMITED DISEASE
▪ response rate of 70 - 80% to chemotherapy and thoracic radiation
therapy, with a complete clinical response rate of 50–60%.
o EXTENSIVE DISEASE
▪ response rate of 60–80% to chemotherapy, with only 20% of
patients achieving complete clinical remission.
PROGNOSTIC FACTORS
Strongest predictors of survival:
o Good performance status (Karnofsky scale)
o Lesser extent of disease
o Younger age
o Absence of weight loss
Other predictors of better survival:
o Smoking cessation
o Standard uptake value of the primary tumor on positron emission
tomography (PET) scan.
Histologic subtype not considered a predictor of survival.
Pt’s may present with common OI syndromes like TB, Anaemia, cryptococcal
meningitis, esophagial candidiasis etc.
If a known RVI patient → ask the following on your hx
o For how long he/she was Diagnosed to have RVI in his/her blood
▪ e.g a known RVI pt for the past 10 years or you can say 10
years back he/she was told to have RVI (you have to ask
what was the presentation at that time and how Dx was
made… you may not need to write on your HPI)
o What is the regimen he/she is taking and for how long s/he was on
HAART?
▪ if there is gap between RVI Dx and initiation of regimen ask
the reason for delay of initiation of ART
o What was the baseline and current CD4 count and viral load?
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Oesophageal candidiasis hx
➢ Odynophagia or dysphagia
Scraping type of retrosternal pain during swallowing solid foods
and/or fluid diet
Relieving and aggravating factors
Radiation
➢ Loss of appetite
➢ Nausea, Vomiting (characterize vomiting)
Non bilious/bilious
Non projectile/ projectile
Non blood tingled/ blood mixed
Non foul smelling / foul smelling
Vomiting of ingested matter
Frequency of vomiting (x-y days per day)
➢ Hematemesis and/or melena
➢ Diarrhoea (characterize diarrhoea)
Large volume
Watery
Associated abdominal pain
➢ Easy fatigability
➢ Fever (characterize fever)
o Low/ high grade
o Intermittent/ continuous 266
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➢ MSP
➢ Blood transfusion
➢ IV drug abuse (sharing of needle)
➢ Sharing of needle, blade and other sharp materials
➢ Occupation → prostitute
➢ MTCT (mother to child transmission)
Complication
➢ OI
✓ TB → Pulmonary/extra pulmonary TB
✓ PCP
✓ Cryptococcal meningitis
✓ Toxoplasmosis
➢ Every system Involvement
➢ IRIS
Sample history
Chief compliant
HPI
This is a known RVI patient for the past 04 years initially on TDF + 3TC + EFV for
03 years later the regimen changed to TDF + 3TC+ DTG when DTG was introduced
to the market, with unknown baseline CD4 count and current CD4 count of 50
cells/mm3 with current viral load of 150 copies/ml. He discontinued his follow up from
UOG hospital and his medications 07 months back, because of the current pandemic
(covid -19), financial and transport problem, since he lives in very remote area from
gondar town.
Currently presented with cough of a month duration which is non position dependent
productive cough with Mucoid, non-position dependent, Non blood tingled, non-foul-
smelling sputum of 2 - 3 Arabic coffee cup per day that increase in frequency and
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amount progressively. Associated with this he also experienced low grade intermittent
fever, Night sweet and significant weight loss from 61 kg to 53 kg which is 13% of
his initial body weight.
Two weeks before admission, he also developed a gradual onset of dyspnea while
doing ordinary activities like going to church which progressively increase in severity
and he began to experience shortness of breath at rest within 01 week duration
associated with Sudden, sharp, stabbing and localized Chest pain which is aggravated
by deep breathing, coughing, sneezing, laughing and relieved by lying down on right
lateral decubitus position.
1 GA → CSL
2 Vital signs
3 HEENT 268
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➢ Necrotizing Gingivitis
4 LGS
5.RS
6. CVS
➢ CHF 2ry to DCMP (ZDV, RVI by itself)
7. Abdominal examination
➢ HSM (hepatosplenomegaly) → hematologic malignancy like NHL, ARS
(acute retroviral sxx) Phase of RVI
8. GUS
➢ Genital ulcer (genital herpes)
10. IS
Picture;left) Herpes zoster over the left posterior chest. Right) left lateral side of the
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same patient
➢ Mucocutaneous ulcer
➢ Erythematous maculopapular rash of PPE (Pruritic papular eruption)
o Intensely pruritic, discrete, firm papules with variable stages of
development and predilection for extremities, though it can
involve trunk and face.
o Excoriation results in pigmentation, scarring and nodules
11. NS
C. meningitis
Rarely toxoplasmosis
➢ Motor
FND (e.g. hemiplegia) → space occupying lesions like primary
CNS lymphoma
Multiple lesions from CNS toxo, tuberculoma
➢ Sensory
TM (Transverse myelitis with distinct sensory level)
Paraesthesia
➢ Coordination, gait and drift
Impaired rapid alternation movement
Ataxia
Seizure→ encephalopathy, CNS toxoplasmosis, C. Meningitis and
other aetiologies of meningitis, primary CNS lymphoma, PMLE
➢ Meningeal irritation sign +ve in
C. meningitis
Aseptic meningitis
Syphilitic meningitis
Lymphomatous meningitis
HIV meningoencephalopathy
PMLE (progressive multifocal leukoencephalopathy)
DDX
✓ Cryptococcus
✓ Histoplasmosis
✓ Aspergilloma
6) Bronchogenic ca → Family hx, Smoking hx, Bloody sputum (Haemoptysis)
7) Lung Abscess
✓ Offensive foul-smelling sputum which is copious in amount
✓ Fever
✓ If rupture → Bronchopleural fistula → effusion
1) Esophageal candidiasis
AIDS Defining disease
Occur when CD4 count is < 200
N.B. AIDS defining Diseases include
▪ Kaposi Sarcoma
▪ Cervical ca
▪ OHL
▪ Cerebral toxo
▪ Esophageal ca
▪ ADC
2) Infectious esophagitis
CMV → Fever, odynophagia, substernal chest pain, nausea
HSV → odynophagia and/or dysphagia, fever, retrosternal chest pain,
coexisting herpes labialis
3) Drug induced esophagitis
Characterized by severe dysphagia to the extent difficulty of
swallowing saliva
4) Lymphoma to esophagus
Lymphoma
MALToma
5) Esophageal ca
6) Esophageal stricture
IX
▪ ELISA
▪ Western blot
2. CBC→ Megaloblastic anemia from AZT toxicity, pancytopenia
3. RBS
4. U/A → proteinuria in HIVAN
5. CXR
r/o TB, pneumonia
PCP → perihilar infiltrate, ground glass appearance
6. Sputum examination (gene x-pert for TB screening)
Gram stain from BAL, induced sputum, Transbronchial biopsy→ definitive dx for
PCP
AFB
Culture
Gene x-pert
PCR
7. RFT → for drug toxicity, HIVAN
8. LFT → for drug toxicity
9. Lipid profile (Triglyceride, Cholestrol, HDL and LDL)
10. Hepatitis screening → before initiation of ART since HBV also treated with
TDF
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11. CXR
TB features on CXR
o Early typical adult features
☛ Upper lobe infiltration/cavitation
☛ No significant LAP/ pleural effusion
✓ Late atypical features
o Lower/middle lobe opacity
o Little/no cavitation
o Miliary/interstitial pattern
o Hilar/paratracheal LAP
o Pleural/pericardial effusion
o May be normal finding
13. Pleural fluid analysis → refer under short cases of Nitsbin (click here →
pleural fluid analysis)
12. Chest U/S → can differentiate
✓ Loculated effusion from tumor
✓ Pleural effusion from pleural thickening
13. Chest CT → also differentiate pleural effusion from pleural thickening
14. Culture → gold standard Ix in RVI-TB
15. RFT and LFT for Anti TB toxicity
N.B
if you suspect esophageal candidiasis in RVI patient there is no
specific investigation modality. Rather, treat with systemic
antifungals and if odynophagia improves within 3-4 days, the
cause of odynophagia is highly likely esophageal candidiasis
✓ RFT
✓ RBS
✓ Pregnancy test
✓ Lipid profile
❖ Follow up
✓ Baseline Ix Repeated monthly (particularly at the initiation of ART)
then every 3 months once stabilized. Then at any time if indicated
Discussion
5.1 HIV/AIDS
➢ HIV (Human Immuno-deficiency Virus) is an infectious disease caused by HIV,
a human retrovirus
➢ It is essentially a disease of the immune system, which results in progressive
immunodeficiency state leaving the individual susceptible to various types of
infections and the development of malignancies.
➢ HIV disease should be viewed as a spectrum ranging from primary infection,
with or without the acute syndrome, to an asymptomatic stage, to advanced
disease characterized by profound immunodeficiency and susceptibility to
opportunistic infections (OI).
➢ The most advanced stage of HIV infection is called AIDS
➢ AIDS (Acquired Immunodeficiency Syndrome) is the late /most advanced/ stage
of HIV infection
➢ Current case definition for AIDS;
☛ Any HIV-infected person with a CD4+ T-cell count <200/μl
☛ Development of an AIDS-defining clinical condition (see staging below)
Etiology
➢ Human retroviruses; HIV-1 and HIV-2
✓ Family of human retroviruses (Retroviridae), Subfamily of lentiviruses
✓ RNA viruses whose hallmark is the reverse transcription of its genomic
RNA to DNA by the enzyme reverse transcriptase
➢ HIV-1 is the most common cause of AIDS worldwide.
➢ HIV-2 has been identified predominantly in western Africa but Small numbers
of cases have also been reported in Europe, South America, Canada, and the
U.S. Has ~40% sequence homology with HIV-1 and More closely related to
simian immunodeficiency viruses
Transmission
❖ Sexual contact (unsafe): heterosexual and homosexual. It is major means of
transmission.
❖ Contact with blood, blood products, or other bodily fluids (as in drug abusers
who share contaminated intravenous needles)
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Diagnostic Approach
➢ Diagnosis of HIV infection → Diagnosis depends on demonstration of
antibodies to HIV and/or direct detection of HIV or one of its components.
Antibodies to HIV appear 2 - 12 weeks after infection
➢ Diagnosis of AIDS → CD4+ T-cell count <200/μL or AIDS-defining clinical
condition
Effects of HIV
➢ Direct effects:
✓ Nervous (encephalopathy and peripheral neuropathy)
✓ Kidney (HIVAN = HIV-associated nephropathy)
✓ Cardiac (HIV cardiomyopathy)
✓ Endocrine (hypogonadism in both sexes)
✓ GI tract (dysmotility and malabsorption/ ?HIV enteropathy)
➢ Indirect effects:
✓ Opportunistic infections and tumors as a consequence of
immunosuppression
1. Phase 1: Transmission
2. Phase 2: Acute retroviral syndrome
✓ IP - 2-6 weeks post exposure
✓ Present with Fever, Sore throat, Nausea /Vomiting/diarrhea, Weight loss
/myalgia /arthralgia, Maculopapular rash (face, trunk, extremities),
Hepatosplenomegaly, Neurologic abnormalities (Aseptic meningitis,
Encephalitis, Peripheral neuropathy, GBS, Facial Palsy, Brachial neuritis,
Psychosis
✓ HIV Ab test negative
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✓ CD+4 T cells number and function decline; But high viremia, high HIV RNA
levels and P24 antigenemia (high viral load) …
✓ Period of extreme infectiousness
✓ Be aware of false negatives
✓ Using rapid tests >95% of patients will test positive within 6 months
5. Phase 5: AIDS
CD 4 cell count A B C
(asymptomatic, (symptoms not in A (AIDS indicators)
PGL, acute retro or C)
viral syndrome)
> 500 cells/µl A1 B1 C1
200 - 499 cells/µl A2 B2 C2
< 200 cells/µl A3 B3 C3
N.B for clinical practice, WHO classification is used commonly and CDC
classification is not used most of the time.
T- staging
➢ T-staging refers to clinical staging while on ART for at least 6 months
➢ Based on T-staging WHO stage 1 corresponds to stage T1, Stage 2 to T2,
stage 3 to T3 and Stage 4 to T3
➢ Used as an indicator of treatment outcome
➢ Prompts consideration to switch therapy
➢ Clinical events before the first six months of therapy are excluded from this
definition
Objective
➢ Suppress viral replication to undetectable levels durably;
➢ Restore and preserve immunologic function;
➢ Prevent HIV transmission;
➢ Prevent opportunistic infections;
➢ Rehabilitate the patient and allow full function and survival.
Non pharmacologic
➢ Counseling and psychological support
➢ Nutritional support
➢ Socio-economic support
Pharmacologic
➢ Management of HIV disease includes prevention and treatment of OI and
controlling viral replication with HAART. 282
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Goal of HAART
starting ART.
Medicine Regimens
First-line regimens for adults and adolescents: for treatment naive patient for the
first time.
➢ TDF + 3TC + DTG/EFV as a once-daily dose.
✓ FDC (Fixed-dose combinations) and once-daily regimens are preferred.
✓ For HIV/TB co-infected adults and adolescents, the recommended dose of
DTG is 50 mg twice daily.
Table Summary of first-line ART regimens for adults, pregnant & breastfeeding women, adolescents and
children.
Population Preferred first-line regimens Alternative first-line regimens a
Adults (including those with TB/ ➢ TDF + 3TC + DTG (FDC)* ➢ AZT + 3TC + EFV/NVP OR
HIV b-coinfection) OR ➢ TDF + 3TC + NVP
➢ TDF + 3TC + EFV (FDC)**
Pregnant and breastfeeding ➢ TDF + 3TC + EFV (FDC)
women
Adolescents (10 to 19 years) ➢ TDF + 3TC + DTG (FDC)* ➢ AZT + 3TC + EFV/NVP OR
weight ≥35 kg (Including those OR ➢ TDF + 3TC + NVP OR
with TB/HIV b-coinfection.) ➢ TDF + 3TC + EFV (FDC)** ➢ ABC + 3TC + EFV
Children 3 years to <10 years ➢ AZT/ABC + 3TC + EFV ➢ AZT + 3TC + NVP OR
and adolescents’ weight <35 kg ➢ TDF + 3TC + EFV OR
➢ TDF + 3TC + NVP OR
➢ ABC + 3TC + NVP***
Children <3 years ➢ ABC/AZT + 3TC + LPV/r ➢ ABC/AZT+ 3TC + NVP
a
ABC or boosted PIs (ATV/r, LPV/r) can be used in special circumstances
b
In case of TB-HIV coinfection, the dose of DTG should be 50mg BID.
*If available as triple FDC, TDF+3TC+DTG is the preferred regimen for HIV positive adult and
adolescent patients.
**TDF+3TC+EFV400 (FDC) will replace the TDF+3TC+EFV600 (FDC) for adults and adolescents
(except for pregnant mothers and TB/HIV co-infected patients as there is no adequate data for this
groups) up on availability.
*** Caution: co-administration of ABC with NVP in pediatric patients will increase the risk of
hypersensitivity reaction and requires extreme precaution.
Second line drugs are used if there is treatment failure or if there is serious side
effect develops from 1st line drugs.
➢ Routine viral load testing is a more sensitive and earlier indicator of treatment
failure.
➢ To detect treatment failure proactively, routine viral load testing should be done
at 6 and 12 months of initiating ART and then every 12 months thereafter and
plus whenever there is clinical or immunologic suspicion of treatment failure.
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Table: Definitions of clinical, immunological and virologic failure for the decision to switch ART regimens
Failure Definition Remark
Clinical Adults and adolescents ➢ The condition must be
failure ➢ New or recurrent clinical event indicating severe differentiated from IRIS
immunodeficiency (WHO clinical stage 4 condition and occurring after initiating ART.
certain WHO clinical stage 3 conditions (pulmonary TB
and severe bacterial infections) may also indicate
treatment failure) after 6 months of effective treatment.
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Figure. Algorithm for routine clinical and viral load monitoring. * For those patients
with identified significant adherence barriers, it is advisable to extend the provision of
Enhanced adherence counseling for 6 months before doing the second Viral load testing
in order to properly address the barriers and give optimal time for viral suppression to
happen
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10
‘’Start ART for HIV positive mothers who are breastfeeding even if it was not started
before (currently recommended regimen TDF/3TC/ DTG)’’ MANAGEMENT PROTOCOL ON
290
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➢ Patients who are on 2nd line regimen and have high viral load level (>1000
copies/ml) after 6 months of treatment need to go through the algorithm as
described for first line treatment failure with enhanced adherence support and
repeat test after 3 months to decide second line treatment failure.
➢ If confirmed to have 2nd line failure, consult (or refer to) experienced physicians
for initiation of 3rd line regimens.
➢ Before switching to 3rd line regimen, ensure the following.
✓ Two consecutive viral load measurements > 1000 copies/ml at least 3
months apart.
✓ First viral load measurement done at least 6 months after switching to 2nd
line regimen.
✓ The repeat viral load test should be done after 3 months of enhanced
adherence support.
✓ The approach in switching to 3rd line should follow the guiding principles
listed out for switching to 2nd line drugs.
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What to expect in the first months of ART and how to manage them?
➢ ART initiation may be associated with IRIS as well as early adverse drug
events, such as drug hypersensitivity, in the first three months of ART
➢ Be alert to OIs and/or IRIS as well as adverse drug events, in the early phase
of ART initiation.
➢ Especially a high mortality seen in the first three to six months of ART
initiation among people who started ART with advanced HIV disease with
existing co-infections and/or co- morbidities, severely low hemoglobin, low body
mass index (severe malnutrition) and/or very low CD4 counts.
➢ Failure to achieve CD4 recovery or presence of CD4 decline after treatment
initiation particularly after one year (common in those with very low CD4 cell
on ART initiation) should alert to potential adherence problems or primary non-
response to ART, and consideration should be given to continue prophylaxis
for OI such as CPT till patients recovers immunologically.
➢ IRIS is not indicative of treatment failure or drug side effect and doesn’t need
discontinuation or change of ARVs. It is generally self-limiting, and interruption
of ART is rarely indicated, but people may need to be reassured in the face
of protracted symptoms to prevent discontinuation of or poor adherence to
ART.
➢ (NB: Actively watch for IRIS in patients starting with first-line regimens
containing integrase-inhibitors such as DTG)
➢ The most important steps to reduce the development of IRIS include:
✓ Earlier HIV diagnosis and initiation of ART before a decline to < 200 CD4
cells/mm3
✓ Improved screening for OIs before ART, especially TB and Cryptococcus;
and
✓ Optimal management of OIs before initiating ART.
➢ Timing of ART in people with OIs requires; balancing a greater risk of IRIS
after early initiation against continuing high mortality if ART is delayed.
Management of IRIS
➢ Patients should generally be treated for the underlying OI ASAP.
➢ Continuation of ART when IRIS occurs.
Follow up
Guiding principles
✓ Establish whether the clinical condition is due to ARV toxicities, other
drugs, or other illness including new OI’s
✓ Try to identify the responsible ARV drug.
✓ Assess the severity using toxicity grading matrix.
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➢ The major causes of drug discontinuation in the first 3-6 months after initiating
ART are due to drug toxicities; and hence, they must be closely monitored.
They occur from few weeks to months.
➢ All patients require clinical evaluation at least every month in the first 6
months for ARV related toxicity. Subsequent follow-up can be done by
months.
➢ The most frequent drug adverse reactions include:
✓ Toxicities of NNRTIs (NVP and EFV) occurring in the first few weeks, and
may be life- threatening.
✓ ABC hypersensitivity reaction starting from first week following initiation.
✓ Anemia and neutropenia due to AZT occur in the first 3 months.
✓ Intolerance to certain drugs, in particular AZT induced gastrointestinal
problems, are important barriers to adherence unless appropriate
measures are taken.
➢ The clinical manifestations due to hypersensitivity reactions (ABC and NVP)
may be confused with IRIS.
➢ Laboratory monitoring for toxicity of ART: look at IX section Above
symptoms suggesting HIV infection or risky exposure setting (e.g., needle stick
from a sharps container in an HIV clinic).
➢ Testing source:
✓ If the source is negative no need for further assessment of the exposed
victim is needed. If the source is positive, tasting the exposed person is
needed.
➢ HIV serology test of the exposed person:
✓ Immediately after exposure.
✓ If the result is positive no need for PEP, but if negative administer PEP
ASAP as outlined above and then repeat serology at 6 weeks, 3 months,
and 6 months.
✓ HBV Testing (screening) is also recommended. 296
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➢ NB: initiate PEP immediately after exposure until test result confirms the HIV
status of the victim. Stop PEP if the health worker is positive for HIV
antibodies.
➢ Following HIV exposure there is a need for psychosocial support.
➢ Oral PrEP of HIV is the use of ARV drugs by people who are not infected
with HIV but at a substantial risk.
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11
5.5 PMTCT and treatment of RVI exposed infant
➢ PMTCT (Prevention of mother to child transmission) of HIV have four prongs
✓ Prong 1: Primary prevention of HIV infection
✓ Prong 2: Prevention of unintended pregnancies in HIV-positive women →
emphasizes reducing the number of unplanned or unwanted pregnancies
and effective family planning counseling service
✓ Prong 3: Prevention of HIV transmission from women living with HIV to
their infants → addresses care for HIV-positive women during pregnancy,
labor and childbirth, and breastfeeding and care for their infants.
✓ Prong 4: Provision of treatment, care, and support to women living with
HIV, and their infants, partner, and families → including on-going, chronic
care and treatment for HIV-positive pregnant/postpartum women and their
HIV-exposed and HIV-positive children both during and beyond the
PMTCT intervention period.
➢ All HIV positive pregnant, laboring and lactating mothers will be initiated on
HAART for life (TDF, 3TC and DTG).
➢ HIV positive woman already on ART at time of pregnancy should continue and
stay on the same regimen.
11
Details of PMTCT are beyond the scope of this text book. Here is a highlight to have knowhow only. It is
better to link mothers, to PMTCT clinic, special ANC follow up and labor management is mandatory. 298
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➢ Start ART for HIV positive mothers who are breastfeeding even if it was not
started before (currently recommended regimen TDF + 3TC + DTG)
➢ For mothers who fulfill Acceptable, Feasible, Affordable, Sustainable and Safe
(AFASS) feeding, formula feeding should be considered after thorough
discussion with the family.
➢ For those who do not fulfill AFASS, breastfeeding must be exclusive for 6
months and complementary feeding should start at 6th month. Breastfeeding
should be continued until the first year of life but not more than two years.
Further reading
➢ MANAGEMENT PROTOCOL ON SELECTED OBSTETRICS TOPICS FOR HOSPITALS, December
2020, FMOH, Ethiopia
➢ WHO PMTCT guideline; ANTIRETROVIRAL DRUGS FOR TREATING PREGNANT WOMEN AND
PREVENTING HIV INFECTION IN INFANTS: TOWARDS UNIVERSAL ACCESS
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Fluconazole prophylaxis
➢ Indication
✓ After completing treatment for Cryptococcal meningitis
➢ Dose: 200mg Po daily
Impact of HIV on TB
Impact of TB on HIV
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➢ All HIV positive clients should be informed about risk of developing active TB
and the advantages of being screened for TB.
➢ Asses sign and symptoms of active TB (may have atypical presentation) and
contact history with TB case
➢ If the evaluation shows no TB, children should be offered IPT, if no
contraindications, regardless of their age.
➢ Diagnosis of TB is challenging in HIV positive individuals, especially when the
stage of the disease is advanced.
➢ Thorough clinical evaluation, including exclusion of other OI, should be done.
Acute bacterial pneumonia or PCP may occur in patients with underlying
tuberculosis and patients should therefore be reevaluated for tuberculosis,
particularly if respiratory symptoms persist after treatment.
Clinical manifestations:
➢ Variable, depending on CD4 count
➢ In early HIV - TB presents in a typical manner
➢ In late stages of HIV, when CD4 is <200, a primary TB - like pattern with
atypical clinical & CXR findings are common
✓ Extra-pulmonary and disseminated disease is more likely (70%)
✓ Common extrapulmonary sites are: LNs, Pleura, Pericardium, CNS, GI,
Kidney, Bone.
➢ TB IRIS: Paradoxical or Unmasking type
Diagnosis and IX
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shows RR-TB again; link the patient to TIC for Second line TB treatment; but
if the repeat test result identifies TB but not RR-TB, initiate first line TB
regimen as bacteriologically confirmed susceptible TB at TB clinic.
☛ Antibiotic trial: has a role to treat concomitant bacterial infection for people
living with HIV having cough or serious illness, but not helpful in the diagnosis
of TB in HIV positives.
Disseminated TB
is due to TB.
➢ Patients with weight loss, night sweats,
308
Start anti-TB treatment (add antibiotics if
Contraindications of IPT;
➢ Individuals with any one or more of the following conditions should not receive
IPT:
✓ Symptoms compatible with tuberculosis even if the diagnosis isn’t yet
confirmed.
✓ Active hepatitis (chronic or acute)
✓ Regular and heavy alcohol consumptions
✓ Prior allergy or intolerance to isoniazid
✓ Symptoms of peripheral neuropathy
National policy:
☛ IPT should be administered at enrolment to HIV care after ruling out active TB.
☛ IPT is to be administered once and should not be repeated unless there is
strong indication on its benefits which is to be decided by senior physician.
☛ IPT should be administered only for 6 months.
☛ IPT should not be administered right after completing full course of TB
treatment
☛ IPT can be administered for patients who had history of TB treatment before 3
years.
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Infection control
➢ People living with HIV are at high risk of acquiring TB in health care facilities
and congregate settings.
➢ Each health care facility should have a TB infection control plan for the facility
that includes administrative, environmental and personal protection measures to
reduce the transmission of TB in health care and congregate settings and
surveillance of TB disease among workers.
1. Bacterial pneumonia
➢ Bacterial pneumonia tends to be more severe and recurrent as the CD4 counts
drops significantly.
➢ Pneumonia can also concomitantly present with sinusitis and/or bacteremia.
➢ If not treated promptly, extra pulmonary complications like empyema,
meningitis, pericarditis, hepatitis and arthritis can follow.
➢ Management is the same as non-RVI patients (for more click here →
Pneumonia (የሳንባ ምች))
Clinical manifestation
➢ Typical have an insidious (sub-acute onset over 2 to 4 weeks) onset of low-
grade fever, dry cough, fatigue and progressive dyspnea exacerbated by
exertion.
➢ Patients will have an increasing tachypnea, tachycardia and cyanosis as the
disease progresses.
➢ Physical examination reveals fever, tachypnea, tachycardia and scattered rales
in the lungs but examination of the lungs can appear normal in some patients.
➢ In children highest incidence is seen between 2-6 months of age and is
characterized by abrupt onset of fever, tachypnea, dyspnea and cyanosis.
➢ Due to non-specific presentation, PCP should always be considered in those
patients with evidence of moderate to severe immunosuppression who come up
with cough, progressive dyspnea or fatigue.
Picture; Bilateral interstitial infiltrates beginning in the perihilar regions (ground glass
appearance)
Treatment
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First line:
➢ Cotrimoxazole, 960mg (15-20mg/kg/day), P.O/IV, TID/QID for 3 weeks
✓ Give the same medicine IV if the patient is not able to swallow the
medicine and shift orally when tolerable.
✓ Close monitoring is necessary during the initial 5 days of treatment and if
patient grows sicker, administration of oxygen is useful.
✓ In severely ill patients with marked respiratory distress and extensive
chest X-ray findings prednisolone has to be given simultaneously
✓ Toxicity of co-trimoxazole, like skin rash, bone marrow suppression,
hepatitis and renal failure can be troublesome in some patients with
advanced HIV disease and requires close monitoring. SJS (Steven
Johnson syndrome) may occur if the patient is allowed to take the
medicine after the development of rash.
✓ Secondary prophylaxis after completion of the course of treatment with
CPT should be continued.
Alternative:
➢ Clindamycin+ Primaquine or Dapsone for 3 weeks
✓ Clindamycin, 600 mg BID (300-450mg P.O., TID) for 3 weeks PLUS
✓ Primaquine, 30mg base P.O, daily (15 mg BID) for 3 weeks.
OR
✓ Clindamycin 600 mg QID, for 3 weeks plus
✓ Dapsone 100 mg daily for 3 weeks.
OR
✓ Trimethoprim, 20mg/kg/day, P.O, QID for 3 weeks PLUS
✓ Dapsone, 100mg P.O., daily for 3 weeks
OR
✓ Pentamidine Isethionate, 4mg/kg I.V. daily for 3 weeks. It should be given
to those who fail to tolerate the above regimen.
N.B.
☛ Typically, a mild rash with fever develops 7 to 10 days after initiation of
therapy.
☛ Bone marrow suppression may occur, and CBC monitoring is useful.
☛ Possible hepatotoxicity and nephrotoxicity may also be evaluated at the 3rd
week of therapy.
☛ Consider spontaneous pneumothorax in patients with sudden deterioration in
clinical condition.
Adjuvant treatment
➢ Corticosteroids → Indicated if SPO2 <90%, In the absence of pulse oximetry,
clinical judgment should be used to select moderately to severely sick patients
who benefit from corticosteroids.
✓ Prednisolone 40mg BID (i.e. 80 mg) for 5 days, then 20mg BID for 5
days, then 20mg daily until completion of intensive co-trimoxazole therapy
(for 11 days). No tapering from the 20 mg dose is necessary.
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✓ For severe PCP in children: prednisolone 2mg/kg per day for the first 7 -
10 days followed by a tapering regimen for the next 10 - 14 days.
Pregnancy considerations
➢ The management and the prophylaxis for pregnant is similar to non-pregnant
mothers.
➢ TMP-SMX is the preferred drug in pregnant. However, be aware of the
theoretical risk of teratogenicity in the first trimester with the use of TMP-SMX.
➢ Aerosolized pentamidine or oral atovaquone can be used as alternative than
discontinuing chemoprophylaxis in the first trimester
Clinical manifestations
➢ Ranges from asymptomatic disease with isolated radiographic findings to
bullous lung disease with pulmonary insufficiency.
➢ Symptomatic children present with insidious onset of tachypnea, cough, and
mild to moderate hypoxemia with normal auscultatory findings or minimal rales
or wheezing.
➢ Progressive disease is accompanied by digital clubbing and symptomatic
hypoxemia.
➢ Associated physical findings include generalized, hepatosplenomegaly and
parotid enlargement.
Diagnosis
➢ Usually based on clinical examination findings, diffuse bilateral reticulonodular
infiltrate on X-ray with mediastinal lymphadenopathy.
➢ It is important to exclude tuberculosis and other infectious etiology.
Treatment
➢ Symptomatic treatment (hydration, oxygen).
➢ Antibiotics: if there is a superimposed bacterial infection.
➢ Bronchodilators: may be helpful in mild to moderate disease.
➢ Corticosteroids: reserved for children with significant hypoxemia and symptoms
of pulmonary insufficiency. Give prednisolone 1- 2 mg/kg/day for 6 - 8 weeks
and then taper as tolerated.
➢ GI OIs commonly manifest with diarrhea, nausea and vomiting, dysphagia and
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➢ Most common causes among HIV infected are Isospora belli, cryptosporidium,
shigella and salmonella, CMV etc.
➢ A scenario of multiple concurrent GI infections is fairly common.
➢ A number of drugs with similar effects can pose challenges in differential
diagnosis.
➢ Infectious OI
✓ Candida
✓ Bacterial
✓ HSV
✓ EBV
✓ CMV
➢ Non- Infectious
✓ Angular chelitis
✓ Malignancies (kaposi’s sarcoma/KS/, lymphoma)
✓ Aphthous ulcers
➢ Oral – candidiasis, aphthus ulcer, kaposi’s sarcoma, gingivitis, periodontitis,
oral hairy leukoplakia
➢ Esophagus – esophagitis due to candida, CMV, HSV, KS
Prevention
➢ Administration of ART and immune restoration is an effective means to prevent
disease.
➢ ART failure should be investigated if there is recurrent infection.
➢ Routine primary prophylaxis is not recommended.
➢ Secondary prophylaxis or chronic suppressive therapy is not also recommended
unless frequent or sever recurrence, if used (Fluconazole 100 mg PO once
daily for oral/esophageal and 150 weekly for VVC), discontinue therapy if CD4
count >200 cells/mm3.
Pregnancy
➢ Pregnancy upsurges the risk of vaginal colonization with Candida species.
➢ Topical therapy is preferable for treatment of oral candidiasis in pregnancy, but
is essential for vulvovaginal candidiasis, especially during the first trimester.
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➢ Unknown etiology
➢ Usually painful & self-limiting
➢ May interfere with swallowing.
➢ Look at image under physical examination (patient approach in RVI) section of
this chapter.
➢ Rx:
✓ General measures
• Oral hygiene
• Avoidance of exacerbating factors – Where possible, reduce
traumatic factors inside the mouth (eg, sharp/rough dental
restorations, braces). Avoid habits that cause trauma (eg, biting
cheeks or lips) and foods that seem to exacerbate the process
(Avoid spicy foods).
• Pain control – Topical anesthetics provide immediate symptomatic
relief of short duration;
o 2% lidocaine, may be applied directly to surface of ulcers or
used as a swish and spit
o Diphenhydramine liquid: 12.5 mg/5 mL; 5 mL swish and spit
o Aluminum hydroxide, magnesium hydroxide, and simethicone
suspension: 5 to 10 mL swish and spit
• Control of secondary infection; Nystatin suspension (400,000 to
600,000 units) swish and swallow four times daily or Clotrimazole
troches (10 mg) four to five times daily
✓ Topical steroids (Triamcinolone oral paste)
• Triamcinolone oral paste; Press a small amount (about 1/4 inch) to
the lesion at bedtime; a larger quantity may be required for
coverage of some lesions. For severe lesions, may be used 2 or 3
times daily after meals.
✓ A short course of oral corticosteroids may be beneficial in patients with
severe Recurrent aphthous stomatitis that is not controlled with topical
therapies
• Prednisone, 20 to 40 mg, PO, daily for 4-7 days.
➢ Shallow, clustered ulcers around oral and peri oral area are characteristic
➢ May be solitary and deep in the severely immunocompromised patient
➢ Usually painful
➢ DDx: aphthous ulcers
➢ NOTE: Vesicles are rarely seen in the mouth!
➢ Rx:
✓ Local antiseptics to avoid superinfection
✓ Acyclovir, 400 mg, PO, TID, for 1 week
➢ Protozoal infection:
✓ Cryptosporidium species, Isospora belli, Microsporidium species,
Entamoeba histolytica, G. lamblia,
➢ Bacterial infection:
✓ Campylobacter, Shigella, and Salmonella species
➢ Toxin induced:
✓ E. Coli and Clostridium difficile
➢ Mycobacterial infection:
✓ M. avium complex, M. TB
➢ Helminthic infection:
✓ Strongyloides stercoralis
➢ Viral infection:
✓ CMV, HSV
➢ Fungal infection:
✓ Histoplasmosis, coccidioidomycosis, and penicilliosis, Candida species
(seldom a cause of diarrhoea)
➢ Non-infectious disorders:
✓ Kaposi’s sarcoma, lymphoma
➢ AIDS enteropathy:
✓ Direct cytopathic effect of HIV disease
➢ Drug Side effects:
✓ Antibiotics, ART
Laboratory evaluation
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Management
➢ Fluid and electrolyte replacement, nutritional support → The most important first
step is correction of fluid loss. Depending on the severity of dehydration, ORS
or IV fluid therapy can be given. Patients with severe dehydration need to be
admitted for IV fluid administration.
➢ In children zinc 20mg per day for 10-14 days (10mg per day for infants <
6months of age) should be added
➢ If specific enteric pathogen is identified or strongly suspected on clinical
grounds, it should be treated accordingly
First line
✓ Ciprofloxacin 500–750 mg PO (or 400 mg IV), BID
Alternative
✓ Ceftriaxone,1 g, IV, daily or
✓ Cefotaxime, 1 g, IV, TID.
➢ The treatment duration depends on the expected pathogen and may generally
extend from 7–14 days for uncomplicated cases and 2 to 3 weeks for
complicated (bacteremia, recurrent infection and/or advanced AIDS)
➢ Hospitalize and use IV antibiotic therapy if marked nauseas, vomiting, diarrhea,
electrolyte abnormalities, acidosis, blood pressure instability, and/or when there
is a clinical judgment for severity of disease
➢ For patients with persistent diarrhea (>14 days) but no other severe clinical
signs (e.g., dehydration, blood in stool), antibiotic therapy can be withheld until
a diagnosis is confirmed.
➢ Prophylactic antimicrobial to prevent bacterial enteric illness is not usually
recommended, including for travelers.
colitis microscopy
Giardia
Cryptosporidium <150 Watery diarrhoea Modified AFB ART*
Isospora belli <100 TMP-SMX
Microsporidium < 50 Giemsa stain Albendazole
CMV <50 Watery/bloody Tissue biopsy Ganciclovir
diarrhoea,
colitis
*No specific treatment for Cryptosporidium but it will improve with immune restoration
following ART.
Symptomatic treatment
➢ In adults use anti-diarrhoeal agents Loperamide 4mg stat then 2mg after each
bowel motion or Diphenoxylate 5mg QID.
➢ Necessary caution should be taken to avoid anti- diarrhoeal agents in bacterial
or parasitic infectious colitis or enteritis, since toxic mega colon may occur.
➢ Patients with chronic diarrhoea will develop nutritional deficiencies of variable
severity; therefore, proper nutritional assessment and support are helpful.
➢ Latent or active infection with HSV I and II are common in the general
population, and is usually mild in immune-competent persons.
➢ Severe cutaneous disease or visceral involvement is usually restricted to
patients with advanced immunosuppression with a CD4 count <100 cell/mm3.
➢ The lesions become extensive, persistent, severe and sometimes with bleeding.
➢ Unless thorough evaluation with regular inspection of genital and peri-anal
areas is done, patients very often don’t complain about genital lesions.
➢ The response to Acyclovir is gratifying if it is done in sufficient dose (400mg 4-
5 time/day) and sufficient duration (10 days to 2 weeks in moderately severe
or severe cases).
➢ There is risk of recurrence with severe immunodeficiency. In such cases repeat
treatment and put patient on chronic HIV care including ART.
➢ Herpetic oro-labial infection is treated the same way as ano-genital herpes
➢ The treatment of anal and genital warts is particularly frustrating when
they are large.
➢ Unlike other OIs, the response to ART is not satisfactory.
➢ Patients who have very well responded immunologically with ART continue to
suffer from the warts.
➢ Depending on the size, cauterization, podophyllin treatment and surgical
debulking, etc. may be tried.
➢ Neurological manifestations of HIV can occur at any time from viral acquisition
to the late stages of AIDS.
➢ They are varied and may affect any part of the nervous system including the
brain, spinal cord, ANS and the peripheral nerves.
➢ HIV affects the nervous system in 70-80% of infected patients.
➢ The effect may be due to direct effect of the virus, OIs and/or malignancies.
➢ For certain neurological manifestations, a single aetiology is responsible while
in others it is due to multiple causes.
➢ Most life-threatening neurological complications of HIV occur during the severe
immunodeficiency state and specific aetiological diagnosis in the Ethiopian
setting is often a major challenge.
➢ Diagnosis of neurological disorders in HIV in our setting depends on the
history and standard neurological examinations.
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Clinical Manifestations
➢ Focal encephalitis with headache, confusion, fever and/or signs of FND (motor
weakness) → The most common clinical presentation of T. gondii infection
among patients with AIDS
✓ Focal neurological abnormalities may be present on physical examination,
and in the absence of treatment, disease progression results in seizures,
stupor, and coma.
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Treatment
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Alternative regimen
I.
✓ Sulfadiazine, 1-2 gm PO QID for 6 weeks or 3 weeks after resolution of
lesion PLUS
✓ Pyrimethamine: loading dose of 200 mg stat, followed by 50-75 mg/day
for 6 weeks. PLUS
✓ Folinic acid (Leucovorin): 10-20 mg/d for six weeks
OR
II.
✓ Pyrimethamine and Folinic Acid (Leucovorin): (standard dose) PLUS
✓ Clindamycin: initially 200-400mg I.V. then 600 mg QID (300-900mg)
OR
III.
✓ Sulfadoxin Pyrimethamine, 1000mg/50mg, P.O., BID for 2 days, and then
one tablet/day for 6 weeks. PLUS
✓ Folinic Acid (Leucovorin): (standard dose) for 6 weeks
✓ Followed by Maintenance treatment with Pyrimethamine, 25mg/day PO,
daily
Primary prophylaxis
✓ Cotrimoxazole, 960mg PO, daily
✓ Indications for Initiating Primary Prophylaxis:
• Toxoplasma IgG positive patients with CD4 count <100 cells/mm3
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Pregnancy considerations
➢ Pyrimethamine and sulfadiazine are considered safe in pregnancy.
➢ Pyrimethamine should better be avoided during the first trimester and sulfa
drugs (including Sulphamethoxazole, sulfadiazine) have a potential risk of
neonatal kernicterus upon exposures in late pregnancy though no clearly
convincing data yet.
➢ The use of TMP (TMP-SMX) in the first trimester should also be evaluated
against the potential risk
Clinical features
Sub-acute meningitis, with high mortality:
Complications
➢ Chronic extensive genital HSV
➢ Raised ICP (increasing headache, vomiting, and cranial nerve palsy)
➢ Hydrocephalus, blindness, dementia, and personality change can occur as
permanent sequelae.
➢ Cryptococcomas can develop in the brain, more commonly in patients who
are not immunocompromised.
➢ Coma, cerebral oedema, and death follow if it is untreated, usually due to
elevated ICP.
Management
Non-Pharmacologic
➢ Control of raised ICP: daily LP with withdrawal of 20-30ml of CSF
➢ Coma care (including NG tube feeding) if the patient is unconscious
Pharmacologic
Phases of management: Induction for 2 weeks followed by consolidation for 8
weeks
Plus
➢ Flucytosine, 25 mg/kg, PO, QID
Option B* ➢ Amphotericin, 0.7 - 1 mg/kg/day Fluconazole 400 - 800
Plus mg/day
➢ fluconazole 800 mg/day OR
➢ Flucytosine, 100mg/kg
☛ * If amphotericin used laboratory monitoring and pre-hydration is recommended.
☛ * If the patient has meningitis or pneumonia, treatment with a regimen containing amphotericin is
preferred provided that facilities allow appropriate monitoring (kidney function and electrolytes).
➢ Minimize acute infusion reactions when amphotericin is given (e.g. Fever, chills,
headache, hypotension) by the following ways;
✓ Infuse the initial dose slowly over 3 - 6 hours.
✓ Prophylactic antipyretics or hydrocortisone should only be used in patients
who have previously experienced acute infusion reactions (and in whom
continued treatment with amphotericin is essential).
➢ >90% of death s in the 1st 2 weeks and 40% of deaths in 3rd to 10th weeks
are due to increased ICP. Thus, it is a must to manage.
➢ Daily serial LP should be done by drawing 20-30 ml of CSF based on
patient’s clinical response.
➢ Signs of ICP (headache, altered mental status, meningismus and changing in
hearing or vision) should be closely monitored, if possible opening pressure
should be measured.
➢ There is no role for acetazolamide, mannitol, or corticosteroids to reduce ICP.
➢ NB: Corticosteroids should not be routinely used during induction therapy unless it is used for
management of IRIS
➢ Among the most common causes of painful legs in HIV infection (due to
complication of HIV infection itself, of drug therapy, or of other metabolic or
organ dysfunction or nutritional deficiencies).
➢ Distal symmetrical sensory polyneuropathy is the most common presentation
but mono-neuropathies can also occur.
➢ The neuropathies associated with HIV can be classified as:
✓ Primary → HIV-associated.
✓ Secondary → causes related to medications (INH), OIs or organ
dysfunctions.
Diagnosis
Treatment
Monitoring of events
Clinical features
➢ Pruritus is the most common dermatologic symptom in HIV infected patients.
✓ It can be localized indicating primary skin lesion, or generalized that may
or may not indicate primary skin lesions.
✓ In many patient’s pruritus may be severe and may not be amenable to
available therapy.
✓ The most common skin conditions associated with pruritus in patients with
HIV include the following:
• Excessive dryness of the skin (Xerosis cutis)
• Eczemas like seborrheic dermatitis or contact dermatitis
• Folliculitis (may include S. aureus infection or hypersensitivity to
insects)
• Drug eruptions
• Scabies
• Intertrigo (Candida, tinea, herpes simplex)
Diagnosis
➢ In most patients, diagnosis of skin disorders with HIV disease can be
established by examining the lesions, clinically.
➢ However, as immune deficiency advances it may be useful to use
investigations such as biopsy to diagnose specific dermatosis or use staining
and culture to diagnose specific infections.
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➢ Ivermectin, 200µg/kg stat, for Norwegian (crusted
scabies) and resistant forms of scabies. And it is
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Complications
➢ Complications are more often if HIV acquire as adults, and particularly in
pregnant.
➢ After the introduction of vaccine, the number of complications in children
dramatically declined, although the most common complication has remained
bacterial superinfections;
➢ complications included
✓ Pneumonia
✓ Skin and soft tissue infections (42 %)
✓ Dehydration (11 %), and
✓ Neurologic complications (9 %) → Encephalitis, Reye syndrome
hepatitis or haemorrhagic syndromes
➢ Varicella complications acquired during pregnancy before 28 weeks’ gestation,
will cause congenital abnormalities in the child (also called congenital varicella
syndrome). If acquired around the time of birth, it can cause neonatal varicella,
which carries a high rate of pneumonia and other complications.
Treatment
➢ Start treatment ASAP ideally in < 24 hours after symptom onset.
➢ For oral treatment, the value of starting after 24 hours is not well established
Anti-viral therapy
➢ Acyclovir and its analogues (valacyclovir, famciclovir) are effective for the
treatment of primary varicella in both healthy and immunocompromised hosts
➢ It is recommended for all HIV-positive adults.
➢ D u r a t i o n o f t r e a t m e n t i s f o r 7 - 1 0 d a y s . Consider longer
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Drug options
✓ Acyclovir
• In adults including pregnant women:
o Acyclovir, 800mg, PO, 5 times daily for 7 - 10 days.
• In immunocompromised adults or those with disseminated disease:
o Acyclovir, 10mg/kg, IV, TID for 7 - 10 days (high-dose oral
acyclovir, if no IV available).
Or
✓ Valacyclovir, 1 g, PO, TID for 7 to 10 days o r
✓ Famciclovir, 500 mg, PO, TID for 7 to 10 days
N.B.
☛ For Extensive cutaneous lesions or visceral involvement:
✓ Acyclovir, 10 to 15 mg/kg/dose, IV, TID, until clinical improvement
✓ Switch to oral famciclovir or valacyclovir (preferred) or acyclovir
(alternative) to complete a 10 to 14 days course when formation of new
lesions has ceased and signs/symptoms of visceral infection are
improving
Supportive care
➢ The following general measures can be used for the symptomatic management
of rash and fever, and can also help reduce the risk of developing certain
complications:
✓ Antihistamines or calamine lotion are helpful for the symptomatic
treatment of pruritus.
✓ Paracetamol should be used to treat fever, particularly in children.
• Non aspirin NSAID’s can also be used. However, some providers
discourage NSAIDS because of the uncertain association with
streptococcal superinfection.
• Salicylates should be avoided since aspirin has been associated
with the onset of Reye syndrome in the setting of a viral infection
✓ Fingernails should be closely cropped to avoid significant excoriation and
secondary bacterial infection.
✓ Secondary bacterial infections may require antibiotics.
Clinical features
➢ Painful vesicular rash in a dermatomal distribution of a nerve supply that
does not cross the midline. Pain sometimes comes before the appearance of
the rash. Vesicles form in groups and progress to crusted lesions after a few
days.
➢ The rash is generally limited to one dermatome, but can occasionally affect
two or three neighboring dermatomes.
➢ Some patients can also have a few scattered vesicles located at some
distance away from the involved dermatome.
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➢ Most common areas: trunk, particularly the flanks, and forehead. Can involve
the eye and cause corneal scarring and blindness.
➢ HIV patients have more frequent multidermal involvement, involvement of the
trigeminal nerve, presence of systemic symptoms, and have a higher risk of
disseminated disease.
➢ Myelitis, meningitis, and encephalitis with headache, fever, neck stiffness,
altered motor and sensory function.
➢ Guillain-Barre syndrome.
➢ See pictures from physical examination section of Approach part of this
chapter above.
Complications
➢ Blindness due to corneal involvement.
➢ Post-herpetic neuralgia: chronic pain in the area where the lesions occurred
that can last for months to years after the acute episode.
Treatment
N.B
➢ Acyclovir is available in most setups of Ethiopia. Valacyclovir and Famciclovir
are preferred over acyclovir because of dosage frequency to increase
adherence but there is no clear difference in efficacy.
➢ Acyclovir and its analogues (Valacyclovir, Famciclovir) are dependent upon
renal function for clearance. So, follow up with RFT and dose adjustment is
needed in moderate to severe renal insufficiency.
been as well studied, the risk of adverse events secondary to antiviral therapy
is very low.
➢ Administer antiviral therapy after 72 hours if new lesions are appearing at the
time of presentation, as this indicates ongoing viral replication.
➢ However, the clinical utility of initiating antiviral therapy more than 72 hours
after the onset of lesions in immunocompetent persons is unknown.
➢ There is likely minimal benefit of antiviral therapy in the patient who has
lesions that have encrusted.
3. Immunocompromised hosts
Adjuvant therapies
➢ Unless there is neuropathic pain or post herpetic neuralgia, For patients with
uncomplicated zoster, there is no role for adjuvant agents, such as gabapentin,
TCA (like amitriptyline), or glucocorticoids, in the acute setting.
Patient monitoring
➢ Serial patient monitoring should include standardized pain measures and
frequent follow-up to assess efficacy in relief of symptoms
Recurrent zoster
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Chapter 5; RVI (ኤችአይቪ ኤዲስ)
➢ Patients with recurrent zoster should be treated with antiviral therapy using
similar a dose and duration as treatment of their initial episode.
➢ However, episodes of recurrent zoster are uncommon. Thus, viral cultures or
other detection assays (eg, antigen or DNA detection) if available, should be
performed since some patients (eg, those who present with recurrent herpes
simplex outside of the mouth or genital area) may be misdiagnosed as having
recurrent zoster.
➢ There are no data regarding the potential benefit of zoster vaccine in this
scenario.
Complicated zoster
➢ Certain immunocompetent patients with herpes zoster will present with ocular,
otic, or neurologic manifestations.
➢ Such patients may require IV and/or prolonged therapy.
➢ In addition, there may be a role for adjunctive glucocorticoids in certain
conditions.
D. Neurologic complications
➢ Neurologic complications where viral replication likely plays an important role
(eg, symptomatic meningitis, encephalitis, and myelitis).
➢ Treatment
✓ Acyclovir, 10 mg/kg, IV, TID, for 10 to 14 days
E. Postherpetic neuralgia
➢ The diagnosis is typically made when pain persists beyond four months in the
same distribution as a preceding documented episode of acute herpes zoster
➢ Additional factors supporting the diagnosis are:
✓ Advanced age
✓ Severe prodromal pain with acute herpes zoster
✓ Severe preceding rash
✓ Distribution in trigeminal or brachial plexus dermatomes
✓ The presence of allodynia
➢ Management
✓ Tricyclic antidepressants (e.g. Amitriptyline), gabapentin, and
pregabalin are generally the drugs of first choice.
✓ Amitriptyline 25 - 50mg before bed for neuropathic pain and post-
herpetic neuralgia
➢ For those with active lesions, there are no specific precautions within the
community setting. However, patients should be counseled about the risk of
viral transmission to others. In addition, until the rash has crusted, patients
should be advised to:
✓ Keep the rash covered, if feasible, and to wash their hands often to
prevent the spread of virus to others.
✓ Isolation of the patient to avoid spreading the virus. Contact
should be avoided until all lesions are crusted over → Avoid
contact with pregnant women who have never had chickenpox or the
varicella vaccine, premature or low birth weight infants, and
immunocompromised individuals.
Treatment:
➢ Topical steroid and oral antihistamines.
➢ If refractory (often), short course prednisolone may be used.
➢ ART is often effective.
✓ It can appear anywhere in the body and often is symmetric (skin/ mucous
membrane, GI, chest)
Treatment
➢ ART
➢ Local therapy → cryotherapy, laser, intralesional vinblastin, local radiation
➢ Systemic chemotherapy → indicated for rapidly progressive, severe
lymphedema, pulmonary and other visceral involvement
✓ Regimen → adriamycin, beomycin, vincristin every 2-3 weeks for 6 cycle.
✓ Liposomal daunorubicin/doxorubicin, paclitaxel have better response rate
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✓ Atrial fibrillation, is the most common Genetic disorders like EDS and marfan
cause for cardio-embolic stroke, and it syndrome → increased risk of vascular
is a risk factor for future dissection to result SAH.
cardiovascular disease. Family hx
CAD, PAD
OCP use
Hyperlipidemia (atherosclerosis)
Anticoagulant therapy
Hypercoagulable states (SCA, PCV,
protein S &C deficiency, antithrombin III
deficiency, SLE)
Substance abuse like cocaine,
amphetamine
Trauma → carotid or vertebral artery
dissection
Spinal manipulation → vertebral artery N.B ABCD2 score
dissection
ABCD2 Score
A → age > 60 1
B → BP ≥ 140/90 1
Total 9
Complication of stroke
Early complications
Late complications
✓ Contracture or spasticity
✓ Neurologic disability or paralysis like wheelchair dependent
✓ Epilepsy
✓ Aphasia
✓ Sleep disturbance
✓ Socioeconomic factor related to difficulty in involvement of daily activity and
permanent need of help from family members
✓ Depression/anxiety from prolonged immobility
Sample history
Sample history of a patient from debark with Emergency ward DX of Right sided,
crossed, flaccid hemiplegia 2ry to ischemic stroke 2ry to uncontrolled HTN r/o
hemorrhagic stroke
Chief compliant
Failure to use right upper and lower extremities of 4 hr’s duration
HPI
This is a Right-handed, known hypertensive patient for the past 3 years on amlodipine to
be taken 10 mg po daily and Hydrochlorothiazide to be taken 25 mg po daily, advised to
stop alcohol and on salt restriction. He was Adherent for his medication with regular
follow up at debark general hospital every two to three months.
Currently presented with Sudden onset right sided body weakness of both upper and
lower extremities of 04 hours duration. The weakness happens on his bed time in which
he noticed while he awakes from sleep. It was maximal at onset involving both upper
and lower extremities at a time to the extent he failed to stand from sleeping position
and can’t raise, flex or extend his right-side extremities by himself.
Two hours before admission he experienced failure to communicate but he was able to
understand only gesture associated with face deviation towards the right side but no
LOC, vomiting or headache
While they were coming to our hospital by ambulance (approximately 30 minutes before
admission), he experienced single episode of sudden onset, generalized Abnormal body
movement together with up rolling of the eyes and drooling of saliva followed by
excessive salivation, bleeding from tongue and urinary incontinence (observed by one of
family members in the ambulance), Finally he loses his consciousness and awakes
approximately 3-4 minutes later.
For this, he visited debark general hospital where he was catheterized, glucose level
measured, put on intranasal oxygen, resuscitated with half bag of NS and referred to our
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➢ No hx of DM (RF)
➢ No hx of Dyspnoea, orthopnoea, PND, palpitation (cardioembolic stroke from cardiac
causes)
➢ No hx of head trauma (RF, or DDX in SDH)
➢ No hx of Smoking or chronic alcohol intake (RF)
➢ No hx chat chewing or other drug use (cocaine, amphetamine… for females consider
OCP as hypercoagulable state)
➢ No hx of malar rash, photophobia or joint pain (SLE as RF)
➢ No hx of gum bleeding, epistaxis or bleeding from other sites (bleeding
disorder may be the cause for haemorrhagic stroke, don’t give heparin in bleeding disorders)
➢ No hx of intermittent claudication or leg swelling (DVT as cxn)
➢ No hx of chest pain cough or fever (pneumonia, PE as cxn)
➢ No hx of constipation (cxn)
➢ No hx of Ear discharge, tooth extraction, or sinusitis (brain abscess as DDX)
➢ No Similar hx of illness in the family, previous hx of similar illness or
1 GA
➢ Face deviation
➢ LOC (decreased level of consciousness)
➢ Limb position → Externally rotated limb (in flaccid hemiparesis/plegia), internally
rotated limb (in spastic hemiparesis/plegia)
➢ Speech disturbance
➢ Cardio respiratory distress
2 Vital signs
➢ Irregularly irregular pulse → Atrial fibrillation
➢ HTN as RF, may be hypotensive
o Hypotension is associated with worsening of stroke; can be
associated with serious concomitant conditions like MI, aortic
dissection or sepsis.
o Hypertension is a normal response to stroke but malignant HTN
should be treated.
o Very high HTN may suggest ICH.
➢ Tachypnoea and tachycardia
➢ Febrile
3 HEENT
➢ Eye changes
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6 CVS
➢ Bruit over the carotid artery and other major arteries
➢ Arrythmia (Abnormal pulse rhythm like irregularly irregular pulse from atrial
fibrillation)
➢ CHF Features
➢ Cardiomegaly signs from longstanding HTN
7 Abdominal examination
8 GUS
➢ Bladder distension from urinary retention
9 MSS
➢ DVT (peripheral emboli) → limb ischemia
➢ Injuries sustained during collapse with stroke
10 IS
➢ Skin and mucous membrane bleeding features → bleeding disorders as a
cause of ICH
➢ Xanthelasma, rash → arteritis, splinter haemorrhage, livido reticularis
11 NS
➢ Level of consciousness
❖ May be comatose
➢ CN
❖ CN palsy
✓ CN VII damage → Facial deviation
▪ Infra nuclear if both upper and lower face area
involved
▪ Supranuclear if only lower face part involved
❖ Dilated pupil, decerebrate rigidity → visual field examination is
very important if posterior fossa haemorrhage is suspected
❖ Homonymous visual field defects
➢ Motor examination
Inspection → decreased muscle bulk of the affected limb,
fasciculation
Palpation
✓ Hyper/hypotonic→ i.e. spastic or flaccid weakness
respectively
✓ Decreased power
✓ Hyperreflexia in spastic hemiparesis and hyporeflexia in
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➢ Sensory examination
Sensory loss on the affected side → difficult to assess if
comatose
➢ Meningeal irritation signs are usually -ve but there may be +ve
➢ Coordination
Construction apraxia (inability to perform learned activity e.g.
writing)
Cortical sensory loss
✓ Absent stereognosis
✓ Agraphtesia
✓ Absent two-point discrimination
✓ Absent simultaneous extinction.
N.B
Very critical tests: swallow test; ocular muscles and gaze tests; mental status
assessment and sensori-motor assessment
❖ ACA damage
❖ MCA damage
✓ aphasia
❖ PCA damage
✓ Dysarthria and facial numbness
✓ Ataxia and hornor sxx
✓ Facial weakness
✓ Hemiparesis
✓ Hemisensory loss
✓ Hemianopia
✓ comatose
❖ Thalamic hemorrhage
✓ Down and inward deviation of eye
✓ Unequal pupil with absent pupillary reflex
✓ Ipsilateral horner sxx
✓ Absent convergence
❖ Pontine hemorrhage
✓ Deep coma with quadriplegia
✓ Decerebrate rigidity with pinpoint pupil that react to light
✓ Doll’s head/oculocephalic manoeuvre
➢ The NIHSS is a highly reliable and valid screening assessment for the
rapid evaluation of a patient with acute stroke: Although it’s not a substitute
for comprehensive neurologic examination.
➢ The 11-item scale measures consciousness, orientation, visual fields, gaze,
language fluency and comprehension, speech, sensory loss and neglect,
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➢ The scale can easily be completed in less than 10 minutes and serves as
an initial measure of stroke severity ranging from 0 (no deficits) to 42
(maximum score)
➢ Minor stroke considered when NIHSS score is <5
➢ NIHSS score emphasizes much on dominant hemispheric function than non-
dominant functions
➢ Additionally, the NIHSS may underestimate posterior circulation stroke
deficits compared to anterior circulation stroke deficits
4. Facial Palsy /paresis/ (ask patient to show teeth or raise eyebrows and
close eye)
Normal symmetrical movement (0 points)
Minor paralysis (flattened nasolabial fold, asymmetry on smiling) (1
point)
Partial paralysis (total or near total paralysis of lower face) (2
points)
Complete paralysis of one or both sides (3 points)
5. Motor function of arm
A. right arm
No drift (0 points)
Drift (1 point)
Some effort against gravity (2 points)
No effort against gravity (3 points)
No movement (4 points)
Untestable (amputation or joint fusion at the shoulder) (0 points)
B. Motor function of left arm
No drift (0 points)
Drift (1 point)
Some effort against gravity (2 points)
No effort against gravity (3 points)
No movement (4 points)
Untestable (amputation or joint fusion at the shoulder) (0 points)
6. Motor function of leg
A. right leg
No drift (0 points)
Drift (1 point)
Some effort against gravity (2 points)
✓ No aphasia (0 points)
Mild-to-moderate aphasia (1 point)
Severe aphasia (2 points)
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DDX
1) Stroke
Hemorrhagic stroke
✓ ICH
✓ SAH
Ischaemic stroke
✓ Embolic
✓ Thrombotic
2) Vasculitis
✓ TB
✓ Syphilis
✓ SLE
3) Bleeding to brain tumour→ characterized by seizure, hydrocephalus, acute
neurologic features like FND
✓ Glioblastoma multiforme
✓ Metastasis tumour to brain from melanoma, Bronchogenic ca, RCC
4) Acute SDH
5) Neurosyphilis
✓ Vasculitis
✓ Syphilitic guma
6) Todd’s paralysis → a.k.a post ictal paralysis. paralysis which occurs
following seizure
7) Hemiplegic migraine
8) Encephalopathy
✓ Metabolic → hepatic encephalopathy, ureamic encephalopathy
✓ Toxic → alcohol, illicit drugs
✓ Infectious → meningoencephalopathy, sepsis
9) Brain abscess
Triads of brain abscess include fever, headache, FND
10) Neurocysticercosis
✓ Rare in Ethiopia since pork is not usual food due to cultural and
religious values
11) Space occupying lesions
✓ Take long time course unlike stroke
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Stroke mimics
STROKE is considered when focal deficits occurs abruptly and follow vascular
territory
N.B.
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IX
N.B for stroke pt’s, before going to the list of Ix modalities Do RBS, manage life
threatening conditions, stabilize the patient, then do emergency CT. After that, you
will go to other IX and mgt concomitantly.
‘Time is brain’
1. Perform RBS
If suspected bleeding risk; CBC, PT, PTT
2. Perform CT
3. Start rTPA if indicated
Imaging
11. CT scan
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CT IS important for
1. Large-artery atherosclerotic disease resulting in stenosis or occlusion,
2. Small-vessel or penetrating artery disease (lacunes)
3. Cardiogenic or artery-to-artery embolism,
4. Non-atherosclerotic vasculopathies,
5. Hyper-coagulable disorders
6. Infarcts of undetermined causes
12. MRI
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Discussion
Stroke
Cerebro-vascular diseases include some of the most common and
devastating disorders collectively called as Stroke
A stroke, or cerebrovascular accident, is defined as an abrupt onset of a
neurologic deficit that is attributable to a focal vascular cause.
Include Ischemic stroke, Hemorrhagic stroke, and Cerebro-vascular
anomalies such as intracranial aneurysms and AVMs (Arteriovenous
malformations).
All of which manifest with an abrupt onset of neurologic features that are
often focal in nature: Often follow vascular distributions.
Focal ischemia or infarction is usually caused by thrombosis of the cerebral
vessels themselves or by emboli from a proximal arterial source or the
heart.
A generalized reduction in cerebral blood flow due to systemic hypotension
(e.g., cardiac arrhythmia, MI or hemorrhagic shock) produces Syncope.
If low cerebral blood flow persists for a longer duration, then infarction in
the border zones between the major cerebral artery distributions may
develop: Watershed ischemia
Intracranial hemorrhage (ICH) is caused by bleeding directly into or around
the brain; it produces neurologic deficit by mass effect, blood toxic effect or
increased ICP
Stroke: Classification
1. Ischemic Stroke
2. Hemorrhagic Stroke
Epidemiology
✓ Stroke is the second leading cause of death worldwide
✓ Every 40 seconds there is an occurrence of stroke in USA.
✓ Some 88% of these strokes are ischemic. Around 18-20% of stroke is due
to ICH
✓ In developing areas, the Incidence rate of ICH is relatively higher
✓ In UOG Hospital; among stroke patients admitted to the Hospital, 60-70%
are due to Ischemic stroke commonest cause being arterio-arterial embolic
stroke
✓ Steep decreases in stroke incidence and mortality have occurred in
industrialized nations.
• This is attributed to a declining stroke incidence, and lower case-
fatality rates, with suggestive evidence favoring a trend in declining
stroke severity.
• However, the declining stroke incidence has been reversing with the
aging of the population, greater awareness of stroke symptoms, and
better diagnostic tools
✓ Stroke mortality and incidence are increasing in developing nations.
✓ Socioeconomic factors, dietary and lifestyle behaviors, different patterns of
risk factors, and environmental conditions may explain the different
incidences of stroke observed in different parts of the world
✓ Increased life expectancy; improved awareness and improved diagnostic
facilities contribute to increase in incidence rate
Figure; Acute left middle cerebral artery (MCA) stroke with right hemiplegia but preserved
language. B) Predicted region of infarct (red) and penumbra (green) based on CT
perfusion data. E) CT scan of the brain 2 days later; note infarction in the region
predicted in B but preservation of the penumbral region by successful revascularization.
☛ MCA;
☛ vertebrobasilar arteries
Cardiogenic embolism
❖ Cardio-embolic strokes are associated with substantial morbidity and
mortality.
❖ Embolism of cardiac origin accounts for approximately 15% to 20% of all
ischemic strokes.
❖ These cardiac emboli may be composed of platelet, fibrin, platelet-fibrin,
calcium, micro-organisms, or neoplastic fragments.
❖ Common causes are AF; MI; IE; rheumatic MS; Prosthetic valves; CMP;
atrial myxoma
Cardio-embolic stroke: AF
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Table, CHA2DS2-VASc risk stratification score for estimation of stroke risk for
nonvalvular atrial fibrillation in adults
CHA2DS2-VASc Score
1. CHF 1
2. HTN 1
3. Age
☛ ≤ 64 ---------------------------- 0
☛ 65 - 74 ------------------------- 1
☛ ≥ 75 ---------------------------- 2
4. DM 1
5. Prior Stroke or TIA or 2
thromboembolism (doubled)
6. Vascular disease (MI, PAD, 1
Arterial plaque)
7. Sex category
☛ Female ------------------------- 1
☛ Male ---------------------------- 0
Maximum score 10
❖ The higher the score, the higher the annual stroke risk.
❖ For patients with CHA2DS2-VASc score >1, anticoagulation is generally
indicated unless high bleeding risk/based on HASBLED score/
o Score 0→ No antithrombotic
o Score 1→ Anti-platelet or anticoagulation
o Score ≥ 2 → anticoagulation.
❖ Commonly used Antiplatelets include Aspirin (1st line) & clopidogrel (2nd
line). Commonly used anticoagulants include warfarin, UFH, LMWH
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❖ Occur in the border zone between adjacent arterial perfusion beds of the
major circulations:
– During or after cardiac surgery
– After an episode of sustained and severe arterial hypotension that
can happen after cardiac arrest, prolonged hypoxemia, or bilateral
severe carotid artery disease
❖ May be caused by micro-embolism or hyper-viscosity states.
❖ Often bilateral but can be unilateral if there is severe arterial stenosis on
one side only
❖ Ischemia in the border zone or junctional territory of the ACA, MCA, and
PCA may result in bilateral parieto-occipital infarcts.
❖ There can be a variety of visual manifestations, including bilateral lower
altitudinal-field defects, optic ataxia, cortical blindness, and difficulty in
judging size, distance, and movement.
❖ Ischemia between the territories of the ACA and MCA bilaterally may result
in bilateral fronto-parietal infarctions:
❖ Bi-brachial cortical sensori-motor impairment (“person in a barrel”) and
impaired saccadic eye movements
❖ Ischemia in the border zone between the MCA and PCA may cause
bilateral parieto-temporal infarctions.
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Changing in Epidemiology
Hypertensive hemorrhage:
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➢ Bleeding occurs anywhere in the brain depending on the cause: Often lobar
and multiple hemorrhage
• Hypertension
• Vascular malformations
• Intracranial tumors
• Bleeding Disorders, Anticoagulants, and Fibrinolytic Treatment
•
•
Cerebral Amyloid Angiopathy
Granulomatous Angiitis of the CNS and Other Vasculitides
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• Sympathomimetic Agents
• Hemorrhagic Infarction
Hypertensive ICH
➢ The main cause of ICH is hypertension.
➢ The primary role of HTN in ICH is supported by a high frequency (72% -
81%) of hx of HTN, significantly higher BP measurements at admission in
comparison with patients with other stroke subtypes, high frequency of LVH,
and over-representation of common genetic variants associated with
hypertension.
➢ Excluding patients with hemorrhage associated with ruptured AVMs, tumor,
anticoagulant and thrombolytic therapy, and cocaine ingestion; it was
determined that the cause was hypertension in 72% of patients. Although
the prevalence of HTN in ICH cases is dropping to 50% in recent years
➢ Patients with severe acute hypertension may have a similar risk as those
patients with chronic low-grade hypertension: the issue is uncontrolled HTN
➢ The vascular lesion produced by chronic hypertension that leads to arterial
rupture and ICH is probably lipohyalinosis of small intra-parenchymal
arteries: Ultimately formation of micro aneurysm
➢ The most related risk factors for development of theses vascular changes
with HTN are duration of HTN and older age.
➢ Common sites of bleeding are: Putamen > Lobar > Thalamus > Cerebellum
> Pons……
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Use of anticoagulation
Patients on long-term anti-coagulation have a risk of ICH of approximately
1% per year, although the highest risk is within the first year.
Risk factors include:
✓ Older age
✓ Hypertension
✓ Previous ischemic stroke, and leukoariosis.
ICH risk is significantly increased when the INR is > 3.5 and add on use
of anti-platelets.
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SUSEPTIBLE VESSEL
These vessels are branched from large arteries proximal to arterioles where cerebral
auto -regulation occurs
CHRONIC INJURY
Atherosclerosis and HTN will result a series of injuries to these vessels ultimately
result in thickening and fragile
ICH
The exact mechanism how these vessels bleed is not known but:
Micro anurysm formation; sudden high BP and inability for the vessels to maintain
RBCs in the vessels
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Clinical presentation
The clinical presentation of ICH has two main elements:
1. Symptoms that reflect the effects of intracranial hypertension
2. Those smx’s that are specific for the location of the hematoma
Putaminal hemorrhage
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Lobar hemorrhage
Management principles
1. Differentiate Ischemic from hemorrhagic stroke ASAP (Clinically, Emergency
CT in best setups)
2. ABC of life
✓ Treat and prevent aspiration (target is saturation ≥ 94%)
✓ Treat hypotension and shock (may be cause of stroke)
3. RBS → if low manage as hypoglycemia
4. Emergency CT
✓ Non contrast CT
✓ Can detect ischemia as early as 1hr and hemorrhage within 10 min
(i.e used to r/o hemorrhagic stroke)
✓ If there is no abnormality in CT, treat as ischemic stroke
N.B MRI is very sensitive and specific, but it needs time for Dx
5. Identify the cause
6. Specific and supportive management based on type of stroke
Let’s show you order sheet example for Ischemic stroke in our set up
before going to detailed management principles → it may be different based
on your patient comorbid conditions and complications.
Treatment
New order
❖ Secure double IV line
❖ Put on 100% O2 (if SPO2 is < 95%). E.g. Put on 1L/min of INO2
❖ NG Tube feeding with 300ml of semisolid food every 3 hours and Monitor swallow test daily (this order
is, if swallow test is -ve)
❖ Follow Vital sign strictly
❖ Catheterize and follow input and output strictly (i.e. Maintain fluid balance)
❖ Do RBS QID (control of glucose to be between 140 mg/dL and 180 mg/dL)
❖ Position every 1hr (for critical pt) or every 2hr (for noncritical pt)
❖ Omeprazole, 20mg, PO/via NG tube, BID
❖
❖
UFH, 5,000 IU, Sc, BID (Consider Warfarin if there is CHADVASC score indication)
Aspirin, 325 mg, PO, Loading then 81mg (81-100 mg), PO, daily 375
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❖ Atorvastatin 80 mg daily (for at least 3 months, then 40 mg daily for life long which should be
continued with chronic OPD follow up)
Added order
If BP > 220/110 mmHg
❖ Lasix or HCT Plus
❖ ACE-I (Captopril/enalapril) or CCB (amlodipine)
If Hyperglycemia (>180 mg/dL) give insulin → see dose below
If febrile → antipyretics and cooling cloths (cold compression)
If GCS < 8, insert NG tube and Intubate. Routine NG tube, airway, and catheter care with eye and
mouth care.
If there is DVT and PE
❖ UFH, 5,000 IU, IV, loading then 250 IU/kg/dose, Sc, BID
❖ Add warfarin 2-5mg, PO/IV, on day 1 or 2 of UFH, daily for 2 days, check INR after 2 days and adjust
based on the result
❖ Overlap warfarin and UFH for at least 5 days until desired INR/INR=2-3/ maintained for 24hr then
discontinue UFH.
If there is cerebral edema (increased ICP)
❖ Head position between 30 and 450
❖ Mannitol Loading dose 1g/kg over 30-60min, followed by a maintenance dose of 0.5g/kg every 4-6hrs (if
measuring weight is difficult, mannitol 300ml loading over 30 min then a maintenance dose of 100ml
QID then deescalate)
❖ Maintenance of euvolemia with NS, avoid dextrose solutions
Treat causes and comorbidities → Atrial fibrillation, MI, UTI, Pneumonia….
Treat electrolyte disturbance
❖ Link to physiotherapy (when patient is stable and before discharge)
1.1 IV Thrombolysis
ABSOLUTE CONTRAINDICATIONS
BP > 185/110;
OTHER CONSIDERATIONS
Minor stroke (Typically NIHSS score <5) and rapidly improving deficits
Pregnancy
Seizure at onset with post-ictal residual deficits
Major extra cranial injuries and surgery in the last 15 days
Administration of rtPA
➢ IV access with two peripheral IV lines (avoid arterial or central line placement)
➢ Review eligibility for rtPA
➢ Administer 0.9 mg/kg IV (maximum 90 mg) IV as 10% of total dose by bolus,
followed by remainder of total dose over 1 hour
➢ Frequent cuff blood pressure monitoring
➢ No other antithrombotic treatment for 24 h
➢ For decline in neurologic status or uncontrolled blood pressure, stop infusion,
give cryoprecipitate, and reimage brain emergently
➢ Avoid urethral catheterization for ≥2 h
CXN of rTPA
Oro-lingual angio-edema
✓ is a rare but potentially serious complication of rtPA administration:
especially in those with ACE-I:
✓ Rx with anti-histamines and steroids
ICH: 1.9 % - 6.4%.
✓ Treatment includes;
➢ Control of hypertension (systolic target 140 mmHg to 160 mm
Hg)
➢ Reversal of the fibrinolytic effect with cryoprecipitate (10 units)
or an antifibrinolytic agent (tranexamic acid 10 mg/kg to 15
mg/kg IV over 20 minutes or έ-aminocaproic acid 5 g IV
followed by an infusion of 1 g/h if necessary
Clinical indications
Age ≥ 18 years
NIHSS score ≥ 6
Time from Symptom onset to groin puncture < 6 hours
Good prestrike functional status
Presence of proximal intracranial artery occlusion
ASPECTS score ≥ 6 on baseline CT scan (ASPECTS = Alberta stroke
program early CT score)
✓ Failed rTPA
✓ Large thrombus on imaging
➢ BP and Stroke
✓ Higher BP at the onset of stroke is required; part of physiologic
response to perfuse collateral vessels
✓ BP should be lowered if above 220/110 mmHg if rTPA is not used;
reduce by 15% in the first 24 hours: if rTPA to be used keep the
BP below 180/90.
✓ Diuretics and ACE-I are preferred but any treatment choice
✓ BP should be improved if its low; Using IV fluids and vasopressors
➢ Hyperglycemia / hypoglycemia
✓ Keep RBS level between 70 and 180 mg/dl in the acute setting:
Dextrose/insulin
✓ If there is hyperglycemia give insulin with sliding scale principle*
RBS value (mg/dl) Insulin dose (IU) to be given
181 – 200 2 i.e.
201 – 250 3 increase
251 – 300 4 by 1 IU
301 – 350 5 for every
351- 400 6 rise of
> 400 50 mg/dl
✓ Check Urine ketone
and glucose
✓ Consider DKA if S/he
has DM
* Look at DM management for more
➢ Assess for dysphagia; and aspiration using swallow test and GCS
➢ NG tube feeding and intravenous fluid in early states of stroke
❖ NG tube for
✓ Feeding
✓ Prevention of aspiration
✓ Dysphagia
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N.B
➢ Assess for fever; if occurred assess for site of infection and treat; use
antipyretics and cooling cloths (cold compression) to reduce fever
➢ Monitor electrolyte frequently and treat: commonest abnormality is
hyponatremia
➢ Monitor LFT and RFT as well as cardiac evaluation frequently and treat
Bed side care for the clothing and intermittent positioning to prevent
pressure sore
Routine NG tube; airway; and catheter care with eye and mouth care
Monitor swallow daily and act accordingly
3.5.1 Infections
3.5.2 DVT
The development of DVT may take place as early as day 2 after stroke
onset, with a peak incidence between days 2 and 7.
PTE occurs in 1-3% of stroke with mortality rate of 13-25%
Severe disability; old age and dehydration are risk factors
Heparin dose
Prophylaxis Therapeutic
UFH 5,000 IU, Sc, BID 5,000 IU, IV, loading then 250
IU/kg/dose, sc, BID or 80 IU/kg/hr
maintenance dose
LMWH (e.g. 1mg/kg/day (40mg, sc, 1mg/kg/dose, sc, BID
enoxaparin) daily)
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Chapter 6; Stroke (የጭንቅላት ደም ስር በሽታ፣ እስትሮክ)
Treatment includes:
✓ Head position between 30 and 45o
✓ Start osmotic therapy with Hypertonic saline or IV mannitol
✓ Mechanical ventilation: Hyperventilation
✓ Steroid (like dexamethasone, 6mg, IM) → for meningitis, brain tumor,
brain abscess
✓ Consider decompressive surgery
Patients at the highest risk for developing malignant cerebral edema are:
▪ Internal carotid artery or proximal middle cerebral artery with a large
infarction volume;
▪ CT with frank hypodensity within 6 hours; more than 1/3rd of
hemisphere infarction; midline shift > 5 mm in the first two days of
stroke
Clinical factors associated with cerebral edema:
– An NIHSS score > 20 in dominant hemispheric strokes or > 15 in
non-dominant hemispheric strokes has been associated with
malignant infarction.
– Other clinical factors associated with edema are early nausea and
vomiting, female sex, congestive heart failure, and leukocytosis at
presentation.
General managements of cerebral edema include
✓ Frequent neurologic examinations to monitor for neurologic
deterioration
✓ Maintenance of normothermia
✓ Avoidance of hypercarbia
✓ Maintenance of euvolemia while avoiding hypotonic solutions
✓ Control of glucose to between 140 mg/dL and 180 mg/dL
✓ Correction of hyponatremia
✓ Prevention of aggravating factors
➢ Hypercarbia
➢ Hypoxia
➢
➢
Hyperthermia
Acidosis
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Chapter 6; Stroke (የጭንቅላት ደም ስር በሽታ፣ እስትሮክ)
➢ Hypotension
➢ Hypovolemia
Positional
Initial management of elevated ICP includes elevating the head of the bed to
30 degrees (avoidance of flat supine position) and appropriate sedation and
pain control.
Avoidance of head and neck positions compressing jugular veins
Medical management
Fluid management
GENERAL MEASURES
o Antihypertensive agents
o Statin treatment
o Diet and physical activity
The prevention strategy depends on the mechanism of Ischemic stroke
Aspirin
✓ Loading dose of 325 mg then 81-100 mg maintenance should be
given as early as possible and ideally within 48 hours of stroke
onset.
Warfarin
✓ Inhibits the synthesis of factors II, VII, IX, and X, as well as proteins C and
S: follow up with PT; PTT and INR
✓ Indicated for primary and secondary prevention of stroke in patients with
NVAF: depends on CHA2DS2Vas score
✓ Other Indication for secondary prevention includes: cardio-embolic stroke
following structural diseases of the heart like RHD; MI; DCMP…. Or
following large vessel stroke with AF.
✓ Initial dose; 2-5mg, PO/IV, daily for 2 days, check INR after 2days and
adjust based on the result
N.B
➢ Recurrent Stroke
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Chapter 6; Stroke (የጭንቅላት ደም ስር በሽታ፣ እስትሮክ)
4.4 BP management
❖ Administer O2
❖ GI prophylaxis for Cushing ulcer
❖ DVT prophylaxis after 24hrs → early physiotherapy
❖ Bladder care
❖ NG tube
❖ Prevent bedsore
✓ Positioning every 1hr for critical pt and every 2hr for non-critical pt
❖ Treat comorbidities → MI, UTI, Pneumonia…. which increase metabolic
demand of brain and increase 2ry brain injury
❖ Treat electrolyte disturbance
❖ Anti-hypertensive
✓ If s/he was on antihypertensive mgt, resume previous dose after
24hr
✓ For new case treat after 7day
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✓ A significant amount of the neurologic damage that occurs after ICH can be
attributed to secondary processes.
✓ A rationale for surgical removal of ICH is to remove the offending
substances before secondary damage can develop: Unfortunately, only a
few ICHs are candidates for surgical removal.
▪ Cerebellar hemorrhages > 3 cm in diameter should have surgical
evacuation.
The Minimally Invasive Surgery Plus T-PA for ICH Evacuation
The Intra-operative CT-Guided Endoscopic Surgery for ICH
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
✓ heaviness
➢ Back pain
1st smx mostly
Onset → rapid/slow
Localized over the spine (in non-compressive lesions) or radiate to
root distribution like to buttock or LL i.e. radicular pain (in
compressive lesions)
Characterize the pain
✓ Sharp, lancinating, radicular pain, aggravated by coughing,
sneezing, or straining → compressive lesions
✓ Dull aching or burning, bund like, localized pain → non
compressive
Persistent or intermittent
Associated with low grade intermittent fever, chills and rigor (e.g. in
post viral TM/transverse myelitis/)
o N.B if fever is associated with chills and rigor mostly it is high
grade fever
➢ Preceding infection smx → URTI, GI infections, UTI
➢ Incontinence
Faces/flatus, urinary incontinence
Urgency, hesitancy
Constipation, urinary retention
➢ Fever
➢ Ulceration → with foul smelling discharge
➢ Neck stiffness
Risk factors
➢ Infection
Syphilis → Tabes dorsalis
TB → TM (transverse myelitis), TB spondylitis
Viral → TM
Schistosomiasis
▪ TM, granulomatous disease
▪ S.mansoni and S.hematobium typically infect the spinal cord
causing rapidelly progressive TM, affect lower thoracic spinal
cord followed by lumbosacral spinal cord
Brucellosis
➢ Vaccination → GBS from acute rabies vaccine
➢ Diet → guaya → neuro-laterization
➢ Malnutrition
Vitamin B12 deficiency which result in SCDC (severe combined
degeneration of the cord), common in vegetarians
Vitamin B12 deficiency also occurs in post illeal resection
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ Trauma → Disc prolapse (common in heavy weight lifters), SDH over the
spinal cord
➢ Occlusion of anterior spinal artery → anterior cord sxx
Caused by atherosclerosis, embolism, vasculitis…
Other cause of anterior cord sxx is abdominal surgery (rupture of the
aorta) → spinal cord infarction
➢ Malignancy
primary or metastasis to spinal cord
hematologic malignancy involving vertebral bones
other malignancies which metastasize to the back bone like
prostate,breast, bronchogenic ca,RCC, GI malignancy
➢ Family history → ALS (amyotropic lateral sclerosis), hereditary spastic
paraplegia
➢ AF, IE, DCMP, CHF → result in cardiac emboli to anterior spinal artery
➢ DM → Posterior cord sxx, DSPN (Distal symmetric pyelonephropathy)
➢ RVI → vascular myelopathy, SCDC
Complication of paraplegia
➢ DVT
➢ Aspiration pneumonia
➢ Bed sore
Sample history
Sample history of a patient from Metema with the DX of paraplegia 2ry to non-
compressive myelopathy 2ry to acute transverse myelitis.
Chief compliant
Bilateral lower extremity weakness of 10 hrs duration
HPI
This patient was last relatively healthy 10 hours back, at which time he started to
experience sudden onset of bilateral lower extremity weakness while he was
sitting with families in a holiday gathering. The weakness was maximal at onset
to the extent he failed to stand from sitting position and he was unable to raise,
flex or extend the legs by himself. Associated with this he also feels numbness
which starts in the feet and progress upwards, burning sensation, Paresthesia,
Cold sensation heaviness of the legs, Fecal and urinary incontinence.
given unspecified antipain, and red oval tablets to be taken 3 times per day. He
got improvement for the pain and he visited metema primary hospital when he
sustained weakness and after catheterization he was referred immediately to our
hospital for better investigation and management.
➢ He is unmarried daily laboror and has hx of unsafe sexual practice with
multiple sexual partners but no genital ulcer or penile discharge (tabes
dorsalis/tertiary syphilis/ i.e. posterior cord sxx, post viral TM, RF for herepes zoster)
➢ NO hx of chronic cough, contact with chronic cougher or a known TB
patient (TM /transverse myelitis/, TB spondylitis]
➢ No hx of vaccination (GBS from acute rabies vaccine)
➢ He/she usually eats injera made of ‘‘teff’’ and ‘‘machilla’’ and ‘’wott’’
made of ‘‘atter’’ and ‘‘dagusa’’ 3-4 times per day. Occasionally he/she
eats meat during holidays (guaya → neurolateralization, vitamin B12 deficiency → SCDC,
copper deficiency → myeloneuropathy)
➢ No hx of smoking or chronic alcohol intake
➢ No hx of river water contact (RWC) or post RWC itching (schistosomiasis)
➢ No hx of abdominal surgery (rupture of the aorta → spinal cord infarction)
➢ No hx of pesticide or herbicide exposure, radiotherapy to the back
(Lymphoma is the commonest cause of compressive myelopathy, radiation myelopathy)
➢ No hx of Bone pain, epistaxis, swelling over the neck, axilla or groin
(hematologic malignancy involving vertebral bones, also r/o other malignancies which metastasize to the back
bone like prostate, breast, bronchogenic ca, RCC, GI malignancy)
➢ No hx of trauma to the back (SDH over the spinal cord)
➢ No family hx of similar illness (ALS, hereditary spastic paraplegia)
➢ No hx of dspnea, orthopnea, PND or palpitation (cardiac emboli resulting in anterior
spinal cord sxx)
➢ No hx of tinnitus, blurring of vision or light headedness (Vitamin B12 deficiency
→ SCDC)
➢ NO hx of DM, HTN or asthma (DM cause posterior cord sxx without weakness)
➢ Screened for RVI and found to be NR (GBS, TM, Vascular myelopathy, SCDC)
1 GA
2 Vital signs
❖ GBS or other causes of autonomic dysfunction
➢ OHT ❖ In compressive myelopathy autonomic dysfunction happens late in the disease
➢ Tachycardia progression since autonomic pathway is in the center of spinal cord which will
➢ Tachypnea
be affected later when the mass is huge enough
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
4 LGS
Breast ca features
Cervical LAP from lymphoma which result in compressive myelopathy
Anhidrosis and sweat level
5 RS
6 CVS
7 Abdominal examination
8 GUS
Urinary retention
Sexual dysfunction
9 MSS
DDX
DDX of Paraplegia
UMNL LMNL
Brain Spinal cord Plexopathy
Parasagittal Compressive non-compressive Radiculopathy
sinus o Bilateral
thrombosis Primary spinal cord tumours Infectious poliomyelitis
Mass over the o Intramedullary o TM (transverse Neuropathy
parasagittal ▪ Ependymoma myelitis) NMJ disorders
area ▪ Astrocytoma o Neurosyphilis o Myasthenia gravis
ACA stroke o Extramedullary (tabes dorsalis) Myopathy
Hydrocephalus ▪ Neurofibroma o Rabies vaccine GBS
▪ Meningioma o HSV2, CMV, EBV, Cauda equina sxx
▪ schwannoma HIV, HTLV Conus medullaris
2ry spinal cord tumours o Lyme disease MND (motor neuron
(metastasis to spinal cord) Metabolic disease)
o Bronchogenic ca o Vitamin B12
o Breast ca deficiency →
o Prostatic ca SCDC
o Lymphoma Vascular (Spinal cord
o Multiple myeloma syndromes)
o GI cancers o Anterior spinal
o RCC cord sxx (Spinal
Granulomatous infections cord infarction)
o TB o Posterior cord
o Schistosomiasis SXX
o CTD (connective tissue o Central cord sxx
disease) o BSS
o Brucellosis o Complete cord
Disc prolapse (herniation) transaction
Syringomyelia o Cauda equina sxx
Epidural abscess in spinal and conus
cord medullaris →
Sarcoidosis LMNL
Early stage of foramen
magnum sxx
Spinal stenosis
Mixed
Have mixed features of UMNL and LMNL
ALS
MS
Spinal shock
SCDC
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
N.B
Compressive non-compressive
➢ Back pain ➢ Back pain
radicular pain radiates to root distribution. Localized over the spine
For example, to buttock or LL Dull aching or burning, bund like,
Sharp, lancinating, radicular pain, localized pain
aggravated by coughing, sneezing, or ➢ After back pain all other manifestations
straining like weakness, sensory loss and
➢ 1st pt present with back pain then progress autonomic dysfunction may happen at the
sequentially to weakness → sensory loss → same time especially in complete cord
autonomic dysfunction (like urinary incontinence involvement. Typical example is TM.
and sexual dysfunction). This is due to horizontal ➢ Separate sensory loss is cmn in non-
localization in spinal cord. compressive lesions. For example
autonomic area Pain and temperature loss →
sensory area anterior cord sxx
motor area Position and vibration loss →
posterior cord sxx
Compressive
▪ Primary spinal cord tumours
➢ Intramedullary → sphincter abnormality is the earliest manifestation
o Ependymoma
o Astrocytoma
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ extramedullary
o neurofibroma
o meningioma
o schwannoma
▪ secondary spinal cord tumours (metastasis to spinal cord)
➢ Bronchogenic ca
➢ Breast ca
➢ Prostatic ca
o Commonly involve lumbosacral area
o Osteoblastic tumour unlike all other malignancies (osteolytic)
➢ Lymphoma
➢ Multiple myeloma
➢ GI cancers
➢ RCC
▪ Granulomatous infections
➢ TB → can cause of TM
o TB spondylitis a.k.a pott’s disease
o Gibbus (wedge shaped fusion of two vertebrae) deformity is
typical feature
o Usually occur in the absence of extra spinal TB
o Cmn in lower thoracic and upper lumbar area
➢ Schistosomiasis
➢ CTD (connective tissue disease)
➢ brucellosis
▪ Disc prolapse (herniation)
➢ Heavy weight lifters and overweight are at risk
➢ C/F → chronic low back pain and prolonged weakness
▪ Syringomyelia
➢ Cavity formation within the cord
➢ Chronic and progressive
➢ Caused by Acquired or congenital factors (acquired causes can be
from post infectious, trauma/from hyperextended neck during caring
objects by head/)
➢ Spare the posterior column
➢ Sensory loss (pain and temperature loss) involved
➢ There is wasting of small hand muscles
▪ Sarcoidosis
▪ Epidural abscess in spinal cord
➢ Triads include fever, back pain and FND (Paraplegia)
➢ Tender over the involved area
➢ There may be Sensory level
➢ Cmn in immunocompromised pt’s
➢ Staphylococcus is the cmn etiologic agent
▪ Early stage of foramen magnum sxx → Clock wise rotation of weakness
▪ Spinal stenosis
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Non compressive
▪ infectious
➢ TM (transverse myelitis)
o Sudden, rapid weakness which manifest with in hrs to days
o Present with fever, back/limb pain followed by sensory level, bladder
disturbance within hrs
o Usually happens following infection with MMRV (measles, mumps,
rubella, varicella), EBV, CMV, influenza virus
o Having sharp sensory level differentiate it from GBS
o DX criteria
• Bilateral motor, sensory and autonomic dysfunction occurring
simultaneously
• Sensory level
• Progression to nadir of clinical deficit between 4hrs and 21 days
of onset
• Exclusion of compressive, post radiation, neoplastic and vascular
causes
➢ Neurosyphilis → tabes dorsalis
o Cause posterior cord sxx
• No weakness
• Pain and temperature preserved
• Only position and vibration sensation lost
o Happen after 2-3 decades of syphilis infection unless congenital
syphilis
➢ Rabies vaccine
➢ HSV2, CMV, EBV, HIV, HTLV
➢ Lyme disease
▪ Metabolic
➢ Vitamin B12 deficiency → SCDC
▪ Vascular (Spinal cord syndromes)
➢ Anterior spinal cord sxx (Spinal cord infarction)
o Rare, if it occurs commonly occur in mid thoracic spinal cord (water
shed area)
o Common in anterior spinal cord because anterior spinal artery is
single artery unlike posterior spinal cord arteries
o Spare position and vibration sensation
o More sudden in onset than TM
o RF include cardiogenic emboli, thrombus, vasculitis, hypotension,
atherosclerosis, aortic dissection
➢ Posterior cord SXX
➢ Central cord sxx
➢ BSS
➢ Complete cord transaction
➢ Cauda equina sxx and conus medullaris → LMNL
❖ LMNL (lower motor neuron lesion)
✓ Plexopathy
✓ Radiculopathy
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Bilateral poliomyelitis
▪ Typically affect anterior horn
▪ Acute in onset
✓ Neuropathy
✓ NMJ disorders
Myasthenia gravis
✓ Myopathy
✓ GBS
Variants of GBS include
▪ AMAN (acute motor axonal neuropathy)
▪ ASMAN (acute sensorimotor axonal neuropathy)
▪ AIDP (acute inflammatory demyelinating polyradiculoneuropathy)
▪ MFS (Miller Fisher syndrome)
Nowadays CIDP (chronic inflammatory demyelinating
polyradiculoneuropathy) is out of GBS variant
8 A’s of GBS
o Autoimmune
o Areflexia
o Ascending paralysis
o Acute
o Afebrile
o Absence of sensory level
o Autonomic involvement → OHT, arrythmia
o Acellular CSF (albumin cytogenic dissociation → decreased
number
of cells but, increased protein/albumin of CSF)
✓ Cauda equina sxx
✓ Conus medullaris
✓ MND (motor neuron disease)
Spare sensory system
Idiopathic
Cmn in old age pt’s (>55)
Chronic in onset
Initially Unilateral which progress to the other side
e.g. bulbar palsy, ALS (corticospinal + anterior horn cell
degeneration), primary lateral sclerosis (only cortico spinal tract
degeneration)
❖ Mixed
✓ ALS
✓ MS
✓ Spinal shock
✓ SCDC
If the lesion is in thoracic area it cause paraplrgia, if it is in cervical
area it cause quadriplegia
Present with
▪ ascending parasthesia (tingling, numbness)
▪ glove and stocking pattern
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IX
1. Spinal X-ray
Request to the target level depending on the site of lesion (for
example if lesion is at T8 with sensory level at T10 the request
should be ‘’thoracic veretebral X-ray centered at T8’’)
Important for
✓ Gibbus in TB (TB spondylitis) → wedge shaped fusion of
lower part of the upper vertebrae and upper part of the lower
vertebrae (if you suspect TB spondylitis do Spinal x-ray, CBC,
ESR, CXR and other TB work up)
✓ Herniated inter vertebral disc
✓ 2ry deposit of malignancy
▪ Osteblastic in prostatic ca but osteolytic in other
malignancies
✓ Fracture or dislocation of vertebrae, bone density
✓ Cervical spondylosis
2. Spinal MRI
Ix of choice which confirm the site of lesion
✓ Have excellent anatomic resolution and extent of tumour
Distinguish between malignancy and other lesions like epidural
abscess, tuberculoma, epidural haemorrhage
If MRI is not available do CT myelography
✓ Permit CSF analysis
3. ESR and blood culture → for epidural abscess
4. CBC
Megaloblastic Anaemia in vitamin B12 deficiency (low hemoglobin
with MCV > 100)
Leucocytosis in epidural abscess and malignancy
Multiple myeloma → plasmacytosis
5. CSF analysis
Low opening pressure
Acellular CSF (albumin cytogenic dissociation → No cell/decreased number of
cells but, increased protein/albumin of CSF) in GBS
Xanthochrome
Important for epidural abscess
6. PICT → SCDC, TM
7. RBS → DSPN (distal symmetric polyneuropathy) characterized by glove and
stocking pattern
8. Nerve conduction test (NCT) → neuropathy
9. Muscle biopsy → from largest muscle involved for myopathy dx
10. S/E → TM, GI source of infection like campylobacter in GBS
11. U/A and urine culture → TM
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Discussion
Regional localization
If UMNL
✓ The cortex; hemispheres
✓ Subcortical white matter
✓ Diencephalon; basal ganglia, thalamus
✓ Brain stem
✓ Spinal cord
If LMNL
✓ Spinal nerves
✓ Plexus
✓ Peripheral nerve
✓ NMJ
✓ Muscle
Interpret the characteristic motor, Gait and sensory abnormality to locate
regional neurologic disease.
Use the specific function of region for best localization.
For example: Cortical functions like speech, cortical sensory functionRegional
Motor localization
CST (corticospinal tract) and CBT (corticobulbar tract) originates from pre-
central frontal gyrus called motor nucleus
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
The motor fibers are somatotopically organized in patterns that reflect their
functional importance: Motor homunculus
✓ Medial to lateral: Bladder function – legs – arms – face – oro-buchal
CST and CBT progress down wards via corona-radiata as the fibers dispersed
widely before reaching the internal capsule: Differential hemiparesis (arm >
face > leg, or vice versa)
In the internal capsule, the CST and CBT converge independently to rest at
the posterior limb and genu of internal Capsule: Dense hemiparesis 403
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
In the brainstem: CST and CBT join together to pass through cerebral
peduncle and basis pontis: Dense hemiparesis and bulbar palsy
Transverse localization: CBT are crossed in the brainstem before supplying CN
nuclei.
At the medulla: CST cross the midline to the opposite side to run to the
respective level of the spinal cord
At the point of decussation, crossed and uncrossed fibers are found near each
other which can result various types of weaknesses: Crural paresis, diplegia,
hemiplegia, quadriplegia depending on the specific location.
At the spinal cord CST ends to excite the alpha motor N: Paraplegia;
quadriplegia
Transverse Localization: The lower four CN lesions cause crossed paralysis
with body weakness
➢ CST and CBT projections to the basal ganglia and cerebellum have an active
role in the planning and execution of movements.
➢ The cerebellum and basal ganglia are critically important for coordinated and
organized finely tuned motor functions
➢ The cerebellum has a major role in the coordination of movements and control
of equilibrium and muscle tone. The cerebellum controls the ipsilateral limbs
through connections with the SC and BS; but opposite to the cortex → Ataxia
➢ The basal ganglia play a major role in the control of posture and movt.
Participate in motor planning through reciprocal connections. The cortico-striate
pathway includes direct and indirect projections from the cerebral cortex to the
striatum → movement disorders 404
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Figure; left) The main somatosensory pathways. The spinothalamic tract (pain, thermal sense) and
the posterior column–lemniscal system (touch, pressure, joint position) are shown. Offshoots from
the ascending anterolateral fasciculus (spinothalamic tract) to nuclei in themedulla, pons, and
mesencephalon and nuclear terminations of the tract are indicated.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
movement disorders
Compressive
✓ Epidural, intradural, or intramedullary neoplasm
✓ Epidural abscess
✓ Epidural hemorrhage
✓ Cervical spondylosis
✓ Herniated disk
✓ Posttraumatic compression by fractured or displaced vertebra or
hemorrhage
Vascular
✓ Arteriovenous malformation and dural fistula
✓ Antiphospholipid syndrome and other hypercoagulable states
Inflammatory
✓ Multiple sclerosis
✓ Neuromyelitis optica
✓ Transverse myelitis
✓ Sarcoidosis
✓ Sjögren-related myelopathy
✓ SLE-related myelopathy
✓ Vasculitis
Infectious
✓ Viral: VZV, HSV-1 and 2, CMV, HIV, HTLV-1, others
✓ Bacterial and mycobacterial: Borrelia, Listeria, syphilis, others
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
✓ Mycoplasma pneumoniae
✓ Parasitic: schistosomiasis, toxoplasmosis, cystercercosis
Developmental
✓ Syringomyelia
✓ Meningomyelocele
✓ Tethered cord syndrome
Metabolic
✓ Vitamin B12 deficiency (subacute combined degeneration)
✓ Copper deficiency
➢ The spinal cord has 31 segments, each defined by an exciting ventral motor
root and entering dorsal sensory root.
➢ The mature spinal cord ends at approximately the first lumbar vertebral body.
➢ The lower spinal nerves take an increasingly downward course to exit via
intervertebral foramina.
➢ The first seven pairs of cervical spinal nerves exit above the same-numbered
vertebral bodies, whereas all the subsequent nerves exit below the same-
numbered vertebral bodies because of the presence of eight cervical spinal
cord segments but only seven cervical vertebrae (see table below).
➢ These relationships assume particular importance for localization of lesions that
cause spinal cord compression.
➢ Sensory loss below the circumferential level of the umbilicus, for example,
corresponds to the T10 cord segment but indicates involvement of the cord
adjacent to the 7th or 8th thoracic vertebral body.
➢ In addition, at every level, the main ascending and descending tracts are
somatotopically organized with a laminated distribution that reflects the origin or
destination of nerve fibers.
Cervical Cord
➢ Upper cervical cord lesions produce quadriplegia and weakness of the
diaphragm.
➢ The uppermost level of weakness and reflex loss with lesions at C5-C6 is in
the biceps; at C7, in finger and wrist extensors and triceps; and at C8, finger,
and wrist flexion.
➢ Horner’s syndrome (miosis, ptosis, and facial hypohidrosis) may accompany a
cervical cord lesion at any level.
Thoracic Cord
Lesions here are localized by the sensory level on the trunk and, if present,
by the site of midline back pain.
Useful markers of the sensory level on the trunk are the nipples (T4) and
umbilicus (T10).
Leg weakness and disturbances of bladder and bowel function accompany the
paralysis.
Lesions at T9-T10 paralyze the lower—but not the upper—abdominal muscles,
resulting in upward movement of the umbilicus when the abdominal wall
contracts (Beevor’s sign).
Lumbar Cord
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ Lesions at the L2-L4 spinal cord levels paralyze flexion and adduction of the
thigh, weaken leg extension at the knee, and abolish the patellar reflex.
➢ Lesions at L5-S1 paralyze only movements of the foot and ankle, flexion at the
knee, and extension of the thigh, and abolish the ankle jerks (S1).
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Figure; Transverse section through the spinal cord, composite representation, illustrating the principal
ascending (left) and descending (right) pathways. The lateral and ventral spinothalamic tracts ascend
contralateral to the side of the body that is innervated.
C, cervical; D, distal; E, extensors; F, flexors; L, lumbar; P, proximal; S, sacral; T, thoracic.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ Most fiber tracts—including the posterior columns and the spinocerebellar and
pyramidal tracts—are situated on the side of the body they innervate. However,
afferent fibers mediating pain and temperature sensation ascend in the
spinothalamic tract contralateral to the side they supply.
➢ The anatomic configurations of these tracts produce characteristic syndromes
that provide clues to the underlying disease process.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ This syndrome results from selective damage to the gray matter nerve cells
and crossing spinothalamic tracts surrounding the central canal.
➢ In the cervical cord, the central cord syndrome produces arm weakness out of
proportion to leg weakness and a “dissociated” sensory loss, meaning loss of
pain and temperature sensations over the shoulders, lower neck, and upper
trunk (cape distribution), in contrast to preservation of light touch, joint position,
and vibration sense in these regions.
➢ Spinal trauma, syringomyelia, and intrinsic cord tumors are the main causes.
Lesions in this area interrupt decussating pyramidal tract fibers destined for the
legs, which cross caudal to those of the arms, resulting in weakness of the
legs (crural paresis).
Compressive lesions near the foramen magnum may produce weakness of the
ipsilateral shoulder and arm followed by weakness of the ipsilateral leg, then
the contralateral leg, and finally the contralateral arm, an “around the clock”
pattern that may begin in any of the four limbs.
There is typically suboccipital pain spreading to the neck and shoulders.
Causes
✓ Trauma
✓ Metastatic carcinoma
✓ Multiple sclerosis
✓ Spinal epidural haematoma
✓ Autoimmune disorders
✓ Post vaccinial syndromes
✓ Infectious and postinfectious disorders
All ascending tracts from below and descending tracts from above are
interrupted
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
✓ Sensory
▪ all sensations are affected
▪ Pin prick test is very valuable
▪ Segmental paresthesia occurs at the level of lesion
✓ Motor
▪ Paraplegia due to corticospinal tract
▪ First spinal shock-followed by hypertonic hyper reflexic paraplegia
▪ Loss of abdominal and cremasteric reflexes
▪ At the level of lesion LMN signs occur
✓ Autonomic-
▪ Urinary retention and constipation
▪ Anhidrosis, trophic skin changes, vasomotor instability below the level
of lesion
▪ Sexual dysfunction can occur
Causes;
✓ Vit B12 deficiency
✓ AIDS
✓ HTLV Associated myelopathy
✓ Cervical spondylosis
Affects both the dorsal column and the lateral corticospinal tracts
Paresthesia in feet
Loss of proprioception and vibration in legs
Sensory ataxia
positive rhomberg sign
Bladder atony
Corticospinal tract involvement
✓ Spasticity
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
✓ Hyperreflexia
✓ Bilateral Babinski sign
AIDS associated dementia and spastic bladder is present
HTLV associated myelopathy
✓ slowly progressive paraparesis
✓ increase in csf igG antibodies to HTLV1
Compressive myelopathies
Figure; Epidural spinal cord compression due to breast carcinoma. Sagittal T1-weighted (A) and T2-
weighted (B) magnetic resonance imaging scans through the cervicothoracic junction reveal an
infiltrated and collapsed second thoracic vertebral body with posterior displacement and compression
of the upper thoracic spinal cord. The low-intensity bone marrow signal in A signifies replacement by
tumor.
Intradural mass
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Figure; MRI of a thoracic meningioma. Coronal T1-weighted postcontrast image through the
thoracic spinal cord demonstrates intense and uniform enhancement of a well-circumscribed
extramedullary mass (arrows) that displaces the spinal cord to the left.
Neurofibromas are benign tumors of the nerve sheath that typically arise from
the posterior root; when multiple, neurofibromatosis is the likely etiology.
Symptoms usually begin with radicular sensory symptoms followed by an
asymmetric, progressive spinal cord syndrome.
Therapy is surgical resection.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Investigations
Figure; MRI of a spinal epidural abscess due to tuberculosis. A. Sagittal T2-weighted free
spin-echo MR sequence. A hypointense mass replaces the posterior elements of C3 and
extends epidurally to compress the spinal cord (arrows). B. Sagittal T1-weighted image after
contrast administration reveals a diffuse enhancement of the epidural process ( arrows) with
extension into the epidural space.
➢ Blood cultures
✓ Are positive in > 50% of cases, but direct aspiration of the abscess at
surgery is often required for a microbiologic diagnosis.
➢ Lumbar puncture
✓ It Is only required if encephalopathy or other clinical signs raise the
question of associated meningitis, a feature that is found in <25% of
cases.
✓ The level of the puncture should be planned to minimize the risk of
meningitis due to passage of the needle through infected tissue.
✓ A high cervical tap is sometimes the safest approach.
✓ CSF abnormalities in epidural and subdural abscess consist of
▪ pleocytosis with a preponderance of polymorphonuclear cells
▪ an elevated protein level, and
▪ a reduced glucose levels
✓ the responsible organism is not cultured unless there is associated
meningitis.
➢ Hemorrhage into the epidural (or subdural) space causes acute focal or
radicular pain followed by variable signs of a spinal cord or conus medullaris
disorder.
➢ Therapeutic anticoagulation, trauma, tumor, or blood dyscrasias are
predisposing conditions.
➢ Rare cases complicate lumbar puncture or epidural anesthesia.
➢ MRI and CT confirm the clinical suspicion and can delineate the extent of the
bleeding.
➢ Treatment consists of prompt reversal of any underlying clotting disorder and
surgical decompression.
➢ Surgery may be followed by substantial recovery, especially in patients with
some preservation of motor function preoperatively.
➢ Because of the risk of hemorrhage, lumbar puncture should be avoided
whenever possible in patients with severe thrombocytopenia or other
coagulopathies.
Hematomyelia
➢ Hemorrhage into the substance of the spinal cord is a rare result of trauma,
intraparenchymal vascular malformation, vasculitis due to polyarteritis nodosa or
SLE, bleeding disorders, or a spinal cord neoplasm.
➢ Hematomyelia presents as an acute painful transverse myelopathy.
➢ With large lesions, extension into the subarachnoid space results in
subarachnoid hemorrhage.
➢ Diagnosis is by MRI or CT.
➢ Therapy is supportive, and surgical intervention is generally not useful.
✓ An exception is hematomyelia due to an underlying vascular
malformation, for which spinal angiography and endovascular occlusion
may be indicated, or surgery to evacuate the clot and remove the
underlying vascular lesion. 423
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Non-Compressive myelopathies
The most frequent causes of non-compressive acute transverse myelopathy
are;
✓ spinal cord infarction
✓ infectious (primarily viral) causes.
✓ postinfectious or idiopathic transverse myelitis
▪ which is presumed to be an immune condition related to acute
disseminated encephalomyelitis
✓ systemic inflammatory disorders, including SLE and sarcoidosis
✓ demyelinating diseases, including multiple sclerosis (MS)
✓ neuromyelitis optica (NMO)
After spinal cord compression is excluded, the evaluation generally requires a
lumbar puncture and a search for underlying systemic disease
Acute transverse myelopathies
✓ Rapidly progressive
✓ Maximum deficit in hrs to days
✓ The inflammation is generally restricted to one or two segments, usually
in the thoracic cord
✓ Symptoms develop rapidly over hrs; occasionally over several weeks
✓ Typically, the inflammation is bilateral, producing weakness and
multimodality sensory disturbance below the level of the lesion
✓ Unilateral syndromes have been described as well
✓ Almost all patients develop Leg weakness of varying severity, arm
weakness if the lesion is in the cervical cord
✓ Bowel and bladder dysfunction also occur
✓ Rapid onset complete paraplegia & spinal shock are associated with
poorer outcomes
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ The cord is supplied by three arteries that course vertically over its surface:
✓ a single anterior spinal artery and
✓ paired posterior spinal arteries.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ The anterior spinal artery originates in paired branches of the vertebral arteries
at the cranciocervical junction and is fed by additional radicular vessels that
arise at C6, at an upper thoracic level, and, most consistently, at T11-L2
(artery of Adamkiewicz).
➢ At each spinal cord segment, paired penetrating vessels branch from the
anterior spinal artery to supply the anterior two-thirds of the cord; the posterior
spinal arteries, which often become less distinct below the midthoracic level,
supply the posterior columns.
➢ Spinal cord ischemia can occur at any level; however, the presence of the
artery of Adamkiewicz below, and the anterior spinal artery circulation above,
creates a region of marginal blood flow in the upper thoracic segments.
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Many viruses have been associated with an acute myelitis that is infectious in
nature rather than postinfectious.
Nonetheless, the two processes are often difficult to distinguish.
Etiologies
✓ Viral → most common
▪ Herpes zoster
▪ HSV types 1 and 2
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
* Clinical events that are consistent with transverse myelitis but that are not associated
with cerebrospinal fluid abnormalities or abnormalities detected on
MRI and that have no identifiable underlying cause are categorized as possible
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
Management
➢ In cases of suspected viral myelitis, it may be appropriate to begin specific
therapy pending laboratory confirmation.
➢ Herpes zoster, HSV, and EBV myelitis are treated with
✓ Acyclovir,10 mg/kg, IV, TID for 10 - 14 days or
✓ valacyclovir 2 g PO, TID for 10 - 14 days
➢ CMV is treated with
✓ Ganciclovir, 5 mg/kg IV BID) for 2 weeks
plus
✓ Foscarnet, 60 mg/kg IV TID) for 2 weeks or
✓ Cidofovir, 5 mg/kg per week for 2 weeks.
3. Postinfectious myelitis
1) Syringomyelia
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
➢ Images of the brain and the entire spinal cord should be obtained to delineate
the full longitudinal extent of the syrinx, assess posterior fossa structures
for the Chiari malformation, and determine whether hydrocephalus is present.
Treatment of syringomyelia
3) Tabes dorsalis
Reading Assignment
Clinical Manifestations
8 A’s of GBS
✓ Autoimmune
✓ Areflexia
✓ Ascending paralysis
✓ Acute
✓ Afebrile
✓ Absence of sensory level
✓ Autonomic involvement → OHT, arrythmia
✓ Acellular CSF (albumin cytogenic dissociation → decreased number
of cells but, increased protein/albumin of CSF)
GBS manifests as a rapidly evolving areflexic motor paralysis with or without
sensory disturbance.
The usual pattern is an ascending paralysis that may be first noticed as
rubbery legs.
Weakness typically Acute evolving over hours to a few days and is frequently
accompanied by tingling dysesthesias in the extremities.
The legs are usually more affected than the arms, and facial diparesis is
present in 50% of affected individuals.
The lower cranial nerves are also frequently involved, causing bulbar weakness
with difficulty handling secretions and maintaining an airway; the diagnosis in
these patients may initially be mistaken for brainstem ischemia.
Pain in the neck, shoulder, back, or diffusely over the spine is also common in
the early stages of GBS, occurring in ~50% of patients.
Most patients require hospitalization, and in different series, up to 30% require
ventilatory assistance at some time during the illness.
The need for mechanical ventilation is associated with more severe weakness
on admission, a rapid tempo of progression, and the presence of facial and/or
bulbar weakness during the first week of symptoms.
Fever and constitutional symptoms are absent at the onset and, if present,
cast doubt on the diagnosis.
Deep tendon reflexes attenuate or disappear within the first few days of onset.
Cutaneous sensory deficits (e.g., loss of pain and temperature sensation) are
usually relatively mild, but functions subserved by large sensory fibers, such as
deep tendon reflexes and proprioception, are more severely affected.
Bladder dysfunction may occur in severe cases but is usually transient.
If bladder dysfunction is a prominent feature and comes early in the course or
there is a sensory level on examination, diagnostic possibilities other than GBS
should be considered, particularly spinal cord disease.
Once clinical worsening stops and the patient reaches a plateau (almost
always within 4 weeks of onset), further progression is unlikely.
Autonomic involvement is common and may occur even in patients whose
GBS is otherwise mild.
✓ The usual manifestations are loss of vasomotor control with wide
fluctuations in blood pressure, postural hypotension, and cardiac
dysrhythmias.
✓ These features require close monitoring, and management and can be
fatal.
Pain is another common feature of GBS 434
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
✓ in addition to the acute pain described above, a deep aching pain may
be present in weakened muscles that patients liken to having over
exercised the previous day.
✓ Other pains in GBS include dysesthetic pain in the extremities as a
manifestation of sensory nerve fiber involvement.
✓ These pains are self-limited and often respond to standard analgesics.
Subtypes of GBS
Antecedent Events
Laboratory Features
➢ CSF findings are distinctive, consisting of an elevated CSF protein level (100 -
1000 mg/dL]) without accompanying pleocytosis.
➢ The CSF is often normal when symptoms have been present for ≤48 h; by the
end of the first week, the level of protein is usually elevated.
➢ A transient increase in the CSF white cell count (10 - 100/μL) occurs on
occasion in otherwise typical GBS; however, a sustained CSF pleocytosis
suggests an alternative diagnosis (viral myelitis) or a concurrent diagnosis such
as unrecognized HIV infection, leukemia or lymphoma with infiltration of nerves,
or neurosarcoidosis.
➢ Electrodiagnostic studies
Treatment of GBS
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Chapter 7; Paraplegia (ከወገብ በታች ሽባነት)
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Chapter 8; Meningitis (ማጅራት ገትር)
History
Occurs ‘’X’’ times per month and lasts for ‘’Y’’ minutes
May/may not be responsive to analgesics
➢ Neck stiffness
➢ Fever
Low grade (in viral, fungal and TB meningitis) or high grade (in
pyogenic/bacterial meningitis)
Intermittent / persistent
Associated with chills and rigor. In most cases (especially in viral
fungal and TB meningitis) there may not be chills or rigor
➢ Vomiting
Projectile (if there is increased ICP), if vomiting is projectile there is
no preceding nausea i.e. projectile doesn’t merely mean project
forward
➢ Photophobia
➢ Associated with Abnormal body movement
Starts abruptly
With or without warning manifestations
Generalized/partial
With up rolling of the eyes and drooling of saliva
Followed by excessive salivation, bleeding from the tongue (tongue
bite), urinary or faecal incontinence (observed by one of family
members)
Finally, LOC → ask duration of LOC which is mostly less than 5
minutes
➢ Night sweat
Common in TB meningitis
➢ Weight loss
Risk factors
Complication of meningitis
Sample history
Chief compliant
HPI
This patient was last relatively healthy a week back, at which time she began
to experience a gradual onset of globalized, dull aching, persistent type of
headache which is moderate in intensity, aggravated by coughing, sitting
position and loud voice, relieved by sleeping and keeping silent associated
with high grade intermittent fever with chills and rigors.
Two days before admission the headache got worsen and developed painful
neck stiffness associated with 3 episodes of non-projectile, nonfoul smelling,
non-blood tingled vomiting of ingested matter but no photophobia. She also
developed 2 episodes of generalized abnormal body movements which Starts
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She neither visit any health facility nor took any antipain or antibiotics. Finally,
her families bring her to our hospital when she develops abnormal body
movement.
No hx of discharge from the nose, ear, upper facial pain, ear/nose pain,
morning frontal headache or rhinorrhea (URTI → RF)
No hx of smoking or chronic alcohol intake (RF)
No hx of cough, chest pain or contact with a known TB patient (meningitis
from respiratory source like TB meningitis, bacterial meningitis /S.pneumonia, H.influenza/)
No hx of skin rash, joint pain (skin lesions like vesicles are RF for viral meningitis and
petechae suggest meningococcal infection)
No hx of abdominal surgery (splenectomy → RF)
No hx of DM, HTN or Asthma (Chronic medical condition and immunocompromisation → RF)
She was not screened for RVI but no history of MSP, chronic diarrhea,
oral thrush or body rash (immunocompromisation → RF)
No hx of blindness or hearing difficulty (chronic CXN)
No hx of gum bleeding, epistaxis, or bleeding from other sites (DIC → CXN)
No hx of head trauma or neuro surgery (RF for brain abscess, SAH → DDX)
No hx of swelling over the neck, axilla or groin (carcinomatous meningitis → DDX)
No hx of MSP, penile or vaginal discharge (syphilitic meningitis → DDX)
Lives in malaria non endemic area and no hx of malarial attack or
travel hx to malaria endemic area (cerebral mmalaria → DDX)
No family hx of similar illness (migraine → DDX)
No hx of drug intake (NSAIDS, antiepileptics, steroids → cause headache and neck stiffness →
DDX, Steroids are immunosuppressive as RF, if empirical antibiotics was given it is better to consider
partially treated meningitis)
1 GA
2 Vital signs
3 HEENT
5 RS
6 CVS
7 Abdominal examination
8 GUS
9 MSS
10 IS
NS
+ve Meningeal irritation signs (Kerning sign, Brudzinski sign, Neck stiffness)
o Nuchal rigidity (Sensitivity 30%)
o Kernig’s sign → Patient supine, hip flexed at 90, knee flexed at 90;
+ve if passive extension of knee results in resistance
o Brudzinski’s sign → Patient supine and limbs supine; +ve if passive
neck flexion if followed by involuntary hip and/or knee flexion.
➢ Kernig’s and Brudzinski’s signs are +ve in only 5% of Pts, but will be very
specific for meningeal irritation if present.
➢ May be negative in
✓ Very young or elderly patients
✓ Immunocompromised
✓ Severe coma
✓ Partially treated meningitis
Some patients may have focal neurologic findings (about 30%; hemiparesis,
aphasia, visual field cuts, CN palsies)
Raised ICP signs
✓ Change in mentation is the earliest sign
✓ Papilledema
✓ Dilated and poorly reactive pupil which indicate CN III palsy
✓ CN VI palsy
✓ Decerebrate posture
✓ Cushing reflex (bradycardia, hypertension, and irregular respirations).
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Chapter 8; Meningitis (ማጅራት ገትር)
DDX
1. Meningitis
Pyogenic meningitis → i.e. bacterial meningitis
Viral (aseptic) meningitis
TB meningitis
✓ Phases of TB
☛ Prodromal phase → nonspecific smx like fever, night
sweat, weight loss…
☛ Meningitis phase → nuchal rigidity, CN palsy (single
CN involved)
☛ Coma (paralysis) → weakness, multiple CN involvement
Fungal meningitis
Chemical meningitis → also aseptic like viral
Syphilitic meningitis → meningitis occur in all stages of syphilis
Carcinomatous meningitis
✓ Cmnly from ALL, AML, Lymphoma
✓ Initially manifest with cmn C/F of leukaemia (bone pain, BM
failure smx) then progress to meningitis
2. Cerebral malaria
Acute CXN of malaria
Infection with P. falciparum
Have nuchal rigidity, fever and headache
Cmn in endemic area
In repeated malarial attack if the last attack is ≥ 10 years, no risk of
cerebral malaria (i.e. for cerebral malaria the last attack should be <
10 years)
LOC for > 30 minutes
✓ Repeated seizure without gaining consciousness
✓ Cerebral malaria is unlikely in fully awake patients
3. Brain abscess
Triads of brain abscess include fever, headache, FND
Rupture of the abscess is the cause of meningeal irritation
4. Typhoidal meningitis
Rare
Have psychotic features
1st manifest as
✓ Abdominal pain
✓ Diarrhoea
✓ Stepladder fever
✓ Headache
✓ prostration
✓ It needs at least weeks to develop meningitis
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Chapter 8; Meningitis (ማጅራት ገትር)
IX
N.B.
High index of clinical suspicion is very important for early diagnosis of
meningitis to avoid death or unfavorable complications.
❖ LP (CSF Analysis) → refer short case of nitsibin (click here → CSF analysis)
o If LP is delayed (e.g after CT scan) or not indicated (uncontrolled
significant bleeding tendencies), withdraw two sets of blood culture
prior to antibiotics. Repeated (follow-up) LP is important if poor
clinical response after 48hrs of appropriate antibiotic, or CSF shunt
present, otherwise may not be necessary.
❖ Blood cultures before antibiotics are administered. Initial blood tests should
include two sets of blood cultures.
Culture can be done also from CSF, throat swab, stool, urine based
on aetiology
+ve for HiB, S.pneumonia, N.mengitidis
❖ CBC
Neutrophilic dominant leucocytosis in pyogenic meningitis
Leucocytosis also expected in brain abscess
❖ PICT
❖ Serum electrolyte
❖ OFT → RFT, LFT
❖ ESR & CRP
❖ PT & PTT → to r/o DIC
❖ Head CT
to rule out mass effect before LP (To r/o space occupying lesions
if raised ICP is suspected and LP is contra indicated) 445
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Chapter 8; Meningitis (ማጅራት ገትር)
Discussion
Meningitis
Meningitis Vs encephalitis
Meningitis Encephalitis
Inflammation predominantly affecting Inflammation of the brain parenchyma
the subarachnoid space
Commonly caused by bacterial
aetiologies
Nuchal rigidity is the prominent
Caused by viral aetiologies
Pathophysiology
➢ Colonization of the nasopharynx by attaching to the epithelial cells
➢ Invasion of the intravascular space
➢ Avoid phagocytosis by neutrophils and complement mediated bactericidal
activity in the bloodstream because of the presence of a polysaccharide
capsule
➢ Directly infect choroid plexus epithelial cells to reach the CSF
➢ Multiply rapidly within the CSF due to the paucity of effective host immune
defences in the CSF
➢ Bacterial proliferation induces inflammatory response and the formation of
purulent exudate in the subarachnoid space
Management of meningitis
Yes
Blood culture and lumbar No Blood culture urgently
puncture (LP) urgently
Give empiric antibiotic
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Supportive Therapy:
➢ Hydration: both under and over hydration may have unfavorable consequences.
An IV maintenance fluid might be preferred over restricted fluid intake in the
first 48 hours in settings with high mortality and lately presenting patients.
➢ Nutrition support if required (NGT if necessary)
➢ Analgesia and/or antipyretic:
o Paracetamol, 1 g, PO, 4 - 6 hourly when required, with maximum daily
dose of: 4 g in 24 hours.
o Alternative: Ibuprofen, 400 mg, PO, TID with meals, if needed.
➢ Close supervision with regular monitoring of vital signs and neurological state.
➢ Institution of coma care for complicated cases.
➢ The use of adjunctive corticosteroids is controversial. Based on the existing
current evidence they are not recommended in low- and middle-income
countries as they do not demonstrated benefit
o If used; Dexamethasone 10 mg IV QID for 04 days
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Chapter 8; Meningitis (ማጅራት ገትር)
Age < 1 Gram negatives ➢ Ampicillin, 150 to 200 mg/kg/day in ➢ Ampicillin PLUS
month Staphylococcus, divided doses every 3 to 4 hours, IV ➢ gentamycin, 2 to
(rarely up Enterococcus, PLUS 2.5 mg/kg/dose, IV,
to 3 Pneumococcus ➢ Cefotaxime, 225 to 300 mg/kg/day, IV, TID
months) TID or QID OR
➢ Meropenem only
Duration; for up to 21 days (if specific o 40 mg/kg, IV,
agent not identified) TID (maxi: 2g,
TID)
1 month/3 S. pneumoniae, ➢ Ceftriaxone, 100mg/kg/day, IV BID -
months to 50 H. influenzae, PLUS
Years Meningococcus ➢ Vancomycin, 15 mg/kg/dose, IV, QID
➢ Fluroquinolones for sever allergy (e.g anaphylaxis) in place of 3rd generation cephalosporins.
Cephalosporin or carbapenems can be retained for mild cases (e.g. no hives or anaphylaxis etc).
➢ WHO recommends chloramphenicol as an alternative for penicillin allergy in meningitis endemic
countries. However, recent data demonstrated increased mortality with CAF
o CAF, 500mg I.V. QID
➢ For listeria, cotrimoxazole should be used in place of ampicillin.
o Cotrimoxazole, 20mg/kg/day, BID to QID 450
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Increased ICP
➢ Admit to ICU
➢ Elevation of the patient’s head to 30-450
➢ Intubation and hyperventilation (Paco2 25-30 mmHg)
➢ mannitol
Supportive Therapy
➢ Hydration: both under and over hydration may have unfavorable
consequences.
➢ IV maintenance fluid IS preferred over restricted fluid intake in the first 48
hours in settings with high mortality and lately presenting patients.
➢ Nutrition support if required (NG tube feeding, if necessary)
➢ Analgesia and/or antipyretic:
o Tepid sponging
o Paracetamol oral, 1 g 4–6 hourly when required, maximum daily dose of:
4 g in 24 hours. Alternative: Ibuprofen, Diclofenac
Prevention
➢ Prophylaxis of contacts: Close household contacts for H. influenza and N.
meningitides. eg. Ciprofloxacin, oral, 500 mg as a single dose.
➢ Avoiding sharing utensils or close contacts with people with upper respiratory
tract infections.
➢ Prompt treatment of primary infection (e.g. upper respiratory tract infections)
➢ Using tissue or sleeve to cover sneezes and coughs and avoid kissing during
infection.
➢ Avoiding overcrowding
➢ Proper hand washing and other peculiar precautions.
➢ Immunization as per national schedules (Ethiopia introduced H. influenza B
vaccine (Hib) since 2007 and Pneumococcal Conjugate Vaccine (PCV) since
2013)
➢ Mass immunization if N. Meningitis epidemic (Men A vaccine is available in
Ethiopia)
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Chapter 8; Meningitis (ማጅራት ገትር)
Prognosis
➢ Mortality rate is
o 3 - 7% for meningitis caused by H. influenzae, N. meningitidis, or group
B streptococci
o 15% for that due to L. monocytogenes; and
o 20% for S. pneumoniae.
➢ Poor prognostic factors
o Decreased level of consciousness on admission
o Onset of seizures within 24 h of admission
o Signs of increased ICP
o Young age (infancy) and age >50
o The presence of co-morbid conditions including shock and/or the need for
mechanical ventilation, and Delay in the initiation of treatment.
Cryptococcal meningitis
Refer from chapter 5; RVI (click here → Cryptococcal meningitis)
TB Meningitis
Refer from Chapter 3; TB (click here → Tuberculous meningitis)
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Chapter 9; CLD/ Chronic liver disease/ (የጉበት በሽታ)
☛ N.B. all the manifestations (history and P/E) we discussed here range
from acute hepatitis to end stage cirrhosis. So, you have to correlate
with your patient condition
N.B
Risk factors
For more see the section below on Liver Cirrhosis and Complications of CLD
with their Treatment
Sample history
Sample history of a patient from tach armachiho with the DX of Decompensated CLD
(evidenced by ascites + Splenomegaly 2ry to portal HTN) secondary to Alcoholic Liver
disease r/o Chronic viral hepatitis
Chief compliant
abdominal distension of 3 months duration
HPI
This patient was last relatively healthy 03 months back, at which time he noticed
Abdominal distension which initially started from RLQ, which gradually increase in size
and progress to involve the whole abdomen and lower extremities within one month
duration. Together with dragging sensation in the left upper abdomen, sense of fullness
and early satiety.
Four months before the onset of abdominal distension, he experienced a stabbing RUQ
abdominal pain which is moderate in severity and radiates to the back associated with
low grade intermittent fever, coca colored urine and his families accidentally noticed
yellowish discoloration of his eyes but no stool color change or itching sensation. He has
also unquantified but significant weight loss to the extent his trousers become loose, loss
of appetite and easy fatigability.
For these, he visited a traditional healer where he was given unspecified herbal
medication and cauterized at his arms, forearms, over the abdomen and back but he
didn’t get any relief. Finally, he came to our hospital for better investigation and
management.
He drinks traditional areki half bottle 2 - 3 times per week for 5 years
and then changed his drink to a beer of 10 to 15 bottles every
Tuesday, Saturday and Sunday (average 37 bottles per week) for the
past 8 years that means he drinks for a total of 13 years. which is
estimated to be 70g alcohol intake daily for 13 years. (RF, hint for estimation; 37 458
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bottles divided by 7 days = 5.3 bottles daily, estimated alcohol content of one bottle is 13.2 g → look at RF
section above, 5.3 x 13.2 g = 69.77 g ≈ 70g)
No hx of blood transfusion, tattooing, contact with a jaundiced patient,
IV drug abuse or MSP, (RF for hepatitis virus transmission)
No hx of drug intake other than mentioned above (mentioned above under RF of
CLD)
No family hx of similar illness (genetics → etiology)
He usually eats injera made of ‘‘teff’’ and ‘‘machilla’’ and ‘’wott’’ made of
‘‘atter’’ and ‘‘dagusa’’ 3-4 times per day. Occasionally he eats meat
during holidays (aflatoxin is RF for HCC, hemochromatosis)
No hx of reddish discoloration of urine, pain during urination, urgency,
frequency or flank pain (HRS → CXN)
No hx of nasal bleeding, bloody vomiting or melena (bleeding tendency from
coagulopathy, variceal bleeding/painless, coffee ground appearance,nonprojectile/ → CXN)
No hx of tinnitus, blurring of vision, light headedness or easy fatigability
(anaemia 2ry to blood loss especially in variceal bleeding which may lead to shock, vitamin B12 deficiency
or IDA → CXN)
No hx of sleep disturbance, confusion, Forgetfulness, Abnormal body
movement or LOC (HE → CXN)
Has hx of river water contact but no hx of post river water contact
itching (HSS → DDX)
No hx of dyspnea, orthopnea, PND or palpitation (CHF → DDX)
No hx of chronic cough, contact with chronic cougher or previous TB
treatment
No self/family hx of DM, HTN or asthma (DM cause Fatty liver disease, NAFLD in HTN
and metabolic sxx)
He was screened for RVI 2 months back and found to be NR.
1 GA
2 Vital signs
3 HEENT
ascites, it indicates significant weight loss
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Chapter 9; CLD/ Chronic liver disease/ (የጉበት በሽታ)
LGS
Gynecomastia in males
o This is caused by increased estradiol due to decreased estrogen
metabolism in liver
o can occur in up to 66% of patients.
o Rarely from side effect of spironolactone treatment for ascites
Parotid enlargement
o likely due to alcohol use and not cirrhosis per se.
o ?2ry to collagen deposition
Testicular atrophy → due to hyper estroginism (estradiol)
5 RS
6 CVS
7 Abdominal examination
▪ straie alba/atrophica
N.B
✓ Straie gravidarum→ in pregnancy
✓ Purple straie → cushing sxx
caput medusae
o Latin word for head of medusa. In cirrhosis, distended and engorged
superficial epigastric veins which are seen radiating from umbilicus
across the abdomen and apparently similar to medusa head
o In portal hypertension, the umbilical vein may open.
o Blood from the portal venous system may be shunted through the
periumbilical veins into the umbilical vein and ultimately to the
abdominal wall veins, manifesting as caput medusa.
Picture; caput medusae (head of medusa) from Greek mythology, which had
venomous snakes in place of hair
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8 GUS
9 MSS
10 IS
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Figure; Palmar erythema. This figure shows palmar erythema in a patient with
alcoholic cirrhosis. The erythema is peripheral over the palm with central pallor.
Leukonychia (from Greek word leuko → white, nychia → nail) and terry
nails
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Palmar pallor
Skin pigmentation → in hemochromatosis
Bruising / purpura
Axillary and pubic hair loss
Scratch marks due to pruritis
11 NS → usually HE features
Asterixis
o Bilateral asynchronous flapping of outstretched, dorsiflexed hands
seen in patients with HE.
o Asterixis can be elicited by having patients extend their arms and
bend their wrists back.
o In this maneuver, patients who are encephalopathic have a ‘’liver
flap’’ — i.e., a sudden forward movement of the wrist.
o This requires patients to be able to cooperate with the examiner and
obviously cannot be elicited in patients who are severely
encephalopathic or in hepatic coma.
Construction apraxia
Coma
hyperreflexia
N.B
DDX
CLD 2ry to
▪ Viral hepatitis
▪ Alcoholic liver disease
▪ Autoimmune hepatitis
▪ HSS
✓ hepatocellular function remains normal and cirrhosis is rare
✓ Chronic schistosomiasis after 5-10 years
✓ Post river water contact itching may be forgotten so, endemicity is
important than asking post river water contact itching (e.g. living around
lake tana)
✓ Phases of schistosomiasis
o Dermatitis/swimmer’s itch
▪ popular pruritic rash at skin penetration site in 24-48hrs
o Katayama fever
▪ serum sickness like illness
▪ associated with excess antigenemia and formation of
soluble immune complexes
o Chronic schistosomiasis
✓ Granulomatous reaction around the ova results in organomegaly,
obstruction and fibrosis
✓ Fibrosis of the portal veins known as periportal fibrosis or Symmers'
clay pipe–stem which result in portal HTN (which in turn result in
ascites, varices & splenomegaly)
✓ Similar pathologic changes occur in other organs also
o bladder → obstructive uropathy, urosepsis, risk of bladder cancer
(SCC). S.hematobium is the etiologic agent
o Lung → pulmonary HTN and corpulmonale
o Brain and spinal cord → transverse myelitis
o GIT – bloody diarrhea and abdominal pain
o For more click here and refer ‘’ Intestinal Helminthic Infestations
(የአንጀት ጥገኛ ተውሳክ ፣የአንጀት ትላትል) and blood flukes section
from Short case of Nitsibin → Schistosomiasis (ቢሊሃርዚያ)
▪ Drug associated chronic hepatitis
o Direct toxic effect (Dose dependent) → Acetaminophen, Carbon
tetrachloride
o Idiosyncratic → isoniazid, valproate, phenytoin, Ciprofloxacin,
Augmentin 465
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TB peritonitis
✓ disseminated TB to liver and peritoneum
✓ present with very huge ascites
✓ cmn in our setup
lymphoma
✓ peritoneal carcinomatosis causing ascites with liver involvement
RSHF
Constrictive pericarditis
Nephrotic sxx
Chronic pancreatitis
Meig’s sxx → ovarian ca + pleural and peritoneal effusion
IVC sxx
Hypothyroidism → rare
PLE (protein losing enteropathy) → very rare condition
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N.B
Fluid → ascites
Feces → failure to pass feces but no flatus indicates
incomplete intestinal obstruction
Flatus → failure to pass both feces and flatus indicates
complete intestinal obstruction
Fat → obesity
Fetus → pregnancy
Fatal growth → organomegaly, malignancy, AAA (abdominal
aorta anourysm)
HE
Cerebral malaria
Acute alcohol toxicity
SDH
Meningoencephalitis
DKA
Metabolic encephalopathy
Sedation overdose
For more refer under short case of nitsibin (click here → Upper GI bleeding)
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N.B
Portosystemic anastomotic area include
Haemorrhoidal plexus
Gastro oesophageal junction
Retroperitoneal area
Peri umbilical area
Ass’t example
Decompensated CLD (evidenced by ascites + SBP + Splenomegaly 2ry to
portal HTN) secondary to Alcoholic Liver disease r/o Chronic viral hepatitis
IX
1. LFT and liver enzymes → for normal values refer short case of nitsibin (click
here → Chapter 11; Reference Intervals for Laboratory Tests)
LFT
✓ Serum bilirubin level → indicates metabolic activity
✓ Albumin and total protein → indicates synthetic function
✓ PT, aPTT and INR → prolongs earlier than hypoalbuminemia,
also indicates synthetic function
N.B
☛ albumin completely synthesized by liver. But globulin
synthesized also by lymphoid tissue. So, in CLD there will be
low albumin/due to impaired synthetic function of the liver / with
high globulin.
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𝒅𝒊𝒓𝒆𝒄𝒕 𝒃𝒊𝒍𝒊𝒓𝒖𝒃𝒊𝒏
𝒊. 𝒆 𝒓𝒂𝒕𝒊𝒐 = 𝒙 𝟏𝟎𝟎 %
𝑻𝒐𝒕𝒂𝒍 𝒃𝒊𝒍𝒊𝒓𝒖𝒃𝒊𝒏
𝑹𝒂𝒕𝒊𝒐 > 𝟏𝟓% 𝒊𝒎𝒑𝒍𝒊𝒆𝒔 𝒅𝒊𝒓𝒆𝒄𝒕 𝒉𝒚𝒑𝒆𝒓𝒃𝒊𝒍𝒊𝒓𝒊𝒃𝒊𝒏𝒆𝒎𝒊𝒂
𝑹𝒂𝒕𝒊𝒐 < 𝟏𝟓% 𝒊𝒎𝒑𝒍𝒊𝒆𝒔 𝒊𝒏𝒅𝒊𝒓𝒆𝒄𝒕 𝒉𝒚𝒑𝒆𝒓𝒃𝒊𝒍𝒊𝒓𝒊𝒃𝒊𝒏𝒆𝒎𝒊𝒂
N.B
2. Viral markers
HBsAg
✓ First evidence of infection (before biochemical abnormality)
✓ Signifies Infection & implies infectivity
✓ Commonly done in our setup
HBcAg → Induces cellular immune response
HBeAg → Marker for active viral replication / INFECTIVITY
HBxAg
Anti HBsAg
✓ Antibody which confers PROTECTIVITY
✓ signifies recovery from HBV infection, non-infectivity,
vaccination
Anti HBcAg
✓ Antibody detected in anyone with previous exposure
✓ Does NOT confer protectivity
✓ IgM → acute infection / lasts 3-6 months.
✓ IgG → implies chronic hepatitis infection
✓ present in “window period”
Anti HBeAg
✓ Antibody which indicates antigen is cleared / virus not
replicating
✓ Decrease infectivity
HBV DNA (PCR) → Best indicator of viral replication, Usually
parallel’s HBeAg
HCV RNA (PCR)
3. Ascitic fluid analysis → refer short case of nitsibin (click here → Ascitic fluid
analysis)
4. CBC
Anaemia 2ry to
✓ Variceal bleeding
✓ Hypersplenism
▪ Splenomegaly + pancytopenia + normal cellular BM
(compensatory proliferative response in BM)
▪ Cell count corrected in post splenectomy
✓ Nutritional deficiency → IDA, Vitamin B12 deficiency
✓ Direct alcohol toxicity to BM
Leukocytosis in SBP
Thrombocytopenia or pancytopenia
Macrocytosis in the absence of anaemia → alcoholic liver disease or
from Vitamin B12 deficiency
5. PM (peripheral morphology)
Microcystic hypochromic anaemia → IDA
Macrocytosis /megaloblastic anaemia/ → Vitamin B12 deficiency
6. Co-infection: HIV and HCV screening
7. Serum electrolyte
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N.B
Non-invasive screening for liver fibrosis: use one of the score available e.g. APRI
score
APRI Score
𝐀𝐒𝐓
[𝐔𝐍𝐋 𝐨𝐟 𝐀𝐋𝐓] 𝒙 𝟏𝟎𝟎
𝑨𝑷𝑹𝑰 𝒔𝒄𝒐𝒓𝒆 =
𝐩𝐥𝐚𝐭𝐞𝐥𝐞𝐭 𝐜𝐨𝐮𝐧𝐭 (𝟏𝟎𝟗/𝐋)
o APRI >0.5 but ≤ 1.5: Significant fibrosis or cirrhosis possible
o APRI >1.5 but ≤ 2: Likely significant fibrosis, cirrhosis possible
o APRI >2: Likely cirrhosis
Upper Normal limits (UNL) for normal ALT
o 30 U/L for men and 19 U/L for women
o Use the above cut point rather than the highly variable upper normal limits of
different laboratories.
Transient elastography (Fibro scan) if readily available
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Discussion
Cirrhosis
Definition: irreversible, chronic parenchymal injury with fibrosis and nodular
degeneration causing distortion of vascular bed of liver & disorganization of
normal architecture.
Cirrhosis represents a late stage of progressive hepatic fibrosis with distortion
of the architecture of the liver with formation of regenerative nodules.
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It can result from any cause of chronic liver disease e.g. chronic viral hepatitis,
alcoholic liver disease.
Patients with cirrhosis develop a variety of complications which cause marked
morbidity and mortality.
o The common complications include ascites, SBP, variceal bleeding, HE,
HRS and HCC.
Causes of cirrhosis
o Alcoholism
o chronic viral hepatitis (Hep. B &C)
o Autoimmune hepatitis
o nonalcoholic steatohepatitis
o biliary cirrhosis
▪ Primary biliary cirrhosis
▪ Primary sclerosing cholangitis
o cardiac cirrhosis
o Inherited metabolic liver disease
▪ Hemochromatosis
▪ Wilson’s disease
▪ AAT deficiency
▪ Cystic fibrosis
Factors which lead to cirrhosis include
o Viral factors → HBV
o Host factors
▪ Immunosuppression
▪ NAFLD
▪ Chronic alcohol intake
▪ Hepatotoxic drugs
▪ Concomitant infection → HBV + HCV, HBV+HDV
o External factors
Childs-Pugh classification
Don’t try to rehearse this, just know the name and the principle only.
It is a scoring system used to assess how risky surgery will be in pts with
liver disease
MELD scores and MAYO scores used to assess pts for liver transplant and
transplant allocation
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Close follow-up
9.1.1.2 Ascites
Management
➢ Salt restriction (< 2 g/day) (post at the bedside of the pt like this → ‘’salt free
diet/ ጨው ክልክል’’)
➢ See general management principles above
First line
➢ Spironolactone
o Starting dose 100 mg/day daily or BID
o If there is no response; increase doses every 3-7days (in 100 mg steps).
Maximum dose 400mg/day
o Serum potassium should be checked regularly: at start, at dose
increments and on each follow up visit
Add- on or alternative
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➢ Furosemide
o Starting dose: 20mg, BID, Increments by 40mg/day. Maximum dose:
160 mg/day (80mg BID)
o Ass add-on: in patients who do not respond to spironolactone (body
weight reduction less than 2 kg in one week)
o As an alternative: in patients who have hyperkalemia or impaired kidney
function at baseline or develop later
N.B
Keep spironolactone to Lasix ratio of 5 : 2 to prevent hypokalemia since
spironolactone is potassium sparing diuretic
Spironolactone is preferred in ascites from CLD unlike other causes of ascites
because of the following reasons
o To prevent hypokalemia
o To prevent dehydration from lasix (since loop diuretics like Lasix are
strong diuretics which may cause dehydration. Hypokalemia and
dehydration are precipitant of hepatic encephalopathy)
o Loop diuretics are less effective in ascites from CLD because there is
low albumin for their mechanism of action
o RAAS is the cause of ascites in CLD
loop diuretics like Lasix are strong diuretics and preferred in other causes of
ascites like CHF, Nephrotic syndrome, AKI/CKD….
o Enterococcus sp
o Klebsiella
Clinical manifestations:
o Fever
o abdominal pain and tenderness
o diarrhea
o rarely worsening of jaundice and HE (altered mental status)
Diagnosis:
o Positive ascitic fluid bacterial culture and
o ANC (Absolute neutrophil count) > 250 cells / μL
Bacterial peritonitis
SBP Secondary peritonitis due to rupture of abdominal viscus
➢ WBC > ➢ WBC > 10,000/mm3 (significant leucocytosis)
500/mm3 ➢ Multiple organisms identified
(neutrophil ≥ ➢ Increased LDH level
50%) ➢ Glucose < 50
➢ Mono microbial ➢ Protein significantly decreased
➢ PH
➢ With obvious cause of 2ry peritonitis like intestinal
perforation
➢ Failure to improve after standard treatment with in 48
hr’s
Treatment of SBP
First line:
✓ Ceftriaxone, 1g, IV, BID for 7-10 days
Alternative:
✓ Ciprofloxacin, 200mg, IV, BID for 7-10 days
➢ Screening studies have shown that approximately one third of patients with
histologically confirmed cirrhosis have varices. Approximately 5 - 15% of
cirrhotic patients per year develop varices.
➢ Varices develop in order to decompress the hypertensive portal vein and return
blood to the systemic circulation
➢ Clinical feature
o Signs and symptoms of CLD
o Painless but massive hematemesis
o Hypotension with/without shock
➢ Investigation
o Emergency endoscopy
o blood type and cross match
o CBC, OFT, PT and PTT…
There are four major issues related to the prevention and treatment of variceal
hemorrhage:
Prediction of patient at risk
Primary and pre-primary prophylaxis against variceal hemorrhage in patients
with cirrhosis
Treatment of an active bleeding
Prevention of rebleeding
Location of varices
Size of varices
Appearance of varices
Clinical features of the patient
Variceal pressure
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10) Prevention of variceal bleeding (Both Pre-primary and Primary, some expertise
uses the term primary and secondary)
➢ Primary prophylaxis aims to prevent variceal hemorrhage in patients with
esophageal varices who do not have a history of hemorrhage.
➢ Pre-primary prophylaxis refers to measures aimed at preventing the
development of varices.
➢ These measures are aimed at achieving one of the following results:
o Decreasing portal hypertension
✓ beta blockers → Propranolol, 20mg - 40mg, PO, BID or TID. Start low
dose and escalate gradually.
✓ surgical portal decompression
✓ TIPS (trans jugular intrahepatic portosystemic shunts) → functions like
side-to-side surgical portocaval shunt, but does not require general
anesthesia or major surgery for placement.
o Treating the varices directly
✓ Endoscopic variceal band ligation
Pharmacologic treatment
Endoscopic treatment
endoscopic therapy can be done at the time of diagnosis and it’s the definitive
treatment of choice for active variceal hemorrhage
There are two forms of endoscopic treatment
o Sclerotherapy involves injection of a sclerosant solution into the varices
through an injection needle
o Variceal band ligation involves placing small elastic bands around
varices in the distal 5 cm of the esophagus
Balloon tamponade → is an effective way to achieve short-term hemostasis, but
due to complications and rebleeding upon balloon deflation, its use is reserved
for temporary stabilization of patients until more definitive treatment can be
instituted.
➢ Band ligation
➢ Non selective beta blockers
➢ Beta blockers plus band ligation → Combination therapy with a beta blocker
plus endoscopic band ligation is more effective at preventing rebleeding than
band ligation alone or beta blockers alone.
Precipitating Factors
Clinical Assessment
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Management of HE
Management principles
o supportive care
o Treatment of precipitating factors
o Treatment of concomitant cause of encephalopathy
o Specific treatment for HE
Supportive Care
➢ Correction of dehydration
➢ Correction of electrolyte imbalance
➢ Treatment of infection
➢ Control of GI bleeding
➢ Dietary protein management → In the past, restriction of dietary protein was
considered for patients with encephalopathy; however, the negative impact of
that maneuver on overall nutrition is thought to outweigh the benefit when
treating encephalopathy, and it is thus discouraged. There may be some
benefit to replacing animal-based protein with vegetable-based protein in some
patients with encephalopathy that is difficult to manage.
PLUS
➢ Metronidazole, 250mg, PO, TID, for 5 to 10 days or
➢ Neomycin, 4 to 12 g daily divided every 4 to 6 hours for 5 to 6 days
o For Chronic hepatic insufficiency: 4 g PO daily for an indefinite period
or
➢ Rifaximin, 400 mg PO TID, for 5 to 10 days
PLUS
➢ Zinc supplementation
Types of HRS
Type 1 HRS
o more serious type
o 2X increase serum creatinine to a level > 2.5 mg/dl within 2 wks
Type2 HRS
o decreased GFR with an increase in serum creatinine but is fairly stable
and with better outcome
o major feature is ascites that is resistant to diuretics
Precipitants
Pathogenesis
Treatment
Prevention
HRS regularly develops in pts with SBP or severe alcoholic hepatitis. The
following therapies may Prevent development of HRS
o IV albumin
o Norfloxacin
o pentoxifylline
Prognosis
Treatment
➢ No effective medical therapy
➢ Rather supplemental O2 and liver transplantation have promising out come
Prognosis
➢ Prognosis of Pt with HPS is worse than that of cirrhosis pt without HPS
(median survival is 24 months for pt with HPS and 5 yr Survival is only 23%
while pt without HPS have 5 yr survival of 63% & median Survival of
87months).
➢ But with liver transplantation survival is comparable.
A. Hypoalbuminemia
B. Coagulopathy in liver disease
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Treatment of bleeding
➢ Proper treatment requires answers to the following questions
o Any comorbidity presents?
o Is vit k deficiency present (more likely in primary cholestatic diseases)?
o Is DIC present?
o Is platelet count adequate?
o What is the status of fibrinogen and is fibrinolysis present?
o Is there danger of volume overload?
o Is there oral mucosal bleeding w/c can be corrected by antifibrinolytics?
➢ There are various disorders that cause CLD (look at DDX above)
➢ We will discuss some of the causes here (viral hepatitis, alcoholic liver
disease, autoimmune hepatitis, Wilson disease, hemochromatosis, AAT
deficiency, NAFLD and NASH)
➢ Non hepatotropic viruses (viruses that indirectly affect the liver) include; EBV,
CMV, HSV, measles, Ebola, & others
➢ Viral hepatitis can be;
o Acute viral hepatitis or
o Chronic viral hepatitis
Treatment
Chronic hepatitis
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➢ Having evidence of HBV infection does not necessarily indicate liver injury
(hepatitis) or the consequences of liver injury (liver cirrhosis and HCC).
➢ The presence of liver injury (hepatitis) is confirmed by a rise in transaminases
(mainly ALT) or imaging/clinical evidence of liver fibrosis and cirrhosis. (for
terminologies see table 1 below)
➢ The diagnosis of HBV infection starts with HBsAg. If +ve do the IX listed
under Ix section above
➢ In addition to those suspected of having liver disease, certain group of
individuals need routine screening with HBsAg.
o Pregnant mothers
o Infants born to infected mothers
o Health care workers (including health professionals and supporting staff)
o Hemodialysis patients and organ transplant recipients
o People with multiple sexual partners and I.V drug users
o Sexual partners of infected individuals
o HIV or HCV positive patients
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infection with
no evidence of Positive
current hepatitis
phase HBeAg +ve high (104 - 107 Elevated present Immune
(moderate reactive
2 chronic HBV IU/ml) (persistently
or severe) HBeAg
hepatitis or
positive
intermittently)
HBeAg phase HBeAg -ve Positive Negative low (<2,000 Normal None Inactive
Negative 3 IU/ml) or carrier
chronic HBV
infection with undetectable
no evidence of
current hepatitis
phase HBeAg -ve high (>2,000 Elevated Present HBeAg
4 IU/ml) (persistently (moderate negative
chronic HBV
or severe) chronic
hepatitis or hepatitis
intermittently)
HBsAg- phase Negative HBV Normal None occult HBV
infection
negative 5 antibodies =
phase +ve anti-
HBcAg with or
without anti-
HBsAg.
Follow up tests
➢ In patients with chronic HBV but no indications for antiviral therapy, liver injury
as well as viral replication can be variable; hence, regular monitoring is
required.
o ALT, APRI score, clinical evaluation every 3 months in all patients
o HBeAg initially negative: HBeAg and HBV DNA level every 6 -12 months
o HBeAg positive initially: HBV DNA level every 6 -12 months
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Treatment
Objectives of treatment
The main objectives of HBV treatment
o Reduce progression to cirrhosis, HCC and associated mortality
o Improve liver fibrosis
o Preventing acute or subacute liver failure in acute HBV infection
o Controlling extrahepatic manifestations.
o Prevention of HBV reactivation.
o Prevention of mother to child transmission.
Intermediate objectives of treatment
o Suppression of HBV DNA levels
o Induction of HBeAg loss, with or without anti-HBe seroconversion
o Biochemical response; ALT normalization
o HBsAg loss: optimal goal but rarely achievable
Pharmacologic treatment
o Patients with HBsAg positivity with or without elevated transaminases or
evidence of CLD need evaluation for indications of therapy i.e. HBeAg
status, HBV DNA level
Antiviral choices
First line
✓ Tenofovir (Tenofovir disoproxil fumarate) (TDF) 300mg, PO, daily
• Avoid in patients with GFR <60ml/min
OR
✓ Entecavir 0.5mg, PO, daily.
• For patients with decompensated cirrhosis or those with previous
exposure to Lamivudine the dose should be increased to 1mg,
daily.
• Entecavir is preferred over Tenofovir in patients age > 60, CKD,
osteoporosis or steroid use.
Alternatives
✓ Telbivudine 600mg, PO, daily.
• It should only be used when both first lines are not available or
in patients with renal impairment when Entecavir is not available.
Treatment options
➢ ART should be initiated in all HIV patients regardless of WHO staging or CD4
count in individuals co-infected with HIV and HBV with evidence of severe
CLD.
➢ If HBV treatment is indicated among HBV/HIV co-infection, combination ART
should be initiated with drugs containing TDF + 3TC (or FTC) + EFV as a
preferred regimen.
➢ Use of lamivudine as mono-therapy in any of these diseases is contraindicated
due to high resistance.
➢ When switching treatment in patients with HIV on ART failure, the regimen that
will continue should have two of the drugs having activity against HBV.
➢ If tenofovir-associated renal toxicity occurs, the dose of tenofovir should be
adjusted according to the renal clearance.
HCV coinfection:
➢ Treatment of HCV with direct-acting antivirals (DAAs) may cause reactivation of
HBV.
➢ Patients fulfilling the standard criteria for HBV treatment should receive
treatment.
➢ HBsAg-positive patients undergoing HCV treatment with DAA therapy should be
given concomitant treatment.
Pregnancy:
➢ In all pregnant women with high HBV DNA levels >200,000 IU/ml Tenofovir
(TDF) should be started at 24 - 18 weeks of gestation and continue for up
to 12 weeks after delivery.
➢ Pregnant women already on NA therapy, Tenofovir should be continued, if on
another agent it should be switched to Tenofovir.
➢ Tenofovir is not contraindicated in breast feeding.
➢ Sexual partners and close contacts of infected individuals receive three doses
of HBV vaccine.
Vaccination schedule
✓ Standard schedule: 0, 1, and 6 months.
✓ Accelerated schedule: 0, 1 and 2 months.
• Accelerated schedule, if requested for rapid protection within 48
hours of exposure: 0, 7 and 21 days.
• After an accelerated course, a booster at one year is
recommended.
HBV Immunoglobulin
➢ HBV immunoglobulin provides passive immunity
➢ Indications: In individuals who have not been immunized or have not completed
the immunization and have the one of the following indications
o Perinatal exposure of an infant born to a HBsAg positive mother within
24 hours.
o Percutaneous or mucosal exposure to HBsAg-positive blood preferably
within 24-48 hr.
o Sexual exposure to an HBsAg-positive person
Screening test
o Serum anti-HCV antibody rapid test or enzyme immunoassay EIA (ELISA)
o In the case of suspected acute hepatitis C, in immunocompromised
patients and in patients on hemodialysis, HCV RNA testing can be done
as an initial test.
Confirmatory test
➢ CBC, Liver enzymes and function test (AST, ALT, ALP, Bilirubin, ALB and
INR), Serum Creatinine, BUN
➢ Quantitative HCV RNA (IU/ml)
➢ Prégnancy test for reproductive Age group women.
➢ HIV and HBV screening
➢ Other tests; see IX section above
Treatment
➢ All patients with HCV should be offered treatment. Those with liver disease or
extrahepatic manifestations should be treated more urgently.
Objectives of treatment
➢ To eradicate HCV RNA (attainment of a sustained virologic response (SVR)).
➢ SVR is defined as an undetectable HCV RNA level after 12 weeks of therapy.
Alternative regimen
✓ Sofosbuvir 400 mg, PO, daily plus Daclatasvir 60mg PO, daily for 12
weeks or
✓ Sofosbuvir 400mg, PO, daily plus Ledipasvir 90mg, PO, daily for 12
weeks.
o For cirrhotic patient duration will be extended to 24 weeks for above
treatment options.
OR
✓ Sofosbuvir 400mg, PO, daily plus Ribavirin 1g (weight < 75kg), 1200mg
(weight ≥ 75Kg) twice on divided doses for 24 weeks.
Treatment monitoring
➢ HCV RNA at baseline, at the end of therapy (12 weeks) and after completion
of treatment.
➢ Toxicity of concurrent drugs given for comorbidities and potential drug-drug
interactions should be monitored.
HCV/HIV co-infection
➢ HIV patients are among high risk groups for HCV. Therefore, all HIV patients
should be screened and confirmation Viral load test should be done for HCV
screened positives
➢ All chronic HCV infected individuals should be treated to eradicate the virus
and achieve cure so that complications can be avoided.
➢ Follow up quantitative or qualitative HCV RNA viral load is required to confirm
if the patient has achieved Sustained Virologic Response (SVR). This should
be performed 12 weeks after the completion of therapy.
➢ Treatment of HCV in HIV infected individuals is not different from non-HIV
infected or HCV mono-infected. In case of Sofosbuvir + Daclatasvir
combination, dose of Daclatasvir be adjusted to 90 mg with Efavirenz and 30
mg with Atazanavir/r instead of 60mg dose of non RVI patients
3. Cirrhosis
➢ The transition between fatty liver and the development of alcoholic hepatitis is
blurred. In fatty liver stage, cessation of drinking results in normalization of
hepatic architecture and fat content within the liver.
➢ Clinically, Differentiation of alcoholic fatty liver from nonalcoholic fatty liver is
difficult unless an accurate drinking history is ascertained
➢ Alcoholic hepatitis is thought to be a precursor to the development of cirrhosis.
However, like fatty liver, it is po tentially reversible with cessation of drinking.
➢ Cirrhosis is present in up to 50% of patients with biopsy-proven alcoholic
hepatitis and its regression is uncertain, even with abstention of alcohol.
➢ Chronic infection with HCV is an important comorbidity in the progression of
alcoholic liver disease to cirrhosis in chronic and excessive drinkers.
o Even moderate alcohol intake of 20 - 50 g/d increases the risk of
cirrhosis and HCC in HCV-infected individuals.
o Patients with both alcoholic liver injury and HCV infection develop
decompensated liver disease at a younger age and have poorer overall
survival.
Management
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Prognosis
➢ Critically ill patients with alcoholic hepatitis have short-term (30-day) mortality
rates >50%.
➢ The mortality of patients with alcoholic hepatitis concurrent with cirrhosis is
nearly 60% at 4 years
➢ The presence of Ascites, Variceal hemorrhage, Deep encephalopathy, or
Hepatorenal syndrome Predicts a dismal prognosis.
Classification
I. Type I autoimmune hepatitis
Diagnosis
Diagnostic Criteria
➢ Exclusion of other causes of liver disease (genetic disorders, viral hepatitis,
drug hepatotoxicity, & alcohol).
➢ Marked hyperglobulinemia and high-titer circulating ANA and other
autoantibodies;
➢ Characteristic histologic features (interface hepatitis, plasma cells, rosettes)
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Management
TREATMENT REMISSION
➢ Disappearance of symptoms
➢ Normal serum bilirubin and IgG
➢ Serum aminotransferases normal or less than twice normal
➢ Normal hepatic tissue or minimal inflammation and no interface hepatitis.
➢ Action: d/c azathioprine and taper prednisone
TREATMENT FAILURE
INCOMPLETE RESPONSE
➢ Some or no improvement in clinical, laboratory or histologic feature
➢ Failure to achieve remission after 3 years
➢ Action: indefinite treatment
LIVER TRANSPLANTATION
Prognosis
➢ If untreated approximately 40% die within 6 months, 40% will develop cirrhosis
➢ the natural history of milder disease is variable, often accentuated by
spontaneous remissions and exacerbations. In treated autoimmune hepatitis, the
10-year survival is 80 - 90%.
➢ 13-20% of patients can have spontaneous resolution.
➢ Poor prognostic signs include:
o The presence histologically of multi lobular collapse at the time of initial
presentation
o ascites and hepatic encephalopathy
o Failure of the bilirubin to improve after 2 weeks of therapy
➢ Death may result from hepatic failure, hepatic coma, other complications of
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Treatment
➢ weekly phlebotomy aimed to reduce iron stores, recognizing that each unit of
blood contains 200 to 250 mg of iron.
➢ Maintenance phlebotomy is required in most patients and usually can be
achieved with 1 unit of blood removed every 2 - 3 months
Treatment
Treatment
DIAGNOSIS
TREATMENT
➢ It should be kept in mind that the kidney can serve as an “overflow valve” for
conjugated bilirubin.
𝒅𝒊𝒓𝒆𝒄𝒕 𝒃𝒊𝒍𝒊𝒓𝒖𝒃𝒊𝒏
𝒊. 𝒆 𝒓𝒂𝒕𝒊𝒐 = 𝒙 𝟏𝟎𝟎 %
𝑻𝒐𝒕𝒂𝒍 𝒃𝒊𝒍𝒊𝒓𝒖𝒃𝒊𝒏
𝑹𝒂𝒕𝒊𝒐 > 𝟏𝟓% 𝒊𝒎𝒑𝒍𝒊𝒆𝒔 𝒅𝒊𝒓𝒆𝒄𝒕 𝒉𝒚𝒑𝒆𝒓𝒃𝒊𝒍𝒊𝒓𝒊𝒃𝒊𝒏𝒆𝒎𝒊𝒂
𝑹𝒂𝒕𝒊𝒐 < 𝟏𝟓% 𝒊𝒎𝒑𝒍𝒊𝒆𝒔 𝒊𝒏𝒅𝒊𝒓𝒆𝒄𝒕 𝒉𝒚𝒑𝒆𝒓𝒃𝒊𝒍𝒊𝒓𝒊𝒃𝒊𝒏𝒆𝒎𝒊𝒂
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FIGURE 45-1 Evaluation of the patient with jaundice; ALT, alanine aminotransferase; AMA,
antimitochondrial antibody; ANA, antinuclear antibody; AST, aspartate aminotransferase; CMV,
cytomegalovirus; EBV, Epstein-Barr virus; LKM, liver-kidney microsomal antibody; MRCP, magnetic
resonance cholangiopancreatography; SMA, smooth-muscle antibody; SPEP, serum protein
electrophoresis.
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N.B Type one DM patients usually present with poly symptoms. But type two
DM patients may present with complication or Asymptomatic and
diagnosed accidentally while patients visit a health facility for other
reason.
Poly symptoms (3P)
➢ Poly urea → Write in terms of Day to Night ratio (e.g. poly urea of 8:6
day to night ratio).
☛ The 24-hour urine voided by a healthy adult range from
600 to 2000ml
☛ Polyuria considered when there is consistent elimination of
an abnormally large volume of urine, > 2000ml/24hr
➢ Polydipsia → ask How much litre of water he/she drinks per day
➢ Polyphagia → less common smx than Polydipsia and Poly urea
Weight loss despite increased appetite
Generalized weakness or malaise
DKA smx’s like Vomiting, Abdominal pain and LOC
Recurrent skin infections
Recurrent itching of the vulva (candida infections)
Symptoms related to chronic complications can be present at initial diagnosis in
type II diabetic patients
➢ Numbness or pain over the lower limbs
➢ Visual impairment Or Blurred vision
➢ Foot abnormalities (ulcer, ischemia, deformity)
➢ Body swelling
Hyperglycemia features include → 3P, DKA/HHS, blurring of vision, dry mouth
and other signs of DHN especially in HHS
Risk factors
For Type II DM* For Type I DM*
The ADA recommends screening All Individuals >45 ✓ Genetic (abnormality in HLA region on
years every 3 years and Screening individuals at An Chromosome 6)
Earlier Age if they are Overweight [ BMI >25 kg/m2] and
Have One additional Risk Factor for diabetes
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o The concordance of type 1 DM
in identical twins ranges between
Individuals with any one of the following need screening 40 and 60%, indicating that
for type II diabetes. If the result is normal, repeat additional modifying factors are
screening every 3 years; but if the result is in the likely involved in determining
whether diabetes develops.
prediabetes range repeat the test every year.
o Although the risk of developing
type 1 DM is increased tenfold in
✓ HTN relatives of individuals with the
✓ Dyslipidemia (HDL < 35mg/dl and/or triglyceride level >
disease, the risk is relatively low:
250mg/dl) 3–4% if the Parent has type 1
✓ Family history (First-degree relative with diabetes) diabetes and 5–15% in a Sibling
o Type II DM pts have strong genetic association (depending on which HLA
than type I DM haplotypes are shared). Hence,
o The concordance of type II DM in identical twins most individuals with type 1 DM
is between 70 and 90%. do not have a first-degree
o If both parents have type II DM, the risk relative with this disorder.
approaches 40%. ✓ Autoimmunity→ like Hashimoto’s
✓ Environmental factors thyroiditis
o Overweight or central obesity (BMI >25kg/m2) ✓ Environmental factors
▪ ≥ 80% of type II DM pt’s are Obese o Diet→cow milk during infancy→
o Physical inactivity antibody to cow insulin is similar
o Increased intake of Raw meat, fat and lipid to human insulin known as
containing food antigen mimickeracy
o Smoking
o Toxin → which affect pancreatic
o Alcohol intake B cells
✓ Old age (age ≥ 45) o Mumps, rubella, coxsackie
✓ Ethnicity→ common in African American infection
✓ Individuals with prediabetes should be tested yearly ✓ Young age (age <30)
✓ PCOS (polycystic ovary sxx) in females or acanthosis
nigricans
✓ History of atherosclerotic Cardiovascular disease
✓ Drugs → steroids (prednisolone), Phenytoin, thiazide
✓ Women with history of GDM (gestational DM)
✓ Chronic pancreatitis
✓ Pheochromocytoma
✓ Acromegaly
*no clear-cut boundary for Type I & II DM in RF. One can be RF for the other.
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1. Acute complications
▪ DKA
▪ HHS
▪ Hypoglycaemia
▪ Infection
▪ Lactic acidosis
➢ Acute complications may occur at any stage of the disease
Chronic complications
Sample history
Chief compliant
HPI
This patient was last relatively healthy 03 weeks back at which time he started to
experience polyuria of 7- 8 times during night and 10-12 times during daytime with
increased feeling of thirst for which he drinks 4 - 6 liters of water per day but no
polyphagia.
Associated with this he also experienced unquantified but significant weight loss to
the extent his trousers become loose despite increased appetite, generalized
weakness to the extent he couldn’t perform his routine daily activities.
For this complaint he visited a private clinic in Gondar town where he was told to
have increased blood sugar level and referred to our hospital for better investigation
and management. From the referral paper, RBS was 350mg/dl and repeated on next
day of first determination and the value was 289 mg/dl, FBS was 194 mg/dl, from
U/A glucose was +2 and ketone free but no treatment given.
▪
Hashimoto’s thyroiditis can occur concomitantly with Type I DM)
No hx of LOC, Abdominal pain or Vomiting (DKA→CXN)
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1 GA
✓ Obesity
✓ Cushionoid face
Vital signs
✓ OHT→ due to Autonomic neuropathy
✓ HTN → >130/80 is HTN in DM
✓ Resting tachycardia → due to Autonomic neuropathy
✓ Obesity → calculate BMI and measure Waist circumference
HEENT
✓ Hair loss
✓ Periorbital swelling → Mucor mycosis
✓ Active Ear discharge → Malignant otitis externa
✓ Oral thrush → oral candidiasis
✓ Poor dental hygiene (tooth loss)
✓ Xanthelasma → N.B it is common around eye lids and Achilles tendon
✓ Cataract
LGS
✓ Thyroid enlargement → poly glandular autoimmune disorder (PGAID)
✓ Loss of sweating → due to Autonomic neuropathy
RS
✓ Signs of consolidation → pneumonia (common infection in DM) 519
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CVS
✓ Arterial examination especially posterior tibial artery and dorsalis pedis
artery (PAD)
✓ IHD
Abdominal examination
✓ Hepatomegaly → from fatty liver
✓ Abdominal distention → from Gastroparesis or atony
✓ Intestinal obstruction → from autonomic neuropathy
✓ Murphy sign +ve → acalculous cholecystitis
GUS
✓ Supra pubic tenderness or CVAT → UTI, pyelonephritis
✓ Active vaginal discharge or whitish plaque → vaginal candidiasis (common
than oral candidiasis)
✓ Urinary bladder atony → voiding difficulty → due to Autonomic neuropathy
✓ Impotence → due to Autonomic neuropathy
MSS
✓ Diabetic foot ulcer
✓ Deformities → hammer toes, claw toes, prayers hand sign
✓ Duptyrens contracture
✓ Sensory
multiplex
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N.B several Rare Infections are seen almost exclusively in the diabetic population.
Examples include
❖ Rhino-cerebral Mucor-mycosis
❖ Emphysematous Infections of the Gall Bladder and Urinary Tract
❖ "Malignant" or Invasive Otitis Externa.
DDX
1. DM
2. Diabetic insipidus (DI)
DI is a disorder resulting from abnormalities of Antidiuretic hormone (ADH)
production from the hypothalamus or ADH action in the kidney. Final common
pathway → no response to ADH
Characterized by polyuria and polydipsia → the passage of copious amounts of
dilute urine (low specific gravity, usually < 1.010).
There are 4 Types of DI, the 1st two are common forms
Nephrogenic DI → a.k.a peripheral DI. Due to increased resistance of ADH
receptors in kidney to ADH
✓ Nephrogenic causes
• Congenital
• Acquired
o CRF
o Lithium
o Hypokalemia
o Hypercalcemia
Neuropathic DI → a.k.a central, hypothalamic, pituitary or neurohypophyseal DI.
Caused by decreased secretion or lack of secretion of ADH from posterior
pituitary. Head injury or neurosurgery are risk factors for central DI.
▪ Central/Cranial causes
➢ Congenital
➢ Acquired
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Post traumatic
Iatrogenic (post-surgical)
Tumours
Infection
Idiopathic
Gestational DI → Caused by a deficiency of the antidiuretic hormone, vasopressin,
that occurs only during pregnancy
Dipsogenic DI → a form of primary polydipsia. Caused by Abnormal thirst and
Excessive intake of water or other liquids
IX
1. Blood sugar → look at table below under discussion part for ADA diagnostic
criteria of DM
✓ RBS
N.B FBS and HbA1c are
✓ FBS
✓ OGTT reliable for screening
✓ HbA1c → tells about the past 3 months sugar level. Normal value is 4 -
5.6% of body Haemoglobin.
2. U/A → what do you expect from U/A
✓ Glucosuria (glucose +2, +3…)
✓ Ketonuria from DKA (ketone +2, +3…)
✓ Albuminuria from DM nephropathy
✓ WBC casts → suggest infection like UTI, pneumonia, sepsis
3. CBC → what do you expect from CBC
✓ Leukocytosis
✓ Anemia
✓ Ketone bodies
4. Serum electrolyte → hyperkalaemia despite decreased K+ level in cells because
acidosis impairs H+/ K+ pump (i.e. impair K+ absorption from blood stream). K+
Increase in blood during analysis but hypokalaemia in cells.
5. RFT
6. Lipid profile → increased LDL, Triglyceride, and cholesterol but decreased HDL
7. PICT
8. ECG & CXR → if indicated
9. Serum insulin level and C-peptide → C-peptide < 0.6 ng/dl in Type I DM
and > 1 ng/dl in >1-2 years for type II DM (Serum insulin or C-peptide
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measurements do not always distinguish type 1 from type 2 DM, but a low C-
peptide level confirms a patient's need for insulin.
10. Islet cell auto antibody → Anti - GAD (Glutamic acid decarboxylase) & Anti -
insulin antibody
11. Blood and urine culture
12. Serum PH and ketone
13. ABG (Arterial blood gas) analysis
✓ PH → acidosis
✓ Serum bicarbonate → low which shows metabolic acidosis
✓ Anion gap = 2Na+ - (CI- + HCO3-) or (Na+ + K+) - (CI- + HCO3-)
✓ O2 & CO2 → low CO2 due to respiratory compensation.
Discussion
Diabetes Mellitus (DM) was derived from two words; Diabetes = “siphon” or
“running through” meaning Large urine volume and Mellitus = sweet to indicate
Glucose in urine.
DM refers to a heterogenous group of common metabolic disorders that share
the phenotype of hyperglycemia.
Several distinct types of DM are caused by a complex interaction of genetics
and environmental factors.
Depending on the etiology of the DM, factors contributing to hyperglycemia
include Reduced Insulin Secretion, Decreased Glucose Utilization, and
Increased Glucose Production.
Diabetes is the leading cause of cardiovascular disease, CKD (ESRD), visual
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The clinical course and treatment of the different types of diabetes are
different; hence, classification of the type of diabetes is very important to
determine therapy.
The traditional thinking that type II diabetes as the disease of adults and type
I diabetes as the disease of children is not accurate as both diseases can
occur in both age groups. So, age is not a criterion in the classification
system.
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02-hour plasma < 140 mg/dl 140-199mg/dl >200mg/dl At least 2 tests needed
glucose tolerance
test (OGTT)
Random blood 65 to < 140 ? 140-199mg/dl >200mg/dl DM diagnosed Only if RBS
glucose (RBS) mg/dL
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>200mg/dl is accompanied
by Classic Symptoms of DM
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Chapter 10; DM /Diabetes Mellitus/ (የስኳር በሽታ)
Glucose is the key regulator of insulin secretion by the pancreatic beta cell,
although amino acids, ketones, various nutrients, gastrointestinal peptides, and
neurotransmitters also influence insulin secretion.
Insulin is the most important regulator of this Metabolic Equilibrium, but neural
input, metabolic signals, and other hormones (e.g., glucagon) result in
integrated control of glucose supply and utilization
Postprandially
the glucose load elicits a rise in insulin and fall in glucagon, leading to a
reversal of these processes.
Insulin, An Anabolic Hormone, Promotes the Storage of Carbohydrate and Fat
and Protein Synthesis.
The major portion of Postprandial Glucose is utilized by Skeletal Muscle, an
effect of insulin-stimulated glucose uptake.
Other tissues, most notably the Brain, utilize glucose in an insulin-independent
fashion.
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Pathophysiology
Type I DM
Type 1 DM is the result of interactions of Genetic, Environmental, and
Immunologic Factors that ultimately lead to the destruction of the pancreatic
beta cells and insulin deficiency.
Type 1 DM results from Autoimmune Beta Cell Destruction, and most, but not
all, individuals have evidence of Islet-directed Autoimmunity.
Individuals with a Genetic Susceptibility have normal beta cell mass at birth but
begin to lose beta cells secondary to autoimmune destruction that occurs over
months to years.
This autoimmune process is thought to be triggered by an Infectious or
Environmental Stimulus and to be sustained by a Beta Cell–specific Molecule.
Features of diabetes do not become evident until a majority of beta cells are
destroyed (70 - 80%).
After the initial clinical presentation of type 1 DM, a "honeymoon" phase may
ensue in the first 1 or 2 years after the onset of diabetes.
During which time Glycemic control is achieved with Modest Doses of Insulin
or, rarely, Insulin is Not Needed.
However, this fleeting phase of endogenous insulin production from residual
beta cells disappears as the autoimmune process destroys remaining beta
cells, and the individual becomes insulin deficient.
Some individuals with long-standing type 1 diabetes produce a small amount of
insulin (As reflected by C-peptide production)
And some individuals have insulin-positive cells in the pancreas at autopsy.
Islet Cell Autoantibodies (ICAs) are present in the majority of individuals
(>85%) diagnosed with New-onset type 1 DM.
Type II DM
Type 2 DM is characterized by Impaired Insulin Secretion, Insulin Resistance,
Excessive Hepatic Glucose Production, and Abnormal Fat Metabolism. Insulin
Resistance and Abnormal Insulin Secretion are central to the development of
Type II DM.
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Although the primary defect is controversial, most studies support the view that
Insulin Resistance precedes an Insulin Secretory Defect but that diabetes
develops only when insulin secretion becomes inadequate.
In the early stages of the disorder, glucose tolerance remains near-normal,
despite insulin resistance, because the pancreatic beta cells compensate by
increasing insulin output
In Asian, African, and Latin American), DM that is Ketosis Prone (Often
Obese) or Ketosis-Resistant (Often Lean) is commonly seen.
The disease is polygenic and multifactorial, since in addition to Genetic
Susceptibility, Environmental Factors (Such as Obesity, Nutrition, and Physical
Activity) modulate the phenotype.
Even though, HLA gene Abnormality is speculated in type I DM, the genes
that predispose to type 2 DM are incompletely identified. Genetic
Polymorphisms associated with type 2 diabetes have also been found
Management of DM
Principle of management
Administration
▪ Morning → periumbilical
▪ Evening → extremities
• This variation is because of exercise increase insulin absorption
(extremities involved in daytime activity)
storage of insulin
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Chapter 10; DM /Diabetes Mellitus/ (የስኳር በሽታ)
General advice
Avoid refined sugars: soft drinks with sugar, or adding sugar/honey to
teas/other drinks.
Carbohydrate
Reduce overall carbohydrate intake
Carbohydrate sources high in fiber and minimally processed are preferred:
whole grains, non-starchy vegetables, fruits, and dairy products Be
encouraged to have complex carbohydrates
Fat
Reduce saturated fat (animal fat) intake: butter, ghee, fatty cuts of meat,
cheese.
Reduce Trans-fat (hydrogenated oil): solidified vegetable oils
Mono-saturated and polyunsaturated vegetable oils are preferred
Protein
Should be left to the individual choice.
When there is CKD, reduction (not stopping) protein intake.
Sweetened beverages
Individuals who have had the habit sugar added beverages, taking low-
calorie or nonnutritive- beverages can serve as short-term transition.
However, they should be encouraged to replace with water intake.
2. Exercise
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3. Weight management
For obese and overweight individuals
Eating plans (focusing on reduction of overall carbohydrate intake) and
exercise
4. Stop smoking
5. Moderation of alcohol intake
A maximum 1 drink for women and 2 drinks for men.
- One drink is roughly equivalent to a bottle of beer, a glass of wine, or a
unit of spirit.
F. Self-blood glucose monitoring (SBGM)
G. Screening for micro and macro vascular complications
12
Reference from 2021 STG for General Hospitals in Ethiopia. According to Harrison 20th edition, the target
range of glycemic control is RBS < 180mg/dl, FBS = 80 - 130mg/dl, HbA1c < 7.0 %. As recommended by the
ADA; goals should be individualized for each patient with a different goal for different patients. HbA1c is primary
goal.
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Post meal < 180mg/dl Done 1-2hr from the beginning of meal
glucose level
Treatment of Type - I DM
Pharmacologic
❖ Insulin is the main stay of treatment in type I diabetes
Treatment of Type - II DM
Sulfonylureas
✓ Glibenclamide (Glyburide)
• Starting dose is 2.5-5mg/day, 30 minutes before breakfast.
• Titrate dose slowly to maximum of 20mg/day
• When 10mg/day is needed, divide the total dose into two, with the
larger dose in the morning.
• Avoid in the elderly and patients with renal impairment.
✓ Glimepiride
• Starting dose is 1-2 mg/day, 30 minutes before breakfast.
• Titrate dose slowly to maximum of 8mg/day
✓ Gliclazide, modified release
• Starting dose 30mg/day
• Titrate the dose slowly to a maximum dose 120mg/day
Other oral diabetic medications for the care of patients with type
II DM.
4 Each of these drugs are also Dose reduction need in patients with CKD.
inhibitors) available as FDC with Metformin
500mg or 1000mg)
4) Antiplatelet therapy
➢ Aspirin (81-162mg/day)
It is only indicated for patients who have CV disease (coronary artery
disease, ischemic stroke or peripheral arterial disease)
Diabetic diarrhea
Symptomatic treatment
Loperamide 2-4mg, PO, TID or QID or
Codeine 30mg, PO, TID or QID
Treatment of bacterial overgrowth: Antibiotics for 7-
10days
Norfloxacin 400mg, PO, BID Or
Metronidazole 500mg, PO, TID
PLUS
Cephalexin 500mg, PO, TID or
Cotrimoxazole 960mg BID
Postural hypotension
Change posture slowly
Elevate head by 10-200
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Dorsiflexion of feet and handgrip (before standing
Tensing legs by crossing (when standing)
Bladder dysfunction
Remove drugs which worsen it (Amitriptyline, CCB)
Strict voluntary voiding schedule
Crede maneuver (lower abdominal pressure by
hands)
If severe: Self intermittent catheterization
Erectile dysfunction
Use PDE5 inhibitors
Sildenafil 25 -100mg (start with 50mg)
Vardenafil 10-20mg
Tadalafil 10-20mg
If refractory
Tadalafil 2.5-5mg/daily
Diabetic foot Initial visit Every visit Look at diabetic foot ulcer section
Screening tools below
Assessment of skin
& foot deformities
Neurologic exam
PAD evaluation
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History
If a known DM patient → ask the following on your HPI
➢ Type I DM
o For how long he/she was diagnosed to have DM
o Ask the dose and frequency of insulin injection. → Usually a mixture
of 2/3 of NPH and 1/3 of regular insulin. From this mixture 2/3 of
the dose taken in the morning and 1/3 at night.
o Specify alternative injection sites
o Where he/she does store their insulin→ wet sand bags or refrigerator
o Adherent or not
o Where was the follow up and frequency (every month, every two
months….)
o How was his/her smx’s in between… improving, worsening or no
change at all… if not improving or worsening what was the reason
(non-adherence, wrong diagnosis ……)
A known DM pt for the past 6 years or you can say 6 years back s/he
was told to have DM (you can ask what was the presentation at that time and how Dx was
made… no need to write on your HPI) taking insulin injection 20 units in the
morning and 10 units at night. With alternative injection sites between
his/her upper arms, thighs and periumbilical area. Stores his/her insulin in
wet sand bag /refrigerator/. S/he was adherent for his/her medication with
regular follow up every 3 months here in our hospital.
➢ Type II DM
o For how long he/she was diagnosed to have DM
o What medication he was taking and ask the dose and frequency of
each medication. If the pt’ doesn’t remember or doesn’t know the
name of the drug ask the colour, frequency, and route of the
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medication (e.g he/she was taking white coloured tablet 3 times per
day).
o Does he/she start insulin other than oral hypoglycaemic drugs? If
yes what is the reason of shifting to insulin.
o Adherent or not
o Where was the follow up and frequency (every month, every two
months….)
o How was his/her smx’s in between… improving, worsening or no
change at all… if not improving or worsening what was the reason
(non-adherence, wrong diagnosis ……)
A known DM pt for the past 6 years or you can say 6 years back he
was told to have DM (you can ask what was the presentation at that time and how Dx was
made… no need to write on your HPI) On metformin 500 mg, PO, daily . He was
adherent for his medication with regular follow up every 3 months here in
our hospital.
➢ intermittent claudication
o Left/right calf stabbing type of pain which radiates to toes → usually
after waking of >200 meters
o Occur while walking and relieved by massage, sitting or lying down
➢ Numbness which spread upwards usually up to the knees (ask with in how
many days it reaches the knee).
➢ Burning sensation (over where?) which worsen by walking and relieved by
massage, cold water and pain killer
➢ Foot swelling→ where?
o Gradual in onset
o Overlying skin colour change
▪ Blackish discoloration of overlying skin→ up to where?
Subside or not?
o Painful or painless?
o Ulcerated or not?
o If ulcerated
▪ When does it ulcerate?
▪ What is the colour of discharge?
▪ Size→ Usually small in size, which increase gradually (with in
how many days does it attain it’s current size)
➢ Associated smx’s like fever, chills, palpitation, headache…. when does they
occur and frequency of smx’s within the day (morning, afternoon, night,
throw-out the day)?
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Risk factors
✓ Long standing DM → Diabetes >10 years' Duration
✓ Poor glycemic control
✓ Wearing unfit shoes
✓ Waking bare foot
✓ Unclean foot
✓ Trauma
✓ Male Sex
✓ Abnormal Structure of Foot (Bony Abnormalities, Callus, Thickened Nails)
✓ PAD
✓ Smoking
✓ History of Previous Ulcer or Amputation
✓ Concurrent DM complications
• Chronic sensory motor neuropathy or autonomic neuropathy
• Vascular disease like ischemia
• Infection
• Impaired immune function
Neuropathy
Trauma
Ulcer
Ischemia Infection
N.B Complications of DM like Diabetic foot ulcer are common in Type II DM than
Type I DM
▪ Cellulitis
▪ Abscess formation
▪ Joint sepsis
▪ Osteomyelitis
▪ Gangrene and Amputation→ DM is the most common cause of non-
traumatic foot amputation
Sample history
Chief compliant
HPI
A known DM patient for the past 8 years on metformin 500 mg, PO, daily for 5
years and she was adherent for her medication with regular follow up every 3
months here in Black Lion Hospital. For the last 3 years insulin was added
because she was told that her blood glucose level was not well controlled by oral
hypoglycemic drugs. Currently she took 24 units of insulin in the morning and 12
units at night with alternative injection sites between her upper arms, thighs and
periumbilical area. Stores her insulin in refrigerator.
She was relatively healthy until three months ago at which time she started to
experience a gradual onset of left calf stabbing pain which radiates to the toes
and numbness of both feet. Both symptoms were intermittent occurring mainly
when walking and relived by massaging of the legs, sitting and lying down. The
numbness started to spread upwards from the toes and involved the knees within
2 weeks duration associated with burning sensation of the left sole of the foot
which was constant but increased in intensity when walking while painkillers and
massaging in cold water eased the pain. Following this she came to Black Lion
Hospital. Since no bed was available, she was scheduled to come three weeks
later and was sent home.
she missed her appointment due to unknown reason and around one month
before admission, she noticed swelling of the left foot and a small black
discoloration on the plantar surface of the left big toe. The swelling involved up to
the knee but subsided after 4 days of constant massaging while the black
discoloration of the toe increased in size and ulcerated one week later with non-
foul-smelling blood mixed pussy discharge. The ulcer was small at first but within
the following two weeks it enlarged constantly involving the whole plantar surface
of the left big toe. One week before admission she started experiencing a sudden 541
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Following this She came to black lion hospital emergency OPD and was admitted
to B8 ward on the same day.
➢ She has a history of foot ulcer two years ago on the same toe. She went to
Ras Desta Hospital and was advised to have an amputation of the toe but she
refused and was discharged. But the patient claims that after two weeks of
washing the foot with salt water the ulcer subsided and disappeared.
➢ She has history of blurring of vision 8 years back at the time of diagnosis of
the diabetes. Laser eye surgery was done at Menelik hospital on the left eye
but the patient refused for the right eye due to discomfort. Following that the
eye sight on the left eye corrected but on the right eye, the blurring of vision
and shadowing progressed to total blindness.
➢ She wears well fitted shoes and doesn’t walk bare foot (RF)
➢ She dry skin of foot after washing leg, check between toes, and she
adds lotion to leg (unclean foot is RF)
➢ No hx of Leg trauma (traumatic ulcer →DDX)
𝐒𝐁𝐏 𝐨𝐟 𝐚𝐧𝐤𝐥𝐞
𝐀𝐁𝐈 = 𝐒𝐁𝐏 𝐎𝐅 𝐁𝐫𝐚𝐜𝐤𝐢𝐚𝐥 𝐚𝐫𝐭𝐞𝐫𝐲
= 𝟎. 𝟗 − 𝟏. 𝟏
IX
Discussion
❖ Diabetic foot ulcers are Slowly healing plantar ulcers that result from
apparently insignificant trauma
❖ The lifetime risk of a foot ulcer in patients with diabetes (type 1 or 2) may
be as high as 25 %.
❖ Diabetic foot ulcers are a major cause of morbidity and mortality,
accounting for approximately 2/3rd of all nontraumatic amputations performed
in the United States
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Ulcer Classification
The first step in managing diabetic foot ulcers is assessing, grading, and
classifying the ulcer.
Classification is based upon clinical evaluation of the extent and depth of the
ulcer and the presence of infection or ischemia, which determine the nature
and intensity of treatment.
To assess for ischemia, all patients with diabetic foot ulcers should have
ankle-brachial index (ABI) and toe pressure measurements.
There are many Classification systems of diabetic foot ulcer. We will see
common ones here.
Wagner classification system
University of Texas classification system
IDSA classification system
WIFI classification system
PEDIS classification system
(where; IWGDF = International Working Group on the Diabetic Foot,
IDSA = Infectious disease society of America, WIFI =
Wound/Ischemia/Foot Infection, PEDIS = Perfusion, extent, depth,
infection, and sensation)
N.B.
➢ Only two classification systems have been developed that provide
stratification that aligns to clinical decision-making: IWGDF/IDSA and WIFI.
➢ whilst the IWGDF/IDSA is incorporated into the WIFI, in situations where
only infection is being assessed and equipment is not available to use
WIFI, the IWGDF/IDSA infection classification can stand alone.
➢ IDSA is the recommended classification system for management and clinical
use in our setup.
Even though we are using in our setup, it is outdated from use in most
countries because it is a local grading system which doesn’t consider systemic
conditions like loss of protective sensation, infection, and ischemia.
It includes:
Grade 1: Skin and subcutaneous tissue
Grade 2: To bone
Grade 3: Abscess or osteitis
Grade 4: Partial foot gangrene
Grade 5: Whole foot gangrene
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Grade
✓ Grade 0: Pre- or post-ulcerative (Stages A to D)
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Foot care prescription for diabetic patients with lower extremity sensory neuropathy
Do’s
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Don'ts
Don’t apply hot water or irritant
chemicals
Don’t ignore numbness
Don’t treat calluses, corns, or ingrown
toenails at home
Don’t cross your legs or ankles for a
long period of time. Doing so can
create pressure points and lead to
unwanted breaks in skin
Don’t go bare foot
Don’t wear unfit shoes or tight socks
Don’t forget you follow up at health
facility
etc.
Despite preventive measures, Foot Ulceration and Infection are common and
represent a serious problem.
Due to the Multifactorial Pathogenesis of lower extremity ulcers, Management
of these lesions is multidisciplinary and often demands expertise in
Orthopedics
Vascular Surgery
Endocrinology
Podiatry and
Infectious Diseases.
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1) Mechanical Off-loading
2) Debridement or local wound care
3) Wound Dressings,
4) Appropriate Use of Antibiotics (treatment of infection)
5) Revascularization and
6) Limited Amputation.
I. Off-Loading
➢ It is the complete avoidance of weight bearing on the ulcer Which removes
the mechanical trauma that retards wound healing.
➢ Bed Rest and a variety of Orthotic Devices or Contact Casting limit weight
bearing on wounds or pressure points.
III. Dressings
➢ Dressings such as Hydrocolloid Dressings promote wound healing by
creating a moist environment and protecting the wound.
➢ Antiseptic agents should be avoided.
➢ Topical antibiotics are of limited value.
➢ Physiotherapy, Orthotic Evaluation, and Rehabilitation Should occur once the
infection is controlled.
Uninfected
Treatment of risk factor and follow up
Mild infection
Can be treated with broad spectrum oral antibiotics at OPD with close
follow up.
Antibiotics include; Cephalosporin, Clindamycin or metronidazole,
Amoxicillin/Clavulanate, and Fluoroquinolones
Moderate to severe infections
Need hospital admission for IV antibiotics (ceftriaxone or cefotaxime with
metronidazole are available in most setups of Ethiopia).
Consider anaerobic coverage
Modify Antibiotics based on culture result
Duration is at least for 4 to 6 weeks (parenteral antibiotics for at least 2
weeks, the rest completed with PO antibiotics)
Surgical debridement required for tissue abscess and local gangrene.
Those with extensive and life-threatening gangrene may require
amputation.
Debridement
Initiate Antibiotics: Triple antibiotics
Grade 4: Localized Gangrene
Treat Like Grade 3
Improve Circulation
Diffuse Arterial Disease May Require Major Amputation
Grade 5: Gangrene of Whole Foot
Urgent Hospital Admission
Antibiotics
Surgical consultation and Amputation
History
DKA patients usually present with LOC or severe abdominal pain and vomiting
that mimics acute abdomen.
N.B
Complication of DKA
DKA, if not detected and treated early it may end up with complications like;
Sample history
Chief compliant
HPI
A known DM patient for the past 4 years taking insulin injection 20 units in the
morning and 10 units at night. With alternative injection sites between his upper arms, 556
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thighs and periumbilical area. Stores his insulin in wet sand bag. He was adherent for
his medication with regular follow up every 2 - 3 months in UOG hospital.
Currently presented with severe, crampy, localized, Peri umbilical abdominal pain and
non-blood tingled, non-projectile, non-foul-smelling Vomiting of ingested matter 3 - 4
times per day of 03 days duration, but no change in mentation.
➢ Ask those +ve and -ve statements listed on the sample hx of a DM patient
above.
➢ Two weeks before admission, he also experienced dry cough occurring mostly
at night which was exacerbated by deep breathing associated with chest pain
and high grade intermittent fever where he visited a private clinic and he was
given a tablet to be taken 3 times per day for 7 days and another tablet to be
taken once daily for 3 days and he was improved. (pneumonia is precipitant factor for
this patient)
➢ No hx of burning sensation during urination, flank pain or hematuria (UTI as
precipitant)
➢ No hx of diarrhea, nausea or vomiting (gastroenteritis as precipitant)
➢ He is not from malaria endemic area and no travel hx to malaria endemic
area (malaria as precipitant)
➢ No hx chest pain, dyspnea or family hx of sudden cardiac death (MI as precipitant
factor)
➢ No hx of headache, body weakness or head trauma (stroke, SDH as precipitant factor)
1 GA
2 Vital signs
3 HEENT 557
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4 LGS
5 RS
6 CVS
✓ Decreased JVP
7 Abdominal examination
✓ Abdominal tenderness
✓ Reduced skin turgor(dehydration)
8 GUS
9 MSS
10 IS
✓ Dry skin
11. NS
N.B Dehydration signs are common in DKA (more common in HHS than DKA)
DDX of DKA
1. HHS
2. Alcoholic ketoacidosis
3. Starvation ketoacidosis
4. Lactic acidosis
5. CKD
6. Drugs → salicyclates, methanol, ethylene glycol
7. For more refer on NS examination /coma/ (click here → 1.4.5 Coma)
IX
Discussion
DKA HHS
RBS > 250 mg/dl RBS > 600 mg/dl
Common in type 1 DM Common in type 2 DM
Present with severe abdominal Present with profound
pain, vomiting or LOC dehydration, hypotension,
Strong hx of poly smx’s and tachycardia or LOC
weight loss Weak hx of polyuria or weight
Urine and serum ketone highly loss
rise Urine and serum ketone normal
5% mortality or slightly rise
Have 3 cardinal features 15% mortality
☛ Hyperglycaemia Severe osmotic diuresis, insulin
☛ Acidosis sufficient to suppress lipolysis
☛ ketosis Osmolality > 320
Variable osmolality
Management of DKA
Principles of mgt
➢ ABCD of life
➢ Resuscitation by expanding intravascular volume (fluid replacement therapy)
➢ Potassium replacement therapy
➢ Insulin therapy
➢ Treat complications
➢ Treat precipitating factors
➢ Monitoring
Non-Pharmacologic
Pharmacologic
1. Replace fluids: Individualize fluid needs based on the patient hydration status;
the following is a guide to severely dehydrated patients.
o Initial fluid
✓ 1000ml NS over the first one hour. (for pediatrics, 10 ml/kg over 1hour, and
may be repeated if necessary. In the rare patient with DKA who presents in shock, give
isotonic saline in 20 ml/kg bolus infused as quickly as possible)
✓ Reassess for hydration status: if still severely dehydrated, give
another 1000ml NS over the next 01 hour.
o Subsequent fluid
✓ Depends on the hydration status and urine output of the patient.
✓ On average give about 250 mL/hour (1000ml over 04 hour) in the
first 24 hours or until patient is able to take enough oral fluids.
✓ Reassess the patient hydration status to decide subsequent Iv fluid
needs.
✓ For pediatrics, calculate the fluid required.
fluid required =
Maintenance fluid (48 hours) + Deficit fluid ( 85 X Wt)− Minus Bolus fluid ( which you gave above )
48ℎ𝑟𝑠
o Changing fluid
✓ Change the NS to DNS (5%DW9D) when plasma glucose reaches
250 mg/dl in DKA and 300mg/dl in HHS. (i.e. If blood glucose drops
below 250mg/dl Change fluid to 5% DW in ½ NS (half of the fluid
NS and half DW)). This will continue until urine is ketone free.
✓ As long as the patient remains acidotic, insulin administration should
never be stopped. if instead drop in the blood sugar need to be
addressed by adding or increasing glucose administration in the IV
fluid;
✓ Maintain the blood glucose between 150 and 250 mg per dL.
o Fluid is used to treat
✓ DHN
✓ Hyperglycaemia (since fluid induce glucosuria)
✓ Metabolic acidosis
o HHS requires more fluid.
o Assess hydration status, BP and urine output frequently.
o In patients with impaired kidney function and cardiac disease more frequent
monitoring must be performed to avoid iatrogenic fluid overload.
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3. Potassium
o All patients with DKA have potassium depletion irrespective of the serum K+
level.
o N.B. total K+ level is low in DKA, but serum K+ level can be normal, high
or low
✓ If the initial serum K+ is <3.3 mmol/l, do not administer insulin until
the K+ is corrected.
✓ If the initial serum K+ is > 5.3 mmol/l, do not supplement KCl until
the level reaches < 5.3.
✓ If K+ determination is not possible delay initiation of K+ replacement
until there is a reasonable urine put (>50 ml/hr)
o Add intravenous KCl in the IV fluids (20-40 meq of KCl in each bag of NS)
N.B. 1 vail of Kcl = 20 meq
✓ Add 40 meq of Kcl in IV fluid when serum K+ is within 3.4 - 4.5
mmol/l
13
IV administration of regular insulin is usually preferred because it ensures rapid distribution and allows
adjustment of the infusion rate as the patient responds to therapy. DKA can also be treated with SC short-acting
insulin analogues.
14
Acidosis and ketosis resolve more slowly than hyperglycemia. As ketoacidosis improves, β-hydroxybutyrate is
converted to acetoacetate. Ketone body levels may appear to increase if measured by laboratory assays that use
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6. Follow up of response
o Blood glucose every 1 - 2hrs
o Urine ketones and glucose every 2 - 4hr
o Electrolytes (especially K+) every 6 hr for first 24 h.
7. Continuation of treatment
o The above treatment should continue until the patient is stable, clinically
acidosis improves, and patient is able to take oral feeding.
o The urine ketone might still be positive, as it usually lags behind the
improvement of acidosis.
8. Transition
o Once the patient is able to take oral feeding and clinically the acidosis
improved (i.e out of DKA).
✓ Reduce regular insulin: 2-3 units hourly (5 units every 2 hour) or for
continuous infusion by 0.05/kg per hour
✓ Overlap regular insulin infusion with subcutaneous (SC) NPH insulin
for 2-3 hours to avoid rebound hyperglycemia. And this facilitates
transition to an outpatient insulin regimen and reduces length of
hospital stay.15
15
It is crucial to continue the insulin infusion until adequate insulin levels are achieved by administering Sc NPH.
Even relatively brief periods of inadequate insulin administration in this transition phase may result in DKA
relapse.
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Chapter 10; DM /Diabetes Mellitus/ (የስኳር በሽታ)
10.3 Hypoglycaemia
Clinical features
☛ Irritable
☛ Sweating
☛ Tachycardia
☛ Incoordination
☛ Restless
☛ Excessive hunger
☛ Dizziness
In DM pt
✓ Insulin a n d sulfonylureas e x c es s dose or previous doses with
unaccustomed exercise
✓ omission of meals.
✓ Development of CKD, AKI, and sepsis.
In non-diabetic patients with critical illnesses
✓ Hepatic or renal failure
✓ Adrenal insufficiency
✓ Sepsis
✓ Malaria.
In Seemingly normal patients
✓ Endogenous hyperinsulinemia
✓ Accidental or surreptitious use sulfonylureas or insulin.
Diagnosis
Investigations
✓ Glycemia related: FBS, postprandial blood sugar and HbA1c
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Management of hypoglycaemia
Non-pharmacologic
➢ The main stay of management of level 1-2 (mild to moderate) and level-3
(severe) hypoglycemia with preserved consciousness taking or providing
glucose rich food/drinks(sweets).
o Pure glucose is preferred but any carbohydrate rich food can be
used
✓ Give 04 teas spoon of sugar diluted in water
✓ Monitor blood sugar every 20-30 minutes
✓ If no improvement repeat the above
✓ Once blood sugar improves, the patient must take a meal or snack
o Alternatives: regular soft drinks
✓ 200ml of Mirinda® or Cola® contains about 20gram sugar can replace the
above.
o Avoid protein rich foods as they increase insulin response
➢ For hypoglycemia unawareness: a 2-3 weeks period of avoiding
hypoglycemia through frequent self-monitoring of blood glucose and keeping
the blood glucose at higher levels may restore awareness.
Pharmacologic
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Complication of AKI
Complication of CKD
Sample history
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በሽታ)
Sample hx of a pt’ from Maksegnit with a DX of AKI on CKD. (sample taken from our friend Dr.
Natnael Bedilu (GP), which was his round case during our C-I attachment)
Chief compliant
GBS of 2 weeks duration
HPI
This patient was last relatively healthy 2 weeks back, at which time his father noticed swelling
around the eyes and face that was more marked early in the morning. Over a period of 3 days the
swelling progress to involve the abdomen and the legs then becomes generalized. Concomitantly
the patient starts to experience shortness of breath which was felt initially while doing supra
ordinary activities like going uphill’s which later worsen over a week to be felt at ordinary
activities like going 15minute walk to the school he was attending associated with palpitation but
no orthopnea, PND, chest pain or intermittent claudication.
In addition to this the patient was complaining of nausea, loss of appetite and dull aching type of
epigastric pain without radiation or any aggravating or relieving factor but no history of
vomiting, bowel habit change or weight loss. (ureamic sxx, ESRD, Gastritis and PUD → CXN)
For this compliant he visited local health center at tseda where he was given unspecified white
oval tablet to be taken 3X per day prescribed for 10 days but he discontinued the treatment since
he was not getting any improvement of the symptoms and he come to our hospital for better
investigation and management.
12 years back he had experienced reddish discoloration of urine and generalized body swelling
for which he was admitted at UOG hospital where he was told that he was having kidney disease.
He was then given unspecified tablets and injectable medications and he was on salt free diet.
After 3 weeks of hospital stay, he was discharged with follow up and improved. He was relatively
fine until the current admission.
No hx of DM, HTN or asthma (DM and HTN cause CKD, DM cause 2ry nephrotic sxx →
RF)
No hx of drug intake other than those mentioned above (Drugs like
Aminoglycosides, NSAID’s, Metformin are RF for Intrinsic AKI and CKD)
No family hx of similar illness (RF for PCKD)
No hx of tinnitus, blurring of vision, light headedness or easy fatigability
(anaemia → CXN)
No hx of LOC, confusion, bizarre behaviour, forgetfulness, disturbance of
speech, visual disturbance or abnormal body movement (ureamic encephalopathy
→ CXN)
No hx of nasal/gum bleeding or bleeding from other sites (hematologic CXN of
CKD)
He has dyspnoea but no hx of chest pain, orthopnea or PND (IHD,
pericarditis, CHF → CXN of CKD or DDX for GBS)
No hx of malar rash, photosensitivity or joint pain
→ DDX)
(SLE cause 2ry Nephrotic SXX
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በሽታ)
No hx of chronic cough, contact with chronic cougher or previous TB
treatment (TB enteritis, renal TB → DDX)
No hx of RUQ abdominal pain, yellowish discoloration of the eye or
contact with a jaundiced person (CLD → DDX)
2 Vital signs
3 HEENT
4 LGS
5 RS
6 CVS
➢ CHF features
➢ Pericardial friction rub and knock from pericarditis
7 Abdominal examination
8 GUS
9 MSS
10 IS
11 NS 575
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በሽታ)
➢ Stroke features
➢ Coma
1. CKD
2. Nephrotic sxx
3. CHF
4. Constrictive pericarditis
5. CLD
6. Advanced Lymphoma (NHL)
7. Disseminated TB to pleura, Peritoneum…..
8. Hypothyroidism
9. ? PLE
IX
U/A
✓ Abnormal sediment or cast (hyaline cast, RBC cast, WBC cast) →
indicate kidney damage
✓ Proteinuria → indicate kidney damage
✓ Haematuria → glomerulonephritis
✓ cells
Urine culture and sensitivity → UTI (Pyelonephritis)
RFT (BUN and Creatinine)
✓ Creatinine clearance (GFR) estimate by Cockcroft-Gault equation in adults and
older adolescents (age ≥18 years).
(140 − 𝑎𝑔𝑒) 𝑥 𝑤𝑒𝑖𝑔ℎ𝑡(𝑖𝑛 𝑘𝑔)
(𝑚𝑢𝑙𝑡𝑖𝑝𝑙𝑦 𝑡ℎ𝑒 𝑟𝑒𝑠𝑢𝑙𝑡 𝑤𝑖𝑡ℎ 0.85 𝑓𝑜𝑟 𝑓𝑒𝑚𝑎𝑙𝑒𝑠)
72 𝑥 𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 𝑙𝑒𝑣𝑒𝑙 (𝑚𝑔/𝑑𝑙)
Discussion
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በሽታ)
Stage 1 Increase from baseline: 1.5 - 1.9 < 0.5 ml/kg/h for 6 - 12
times (>50% but <100%) or > hours
0.3mg/dl
Stage 2 Increase from baseline 2.0 -2.9 Urine output < 0.5 ml/kg/h for
times (>100% but < 300%) ≥ 12 hours
Stage 3 Increase from baseline ➢ <0.3 ml/kg/h for >24 hours
➢ 3 times (>300%) OR OR
➢ An increase to a level >4.0 ➢ Anuria for >12 hour
mg/dl Or
➢ Initiation of renal replacement
therapy
* KIDGO is a modification to RIFLE (Risk, Injury, Failure, Loss, ESRD) and AKIN
.
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በሽታ)
Postrenal AKI occurs when the normally unidirectional flow of urine is acutely
blocked either partially or totally, leading to increased retrograde hydrostatic
pressure and interference with glomerular filtration
For AKI to occur in individuals with two healthy functional kidneys, obstruction
must affect both kidneys in order to observe large increases in SCr.
Unilateral obstruction may cause AKI in the setting of significant underlying
CKD or, in rare cases, from reflex vasospasm of the contralateral kidney.
Obstruction to urinary flow may be caused by functional or structural
derangements anywhere from the renal pelvis to the tip of the urethra
Causes of obstruction include
o Bladder neck obstruction is a common cause of postrenal AKI
▪ BOO (Bladder outlet obstruction)
▪ Prostate cancer
▪ Neurogenic bladder, or
▪ therapy with anticholinergic drugs.
o Obstructed Foley catheters (if not recognized and relieved.)
o Urethral strictures
o bilateral ureteral obstruction
o Stones, blood clots, external compression, tumor, retroperitoneal fibrosis
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
Clinical features
➢ The clinical features of AKI are dominated by those of the underlying cause
unless the AKI is severe.
Symptoms
Prerenal azotemia should be suspected in the setting of vomiting, diarrhea,
glycosuria causing polyuria, and several medications including diuretics,
NSAIDs, ACE inhibitors, and ARBs
A reduction in urine output (oliguria, defined as <400 mL/24 h) usually denotes
more severe AKI (i.e., lower GFR) than when urine output is preserved.
Red or brown urine may be seen with or without gross hematuria
Fatigue
Body swelling
Shortness of breath
Poor appetite, nausea and vomiting
Hiccups
Bleeding, mucocutaneous
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በሽታ)
Symptoms of the underlying cause: e.g. tea/cola colored urine in
glomerulonephritis, fever in sepsis/malaria
Signs
Investigations
Serum urea and creatinine
Urinalysis
Figure; Interpretation of urinary sediment findings in acute kidney injury (AKI). 582
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
ATN, acute tubular necrosis; GN, glomerulonephritis; HUS, hemolytic-uremic syndrome; RBCs,
red blood cells; RTE, renal tubular epithelial; TTP, thrombotic thrombocytopenic purpura; WBCs,
white blood cells.
Serum electrolytes
Abdominal ultrasound: to exclude urinary tract obstruction and assess kidney
size
Other investigation should be done based on the suspected specific cause
Renal biopsy:
Treatment of AKI
Objectives of treatment
➢ Correct reversible causes of AKI
➢ Avoid worsening of kidney injury
➢ Maintain normal volume and electrolyte status
➢ Avoid overdoses of medications with renal clearance
The management of individuals with and at risk for AKI varies according to the
underlying cause
Common to all are several principles
Pharmacologic treatment
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
➢ There is no specific pharmacologic treatment for AKI caused by ischemic or
nephrotoxic acute tubular necrosis.
➢ The specific treatment depends on the cause of the AKI.
➢ Intravenous fluids
✓ Indicated only in patients who are hypotensive or dehydrated on clinical
evaluation.
✓ In patients with hypovolemia or clinical hydration, fluids should be given to
keep the fluid balance in the positive side.
✓ Do not give (“challenge’) fluid for all patients unless there is evidence of
volume depletion)
✓ Urine output and fluid balance should closely followed as oliguric patients
can easily develop pulmonary edema.
➢ Furosemide:
✓ Indicated in patients with signs of fluid overload (edema, evidence of
pulmonary congestion or high BP)
✓ Starting dose 40mg, intravenously. If no response increase the dose every
1-2 hour till adequate response.
✓ Do not go beyond 200mg/dose.
✓ Doses above 100mg should be given diluted (1-2mg/ml of fluid) and given
slowly (4mg/min).
☛ E.g. 200mg in 100ml NS/01 hr, 160mg in 100mL NS/ 40min
✓ Response can be considered adequate, if the urine output is 50-100ml in
01 hour, or 100-200ml in 02 hours.
➢ Treatment of hyperkalemia → Click and see section on Hyperkalemia
➢ Treatment of hypertensive emergency → see section on hypertension from
chapter one (click here → Hypertension (የደም ግፊት) and HHD)
➢ Treatment of specific cause:
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
Prevention
➢ A significant proportion of AKI is preventable.
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
✓ Rapid and adequate fluid replacement in volume depleted patients
✓ Early detection and management of sepsis, malaria, pre-eclampsia
✓ Avoiding nephrotoxic medications in high risk patients, whenever possible
e.g. NSAIDS, aminoglycosides, iodinated intravenous contrast agents.
✓ Close monitoring of renal function and urine output in hospitalized patients
✓ Dose adjustment of drugs with renal clearance.
CKD is defined as the presence of kidney damage for more than 3 months as
evidenced decreased GFR of < 60m/min or the presence of other markers of
kidney damage with or without decreased GFR
Other makers of kidney damage
o Abnormalities on urinalysis: Persistent proteinuria is the most important
one.
o Abnormalities on imaging: shrunken kidneys, polycystic kidneys,
hydronephrosis.
o Histologic abnormalities findings on renal biopsy specimens
CKD encompasses a spectrum of pathophysiologic processes associated with
abnormal kidney function and a progressive decline in GFR.
The risk of CKD progression is closely linked to both the GFR and the amount
of albuminuria.
For determination of estimated GFR in adult patients with stable serum
creatinine, use the MDRD (Modification of Diet in Renal Disease Study) or
CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, which
are freely accessible on line.
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
In our setup, during our internship, we were using Cockcroft-Gault equation for
GFR estimation, since it was easy for calculation (we used it from UpToDate 2018, we are
not sure for the approval by KIDGO)
o Creatinine clearance (GFR) estimate by Cockcroft-Gault equation in adults and older
adolescents (age ≥18 years).
(140 − 𝑎𝑔𝑒) 𝑥 𝑤𝑒𝑖𝑔ℎ𝑡(𝑖𝑛 𝑘𝑔)
𝐺𝐹𝑅 =
72 𝑥 𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 𝑙𝑒𝑣𝑒𝑙(𝑖𝑛 𝑚𝑔/𝑑𝑙)
The five most frequent causes of CKD, cumulatively accounting for >90% of
the CKD disease burden worldwide (Relative contribution of each category varies with
geographic region and race)
o Diabetic nephropathy
o Glomerulonephritis
o Hypertension-associated CKD
o PCKD (polycystic kidney disease) / Autosomal dominant form/
o Other cystic and tubulointerstitial nephropathy
End stage renal disease (ESRD) → refers to a state of advanced CKD with
estimated GFR being < 15ml/min where lifelong renal replacement therapy
(dialysis or kidney transplantation) is necessary to sustain a reasonable quality
of life and survival.
Table. KIDGO Classification of CKD based on CAG (cause, albuminuria and GFR) 587
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
GFR categories (ml/min/1.73 m2) description and range
Categories (G) Description GFR (ml/min/1.73m2)
G1 Normal or high ≥ 90
G2 Mildly decreased 60-89
G3 G3a Mildly to moderately 45-59
decreased
Clinical features
Symptoms
Generally asymptomatic in the early stages (Stages 1 and 2 /i.e G1 and G2/CKD are usually
asymptomatic)
As CKD advances some non-specific symptoms might develop
Common but nonspecific symptoms:
o Nocturia
o Fatigue
o Loss of appetite, nausea, vomiting, hiccup
o Weight loss
o Muscle cramps, paresthesia
o Pruritus
o Body swelling, shortness of breath
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
o Sleep disturbance, depression, anxiety, sexual dysfunction
Signs
There are specific signs for CKD.
Early stages of CKD might not have any signs apart from signs of the
underlying disease
Advanced stages
o Edema, pleural effusion or crackles on lower lung field
o Dry skin, excoriation marks, papular eruptions, uremic frost
o Pericardial friction rub or distant heart sounds
o Uremic fetor, decrement in cognition, flapping tremor, lethargy
Investigations
Serum creatinine and urea: Estimated GFR
Urinalysis
Quantification of proteinuria or albuminuria: 24urine protein/albumin, spot urine
albumin to creatinine ratio (ACR)
Abdominal ultrasound
Calcium, Phosphate, PTH levels (preferably intact PTH level than total PTH)
Alkaline phosphatase
Serum electrolytes
Abdominal ultrasound
CBC
Estimated GFR (eGFR) should be used for follow up of patients with CKD
than serum creatinine alone
Treatment of CKD
Objectives of treatment
Slow the progression of decline in GFR
Prevent, detect and manage complications
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
Principles of CKD management:
➢ Establish the cause of CKD and treat (if possible)
➢ Identify and manage unexpected (acute) deterioration in kidney function
➢ Preventing or slowing disease progression
➢ Treatment of the complications
➢ Identification and adequate preparation for RRT
General health advice e.g. smoking cessation, weight reduction for obese
individuals
Restrict salt intake
Dietary protein reduction
o Physicians should not overemphasize on protein restriction as the benefits
are modest.
o In malnourished individuals, which many advanced CKD patients are,
protein restriction should not be advised.
Medication Dose Adjustment
o Some drugs that should be avoided include
▪ Metformin and other oral anti-hyperglycemics that are eliminated by the
kidney.
▪ NSAIDs
▪ Meperidine
o Many antibiotics, antihypertensives, and antiarrhythmics may require a
reduction in dosage or change in the dose interval.
o Several online Web-based databases for dose adjustment of medications
according to stage of CKD or estimated GFR are available (e.g.
http://www.globalrph.com/ index_renal.htm).
o Or you can search a specific drug dose adjustment for renal impairment, from
UpToDate as shown in the picture below
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Chapter 11; AKI/Acute kidney injury/ and CKD/ Chronic kidney disease (የኩላሊት
በሽታ)
Picture; diagrammatic example on, how to search, a specific drug dose adjustment
for renal impairment, from UpToDate
First line
Alternatives
ARB’s
Treatment of hyperphosphatemia:
o Phosphate binders are indicated if serum phosphorus is > 5.5mg/dl
First line
o Sevelamer (as hydrochloride or carbonate)
▪ Initial dose 800mg, PO, TID with meal. If serum phosphorus >9mg/dl,
1600mg, PO TID can be started.
▪ Adjust the dose to target to a target serum phosphorus near normal
(< 5.5mg/dl)
Alternative:
o Calcium carbonate: starting dose 500 - 1000mg, PO, TID, chew, with meal
o Calcium acetate: starting dose 1334mg, PO, TID with meal
o If total serum calcium increase >10mg/dl: hold calcium
o If there is hypocalcemia, calcium-based phosphate binders are preferred
over sevelamer.
N.B. All AKI/CKD Patients need nephrologist evaluation. But, in the following
conditions, Nephrologist intervention in referral setup is mandatory.
Patients with known causes of CKD (e.g. diabetic kidney disease, obstructive
uropathy) when the GFR is less than 30ml/min.
If the cause of CKD is not known or suspected to be glomerular disease
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Nephrotic syndrome (NS) is a clinical sate which results from heavy (massive)
proteinuria.
The presence of nephrotic syndrome (NS) is a definitive indicator of glomerular
pathology.
Nephrotic syndrome is defined if all the following 1st three clinical and
laboratory findings are fulfilled
1) Heavy proteinuria: defined as urine protein >3000mg (3gm) in a 24hr urine
protein
2) Hypoalbuminemia: Defined as serum albumin <3g/dl
3) Edema/anasarca
4) Hyperlipidemia (hypercholesterolemia) → usually severe, is a common
finding. Some experts include it as requirement for the diagnosis of NS..
5) Hypertension
6) Minimal microscopic hematuria;
Notice
o Proteinuria (nephrotic range) and edema are marked in nephrotic syndrome
than nephritic syndrome
o Hypertension and Hematuria are marked in nephritic syndrome than
nephrotic syndrome
Some patients might have heavy proteinuria (>3000mg in 24-hour urine) but do
not have the other features of the NS. They are said to have nephrotic range
proteinuria, but not the nephrotic syndrome.
If left undiagnosed or untreated, some of these syndromes will progressively
damage enough glomeruli to cause a fall in GFR, producing renal failure
The GFR in these patients may initially be normal or, rarely, higher than
normal, but with persistent hyperfiltration and continued nephron loss, it
typically declines over months to years.
Patients with a basement membrane syndrome either have genetically
abnormal basement membranes (Alport’s syndrome) or an autoimmune
response to basement membrane collagen IV (Goodpasture’s syndrome)
associated with microscopic hematuria, mild to heavy proteinuria, and
hypertension with variable elevations in serum creatinine.
Increased susceptibility to infection, venous thrombosis, and acute kidney injury
are the major complications of the NS.
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Clinical features
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
The following steps are helpful in guiding the diagnosis of nephrotic syndrome in
adults
Step 1: Confirming the presence of nephrotic syndrome:
o 24-hour urine protein
o Serum albumin
o Lipid profile
Step 2: Investigation for common causes of nephrotic syndrome
o Retinal screening for diabetic retinopathy: any time for type 2 diabetics and
after a minimum of five year of type 1 diabetes
o HBSAg, HCV antibody, HIV screening, VDRL(RPR), ANA
o AntiPLA2R antibody: For screening primary membranous nephropathy
o Work up for multiple myeloma: If suspected, serum free light chains and
serum electrophoresis.
o Work up for other malignancies: only if there are clinical clues.
Step 3: Renal biopsy
o Unlike pediatric patients almost all non-diabetic adult patients with nephrotic
syndrome need renal biopsy to confirm the etiology. Hence, they need to
be referred to a hospital with nephrology service.
Investigations: Additional helpful investigations
Urinalysis: hematuria and proteinuria
o Hematuria can be gross or microscopic hematuria. More common in
nephritic syndrome than nephrotic syndrome
o In early nephropathy, such as in diabetic nephropathy, proteinuria
increases to 30 - 300 mg/24 h and is called microalbuminuria and
represents the presence of renal disease.
o Greater than 300 mg/24 h of albuminuria represents frank proteinuria and
more advanced renal disease
Renal function tests (serum creatinine): AKI can occur as a complication of the
NS or over-diuresis or could be part the glomerular disease (nephrotic-nephritic
presentation)
Serum electrolytes: As baseline for diuretic therapy
Abdominal ultrasound: to see kidney sizes
Investigations when complications are suspected: e.g. if deep vein thrombosis
(a common complication is suspected), do doppler ultrasound of suspected limb
veins.
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Treatment
Non-pharmacologic treatment
➢ Salt restriction
➢ Fluid restriction (less than 1 - 1.5 liter/day)
➢ Encourage ambulation
➢ Protein should not be restricted rather encourage patients to take adequate
protein and high calorie diet
Pharmacologic treatment
1. Treatment of the edematous state
Loop diuretics: nephrotic syndrome is associated with relative diuretic resistance
o Oral Furosemide:
▪ Starting dose 40mg, PO, BID -TID.
▪ Increase the dose to 80 mg PO BID-TID, then 120mg. PO, BID-TID.
o Aim: decrease weight by 0.5 to 1kg/day.
o IV Furosemide: If no adequate weight loss with increasing dose, admit for
IV Furosemide
▪ Start with 40mg, IV, TID.
▪ Increase the dose to 80 mg IV TID, then 120mg. PO, TID
▪ If no adequate response with IV Furosemide, add hydrochlorothiazide
12.5 to 25mg BID (to be given 30 minutes before the IV Furosemide)
o Add prophylactic KCl tablets (600mg BID-TID) or Spironolactone 25-50mg
PO/daily and monitor serum electrolytes every 2-3days.
2. Anti-proteinuric treatment
ACE inhibitors or Angiotensin receptor blockers (ARBS)
o Start after adequate diuresis.
o The kidney function must be stable before starting.
o The dose should be escalated gradually with monitoring of serum
creatinine and potassium. Monitoring should be done within 2 weeks of
initiation and dose escalation.
o ACE inhibitors (particularly Enalapril) are preferred over ARBs due to their
low cost and wide availability.
Preferred
o Enalapril: starting dose 5mg BID, Maximum dose 20mg BID
Alternatives
o Lisinopril: starting dose 5mg/day, Maximum dose 40mg/day
o Perindopril: starting dose 5mg/day. Maximum dose 15mg/day
ARB
o Telmisartan: Starting dose: 40mg/day maximum dose 80mg/day
o Irbesartan: Starting dose: 75-150mg/day, maximum dose 300mg/day
o Losartan: Starting dose 50mg/day maximum dose 100mg/day
o Valsartan: Starting dose 80 -160mg/day, maximum dose 320mg/day
o Candesartan: Starting dose 8-16mg/day maximum dose 32mg/day 599
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Clinical features
Clinical features of the AGN/RPGN: the nephritic syndrome
o Acute onset body swelling (Edema) and shortness of breath
o Decreased urine amount (oliguria)
o Reddish urinary discoloration (typically tea or cola colored urine)
o High blood pressure
Clinical features of suggesting the underlying causes (systemic diseases)
o Hair loss/diffuse non-scaring alopecia – SLE
o Malar rash, photosensitive rash, non-pruritic rash over the body– SLE
o Joint pain, evidence of arthritis (swelling and tenderness of joints) – SLE
o Hemoptysis, cough and dyspnea – Vasculitis, Anti-GBM disease or
pulmonary edema
o Petechiae/purpura – Vasculitis or SLE
o Pleural effusion – Part of the complication or SLE associated
o Pericarditis (friction rub or distant heart sound) – SLE or uremic
pericarditis
o Cardiac murmurs – Infective endocarditis or SLE
o Focal neurologic deficit – SLE (Lupus cerebritis) or vasculitis
Clinical features related to marked decrement in the kidney function
o Pulmonary crackles – pulmonary congestion
o Nausea and vomiting – uremic gastropathy
o Change in mental status – uremic or hypertensive encephalopathy
o Mucocutaneous bleeding – uremic bleeding
Investigations
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Urinalysis:
o Hematuria and proteinuria
o The RBCs in the urinalysis: Significant proportion are dysmorphic
o RBC casts: may or may not be present. Their presence is not mandatory
for diagnosis)
24hour urine protein: above 500mg (usually>1000mg), it can sometimes be
nephrotic range(>3000mg)
Serum creatinine and ureaii
Treatment
Non-pharmacologic treatment
Salt and fluid restrictions
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Dialysis: if there are indications (see the topic acute kidney injury for
indications)
Pharmacologic treatment
1. Supportive (symptomatic) management
Loop diuretics
o Oral Furosemide:
▪ For patients with mild peripheral edema.
▪ Starting dose 40mg PO BID.
▪ Follow every 2-3 days, increase the dose to higher dose (Maximum
dose 600mg/day) or admit for IV diuresis, if response is suboptimal or
there is worsening.
o IV Furosemide:
▪ For patients with pulmonary congestion or sever edematous state
▪ Start with 40mg IV, stat. See response every 2 hours. If urine output
of 150ml and above is achieved in 2 hours and give the 40mg IV BID
or TID.
▪ If urine output is <150ml in 2hours, increase the dose by 40mg and
reassess the urine output in another 2 hours.
▪ Give the dose which resulted in adequate once diuresis
(>150ml/2hour) as standing e.g. 80mg or 120 IV BID or TID.
Maximum bolus dose 200mg.
▪ IV Furosemide above 100mg should be given slowly (over 15-
20minutes)
o Avoid prophylactic potassium tablet or spironolactone: due to the risk of
hyperkalemia in patients with AGN/RPGN.
Antihypertensives
o Loop diuretics are the preferred Antihypertensives: see above on diuretic
o Additional Antihypertensive: If BP is not well controlled with loop diuretics
alone
▪ Add Calcium channel blocker on loopr diuretics:
• Amlodpine 5-10mg PO once daily OR
• Nifedipine 20-40mg PO BID.
▪ If a third agent is needed (on top of Furosemide and Calcium channel
blocker combination) add a beta-blocker:
• Carvedilol 6.25 to 25mg BID or
• Bisoprolol 2.5 to10mg/day or
• Metoprolol 25-100mg/day or
• Atenolol 25-100mg/day
▪ Avoid ACE inhibitors, Angiotensin receptor blockers (ARBS): due to
the risk of hyperkalemia and potential for deterioration in kidney
function.
▪ Avoid Spironolactone in patients with AGN/RPGN: due to risk of
hyperkalemia and worsening kidney function.
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Management of hyperkalemia
o Start shifting treatment with regular insulin if serum potassium is
>6.0mmol/l
▪ Regular Insulin: 10IU regular insulin IV, immediately followed by
03vials (60ml) of 40% dextrose IV, to be given every 6 hour. Monitor
blood sugar every 4-6 hourly.
▪ If potassium is >7mmol/l or there are ECG changes hyperkalemia start
IV calcium
• Calcium gluconate (10%) 10ml, IV, to be given over 5 minutes
followed by regular insulin (as above).
Clinical features
o Edema
o Hypertension, and
o Oliguric renal failure
Symptoms and signs may be severe enough to appear as RPGN.
Systemic symptoms of headache, malaise, anorexia, and flank pain (due to
swelling of the renal capsule) in as many as 50% of cases.
5% of children and 20% of adults have proteinuria in the nephrotic range
A subclinical disease is reported in some series to be 4 - 5 times as common
as clinical nephritis, and these latter cases are characterized by asymptomatic
microscopic hematuria with low serum C3 complement levels.
Investigations
In the first week of symptoms, 90% of patients will have a depressed CH50
and decreased levels of C3 with normal levels of C4.
Positive rheumatoid factor (30 - 40%)
Positive cultures for streptococcal infection (10–70%)
Increased titers of ASO (30%), anti-DNAse (70%), or antihyaluronidase
antibodies (40%) can help confirm the diagnosis.
Treatment
IgA nephropathy
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
Clinical features
➢ The two most common presentations of IgA nephropathy are
✓ recurrent episodes of macroscopic hematuria during or immediately
following an upper respiratory infection often accompanied by proteinuria or
✓ persistent asymptomatic microscopic hematuria.
➢ Nephrotic syndrome is uncommon.
➢ Proteinuria can also first appear late in the course of the disease.
➢ Rarely patients present with acute renal failure and a rapidly progressive
clinical picture. 607
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Chapter 12; Glomerular disease (Nephrotic syndrome and Nephritic syndrome)
➢ IgA nephropathy is a benign disease for the majority of patients, and 5 - 30%
of patients may go into a complete remission, with others having hematuria but
well-preserved renal function.
➢ In the minority of patients who have progressive disease, progression is slow,
with renal failure seen in only 25–30% of patients with IgA nephropathy over
20–25 years.
➢ Risk factors for the loss of renal function include
✓ the presence of hypertension or proteinuria
☛ persistent proteinuria for ≥ 6 months has poor prognosis
✓ the absence of episodes of macroscopic hematuria
☛ male sex
☛ older age of onset, and
☛ extensive glomerulosclerosis or interstitial fibrosis on renal biopsy.
Management
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Clinical Diagnosis
Clinical signs and symptoms associated with VL include fever for more than
two weeks, fatigue, weakness, loss of appetite, weight loss, malaise, cough,
diarrhea, epistaxis, cachexia, abdominal pain, anemia, pancytopenia, and,
associated with parasitic invasion of blood and reticulo-endothelial system,
enlargement of lymph nodes, spleen, and liver.
Some of these clinical signs and symptoms are similar to other diseases
prevalent in the areas where VL is endemic.
The clinical diagnosis of VL is therefore based on the standard case
definition of visceral Leishmaniasis, as given above
Symptoms often persist for several weeks to months before patients seek
medical care or die from the bacterial co-infection, massive bleeding or severe
anemia.
Fever
Abdominal Swelling over the LUQ (ጓቋ)
Anaemia features
➢ Fever
Chronic fever lasting for ≥ 2 weeks
Gradual in onset
High gr ade and intermittent / sometimes Low grade and
continuous
Associated with chills and rigor
Peak in the afternoon and night, relieved in the morning
✓ Usually double or triple onset daily
➢ Swelling over the LUQ of abdomen
Painless
Starts from the LUQ and grows towards the umbilicus (mid
abdomen) which increase in size progressively to involve the
whole abdomen with in ‘’X’’ days
Associated with
✓ Dragging sensation and feeling of abdominal fullness
✓ Early satiety
✓ Anorexia, vomiting and weight loss
How many days after the onset of fever, does the swelling
begins? → e.g. pt noticed the swelling 2 weeks after the onset
of fever
➢ Easy fatigability (weakness)
From supra ordinary to sub ordinary activity through time to
the extent s/he unable to perform his/her daily activities
➢ Anaemia smx’s
➢ Weight loss
➢ If s/he Lives in kalazar and malaria endemic area (RF)
✓ Or travel hx to endemic area (when, how long s/he
stayed there)
✓ Similar illness in the vicinity
✓ Malarial attack (how many times is the recurrence; last
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
The clinical manifestations of the disease are caused by multiple factors. The
most common causes are mainly due to:
▪ Splenomegaly resulting in
• Sequestration of blood
• Pressure effect of massive spleen
▪ Pancytopenia resulting in
• Low hemoglobin
• Low WBC → low immunity and high incidence of infections
• Low platelets → bleeding
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Complication of VL
➢ 2ry infection
The infection of the lymphoid tissue results in suppression of the
immune response
which is a predisposition for other infections.
commonly encountered infections include;
o Ear infection (e.g. Otitis media)
o Pneumonia
o TB (2ry TB infection is common in VL patients)
o GI infection (gastroenteritis, dysentery, diarrhea)
▪ Diarrhea and cough can occur due to mucosal
involvement of the gastro-intestinal and respiratory tract.
o sepsis
▪ for VL patients, Signs of bacterial co-infection should
be ruled out because bacterial pneumonia and gastro-
intestinal infections are common.
➢ Anaemia → 2ry to
Hypersplenism
Haemolysis
Bleeding
Short life span of RBC
Ineffective erythropoiesis → due to infiltration of BM by parasite
o All cell lines are often affected causing pancytopenia
➢ Bleeding
Due to pancytopenia or post SSG treatment
➢ In Patients with an advanced stage of the disease;
o Cachexia and edematous from hypoalbuminemia or CHF due to the
anemia.
o Hepatic dysfunction, jaundice and ascites can also occur.
o Chronic diarrhea, malabsorption → rarely due to invasion of the
intestine by parasite
➢ Malnutrition
o Over 1/3rd of VL patients present with moderate to severe state of
malnutrition which further predisposes them to infections and affects
the prognosis of VL treatment.
➢ PKDL (post kalazar dermal leshmaniasis)
o Chronic skin rash (erythematous macule, plaque and nodule)
following clinical response to VL treatment
N.B
Common cause of death in VL are bleeding,
severe anemia and 2ry infection 612
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Sample history
Chief compliant
HPI
This patient was last relatively healthy two months back, at which time he
began to experience insidious onset of low-grade intermittent fever sometimes
high grade especially in the afternoon and night. for such compliant he visited
a nearby clinic and was given a white circular tablet to be taken twice a day
and unspecified injection but no improvement.
For this he visited quara primary hospital where unspecified blood tests were
done, transfused with one bag of blood and he was told that he may have
kalazar (“guaqua”) and referred to our leishmaniasis center for confirmation
and better management.
He lives in kalazar and malaria endemic area and there is similar illness
in the vicinity. He had Hx of repeated malaria attack. His last attack
was 2yrs back where he was treated and got relieved. But he has no
hx of kalazar attack
No hx of HTN, DM or asthma (immunocompromisation → RF)
No hx of nasal bleeding, gum bleeding, melena or haematochezia (bleeding
disorder → CXN)
No hx of abdominal pain, diarrhoea or vomiting (gastroenteritis, dysentery → CXN)
No hx of yellowish discoloration of the eyes, RUQ abdominal pain,
itching sensation, stool or urine colour change (cirrhosis→ CXN or amoebic liver
abscess → DDX)
No hx of river water contact or post river water contact itching
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1 GA
Cachexia (in advanced VL)
Ashen Gray appearance (darkening of face)
o The term ‘’kala-azar’’, from Hindu for “black fever”, may be related
to this clinical feature
2 Vital signs
Febrile
Tachycardia and bounding pulse → sign of high output failure (CHF)
in response to anaemia
3 HEENT
Pale conjunctiva → anaemia
Active nasal bleeding or clotted blood over the nostrils → bleeding
2ry to thrombocytopenia
Ear discharge, sinusitis → 2ry infection
Subconjunctival haemorrhage → IE, VL
Jaundice → haemolytic anaemia
4 LGS
LAP → VL, NHL/HL, Other malignancies
5 RS
6 CVS 614
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7 Abdominal examination
HSM (Hepatosplenomegaly) ± (LAP, per splenitis)
✓ Non tender (rarely tender due to capsular pressure)
✓ Soft
✓ Firm in consistency
✓ Smooth surface
✓ Massive splenomegaly
▪ The accumulation of infected mononuclear phagocytic cells in the spleen
and the kupfer cells in the liver result in the hypertrophy of the organs
to a clinical apparent hepatosplenomegaly.
8 GUS
9 MSS
Oedema → advanced kalazar, lymphoma, CHF 2ry to severe
anaemia
Spine tenderness → NHL
10 IS
Pallor → anaemia
Dry, scaly skin (sometimes diffuse, warty, non-ulcerated skin lesion)
Purpura, petechiae → bleeding tendency
Hyperpigmentation and ashen Gray appearance
11 NS
DDX
1. Lymphoma (NHL)
Extra nodal involvement of lymphoma includes BM (DDX for
VL), thyroid, lung, brain, skin, testes
LAP→ painless, discrete, firm
HSM
Fever, weight loss, night sweat, easy fatigability
Bone pain
Paraplegia
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N.B
Lymphoma can be classified as
Very aggressive
✓ Burkitt lymphoma
✓ ALL (Acute lymphoblastic leukemia)
✓ Oncologic emergencies
Aggressive
✓ Mantle cell lymphoma
✓ DLBCL (diffuse large B cell lymphoma)
Indolent
2. Leukaemia (CML)
▪ These patients have fever, malaise, bleeding tendencies, weight loss and
splenomegaly.
▪ They are also susceptible to other infections.
▪ Blood tests in the laboratory show a high white blood cell count.
▪ Phases of CML include;
a) Chronic phase (<10 % blast cells)
✓ Low grade fever, night sweat, fatigue
✓ Bone pain due to infiltration by malignant cells
✓ HSM
✓ Leucocytosis (hyper viscosity SXX) sensitive to treatment
b) Accelerated phase (10 - 20 % blast cells)
✓ Fever without infection
✓ Bone pain
✓ Splenomegaly
c) Blast crisis (>10 % blast cells)
✓ Have acute leukaemia manifestations (AML→ 80%, ALL
→ 20%)
✓ BM failure → bleeding, infection
✓ Resistant to treatment
3. Malignancy in general → FUO
N.B FUO (fever of unknown origin caused by)
Malignancy
TB
Intra-abdominal abscess
CTD (connective tissue disorders)
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8. Disseminated TB to spleen
▪ The patients will present with malnutrition and a history of fever and
other constitutional symptoms of TB for several months.
▪ They may have an enlarged spleen (tipped splenomegaly) or lymph
nodes as in miliary Tuberculosis.
9. HSS
▪ The patients can have a very large liver and spleen, which they have
often had for a very long time.
▪ Patients may not have fever but can present with ascites and other
portal hypertension signs.
▪ Stool or urine analysis will show eggs of Schistosoma.
▪ Refer from the following
• HSS from DDX of CLD under long case of Nitsibin (click here → Chapter
9; CLD/ Chronic liver disease/ (የጉበት በሽታ))
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12. SLE
Common source of FUO
Present with photo sensitivity, malar rash, migratory joint pain,
myalgia, arthralgia
15. Brucellosis
▪ rare, mis diagnosed as TB
▪ there is history of contact with animal abortus
▪ Patients have a long history of fever, small or moderate splenomegaly
and an enlarged liver.
▪ Usually there is also involvement of the joints or bones that results in
musculoskeletal pains and arthritis.
16. HIV/AIDS
▪ HIV damages the immune system so that the body of an infected person
cannot properly fight against diseases.
▪ Patients often suffer from recurrent diarrhoea, which may lead to
malnutrition/wasting and dehydration, as in a kala azar patient.
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IX
1. Aspiration
Gold standard diagnostic IX modality
Amastigotes (ovoid body) seen from the aspirate
o As discussed above, The Diagnosis of VL relies on clinical,
serological, parasitological and molecular findings.
o Definitive diagnosis of VL is made by visualization of the
amastigote form of the parasite by microscopic examination of
aspirates from lymph nodes, bone marrow or spleen aspiration.
RK39, LD body from PM and kalazar latex agglutination test confirmed
by aspiration
Used for VL or hematologic malignancy DX (mainly for leukaemia,
lymphoma staging /BM involvement/)
This diagnosis has a high specificity but the sensitivity of the
microscopy varies for VL Dx
2. Antibody Detection
Immunodiagnostic techniques, which have been extensively used for the
diagnosis of VL include;
o Enzyme-linked immunosorbent assay (ELISA)
o Immunofluorescent antibody test (IFAT)
o Freeze-dried direct agglutination test (FD-DAT) or aqueous
antigen direct agglutination test (AQ-DAT)
o Fast Agglutination Screening Test (FAST)
o Indirect hemagglutination test (IHA)
o rK39 immunochromatographic (rk39-ICT) strip test and
o rK39 ELISA
However, all of these tests have two major limitations;
o First, they do not distinguish between present and past infections,
as the serum antibody level remains high after successful
treatment. Detection of relapse is not possible with these
methods.
o Second, all these tests fail to differentiate between symptomatic
and asymptomatic infections.
o As a consequence, a significant proportion of healthy individuals
in the endemic area with no history of VL are positive for anti-
Leishmanial antibodies.
The performance of the various serological tests in the diagnosis of VL
is found to be
good to excellent; their sensitivity and specificity is ranging from 70 to
100%.
However, the facilitation of some of these tests (ELISA, IFAT, IHA) in
the field where the disease is prevalent is limited because they need
well-equipped laboratory and skilled personnel.
Of all these tests, DAT and rK39 have been extensively evaluated and
used for the diagnosis of VL in the field and in laboratory settings.
PCR-based assay
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Discussion
13.1 Leishmaniasis
➢ Leishmaniasis is a vector-borne disease caused by protozoan parasite of the
genus Leishmania.
➢ It is transmitted by the vector phlebotomine sand fly.
➢ Some of the Leishmania species known to cause disease in humans are:
▪ L. donovani species complex (including L. donovani and L.
infantum/chagasi)
▪ L. major
▪ L. tropica
▪ L. aethiopica,
▪ L. braziliensis and
▪ L. mexicana species complex.
Epidemiology
➢ The disease is endemic in environments that range from deserts to rain forests
in rural and urban settings in over 98 countries of the tropics, subtropics, and
southern Europe.
➢ Estimations of the burden caused by the Leishmaniasis disease in the world is
challenging.
Leishmania parasites are digenetic parasites that need two hosts, the sandfly
and a mammalian host, to complete their life cycle (see picture below).
Over 20 Leishmania species are pathogenic to humans and 30 sandfly species
are proven in the vectors.
There are two ways of transmission of Leishmaniasis. These are;
▪ Zoonotic → which includes animal reservoir hosts, mainly dogs, in the
transmission cycle, or
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P.
orientalis
All over the world
Old world L. aethiopica Cutaneous leishmaniasis (CL)
L. tropica
L. major
New world L. panamensis
L. guyanensis
L. peruviana
L.mexicana
L. brazilliensis
Old world L. aethiopica Mucocutaneous leishmaniasis
new world L. panamensis (MCL)
L. guyanensis
L. brazilliensis
Old world L. aethiopica Diffuse cutaneous leishmaniasis
new world L. amzonensis (DCL)
L.mexicana
Old world L. donovani Visceral leishmaniasis (VL)
old & new L. Infantum
world
new world L. Chagasi
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The clinical forms range from the self-healing localized cutaneous form (LCL)
to the more complicated non-self-limiting mucocutaneous form (MCL) and
diffused cutaneous (DCL) forms to the potentially fatal visceral form (VL, also
called kala-azar).
13.2.1 Management of VL
Supportive Management
Nutrition:
▪ VL patients require adequate nutrition, vitamin and micro-nutrient
supplementation to speed up recovery, improve treatment response and
decrease or avoid the risk of relapse.
▪ Measure nutritional status with BMI or weight for height and follow the
national nutrition guideline (national protocol) for management.
Management of Anemia:
▪ VL patients often present with moderate to severe degree of anemia due
to bone marrow infiltration by the Leishmania parasite, hypersplenism,
auto-immune reactions or bleeding.
▪ Epistaxis could occur due to thrombocytopenia and mucosal infection. If it
is severe nasal packing and posterior epistaxis balloon might be
required.
▪ The anemia may require transfusion if severe.
Pharmacologic management
First-Line Regimens for Primary VL
Precautions during the use of antimonials : These may require stoppage of the
drug and a possible shift of treatment to AmBisome:
Miltefosine
C) Paromomycin (Aminosidine)
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Evaluating Cure
Clinical Response
Many patients get worse during the first few days of treatment with SSG.
After 7 to 10 days, patients become afebrile and begin to look stronger with
increased alertness and
appetite.
By day 14, the spleen size regresses, the Hgb level rises and there is weight
gain in the absence of edema.
At the end of successful treatment, patients look improved, afebrile, and usually
have a smaller spleen size than on admission and have an increased Hgb
level.
Look for signs of co-existing TB or HIV, both of them will increase the risk of
treatment failure.
Cure is best defined as the absence of clinical features of the disease after
completion of the recommended dose and duration of treatment for VL in
addition to a negative parasitological test for LD bodies.
f the TOC is scanty positive, continue the same treatment until two consecutive
weekly aspirates are negative.
The limit of duration of therapy is 60 days for SSG and a total dose of
40mg/kg for AmBisome, if at this point the TOC is still positive, use a 2nd line
treatment.
Non-response is defined as failure to decrease the parasitological grade after
adequate treatment.
13.2.3 VL Relapse
A patient who is diagnosed with VL for the first time is called a primary VL
case.
A definitive cure is the absence of VL signs and symptoms and a negative
test of cure 6 months after initial cure, i.e., 6 months after active diseases
treatment.
Patient follow-up is important to establish a definite cure with proper evaluation
on appointment or when presented with fever, loss of weight, anemia and
splenomegaly.
▪ For definitive cure, one looks at the clinical picture of the patient; tissue
aspirate may not be necessary at follow-up sessions unless a relapse is
clinically suspected.
If a person returns with clinical features and a positive parasitology consistent
with visceral Leishmaniasis, after having been successfully treated for primary
VL and discharged improved or with a negative test of cure (TOC), the patient
is known as relapse VL case. 635
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Note:
Severely ill VL patients may require an extended dose of AmBisome if the test
of cure (TOC) is positive after the end of 40mg/kg total dose of AmBisome.
Patients with an extended dose of SSG require close safety monitoring.
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➢ These group of patients require test of cure (ToC) at the end of the treatment
Prognosis of VL Treatment
Diagnosis
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
First-Line Drugs for First Episode (Primary) Kala Azar in VL/HIV Co-Infected
Patients:
➢ AmBisome (LAmB)
▪ AmBisome with a total dose of 40mg/kg in divided dose can be used for
the treatment of VL in HIV co-infected individuals.
▪ If TOC is still positive but with a significant parasite load reduction, the
treatment with AmBisome can be repeated until TOC becomes negative.
▪ If TOC positivity persists after repeating AmBisome, a compassionate
treatment regimen should be used.
▪ However, if the parasite load does not decrease significantly after the
initial AmBisome 40mg/kg therapy, SSG for 60 days and above should
be considered as therapy bearing in mind that safety
monitoring by qualified medical personnel is necessary.
▪ If even after the SSG therapy TOC is still positive, a compassionate
regimen should be used.
Pentavalent antimonials
▪ It is administered at a dose of 20mg antimony/kg/day, IV or IM, for 30
days.
▪ Adverse effects of the drug are more frequent in HIV infected patients.
➢ Risk factors for death That should be considered for all VL patients (with more
emphasis for VL/HIV co-infected individuals) include;
▪ Malnutrition
▪ Concomitant opportunistic infection (TB or pneumonia)
▪ Diarrhea or vomiting
▪ Anemia
▪ Bleeding and
▪ Signs of toxicity during treatment (heart failure, arrhythmia, pancreatitis,
jaundice, kidney failure, anemia, severe vomiting or diarrhea).
➢ After treatment of the first episode, assess for fever, weight, general condition,
spleen size, and hematologic values to see the clinical improvement and ideally
demonstrate parasitological cure (TOC) to endure that discharge is appropriate.
➢ If the test is positive, continue treatment, or substitute to a second-line regimen
and exclude other opportunistic infections
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Note:
FIGURE 221-4 (Harrison 20th edition); Post - kala-azar dermal leishmaniasis in an Indian
patient. Note nodules of varying size involving the entire face. The face is erythematous,
and the surface of some of the large nodules is discolored.
➢ Not all PKDL patients need treatment; decision can be made depending on
severity of the lesion (PKDL Grade).
➢ As PKDL patients harbor the parasite, they can be a potential source of
infection and disease transmission.
➢ Patients should be advised to seek medical attention and use impregnated bed
nets (ITNs) if they develop skin rash following VL treatment.
➢ Most PKDL cases are Grade 1. The majority of the lesions heal spontaneously
within 12 months but need close follow-up.
➢ Indication for treatment;
▪ PKDL patients with a severe form of Grade 2 and Grade 3 lesions
and/or disfiguring disease
▪ Those with lesions that have existed for more than 6 months
▪ Those with concomitant anterior uveitis/conjunctivitis and
▪ Young children with oral lesions that interfere with feeding
Antileishmanial options
Antimonials (SSG 20mg/kg/day for 30 days).
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Chapter 13; Leishmaniasis (ካላዛር/ጓቋ/ እና ቁንጭር)
Pregnancy:
Clinical Features
➢ A typical history (an insect bite followed by the events leading to ulceration) in
a resident of or a traveler to an endemic focus strongly suggests CL.
➢ A few days or weeks after the bite of a sandfly, a papule develops and grows
into a nodule that ulcerates over weeks or months.
➢ The base of the ulcer, which is usually painless, consists of necrotic tissue
and crusted serum, but secondary bacterial infection sometimes occurs.
➢ The margins of the ulcer are raised and indurated. Lesions may be single or
multiple and vary in size from 0.5 to >3 cm (see figure below).
➢ Lymphatic spread and lymph gland involvement may be palpable LAP and may
precede the appearance of the skin lesion.
➢ There may be satellite lesions, especially in L. major and L. tropica infections
➢ The lesions usually heal spontaneously after 2–15 months. Lesions due to L.
major and L. mexicana tend to heal rapidly, whereas those due to L. tropica
and parasites of subspecies Viannia heal more slowly.
➢ L. mexicana is responsible for chiclero’s ulcer, the so-called self-healing sore of
Mexico.
➢ CL lesions on exposed body parts (e.g., the face and hands), permanent scar
formation, and social stigmatization may cause anxiety and depression and
may affect the quality of life of CL patients.
Differential Diagnosis
➢ Cutaneous tuberculosis
➢ fungal infections
➢ leprosy
➢ sarcoidosis, and
➢ malignant ulcers
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Laboratory Diagnosis
Withhold Treatment
As the majority of CL lesions heal spontaneously within a year, the best
treatment for patients who fulfill the following criteria are to withhold
treatment or to accept local treatment:
▪ Fewer than 2 lesions requiring immediate treatment;
▪ Lesions are smaller than 5 cm in diameter
▪ Absence of indurations or firmness of surrounding skin, on palpation no
mucosal involvement, or lesions are not close to the nose or the lips;
▪ Lesions are not on the border of the lip, the nostrils or the eyes;
▪ No potentially disfiguring or disabling lesion (on the nose, the joints, the
toes, or the fingers);
▪ No immuno-suppression
Patients who fulfill the above criteria need follow-ups to evaluate the progress
of the lesion(s) and to decide on their subsequent treatment.
B. Local Treatments
➢ A bacterial superinfection is uncommon, but when suspected, it should be
managed with appropriate antibiotics 648
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C. Systemic Treatment
Alternative
➢ Miltefosine and Liposomal Amphotericin B
▪ Miltefosine (2.5 mg/kg for 28 days) and Liposomal Amphotericin B are
effective in the treatment of CL in several countries, but have not yet
been used for L. aethiopica infections.
Adjuvant therapy
Azoles and triazoles have been used with mixed responses in both Old and
New World CL, but have not been adequately assessed for this indication in
clinical trials.
▪ In L. major infection, oral fluconazole (200 mg/d for 6 weeks) resulted in
a higher rate of cure and also cured infection faster.
▪ Ketoconazole (600 mg/d for 28 days) is effective in CL due to L. (V.)
panamensis and L. mexicana in Panama and Guatemala.
Follow-Up
➢ It is recommended that patients are routinely followed up 6 weeks and 6
months after the completion of treatment.
➢ Patients should be advised that recurrence is possible and that they should
return if that happens. Most relapses occur within 6 months after treatment.
16
Harrison [20th edition] recommends SSG, 20 mg/kg for 20 days, national Guideline of
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Clinical Features
The parasite spreads via the lymphatics or the bloodstream to mucosal tissues
of the upper respiratory tract.
Intense inflammation leads to destruction, and severe disability ensues.
Lesions in or around the nose or mouth (see figure below) are the typical
presentation of ML.
Patients usually provide a history of self-healed CL preceding ML by 1 to 5
years.
Typically, ML presents as nasal stuffiness and bleeding followed by destruction
of nasal cartilage,perforation of the nasal septum, and collapse of the nasal
bridge.
Subsequent involvement of the pharynx and larynx leads to difficulty in
swallowing and phonation.
The lips, cheeks, and soft palate may also be affected.
Secondary bacterial infection is common, and aspiration pneumonia may be
fatal. 651
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Laboratory Diagnosis
14.1 Leukemia
EPIDEMIOLOGY
➢ AML is the most common acute leukemia in adults and accounts for
approximately 80 % of cases in this group. In contrast, AML accounts for < 10
% of acute leukemias in children < 10 years of age.
➢ In the United States and Europe, the incidence is reported as 3 to 5 cases
per 100,000 population.
➢ In adults, the median age at diagnosis is approximately 65 years.
➢ The incidence increases with age with approximately 2 and 20 cases per
100,000 population for those under or over 65 years, respectively.
➢ The male : female ratio is approximately 5:3.
➢ This incidence is similar among persons of different races.
ETIOLOGY;
➢ Those have been implicated in the development of AML include.
▪ Heredity
▪ Radiation
▪ Chemical and other occupational exposures
▪ Drugs
➢ No direct evidence suggests a viral etiology.
CLASSIFICATION
Following diagnosis, AML is classified using the WHO classification system
based upon a combination of morphology, immunophenotype, genetics, and
clinical features.
The classification attempts to identify biologic entities in the hopes that future
work will elucidate molecular pathways that might be amenable to targeted
therapies.
There are six main groups of AML recognized in this classification system
▪ AML with recurrent genetic abnormalities
▪ AML with myelodysplasia-related features
▪ Therapy-related AML and MDS
▪ AML, not otherwise specified
▪ Myeloid sarcoma
▪ Myeloid proliferations related to Down syndrome
The French-American-British (FAB) classification system divides AML into eight
subtypes, M0 through to M7, based on the type of cell from which the
leukemia developed and its degree of maturity. 654
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Chapter 14; Hematologic Malignancy (የደም ካንሰር)
CLINICAL PRESENTATION
Symptoms Patients with AML most often present with nonspecific
symptoms that begin gradually or abruptly and are the consequence of
anemia, leukocytosis, leukopenia or leukocyte dysfunction, or
thrombocytopenia. Nearly half have had symptoms for ≤3 months before
the leukemia was diagnosed.
Half of patients mention fatigue as the first symptom, but most complain
of fatigue or weakness at the time of diagnosis. Anorexia and weight
loss are common. Fever with or without an identifiable infection is the
initial symptom in approximately 10% of patients. Signs of abnormal
hemostasis (bleeding, easy bruising) are noted first in 5% of patients.
On occasion, bone pain, lymphadenopathy, nonspecific cough, headache,
or diaphoresis is the presenting symptom
Rarely patients may present with symptoms from a myeloid sarcoma that
is a tumor mass consisting of myeloid blasts occurring at anatomic sites
other than bone marrow. Sites involved are most commonly the skin,
lymph node, gastrointestinal tract, soft tissue, and testis. This rare
presentation, often characterized by chromosome aberrations [e.g.,
monosomy 7, trisomy 8, MLL rearrangement, inv(16), trisomy 4, t(8;21)],
may precede or coincide with AML.
General fatigue is present in the majority of patients and often precedes
the diagnosis for a number of months.
Pallor and weakness are common and attributed to the anemia.
Bone pain is infrequent in adults with AML, although some individuals
describe sternal discomfort or tenderness, occasionally with aching in the
long bones. This may be especially severe in the lower extremities, due
to expansion of the medullary cavity by the leukemic process.
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Chapter 14; Hematologic Malignancy (የደም ካንሰር)
PATHOLOGIC FEATURES;
Peripheral blood
▪ Analysis of the peripheral blood at presentation usually reveals a
normocytic, normochromic anemia that can vary in severity.
▪ The reticulocyte count is normal or decreased.
▪ Approximately 75 % of patients have platelet counts below
100,000 cells/microL (100 x 109/L) at diagnosis, and approximately 25 %
will have counts below 25,000 cells/microL.
▪ Both morphologic and functional platelet abnormalities may be seen.
▪ The median leukocyte count at diagnosis is approximately
15,000 cells/microL; 20 % of patients have a leukocyte count above
100,000 cells/microL and 25 to 40 % of patients have a leukocyte count
less than 5000 cells/microL.
▪ The vast majority of patients (95 %) will have circulating myeloblasts that
can be detected on the peripheral smear.
▪ There may or may not be evidence of myelodysplasia.
Myeloblasts
▪ They are immature cells with large nuclei, usually with prominent nucleoli,
and a variable amount of pale blue cytoplasm (sometimes with faint
granulation) after staining with Wright Giemsa.
▪ The nuclear to cytoplasmic ratio and morphology vary depending upon
the maturity of the cell.
▪ Auer rods, which are pathognomonic of myeloblasts, vary in frequency
depending upon the AML subtype.
▪ They can be identified as pink/red rod-like granular structures in the
cytoplasm.
▪ Sometimes the Auer rods are multiple, and sometimes they form a dense
clump and are referred to as "Auer bodies."
A myeloperoxidase reaction
▪ It is easy to perform, can be done in less than a few minutes, and is a
simple means of determining if the blasts are myeloid.
▪ Absence of a reaction product does not rule out AML, as some cases
are negative.
▪ Evaluation of myeloperoxidase reactivity must be focused on the blast
population and not on mature or maturing myeloid elements on the
smear.
Flow cytometry
▪ Flow cytometry of the peripheral blood or marrow aspirate can identify
circulating myeloblasts in the majority of patients by characteristic
patterns of surface antigen expression.
▪ The specific pattern differs among the AML subtypes, but the majority of
cases express CD34, HLA-DR, CD117, CD13, and CD33.
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Cytogenetic features
▪ All patients with suspected AML should undergo metaphase cytogenetic
analysis of their bone marrow biopsy specimen. Approximately 50 percent
of patients with newly diagnosed AML will demonstrate cytogenetic
abnormalities.
▪ A combination of conventional karyotypic analysis plus reverse
transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ
hybridization (FISH) for specific abnormalities can aid in the diagnosis,
treatment, and post-treatment monitoring of patients with AML:
Molecular studies
➢ Abnormalities in certain genes, such as mutations in FLT3, nucleophosmin
(NPM1), KIT, CEBPA, or RUNX1 as well as gene expression profiles confer
prognostic significance in adult patients with AML.
➢ The diagnosis of AML requires both of the following:
▪ Documentation of bone marrow infiltration – Blast forms must account
for at least 20 % of the total cells of the bone marrow aspirate (from a
500-cell differential count). Whether or not a blast percentage can be
determined in the bone marrow, the presence of 20 percent or more
blasts in the peripheral blood is also diagnostic of AML. Exceptions to
this include leukemias with certain genetic abnormalities, such as those
with t(8;21), inv(16), or t(15;17), and myeloid sarcoma, which are
considered diagnostic of AML without regard to the blast count.
▪ The leukemic cells must be of myeloid origin as demonstrated by either
the presence of Auer rods, cytochemical positivity for myeloperoxidase, or
presence of sufficient myeloid/monocytic markers recognized by
immunophenotyping.
EPIDEMIOLOGY
CML accounts for approximately 15 to 20 percent of leukemias in adults. It
has an annual incidence of 1 to 2 cases per 100,000, with a slight male
predominance.
The median age at presentation is approximately 50 years for patients enrolled
on clinical studies, but the actual median age from cancer registry data may
be 10 years older. Exposure to ionizing radiation is the only known risk factor.
CLINICAL MANIFESTATIONS
CML has a triphasic or biphasic clinical course:
▪ A chronic phase, which is present at the time of diagnosis in
approximately 85 percent of patients;
▪ An accelerated phase, in which neutrophil differentiation becomes
progressively impaired and leukocyte counts are more difficult to control
with treatment; defined as the presence of one of the following
• Blast cells constituting 10 to 19% of the cells in the peripheral
blood or bone marrow
• Basophilia > 20% of the cells in the peripheral blood
• Persistent thrombocytopenia <100,000/µl
• Persistent thrombocytosis >100,000/µl unresponsive to therapy
• Increasing spleen size and WBC count unresponsive to therapy
• Cytogenic clonal evolution
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DIAGNOSIS
Peripheral blood
▪ The peripheral smear typically demonstrates a leukocytosis with a median
white count of approximately 100,000/microL (range 12 to 1000/microL).
▪ The white blood cell differential typically shows virtually all cells of the
neutrophilic series, from myeloblasts to mature neutrophils with peaks in
the percent myelocytes and segmented neutrophils.
▪ Blasts typically account for less than 2 percent.
▪ The presence of a greater percent of myelocytes than the more mature
metamyelocytes ("leukemic hiatus" or "myelocyte bulge") is one of the
classic findings in CML. 661
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TREATMENT
Overview — the two main treatment options for patients with newly diagnosed
chronic phase (CP) CML are:
▪ BCR-ABL1 tyrosine kinase inhibitors (TKIs), such
as imatinib, dasatinib, nilotinib, bosutinib, and radotinib.
▪ Allogeneic hematopoietic cell transplantation (HCT).
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DIAGNOSTIC EVALUATION
➢ Peripheral blood abnormalities
▪ most children with ALL have anemia and/or thrombocytopenia with
either normal or slightly increased WBC counts, and lymphoblasts
on peripheral smear.
▪ These findings suggest the need for bone marrow examination,
which should be performed for the following indications:
• Atypical cells in the peripheral blood
• Unexplained depression of more than one peripheral blood
element (cytopenias). Cytopenias are defined as an absolute
neutrophil count (ANC) of <500/microL, Hgb <8 g/dL, or a
platelet count <150,000/microL.
• Unexplained lymphadenopathy or hepatosplenomegaly
associated with cytopenias
Morphology-In the World Health Organization classification system for
hematologic malignancies, the lymphoblastic neoplasms (which may
present as leukemia and/or lymphoma) are divided into two general
categories based upon lineage
▪ Precursor B cell lymphoblastic leukemia/lymphoma, also called
precursor B cell acute lymphoblastic leukemia (precursor B cell
ALL)
▪ Precursor T cell lymphoblastic leukemia/lymphoma (precursor T-LBL),
also called precursor T cell acute lymphoblastic leukemia (T cell
ALL)
▪ These two entities are morphologically indistinguishable. On peripheral
blood smears and bone marrow aspirates, lymphoblasts vary from small
cells with scant cytoplasm, condensed nuclear chromatin, and indistinct
nucleoli to larger cells with moderate amounts of cytoplasm, dispersed
chromatin, and multiple nucleoli.
▪ The former FAB L3 category is currently described as
Burkitt lymphoma/leukemia in the WHO classification.
➢ Immunophenotype
▪ leukemia cells in ALL are classified according to immunophenotype using
an extensive panel of monoclonal antibodies to cell surface "cluster of
differentiation" (CD) markers. Markers used to classify cells by lineage
are the same as those used in adult ALL.
▪ Approximately 70 to 80 percent of cases of childhood ALL are of B-
precursor lineage (ie, precursor B cell leukemia or early pre-B cell ALL).
B-precursor leukemia typically is CD10+, CD19+, and sometimes CD20+.
▪ Leukemic lymphoblasts with the L3 morphology usually have markers for
mature B cell ALL (CDs 10 ± 19, 20, 22, 25, and surface
immunoglobulin).
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TREATMENT
Chemotherapy is the initial treatment of choice. Most ALL patients will receive
a combination of medications. There are no surgical options because of the
body-wide distribution of the malignant cells.
In general, cytotoxic chemotherapy for ALL combines multiple antileukemic
drugs in various combinations. Chemotherapy for ALL consists of three phases:
remission induction, intensification, and maintenance therapy.
EPIDEMIOLOGY
CLL is the most common leukemia in adults in Western countries, accounting
for approximately 25 to 30 percent of all leukemias in the United States.
The disorder is more common in men, with a male to female ratio of
approximately 1.3:1 to 1.7:1.
CLL is considered to be mainly a disease of older adults, with a median age
at diagnosis of approximately 70 years; however, it is not unusual to make this
diagnosis in younger individuals from 30 to 39 years of age.
Genetic rather than environmental factors are the most likely explanation for
these differences.
CLINICAL PRESENTATION
The clinical presentation of CLL or SLL relate to tissue infiltration
(lymphadenopathy, organomegaly), peripheral blood cytopenia (anemia,
bleeding, infections), or immune suppression (infections and malignancies) and
autoimmune phenomenon (hemolytic anemia).
Most patients feel entirely well with no symptoms when a routine blood count
reveals an absolute lymphocytosis, leading to a diagnosis of CLL.
5 to 10 % of patients present with the typical "B" symptoms of lymphoma
which include one or more of the following:
▪ Unintentional weight loss ≥10 percent of body weight within the previous
six months.
▪ Fevers of >100.5°F (>38°C) for ≥2 weeks without evidence of infection.
▪ Drenching night sweats without evidence of infection.
▪ Extreme fatigue (ie, ECOG Performance status 2 or worse; cannot work
or unable to perform usual activities)
Signs
Lymphadenopathy
▪ The most common abnormal finding on physical examination of the
patient with CLL is lymphadenopathy, present in 50 to 90 percent of
patients among various series.
▪ Lymph node enlargement may be generalized or localized, and individual
lymph nodes can vary greatly in size.
▪ The most commonly affected sites are cervical, supraclavicular, and
axillary.
▪ Characteristically, enlarged nodes in CLL are firm, rounded, discrete,
nontender, and freely mobile upon palpation. Exceptions to these
generalizations are encountered, particularly when the nodes have grown
rapidly.
▪ Occasionally, several enlarged nodes in the same anatomical site (eg,
cervical triangle, axilla or femoral-inguinal areas) may become confluent,
forming large spherical lymphoid masses.
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▪ In addition, new lymph nodes may appear in places other than the usual
lymph node-bearing sites, such as over the sacrum or the thorax.
Splenomegaly
▪ The spleen is the second most frequently enlarged lymphoid organ, being
palpably enlarged in 25 to 55 percent of cases.
▪ As is the case with enlarged lymph nodes, an enlarged spleen in CLL is
usually painless and nontender to palpation, with a sharp edge and a
smooth firm surface. Painful and infarcted splenic enlargement is an
unusual presenting feature.
Hepatomegaly
▪ Enlargement of the liver may be noted at the time of initial diagnosis in
15 to 25 percent of cases.
▪ The liver is usually only mildly enlarged, ranging from 2 to 6 cm below
the right costal margin, with a span of dullness to percussion of
approximately 10 to 16 cm.
▪ Upon palpation, the liver is usually nontender and firm with a smooth
surface.
Skin
▪ Infiltration with CLL cells may occur in any organ, but, at the time of
diagnosis, the skin (leukemia cutis) is the most commonly involved non-
lymphoid organ.
▪ These lesions most commonly involve the face and can manifest as
macules, papules, plaques, nodules, ulcers, or blisters. Diagnosis is made
based upon biopsy of the involved skin.
DIAGNOSIS
➢ The diagnosis of CLL should be strongly considered in patients with absolute
lymphocyte count above 5000/ μL. However, confirmation requires review of
peripheral blood smear morphology by hematologist or pathologist
➢ Definitive diagnosis of CLL requires the presence of the following three
parameters.
▪ Absolute lymphocytosis defined as lymphocyte count more than 5000
cells/μl.
▪ Confirming the presence of excess mature appearing lymphocytes on the
peripheral blood smear.
▪ Immunophenotyping (Flow cytometry) from peripheral blood: to confirm
the presence B-cell markers on the neoplastic lymphoid cells and their
clonality.
LABORATORY ABNORMALITIES.
Lymphocytosis
▪ the most noteworthy laboratory abnormality found in CLL is
lymphocytosis in the peripheral blood and bone marrow.
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▪ Although the absolute blood lymphocyte threshold for diagnosing CLL has
been placed at >5000/microL [5 x 109/L] B lymphocytes, a significant
proportion of patients present with counts as high as 100,000/microL [100
x 109/L].
Cytopenias
▪ Neutropenia, anemia, and thrombocytopenia may be observed at the
time of initial diagnosis, and are usually not severe.
▪ These can be related to autoimmune hemolytic anemia, pure red cell
aplasia, autoimmune thrombocytopenia, or agranulocytosis.
Patients with CLL have an increased incidence of autoimmune hemolytic
anemia (AIHA). The direct antiglobulin (Coombs) test (DAT) may be positive at
some time during the course of the disease in up to 35 percent of cases;
overt AIHA occurs in 11 percent of cases.
Other abnormal findings — There are no characteristic abnormalities in blood
chemistry, but elevated levels of serum lactate dehydrogenase (LDH) and beta-
2 microglobulin were found in approximately 60 percent in one series of
patients with progressive or advanced CLL entering a therapeutic trial.
Elevations of uric acid, hepatic enzymes (ALT or AST) and, rarely, calcium
may also be observed.
PATHOLOGIC FEATURES
Morphology
▪ The peripheral blood smear of patients with CLL demonstrates a
lymphocytosis.
▪ The leukemic cells are typically small, mature appearing lymphocytes with
a dense nucleus, partially aggregated (clumped) chromatin, and without
discernible nucleoli.
▪ There is a narrow border of clear to slightly basophilic cytoplasm.
Immunophenotype
▪ Immunophenotypic analysis, usually by flow cytometry, is a key
component to the diagnosis of CLL. There are three major characteristic
immunophenotypic findings:
• Expression of B cell associated antigens including CD19, CD20,
and CD23. Expression of CD20 is usually weak. Expression of
CD21 and CD24 can be seen, but is not required for diagnosis.
• Expression of CD5, an antigen commonly expressed by T cells.
• Low levels of surface membrane immunoglobulin (ie, SmIg weak).
The immunoglobulin is most often IgM or both IgM and IgD, and
only a single immunoglobulin light chain is expressed (ie, either
kappa or lambda but not both), confirming the clonal nature of
these cells. In rare cases, several Ig clones may coexist.
Bone marrow aspirate and biopsy
▪ Bone marrow aspirate and biopsy are not required for the diagnosis of
CLL.
▪ If bone marrow biopsy and aspiration are performed at the time of initial
diagnosis, they usually demonstrate normal to increased cellularity, with
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The Rai system is based upon the concept that in CLL there is a gradual and
progressive increase in the body burden of leukemic lymphocytes, starting in
the blood and bone marrow (lymphocytosis), progressively involving lymph
nodes (lymphadenopathy), spleen and liver (organomegaly), with eventual
compromise of bone marrow function (anemia and thrombocytopenia).
Stage 0 (lymphocytosis) – 25 percent
Stages I to II (lymphadenopathy, organomegaly) – 50 percent
Stages III to IV (anemia, thrombocytopenia) – 25 percent
In the original series describing the Rai system, the median survival from the
time of diagnosis according to stage was:
▪ Stage 0 – 150 months
▪ Stage I – 101 months
▪ Stage II – 71 months
▪ Stages III and IV – 19 months
The Binet staging system takes into consideration five potential sites of
involvement: cervical, axillary, and inguinal lymph nodes (whether unilateral or
bilateral, each area is counted as one), spleen, and liver. Involvement is
judged only by physical exam and does not take into consideration the results
of imaging studies for staging purposes.
Patients are classified according to the number of involved sites plus the
presence of anemia (hemoglobin <10 g/dL) and/or thrombocytopenia
(platelets <100,000/microL).
Stage A – Fewer than three involved lymphoid sites
Stage B – Three or more involved lymphoid sites
Stage C – Presence of anemia and/or thrombocytopenia
While survival by stage has improved with the evolution of treatment since this
publication, median survival for the prognostic groups studied by Binet was:
▪ Stage A – Comparable to age-matched controls
▪ Stage B – 84 months
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▪ Stage C – 24 months
Treatment options
➢ Treatment should be decided and provided by a hematologist.
1. Wait and watch with no treatment: for asymptomatic patients
2. Combination chemotherapy
3. Targeted therapies
4. Monoclonal antibody therapies
➢ Indications for treatment
▪ Symptomatic disease: B-symptoms, bulky lymph node or splenomegaly >
6cm
▪ below the left costal margin.
▪ Anemia
▪ Thrombocytopenia
14.2 Lymphomas
➢ HL, formerly called Hodgkin's disease, arises from germinal center or post-
germinal center B cells.
➢ HL has a unique cellular composition, containing a minority of neoplastic cells
(Reed-Sternberg cells and their variants) in an inflammatory background.
➢ It is separated from the other B cell lymphomas based on its unique
clinicopathologic features, and can be divided into two major sub-groups, based
on the appearance and immunophenotype of the tumor cells.
➢ Hodgkin ‘s lymphoma is a distinct group of lymphomas with few histologic sub-
types.
➢ It predominately involves lymph nodes; extra-nodal involvement is not common.
➢ It progresses from one lymph node region to other in fairly predictable fashion.
➢ Classical HL
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▪ The tumor cells in this group are derived from germinal center B cells,
but typically fail to express many of the genes and gene products that
define normal germinal center B cells. Based on differences in the
appearance of the tumor cells and the composition of the reactive
background, classical HL is further divided into the following subtypes:
• Nodular sclerosis classical HL (NSHL)
• Mixed cellularity classical HL (MCHL)
• Lymphocyte rich classical HL (LRHL)
• Lymphocyte depleted classical HL (LDHL)
▪ Nodular lymphocyte predominant HL – The tumor cells in this subtype
retain the immunophenotypic features of germinal center B cells.
EPIDEMIOLOGY
Represents ~10% of all cases of malignant lymphoma. Typically affects young
adults Presents with painless lymphadenopathy involving the neck and chest;
systemic symptoms are common.
HL has a bimodal age distribution curve. The pattern of age-specific incidence
differs by geographic location and appears to parallel the level of industrial
development: In the US and other economically advantaged countries, there is
one peak in young adults (approximately age 20 years) and one in adults of
older age (approximately age 65 years); the majority of patients are young
adults.
In the US and Europe, the approximate percentage of classic HL cases from
each subgroup are as follows:
▪ Nodular sclerosis classical HL (70 percent)
▪ Mixed cellularity classical HL (20 to 25 percent)
▪ Lymphocyte rich classical HL (5 percent)
▪ Lymphocyte depleted classical HL (less than 1 percent)
Risk factors
Socioeconomic status and the environment
▪ In economically advantaged countries, the risk of developing HL as a
young adult is consistently associated with factors indicative of a high
standard of living in early childhood, including single family housing and
small family size.
▪ These associations appear to be specific for the nodular sclerosis
subtype of HL and for disease occurring from early childhood through
middle adulthood.
Immunosuppression
▪ the incidence of HL is increased in a number of settings associated with
immunodeficiency, including solid organ or hematopoietic cell
transplantation, therapy with immunosuppressive drugs (e.g, in patients
with autoimmune disease), and HIV infection. 672
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Autoimmune disorders
▪ Patients with a history of autoimmune disorders are at increased risk for
the development of HL and can pose challenging management issues
due to comorbidities and late treatment related toxicities.
▪ A personal history of rheumatoid arthritis, SLE or sarcoidosis
▪ A family history of sarcoidosis or ulcerative colitis
EBV infection
▪ Incidence of HL is high among pts with history of EBV.
▪ The risk of EBV positive pts are four times; latency period is 4 years.
CLINICAL PRESENTATION
Non tender lymphadenopathy central pattern, 70 - 80 % left supraclavicular and
mediastinal B symptoms
▪ Common in patients with advanced stage disease.
Pruritis, typically is not associated with a rash
Intense pain in the sites of disease upon alcohol ingestion
Obstructive symptoms
Fluid collections in the third space
Organomegally
The clinical presentation also varies according to the histologic subtype of
classic HL NS
▪ Accounts for 70% of cases in the Western world.
▪ Mediastinal involvement is common
▪ Males and females are affected in equal proportion
▪ Most patients are between the ages of 15 and 35 years.
Mixed cellularity
▪ The second-most-common subtype in the industrial world, representing
20% of cHL.
▪ The median age of presentation is 38
▪ Males are affected more commonly.
▪ Patients typically present with peripheral lymphadenopathy
▪ Splenic involvement occurs in 30%
▪ Advanced at the time of presentation
▪ Associated with a poorer prognosis than NS.
LR cHL
▪ Early stage disease
▪ Peripheral nodes
▪ Patients are older 43 years
LD cHL
▪ Is the least common subtype
▪ It is more common in the industrial world and in HIV-infected individuals
▪ The median age of onset is in the 30
▪ Males are more often affected 673
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Diagnosis
LN biopsy is diagnostic
▪ RSC with surrounding inflammatory cells
▪ RSC not specific for HL
Immunostaining
▪ Confirm the diagnosis of HL
▪ cHL is positive for
• CD 30 in all cases
• CD 15 in 85 %
• CD 20 in 20%
• Negative CD 45
Lab features; No diagnostic lab features
▪ CBC; anemia, thrombocytopenia, lymphopenia
▪ ESR elevated
▪ LFT increased
▪ LDH and , uric acid will be elevated
▪ Serum albumin will be low
▪ B2 microglobuline high
▪ HIV test
Imaging
▪ CXR, CT, PET
▪ Cardiac evaluation and pulmonary function tests
▪ BM biopsy for staging, can be deferred in most patients
STAGING
➢ Main determinant of prognosis and treatment
➢ The Ann Arbor staging system has been employed in HL for more than 25
years.
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➢ The Ann Arbor staging system with Cotswolds modifications is the current
staging system
➢ There are four stages
▪ Stage I — Involvement of a single lymph node region (I) or of a single
extra lymphatic organ or site (IE).
▪ Stage II — Involvement of two or more lymph node regions on the same
side of the diaphragm alone (II) or with involvement of limited,
contiguous extralymphatic organ or tissue (IIE).
• The number of anatomic regions should be indicated by a subscript
(eg, II-3).
▪ Stage III — Involvement of lymph node regions or lymphoid structures on
both sides of the diaphragm (III) which may include the spleen (IIIS) or
limited, a contiguous extralymphatic organ or site (IIIE) or both (IIIES).
• Subdivided into stage III-1 or III-2:
• Stage III-1 is used for patients with involvement of the spleen or
splenic hilar, celiac or portal nodes
• Stage III-2 is used for patients with involvement of the paraaortic,
iliac, inguinal, or mesenteric
▪ Stage IV — Diffuse or disseminated foci of involvement of one or more
extralymphatic organs or tissues, with or without associated lymphatic
involvement.
N.B, all cases are sub classified to indicate the absence (A) or presence (B)
of one or more of the following three systemic symptoms
significant unexplained fever, night sweats, or unexplained weight loss
exceeding 10 percent of body weight during the six months prior to diagnosis.
Treatment
Depends on the stage of the disease and the presence of adverse prognostic
factors.
Treatment group includes
▪ Early stage favorable and unfavorable
▪ Advanced stage
Treatment of early stage HL
Early stage Includes CS I and II;Further classified in to two
▪ Early stage favorable; no risk factors
▪ Early stage unfavorable; one or more risk factors
Risk factors in early stage Hodgkin lymphoma. A number of prognostic
indicators have been identified in early stage cHL
The GHSG scale includes five risk factors
▪ Bulky mediastinal disease
▪ ESR of ≥30 in the presence of B symptoms or ≥50 without B symptoms
▪ Extranodal extension of disease
▪ Three or more lymph node sites of involvement. 675
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Epidemiology
Incidence of NHL has been increasing steadily in North America and other
industrial countries with a doubling of cases between 1970 and 1990 and
stabilization thereafter.
Fifth most common ca in USA – 4.2% of all cases of ca
▪ Mean age at Dx 45- 55 years
▪ More common in male
▪ Higher in whites than blacks
Risk factors
▪ Infection; EBV, HTLV-I, HHV-8, HCV, H. Pylori, Chlamydia psittaci,
Campylobacter jejuni, Borrelia burgdorferi
▪ Occupational exposure to certain pesticides and herbicides
▪ Drugs
▪ Congenital disease; ataxia-telangiectasia, Wiskott-Aldrich syndrome.
▪ Acquired; Immunosuppression associated with HIV infection,Iatrogenically
induced immune suppression in the organ transplantation
setting,Autoimmune disorders :- rheumatoid arthritis, Sjögren syndrome,
and Hashimoto thyroiditis, IBD, SLE;HL.
CLINICAL PRESENTATION
The clinical presentation of NHL varies tremendously depending upon the type
of lymphoma and the areas of involvement. Some NHLs behave indolently with
lymphadenopathy waxing and waning over years. Others are highly aggressive,
resulting in death within weeks if left untreated. In typical cases:
Aggressive lymphomas commonly present acutely or subacutely with a rapidly
growing mass, systemic B symptoms (ie, fever, night sweats, weight
loss), and/or elevated levels of serum lactate dehydrogenase and uric acid.
Examples of lymphomas with this aggressive or highly aggressive presentation
include diffuse large B cell lymphoma, Burkitt lymphoma, adult T cell leukemia-
lymphoma, and precursor B and T lymphoblastic leukemia/lymphoma.
Indolent lymphomas are often insidious, presenting only with slow growing
lymphadenopathy, hepatomegaly, splenomegaly, or cytopenias. Examples of
lymphomas that typically have indolent presentations include follicular
lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and
splenic marginal zone lymphoma.
The natural history of these tumors shows significant patient-to-patient
variability.
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Oncologic emergencies
Potentially emergent complications of NHL need to be considered during the
initial workup and evaluation.
Prompt recognition and therapy is critical for these situations, which may be
life-threatening and/or interfere with and delay treatment of the underlying NHL
These can include:
▪ Spinal cord compression
▪ Pericardial tamponade
▪ Hypercalcemia (eg, adult T cell leukemia-lymphoma)
▪ Superior or inferior vena cava obstruction
▪ Hyperleukocytosis (eg, B or T cell lymphoblastic leukemia/lymphoma)
▪ Acute airway obstruction (eg, mediastinal lymphoma)
▪ Lymphomatous meningitis and/or CNS mass lesions
▪ Hyperuricemia and tumor lysis syndrome
▪ Hyperviscosity syndrome (eg, lymphoplasmacytic lymphoma with
Waldenstrom macroglobulinemia)
▪ Intestinal obstruction, intussusception
▪ Ureteral obstruction, unilateral or bilateral hydronephrosis
▪ Severe hepatic dysfunction
▪ Venous thromboembolic disease
▪ Severe autoimmune hemolytic anemia and/or thrombocytopenia (eg, small
lymphocytic lymphoma
If patients with NHL develop angioedema, they may have an acquired form of
C1 inhibitor deficiency that requires emergent treatment with infused C1
inhibitor concentrates
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TREATMENT
Indolent
▪ Potential cure only through HSCT (Hematopoietic stem cell
transplantation).
▪ Watchful waiting early on for some patients
▪ Chemotherapy/immunotherapy/radiotherapy/ combination with indication
Aggressive
▪ Chemotherapy as soon as the dx is established
▪ Radiotherapy for the right indications
▪ HSCT
Highly aggressive
▪ Highly chemo sensitive. SO, Chemotherapy ASAP
NB; The most common chemotherapy used for non-Hodgkin lymphoma is
CHOP-R. (C-cyclophosphamide, H-hydroxydaunorubicin, O-oncovin, P-
prednisone, R-rituximab)
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Special considerations
PATHOGENESIS
In the setting of a malignancy with a high proliferative rate, large tumor
burden, and/or a high sensitivity to treatment, initiation of cytotoxic
chemotherapy, cytolytic antibody therapy, radiation therapy, or sometimes
glucocorticoid therapy alone can result in the rapid lysis of tumor cells.
This releases massive quantities of intracellular contents (potassium, phosphate,
and nucleic acids that can be metabolized to uric acid) into the systemic
circulation. The metabolic consequences include;
▪ Hyperkalemia
▪ Hyperphosphatemia
• The phosphorus concentration in malignant cells is up to four times
higher than in normal cells. Thus, rapid tumor breakdown often
leads to hyperphosphatemia, which can cause secondary
hypocalcemia.
• When the calcium concentration times phosphate concentration (the
calcium phosphate product) exceeds 60 mg2/dL2, there is an
increased risk of calcium phosphate precipitation in the renal
tubules, which can lead to acute kidney injury.
• In addition, precipitation in the heart may lead to cardiac
arrhythmias. Renal replacement therapy may be needed if the
calcium phosphate product is ≥70 mg2/dL2. 680
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▪ secondary hypocalcemia
▪ hyperuricemia
• Hyperuricemia is a consequence of the catabolism of purine nucleic
acids to hypoxanthine and xanthine, and then to uric acid via the
enzyme xanthine oxidase
▪ acute kidney injury.
Xanthinuria
Allopurinol blocks the catabolism of hypoxanthine and xanthine, leading to an
increase in the levels of these metabolites.
Xanthine is much less soluble than uric acid, and urinary alkalinization
increases the solubility of xanthine much less than the solubility of uric acid
because the pKa is much higher for xanthine
Thus, patients with massive TLS who are receiving allopurinol are at risk for
xanthine precipitation in the tubules, resulting in xanthine nephropathy or
xanthine stone formation.
Because the serum xanthine level is not routinely measured, its effect on the
risk of acute kidney injury is not certain. In contrast to the effect of allopurinol,
xanthine concentration is not increased by rasburicase (recombinant urate
oxidase), which is now preferred in most patients at high risk for TLS.
Rasburicase promotes the degradation of uric acid to the much more water-
soluble compound allantoin.
However, in patients with glucose-6-phosphate dehydrogenase (G6PD)
deficiency, hydrogen peroxide, a breakdown product of uric acid, can cause
methemoglobinemia and, in severe cases, hemolytic anemia. For this reason,
rasburicase is contraindicated in patients with G6PD deficiency.
CLINICAL MANIFESTATIONS
The symptoms associated with tumor lysis syndrome (TLS) largely reflect the
associated metabolic abnormalities (hyperkalemia, hyperphosphatemia, and
hypocalcemia).
They include nausea, vomiting, diarrhea, anorexia, lethargy, hematuria, heart
failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and
possible sudden death.
Cairo-Bishop definition — The Cairo-Bishop definition, proposed in 2004, provided
specific laboratory criteria for the diagnosis of TLS both at presentation and
within seven days of treatment. It also incorporated a grading system to help
delineate the degree of severity of TLS.
Laboratory TLS was defined as any two or more abnormal serum values
(hyperuricemia,hyperkalemia,hyperphosphatemia and hypocalcemia), present
within three days before or seven days after instituting chemotherapy in the
setting of adequate hydration (with or without alkalinization) and use of a
hypouricemic agent. 681
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Clinical TLS was defined as laboratory TLS plus one or more of the following
that was not directly or probably attributable to a therapeutic agent: increased
serum creatinine concentration (≥1.5 times the upper limit of normal [ULN]),
cardiac arrhythmia/sudden death, or a seizure.
RISK STRATIFICATION
High risk
Included in the high-risk group (>5 percent risk of TLS) are:
All Burkitt leukemia, stage III or IV Burkitt lymphoma or early stage Burkitt
lymphoma with serum LDH level two or more times the upper limit of normal
(≥2X ULN)
Other acute lymphoblastic leukemia (ALL) with a white blood cell (WBC) count
≥100,000 per microL and/or serum lactate dehydrogenase (LDH) level ≥2X ULN
AML with WBC count ≥100,000 per microL
Stage III or IV lymphoblastic lymphoma or early stage lymphoblastic lymphoma
with serum LDH level two or more times the upper limit of normal (≥2X ULN)
Chronic lymphocytic leukemia (CLL) treated with venetoclax and lymph node ≥10
cm or lymph nodes ≥5 cm plus absolute lymphocyte count ≥25 x
109/L, and elevated serum uric acid level
Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell
lymphoma, transformed lymphoma, or mantle cell lymphoma with serum LDH
level above the ULN and a bulky tumor mass
Stage III or IV childhood diffuse large B-cell lymphoma with serum LDH level
≥2X ULN
Patients with intermediate-risk disease (see below) with renal
dysfunction and/or renal involvement or uric acid, potassium, or phosphate levels
above the ULN
Intermediate risk
The intermediate-risk group (risk of TLS 1 to 5 percent) includes:
Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell
lymphoma, transformed lymphoma, or mantle cell lymphoma with serum LDH
level above ULN but without bulky disease
Stage III or IV childhood anaplastic large cell lymphoma with serum LDH level
<2X ULN
Stage III or IV childhood diffuse large B-cell lymphoma with serum LDH level
≥2X ULN
Early stage Burkitt lymphoma with serum LDH level <2X ULN
ALL with WBC <100,000/microL and serum LDH level <2X ULN
AML with WBC 25,000 to 100,000/microL or AML with WBC<25,000/microL and
LDH ≥ 2X ULN
Early stage lymphoblastic lymphoma with serum LDH level <2X ULN 682
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Low risk — Patients at low risk for TLS (<1 percent risk) include [16]:
AML with WBC count <25,000/microL and serum LDH level <2X ULN
CLL/SLL with a WBC count ≤50,000/microL and not treated
with fludarabine/rituximab or venetoclax
Multiple myeloma and chronic myelogenous leukemia (CML)
Other adult non-Hodgkin lymphomas (NHL) that do not meet the criteria for
high risk or intermediate risk, with serum LDH level within normal limits
Other solid tumors
EPIDEMIOLOGY
The incidence of hyperleukocytosis and leukostasis vary by leukemia type and
patient population. In general, symptoms of leukostasis are more common in
leukemias with large, poorly deformable blasts, such as acute myeloid
leukemia.
Acute myeloid leukemia – Hyperleukocytosis is present in 10 to 20 percent of
patients with newly diagnosed acute myeloid leukemia (AML). Symptoms of
leukostasis occur less frequently and typically affect patients with white blood
cell (WBC) counts over 100 x 109/L (100,000/microL).
Acute lymphoblastic leukemia – Hyperleukocytosis is seen in 10 to 30 percent
of patients with newly diagnosed acute lymphoblastic leukemia (ALL).
Symptoms of leukostasis occur less frequently and typically affect patients with
white blood cell (WBC) counts over 100 x 109/L (100,000/microL).Tumor lysis
syndrome and disseminated intravascular coagulation are more common
complications related to the elevated WBC count.
Chronic lymphocytic leukemia – A significant proportion of patients with
chronic lymphocytic leukemia (CLL) present with hyperleukocytosis. Symptoms 684
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DIAGNOSIS
Leukostasis (symptomatic hyperleukocytosis) is diagnosed empirically when a
patient with leukemia and a white blood cell (WBC) count over 100 x
109/L (100,000/microL) presents with symptoms thought to be due to tissue 685
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MANAGEMENT
Cytoreduction - can be achieved through the use of chemotherapy
(hydroxyurea or remission induction chemotherapy) or leukapheresis.
The initial management of a patient with hyperleukocytosis is directed at rapid
lowering of the WBC count.
▪ For patients with symptomatic or asymptomatic hyperleukocytosis, we
suggest initial cytoreduction with induction chemotherapy rather
than hydroxyurea or leukapheresis.
▪ For patients with asymptomatic hyperleukocytosis who must have
induction chemotherapy delayed, we suggest cytoreduction
with hydroxyurea rather than leukapheresis
▪ For patients with symptoms of leukostasis who must have induction
chemotherapy delayed, we suggest initial leukapheresis in addition
to hydroxyurea (if possible) to lower or stabilize the WBC count.
Supportive care measures:
▪ Red blood cell transfusions should be withheld, if possible, until the blast
count is reduced. If a transfusion is necessary, it should be administered
slowly.
▪ Most patients with hyperleukocytosis are candidates for tumor lysis
syndrome prophylaxis with aggressive intravenous hydration
and allopurinol or rasburicase to decrease serum uric acid levels.
▪ Coagulation abnormalities require aggressive treatment with platelet
transfusions and coagulation factors.
3) Neutropenic fever
APPROACHES TO MANAGEMENT
Approaches to the management of infection in patients at risk for neutropenic
fever include primary prophylaxis, secondary prophylaxis, empiric therapy, and
preemptive therapy.
Primary prophylaxis — Primary prophylaxis involves the administration of an
antimicrobial drug to prevent infection in patients at increased risk.
Secondary prophylaxis — Secondary prophylaxis involves the administration of
prophylactic doses of an antimicrobial drug to prevent recurrent infection
Empiric therapy — In patients with chemotherapy-induced neutropenia, empiric
therapy involves the initiation of therapy at the time of the onset of neutropenic
fever but before a firm diagnosis of infection has been established. Empiric
antimicrobial therapy is a standard part of the management of neutropenic
fever.
Preemptive therapy — Preemptive therapy involves the initiation of therapy based
upon screening with a sensitive microbiology assay (eg, antigen detection or
molecular assays) in an attempt to detect the presence of a putative pathogen
or early subclinical infection. Patients whose infections are detected using a
preemptive approach are treated to avoid progression to invasive disease. A
preemptive approach is sometimes used for antifungal therapy.
The following observations have been made about bacterial infections in
neutropenic patients: 688
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EMPIRIC THERAPY
General principles — Fever in a neutropenic patient should be considered a
medical emergency. Broad-spectrum antibacterials should be given as soon as
possible (within 60 minutes of triage) and at full doses, adjusted for
renal and/or hepatic function. In addition, the diagnostic evaluation should be
obtained quickly.
In high-risk patients, antibiotics should generally be administered intravenously
(IV) in a hospital setting.
Febrile neutropenic patients should be monitored frequently with respect to vital
signs (blood pressure, heart rate, respiratory rate, and temperature),
performance status (the clinical burden of the neutropenic fever syndrome), and
the ability to achieve adequate oral intake in the presence of oral or
gastrointestinal mucositis. Temporarily holding administration of systemic
chemotherapy should be considered during the management of the sepsis
syndrome until the patient stabilizes. Attention to fluid and electrolyte
management is important given the dehydrating effects of fever, 689
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vomiting, and/or diarrhea. Urine output of >0.5 mL/kg per hour should be
maintained.
the initial therapy of high-risk neutropenic patients with fever;
Initiation of monotherapy with an antipseudomonal beta-lactam agent, such
as cefepime, meropenem, imipenem-cilastatin, or piperacillin-
tazobactam. Ceftazidime monotherapy has also been shown to be effective and
continues to be used at some cancer centers. However, many experts avoid
ceftazidime monotherapy because of rising resistance rates among gram-
negative bacteria and its limited activity against gram-positive bacteria, such as
streptococci, compared with newer alternatives. The dosing of these agents for
patients with normal renal function using traditional dosing (ie, over 30 minutes)
are:
▪ Cefepime – 2 g IV every eight hours
▪ Meropenem – 1 g IV every eight hours
▪ Imipenem-cilastatin – 500 mg IV every six hours
▪ Piperacillin-tazobactam – 4.5 g IV every six to eight hours; if there is
significant concern for Pseudomonas infection (particularly in those who
are severely ill or were not receiving fluoroquinolone prophylaxis at the
time of onset of illness), 4.5 g IV every 6 hours should be given
▪ Ceftazidime – 2 g IV every eight hours
Other antibiotics (eg, aminoglycosides, fluoroquinolones, and/or vancomycin) may
be added to the initial regimen in patients with complicated presentations (eg,
hypotension and/or mental status changes), focal findings (eg, pneumonia or
cellulitis), or if antimicrobial resistance is suspected or proven.
Vancomycin (or other agents that target gram-positive cocci) is not recommended
as a standard part of the initial regimen but should be added in certain
patients, such as those with suspected catheter-related infection, skin or soft
tissue infection, pneumonia, or hemodynamic instability.
The following antibiotics can be used when resistant infections are suspected
▪ MRSA – Vancomycin, linezolid, or daptomycin; daptomycin should be
avoided in patients with pneumonia because it does not achieve
sufficiently high concentrations in the respiratory tract.
▪ VRE (vancomycin resistant enterococci) – Linezolid or daptomycin
▪ ESBL (extended-spectrum beta-lactamases)-producing gram-negative
bacilli – A carbapenem (eg, imipenem, meropenem).
▪ Carbapenemase-producing bacteria, including Klebsiella
pneumoniae carbapenemase – Colistin or tigecycline.
CLINICAL MANIFESTATIONS
➢ Signs and symptoms — Neutropenic enterocolitis must be considered in any
severely neutropenic patient (absolute neutrophil count <500 cells/microL) who
presents with fever and abdominal pain. The location of abdominal pain
depends upon the location of the neutropenic colitis and is often in the right
lower quadrant. Symptoms, including fever, frequently appear during the third
week (median 17 days) after receiving cytotoxic chemotherapy, at a time when
neutropenia is most profound. Additional symptoms may include abdominal
distension, cramping, tenderness, nausea, vomiting, watery or bloody diarrhea,
and frank hematochezia. Paralytic ileus may occur but is uncommon. Peritoneal
signs and shock suggest the possibility of bowel wall perforation. Stomatitis
and pharyngitis, suggesting the presence of widespread mucositis, may be
present.
➢ Patients may remain febrile until recovery from neutropenia, independent of
antimicrobial therapy. Patients developing neutropenic enterocolitis during
chemotherapy are prone to develop this complication again during subsequent
treatments.
DIAGNOSIS;
➢ Neutropenic enterocolitis is usually diagnosed by detection of the characteristic
computed tomography (CT) findings in neutropenic patients presenting with
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fever and abdominal pain and tenderness. All patients suspected of having
neutropenic colitis should undergo abdominal CT scanning.
➢ CT findings included bowel wall thickening (100 percent), mesenteric stranding
(51 percent), bowel dilatation (38 percent), mucosal enhancement (28 percent),
and pneumatosis (21 percent).
➢ ultrasound or plain radiographs of the abdomen( with 23 percent and 48
percent false negative respectively,which is 15% for CT )
➢ In addition to CT scanning, blood and stool cultures and C. difficile toxin assays
should be performed.
TREATMENT
➢ Patients without complicated neutropenic enterocolitis (ie, perforation or severe
bleeding) should receive nonsurgical management with broad-spectrum
antimicrobials, bowel rest, nasogastric suction, intravenous fluids, nutritional
support, and blood product support (packed red blood cells and fresh frozen
plasma as needed). Although surgery is typically avoided in neutropenic and
thrombocytopenic patients, surgical intervention is recommended for those with
free perforation or another process that cannot be controlled medically (eg,
persistent bleeding despite correction of coagulopathy and cytopenias ).
➢ The antimicrobial regimen should target likely pathogens as well as pathogens
that have been detected from the patient’s bloodstream. The regimen should
include agents that are active against Pseudomonas aeruginosa, Escherichia
coli, other enteric gram-negative bacilli, and anaerobes.
➢ We suggest one of the following empiric regimens for patients with neutropenic
enterocolitis provided that the patient does not have bacteremia with an
organism that is resistant to the following agents:
➢ Piperacillin-tazobactam(for adults: 4.5 g IV every six hours; for infants <9
months: 80 mg/kg of piperacillin component IV every eight hours; for infants and
children ≥9 months and ≤40 kg: 100 mg/kg of piperacillin component IV every
eight hours; for children >40 kg: 3 g of piperacillin component IV every six
hours or 4 g of piperacillin component IV every six to eight hours; the
maximum daily dose of the piperacillin component is 16 g/day)
➢ Cefepime plus metronidazole(for adults: 2 g IV every eight hours; for children:
50 mg/kg IV every eight hours up to a maximum of 2 g per
dose),metronidazole(for adults: 500 mg IV every eight hours; for children: 30 to
40 mg/kg IV per day in divided doses every six to eight hours, maximum daily
dose 1500 mg/day).
➢ Ceftazidime plus metronidazole (for adults: 2 g IV every eight hours; for children:
50 mg/kg IV every eight hours up to a maximum of 2 g per dose)
➢ An antipseudomonal carbapenem (imipenem or meropenem) can also be used,
but we reserve these agents for patients who are allergic to the other options
or who are infected or colonized with an organism that is resistant to the other
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PROGNOSIS
➢ Initial reports of patients with neutropenic enterocolitis described mortality rates
between of 50 percent or higher. Most deaths are attributed to transmural
bowel necrosis, perforation, and sepsis. More recently, early recognition and
progress in management have reduced mortality substantially, although no large
series have been published.
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Case reporting format for bedside, round, exam and case discussion
➢ This is a case report of CLD patient from my clinical year attachment bedside
case at UOG Hospital.
History
Identification
➢ This is Ato Meazaw wubie, a 56 years old, male, married, orthodox Christian,
farmer, from Tach armachiho woreda, north Gondar zone, admitted to
University of Gondar hospital, department of Internal medicine, Medical ward D,
bed no #27 on Tikimt 24/2010 E.C.
Previous Admission
➢ None
➢ If there is previous admission which is unrelated to the current illness, you can
document like these; E.g. 2003 E.C, TASH, Addis Ababa, HIV-associated
cerebral toxoplasmosis, admitted for 03 months, treated with ART drugs and
anti-toxoplasmosis drugs and discharged improved.
Chief compliant
HPI
This patient was last relatively healthy 03 months back, at which time he noticed
Abdominal distension which initially started from RLQ, which gradually increase in
size and progress to involve the whole abdomen and lower extremities within one
month duration. Together with dragging sensation in the left upper abdomen,
sense of fullness and early satiety.
He has also unquantified but significant weight loss to the extent his trousers
become loose, loss of appetite and easy fatigability.
For these, he visited a traditional healer where he was given unspecified herbal
medication and cauterized at his arms, forearms, over the abdomen and back but
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he didn’t get any relief. Finally, he came to our hospital for better investigation
and management.
➢ He drinks traditional areki half bottle 2 - 3 times per week for 5 years
and then changed his drink to a beer of 10 to 15 bottles every
Tuesday, Saturday and Sunday (average 37 bottles per week) for the
past 8 years that means he drinks for a total of 13 years. which is
estimated to be 70g alcohol intake daily for 13 years.
➢ No hx of blood transfusion, tattooing, contact with a jaundiced patient, IV drug
abuse or MSP
➢ No hx of drug intake other than mentioned above
➢ No family hx of similar illness
➢ He usually eats injera made of ‘‘teff’’ and ‘‘machilla’’ and ‘’wott’’ made of
‘‘atter’’ and ‘‘dagusa’’ 3-4 times per day. Occasionally he eats meat during
holidays
➢ He has coca colored discoloration of urine but no pain during urination,
urgency, frequency or flank pain
➢ No hx of nasal bleeding, bloody vomiting or melena
➢ He has easy fatigability but no hx of tinnitus, blurring of vision or light
headedness
➢ No hx of sleep disturbance, confusion, Forgetfulness, Abnormal body movement
or LOC
➢ Has hx of river water contact but no hx of post river water contact itching
➢ No hx of dyspnea, orthopnea, PND or palpitation
➢ No hx of chronic cough, contact with chronic cougher or previous TB treatment
➢ No self/family hx of DM, HTN or asthma
➢ He was screened for RVI 2 months back and found to be NR.
Past illnesses
➢ No history of childhood illnesses like chicken pox, mumps or small pox. Not
vaccinated.
➢ No history of previous surgery, trauma, psychiatry problems or drug allergy.
H.E.E.N.T
▪ Head: No history of headache or head injury
▪ Eyes: No history of blurring of vision, pain in the eyes, eye itching, or
spontaneous
lacrimation
▪ Ears: No history of Earache, difficulty of hearing, ear discharge, vertigo
or tinnitus
▪ Nose: No history of nasal bleeding or discharge
▪ Mouth and throat: No history of gum bleeding, tooth extraction 695
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Personal History
➢ He was born and raised in Tach armachiho in 1954 E.C, where he lived all
his life. He had a healthy childhood and was an active boy who liked helping
his father around the farm. He didn’t attend formal education but he is able to
read and write.
➢ He is a farmer and also raises cattle, sheep and goat. He claims his income
is enough to support the family.
➢ He has 4 boys and one daughter. All are alive and healthy.
Family History
➢ Both his father and mother are dead. His father died while he was child at
unknown age by unknown cause while his mother died 5 years ago at age 69
by natural cause.
➢ He has two sisters and one brother. All are alive & well.
➢ No family history of DM, hypertension, Asthma, tuberculosis, allergy or sudden
deaths.
Physical examination
General Appearance
Vital signs
H.E.E.N.T
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➢ Head: Normal male type hair distribution, No visible scar over the scalp or
tenderness
➢ Ears: Normal contour of pinna, Clear external ear canal, No mastoid or tragus
tenderness
➢ Eyes: Icteric sclera, Pink conjunctivae, No periorbital edema
➢ Nose: central nasal septum. There is no polyp or active discharge
➢ Mouse and throat: No fissure or ulceration on the lip, the gums are intact, no
active bleeding. There are no carious teeth, extraction, dentures or filling. no
atrophied papillae of tongue, the buccal mucosa is pink & wet.
Inspection
▪ There is grade II clubbing of fingers, but no central or peripheral
cyanosis
▪ Symmetric chest wall that moves with respiration
▪ No chest wall deformity
▪ No subcostal or intercostal retraction
▪ No use of accessory muscles of respiration\
▪ Shallow and regular breathing pattern
Palpation
▪ There is no chest wall tenderness or subcutaneous emphysema
▪ Centrally located trachea
▪ Comparable tactile fremitus bilaterally
▪ Symmetrically normal chest expansion bilaterally which slides 5cm by
measuring tape method.
Percussion
▪ Resonant percussion note all over the lung field
▪ There is no dullness
▪ diaphragmatic excursion = 5cm bilaterally
Auscultation
▪ Vesicular breath sound all over the lung field
▪ No added respiratory sound
▪ Comparably normal air entry bilaterally
Arterial examination
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▪ All accessible peripheral arteries are palpable, full in volume and regular
in rhythm
Venous examination
▪ No distended neck veins
▪ JVP = 3cm
Precordial Examination
▪ Inspection
• Active precordium
• AI @5th ICS medial to left MCL
• No precordial buldge or scar
▪ Palpation
• Palpable heart sounds
• PMI @5th ICS medial to left MCL which is Localized, tapping and
non-sustained
• No heave or thrill
▪ Auscultation
• S1 & S2 are well heard
• No murmur or gallop
Abdominal examination
Inspection
▪ Grossly / Symmetrically distended abdomen
▪ Flanks are full
▪ Everted umbilicus with circular slit
▪ superficially distended and tortuous abdominal vessels which drain away
from umbilicus during palpation
▪ No visible scar, straie, pigmentation or peristalsis
▪ Hernia sites are free
Auscultation
▪ Normoactive bowel sounds (18 kicks/min)
▪ No bruit over abdominal aorta, renal arteries, iliac arteries, liver or spleen
Palpation
▪ Superficial palpation
• No superficial tenderness
• No superficially palpable mass
▪ Deep palpation
• Enlarged/ ballotable mass over the LUQ which is 13 cm from left
costal margin along the splenic growth line, non-tender, firm in
consistency, smooth surface, sharp edge, Palpable medial notch,
doesn’t allow finger to pass below left costal margin, Moves with
respiration, Not bimanually palpable
• No direct/rebound tenderness, guarding or rigidity
• Liver is not palpable
• kidney is not bimanually palpable bilaterally.
Percussion
▪ Tympanic percussion note except the flanks (i.e. dullness over the flanks) 698
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N.B. these finding are pertinent negative for CLD, in other cases you can report
like these;
Musculoskeletal System
Nervous system
Level of consciousness
▪ GCS = 15/15 (E4V5M6), conscious and alert
CN examination
▪ CN-I: He can smell soap via each nostril.
▪ CN-II:
• He can differentiate 2 fingers at about 6 meters. (Visual Acuity)
• He sees waggling of finger approximately 1000 from axis of eye.
(Visual Fields)
• He differentiates green and red colours. (Colour Appreciation)
• Normal direct and consensual pupillary light reflex
▪ CN-III, IV & VI:
• The eyes can move in all directions. There is no nystagmus or
diplopia. The pupils are round, regular in outline and equal in size.
They react to light directly and consensually.
▪ CN-V:
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TONE POWER
Upper Lower Upper Lower
Right Normo- Normo-tonic 5/5 5/5
tonic
Left Normo- Normo-tonic 5/5 5/5
tonic
• Reflexes
o Superficial
✓ Abdominal reflex is present both in upper and lower
quadrants.
✓ Corneal reflex is intact in both eyes.
✓ Plantar reflex is down going on both sides.
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o DTR
Sensory examination
▪ Primary sensory exam
• He identifies light touch and pin prick over the extremities and
trunk.
• He is able to recognize different movements of the toes with his
eyes closed. (Position sense)
• Vibration sense was not assessed due to lack of Tuning Fork.
▪ Cortical sensory exam
• He appreciates the form of a key by means of only touch
(Stereognosis)
• He recognizes writings of different numbers on his palm
(Graphesthesia)
• He is able to differentiate 2 pin pricks up to 4 mm apart over the
finger tips (2 pt discrimination).
Coordination
▪ Finger to nose, heal to shin and rapid alternating movement of the arm
were done without any abnormalities.
Meningeal irritation signs
▪ No neck stiffness.
▪ Kernig's Sign is negative.
▪ Brudzinski's Sign is negative
Subjective summary
Objective summary
➢ conscious & cooperative, chronically sick looking, not in cardiopulmonary stress,
looks well nourished
➢ BP: 110/70mmHg
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Case reporting format for bedside, round, exam and case discussion
➢ PR: 95 bpm
➢ RR: 18 breath/min
➢ T0: 36.20c
➢ He has
▪ Icteric sclera
▪ grade II clubbing of fingers
▪ Grossly distended abdomen
▪ Flank fullness
▪ Everted umbilicus with circular slit
▪ superficially distended and tortuous abdominal vessels which drain away
from umbilicus during palpation
▪ shifting dullness of 2cm
▪ flank dullness
▪ Ballotable mass over the LUQ which is 13 cm from left costal margin
along the splenic growth line, non-tender, firm in consistency, smooth
surface, sharp edge, Palpable medial notch, doesn’t allow finger to pass
below left costal margin, Moves with respiration, Not bimanually palpable
→ marked splenomegaly
▪ grade II pedal and pretibial pitting edema
Investigations done
PM
Culture = no organism identified
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Case reporting format for bedside, round, exam and case discussion
A) HBsAg
B) Direct and total bilirubin
C) Abdominal U/S
D) Echo
Definition;
Etiology; write from the corresponding topics of nitsbin above,
Pathophysiology; Harrison and uptodate (this is for other DDX also)
Epidemiology;
Clinical features;
Conclusion;
This patient has ascites with grade II pedal and pretibial edema, easy fatigability
and loss of appetite which support nephrotic syndrome. But stabbing RUQ
abdominal pain jaundice and the pattern of edema can’t be explained by NS. For
the diagnosis of NS, Nephrotic range proteinuria and Serum albumin concentration
< 3 g/dL are used. But this patient has only protein +1 and serum albumin of
3.6g/dl which doesn’t support NS. Epidemiologically, unlike children, NS is not
common in adults. So, nephrotic syndrome as a diagnosis is unlikely for this case.
Conclusion;
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Case reporting format for bedside, round, exam and case discussion
This patient has ascites with grade II pedal and pretibial edema, easy fatigability
and weight loss which goes with constrictive pericarditis. The absence of
retrosternal chest pain, elevated JVP, tender hepatomegaly and pericardial friction
rub goes against constrictive pericarditis. In developing world infectious (especially
TB) is the most common cause of constrictive pericarditis. This patient has no hx
of contact or TB infection and from ascitic fluid analysis AFB is negative which
may help us to r/o constrictive pericarditis. So, constrictive pericarditis as a
diagnosis is less likely for this case.
Conclusion;
This patient has Ascites, leg edema and splenomegaly which can be explained by
Portal Hypertension secondary to decompensated CLD.
He has history of chronic alcohol intake for the past 13th years which strongly
suggest alcoholic liver disease.
Final assessment
References
➢ Harrison’s principle of internal medicine 20th edition
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Case reporting format for bedside, round, exam and case discussion
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Part II; Short cases
Part II
Part II; Short cases
Short cases
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Chapter 1; Physical examination
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Chapter 1; Physical examination
Pneumothorax
Consolidation
Atelectasis
fibrosis
✓ bilateral
Emphysema
ILD
Bilateral fibrotic lung
☛ Abnormal breathing patterns → causing examples
✓ Tachypnia → severe pneumonia, decreased CO
✓ Bradypnea → barbiturate poisoning
✓ Paradoxical breathing → diaphragmatic paralysis
✓ Kussmauls breathing (deep, labored, fast breathing followed by apnoea)
→ Metabolic acidosis (DKA, ureamic encephalopathy, hepatic
encephalopathy)
✓ Chyne stokes breathing → CHF, stroke
✓ Apneustic breathing → pontine damage
708
✓ Ataxic breathing → medullary compression (trans tentorial herniation)
☛ Chest wall deformities → causing examples
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Chapter 1; Physical examination
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Chapter 1; Physical examination
Absent air entry over the posterior lower 1/3rd of right/left chest
1.1.3 Consolidation
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Chapter 1; Physical examination
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Chapter 1; Physical examination
1.1.5 Pneumothorax
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Chapter 1; Physical examination
N.B. CT scan
From the three mechanisms of lung Other Baseline IX
collapse, all are reversible except IX based on the
contraction underlying cause
Reporting format of atelectasis
❖ Inspection
❖ Palpation
Trachea deviated to the same side of lesion (please say right or left based on your finding), decreased chest expansion
over the right/left side by hand grip method
❖ Percussion
There is relative dullness over the posterior right/left chest
❖ Auscultation
Absent air entry over the posterior right/left chest
1.1.8 emphysema
PR reporting example
PR = 72 BPM, regular and full in volume
Reporting of normal arterial examination
☛ All accessible peripheral arteries are palpable, full in volume and regular in rhythm
Distended
neck vein
JVP ✓ Normal→ 3-4 cm (8-9 mmhg)
✓ Raised JVP → CHF, constrictive pericarditis, SVC sxx, cardiac tamponade, rarely in CLD,
Nephrotic sxx and obstructive lung disease
✓ +ve kussmauls sign → raised JVP during inspiration
▪ Constrictive pericarditis
▪ rCMP
▪ MI (right ventricular infarction)
Venous Examination
Precordial examination
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Chapter 1; Physical examination
✓
▪ Normally @ 4th or 5th ICS, @ or medial to left MCL
▪ Not visible → pericardial effusion, constrictive pericarditis, highly
muscular individuals
▪ Displaced downwards and laterally → Cardiomegaly of different causes
(see below)
✓ Precordial buldge → long standing CHD
✓ Scar → evidence for surgical treatment of CHD
☛ Diffuse → palpable by 2nd & 4th finger while 3rd is off from the
precordial area, > 2.5cm in size or occupy > 1 ICS
☛ Sustained → occupies more than 2/3rd of cardiac cycle
✓ Heave → indicate cardiomegaly
▪ Left parasternal heave → RVH
▪ Apical heave → LVH
✓ Thrill
▪ Palpable murmur like purring of a cat
▪ Indicate grade 4 and above murmur
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Chapter 1; Physical examination
1. GA
Cardiopulmonary distress
Edematous
2. Vital signs
Tachycardia ± Tachypnea
3. HEENT
Facial puffiness
4. RS
Basal rales /creptation and other pulmonary edema features
Pleural effusion
5. CVS
Distended neck vein
Raised JVP
S3 gallop
Cardiomegaly
6. Abdomen
Positive Hepatojugular reflex
Tender hepatomegaly
Ascites 720
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Chapter 1; Physical examination
7. MSS
Bilateral pitting edema
1.2.2. Murmur
Murmur characterization
Mnemonic for rehearsal of murmur characterization components
MR TR AR AS MS
Grade Usually III Usually II to III
Pitch Medium to High pitched Low pitched
Quality Blowing Rasping Rumbling
Time Pan systolic murmur Early diastolic murmur Mid systolic Mid diastolic
murmur murmur
Location Best heard at the Best heard at the Best heard at the Best heard at Limited to the
Apex of the heart LLSB erb’s point the aortic area apex
Radiation to the left axilla/ to the epigastrium to the neck
base of heart
Manoeuvre Accentuated by deep
inspiration
Accentuated by
leaning forward and
expiration
722
Accentuated by
left lateral
positioning and
exercise
Other ✓ Laterally and ✓ Laterally and down ✓ Laterally and ✓ Accentuated
down ward ward displaced AI down ward S1
associated
displaced AI ✓ Wide pulse pressure displaced AI ✓ Opening snap
findings ✓ Muffled S1 ✓ Water hammer pulse ✓ Anacrotic following S2
✓ Prominent S3 ✓ Absent S2 arterial pulse
gallop
Reporting ✓ Grade III, High ✓ Grade III, High ✓ Grade III, High ✓ Grade II, ✓ Grade II,
format pitched, pitched, Blowing, pitched, Blowing, low pitched, low pitched,
Blowing, Pansystolic early diastolic rasping, mid rumbling,
Pansystolic murmur, Best murmur, Best systolic mid
murmur, Best heard at the LLSB, heard at the erb’s murmur, diastolic
heard at the which radiates to point, accentuated Best heard murmur,
Apex of the the epigastrium, by leaning forward at the Aortic limited to
heart, which Accentuated by and expiration area, which the apex,
radiates to the deep inspiration radiates to accentuated
left axilla/ the neck by left
base of heart lateral
positioning
and
exercise
Causes ✓ Primary (organic) ✓ Acute ✓ Rheumatic ✓ Rheumatic
(DDX) ❖Acute • Rheumatic o IE fever or fever/RHD
o IE fever/RHD o Trauma ✓ CRMVHD (>95%)
Click here o Papillary • IE o Aortic dissection ✓ Congenital ✓ Other less
→ • Papillary (bicuspid, common
muscle o Trauma
Valvular muscle injury unicuspid) causes
heart rupture ✓ Chronic
(post-MI) ✓ Degenerative o IE
disease (Post MI) • Myxomatous o Primary valvular calcification o Congenita
(VHD) o Chordae (tricuspid valve disease: ✓ Radiation l
tendineae prolapse) ▪ Rheumatic o Severe
rupture • Leaflet trauma fever (RHD) mitral
o Blunt • Radiation ▪ IE annular
• Carcinoid heart calcificatio
trauma ▪ Congenital
disease n with
❖Chronic • Endomyocardial Bicuspid leaflet
o Primary MR- fibrosis aortic valve involveme
▪ RHD • CHD in ▪ SLE nt
▪ IE children ▪ Syphilitic o SLE
▪ Mitral (Ebstein’s aortitis o RA
valve malformation of o Myxoma
▪ Ankylosing
the tricuspid
prolapse spondylitis.
valve)
(MVP) ✓ Secondary ▪ Myxomatous
▪ Trauma (functional) /cause (prolapse)
▪ Congenital of > 80% of TR/ o Aortic root
(cleft, AV • MI disease
canal) • Cardiomyopath ✓ Aortic
y (HCMP,
o Secondary dissection
DCMP)
(functional) ✓ Systemic
• Atrial fibrillation
MR (AF) severe HTN
▪ IHD • Longstanding ✓ Cystic medial
▪ DCMP
▪ HCMP
▪ Chronic
pulmonary HTN
• Left-sided valve
disease
degeneration
of the
ascending
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Chapter 1; Physical examination
Atrial aorta
Fibrillation ✓ Marfan
o Mitral annular syndrome
calcification ✓ Bicuspid
aortic valve
✓ Nonsyndromic
familial
aneurysm
✓ Aortitis
✓ Idiopathic
dilation of the
aorta
✓ Annuloaortic
ectasia
✓ Osteogenesis
imperfecta
IX Refer long case of nitsibin → IX of HF (click here → Chapter 1; Heart failure (ልብ ድካም))
Mgt Refer long case of nitsibin → mgt of HF (click here → Management of heart failure) and VHD mgt
principle (Click here → Valvular heart disease (VHD))
N.B
✓ Peripheral signs of AR
☛ deMusset's sign – head bob occurring with each heart beat
☛ Traube's sign – a pistol shot pulse (systolic and diastolic
sounds) heard over the femoral arteries
☛ Duroziez's sign – a systolic and diastolic bruit heard when the
femoral artery is partially compressed
☛ Quincke's pulses – capillary pulsations in the fingertips or lips
☛ Mueller's sign – systolic pulsations of the uvula
☛ Becker's sign – visible pulsations of the retinal arteries &
pupils
☛ Hill's sign – popliteal cuff systolic pressure exceeding brachial
pressure by more than 60 mmHg
☛ Mayne's sign – more than a 15 mmHg decrease in diastolic
blood pressure with arm elevation from the value obtained with
the arm in the standard position
☛ Rosenbach's sign – systolic pulsations of the liver
☛ Gerhard's sign – systolic pulsations of the spleen
❖ DCMP
❖ HCMP
❖ CAD (MI)
❖ CHD
❖ Peripartum CMP
❖ Pulmonary HTN
❖ Pericardial effusion
❖ Hemochromatosis
❖ Amyloidosis
❖ Idiopathic
Edema grading
✓ Palpate behind the medial malleolus and the distal shaft of the tibia, and
dorsum of foot for pitting edema by gently compressing the area for at least
15 seconds with the thumb
diarrhoea
❖ reduced then absent → generalized peritonitis, paralyzed ileus
✓ Bruit
❖ Over Abdominal aorta → partial obstruction of aorta
❖ Over renal arteries → renal artery stenosis
❖ Over liver → HCC, alcoholic hepatitis
❖ Over femoral and iliac arteries
✓ Friction rub
❖ Liver → liver tumour
❖ Spleen → splenic infarct
Reporting format for normal abdomen auscultation finding
☛ Normoactive bowel sounds (18 kicks/min), no bruit over abdominal aorta, renal arteries, iliac arteries or
liver
Superficial ✓ Guarding, rigidity, direct/rebound tenderness → acute abdomen (firm and
✓ Tenderness board like in generalized peritonitis)
✓ Superficial palpable mass ✓ CVAT → pyelonephritis
Deep → Search for ✓ Abdominal mass
▪ Guarding ▪ Origin from Abdominal wall → protrudes when pt head lifts up
▪ Rigidity ▪ Origin from upper abdomen which doesn’t allow finger to pass
▪ Mass above the mass → mass from liver, spleen, stomach
▪ Direct / rebound ▪ Origin from lower abdomen which doesn’t allow finger to pass
tenderness below the mass → mass from urinary bladder, upper rectum
Palpation
▪ Organomegaly (liver, ▪ Origin from RUQ → mass from Liver, right kidney, hepatic flexure
spleen, kidney) of colon
▪ Ballotable mass in
ascites
N.B
If spleen is not palpable, turn the pt to the right with flexion of left heep and knee then repeat palpation. If still
not palpable go to percussion methods (Nixon, castles, troubes)
Reporting format for normal abdomen palpation finding
☛ Superficial palpation
No superficial tenderness, no superficially palpable mass
☛ Deep palpation
No direct/rebound tenderness, guarding or rigidity, Liver and spleen are not palpable, kidney is not
bimanually palpable bilaterally.
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Chapter 1; Physical examination
Castell’s method
✓ Ask the pt to be on supine position
✓ Percuss the lower intercostal space at 8th or 9th interspace along left anterior axillary line during full
inspiration and expiration
✓ Dullness on full inspiration suggests splenomegaly
Traube’s method
✓ Borders of Traube’s space:
Percussion
1.3.2 Ascites
✓ symmetrically distended
abdomen
Transudative Ascitic fluid
❖ Salt restriction: < 2g per day
❖ Diuretics:
▪ flanks are full CLD → refer analysis a. Spironolactone 100-
secondary causes from
▪ eversion of umbilicus LFT and liver 200mg/day, escalate to a
with transverse or long case of nitsibin enzymes max. dose of 400-
circular slit (under DDX of CLD) Viral markers 600mg/day.
RSHF
▪ fluid thrill and shifting (HBsAg for b. Furosemude(lasix) 40-
dullness Constrictive pericarditis screening) 80mg /day, escalate to a
▪ superficially distended Nephrotic sxx (NS), CXR, ECG, max. dose of 120-
AKI, CKD
and tortuous abdominal ECHO → 160mg/day.
vessels Chronic pancreatitis RSHF
▪ drain away from SLE If ascites is still present despite the
Meig’s sxx → ovarian U/A → NS
umbilicus during above measurements, it is defined as
palpation which ca + pleural and refractory ascites.
indicate portal HTN peritoneal effusion
IVC sxx
(William Harvey ❖ Alternative treatment modalities
method) Hypothyroidism → rare include:
▪ straie alba/atrophica PLE (protein losing 1) large-volume paracentesis
enteropathy) → very
▪ associated ballotable rare condition
(therapeutic tap)
mass (e.g. HSM) 2) TIPS (trans jugular intra
Exudative hepatic portosystemic shunt)
Infectious → TB procedure
peritonitis 3) Liver transplant
Malignancy
(carcinomatous
infiltration) →
lymphoma, leukaemia
1.3.3 Splenomegally
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Chapter 1; Physical examination
1.3.5 Renomegaly
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Chapter 1; Physical examination
blinking to breathing
command pattern
eyelids localizing to one pupil not 3
open but pain wide and intubated,
not tracking fixed Cheyne-
Stokes
breathing
pattern
eyelids flexion pupil or not 2
closed but response to corneal intubated,
open to pain reflexes irregular
loud voice absent breathing
eyelids extension pupil and breathes 1
closed but response to corneal above
open to pain reflexes ventilator
pain absent rate
eyelids no response absent breathes 0
remain to pain or pupil, at
closed with generalized corneal, ventilator
pain myoclonus and cough rate or
status reflex apnea
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Chapter 1; Physical examination
❖ CN VIII
➔ Can hear finger rub
➔ Rinne and weber test if possible
❖ CN IX & X
➔ Listen patients voice
➔ Ask to swallow
➔ Ask to say ‘’AH’’ and check location of uveola
➔ Check gag reflex
❖ CN XI
➔ Check atrophy/asymmetry of trapezius
➔ Can shrug shoulder against resistance
➔ Can turn his/her head against resistance
❖ CN XII
➔ Listen articulation of words
➔ Tongue inspection
➔ Can protrude tongue
➔ Can move tongue from side to side
➔ Push cheeks by tongue
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Chapter 1; Physical examination
❖ Inspection TONE
➢ position of the extremities after repositioning by ✓ Can be normotonic, hypotonic (in flacid
the examiner lesions) or hypertonic (in spastic lesions)
☛ outward rotation → flaccid paresis/plegia Types of spasticity
☛ inward rotation → spastic paresis/plegia
➢ fasciculation 1. Klasp-knife spasticity: velocity-dependent
➢ Muscle Symmetry → compare proximal with spasticity with sudden release after reaching
distal, left with right a maximum, commonly seen in pyramidal
➢ Atrophy tract lesions
❖ Palpation 2. Lead-pipe spasticity: Increased tone
➢ Tone present throughout the range of motion is
➢ Power observed in frontal lobe disease
➢ Reflex 3. Cogwheel spasticity: Spasticity enterwined
☛ DTR ± Clonus, janderasik manoeuvre by tremor, commonly seen in extrapyramidal
☛ Superficial lesions
Plantar
Abdominal ➢ POWER
Scapular Grade Description
Anal 0/5 No muscle movement
Bulbocavernosus 1/5 Visible flicker muscle movement,
Cremasteric but no movement at the joint
Corneal 2/5 Movement at the joint (horizontal
➢ Arm drift mov’t), but not against gravity
☛ Pronator Drift 3/5 Movement against gravity, but not
☛ Cerebellar drift against added resistance
☛ Parietal drift 4/5 Movement against resistance, but
➢ Coordination less than normal
☛ Rapid Alternating Movements 5/5 Normal strength
✓ strike one hand on the thigh,
raise the hand, turn it over Power interpretation
✓ tap the distal thumb with the tip ➢ 0/5 & 1/5 → plegia
of the index finger
✓ tap your hand with the ball of
➢ 2/5 - 4/5 → paresis
each foot ➢ 5/5 → normal
☛ Point-to-Point Movements
✓ finger-to- nose test DTR Grading Scale
✓ Heel-to-Shin test
➢ Gait Grade Description
☛ Walk across the room, turn and come 0 Absent (with Jendrasik maneuver)
back 1+ or + Hypoactive (less brisk)
☛ Walk heel-to-toe in a straight line 2+ or ++ "Normal" (brisk)
(tandem walk) 3+ or Hyperactive without clonus (very
☛ Walk on their toes in a straight line +++ brisk)
☛ Walk on their heels in a straight line 4+ or Hyperactive with clonus
☛ Hop in place on each foot
Motor examination
++++
☛ Do shallow knee bend
☛ Rise from a sitting position Difference between UMNL and LMNL
Plantar No Up
reflex response going/Babinsk
i +ve
Plantar reflexces
✓ Upgoing /babniski +ve → normal or
UMNL
✓ Down going
✓ No response / equivocal → LMNL
❖ Primary sensory test Positive sensory phenomena by neurologic
☛ Pain, temperature, light touch → test for examination
anterolateral tract ✓ Hypesthesia/hypoesthesia
☛ Position and vibration → test for posterior tract ✓ Anesthesia
❖ Cortical sensory test ✓ Hypalgesia
☛ Extinction or simultanagnosia ✓ Hyperesthesia
Sensory examination
☛ Graphesthesia ✓ Allodynia
☛ Stereognosis ✓ Hyperalgesia
☛ Two Point Discrimination ✓ Hyperpathia
Negative sensory phenomena by neurologic
☛ Double simultaneous stimulation (DSS)
examination
✓ Impaired or absent primary sensory
modalities like to touch, vibration,
position, and temperature
☛ Neck stiffness
☛ Kernig's sign
signs
☛ Brudzinski's sign
☛ Jolt accentuation of headache
Reporting format for normal NS Examination finding
☛ Level of consciousness
➢ GCS = 15/15 (E4V5M6), conscious and alert
☛ CN examination
➢ CN-I:
▪ S/he can smell soap via each nostril.
➢ CN-II:
▪ S/he can differentiate 2 fingers at about 6 meters. (Visual Acuity)
▪ S/he sees waggling of finger approximately 1000 from axis of eye. (Visual Fields)
▪ S/he differentiates green and red colours. (Colour Appreciation)
▪ Normal direct and consensual pupillary light reflex
➢ CN-III, IV & VI:
▪ The eyes can move in all directions. There is no nystagmus or diplopia. The pupils
are round, regular in outline and equal in size. They react to light directly and
consensually.
➢ CN-V:
▪ S/he identifies light touch and pin prick over the mandibular, maxillary and
ophthalmic areas of the face.
▪ S/he closes her/his eyes at the touch of the cornea with a cotton swab.
▪ Contraction of the temporal and masseter muscles is symmetrical and strong while
clenching her/his teeth.
➢ CN-VII:
▪ The face is symmetrical at rest and during voluntary movements (smiling, frowning).
▪ S/he can smile, frown her/his forehead, puff out her/his cheeks
▪ can close both eyes equally and forcefully against resistance.
▪ Intact nasolabial fold
▪ Intact corneal reflex
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➢ CN-VIII:
▪ S/he can hear rubbing of the fingers on both ears.
➢ CN-IX & X:
▪ The soft palate rises in the midline when saying ‘ah!
▪ Centrally located uvula
▪ S/he can swallow his saliva
➢ CN-XI:
▪ The Sternocleidomastoid and trapezius muscles contract on turning the head and on
shrugging the shoulder against resistance, respectively
➢ CN-XII:
▪ The tongue protrudes in the midline and shows no fasciculation or atrophy.
☛ Motor examination
❖ Inspection
▪ The limbs are centrally positioned, no inward or outward rotation
▪ Comparable muscle bulk between the left and the right side of both upper and lower
extremities.
▪ There is no spontaneous as well as induced fasciculation.
❖ Palpation
➢ Tone and power
TONE POWER
Upper Lower Upper Lower
Right Normo-tonic Normo-tonic 5/5 5/5
Left Normo-tonic Normo-tonic 5/5 5/5
➢ Reflexes
▪ Superficial
o Abdominal reflex is present both in upper and lower quadrants.
o Corneal reflex is intact in both eyes.
o Plantar reflex is down going on both sides.
▪ DTR
Biceps Triceps Brachioradialis Patellar Ankle
Right ++ ++ ++ ++ ++
Left ++ ++ ++ ++ ++
☛ Sensory examination
Primary sensory exam
➔ S/he identifies light touch and pin prick over the extremities and trunk.
➔ S/he is able to recognize different movements of the toes with his eyes
closed. (Position sense)
➔ Vibration sense was not assessed due to lack of Tuning Fork.
Cortical sensory exam
➔ S/he appreciates the form of a key by means of only touch (Stereognosis)
➔ S/he recognizes writings of different numbers on his palm (Graphesthesia)
➔ S/he is able to differentiate 2 pin pricks up to 4 mm apart over the finger tips (2 pt
discrimination).
☛ Coordination
❖ Finger to nose, heal to shin and rapid alternating movement of the arm were done without
any abnormalities.
☛ Meningeal irritation signs
❖ No neck stiffness.
❖ Kernig's Sign is negative.
❖ Brudzinski's Sign is negative
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Chapter 1; Physical examination
1.4.2 Paraplegia/paresis
Refer long case of nitsbin (click here → Chapter 7; Paraplegia
(ከወገብ በታች ሽባነት))
1.4.3 Monoplegia/paresis
1.4.4 Quadriplegia/paresis
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Chapter 1; Physical examination
1.4.5 Coma
DDX IX Mgt
principle
Symmetrical, Symmetrical, Asymmetrical, structural Screening ABCs:
nonstructural structural laboratories ☛ Secure IV line
Metabolic Supratentorial Supratentorial (CBC, RBS, ☛ Intubate if
☛ Hypoglycemia ☛ Sagittal sinus ☛ SDH electrolytes, GCS ≤8
☛ DKA thrombosis ☛ Bilateral ICH BUN, creatinine, ☛ Stabilize C
☛ Lactic acidosis ☛ SAH ☛ Subdural PT, PTT, ABG, Spine
☛ Hyperglycemic ☛ Trauma- empyema LFTs, drug ☛ Supplement
nonketotic contusion, ☛ Thrombophlebitis screen) O2
coma concussion ☛ Unilateral ECG ☛ Blood
☛ Hepatic ☛ Bilateral hemispheric Head CT scan pressure
encephalopathy internal carotid mass (tumor, → prioritize support as
☛ Uremia occlusion abscess, bleed) emergent if focal needed
☛ Bilateral with herniation neurologic signs, Glucose 50
☛ Hypertensive
anterior ☛ Cerebral papilledema, percent IV 50
encephalopathy
cerebral artery vasculitis fever mL (after
☛ Wernicke
occlusion LP → prioritize blood drawn,
encephalopathy ☛ Cerebral abscess
☛ Thalamic emergent after before results
☛ Dialysis ☛ TTP
hemorrhage CT scan if fever, back)
encephalopathy ☛ DIC
elevated WBC, Consider
☛ Hypoxia ☛ Hydrocephalus ☛ Multiple sclerosis meningismus; empiric
☛ Hypercapnia Infratentorial ☛ Acute otherwise do treatments:
☛ Hyper/hypother ☛ Midline disseminated according to ☛ For possible
mia brainstem encephalomyelitis
☛ Hypernatremia tumor
☛ Basilar
occlusion
level of suspicion
for diagnosis or 741
infection →
Ceftriaxone
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Chapter 1; Physical examination
1.5 HEENT
1.5.1 physical Examination findings
1.5.2 Icteric sclera
The differential diagnosis for yellowing of the skin is limited. It includes:
Pale conjunctiva
1.6 LGS
1.6.1 physical Examination findings
1.6.2 LAP
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Chapter 2; common medical procedures and result analysis
Positioning
✓ Positioning depends on what is required from LP
✓ To increase yield use sitting posture
✓ For treatment purpose use sitting posture
✓ To reduce post LP headache, use fetal posture
✓ To measure CSF pressure, use fetal posture
L3-L4, L4-L5, and L5-S1 interspaces are appropriate for needle puncture. These
interspaces can be identified via palpation of bony landmarks
Procedure
Cleanse skin with povidone iodine from puncture site radially out to 10cm to allow to
dry
Drape below patient and around site with fenestrated drape
Anesthetize with lidocaine if topical not used by
✓ Intradermally raising a wheal at needle insertion site
✓ Advance needle through wheal to desired interspace → careful not to inject into
a blood vessel or spinal canal
Insert spinal needle with stylet with bevel up to keep cutting edge parallel with nerve
and ligament fibers
LP: Resulting in a “pop” with sudden decrease in resistance when the dura is pierced
and the subarachnoid space is entered
if instead CSF does not flow. The stylet should be replaced, the needle advanced or
withdrawn incrementally, with frequent removal of the stylet Until CSF is obtained or
bone encountered.
When CSF flows
☛ Take adequate sample: If needed 20 up to 30 ml
☛ Observe the appearance: Color/Consistency/Pressure
☛ If contaminated with blood: Wait until CSF clears
When CSF flows, attach a monometer to obtain pressure if desired. Pressure can only
be accurately measured in lateral decubitus position and in relaxed patient
Attach manometer with a 3-way stopcock when free flow of CSF is obtained
Read column when highest level is achieved and respiratory variation noted
The recommended studies include (this order can be changed); collect 1ml of CSF in
each of vials
✓ Tube # 1; gram stain, culture and sensitivity
✓ Tube # 2; Glucose and protein
✓ Tube # 3; cell count and differentials
✓ Tube # 4; any special studies you require (fungal/viral/chemical studies)
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https://youtu.be/YmzDT-LXQPY
Opening pressure
✓ Normal value is 70 - 180 mmH2O → see tables below
✓ Measured with manometer
✓ In our set up since we don’t have manometer, we use flow rate to estimate
opening pressure
☛ Dropping → normal opening pressure
☛ Continues flow (i.e. stream like flow) → increased opening pressure
which may suggest increased ICP and give special attention for this
patient.
Appearance and CSF pressure
☛ Turbidity
✓ Crystal clear → normal
✓ Cloudy → bacterial, TB, fungal
✓ Clear → viral
☛ Color → normal CSF has crystal color
✓ Bloody (hemorrhagic) → SAH (usually xanthochromic), traumatic
✓ If CSF is bloody, how do you differentiate traumatic CSF from SAH
Traumatic CSF SAH
Blood stopes with in short Continuous blood comes
period of time and you may throughout the procedure
see clear CSF Blood in CSF doesn’t clot
Blood in CSF clots after after centrifugation
centrifugation Xanthochromic in color (due
Bright red blood to hemolysis → bilirubin →
yellow in color)
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☛ Viscosity
Microscopic and Microbiologic tests
☛ Cell count with differential
☛ CSF organisms (gram stain)
✓ CSF gram stain has 60-90% sensitivity
☛ CSF Cytology
☛ CSF culture → has 70-80% sensitivity
Chemical analysis
☛ Glucose
☛ Protein
☛ Lactate and LDH
☛ PH
☛ Glutamine and acid-base tests
Specific tests
In our set up, we usually collect 2-3 ml of CSF with one bottle
(rather than using 4 bottles as a standard) and we request with
different request papers like below
✓ Request # 1; cell count with differentials
✓ Request # 2; Gram stain and AFB
✓ Request # 3; Glucose and protein
✓ Request # 4; culture
You may keep the sample for other available investigations
based on indication like
✓ Gene expert → TB meningitis
✓ Cytology → carcinomatous meningitis
✓ Indian ink → cryptococcal meningitis especially in RVI Pt
➔ Glucose < 20
➔ Total protein > 200
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Equipment’s
✓ Sterile gloves, mask, and gown.
✓ Iodinated skin preparation with sterile sponges.
✓ Sterile towels.
✓ Local anaesthetic (1% lidocaine without epinephrine).
✓ 5-mL syringe with 25-gauge needle.
✓ 18-gauge 2-inch needle.
✓ Collection basin.
✓ 3-way stopcock.
✓ 20-60ml syringe.
✓ For therapeutic tap, in our setup, we were using IV set with needle tip and locally
available Highland/or empty RL bag as a container for fluid collection
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Patient preparation
➢ Patient should have intravenous access.
➢ Oxygen should be available.
➢ Monitor oxygen saturation with pulse oximetry.
➢ Younger patients may need sedation for procedure.
➢ Explain procedure before and during procedure.
Patient positioning
Pleural effusion.
☛ Sitting upright with arms supported on table in front of patient
☛ Lying in lateral decubitus position with effusion side down.
Pneumothorax: Supine with head of bed up 30 degrees.
procedures
Locate Effusion
✓ Chest radiograph.
✓ Manual percussion to find onset of dullness.
☛ One to two interspaces below the level at which breath sounds decrease or
disappear on auscultation, percussion becomes dull, and fremitus
disappears.
☛ Above the ninth rib, to avoid subdiaphragmatic puncture.
☛ Midway between the spine and the posterior axillary line, because the ribs
are easily palpated in this location.
✓ Effusion is usually accessible via the sixth or seventh intercostal space just distal
to the scapular tip in the mid scapular line or posterior axillary line
✓ If pneumothorax is present, it is usually accessible via the second intercostal space
anterior
Ultra-sonogram marked location.
✓ Mark location of effusion with the patient in the same position as necessary for
procedure.
✓ If possible, do not move patient after marking the location because the fluid may
shift.
Use a 25-gauge needle and 5-ml syringe to infiltrate the skin and make a wheal
under the skin.
Change needle to 18 gauge with 2-inch needle.
Going over top of sixth rib, infiltrate through wheal, over top of rib to anesthetize
the periosteum, and into pleural space.
Be sure to aspirate first, and know when you are in the pleural space.
The parietal pleura needs to be anesthetized. but, to avoid a puncture of the lung,
do not advance the needle further.
When in the pleural space, a ‘pop’ may be felt and fluid or air will enter syringe.
1. Gross appearance
✓ Pale yellow (Straw) → transudative effusion, some exudates
✓ Milky → chylothorax (thrombus in left subclavian vein, malignancy, trauma,
TB)
✓ Bloody → haemothorax (malignancy, trauma, TB, pulmonary infarction),
traumatic procedure
✓ Frank pus → empyema (TB, pulmonary infection, trauma, oesophageal
rupture)
✓ Turbid → inflammatory exudate
7. Others
☛ PH
☛ Cytology → sensitivity of approximately 60 % for the diagnosis of malignant
effusion (sensitivity in lung cancer; 78 % for adenocarcinoma, 53 % for small cell
carcinoma, and 25 % for squamous cell carcinomas)
☛ LDH
☛ Amylase → increase in acute/chronic pancreatitis (one cause of exudative
effusion)
☛ ADA (Adenosine deaminase)
o may be helpful to distinguish between malignant and tuberculous
pleurisy when an exudative effusion is lymphocytic, but initial cytology
and smear and culture for tuberculosis are negative
o > 35 to 50 U/L in tuberculous pleural effusions (The most common
o
diagnostic threshold used to establish tuberculous pleural effusions is a
value >40 U/L)
< 40 U/L in 94 % of malignant pleural effusions.
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N.B
Pleural tap should be done
☛ over the area of dullness
☛ above the rib to avoid neurovascular injury
don’t go below 9th ICS to avoid visceral injury
estimated volume of fluid to be drawn
☛ for culture → 20 ml
☛ for cytology → 20 ml
☛ for biochemical and microbiology (protein, glucose, cell count, gram stain
and AFB, LDH, PH) → 10 ml
Lights Criteria
Characteristics Transudative Exudative
1. Pleural fluid protein / < 0.5 > 0.5
serum protein ratio
2. Pleural fluid LDH / < 0.6 > 0.6
serum LDH ratio
3. Pleural fluid LDH < 2/3rd the upper limit of > 2/3rd the upper limit of
the normal laboratory the normal laboratory
serum LDH level serum LDH level
At least One of the three criteria should qualify to diagnose exudative effusion
other Criteria
Criteria Transudative Exudative
1. Cell count < 100 x106 / L > 500 x106 / L
2. Differential cell Lymphocyte Different
3. Pleural fluid LDH < 0.45 times the upper > 0.45 times the upper
normal limit serum LDH normal limit serum LDH
4. LDH < 200 IU/ L > 200 IU / L
5. Pleural fluid cholesterol < 45 mg/dL > 45 mg/dL
6. Pleural fluid protein < 3 g/dL (<30g/L) > 3 g/dL (>30g/L)
7. Cause non-inflammatory inflammatory, tumour
8. Appearance light yellow yellow, purulent
9. pleural fluid pH 7.40 to 7.55 7.30 to 7.45
10. Specific gravity <1.018 >1.018
NB: - CHF patients with acute diuresis can have pleural fluid protein > 3g/dl;
However, such patients have a pleural fluid to serum albumin gradient > 1.2 g/Dl
Glucose
Glucose < 30 mg/dl
☛ Empyema
☛ Rheumatoid disorders
Glucose between 30 - 50 mg/dl
☛ SLE
☛ Malignancy
☛ TB
Lymphocytes
Lymphocytes 85% - 95 %
▪ TB
▪ Lymphoma
▪ Chylothorax
▪ Sarcoidosis
▪ Rheumatoid disorders
Lymphocytes between 50 - 70%
▪ Malignancy
Eosinophilia — defined by pleural fluid eosinophils representing >10 % of the total
nucleated cells
o Pneumothorax, Hemothorax, Pulmonary infarction
o Parasitic disease
o Fungal infection (coccidioidomycosis, cryptococcosis, histoplasmosis)
o Malignancy (carcinoma, lymphoma, myeloma)
o Tuberculous pleurisy
o Parapneumonic effusions
o Chronic eosinophilic pneumonia
o Drugs
o Benign asbestos pleural effusion
Mesothelial cells
▪ prominent in transudative pleural effusions, and are variable in exudative
effusions.
▪ in exudative effusion; tuberculosis is unlikely if there are > 5% mesothelial cells
ADA
▪ > 35 - 50 U/L (especially when lymphocytes > 75%) Supports TB
▪ < 40 U/L, suggests malignancy, rarely caused by TB
Amylase: pleural/serum Amylase ratio > 1.0
▪ Acute/chronic pancreatitis
▪ Oesophageal rupture
▪ Malignancy
Equipment
☛ Alcohol swabs, povidone-iodine.
☛ 23-gauge and 21-gauge needles or angiocatheters with syringes.
☛ Local anesthetic (e.g. 1% lidocaine).
☛ Large bore needle with plastic catheter.
☛ Sterile containers for fluid collection.
☛ Appropriate culture tubes for microorganisms.
☛ For therapeutic tap, in our setup, we were using IV set with needle tip and locally
available Highland/or empty RL bag as a container for fluid collection
Procedure
☛ The puncture site should be shaved, if necessary, and cleansed with povidone-
iodine.
☛ Inject local anaesthetic, infiltrating the skin first and then penetrating into deeper
layers.
☛ A small 3-mm incision can be made with a scalpel to help insert the needle. Using
Z-track technique (to prevent fluid leakage), insert the tap needle 1-2 inches into
the abdomen
☛ Obtain a sample of fluid or withdraw as much fluid as necessary with a syringe (in
case of therapeutic lavage)
☛ Remove the needle and apply a pressure dressing to the puncture site.
☛ If an incision was made, it may be closed using 1 or 2 stitches.
☛ The ascitic fluid removed may be replaced 1:1 with 5% albumin IV.
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Bacterial peritonitis
SBP Secondary peritonitis due to rupture of abdominal
viscus
✓ WBC > 500/mm3 ✓ WBC > 10,000/mm3 (significant leucocytosis)
(neutrophil ≥ 50%) ✓ Multiple organisms identified
✓ Mono microbial ✓ Increased LDH level
✓ Glucose < 50
✓ Protein significantly decreased
✓ PH
✓ With obvious cause of 2ry peritonitis like
intestinal perforation
✓ Failure to improve after standard treatment
with in 48 hr’s
✓ Lymphocyte dominant
☛ TB peritonitis
☛ Abdominal carcinomatosis
c) Glucose and protein
d) Gram stain and AFB
e) Culture → inoculation at bedside increase sensitivity to 85% to identify infection
f) SAAG (serum ascitic albumin gradient)
☛ SAAG = serum albumin level - ascitic albumin level
☛ SAAG > 1.1 g/dl → Cause of ascites is most likely Portal HTN (e.g.
cirrhosis, chronic hepatic congestion from CHF)
☛ SAAG < 1.1 g/dl → Non-Portal HTN (e.g. TB peritonitis, Nephrotic sxx,
peritoneal carcinomatosis, hypalbuminemia)
☛ 95% accurate but can’t r/o malignancy
☛ Ascitic fluid protein < 1g/dl predispose to SBP
g) Other
✓ RBC → > 50,000 RBC/µl suggest haemorrhagic ascites
✓ PH → PH < 7 suggest bacterial infection
✓ Cytology → for malignancy
✓ Amylase → increased level in ascites 2ry to chronic pancreatitis
In our set up, we usually collect ascitic fluid with one bottle and we request with
different request papers like below
✓ Request # 1; cell count with differentials
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2.4 BM aspiration
Equipment
Site Preparation
❖ 10% povidone-iodine.
❖ Alcohol preparation pads or swabs.
❖ Sterile gloves, gown, and drape
❖ Spinal and subcutaneous needles, 20 to 26 gauge.
❖ 1% lidocaine hydrochloride, injection.
❖ 8.4% sodium bicarbonate, injection, USP
Marrow Aspiration
✓ Bone marrow aspiration needles
Biopsy aspiration needles recommended
sizes
Regular/Adults 4-inch, 11-gauge
Adults: 4-inch, 8-gauge
Orthopedic: 6-inch, 10/11-
gauge
Pediatric: 3½-inch, 13-gauge
Infant: 2-inch, 13-gauge
✓
✓
Sterile syringes, 10 to 20 mL
clean microscope slides
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Choice of site
Posterior superior iliac spine
Anterior iliac crest in obese patients
1st part of body of manubrium of sternum
Procedure
Place the patient in a right or left lateral decubitus position with the back
comfortably
flexed and the top knee drawn toward the chest.
Locate the posterior iliac spine and mark it with ink or thumb nail pressure.
Using sterile technique, prepare the skin with anti-septics and drape.
Using a sterile syringe, infiltrate the marked area with local anesthesia especially
the periosteum.
Make a 3-mm skin incision with a scalpel blade over the marked area
Hold the needle with the proximal end between the palm and the index finger
against the shaft near the tip.
With the stylet locked in place, introduce the needle through the incision pointing
toward the anterior superior iliac spine and bring it into contact with the posterior
iliac spine.
Using gentle but firm pressure, advance the needle to bore through the iliac spine.
Rotate the needle in an alternating clock-wise and counter-clockwise motion.
Entrance into the marrow cavity is generally detected by decreased resistance.
Remove the stylet, and check for marrow material. If not present, proceed to bore
until marrow is found in the tips of the stylet.
With a syringe locked into the proximal portion, apply a negative pressure.
This first pull contains the marrow particles or spicules that should be used for
preparing initial smears.
A heparinized, larger syringe (30 mL) may be used to obtain additional marrow for
cytogenetic analysis, flow cytometry, and other studies.
Bone marrow aspiration - Click on the link below and watch the video
https://youtu.be/svTQ-zJHY9M
Prerequisite
❖ The two important prerequisites for the safety of the procedure are;
• Rapidity so that the needle remains within the spleen for less than l second
and
• precision so that the entry and exit axes of the aspirating needle are
identical to avoid tearing the splenic capsule.
❖ splenic aspiration should be performed in a hospital setting where blood transfusion
is possible because the procedure is associated with a risk of fatal internal
bleeding.
❖ This procedure also requires considerable technical expertise for making the
aspiration and facilities for nursing surveillance, blood transfusion, and surgery.
Procedure
i. Clean three glass slides and label them. If culture medium is required, label in the same
way as the slides. Attach a 11/4-inch × 21-gauge (32 × 0.8-mm) needle to a 5ml syringe.
ii. Inform the patient about the procedure. Check all clinical and biological contraindications
again. Palpate the spleen and outline its margins on the patient’s abdomen with a pen.
For safety, the spleen should be palpable at least 3 cm below the costal margin on
expiration. Use an alcohol swab to clean the skin at the site of aspiration and allow the
skin to dry.
iii. With the 21-gauge (0.8 mm) needle attached to the 5ml syringe, just penetrate the
skin, midway between the edges of the spleen, 2–4cm below the costal margin. Aim
the needle cranially at an angle of 45° to the abdominal wall. The actual aspiration is
done as follows:
❖ pull the syringe plunger back to approximately the 1ml mark to apply suction and
with a quick in-and-out movement push the needle into the spleen to the full
needle depth and then withdraw it completely, maintain suction throughout.
iv. For young, restless children, have two assistants hold the child (arms folded across the
chest, with shirt raised to obstruct the line of vision, and pelvis held firmly). Carry out
the aspiration as a single-stage procedure using the same landmarks, angles and suction
as in
step 3 – all in one quick motion. The insertion should be timed with the patient’s
breathing so that the diaphragm is not moving. This should be done during fixed
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expiration if the child is crying. Only a minute amount of splenic material is obtained for
culture and smear.
v. If culture is available: slowly pull the plunger back to the 2–3ml mark and, by using
sterile techniques, insert the needle into a tube containing culture medium and briskly
push the plunger into the barrel to expel the contents of the needle onto the side walls
of the tube. If necessary, repeat once or twice until splenic material is visible in the
tube. Replace the cap on the tube and invert to wash splenic material on the side of
the tube. Repeat the procedure for the second tube of culture medium. Sterile
techniques are essential throughout.
vi. Expel material gently onto glass slides, holding the needle tip on the surface of the
slide. Immediately spread evenly with the needle, using a linear (not circular) motion.
The smear should be slightly thinner than a thick blood film for malaria. Remove the
needle and use the end of it to obtain additional material from the tip of the syringe and
spread it on slides. Further material found on the end of the plunger may be dabbed
directly onto a slide and spread. Allow the slides to dry.
vii. Write the time of aspiration on the patient ‘s chart with the instructions: “Record pulse
and blood pressure every half hour for 4 hours, then every hour for 6 hours. Patient
must remain in bed for 12 hours!” Ensure that the patient understands the instructions.
Enter the procedure in the notes and sign.
viii. Take the slides (and medium) to the laboratory for preparation and microscopic
examination.
Splenic aspiration - Click on the link below and watch the video
https://youtu.be/6egWxe4VFT4
2.6 LN aspiration
Materials required:
❖ Sterile needle (21G)
❖ Syringe (10ml)
❖ Clean glass slide
❖ Iodine (disinfectant) or sterile cotton swabs
❖ Cotton wool
Procedure
❖ Allow the patient to lie comfortably. Prepare the syringe by pulling the piston
back as far as possible.
❖ Feel and locate a swollen gland.
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❖ Disinfect the chosen site with swollen glands using a piece of cotton wool soaked
in iodine or another suitable disinfectant.
❖ Take the gland between the thumb and index finger of the left hand. Hold it
steady and make it at the same time standing out.
❖ Introduce the needle with a right angle into the center of the gland in two stages:
• First pierce the skin
• Second penetrate the gland
❖ With your left hand, gently knead the gland. With your right hand, revolve the
needle in both directions. The glandular fluid will ooze into the needle.
❖ Withdraw the needle in one rapid movement while holding the thumb over
the hub. Then apply a swab dipped in iodine to the point of entry.
❖ Attach the syringe (piston pulled back) to the needle. Place the needle on the
slide. Push the piston gently down the barrel to discharge the glandular fluid
contained in the needle onto the slide.
❖ Make a thin film using the fluid on the slide. The fluid can be discharged in more
than one slide.
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3.1 Shock
✓ Shock is the clinical condition of organ dysfunction resulting from an imbalance
between cellular oxygen supply and demand.
✓ There are a multitude of heterogeneous disease processes that can lead to
shock.
✓ The organ dysfunction seen in early shock is reversible with restoration of
adequate oxygen supply.
✓ Left untreated, shock transitions from this reversible phase to an irreversible
phase and death from multisystem organ dysfunction (MSOF).
Classification of shock
Major shock types and specific disease processes that can result in that
physiologic derangement.
Hypovolemic shock
❖ Hemorrhagic shock
❖ Non hemorrhagic
▪ GI losses
▪ Burns
▪ Polyuria
• DKA
• Diabetes insipidus
Cardiogenic shock
❖ Myocardial infarction
❖ Myocarditis
❖ Arrhythmia
❖ Valvular
▪ Severe aortic valve insufficiency
▪ Severe mitral valve insufficiency
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Obstructive shock
❖ Tension pneumothorax
❖ Cardiac tamponade
❖ Restrictive pericarditis
❖ Pulmonary embolism
❖ Aortic dissection
Distributive shock
❖ septic shock.
❖ Anaphylactic shock
❖ neurogenic shock
❖ Pancreatitis
❖ Severe burns
❖ Endocrine shock
❖ Adrenal crisis
Mixed Shock
The types of shock outlined in this classification scheme are not mutually
exclusive; not uncommonly, a patient will present with more than one type of
shock.
The initial physiologic disturbance leading to reduced perfusion and cellular
hypoxia in sepsis is distributive shock. In this setting, a sepsis-induced
cardiomyopathy can develop, which reduces myocardial contractility, thus
producing a cardiogenic component to what now would be described as a
mixed type of shock.
Undifferentiated Shock
Stages of shock
✓ Cold extremities
✓ Fast and weak pulse, or absent pulse
✓ Prolonged capillary refill time > 3 seconds (clinically 3 second is
approximated with counting ‘’1001, 1002, 1003 = 3sec’’)
History
Physical Examination
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questions.
o Is shock present (either in compensated stage prior to overt evidence of
organ dysfunction or decompensated indicated by the presence of new
organ dysfunction)?
o Secondly, what type of shock is present (distributive, cardiogenic,
hypovolemic, or obstructive)?
The physical examination findings present during the compensated
phase of shock tend to be nonspecific. These include;
o Tachycardia → with the body’s attempt to increase CO
▪ Fast and weak pulse, or in severe cases, absent pulse
o Tachypnea → to compensate for the developing metabolic acidosis.
Hypotension (MAP of <60 mmHg or SBP < 90 mmHg)
o but this finding is not always present.
o Many patients may have underlying conditions that
cause longstanding low blood pressure without any evidence of organ
dysfunction.
o Alternatively, patients with underlying hypertension may
develop organ dysfunction at higher blood pressures.
The CNS, kidney, and skin examination are “windows” through which we can
identify organ dysfunction.
o Confusion and encephalopathy → due to decreased oxygen delivery to
the brain is manifest as
▪ In the early stage of shock, the body will redirect blood flow to
the CNS to maintain adequate perfusion. In the patient with
shock and altered mental status, all the usual compensatory
mechanisms have been outstripped by the magnitude of shock
pathophysiology.
▪ New encephalopathy represents decompensated shock.
o In patients with normal baseline renal function, oliguria
(<0.5 mL/kg per h) may indicate shock.
▪ a urinary catheter should be placed for accurate hourly
assessment of urine output
o Finally, decreased capillary refill and cold and clammy skin are signs of
hypoperfusion and shock.
Raised JVP and peripheral edema can provide insight into right-sided cardiac
pressures overload.
Pulmonary auscultation can identify signs of left-sided cardiac dysfunction.
The physical examination may be used to differentiate shock with high CO
(distributive)
from that with low CO (cardiogenic shock, hypovolemic shock, and
obstructive shock).
findings suggestive of high output shock (distributive) include;
o warm peripheral extremities
o brisk capillary refill (<2 s), and
o bounding pulses.
Findings suggestive of low CO shock (cardiogenic shock, hypovolemic shock,
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o cool extremities
o delayed poor capillary refill, or
o weak pulses
The JVP may be elevated cardiogenic shock (with right-sided failure) and
reduced (JVP <8 cm) in hypovolemic shock.
The presence of cardiogenic shock would be further supported by an S3
gallop.
Notice; patients with chronic heart failure do not present with the classical
findings of acute heart failure. At times, the physical examination may identify
the specific etiology of shock. This is particularly helpful in the patient who
cannot provide a detailed history.
Identify the site of untreated infection (cellulitis, abscess, infected pressure
injury, or focal) as a source of septic shock.
a brady- or tachyarrhythmia may be leading cause to development of shock.
large ecchymosis may indicate a significant bleed related to trauma or
spontaneous retroperitoneal bleeding.
The rectal examination may reveal GI hemorrhage.
Pulsus paradox and elevated JVP may suggest the presence of cardiac
tamponade.
Patients with a tension pneumothorax may have;
o a paucity of breath sounds over the affected side
o deviation of the trachea away from the affected
side, or
o subcutaneous emphysema.
Management of shock
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Before considering hypovolemic shock rule out cardiogenic shock since the
fluid management in cardiogenic shock is challenging with 250ml of NS over
30 min only. If there is misdiagnosis of Cardiogenic shock as hypovolemic
shock, iatrogenic fluid overload (like pulmonary edema) will develop during
infusion of fluid and worsen the condition.
If cardiogenic shock is ruled out, search the cause of hypovolemia (is that
haemorrhagic or non-haemorrhagic)
Infusion of fluid (NS or RL), 1-2 litres fast for adults and 20 mL/kg for
paediatric patients.;
reassess the patient for adequacy of treatment by Following the BP, PR, UoP
& mental status
✓ If responsive, the fluids are slowed to maintenance rates
✓ If not responsive repeat 1x in adult (total 2x) & 2x in paediatrics (total
3x) with maximum tolerated dose being 60 - 80 ml/kg with in the first
1 - 2 hr
✓ If not responsive with the above fluid give blood
✓ If still not responsive consider septic shock
✓ if needed open double IV line.
If due to hemorrhage, apply transfusion of packed Red Blood Cells (RBC) or
whole blood 20ml/kg over 4 hrs, repeat as needed until hemoglobin level
reaches 10gm/dl and the vital signs are corrected.
Better to follow UOP with catheterization
Clinical features
o Most patients initially are;
▪ Dyspneic
▪ appear pale
▪ cold extremity
▪ poor capillary refill
▪ apprehensive and diaphoretic
▪ mental status may be altered.
o The pulse is typically weak and rapid or occasionally severe bradycardia
due to high-grade heart block may be present.
o BP is typically reduced (<90 mmHg; or catecholamines required to maintain
blood pressure >90 mmHg), but occasionally BP may be maintained by
very high systemic vascular resistance.
o Tachypnea and jugular venous distention may be present.
o Typically, there is a weak apical pulse and soft S1, and S3 gallop may be
audible.
o Acute, severe MR and VSR usually are associated with characteristic
systolic murmurs.
o Crackles are audible in most patients with LV failure.
o Oliguria/anuria is common.
Diagnosis
For these unstable patients, supportive therapy must be initiated simultaneously
with diagnostic evaluation.
A focused history and physical examination should be performed along
with ECG, chest X-ray, and blood specimens to the laboratory
Initial Echo is an invaluable tool to elucidate the underlying cause of CS.
In addition to the usual treatment of acute MI, initial therapy is aimed at;
o maintaining adequate systemic and coronary perfusion by raising the
blood pressure with vasopressors and adjusting volume status to a
level that ensures optimum LV filling pressure
o Generally adequate perfusion occurs with a mean arterial BP of
60 - 65 mmHg or a systolic BP ~90 mmHg.
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Administer O2 if SaO2<90%
o Hypoxemia and acidosis need to be corrected; up to 90% of patients
require ventilatory support, decreasing the stress from increased work
of breathing
o Often CS patients require early mechanical ventilation (~80%) for
management of acute hypoxemia, increased work of breathing, and
hemodynamic instability;
Administer NS 250ml over 30 min and see the change in BP, UOP and
worsening of HF.
✓ If BP improves then consider hypovolemic shock and continue slowly
replacing the fluid with NS.
✓ If there is no response to fluid or worsening heart failure, use either of the
following vasopressor therapies:
First line
▪ Norepinephrine (noradrenaline)
o 0.2 µg/kg/min escalated to 1µg/kg/min by doubling the
dose q20 min until BP> 90/60 mmHg (or 2 to 4 μg/min
and titrated upward based on blood pressure).
o Maintain the dose that maintained the BP> 90/60 mmHg
for 6hrs, then you will deescalate as the same as the
escalation (look at adrenaline drip preparation below).
o We recommend to use the above dose; in another
reference you may see the dose as: 0.5 - 1 mcg/minute
and titrate to desired response; 8-30 mcg/minute is usual
range
Alternative
Dopamine
▪
o 5 - 20 µg/kg/min IV diluted with dextrose 5% in Water
(D5W), or in sodium chloride solution 0.9%(NS)
o infusion at 5µg/kg/min and escalate up to 40ug/kg/min by
doubling the dose q20 min until BP> 90/60 mmHg.
o Maintain the dose that maintained the BP> 90/60 mmHg
for 6hrs, then you will deescalate as the same as the
escalation (look at dopamine drip preparation below).
▪ Dobutamine
o Start with 2.5 μg/kg per min to be titrated up to
40µg/kg/min IV diluted in dextrose 5%.
o Never initiate Dobutamine alone in a patient with
cardiogenic shock and Systolic BP< 70
▪ Adrenaline infusion:
o 0.01-0.5 µg /kg/minute ( 7-35 µg /minute i n a 70 kg
patient); titrate to desired response
✓ Maintain the dose of vasopressor that maintained the BP> 90/60 mmHg
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for 6hrs (what is the reason behind maintaining for 6hr’s?), then you will
taper the dose of vasopressor in the same way as it was escalated if
BP is maintained. (look at dopamine and adrenaline drip preparation
below).
✓ If myocardial infarction suspected aspirin should be loaded and
immediate reperfusion.
✓ If patient has concomitant pulmonary edema resulting in hypoxia
▪ Continuous infusion of Lasix (frusemide) started at 5-10 mg/hr should
be started through another IV line (escalate dose based on Blood
Pressure).
✓ More frequent follow up of V/S, SO2 and UOP q 20-30min until patient
stabilize
✓ Further follow up and management is similar to other heart failure
syndromes.
✓ Moderate glucose control (≤180 mg/dL) should be a goal and hypoglycemia
must be avoided.
✓ Negative ionotropic agents should be discontinued.
✓ Recurrent ventricular tachycardia or rapid atrial fibrillation may require
immediate treatment
✓ Bradyarrhythmia’s may require transvenous pacing.
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Since weight measurement in shock pt is difficult, you may take approximated weight (let’s say 50kg weight for this
calculation, this will make 5 µg/kg/min =250 µg)
✓ Let’s say we add 4 ampoules (800,000 µg) of dopamine in 1000ml of NS or D5W. the question will be in how many
ml of NS and at what rate (drop) we get 250 µg
✓ 1000ml = 800,000 µg
?? = 250 µg
This will give us 6 drops (i.e. 6 drops will contain 5 µg/kg/min of dopamine for this particular patient)
Source → https://t.me/Debolteam
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Table*; Calculated dose and drop per minute of dopamine based on the
above calculation
Weight in Kg Dopamine dose (µg/min)
3 5 10 15 20 30 40
Drop/minute of dopamine
50 3 drops 5 drops 10 drops 15 drops 20 drops 30 drops 40 drops
60 3.5 drops 6 drops 12 drops 18 drops 24 drops 36 drops 48 drops
70 4.2 drops 7 drops 14 drops 21 drops 28 drops 42 drops 56 drops
80 4.8 drops 8 drops 16 drops 24 drops 32 drops 48 drops 64 drops
90 5.4 drops 9 drops 18 drops 27 drops 36 drops 54 drops 72 drops
100 6 drops 10 drops 20 drops 30 drops 40 drops 60 drops 80 drops
*Prepared by; Dr. Genet Kifle (MD, Emergency and critical care consultant)
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Let’s take 50kg weight for this calculation, this will make 0.2 µg/kg/min =10 µg
✓ Let’s say we add 4 ampoules (4mg = 4,000 µg) of adrenaline in 250ml of NS or D5W. the question will be
in how many ml of NS and at what rate (drop) we get 10 µg
✓ 250ml = 4,000 µg
?? = 10 µg
This will give us ≅12 drops (i.e. 12 drops will contain 0.2 µg/kg/min of adrenaline for this particular
patient)
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Septic shock
Principles of management
o IV Fluids
o broad spectrum antibiotics
o vasopressor therapy.
o Steroids
Adequate organ system perfusion with IV fluids (large volume of IV fluids
are required in septic shock patients).
✓ Initial fluid bolus of 20 mL/kg of RL or NS.
✓ Repeat 2 boluses of 20ml/kg with target of SBP >90mmhg, and
MAP>60mmhg.
✓ If goal not achieved, start vasopressors.
✓ In general, most patients with septic shock are expected to take
around 5-6 liter of IV fluids within 24 hours.
Start Empiric therapy with broad spectrum antibiotics in septic shock patients
as soon as possible at least within 01 hour of the clinical suspicion of septic
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Alternatives
Adrenal crisis
Refer sepsis under short case of nitsibin for more (click here → Sepsis)
3.2 Hypoglycaemia
→ Refer under long case of DM (click here → Hypoglycaemia)
3.3 DKA
→ Refer under long case of DM (click here → DKA and HHS)
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A seizure (from the Latin sacire, “to take possession of”) is a paroxysmal
event due to abnormal excessive or synchronous neuronal activity in the brain.
Depending on the distribution of discharges, this abnormal brain activity can
have various manifestations, ranging from dramatic convulsive activity to
experiential phenomena not readily discernible by an observer.
The meaning of the term seizure needs to be carefully distinguished from that
of epilepsy.
Epilepsy describes a condition in which a person has recurrent seizures (two
or more unprovoked seizures) due to a chronic, underlying process.
This definition implies that a person with a single seizure, or recurrent seizures
due to correctable or avoidable circumstances, does not necessarily have
epilepsy.
Epilepsy refers to a clinical phenomenon rather than a single disease entity,
because there are many forms and causes of epilepsy. However, among the
many causes of epilepsy there are various epilepsy syndromes in which the
clinical and pathologic characteristics are distinctive and suggest a specific
underlying etiology.
Epilepsy refers to a syndrome of recurrent, idiopathic seizures.
Pseudo seizures are not true seizures but are psychiatric in origin; are often
difficult to distinguish from true seizures without an EEG.
So, Epilepsy considered in one of the following conditions
o At least two unprovoked (or reflex) seizures occurring > 24 hours
apart.
o One unprovoked (or reflex) seizure and a probability of further
seizures similar to the general recurrence risk after two unprovoked
seizures (at least 60%), occurring over the next 10 years.
o A known epilepsy syndrome.
Pre- Ictal
o Events that occur Immediately before the seizure, and include Aura and
Prodromal symptoms/signs
Aura
o Some patients describe odd, internal feelings such as fear, a sense of
impending change, detachment, depersonalization, or illusions that
objects are growing smaller (micropsia) or larger (macropsia).
▪ These subjective, “internal” events that are not directly observable
by someone else are referred to as auras
Seizure (Ictal) semiology
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o It is the sign and symptoms observed just before, during and immediately
after the seizure occurrence.
o Ictal Semiology means features occurring during the attack
▪ Simple: Motor; Sensory; Autonomic; Psychic….
▪ Complex: Motor; Sensory; Autonomic; Psychic….
o Motor semiology: Motor manifestations refer to involvement of the
musculature, which can be positive (increased muscle activity) or
negative (decreased muscle activity)
▪ simple motor refers to the contraction of a muscle or group of
muscles that is usually stereotyped and does not include
multiple phases.
▪ Complex motor activity: Automatism
o Motor semiologies can be tonic, myoclonic or clonic
▪ Tonic activity which means a sustained increase in muscle
contraction lasting up to minutes.
▪ A myoclonic jerk refers to a very brief involuntary contraction
usually lasting less than 100 micro sec.
▪ Clonic activity refers to a regularly repetitive jerking that is
prolonged
Post-Ictal features:
o Features occur after the seizure stops
Epidemiology
The incidence and prevalence of epilepsy increase with age in adulthood and
are highest in patients over 65 years.
The prevalence of epilepsy in older adults is approximately 2 - 5%
The annual incidence of epilepsy rises with each decade over 60 years.
Seizures in older patients are frequently underdiagnosed; hence, the incidence
of epilepsy in older patients may be two to three times higher, with an
incidence six to seven times greater than younger individuals.
Classification of seizures
Determining the type of seizure that has occurred is essential for focusing the
diagnostic approach on particular etiologies, selecting the appropriate therapy,
and providing potentially vital information regarding prognosis.
The International League against Epilepsy (ILAE) Commission on Classification
and Terminology (2005 - 2009) has provided an updated approach to
classification of seizures.
o This system is based on the clinical features of seizures and associated
electroencephalographic findings.
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Focal seizures
Focal seizures arise from a neuronal network either discretely localized within
one cerebral hemisphere or more broadly distributed but still within the
hemisphere.
With the new classification system, the subcategories of “simple focal seizures”
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Focal seizures arising from the temporal or frontal cortex may also cause
alterations in hearing, olfaction, or higher cortical function (psychic symptoms).
This includes;
o the sensation of unusual, intense odors (e.g., burning rubber or kerosene)
or sounds (crude or highly complex sounds)
o an epigastric sensation that rises from the stomach or chest to the head.
Auras.
Focal seizures can spread to involve both cerebral hemispheres and produce a
generalized seizure, usually of the tonic-clonic variety.
This evolution is observed frequently following focal seizures arising from a
focus in the frontal lobe, but may also be associated with focal seizures
occurring elsewhere in the brain.
Often, however, the focal onset is not clinically evident and may be established
only through careful EEG analysis.
Nonetheless, distinguishing between these two entities is extremely important,
because there may be substantial differences in the evaluation and treatment
of epilepsies associated with focal versus generalized seizures.
Generalized seizures
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Generalized seizures are thought to arise at some point in the brain but
immediately and rapidly engage neuronal networks in both cerebral
hemispheres.
Several types of generalized seizures have features that place them in
distinctive categories and facilitate clinical diagnosis.
Atypical absence seizures have features that deviate both clinically and electro
physiologically from typical absence seizures.
For example, the lapse of consciousness is usually of longer duration and less
abrupt in onset and cessation, and the seizure is accompanied by more
obvious motor signs that may include focal or lateralizing features.
The EEG shows a generalized, slow spike-andwave pattern with a frequency of
≤2.5 per second, as well as other abnormal activity.
Atonic Seizures
Myoclonic Seizures
Myoclonus is a sudden and brief muscle contraction that may involve one part
of the body or the entire body.
A normal, common physiologic form of myoclonus is the sudden jerking
movement observed while falling asleep.
Pathologic myoclonus is most commonly seen in association with metabolic
disorders, degenerative CNS diseases, or anoxic brain injury.
Myoclonic seizures usually coexist with other forms of generalized seizures but
are the predominant feature of juvenile myoclonic epilepsy.
Not all seizure types can be designated as focal or generalized, and they
should therefore be labeled as “unclassifiable” until additional evidence allows a
valid classification.
Epileptic spasms are such an example.
These are characterized by a briefly sustained flexion or extension of
predominantly proximal muscles, including truncal muscles.
Epileptic spasms occur predominantly in infants and likely result from
differences in neuronal function and connectivity in the immature versus
mature CNS.
Epilepsy syndromes
▪ Stroke
▪ TIA
o Increased ICP:
▪ Trauma (SDH, EDH)
▪ Cerebral edema of different causes
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Seizure and epilepsy are a Clinical diagnosis (see approach to the patient with
active seizure below)
If the patient has a known seizure disorder (epileptic), check adherence.
If the patient history is unclear or if this is the patient’s first seizure, do the
following Investigations;
o RBS
o CBC
o Electrolytes
o LFT
o RFT (BUN and creatinine)
o Urinalysis
o EEG
▪ Although the EEG is the most helpful diagnostic test in the
diagnosis of a seizure disorder an abnormal EEG pattern alone is
not adequate for the diagnosis of seizures.
▪ A normal EEG in a patient with a first seizure is associated with a
lower risk of recurrence.
o LP and blood cultures → if patient is febrile
o Brain imaging
▪ Almost all patients with new-onset seizures should have a brain
imaging study to determine whether there is an underlying structural
abnormality that is responsible.
▪ The only potential exception to this rule is children who have an
unambiguous history and examination suggestive of a benign,
generalized seizure disorder such as absence epilepsy.
▪ MRI has been shown to be superior to CT for the detection of
cerebral lesions associated with epilepsy.
Syncope
o The diagnostic dilemma encountered most frequently is the distinction
between a generalized seizure and syncope.
o Characteristics of a seizure include the presence of an aura, cyanosis,
unconsciousness, motor manifestations lasting >15 s, postictal
disorientation, muscle soreness, and sleepiness. In contrast, a syncopal
episode is more likely if the event was provoked by acute pain or anxiety
or occurred immediately after arising from the lying or sitting position.
o Patients with syncope often describe a stereotyped transition from
consciousness to unconsciousness that includes tiredness, sweating,
nausea, and tunneling of vision, and they experience a relatively brief loss
of consciousness.
Psychogenic seizures
o Psychogenic seizures are nonepileptic behaviors that resemble seizures.
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❖ When the patient is not acutely ill, the evaluation will initially focus on whether
there is a history of earlier seizures
❖ If this is the first seizure, then the emphasis will be to:
Establish whether the reported episode was a seizure rather than another
paroxysmal event
Seizures frequently occur out-of-hospital, and the patient may
be unaware of the ictal and immediate postictal phases; thus,
witnesses to the event should be interviewed carefully.
Determine the cause of the seizure by identifying risk factors and
precipitating events
Clues for a predisposition to seizures include a history of
febrile seizures, earlier auras or brief seizures not recognized as
such, and a family history of seizures.
Epileptogenic factors such as prior head trauma, stroke, tumor, or CNS
infection should be identified.
Precipitating factors such as sleep deprivation, systemic diseases,
electrolyte or metabolic derangements, acute infection, drugs that
lower the seizure threshold, or alcohol or illicit drug use should also
be identified.
Decide whether anticonvulsant therapy is required in addition to treatment
for any underlying illness.
❖ In the patient with prior seizures or a known history of epilepsy, the evaluation
is directed toward:
Identification of the underlying cause and precipitating factors, and
Determination of the adequacy of the patient’s current therapy.
❖ While managing active seizure and life-threatening conditions, pertinent and
targeted physical examination should be done including a search for underlying
cause and precipitants
❖ All patients require a complete neurologic examination, with particular emphasis
on eliciting signs of cerebral hemispheric disease
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If seizure continues
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If seizure continues
Late
refractory SE
✓ Midazolam, IV, loading dose: 0.2 mg/kg followed by
(>48 h)
a continuous infusion 0.2 - 0.6 mg/kg/h and/or
✓ Induce anesthesia with Propofol, IV loading dose 2
mg/kg, then Continuous infusion of 2 - 10 mg/kg/h
or
✓ Phenobarbital (see the above description)
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Figure; Pharmacologic treatment of generalized tonic-clonic status epilepticus (SE) in adults. CLZ,
clonazepam; ECT, electroconvulsive therapy; LCM, lacosamide; LEV, levetiracetam; LZP, lorazepam;
MDZ, midazolam; PGB, pregabalin; PHT, phenytoin or fos-phenytoin; PRO, propofol; PTB,
pentobarbital; rTMS, repetitive transcranial magnetic stimulation; THP, thiopental; TPM, topiramate;
VNS, vagus nerve stimulation; VPA, valproic acid.
❖ Antiepileptic drug therapy is the mainstay of treatment for most patients with
epilepsy.
❖ The overall goal is to completely prevent seizures without causing any
untoward side effects, preferably with a single medication and a dosing
schedule that is easy for the patient to follow.
❖ Seizure classification is an important element in designing the treatment plan,
because some antiepileptic drugs have different activities against various
seizure types.
❖ Indication to start AED
i. All non-symptomatic seizures two or more episodes
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AED choices
Absence
Carbamazepine
Phenytoin
Valproic acid phenobarbital, phenytoin
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Carbamazepine
18
We mentioned these drugs for comparison with Ethiopia setup. Ethiopian standard consideration is based
on availability of drugs. You can use those written in western setup if they are available.
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3. Breast feeding
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Pathophysiology
❖ Results from the proliferation of microbial pathogens at the alveolar
level and the host’s response to those pathogens
❖ Microorganisms gain access to the lower respiratory tract in several
ways;
✓ Aspiration from oropharynx
✓ Inhalation as contaminated droplets
✓ hematogenous spread → rare
Pathology
Pneumonia evolves through 4 interrelated series of pathologic changes
Risk factors
Intrinsic factors- host factors
Extrinsic factors- exposure to a causative agent, pulmonary irritants,
or direct pulmonary injury
Diagnosis of pneumonia
Imaging
Chest X-ray
Typical consolidation
Classification of pneumonia → Lobar, bronchopneumonia, interstitial
pneumonia
May suggest etiologic diagnosis- eg- pneumatoceles suggest infection
with S. aureus
Risk factors for increased severity- cavitation or multilobar
involvement
Complications- eg- parapneumonic effusion, pneumothorax
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Etiologic Diagnosis
❖ CBC
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DDx of pneumonia
1. Acute bronchitis
2. Acute exacerbation of COPD
3. Bronchial asthma
4. Heart failure
5. Pulmonary embolism
6. Radiation pneumonitis
✓ Mycoplasma pneumonia
✓ Chlamydia pneumonia
✓ Legionella (espec. in elderly, smokers, T immunity)
✓ Influenza viruses
✓ Adenoviruses
✓ Respiratory syncytial virus
No organism identified in 40–60% cases
Clinical manifestations
“Typical”:
acute onset of fever
cough with purulent sputum
chest pain
dyspnea
Increased or decreased tactile fremitus and dull percussion note
Crackles, BBS, and/or pleural friction rub
consolidation on CXR
N.B
☛ Signs, symptoms & imaging do not reliably distinguish between
“typical” (S. pneumo, H. flu) and “atypical” (Mycoplasma,
Chlamydia, Legionella, viral)
☛ The clinical presentation may not be so obvious in the elderly, who
may initially display new-onset or worsening confusion
☛ Severely ill patients may have septic shock and evidence of organ
failure
Management of CAP
First line
Second line
✓ Azithromycin, 500mg po daily for 3 days (500mg P.O., first day then
250mg P.O. daily, for 4d) or
✓ Clarithromycin, 500mg P.O. BID for 5-7 days Or
✓ Doxycycline, 100mg P.O., BID for 7-10 days.
Second line
✓ Cefuroxime 250-500mg, po, bid for 5-10 days Plus
✓ Azithromycin, 500mg po daily for 3 days (500mg P.O., first day then
250mg P.O., for 4d.) OR
✓ Clarithromycin, 500mg P.O. BID for 5-7 days
Prevention
➢ Influenza vaccination
➢ Pneumococcal vaccination is critical for at risk patients
✓ may be given for ≥65 years old patients and others with risk factors
(eg, chronic heart, lung, and liver disease, immunocompromised, and
impaired splenic function)
➢ Smoking cessation should be encouraged during the initial visit
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▪ Three key criteria are required for the diagnosis of HAP and VAP
1. A new or progressive lung infiltrate of infectious origin
2. Clinical presentations (after 48 hours of admission for HAP and
after 48 hours of intubation for VAP) ensuring an infection (fever,
purulent sputum, leucocytosis, decline in oxygenation)
3. A positive pathogen identified on microbiologic respiratory samples.
Despite the controversies on the type of samples taken and the
analysis method, microbiologic cultures are absolutely required for
guiding the empiric therapy in HAP/VAP and has to be taken prior
to the first antibiotic dose administration.
Management
The antibiotic choice should depend on the epidemiology and
susceptibility of local pathogens.
Empiric treatment should include antimicrobials effective against
resistant gram-positive and gram-negative organisms particularly
S.aureus and P.aeruginosa.
The following are possible combinations: Empiric treatment for
commonly suspected etiologies of HAP.
First line
✓ Vancomycin 1g I.V. BID for 10-14 days (particularly in the ICU setup
and in ventilator associated pneumonia)
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PLUS
✓ Ceftazidime, 2gm I.V. TID for 10-14days Or
✓ Cefepime, 2 g, IV, TID
2nd line
3rd line → reserved for microbiologic data proven resistance for 1st and
2nd line options
Clinical features
✓ Mostly indolent course over several days or weeks
Fever, cough, purulent sputum, and dyspnea
Systemic disease symptoms: night sweets, weight loss, anemia
Hemoptysis or pleurisy
Copious putrid or malodorous sputum is typical for anaerobic infection
Absence of chills or rigors
Mild to moderate
First line
Second line
Severe
First line
✓ Ampicillin sulbactam 1.5 - 3 g IV QID x 7 days
Second line
Second line
➢ CURB-65 – easy and commonly used scoring system which stands for:
✓ Confusion* (1 point)
✓ Urea >20 mg/dL (7 mmol/L) ** (1 point)
✓ RR ≥30 bpm (1 point)
✓ SBP (<90 mmHg) or DBP (≤60 mmHg) (1 point)
✓ Age ≥65 years (1 point)
3 to 5 points: High severity (risk of death 15 to 40%) In patient, IV antibiotic immediately after culture
➢ CURB-65 predictive rules however, are not used as criteria for high-level
(ICU) care and treatment intensification.
➢ The Infectious Disease Society of America (IDSA) recommends either 1
major criterion or ≥ 3 minor criteria for ICU admission criteria.
➢ Minor criteria (≥ 3)
RR ≥ 30 bpm
Hypothermia (core temperature, <36C)
Hypotension requiring aggressive fluid resuscitation
Multilobar infiltrates
Confusion/disorientation
Uraemia (BUN level ≥20 mg/dl)
Leukopenia /infection related only/ (WBC, <4,000 cells/ml)
Thrombocytopenia (platelet count, <100,000/ml)
PaO2/FI O2 ratio ≤250
Bed rest
Frequent monitoring of V/S in order to detect complications early and
to monitor response to therapy.
Give attention to fluid and nutritional replacements.
Administer Oxygen via nasal prongs or face mask
The Antibiotic choice should be aimed at the most likely causative
agent.
Empiric treatment for pneumonia due to common organisms:
First line
Second line
Clinical features
➢ The clinical features of parapneumonic effusion are similar to pneumonia.
Pleuritic chest pain and prolonged fever are more common in patients who
develop complicated parapneumonic effusion or empyema.
➢ Physical examination: signs of pleural effusion (dullness, decreased or absent
air entry, decreased tactile fremitus) will be present.
Investigations
→ In addition to the investigations mentioned for pneumonia
❖ Pleural fluid cell count with differential, LDH, Protein, glucose, gram
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Treatment
Table: Management of parapneumonic effusion and empyema
Types Treatment
Uncomplicated parapneumonic effusion Antibiotics alone, no drainage
Complicated parapneumonic effusion Chest tube drainage* (also called tube thoracostomy) +
Antibiotics
Empyema Urgent chest tube drainage* (tube thoracostomy) +
antibiotics
*If clinically & radiologically improve and drainage rate fall below <50 ml/day for 2 to 3 days, remove chest
tube
*If no improvement: assess antibiotic coverage (re-culturing, reviewing anaerobic and MDR pathogens
coverage) and evaluate for the presence undrained loculated pockets.
Follow up
❖ Uncomplicated parapneumonic effusion
✓ repeat imaging after 48-72 hour of antibiotic treatment initiation for
any completion
❖ Complicated PE and empyema
✓ has microbiologic (easy to grow) or biochemical evidence of
infection, at risk of poor outcome (may need repeated procedure
or surgery or hospitalization)
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Clinical manifestations
Signs
❖ Tonsillar swelling with hyperemia / exudates (Inflamed and reddened
enlarged tonsils)
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Pictures; Tonsillopharyngitis
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Diagnostic approach
Mc Isaac Scoring
Nonsuppurative complications
➢ ARF (Acute rheumatic fever)
o Due to cross reaction to type 5 M-protein
➢ PSGN (Post streptococcal glomerulonephritis)
o PSGN is an acute glomerulonephritis (AGN)
due to nephritogenic strains
➢ Poststreptococcal reactive arthritis (PSRA)
➢ Scarlet fever
➢ Streptococcal toxic shock syndrome
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Investigation
➢ In our set up it is usually a clinical diagnosis. But ‘’Harrison’’ didn’t
recommend clinical diagnosis
o ‘’Because of the range of clinical presentations of streptococcal
pharyngitis and the large number of other agents that can produce
the same clinical picture, diagnosis of streptococcal pharyngitis on
clinical grounds alone is not reliable’’.
➢ Rapid diagnostic kit (for latex agglutination or enzyme immunoassay of
swab specimens)
✓ is a useful adjunct to throat culture.
✓ >95% specific. but, less sensitive (55–90%).
o Thus, a positive result can be relied upon for definitive
diagnosis and eliminates the need for throat culture
o A negative result should be confirmed by throat culture.
➢ Throat swab culture → Gold standard
o It is hard to differentiate viral and bacterial cause based on symptom
and sign alone. Thus, Throat swab is done to r/o bacterial cause
o Culture of a throat specimen that is properly collected (i.e., by
vigorous rubbing of a sterile swab over both tonsillar pillars) and
properly processed is the most sensitive and specific means of
definitive diagnosis.
o Not required usually. Needed only when suspicion is high and rapid
strep throat swab is negative.
o Pathogens looked for
▪ GAS
▪ C. diphteriae (rare)
▪ N. gonorrhoeae (rare)
➢ ASO
✓ May remain +ve for 1 year
➢ Peripheral smear → BF (to r/o malaria in endemic area)
➢ CBC and ESR
Treatment of GABHS
The goal of antibiotic therapy for streptococcal pharyngitis is multifold and
includes:
o Reducing symptom severity and duration
o Prevention of acute complications, such as otitis media, peritonsillar
abscesses, or other invasive infections
o Prevention of delayed complications or immune sequelae, particularly acute
rheumatic fever
▪ The primary benefit of treatment is the prevention of acute rheumatic
fever, which is almost completely successful if antibiotic treatment is
instituted within 9 days of illness.
o Prevention of spread to others
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Lincosamides* Clindamycin 300 mg, PO, TID for 7 mg/kg/dose (max;300 mg per
10 days dose), PO, TID, for 10 days
@
Penicillin’s (oral penicillin, oral amoxicillin, or single-dose IM benzathine penicillin) are options for patients
with a history of acute rheumatic fever (who are high risk for cardiac complications compared with those
without this history)
➢ IM penicillin appears to be more effective than oral penicillin at eradication of GAS from the oropharynx
and has been most well studied for the prevention of acute rheumatic fever
Δ Cephalosporins are Potential alternatives in cases of penicillin allergy
if the nature of the allergy is mild reactions to penicillin, non-IgE-mediated reactions to penicillin (e.g.
maculopapular rash beginning days into therapy) a 1stgeneration cephalosporin such as cephalexin
For patients with mild, possibly IgE-mediated reactions (e.g. urticaria or angioedema but NOT anaphylaxis),
they use a 2nd- or 3rd-generation cephalosporin, such as cefixime, ceftriaxone, cefuroxime, cefdinir, or
cefpodoxime.
#
Macrolides are alternatives for patients with immediate hypersensitivity reaction (anaphylaxis) or another
potentially life-threatening manifestation (e.g., severe rash and fever). or other IgE-mediated reactions, who
cannot tolerate cephalosporins
In areas with resistance rates exceeding 5–10%, macrolides should be avoided unless results of
susceptibility testing are known.
* Lincosamides (e.g. Clindamycin) are alternative when macrolide resistance is a concern and penicillin’s and
cephalosporins cannot be tolerated.
Antibiotics NOT to be used for GABHS due to the high prevalence of resistance
include;
✓ Tetracycline
✓ Sulphonamides (e.g. Co-trimoxazole)
✓ fluoroquinolones (e.g. Aminoglycosides)
✓ Chloramphenicol
Peritonsillar abscess
Inadequately treated acute or chronic tonsillitis can spread to the
surrounding tissue and form abscess called peritonsillar abscess
Clinical features
Prevention of transmission
GAS can spread among close contacts, leading to clusters of cases and
recurrent infections in households or other close-contact settings.
The rate of GAS transmission from an infectious case to close contacts is
estimated to be between 5 and 50 %.
Antibiotic use believed to eliminate GAS from the oropharynx in about 80 to
90 % of cases after 24 hours of therapy.
If untreated, approximately 50% of patients with streptococcal pharyngitis
will continue to harbor GAS in the oropharynx 3 to 4 weeks after symptom
onset.
Prevention methods
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Hand hygiene
Postexposure prophylaxis
o Testing and treatment of asymptomatic persons who have been
exposed to a patient with GAS pharyngitis are not routinely
recommended
o Indication for post exposure prophylaxis
▪ Patients with a history of ARF during outbreaks of ARF
and/or PSGN, or
▪ When GAS infections are recurring in households or other
close-contact settings.
Epidemiology
✓ Asthma is one of the most common chronic diseases globally and affects
~300 million people worldwide, with ~250,000 deaths annually.
✓ More common in developed countries where it affects,10-12% of adults and
15% of children
✓ In developing countries there is a rising prevalence associated with
increased urbanization.
✓ Occur at any age, peak at 3 years. 50% develop before the age of 10 and
another 35% before 40
✓ During Childhood M: F = 2:1 and in adulthood the ratio equalize.
❖ ENDOGENOUS FACTORS
o Genetic Predisposition
o Atopy
▪ Atopy is the major risk factor for asthma
▪ Patients with asthma commonly suffer from other atopic
diseases, particularly allergic rhinitis, which may be found in >
80% of asthmatic patients, and atopic dermatitis (eczema).
▪ Atopy is due to the genetically determined production of
specific IgE antibody, with many patients showing a family
history of allergic diseases.
▪ It is likely that environmental factors in early life determine
which atopic individuals become asthmatic.
o Obesity → an independent risk factor for asthma, particularly in
women
o Gender
❖ ENVIRONMENTAL FACTORS
o Occupational Exposure
▪ Occupational asthma may be suspected when symptoms
improve during weekends and holidays.
▪ Occupational asthma is relatively common and may affect up
to 10% of young adults
▪ Cleaners commonly develop occupational asthma owing to
exposure to aerosols of cleaning liquids.
o Indoor and outdoor Air Pollution → Indoor air pollution is common
risk factor in our set up
▪ Indoor air pollution is also important risk factor with exposure
to nitrogen oxides from cooking stoves and exposure to
passive cigarette smoke. maternal smoking is a risk factor for
asthma.
o Diet
▪ The role of dietary factors is controversial.
▪ Diets low in antioxidants such as vitamin C and vitamin A,
magnesium, selenium, and omega-3 PUFA (fish oil) or high in
sodium and omega-6 PUFA are associated with an increased
risk of asthma.
▪ Vitamin D deficiency may also predispose to the development
of asthma.
▪ Some foods such as shellfish and nuts may induce
anaphylactic reactions that may include wheezing.
o Acetaminophen → may be linked to increased oxidative stress
especially in children
N.B Smokers with asthma have more severe disease, more frequent hospital
admissions, a faster decline in lung function, and a higher risk of death from
asthma than non-smoking asthmatics. Interferes with the anti-inflammatory actions
of corticosteroids
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❖ Triggers
o Allergens
▪ Allergens Are derived from house dust mites, cat and dog fur,
cockroaches (in inner cities), grass and tree pollens, and
rodents (in laboratory workers).
▪ Other allergens, including grass pollen, ragweed, tree pollen,
and fungal spores, are seasonal.
▪ Pollens usually cause allergic rhinitis rather than asthma
o Infections
▪ URTI such as Rhinovirus, RSV and corona virus are triggering
agents
▪ Atypical bacteria, such as Mycoplasma and Chlamydophila,
have been implicated in the mechanism of severe asthma.
▪ There is an increase in airway inflammation with increased
numbers of eosinophils and neutrophils.
o Drugs → e.g. Beta blockers like Propranolol, Metoprolol
o Stress
o Exercise and hyperventilation
▪ Exercise-induced asthma (EIA) typically begins after exercise
has ended, and recovers spontaneously within about 30
minutes.
o Cold Air
o Irritants (household sprays, paint fumes)
❖ Other Factors
o Lower maternal age
o Duration of breastfeeding
o Prematurity and low birth weight
o Inactivity
Pathophysiology of asthma
❖ Asthma is associated with a specific chronic inflammation of the respiratory
mucosa from the trachea to terminal bronchioles with a predominance in
the bronchi (cartilaginous airways)
❖ Airway inflammation in asthma is associated with airway hyper
responsiveness (AHR)
o AHR is the characteristic physiologic abnormality of asthma and
describes the excessive Broncho constrictor response to multiple
inhaled triggers that would have no effect on normal airways.
❖ Mediated by various inflammatory cells and their products
❖ Chronic inflammation is associated with structural changes in the airway
called airway remodeling
❖ Limitation of airflow
✓ Bronchoconstriction(mainly)
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✓ Airway edema
✓ Vascular congestion
✓ Luminal occlusion with exudate
❖ All the above results in
✓ Decrease FEV1, FEV1/FVC ratio & PEF
✓ Increase airway resistance and RV
The airway wall itself may be thickened and oedematous (i.e. thickening of
basement membrane and smooth muscle).
And there is occlusion of the airway lumen by a mucous plug in fatal asthma.
which is comprised of mucous glycoproteins secreted from goblet cells (from goblet
cell hyperplasia which leads to mucus hyper secretion) and plasma proteins from
leaky bronchial vessels.
There is also vasodilation and increased numbers of blood vessels (angiogenesis).
The airways may be narrowed, erythematous, and oedematous.
Mast cells, which are found at the airway surface in asthma patients and also in
the airway smooth-muscle layer, are important in initiating the acute Broncho
constrictor responses to allergens and several other indirectly acting stimuli, by
releasing several Broncho constrictor mediators
Multiple inflammatory mediators (histamine, PG D2, and leukotriene) contract airway
smooth muscle, increase micro vascular leakage, increase airway mucus secretion,
and attract other inflammatory cells. With final effect of Bronchospasm, Mucus
secretion, AHR, & Structural changes.
Cysteinyl-leukotrienes are potent Broncho constrictors;
Cholinergic pathways, through the release of acetylcholine acting on muscarinic
receptors, cause bronchoconstriction and may be activated reflexly in asthma.
➢ Atopic (extrinsic)
➢ Non-atopic (intrinsic)
➢ Occupational asthma
➢ Aspirin-sensitive and
➢ Paediatric asthma
Symptoms
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Physical signs
❖ Wheeze
❖ Inspiratory, and to a greater extent expiratory rhonchi
❖ Hyperinflation
❖ Respiratory distress
❖ Skin lesion, Nasal discharge → may be related with atopy
❖ Symptoms may be worse at night and patients typically awake in the early
morning hours.
• Circadian variations in Broncho motor tone and bronchial reactivity
reach their nadir between 3 AM and 4 AM (i.e. between 9 and 10
NLT), increasing symptoms of bronchoconstriction.
❖ Some patients, particularly children, may present with a predominant non-
productive cough (“cough-variant asthma”).
❖ Prodromal symptoms may precede an attack
• Itching under the chin
• Discomfort between the scapulae
• Inexplicable fear (impending doom).
❖ Danger signs during acute attacks:
• Paradoxical breathing
• Profound diaphoresis
• Cyanosis
• Exhaustion Arrhythmia
• Silent chest on auscultation
• Mental status change (Drowsiness or confusion)
• Agitation
• SPO2 < 90 %
Diagnosis of asthma
1. Most of the time asthma is a clinical diagnosis
2. Spirometry
o asthma FEV1 ↓sed but FVC is normal so FEV1/FVC ratio
decreased.
☛ In restrictive lung disease FEV1 and FVC decreased
simultaneously so the FEV1/FVC ratio is normal.
o Asthma a >12% and 200-ml increase in FEV1 15 min after an
inhaled short-acting β2-agonist (SABA; such as inhaled albuterol 400
μg) or in some patients by a 2 - 4-week trial of oral corticosteroids
(OCS) (prednisone or prednisolone 30–40 mg daily). But not in
COPD.
3. Bronchoprovocation testing
4. Imaging (CXR &HRCT)
Clinical Features
Patients are aware of increasing chest tightness, wheezing, and dyspnea
that are often not or poorly relieved by their usual reliever inhaler.
In severe exacerbations patients may be so breathless that they are unable
to complete sentences and may become cyanotic.
Examination usually shows increased ventilation, hyperinflation, and
tachycardia.
Pulsus paradoxus may be present, but this is rarely a useful clinical sign.
There is a marked fall in spirometric values and PEF.
Arterial blood gases on air show hypoxemia, and PCO2 is usually low due
to hyperventilation.
A normal or rising PCO2 is an indication of impending respiratory failure
and requires immediate monitoring and therapy.
➢ Bronchodilators
➢ Controllers
1) Bronchodilators
19
The 2021 STG for general hospitals of Ethiopia recommend that, ‘’Sustained-release theophylline
preparations (e.g. theophedrine 120/11mg tablets daily to QID base) are effective in controlling nocturnal
symptoms and as added therapy in patients with moderate or severe persistent asthma whose symptoms
are inadequately controlled by ICS’’.
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2) Controllers
☛ Controllers act primarily to inhibit the underlying inflammatory process
☛ They are taken daily independent of symptoms to achieve and maintain
control of persistent asthma.
☛ Important long-term control medications include
o Corticosteroids → ICS (inhaled corticosteroids) or OCS (oral
corticosteroids)
o Anti-leukotrienes → e.g. montelukast, zafirlukast. montelukast (adult
dose 10 mg once daily
o Chromones → e.g. cromolyn sodium, nedocromil sodium
o Steroid sparing → e.g. methotrexate, cyclosporine, azathioprine, gold,
IV gamma globulin
o Anti IgE → omalizumab
Currently, Anti-leukotrienes, Chromones, Steroid sparing, and Anti IgE are not
available in most set ups of Ethiopia
Corticosteroids
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PEF: peak expiratory flow; ICU: intensive care unit; SABA: short-acting beta agonist (eg, albuterol); SpO2:
pulse oxygen saturation; COPD: chronic obstructive pulmonary disease; MDI: metered dose inhaler; GC:
glucocorticoid; PaCO2: carbon dioxide tension.
* Titrate oxygen to SpO2 93 to 95% for patients with severe exacerbations, particularly if at risk for
hypercapnia. Aim for SpO2 >95% in pregnant patients. Titrate to SpO2 88 to 92%, if asthma-COPD overlap.
¶ Magnesium sulfate is 4.06 mmol/g (2 g = 8.1 mmol).
Δ Please refer to the UpToDate topic on treatment of asthma exacerbations in adults.
◊ Adding ipratropium to albuterol nebulizer treatments is preferred for patients with severe exacerbations;
alternatively, SABA/ipratropium can be given via MDI 4 to 8 inhalations every 20 minutes, as needed for up
to 3 hours.
§ The dose and duration of therapy can be modified based on the patient's past history of response,
severity of exacerbation, and response to current treatment.
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❖ An inhaler is a medical device used for delivering medication into the body
via the lungs.
❖ It is mainly used in the treatment of asthma and COPD.
❖ The two most common forms are:
The medicine is in a small canister, inside a plastic case. When the inhaler
is pressed, a measured dose of medicine comes through the mouthpiece.
MDIs require good technique and coordination by pressing down on the
inhaler and breathing in at the same time.
Because using the inhaler correctly can be difficult, spacer devices are
recommended for use with MDIs. The spacer is attached to the MDI to
make it easier to use the inhaler and get more medicine into the lungs.
1. Remove the cap and check the mouthpiece is clean and free of objects.
2. Shake the inhaler 4 or 5 times.
3. Holding the inhaler upright with your thumb on the base, breathe out as far
as comfortable
4. Place the mouthpiece in your mouth; closing your lips around it to form a
good seal - do not bite.
5. Start to breathe in slowly; press down firmly on the top of the canister to
release a dose; while continuing to breathe in slowly and deeply.
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How to use MDI - Click on the link below and watch the video
https://youtu.be/tp479j15x6Q
N.B
Even though MDI are used correctly, only 10 - 20 % of Active drug (salbutamol,
ICS) is inhaled to lungs. The rest 80 - 90 % is swallowed in to GIT. If there is
incorrect use of MDI, obviously the patient will get less than 10 % of the drug to
the targeted lung. → look at the image
❖ Dry powder inhalers are handheld devices that deliver medication to the
lungs and airways as you inhale through it.
❖ Examples of dry powder inhalers include: Turbuhaler; Accuhaler; Handihaler;
Ellipta inhaler and Breezhaler.
❖ The common forms available in Ethiopia are Turbuhaler (eg.Symbicort) and
Accuhaler (eg. Seritide)
6) Place the mouthpiece in your mouth; closing your lips around it to form a
good seal - do not bite
7) Breathe in as strongly and deeply as possible
8) Removing the inhaler from your mouth; hold your breath for about 10
seconds, or as long as is comfortable
9) Breathe out gently away from your inhaler mouthpiece
10) To close the Accuhaler®, slide the thumb grip back towards you as far as
it will go until it clicks.
How to use Accuhaler® - Click on the link below and watch the video
https://youtu.be/6WOEhIIIHGI
Turbuhaler (DPI)
1) Open: unscrew and remove the cap. Hold the turbuhaler upright.
2) Load the dose: twist the base anticlockwise and then back in the other
direction until you hear a click. Your turbuhaler is now loaded with one
dose of medicine
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3) Breathe out: breathe out, away from the turbuhaler. Do not blow directly into
the turbuhaler.
4) Inhale your dose: place the mouth piece in your mouth and form a seal
with your lips. Breathe in deeply. Remove the turbuhaler and hold your
breath for up to 10 seconds.
5) Close: replace the cap and twist until it is on properly.
6) Cleaning and storing your turbuhaler: wipe the mouthpiece with a clean dry
tissue. Do not wash the mouthpiece or allow it to get wet when cleaning.
Keep the cap on when not in use. The device may clog if exhaled or
dribbled into or if stored in an area of high humidity with the cap off or
unsealed.
How to use Terbuhaler® - Click on the link below and watch the video
https://youtu.be/DqoEdW6dHaI
To get the most benefit, it is important to use the correct technique. Here are a
few common problems:
✓ Not holding your turbuhaler upright (vertical) while loading the dose.
✓ Covering the air inlets with your lips.
✓ Breathing in through your nose instead of your mouth.
✓ Shaking the inhaler to see how much is left.
✓ Storing your turbuhaler in a damp place with the cap off.
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How to use an Inhaler with a spacer - Click on the link below and
watch the video
https://youtu.be/ma_cmlU9DxU
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Table; Assessing severity and initiating treatment for patients who are not currently taking long-term
control medications. The stepwise approach is meant to assist, not replace, the clinical decision-making
required to meet individual patient needs. Level of severity is determined by assessment of both impairment
and risk. Assess impairment domain by patient's/caregiver's recall of previous two to four weeks and
spirometry. Assign severity to the most severe category in which any feature occurs. At present, data are
inadequate to correlate frequencies of exacerbations with different levels of asthma severity. In general, more
frequent and intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or ICU
admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≥2
exacerbations requiring oral systemic glucocorticoids in the past year may be considered the same as
patients who have persistent asthma, even in the absence of impairment levels consistent with
persistent asthma.
FEV1: forced expiratory volume in one second; FVC: forced vital capacity;
Even though this table is for ≥ 12 years of age, it is almost similar for < 12 years
age (if you want to cross check the details, look at the table from UpToDate 2018
‘’asthma in children younger than 12 years” as shown in the picture)
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Patients with poor asthma control should be assessed for the following.
➢ For patients with mild, intermittent asthma, a SABA is all that is required.
However, use of a reliever medication more than twice a week indicates
the need for regular controller therapy.
➢ The treatment of choice for all patients is an ICS given twice daily. It is
usual to start with an intermediate dose (e.g. 200μg BID of beclomethasone
dipropionate) or equivalent and to decrease the dose if symptoms are
controlled after 3 months.
➢ If symptoms are not controlled, a LABA should be added, which is most
conveniently given by switching to a combination inhaler.
➢ The dose of controller should be adjusted accordingly, as judged by the
need for a rescue inhaler.
➢ Low doses of theophylline or an antileukotriene may also be considered as
an add-on therapy, but these are less effective than LABA.
➢ In patients with severe asthma, low-dose oral theophylline is also helpful,
and when there is irreversible airway narrowing, the long-acting
anticholinergic may be tried.
➢ If asthma is not controlled despite the maximal recommended dose of
inhaled therapy, it is important to check adherence and inhaler technique.
In these patients, maintenance treatment with an OCS may be needed and
the lowest dose that maintains control should be used.
➢ Once asthma is controlled, it is important to slowly decrease therapy in
order to find the optimal dose to control symptoms.
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First line
Alternative
PLUS
❖ Fluticasone/Salmeterol (LABA), 250/50 µg oral inhalation, BID
PLUS
❖ Fluticasone/Salmeterol (LABA), 250/50µg oral inhalation, BID
☛ Day-to-day adjustment;
❖ For patients prescribed low-dose ICS/formoterol maintenance and reliever
regimen
Stepping down asthma treatment;
o Consider stepping down if … symptoms well controlled for 3 months +
low risk for exacerbations.
o Stopping ICS is not advised in adults with asthma because of risk of
exacerbations
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o Find each patient’s minimum effective dose that controls both symptoms
and exacerbations.
Special considerations
Refractory Asthma
Although most patients with asthma are easily controlled with appropriate
medication, a small proportion of patients (~5%) are difficult to control
despite maximal inhaled therapy.
There are two major patterns of difficult asthma:
☛ Some patients have persistent symptoms and poor lung function,
despite appropriate therapy,
☛ Whereas others may have normal or near normal lung function but
intermittent, severe (sometimes life-threatening) exacerbations.
The most common reason for poor control of asthma is poor adherence
with medication, particularly ICS. Compliance with ICS may be low because
patients do not feel any immediate clinical benefit or may be concerned
about side effects.
There are several factors that may make asthma more difficult to control,
including;
☛ Exposure to high, ambient levels of allergens or unidentified
occupational agents.
☛ Severe rhinosinusitis may make asthma more difficult to control
☛ Upper airway disease should be vigorously treated.
☛ Drugs such as 𝛽 blockers, aspirin, and other cyclooxygenase (COX)
inhibitors like NSAID’s may worsen asthma.
☛ Some women develop severe premenstrual worsening of asthma, which
is unresponsive to corticosteroids and requires treatment with
progesterone or gonadotropin-releasing factors.
☛ Few systemic diseases make asthma more difficult to control, but
hyper- and hypothyroidism may increase asthma symptoms and should
be investigated if suspected.
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Corticosteroid-Resistant Asthma
It is defined by a failure to respond to a high dose of oral
prednisone/prednisolone (40 mg once daily over 2 weeks), ideally with a 2-
week run-in with matched placebo.
More common is reduced responsiveness to corticosteroids where control of
asthma requires OCS (corticosteroid-dependent asthma).
A few patients with asthma show a poor response to corticosteroid therapy
Complete resistance to corticosteroids is extremely uncommon
There are likely to be heterogeneous mechanisms for corticosteroid
resistance;
Brittle Asthma
Some patients show chaotic variations in lung function despite taking
appropriate therapy.
There are two types of brittle asthma
☛ Type I brittle asthma → patients with this type, show a persistent
pattern of variability and may require OCS or, at times, continuous
infusion of β2-agonists
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☛ Type II brittle asthma →patients with this type, have generally normal
or near-normal lung function but precipitous, unpredictable falls in lung
function that may result in death.
▪ Difficult to manage as they do not respond well to
corticosteroids, and the worsening of asthma does not reverse
well with inhaled bronchodilators.
In some of these patients, there may be allergy to specific foods.
The most effective therapy is subcutaneous epinephrine, which suggests
that the worsening is likely to be a localized airway anaphylactic reaction
with edema.
These patients should be taught to self-administer epinephrine and should
carry a medical warning accordingly.
Asthma in Pregnancy
Approximately 1/3rd of asthmatic patients who are pregnant improve during
the course of a pregnancy, 1/3rd deteriorate, and 1/3rd are unchanged.
It is important to maintain good control of asthma as poor control may have
adverse effects on fetal development (chronic maternal hypoxia is risk factor
for both maternal and neonatal complications, e.g. Perinatal asphyxia).
Adherence may be a problem as there is often concern about the effects of
antiasthma medications on fetal development.
The drugs have been shown to be safe and without teratogenic potential.
☛ These drugs include SABA, ICS, and theophylline;
There is less safety information about newer classes of drugs such as
LABA, antileukotrienes, and anti-IgE.
If an OCS is needed, it is better to use prednisone rather than
prednisolone as it cannot be converted to the active prednisolone by the
fetal liver, thus protecting the fetus from systemic effects of the
corticosteroid. There is no contraindication to breast-feeding when patients
are using these drugs.
☛ This note is from Harrison 20th edition. According to UpToDate 2018, Hydrocortisone
is Category C, Prednisolone and prednisone are Category C/D
☛ what do we do for each Category of drugs in pregnancy? Click here → Chapter 7;
Basics about rational use of antibiotics
Etiology
✓ The 1st three from the following are the dominant bacterial agents
causing bloody diarrhea in Ethiopia.
Salmonella
Shigella
Campylobacter
E. coli.
Entamoeba histolytica and
S. mansoni
☛ Transmission occurs via contaminated water or food.
Clinical features
− watery, mucoid or bloody diarrhea with tenesmus.
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Investigations
− S/E → abundance of leukocytes (pus cells)
− Stool culture, if available, can be used to guide treatment selection
Treatment
Supportive treatment
Pharmacologic
Look at table below
recommendation:
Cysts and trophozoites are passed in feces (1). Cysts are typically found in formed stool, whereas trophozoites
are typically found in diarrheal stool. Infection by Entamoeba histolytica occurs by ingestion of mature cysts (2) in
fecally contaminated food, water, or hands. Excystation (3) occurs in the small intestine and trophozoites (4) are
released, which migrate to the large intestine. The trophozoites multiply by binary fission and produce cysts (5),
and both stages are passed in the feces (1). Because of the protection conferred by their walls, the cysts can
survive days to weeks in the external environment and are responsible for transmission. Trophozoites passed in
the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric
environment. In many cases, the trophozoites remain confined to the intestinal lumen (A: noninvasive infection) of
individuals who are asymptomatic carriers, passing cysts in their stool. In some patients the trophozoites invade
the intestinal mucosa (B: intestinal disease), or, through the bloodstream, extraintestinal sites such as the liver,
brain, and lungs (C: extraintestinal disease), with resultant pathologic manifestations. It has been established that
the invasive and noninvasive forms represent two separate species, respectively E. histolytica and E. dispar.
These two species are morphologically indistinguishable unless E. histolytica is observed with ingested red blood
cells (erythrophagocystosis). Transmission can also occur through exposure to fecal matter during sexual contact
(in which case not only cysts, but also trophozoites could prove infective).
Clinical features
Investigations
Stool examination:
Treatment
Non pharmacologic
❖ Hydration is important in patients who have severe dysentery
Pharmacologic
Look at table below
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Cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites can be
found in the feces (diagnostic stages) (1). The cysts are hardy and can survive several months in cold water.
Infection occurs by the ingestion of cysts in contaminated water, food, or by the fecal-oral route (hands or
fomites) (2). In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites) (3).
Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel where
they can be free or attached to the mucosa by a ventral sucking disk (4). Encystation occurs as the parasites
transit toward the colon. The cyst is the stage found most commonly in nondiarrheal feces (5). Because the cysts
are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. While
animals are infected with Giardia, their importance as a reservoir is unclear.
Clinical
features
☛ The most common presentation is diarrhea which is foul-smelling
with fatty stools (steatorrhea)
☛ Flatulence
☛ weight loss
☛ crampy abdominal pain with bloating
☛ failure to thrive.
Investigation
s
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Treatment
Supportive treatment
☛ Correction of fluid and electrolyte loses due to the diarrhea
Medicine Treatment
Prevention:
Pathogenesis
Epidemiology
Clinical manifestations
❖ IP: 1 to 2 days
❖ Mild disease: loose stool or watery diarrhea
❖ Severe disease (“cholera gravis”): The diarrhoea is classically
voluminous/ profuse (up to 1L/hr)/, non-offensive, and somewhat
looks gray or “rice-water”
diarrhea with flecks of mucous
❖ Fever is absent.
❖ Dehydration, shock, electrolyte imbalance
❖ Usually: no pain, no tenesmus, no blood in stool, no fever
Mortality from cholera
Diagnosis
Management
❖ Non pharmacologic
- advise patients to take fluid
- Symptomatic/Supportive Treatment
❖ For dehydration in mild cases give ORS, PRN and IV fluid for severe
DHN
❖ Treat shock, electrolyte imbalance; KCl solution 20-40mmol/liter may
be added as required
Pharmacologic
Prevention:
Pregnant women:
✓ Third generation cephalosporins should be used in pregnant
mothers in place of fluoroquinolone or azithromycin.
Treatment of invasive colitis consists of a tissue
agent (e.g metronidazole) followed by a luminal
(e.g. parmomycin) agent to eliminate intraluminal
cysts.
Intraluminal infection can be treated with one of
the luminal agents.
First line
✓ Metronidazole, 500-750mg P.O., TID for 5-7
Amoebiasis days.
➢ For children: 7.5mg/kg/dose, P.O., TID
(Entamoeba dispar,
for 5-7 days.
Entamoeba histolytica)
Alternative
✓ Tinidazole, 2g P.O. daily for 3 consecutive
days.
➢ For children: 50-60mg/kg daily for 3
days
Eradication of cysts
First line
✓ Diloxanide Furoate, 500mg, PO, TID, for 10
days. course may be repeated if necessary.
Or
➢ Child over 25kg, 20mg/kg/day, TID, for
10 days;
✓ Paromomycin, 25 - 35mg/kg/day, P.O, TID,
for 7 days Or
✓ Iodoquinol (Diiodohydroxyquin): 650 mg, PO,
TID for 20 days
➢ for children 30 - 40 mg/kg/day, TID, for
20 days
first line
✓ tinidazole, 2 g, PO, stat
Giardiasis (Giardia Alternatives
lamblia) ✓ Metronidazole, 250-500mg P.O., TID for 5
days or
✓ Albendazole, 400 mg, PO, daily for 5 days
or
✓ Nitazoxanide, 500 mg, PO, BID, for 3 days
Adult worms (females 20 to 35 cm; males 15 to 30 cm) (1) live in the lumen of the small intestine. A
female may produce approximately 200,000 eggs per day, which are passed with the feces (2). Unfertilized
eggs may be ingested but are not infective. Fertile eggs embryonate and become infective after 18 days to
several weeks (3), depending on the environmental conditions (optimum: moist, warm, shaded soil). After
infective eggs are swallowed (4), the larvae hatch (5), invade the intestinal mucosa, and are carried via the
portal, then systemic circulation to the lungs (6). The larvae mature further in the lungs (10 to 14 days),
penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed (7). Upon reaching
the small intestine, they develop into adult worms (1). Between two and three months are required from
ingestion of the infective eggs to oviposition by the adult female. Adult worms can live one to two years.
Transmission
Clinical Manifestations
Intestinal Manifestations:
Pulmonary Manifestations:
Diagnosis
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Treatment
Follow-up
Follow with repeat S/E after 2-3 months, and those +ve for eggs
should get repeat treatment.
There are two main species of Taenia for which humans are the only
definitive hosts. These are
1. Taenia saginata /beef tapeworm/ and
2. Taenia solium /pork tapeworm/.
T. saginata occurs worldwide but is most common in areas where
consumption of undercooked beef is customary, such as Europe and
parts of Asia.
The third species, T. asiatica, is found among pigs in some places.
Concurrent infections with more than one Taenia species have been
described.
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Figure; Taeniasis is the infection of humans with the adult tapeworm of Taenia saginata, T. solium, or T. asiatica.
Humans are the only definitive hosts for these three species. Eggs or gravid proglottids are passed with feces
(1); the eggs can survive for days to months in the environment. Cattle (T. saginata) and pigs (T. solium and T.
asiatica) become infected by ingesting vegetation contaminated with eggs or gravid proglottids (2). In the animal's
intestine, the oncospheres hatch (3), invade the intestinal wall, and migrate to the striated muscles, where they
develop into cysticerci. A cysticercus can survive for several years in the animal. Humans become infected by
ingesting raw or undercooked infected meat (4). In the human intestine, the cysticercus develops over two
months into an adult tapeworm, which can survive for years. The adult tapeworms attach to the small intestine
by their scolex (5) and reside in the small intestine (6). Length of adult worms is usually 5 m or less for T.
saginata (however it may reach up to 25 m) and 2 to 7 m for T. solium. The adults produce proglottids that
mature, become gravid, detach from the tapeworm, and migrate to the anus or are passed in the stool
(approximately six per day). T. saginata adults usually have 1000 to 2000 proglottids, while T. solium adults have
an average of 1000 proglottids. The eggs contained in the gravid proglottids are released after the proglottids are
passed with the feces. T. saginata may produce up to 100,000 and T. solium may produce 50,000 eggs per
proglottid, respectively.
Clinical manifestations
Diagnosis
1. microscopy
Picture 1 (A, B) Taenia spp eggs in unstained wet mounts. Four hooks can clearly be seen in figure A.
(C) Cross-section of a proglottid of Taenia spp, stained with hematoxylin and eosin (H&E). Note the thick outer
tegument and the loose parenchyma filling the body. Calcareous corpuscles (red arrows), characteristic of the
cestodes, can be seen in the parenchyma. Eggs (blue arrows) can also be seen.
(D) Higher magnification of figure C showing a close-up of the eggs. Note the characteristic striations, typical for
the taeniids. Not visible in these images are the hooks commonly seen in cestode eggs. Hooks do not stain with
H&E but are refractile and visible with fine focusing of the microscope.
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Picture 2
Treatment
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Eggs are passed in the stool (1), and under favorable conditions (moisture, warmth, shade) larvae hatch in one
to two days. The released rhabditiform larvae grow in the feces and/or the soil (2), and after 5 to 10 days (and
two molts) they become filariform (third-stage) larvae that are infective (3). These infective larvae can
survive three to four weeks in favorable environmental conditions. On contact with the human host, the larvae
penetrate the skin and are carried through the blood vessels to the heart and then to the lungs. They penetrate
into the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed (4). The larvae reach the
small intestine, where they reside and mature into adults. Adult worms live in the lumen of the small intestine,
where they attach to the intestinal wall with resultant blood loss by the host (5). Most adult worms are eliminated
in one to two years, but the longevity may reach several years. Some Ancylostoma duodenale larvae, following
penetration of the host skin, can become dormant (in the intestine or muscle). In addition, infection by A.
duodenale may probably also occur by the oral and transmammary route. Necator americanus, however, requires
a transpulmonary migration phase.
Clinical Manifestations
Diagnosis
Treatment
Prevention
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Life cycle: Eggs are eliminated with feces or urine (1). Under optimal conditions, the eggs hatch and release
miracidia (2), which swim and penetrate specific snail intermediate hosts (3). The stages in the snail include two
generations of sporocysts (4) and the production of cercariae (5). Upon release from the snail, the infective
cercariae swim, penetrate the skin of the human host (6), and shed their forked tail, becoming schistosomulae
(7). The schistosomulae migrate through several tissues and stages to their residence in the veins (8,9). Adult
worms in humans reside in the mesenteric venules in various locations, which at times seem to be specific for
each species (10). For instance, S. japonicum is more frequently found in the superior mesenteric veins draining
the small intestine (A), and S. mansoni occurs more often in the superior mesenteric veins draining the large
intestine (B). However, both species can occupy either location, and they are capable of moving between sites,
so it is not possible to state unequivocally that one species only occurs in one location. S. haematobium most
often occurs in the venous plexus of bladder (C), but it can also be found in the rectal venules. The females
(size 7 to 20 mm; males slightly smaller) deposit eggs in the small venules of the portal and perivesical systems.
The eggs are moved progressively toward the lumen of the intestine (S. mansoni and S. japonicum) and of the
bladder and ureters (S. haematobium), and are eliminated with feces or urine, respectively (1).
Clinical Features
1. swimmers' itch
3. chronic schistosomiasis
☛ intestinal schistosomiasis
☛ may begin a few months after infection and may last for years
☛ colicky abdominal pain, bloody diarrhea, and anemia.
☛ fatigue and an inability to perform daily routine functions
☛ growth retardation.
☛ The severity of intestinal schistosomiasis is often related to the
intensity of the worm burden
☛ colonic polyposis
☛ Hepatosplenic schistosomiasis (HSS)
☛ Hepatomegaly
▪ in 15–20% of infected individuals;
▪ correlates roughly with intensity of infection,
▪ occurs more often in children, and
▪ may be related to specific HLA haplotypes
▪ right-upper-quadrant "dragging" pain
☛ Portal hypertension with splenomegaly and varices
☛ Liver fibrosis
▪ In late-stage disease
▪ liver function deterioration
▪ ascites, hypoalbuminemia, and defects in coagulation
☛ Urinary schistosomiasis
☛ 80% have dysuria, frequency, and hematuria
☛ Urine examination
▪ blood and albumin
▪ high frequency of bacterial urinary tract infection and
✓ urinary sediment cellular metaplasia
☛ hydroureter and hydronephrosis (25–50%)
☛ bladder granulomas undergo fibrosis
▪ squamous cell carcinoma of the bladder
☛ pulmonary schistosomiasis
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Diagnosis
Microscopy
✓ Identification of schistosome eggs in a stool or urine sample via
microscopy is the gold standard for the diagnosis of
schistosomiasis.
✓ It can also be used for species identification and to measure the
parasite burden
✓ Eggs of S. mansoni, S. japonicum, S. haematobium, S. mekongi,
and S. intercalatum can be found in stool (although S.
haematobium is principally found in urine).
✓ In endemic settings, the Kato-Katz method is a common thick-
smear technique using 5 mg of stool examined with a low-power
microscope lens
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Human schistosomiasis eggs: (A) S. mansoni. (B) S. hematobium. (C) S. intercalatum. (D) S. japonicum. (E) S.
mekongi.
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Treatment of Schistosomiasis
☛ Look at table below
❖ cercarial dermatitis
o Antipruritic agents
❖ acute schistosomiasis or Katayama fever
o Initial management: corticosteroids (prednisolone 20 - 40 mg
daily for 5 days).
o Praziquantel should be initiated only after acute symptoms
have resolved and should be administered concomitantly with
corticosteroids
❖ Neuroschistosomiasis
✓ prednisone 1 to 2 mg/kg for 2 weeks to six months → to prevent
irreversible tissue damage.
In settings of long-term corticosteroid use strongyloidiasis
should be excluded.
✓ Praziquantel, 40 mg/kg stat, a few days after (to reduce
paradoxical worsening of neurologic symptoms) initiation of
corticosteroid treatment
✓ The two therapies (prednisolone and praziquantel) should be given
concomitantly.
❖ For all individuals with established infection, treatment to eradicate
the parasite should be administered (table below).
❖ Hepatomegaly and bladder lesions regress with early treatment but
established fibrosis persists
Prevention
Control strategies for Schistosomiasis endemic areas include:
✓ Ingestion of the larvae of the ✓ Mebendazole, 100mg P.O.BID for 3 days or 500mg, stat
parasite together with food
✓ Presence of migrating larvae in Alternative (pregnant women)
the lungs can provoke ✓ Pyrantel pamoate, 700mg P.O. stat
pneumonia
Hookworm (Necator americanus or First line-options
Ancylostoma duodenale) ✓ Albendazole, 400mg P.O. stat (preferred) OR
✓ Mebendazole, 100mg P.O. BID for 3 days or 500mg stat
✓ Penetration of the larvae of the
parasite through skin Alternatives:
✓ Pyrantel pamoate, 700mg P.O. stat
Taeniasis/tape worm/ (T. saginata, First line-Intestinal infestation
T.solium) ✓ Praziquantel P.O. 600mg or 10mg/Kg, stat
Alternative
✓ Ingestion of row meat or milk ✓ Niclosamide, 2g, P.O. stat
from cows and pork
✓ T. solium (pork tapeworm) may
cause fatal cysticercosis Treatment of neurocysticercosis
✓ T.saginata is known as beef ✓ Albendazole P.O. 15mg/kg/day for 8- 28 days or
tape worm ✓ Praziquantel, 50–100mg/kg/day, TID, for 15–30 days.
▪ Longer courses are often needed in patients with
multiple subarachnoid cysticerci
PLUS
✓ High-dose glucocorticoids
✓ Anti-epileptics (if there is seizure)
Shistosomiasis / bilharziasis/ First line
Alternatives
For S. haematobium
✓ Metrifonate, 600 mg P.O., TID at 14 days interval.
For S. mansoni
✓ Oxamniquine, 1250 mg (30 mg/kg) P.O. stat.
☛ It is contraindicated in pregnancy and in general is not
as effective as praziquantel.
✓ Artemisinin derivatives may be used in very early infection to
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disrupt the glucose metabolism of immature schistosomes.
Pregnancy:
Pediatrics:
Alternatives
✓ Niclosamide, 2g P.O. on the first day followed by 1g daily for
6 days
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Etiology
Clinical features
Dyspepsia describes a wide and common clinical entity which presents
in one of the three ways:
1. Epigastric pain/burning (epigastric pain syndrome)
2. Postprandial fullness
3. Early satiety
Investigations
Treatment
Pharmacologic
I. H. Pylori negative
First line→ PPI
✓ Omeprazole, 20mg P.O., BID for 4-8 weeks
✓ Esomeprazole, 40mg P.O., daily for 4-8 weeks
✓ Pantoprazole, 40mg P.O., BID for 4-8 weeks
Alternatives → H2 receptor blockers
✓ Cimetidine, 400mg P.O., BID for 4-8 weeks
✓ Ranitidine, 150mg P.O. BID for 4-8 weeks
✓ Famotidine, 20-40mg P.O. daily for 4-8 weeks
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pump inhibitor, a tricyclic antidepressant can be initiated
as combination therapy with a proton pump inhibitor.
➢ Peptic ulcers are focal defects in the gastric or duodenal mucosa that extend
into the submucosa or deeper.
➢ The natural history of PUD ranges from resolution without intervention to the
development of complications like bleeding, perforation & GOO (Gastric outlet
obstruction).
➢ N.B anterior duodenal ulcer perforates and posterior duodenal ulcer bleeds.
Perforation is more common in males (M:F ratio = 8-10:1)
➢ PUD needs both medical and surgical evaluation
Pathophysiology
➢ PUD occurs due to imbalance between offending factors/risk factors/ and
mucosal defense mechanisms. Any factor and stimuli that can compromise the
protective mechanisms and/or intensify the damaging forces can result in
mucosal injury and inflammation
Clinical features
✓ Hematemesis/Melena
Investigations
1. H.pylori tests (Stool antigen, Serum antibody)
2. Upper GI endoscopy has both diagnostic & therapeutic importance → to look
for ulcers, protruding mass or any active bleeding. Gastric mucosal biopsies should be
obtained at the time of endoscopy to rule out infection with H. pylori.
3. Barium meal → It demonstrates barium within the ulcer crater.
4. ECG
☛ ECG should be done in elderly patients & patients with co-morbid illness
like DM, Hypertension & dyslipidemia who present with dyspeptic
symptoms.
☛ This will help you to rule out the life-threatening condition, acute coronary
syndrome.
☛ The rationale behind this workup is the consideration of the dyspepsia
symptom in such patients could be an angina equivalent.
5. Serum gastrin level
Management of PUD
✓ Medical management is the same as Dyspepsia which is discussed above
✓ Surgical treatment for PUD is indicated for:
▪ Perforation
▪ Hemorrhage
▪ Obstruction
▪ Intractable ulcer
Clinical manifestations
Symptoms
The two major symptoms of GERD which are considered classic
(typical) are heartburn and regurgitation.
o Heartburn is a commonly described by patients as a burning
sensation behind the sternum (retrosternal area).
o Regurgitation is defined as back flow of gastric contests in to
the mouth or pharynx. Patients feel an acidic (sour) content
coming to the mouth mixed with small amounts of undigested
food.
Other symptoms
o Chest pain: GERD associated chest pain can mimic angina
o Triggering asthma attacks (wheezing)
o Hoarsens of voice
o Persistent cough
o Nausea
o Sensation of a lump in the throat (Globus sensation)
o Increased salivation (Water brash)
Investigations
Upper GI (gastrointestinal) endoscopy
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Treatment
Non-pharmacologic treatment
Pharmacologic treatment
First line:
PPIs → No major difference in between the available PPIs
➢ Omeprazole 40mg PO daily for 8 -12 weeks OR
➢ Esomeprazole 40mg PO daily for 8-12 weeks OR
➢ Pantoprazole 40mg PO daily for 8-12 weeks
Stop therapy on symptom resolution to assess response
After the first 8 -12 weeks, resume therapy as needed → Intermittent
OR On demand
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3.8.4 GI bleeding
Gastrointestinal (GI) Bleeding refers to any bleeding that occurs from the
mouth to the anus.
Anatomically GI bleeding is divided in to upper and lower.
The ligament of Treitz is used as the anatomic reference to differentiate
lower and upper GI bleeding.
❖ The two major causes that should be considered in every patient with
overt upper GI bleeding are peptic ulcer disease and esophageal
varices.
5. Esophagitis
6. Vascular malformations,
7. Neoplasm
8. Coagulopathy
9. Obscure upper GI bleeding: often from small intestinal lesions
Clinical features
Symptoms
Nausea
Vomiting of bright red blood or coffee-ground matter
Melena
Hematochezia: rare in upper GI bleeding but can occur in massive acute
bleeding.
Symptoms related to the underlying cause
✓ Medication history: antiplatelet (aspirin, clopidogrel), NSAID or
anticoagulants
✓ Symptoms of portal hypertension or liver cirrhosis in patients with
variceal bleeding e.g. ascites, fatigue.
✓ The bleeding in varices is generally bright red, painless, brisk, and
voluminous.
✓ Long standing epigastric pain: Suggestive of PUD
✓ Preceding forceful vomiting or retching suggests Mallory-Weiss tears
✓ Weight loss: may indicate neoplasm
Signs
☬ Signs suggesting the hemodynamic status of the patient and the degree
of anemia
✓ Orthostatic hypotension
✓ Resting tachycardia
✓ Degree of pallor
☬ Signs of the underlying cause of the upper GI bleeding
✓ Signs of CLD or portal hypertension indicating the possibility of
bleeding varices: Ascites, splenomegaly, encephalopathy.
✓ Other site bleeding: platelet related disorders or coagulopathies
The next step in the diagnosis is trying to establish the cause of the
upper GI bleeding.
Upper GI endoscopy → has both diagnostic and therapeutic value.
Investigations
CBC
Serial hemoglobin/hematocrit every 8 hour→ the initial
hemoglobin/hematocrit may be normal as the loss is whole blood (both
plasma and cells)
Coagulation profile: PT (INR) and PPTT
Urea and Creatinine
Liver enzymes
Upper GI endoscopy
Risk stratification
There are a few risk stratification tools which are useful to assess the
likelihood of a person with upper GI bleeding to need further
interventions like endoscopic treatment and transfusion.
The Glasgow-Blatchford bleeding score (GBS) is one of the scores. It is
simple risk stratification tool which does not require endoscopy. We
recommend using the score
Table.: Glasgow-Blatchford bleeding score (GBS)
100 - 109 1
Systolic BP (mmHg) 99 - 90 2
< 90 3
Pulse ≥100 (per min) 1
Presentation with melena 1
Presentation with syncope
Hepatic disease
2
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Heart failure 2
Interpretation of the score
✓ 0 → low risk
✓ 1-7 → high risk, keep in hospital as the patient is
likely to require transfusion or endoscopic intervention
✓ ≥ 8 → requires ICU admission
Treatment
1. Hemodynamic stabilization
3. Arresting bleeding
Endoscopic therapy is the main stay of therapy to arrest bleeding
After hemodynamic stabilization.
Balloon tamponade may be performed as a temporizing measure for
patients with uncontrollable hemorrhage after tracheal intubation.
4. Open surgery
1. Vascular causes
o Hemorrhoids
o Ischemic bowel
o Vascular dysplasia (angiodysplasia)
o Post procedure (post polypectomy)
2. Neoplastic causes
o Colon cancer
o Polyps
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3. Anatomic causes
✓ Diverticulosis
4. Inflammatory causes
✓ IBD
✓ Infectious colitis
Clinical manifestations
Symptoms
✓ Bleeding from the left colon tends to be bright red in color while
bleeding from the right colon appears to be dark or maroon colored
and may be mixed with stool.
✓ Bleeding from the right colon might rarely cause melena (the stool
itself is dark)
Symptoms of anemia or hemodynamic compromise: fatigue, postural
dizziness, light headedness
Signs
✓ DRE
3. Localization of the bleeding and definitive diagnosis
✓ All patients with a clinical diagnosis of lower GI bleeding require
colonoscopic examination to identify the cause of bleeding, arrest
the bleeding if identifiable.
Investigations
☬ Baseline IX
✓ CBC: in massive acute bleeding the hemoglobin may appear
normal.
✓ Serial hemoglobin; every 8 hours
✓ Coagulation studies: INR (PT) and PTT
✓ Liver enzymes
✓ BUN and creatinine
☬ Colonoscopy: when the clinical diagnosis is lower GI bleeding
☬ Upper GI endoscopy: when the clinical diagnosis is upper GI bleeding.
Treatment
1. Hemodynamic status evaluation and resuscitation
o In patients with hemodynamic compromise secure two wide bore IV
cannula and resuscitate with crystalloids.
o While crystalloids are being given, blood should be requested for
transfusion.
✓ Do not depend on the initial hemoglobin or hematocrit to for
transfusion, as it is apparently (“falsely”) normal.
2. Discontinue antiplatelets, NSAID’s or anticoagulants
3. Correct coagulopathies 905
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Classification of UTI
➢ UTI is classified in different ways that have implication to treatment and
outcome
1. According to anatomic site of involvement:
✓ Lower UTI: cystitis, urethritis, prostatitis
✓ Upper UTI: pyelonephritis, involving the kidney
✓ Uncomplicated UTI:
☛ occurs in individuals who lack structural or functional
abnormalities in the UT that interfere with the normal flow of
urine.
☛ Mostly in healthy females of childbearing age.
✓ Complicated UTI:
☛ occurs in individuals with structural or functional abnormalities in
the UT that can interfere with normal flow of urine such as
▪ congenital distortion of the UT
▪ a stone
▪ an indwelling catheter or the use of intermittent bladder
catheterization
▪ vesicoureteral reflux or other functional abnormalities
▪ BPH
▪ Obstruction
▪ neurological deficit.
☛ UTI in men and pregnant women can be classified as complicated.
☛ RF risks for serious infections
▪ Recent urinary tract instrumentation
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Recurrent UTI
❖ Multiple symptomatic UTIs with asymptomatic periods in between.
❖ Significant when there a r e ≥ 2 symptomatic episodes per year or it
interferes with patient’s quality of life.
❖ It is usually a reinfection than a relapse.
▪ Relapse: Infection with same organism within 14 days of stopping
antibiotics for previous UTI
▪ Reinfection: a completely different organism; most common cause
of recurrent cystitis
Bacteriuria
❖ Asymptomatic bacteriuria:
✓ Bacteriuria > 105 bacteria/ml of urine without symptoms.
✓ It is very common in elderly women and men.
✓ Use of antibiotics for asymptomatic bacteriuria can drive antibiotic
resistance and increase the risk for subsequent symptomatic UTI.
✓ Asymptomatic bacteriuria should be treated in pregnant women and
in men undergoing urological procedures. The benefits of therapy in
other groups were questionable.
❖ Symptomatic abacteriuria:
✓ Symptoms of urinary frequency and dysuria in the absence of
significant bacteriuria
Etiologies
➔ The vast majority of acute symptomatic infections occur in young
women.
➔ E. coli cause approxmatley 80% of acute infections in patients without
catheters, stone or other urologic abnormalities. On the other hand,
organisms like klebsiella, enterobacteria, proteus, serratia and
psuedomonas assume greater importance in complicated and nosocomial
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Clinical features
❖ The range of possible symptoms caused by UTI is extremely broad,
from no symptoms to symptoms referable to the lower urinary tract
(e.g. dysuria and frequency), to symptoms indicative of an upper UTI
(e.g. loin pain, fever, chills and costo-vertebral angle tenderness), to
full-blown urosepsis.
➢ Clinical
☛ signs and symptoms and urinalysis are the common
diagnostic methods
☛ Digital rectal examination (DRE): For men with symptoms of
pelvic or perineal pain, DRE might be warranted to evaluate a
tender or edematous prostate, suggesting acute prostatitis.
➢ Imaging:
☛ e.g. Abdominal U/S (kidneys and urinary tract)- indicated in
complicated UTIs (suspected obstruction, severely ill)
poor responders and recurrent UTIs.
☛ Radiology helps to see calculus or obstruction or abscess
Treatment
Non pharmacologic
❖ Postcoital voiding and liberal fluid intake for women with recurrent
UTI
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abnormality.
☛ Antimicrobials alone might not be effective unless correcting
such underlying conditions.
☛ Patients with neurogenic bladder, indwelling bladder catheters,
nephrostomy tubes, and urethral stents may require additional
intervention, like more frequent catheterization to improve
urinary flow, exchange or removal of a catheter, or
urologic/gynecologic consultation.
Pharmacologic
First line
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Alternative
First line
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Alternative
Alternative
✓ ceftazidime 2 gm IV TID or
✓ cefepime 2 gm IV TID
✓ piperacillin-tazobactam 3.375 gm IV QID
o piperacillin-tazobactam may be used as an initial agent due to its
advantage of covering gram positive cocci (staphylococci and
enterococci) infections.
Vancomycin may be added based on the potential for MRSA (e.g. previous
MRSA isolate from the patient)
E. Recurrent UTI
F. Prostatitis
G. Epididymitis
Pregnancy
Paediatrics
Lower uncomplicated UTI (acute cystitis)
First line agents:
✓ Cotrimoxazole, 48mg/kg/day, PO, BID for 3- 5 days (available
syrup preparation 240mg/5ml)
o not recommended in the first 6 weeks of life.
Alternatives
✓ Augmentin 50-80mg/kg/day, PO, TID for 3-5 days (available syrup
preparation 400mg/5ml or 200mg/5ml) or
✓ Amoxicillin 50-80mg/kg/day, PO, TID for 3-5 days (available syrup
preparation 250mg/5ml, or 125mg/5ml)
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1. Plasmodium-infected Anopheles mosquito bites a human and transmits sporozoites into the
bloodstream.
2. Sporozoites migrate through the blood to the liver where they invade hepatocytes and divide to
form
multinucleated schizonts (pre-erythrocytic stage).
3. Hypnozoites are a quiescent stage in the liver that exist only in the setting of P. vivax and P.
ovale infection. This liver stage does not cause clinical symptoms, but with reactivation and release
into the circulation, late onset or relapsed disease can occur up to many months after initial
infection.
4. The schizonts rupture and release merozoites into the circulation where they invade red blood cells.
Within red cells, merozoites mature from ring forms to trophozoites to multinucleated schizonts
(erythrocytic stage).
5. Some merozoites differentiate into male or female gametocytes. These cells are ingested by the
Anopheles
mosquito and mature in the midgut, where sporozoites develop and migrate to the salivary glands
of the mosquito. The mosquito completes the cycle of transmission by biting another host.
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Epidemiology
❖ Approximately 60% of the Ethiopian population live in malaria risk
areas.
❖ Majority of malaria cases have been due to P. falciparum, with the
remainder caused by P. vivax.
❖ Principal determinants of the epidemiology of malaria
1. Number, Density, human – biting habit and longevity of the
vector. Eg.
Anopheles gambae is long-lived, breed readily, high density in the
tropics,
preferably bites humans to other animals
2. Entomologic inoculation rate • Sporozoite + ve mosquitoes/Person
/Yr (>300 in tropical Africa)
Pathogenesis
The disease in humans is caused by the direct effects of RBC invasion
and destruction by the asexual parasite and the host’s reaction
NB: Almost all deaths are caused by falciparum malaria
Host Factors: -
Geographic distribution of sickle cell disease, thalassemia and G6PD Deficiency
closely resemble that of malaria before introduction of control measures
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clinical diagnosis
❖ a patient from malaria endemic area has fever or history of fever in the
last
48 hours or a patient from non-malaria endemic area has fever or history
of fever in the last 48 hours and has a history of travel to malaria endemic
areas within the last 30 days and spending at least one night.
❖ Making the diagnosis of malaria on clinical features alone is not
recommended, as this often has low specificity and increases the chances
of the patient being misdiagnosed.
❖ The health worker examining a suspected malaria case should look for
other
causes of fever (e.g. typhoid fever, relapsing fever, ARTI, meningitis,
schistosomiasis, visceral leishmaniasis)
Laboratory diagnosis
Microscopy→ Demonstration of the parasite by peripheral blood smear
o Thick and thin blood smear (100 - 200 thick field exam). Light
microscopy using thick blood films can be very sensitive, detecting as
few as 5 parasites/µl of blood.
o Diagnosis of malaria
o Species identification
o Determination of parasitaemia (8000 wbc/µl assumption)
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* Identification of a schizont with >12 merozoites in the peripheral circulation is an important diagnostic clue for
P. vivax. In general, schizonts of P. falciparum are very rarely seen in blood films; they are generally absent
from the peripheral circulation except in cases of severe infection with overwhelming parasitemia.
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Immage; Rapid malaria test; T1 Positive → Positive result for P. falciparum (P.f.), T2 Positive → Positive result
for P. vivax (P.v.) or P. malariae (P.m.) or P. ovale (P.o.) In some cases the appearance of only the T2 Line
may indicate a mixed infection with two or more of P.v., P.m., and P.o., T1 + T2 Positive → Positive result for
P. falciparum (P.f.) In some cases the appearance of both the T1 and T2 Lines may indicate a mixed infection
of P.f. with another species, No T1 or T2 Lines → Negative result (no malaria antigens were detected)
For more about rapid malaria test, click here → Rapid malaria test
P. falciparum
Coartem (Artemether (120mg) - Lumefantrine (20mg)) combined
tablets 4 tabs po bid for 3 days.
AL and single dose primaquine is the recommended first-line drug
So, the usual dosage of coartem for adults is → Coartem,4 tabs, po, BID,
for 3 days
To reduce the transmission of P. falciparum infection, give a single dose of
0.25 mg/kg primaquine with AL (except pregnant women, infants aged < 6
months and women breastfeeding infants aged <6 months. and testing for
G6PD deficiency is not required during primaquine treatment
Supportive treatment:
If patients, especially children present fever of ≥37.50 C, treat with
antipyretics and, if necessary, fanning and tepid sponging.
✓ Paracetamol (acetaminophen) 15 mg/kg every 4 hours is widely
used; it is safe and well tolerated, given orally or as a
suppository
N.B
Clinical features
Unarousable coma/cerebral malaria
Respiratory distress (acidotic breathing/deep breathing or in-drawing
of chest wall) → acidaemia/acidosis
Severe anaemia (normochromic, normocytic) → paleness of palms is most
reliable symptom in children
Renal failure
Pulmonary oedema/ ARDS
Hypoglycaemia
Hypotension/shock
Bleeding/DIC
Convulsions or recent history of convulsions
Haemoglobinuria (cola coloured urine)
Other
• Impaired consciousness/arousable
• prostration, i.e. generalized weakness so that the patient is
unable to walk or sit up without assistance.
• Unable to eat or drink
• Repeated vomiting, resulting in inability to retain oral medication
• Severe dehydration
• Jaundice (yellowish discoloration of the eyes)
• No urine output in the last 24 hours
Laboratory findings
Severe anemia (hemoglobin <5g/dl, haemocrit < 15%)
Hypoglycemia (< 40 mg/dL)
Acidosis (bicarbonate <15 mmol/L)
Hyperlactatemia (>5 mmol/L)
Hyperparasitemia (>4% parasite density or >200,000 parasites per ul of
blood in non-immune person)
Renal impairment (creatinine >3mg/dl)
•Viral encephalitis
• Bacterial meningoencephalitis
• Cerebral typhoid
• Cerebro-vascular event (stroke)
• Complicated typhus, relapsing fever
• Febrile illness with hypoglycaemia
• Sepsis
• Convulsion in a patient with fever
Renal failure
• Glomerulonephritis (AGN)
• Acute tubular necrosis (ATN) due to hypovolemia or hypotension
• Viral hepatitis
• Yellow fever
• Acute cholecystitis
• Choledocholithiasis
Pharmacologic mgt
First line
➢ Artesunate, IV or IM
Alternative
➢ Artemether, IM
➢ Quinine infusion, IV or
➢ Quinine, IM
Clinical features
Management
Ensure ABC of life, coma care, feeding, bladder and bowel care,
detection and treatment of other complications like aspiration
Start artesunate immediately
Broad spectrum antibiotic to cover other DDX like meningitis (if
possible do LP before initiating antibiotic)
1.2 Hypoglycemia
Give 50% dextrose (0.5gm/Kg) followed by infusion of 10% dextrose (0.1
gm/kg/hr)
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1.3 Seizure
Do RBS to R/O hypoglycaemia, if there correct as mentioned above
Diazepam 0.15 mg/kg maximum 10mg IV stat then phenytoin 20mg/kg followed
by 5 mg/kg/day
The IV diazepam can also be given intra-rectally using a rectal tube or NG
tube (0.5-1.0 mg/kg) if injection is not possible.
Diazepam can cause respiratory depression. Therefore, an Ambu bag and
resuscitation equipment should be at hand when used.
Note:
Management
The most common indication for blood transfusion is severe anaemia. 927
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Assess the patient’s clinical condition rather than relying on the haematocrit
and/or Hb level.
As a rule of thumb: Indication for transfusion
➢ If the haematocrit is <15%
➢ Anomia-associated acidosis, shock or the parasitaemia is so high that
you can predict a critical drop
➢ Spontaneous bleeding
Clinical presentation:
Hyperventilation (rapid breathing) is the initial manifestation
Crackles are present on auscultation, and pink frothy sputum (severe
cases).
Management
Semi-erect positioning
Intra nasal O2
Fluid restriction and
Diuretics for overhydration, e.g. furosemide 40 mg IV. If no response
increase dose progressively to maximum 6mg/kg/day
Intubation and mechanical ventilation including positive end expiratory
pressure (PEEP), perform regular suction (via endo tracheal tube or oral/
naso pharangeal airway) for ARDS
Management 928
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Management
Correct rehydration
decrease IV quinine dose by 30-50 % after 2 days of Rx
Avoid nephrotoxic drugs
Follow input-output and serum cr
Haemodialysis when cr > 3mg/dl
1.8 Hemoglobinuria:
➢ Hemoglobinuria results from the rapid breakdown of red blood cells
(massive
intravascular hemolysis) in the circulation.
Clinical presentation:
➢ The urine is dark, and tests strongly positive for blood (Hb) but contains no
red
cells on microscopy.
➢ The plasma may also be dark because of the hemoglobin released from
the red
cells.
Management:
➢ Maintain hematocrit above 15%
➢ monitor JVP to avoid fluid overload and hypovolaemia 929
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➢ If oliguria develops and BUN & cr levels rise, consider peritoneal dialysis or
hemodialysis
➢ continue anti-malarial therapy.
1.9 Jaundice:
Jaundice is more common in adults than in children and is due partly to
hemolysis and partly to liver dysfunction.
Clinical presentation:
Yellowish discoloration of the sclerae of the eyes or the frenulum of the
tongue is quite commonly seen in severe P. falciparum malaria in adults,
but is uncommon in children.
Signs of hepatic failure are rare.
Jaundice in malaria occurs at the same time as fever, unlike jaundice due
to hepatitis.
If jaundice is present, look for other complications.
Management:
❖ Check bleeding time of the patient, crossmatch blood, give whole fresh
blood or
platelet infusion as needed to correct blood loss and bleeding.
Pathogenesis
Abnormal immune response to repeated malarial infection
RES hyperplasia and clearance
Presentation
Massive splenomegaly + peri splenitis
Hepatomegaly
Anaemia (NCNC) + pancytopenia
Prone to skin + respiratory infection, sepsis
Serum titre of IgM and malarial Antibodies
Hepatic sinusoidal lymphocytosis
Peripheral B-Cell lymphocytosis
Hypergammaglobulinemia
At risk of malignant lymphoproliferative disorder
Treatment
Chloroquine 300mg po weekly for 3-6 months. Weekly and daily
dosing’s are said to be equally effective
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Prevention of Malaria
Early detection and prompt treatment of cases
Personal protection measures: Using permethrin impregnated bed nets
/Mosquito repellents
Chemoprophylaxis: 1wk before departure and for 4 wks after leaving
the endemic area. Drug options:
✓ Mefloquine 228mg of base (250mg of salt) or 5 mg/kg po/week
✓ Doxycycline 100mg once a day
✓ Chloroquine 300mg of base orally, once\wk
✓ Proguanil 200mg orally, once \day, in combination with weekly
chloroquine
Pregnancy
Maternal effect
Fetal effects
Paediatrics
➢ AL is currently recommended for the treatment of uncomplicated
malaria in infants under 5 kg as the same dose as 5 kg
➢ Chloroquine is a safe drug that can be used in all children with only P.
vivax infection
➢ Available syrups for infants and children
✓ cotexin syrup /dihydro artemisinin/, 160mg/80ml, 4 mg/kg/day,
PO, BID for 4 days or 4 mg/kg/day, PO, BID in the 1st day
followed by 2 mg/kg/day PO, BID for the next 6 days (used for
all malaria subtypes)
or you can use the following table for dihydro artemisinin syrup
Weight in Day1 (ml, PO, BID) Day 2 to day 7
kg (ml, PO, BID)
< 5 5 2.5
5 - 10 10 5
10 - 15 15 7.5
16 - 20 20 10
> 20 Tablet is recommended
A. Coartem (AL)
Contraindications:
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Contraindications:
C. Primaquine phosphate
➢ dose: 0.25 mg base per kg daily for 14 days for P. vivax (single dose
primaquine for P. falciparum
cases)
Contraindications:
✓ Pregnancy
✓ In breast feeding mothers less than six months infants
✓ Infants under six months
✓ Any condition that predisposes to granulocytopenia, such as active RA &
SLE
❖ Symptomatic anemia
❖ Urine color: a score of 5 or above on the Hillmen urine colour chart
❖ Hemoglobin < 5 g/dL
❖ Hemoglobin drop of >50% of the baseline
❖ Hemoglobin < 7 g/dL AND Hemoglobin drop from baseline of >25%
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Procedure
✓ The day of initial treatment is designated as day zero. The patient will be
seen at the health facility at days 3, 7 and 13 to check symptoms of
anemia, urine color and hemoglobin measurement.
✓ Ask for anemia symptoms at each visit.
✓ Measure hemoglobin on days 0, 3, 7 and 13
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F. Artemether injection
Artemether injection is given at a loading dose of 3.2 mg/kg on the first
day followed by 1.6 mg/kg daily for two days. Then if the condition of the
patient improves, will be followed by full dose AL
Relative Contraindications:
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Salmonellosis
❖ Caused by the genus Salmonella → Non spore-forming gram -ve
bacilli
❖ Enteric fever
o Clinically the most important form
o Caused by:
Salmonella enterica serotype Typhi (formerly S. typhi) –
Causes typhoid fever
Salmonella enterica serotypes Paratyphi A, B and C
(formerly S. paratyphi A, B and C) – Cause paratyphoid
fever
Typhoid fever
Typhoid fever is an acute febrile illness caused mainly by Salmonella
typhi. The mode of transmission is via contaminated food or water.
Clinically the term includes the milder paratyphoid fever
Common in countries with poor access to sanitation
Pathogenesis:
Clinical presentation
✓ IP: 3 to 21 days
Fever and abdominal pain
Diarrhoea (children, HIV infected, malnourished patients) or
constipation (adults)
Skin rashes (rose spots)
Hepatosplenomegaly
Delirium, coma
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Rose spots are small (1 to 5 mm), erythematous, blanchable, nontender papules, which begin early during the
acute febrile period of typhoid fever. Crops of lesions (10 to 20) appear at irregular intervals for approximately 10
to 14 days, typically distributed on the abdomen, chest, and back. Rarely, vesicular or hemorrhagic lesions
appear. The lesions persist for two to three days.
o Abdominal pain
o Diarrhoea or constipation
o Skin rashes (rose spots)
➢ 3 week
rd
o Hepatosplenomegaly
o GI bleeding
o Intestinal perforation (severe abdominal pain)
N.B these features are not always present. But fever is always there the
name so called typhoid fever
Complications
Diagnosis
Management
Symptomatic treatment:
Use of antipyretics, e.g. paracetamol to control fever.
Alternative
First line
Alternative
First line
Alternative
✓ Prednisolone, 20-40mg P.O., (or equivalent) once daily for the first
3
days of antibiotic treatment.
Paediatrics:
Pregnant women:
First line
Alternative
1. Epidemic Typhus
Epidemiology:
Transmission
2. Endemic Typhus
Transmission:
✓ Fleas acquire R. typhi from rickettsemic rats and humans are infected
when rickettsia-laden flea feces are “scratched” into pruritic bite
lesions
and infrequently by direct flea bite
✓ Inhalation of aerosolized flea feces can transmit the infection
✓ IP: 1 to 2 weeks
✓ Prodromal symptoms: headache, myalgia, arthralgia, nausea and
malaise
Followed by abrupt onset of fever (>38°C), chills,
maculopapular rash
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Rash
▪ Usually starts on the 5th day
▪ Macular, maculopapular, petechial
▪ Initially on the trunk -> then becomes generalized
▪ Spares face, palms and soles
✓ Pulmonary involvement is frequently prominent
o Dry cough, bibasilar rales
o CXR: interstitial pneumonia, pulmonary edema, pleural effusion
Tachycardia
Hypotension
Less commonly: abdominal pain, Eye pain, confusion, stupor,
seizures, ataxia,
coma, photophobia, jaundice, conjunctival injection, Splenomegaly
CXN of typhus
➢ Vasculitis resulting in gangrene and cerebral thrombosis is among the
more serious complications of typhus.
➢ Skin necrosis and gangrene of the digits
✓ Respiratory failure
✓ Hematemesis
✓ Cerebral hemorrhage
✓ Greater severity is associated with old age, underlying disease and
treatment with sulfa drugs
✓ Case fatality rate in untreated patients: 1%, may reach up to 40%
Diagnosis of typhus
The Weil Felix serology test with demonstration of a rising/high titer.
o For more about Weil Felix serology test click here → Weil-Felix
slide agglutination test
IFA (Micro immunofluorescent) and plate microagglutination tests have
high sensitivities for typhus
Immunohistology of skin biopsy
PCR
Treatment of typhus
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Non pharmacologic
✓ Delousing:
➢ Regularly washing clothes and body plus long-acting insecticides
should be used.
➢ Pyrethroid permethrin is the delousing agent of choice. It can be
applied as a dust or spray to clothing or bedding.
Pharmacologic
First line
✓ Doxycycline, 100mg, PO, BID (200mg, P.O., daily) for 7-10 days OR
✓ Tetracycline, 250mg, P.O., QID for 7-10 days
Alternatives
Prevention
➢ Delousing:
➢ Antibiotic prophylaxis:
▪ Doxycycline 200mg PO stat.
▪ For travelers to endemic areas a weekly single dose for the
duration of stays and continued for one week after leaving the
area can be used.
➢ Environmental control: Areas where flying squirrels are common like
in campgrounds, roof joists, etc. should be sealed with metal
screening to prevent squirrels from nesting in inside homes or around
human residency areas.
➢ No specific vaccine is on use currently.
Pediatrics:
Pregnant women:
❖ After infection spirochetes enter the blood and are spread to different
sites: liver, spleen, CNS, bone marrow, etc.
❖ Severity of illness depends on the density of spirochetes in the blood
Clinical manifestations
Physical examination:
Diagnosis
Management
Non pharmacologic
❖ Delousing
Pharmacologic
First line
Alternative
Prevention
Pediatrics:
Pregnant women:
N.B.
1. Jarish-Herxheimer reaction:
Males are much more commonly affected than females. It is rare to find
gout in reproductive age woman, after menopause the difference
between men and women narrows.
Even though hyperuricemia is the cause gout, only 10-15% of patients
with hyperuricemia develop gout.
Most patients with hyperuricemia don’t develop clinical Gout in their life
time. Due to this fact hyperuricemia should not be considered equivalent
to Gout.
Clinical features
Symptoms
Severe (excruciating) pain over a joint associated with swelling, redness,
and hotness.
The pain is acute in onset and reaches to its maximum within 6-
12hours, not exceeding 24hours.
Initial attacks involve a single joint. Rarely multiple joints may be
involved.
The majority of the first attacks involve the base of the great toe
(known as podagra) or knee.
Flares usually subside within several days without treatment and few
days with treatment.
Patients might perceive the initial attack as an unnoticed trauma.
The course of gout after the first attack is variable. Some might have
no recurrence while other might have frequent or occasional recurrences.
Multiple joint involvement and upper extremity involvement at initial
presentation should prompt investigation for other causes of polyarthritis.
Most patients do not have any symptoms in the period between flares.
Signs
A swollen, tender, erythematous joint and evidence of joint effusion.
Symptoms
Signs
Clinical dx
Based upon the total score, patients can be identified as having probability of gout as;
➢ low (≤4 points),
➢ intermediate (>4 to <8 points)
➢ high (≥8 points)
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o Ultrasound of joint/s:
Treatment of gout
Pharmacologic management
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B. In individual with impaired kidney function: short course steroids are first
line
Prednisolone, 30mg per day, to be tapered over 10-14 days.
❖ Typical prescription: 30mg x3days, 20mg x3days, 10mg x3days,
5mg x3days
Intramuscular steroid/Intra-articular steroid: If oral prednisolone is not
tolerated
Triamcinolone acetonide 40-60mg, IM, stat.
❖ For intra-articular 40mg for large joints and 20mg for small joints.
Methylprednisolone 40-80mg, IM, stat.
❖ For intra-articular 40mg for large joints and 20mg for small joints,
intra-articular, once
C. In patients with diabetes; worsening of hyperglycemia should be
anticipated and doses of diabetes medication needs to be adjusted
accordingly.
First line
✓ Colchicine 0.5 to 1mg/day
1. Dietary management
Dietary management alone is insufficient to control gout but it is an
important adjunct.
Excessive focus on dietary management without using effective urate-
lowering therapy should be avoided.
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3. Education
All patients with gout should be educated on flare management, the
purpose and the lifelong nature of urate lowering therapy, adherence,
dietary and life style management
Educate patients and their families on the common misconceptions on
the dietary management of gout.
The age of onset also ranges childhood to old age. The common age
of onset is third to 3rd to 5th decade.
Renal disease is the commonest organ/life threatening involvement.
Lupus is associated with increased risk of thrombosis and accelerated
atherosclerosis
Pregnancy increases the risk of flare and should be avoided unless the
lupus in remission for more than six months.
Clinical features
Symptoms
Signs
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Investigations
Autoantibodies
o ANA
o Anti-dsDNA
o Anti-Smith
o Anti-phospholipid antibodies: Lupus anticoagulant, anti-cardiolipin,
beta-2 glycoprotein
Investigations for systemic involvement
o CBC → anemia, thrombocytopenia, leukopenia
o U/A → proteinuria, hematuria
o 24hour urine protein >500mg
o Creatinine and urea
o CXR → pleural effusion, interstitial infiltrates
o Echo
o MRI and MRA
Diagnosis
o The two widely used classification criteria for SLE clinical diagnosis
are the 2012 SLICC and 2019 EULAR/ACR
o Both have good sensitivity and specificity (83.7% to 96.7%); hence, it
is advised to use either of them for the purpose of diagnosis in
patients with clinical features suggestive of SLE.
Treatment
Non-pharmacologic treatment
Exercise
Minimization of sun exposure: hat, umbrella
Stress management
Pharmacologic management
Clinical features
Symptoms 964
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Joints symptoms
o The most typical symptomatic presentation of RA is that of a
symmetric polyarthritis (defined as involving > 5 joints), involving
small joints of the hands, wrists, and/or feet.
o Joint pain
o Joint swelling
o Early Morning stiffness: usually lasts > 02 hours
o Limitation of joint mobility (difficulty of using the joint)
Constitutional symptoms
o Fatigue
o Generalized musculoskeletal pain
o Weight loss
Symptoms from other organ-system involvement (extra-articular
symptoms)
o Occasionally patients may also present with other organ involvements:
o Cough, shortness of breath, chest pain: Lung involvement
o Dryness of the eyes, red and/or painful eyes: Eye involvement
o Swellings(nodules), red/dark lesions, ulcers on the skin : Skin/vascular
involvement
o Numbness or pain over the extremities: Peripheral nerve involvement
Signs
Joint
o Swelling (bogy swelling from effusion or subtle swelling from
thickening)
o Tenderness
o Deformities (swan neck deformity of fingers, ulnar deviation of MCP
joints, Boutonniere deformity of thumb…)
Other organ-systems (extra-articular signs):
o Depending on the systems involved e.g. subcutaneous nodules,
enlarged lymph nodes, signs of pleural/pericardial effusion,
splenomegaly
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These criteria should be restricted to persons with at least one clinically detectable
swollen joint in the absence of a more likely diagnosis
A score of ≥6 points is classified as definite RA. In each domain, consider only the
category with most points.
Joint involvement and distribution (0-5 points)
➢ Any swollen or tender joint on physical examination
➢ Large joints: Shoulders, elbows, hips, knees, and ankles
➢ Small joints: Metacarpophalangeal, proximal interphalangeal, second through fifth
metatarsophalangeal, thumb interphalangeal, and wrists
✓ 1 large joint → 0 point
✓ 2–10 large joints → 1 point
✓ 1–3 small joints → 2 points
✓ 4–10 small joints → 3 points
✓ > 10 joints (and at least 1 small joint) → 5 poin
Treatment
Pharmacologic treatment
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3) Corticosteroids: Indications
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Diagnosis of
RA made
✓ Old age
✓ Overweight/obesity
✓ Female sex
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✓ Occupation
✓ Injury/trauma.
Clinical features
Symptoms
➢ Joint pain
✓ Pain in OA is generally activity related and relived by rest. It is
more intense at the start of activity.
✓ It is worse in the afternoon and evening.
➢ Joint stiffness
✓ The morning stiffness in OA is shorter (<30 minutes) compared to
rheumatoid arthritis and other inflammatory arthritis.
➢ Symptoms of “crepitus”
✓ Clicking, grinding or popping feelings
➢ Instability of joint:
✓ Buckling or giving away feeling, lacking the confidence to use
weight bearing joints
➢ Limitation of movement
➢ Deformity
Signs
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Treatment
Pharmacologic treatment
➢ Pain management:
First line
➢ Non-tramadol opioids
➢ Systemic steroids
➢ Colchicine
➢ Bisphosphonates
➢ Methotrexate
Non-pharmacologic management
➢ Exercise:
✓ Both aerobic (e.g. walking) and local muscle strengthening are
useful
✓ Tai Chi (a form of Chinese martial art practice along with
meditation) and Yoga
➢ Weight loss: For overweight individuals with knee or hip OA
➢ Patient education: including self-management
➢ Cane or walking stick /for knee or hip OA/, braces/ tibiofemoral knee
braces for knee OA / and orthosis / Hand orthosis for first
carpometacarpal joint
➢ Surgical treatment
✓ Total joint replacement hip or knee) can be considered in patients
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➢ Arthroscopic debridement
➢ Abrasion arthroplasty (involving burring and drilling of sclerotic bone)
➢ Synovectomy
Aetiology
Clinical features
➢ Gradual onset varying from few days to weeks of local bone pain, swelling,
low grade fever, malaise and weight loss.
Investigations
➢ Usually Clinical Dx
➢ CBC
➢ ESR & CRP
➢ X-ray of the affected bone
➢ Culture of pus/sequester (if debridement is done)
Treatment
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➢ Rest/immobilization
➢ Surgical debridement (Drainage by surgeon/orthopedic surgeon)
➢ N.B. Osteomyelitis frequently requires both surgical therapy for debridement of
necrotic material together with antimicrobial therapy for eradication of infection.
The debrided necrotic material should be sent for culture.
Pharmacologic
➢ Empiric antibiotic
✓ Empiric treatment with activity against S. aureus (especially MRSA) and
gram-negative organisms is required.
First line
✓ Vancomycin, 30mg/kg/day, IV, BID (initially 20 mg/kg loading dose, not to
exceed 2 g/dose)
PLUS
✓ Ciprofloxacin, 750mg, P.O., BID OR
✓ Ceftriaxone 2 g IV daily
Alternative
✓ Cloxacillin, 2gm, I.V. QID PLUS
✓ Ciprofloxacin, 750mg, P.O., BID
Once susceptibility results were available, specific drugs should be used.
Duration of therapy
✓ Duration of antibiotics is for at least 6 weeks
✓ For patients with residual infected bone that is not amenable to complete
removal should be treated at least for 6 weeks duration after the last
debridement (optimal duration is uncertain).
✓ For patients who undergo amputation or complete removal of all involved
bone warrant a 5 days course of antibiotic therapy after complete
debridement. If there is evidence of soft tissue infection at the operative
side pathogen-directed 10 to 14 days parenteral or highly bioavailable oral
agent can be used.
✓ In the presence of orthopedic hardware, 6 weeks parenteral therapy
following debridement is used. Thereafter, long-term antibiotic suppression
with an oral agent, guided by antimicrobial susceptibility data is
recommended. Suppressive therapy is warranted only for individuals with
retained hardware and/or necrotic bone not amenable to complete
debridement. Oral suppression antibiotics should be continued at least
until fractures are united (demonstrated radiographically).
✓ In addition, ESR & CRP should be obtained at the beginning and end of
parenteral treatment (at any time in between if clinical suspicion for
treatment failure) and at the time of transition to oral suppressive therapy
(if used).
✓ If inflammatory markers persistently elevated two weeks after completion
of antibiotic therapy (in the absence of alternative explanation) possibility
of persistent osteomyelitis be considered.
✓ If a patient has associated symptoms, evaluate completeness of the
debridement, review microbiologic diagnosis and susceptibility data and
thus may warrant repeated debridement and additional antimicrobial
therapy.
✓ If no clinical signs consistent with persistent infection, clinical observation
is reasonable.
✓ For patients on oral suppressive antibiotic therapy:
✓ CBC, creatinine, and ALT at 2, 4, 8, and 12 weeks and then every 6 to
12 months thereafter.
Clinical features
➢ Septic arthritis presents acutely and mostly with a single swollen and painful
joint.
Investigations
➢ CBC
➢ ESR/CRP
➢ Synovial fluid analysis → cell count (WBC count) with differentials, Gram stain,
AFB, culture (two sets), and assessment for crystals.
➢ X-ray of the affected joint
Diagnosis
➢ Septic arthritis should be suspected in patients with acute onset of at least one
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Treatment
➢ In general, management of acute bacterial arthritis involves joint drainage
(since this condition represents a closed abscess) and antimicrobial therapy.
Non pharmacologic
➢ Aspiration/drainage: needle aspiration, arthroscopy, or arthrotomy (open surgical
drainage)
➢ Splintage, but early immobilization if joints are mobile.
➢ The joint must be splinted with a POP slab or skin traction to relieve pain and
prevent contractures
First line
✓ Vancomycin, 30mg/kg/day, IV, BID, not to exceed 2g/day for 4-6 weeks
PLUS
✓ Ceftriaxone, 2gm, I.V, daily for 4-6 weeks or
✓ cefotaxime 2 g IV TID
Alternatives
✓ Cloxacillin, 2g, IV, QID for 4-6 weeks
plus
✓ Ceftriaxone 2gm, IV, daily or
✓ cefotaxime 2 g IV TID
➢ NB: For suspected septic arthritis (in the above regimens) due to MRSA
Vancomycin is a suitable. Alternatives include clindamycin, Cotrimoxazole,
doxycycline, linezolid, and rifampin in combination with either ciprofloxacin or
fusidic acid.
➢ For suspected septic arthritis due to MSSA suitable choices include Cloxacillin,
dicloxacillin (500 mg, PO, QID), flucloxacillin (500 mg, PO, QID), or cephalexin
(500 mg, PO, QID).
➢ Patients who are allergic to penicillin can be treated with clindamycin (600 mg,
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➢ If synovial fluid gram stain shows gram positive cocci → use vancomycin with
the above dose as first line and Cloxacillin as alternative.
➢ If synovial fluid grams stain shows gram negative bacilli -use third-generation
cephalosporin (use ceftriaxone with the above dose) as first line.
➢ If the initial Gram stain of synovial fluid is negative but synovial fluid cell count
is consistent with septic arthritis (purulent fluid of 50,000 to 150,000 cells,
mostly neutrophils), the approach depends on individual clinical circumstances.
✓ For immunocompetent patients without confounding factors (such as
trauma), use vancomycin.
✓ For immunocompetent patients with traumatic bacterial arthritis, use
vancomycin plus a third-generation cephalosporin.
✓ For immunocompromised patients and injection drug users, use
vancomycin plus a third-generation cephalosporin (ceftriaxone).
✓ Ceftazidime (2 g IV TID) or cefepime (2 g IV TID to QID) should be used
in place of ceftriaxone if there is a high risk for Pseudomonas infection.
✓ Consequently, antibiotic therapy should be adjusted to culture and
susceptibility data once available.
Duration of therapy
➢ Duration of antibiotic treatment is 4-6 weeks (optimal duration is uncertain).
➢ At least the first 2 weeks of antibiotics should be through IV route.
➢ For susceptible pathogens durations may be shorter than indicated (e.g.
fluoroquinolone susceptible pathogens can be treated for 5 to 7 days of
parenteral, followed by 14 to 21 days of oral fluoroquinolone with careful
monitoring of the compliance and response).
➢ For staphylococcus bacteremia (in the absence of endocarditis) 4 weeks
parenteral treatment is recommended.
➢ If no staphylococcus bacteremia 1 to 2 weeks oral therapy can be used after
1 to 2 weeks of parenteral therapy.
➢ For patients with septic arthritis with endocarditis, treat for duration required for
endocarditis.
➢ Patients with septic arthritis and contiguous osteomyelitis require a long (4-6
weeks) course of antibiotics.
3.12 Miscellaneous
3.12.1 Anaemia (የደም ማነስ)
Classification of anemia
➢ Designed for systematic approach of different causes of anemia
➢ There are two approaches of classification
I. Kinetic approach→ Based on the mechanisms responsible for the
anemia
II. Morphologic approach → Based on the size of RBCs and the
reticulocyte response
1. Kinetic approach
A) Anaemia due to decreased RBC production
✓ Also known as ineffective erythropoiesis
✓ Causes include
▪ Lack of nutrients- iron, folate, or B12
▪ Bone marrow disorders- aplastic anemia, MDS, tumour
infiltration
▪ Bone marrow suppression- drugs, irradiation
▪ Anemia of chronic disease/inflammation
B) Anemia due to increased RBC destruction
✓ Haemolytic anemias
C) Anemia due to blood loss
✓ Obvious or occult bleeding
Morphologic approach
➢ Chromicity
✓ Normochromic → MCH = 27-33 or central pallor of RBCS < 1/3rd of
the size of RBC
✓ Hypochromic → MCH <27 or central pallor >1/3rd of the size of
RBC
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Clinical features
Symptoms
➢ Fatigue, dyspnea, palpitation, syncope
➢ Headache, lightheadedness, tinnitus, vertigo, difficulty of concentration
➢ Anorexia, nausea, indigestion
➢ Symptoms s of the underlying disease e.g. melena in GI bleeding,
heavy menstrual bleeding, generalized body swelling in CKD,
Signs
➢ Pallor, tachycardia, wide pulse pressure /ejection systolic murmur.
➢ Signs of Heart Failure (raised JVP, S3, hepatomegaly, edema)
➢ Signs of the underlying disease-causing anemia: lymphadenopathy,
splenomegaly, angular chelitis, tumors (abdominal/ pelvic mass) etc.
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Picture; High-power view of a normal peripheral blood smear. Several platelets (arrows) and a normal lymphocyte
(arrowhead) can also be seen. The red cells are of relatively uniform size and shape. The diameter of the
normal red cell should approximate that of the nucleus of the small lymphocyte; central pallor (dashed arrow)
should equal one-third of its diameter.
Picture; peripheral blood smear from a patient with iron deficiency is shown at two different magnifications. Small
(microcytic) red blood cells are shown, many of which have a thin rim of pink hemoglobin (hypochromia).
Occasional "pencil"-shaped cells are also present. A small lymphocyte is shown for size comparison (arrow).
Normal red blood cells are similar in size to the nucleus of a small lymphocyte (arrow), and central pallor in
normal red blood cells should equal approximately one-third of the cell diameter.
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This photo(left) shows two anticoagulated blood-filled Wintrobe hematocrit tubes following high speed
centrifugation. The tube on the left is from a normal subject, with a hematocrit of 38 percent (blue arrow). The
tube on the right is from a 19-year-old female with essential thrombocytosis, a normal white blood cell count, and
a platelet count of 5,000,000/microL. The extreme degree of thrombocytosis can be appreciated by the presence
of a marked increase in the size of the "buffy coat" (white arrow). When the Wintrobe tube is filled to near
capacity (upper arrows), and the white blood cell count is not markedly elevated, the platelet count can be
estimated by the thickness of this layer, with each mm being equivalent to one million platelets/microL. In normal
subjects, the buffy coat, which is comprised of white blood cells and platelets, is only minimally visible.
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Treatment
Non pharmacologic
Pharmacologic
➢ Depends on the underlying cause of anemia.
➢ Patients with anemia suspected due to primary bone marrow disease,
malignancy, autoimmune disease, GI bleeding, and unknown/unclear
cause should get further management at referral hospital level.
Clinical features
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➢ CBC: low Hg and hematocrit, low MCV, low MCH, and increased RDW.
➢ PM; microcystic hypochromic anemia (look at images above)
➢ Iron studies
✓ Serum Ferritin → usually low (it could be high in patients with
chronic inflammation or CKD in spite of iron deficiency)
✓ Serum iron → may be low or normal
✓ Total iron binding capacity (TIBC)→ usually high
𝐒𝐞𝐫𝐮𝐦 𝐈𝐫𝐨𝐧
✓ Transferrin saturation (TSAT) = 𝒙 𝟏𝟎𝟎 %; low (<20%)
𝐓𝐈𝐁𝐂
➢ Clinical evaluation and investigation to identify the possible cause of
bleeding
✓ Stool for ova of parasites
✓ Digital rectal examination
✓ Gynecologic examination
✓ Upper GI endoscopy and/or colonoscopy.
Treatment of IDA
➢ IV iron administration
✓ For patients not on hemodialysis:
▪ Iron sucrose 200mg, IV, administer over 5 minutes, every 3
days for a total of 5 doses (a total of 1g).
• This dose is usually sufficient but if hemoglobin is not
corrected, additional doses can be given.
OR
▪ Iron sucrose 200mg diluted in 100ml NS; administer over 30
minutes.
✓ For patients on hemodialysis
▪ Iron sucrose 100mg, IV, over 2-5 minutes, given early during
dialysis sessions (within the first hour) until iron deficiency is
corrected. It needs to be given again, if iron deficiency
persists or recurs.
Clinical features
Treatment
➢ Folic acid, 1 to 5mg P.O., daily for 1-4 months, or until complete
hematologic recovery.
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✓ Vitamin B12 level should be checked before giving folic acid alone;
as treatment with folic acid alone might worsen neurologic
manifestation of vitamin B12 deficiency.
✓ If vitamin B12 can’t be checked, both Folic acid and vitamin B12
should be started at the same time.
Patients with the following conditions need special care with hematology
and gastroenterology services
✓ If the underlying cause is not clinically obvious.
✓ If other causes of anemia/cytopenia cannot be excluded.
✓ Lack of response to the treatment provided.
Practical points about transfusion (especially for medical interns and ward
Nurses)
➢ Consent → Informed consent for RBC transfusion should be obtained from the
intended recipient before all non-emergent administration of blood components.
According to AABB standards, elements of consent should include: a
description of the risks, benefits, and treatment alternatives; the opportunity for
the intended recipient to ask questions; and the right of the patient to accept
or refuse transfusion.
➢ After determining patient M.HCT, 1st send blood sample for cross match (if BG
&Rh is unknown, request ''BG& Rh with cross match'', if BG is known, write
pt's BG and Rh on request paper and request cross match)
➢ During transfusion, keep the Patient NPO, discontinue any medication (either
Parenteral or oral) until transfusion is finished
➢ Check the blood unit bag about expire date, major/minor reaction, compare the
bag number with the number written on transfusion request paper
➢ For patients who require blood that is warmed (e.g. those at risk of
hypothermia or autoimmune cold-induced hemolysis), put the blood out of the
cold box keep covered with clothes at the bedside, that raise the temperature
closer to body temperature are used. Avoid heating of the blood cells above
40°C, which will cause hemolysis
➢ Use Green IV cannula for transfusion
➢ Transfusion one unit should be completed within 3 hours but not less than one
hour (faster rate may be needed in acute blood loss)
✓ Infusion rate →Suggested rates for adults are 20 to 40 drops per minute
for the first 15 minutes and then as rapidly as tolerated;
✓ The complete infusion should not exceed 4 hours. However, slower rates
of infusion (possibly combined with administration of a smaller unit to
comply with the four-hour infusion requirement) and/or the administration
of diuretics may be indicated for patients who are predisposed to
circulatory overload.
✓ the dose of transfusion for Neonates is 20ml/kg, less than 7 days old
over 3hr (Acute blood loss - Whole blood 20ml/kg less than 7 days old
over 1 hour.)
➢ follow with transfusion follow up sheet
➢ finally, document ‘’transfusion completed without complication at ''X'' DLT/NLT’’
➢ Blood transfusion follow up sheet (include blood component E.g. Whole blood
transfussion follow up sheet)
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➢ Check post transfusion M.HCT of last transfusion (the usual trend in our set
up is after 8hour)
✓ UpToDate 2018 says ‘’The post-transfusion hemoglobin level may be
accurately measured as early as 15 minutes following transfusion, as long
as the patient is not actively bleeding. This practice is based on studies
showing a high degree of concordance between values measured 15
minutes after the transfusion versus longer intervals’’.
✓ Each unit of packed red blood cells (RBCs) contains approximately 200
mL of red cells and, in an adult, will raise the hematocrit by roughly 3 %
points unless there is continued bleeding.
➢ Within one day, it is better not to transfuse more than 3 units of blood unless
there is life threating condition (e.g. massive bleeding, active and uncontrolled
Upper GI bleeding)
➢ Observation following transfusion
✓ In addition to observing the patient during transfusion, continue observing
for 15 to 30 minutes post-transfusion.
Complications of Transfusion
➢ ABO incompatibility
✓ Clinical presentation=hematuria, bilateral flank pain, fever, chills, rigor,
oliguria (ATN)
✓ Rx=stop blood transfusion. send it to blood bank & recheck
▪ Repeat coagulation profile
▪ Iv fluids, monitor UOP, U/A for Hgb
▪ Diuretic- furosemide
➢ Minor incompatibility reaction
✓ Due to extra vascular hemolysis (mild, occur in 2-21days)
✓ Clinical presentation-fever, malaise & jaundice
✓ Rx-supportive
➢ Febrile reaction
✓ Due to sensitization to WBCs or platelets
✓ increase temperature but no hemolysis
✓ Use of 20-40mm filter or leukocyte depleted blood avoids it.
➢ Allergic reaction
✓ Due to allergy to plasma products
✓ Clinical presentation - chills, rigor & rash
✓ Rx- antihistamines
➢ Embolism 996
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➢ Thrombophlebitis
✓ Prolonged infusions into a peripheral vein are associated with venous
thrombosis.
✓ Intravenous infusions that last more than 8 hours are more likely to be
followed by thrombophlebitis, with an increased incidence in the lower
limbs.
✓ Treatment consists of discontinuation of the infusion and the application
locally of warm moist compresses.
✓ Embolization from superficial thrombophlebitis or venous thrombosis is
extremely rare.
➢ Over transfusion and Pulmonary Edema
✓ Volume overload is typically a concern in the elderly, small children, and
those with compromised cardiac function.
✓ Overloading the circulation is an avoidable complication.
✓ It can occur with rapid infusion of blood, plasma expanders, and other
fluids, particularly in patients with heart disease.
✓ To prevent the complication, the central venous pressure should be
measured whenever large amounts of fluid are administered.
✓ Circulatory overload is manifested by a rise in venous pressure, dyspnea,
and cough.
✓ Rales can generally be heard at the lung bases.
✓ Treatment consists of diuresis, placing the patient in a sitting position,
and, occasionally, venesection.
Complications include;
➢ Allergic and immune transfusion reactions can occur in any patient, and are
more common in multiply-transfused patients. including TRALI
➢ Coagulopathy
➢ Hypocalcaemia 998
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➢ Hyperkalaemia/ Hypokalaemia
✓ Hyperkalemia from potassium released from RBCs during blood bank
storage is primarily a concern in massive transfusion, impaired renal
function, and infants/newborns.
➢ Hypothermia
➢ Iron overload
✓ Iron overload becomes a concern after a large number of transfusions for
chronic anemia.
✓ Each transfused unit of RBCs contains 250 mg of elemental iron
Blood components
➢ Banked Whole Blood
✓ With the new preservatives, the shelf life has been extended to 40 ± 5
days.
✓ At least 70% of the transfused erythrocytes remain in the circulation for
24 hours after transfusion and are viable.
✓ The hemolysis that occurs during storage is insignificant.
✓ Preferred for anemia with volume depletion
➢ Platelet
✓ Pooled platelet concentrate containing about 250 x109 cells/L.
✓ Platelets are stored on a special agitator at 20 - 24 0C and have a shelf-
life of only 5 days.
➢ Cryoprecipitate
✓ It is precipitate of FFP
✓ Rich in factor VIII and fibrinogen
✓ Stored at -300C with a 2-year shelf-life
✓ Given in low-fibrinogen states or in factor VIII deficiency
➢ The highest percentage of TBW is found in newborns, with approximately 80% of their
total body weight.
Fluid Balance
➢ Fluid and electrolyte homeostasis is maintained in the body
➢ Neutral balance: input = output
➢ Positive balance: input > output
➢ Negative balance: input < output
➢ Na+ is the major extracellular cation & K+ major intracellular cation
➢ Fluid balance is made through vasopressin, water ingestion & renal
water transport to keep osmolality 280-295 mosm/kg
Types of crystalloids
➢ RL (ringer lactate)
✓ Slightly hypotonic in that it contains 130 mEq of lactate.
✓ It is ideal for the replacement of existing fluid deficits when serum
electrolyte concentrations are normal. Because Lactate is used rather than
bicarbonate because it is more stable in IV fluids during storage. It is
converted into bicarbonate (used to buffer acid base imbalance) by the
liver after infusion, even in the face of hemorrhagic shock.
➢ NS (normal saline /Sodium chloride (0.9%))
✓ It is mildly hypertonic, containing 154 mEq of sodium that is balanced by
154 mEq of chloride
✓ The high chloride concentration imposes a significant chloride load on the
kidneys and may lead to a hyperchloremic metabolic acidosis.
✓ So, it is an ideal solution, for correcting volume deficits associated with
hyponatremia, hypochloremia, and metabolic alkaloids
➢ D5W (5% dextrose)
✓ 50 g of dextrose per liter--supplies 200 kcal/L
✓ Dextrose is always added to solutions containing <0.45% sodium chloride
(hypotonic) to maintain osmolality and thus prevent the lysis of RBCs that
may occur with rapid infusion of hypotonic fluids. The addition of
potassium is useful once adequate renal function and urine output are
established.
colloids
➢ Four major types of colloids are available
✓ Albumin
✓ Dextrans
✓ hetastarch, and
✓ Gelatin
Fluid preparation
➢ Fluid is available in the form of 5% DW, 40% DW, 9% NS, or RL, but there is
no readily prepared fluid 10% DW (D10) in most setups of Ethiopia.
➢ We have to prepare fluid using what is available. To prepare fluid, use
following formula. We need to prepare x% DW from a% DW and b% DW
( a − x ) x Tv. ( X − b ) x Tv.
Vb = (a – x ) + ( x – b)
, Va = (a – x ) + ( x – b)
(Where x = conc. of DW wanted, a = highest conc. of DW , b =
lowest conc. of DW, Va = volume of a, Vb = volume of b, Tv =
total volume needed = Vb + Va )
➢ For example: How to prepare Total volume (Tv) of 10%DW from 40%DW &
5% DW.
✓ Given x = 10%, a = 40, b = 5% , Va = volume of 40%, Vb = Volume
of 5%, Tv = total volume needed = ( Vb + Va)
( 40− 10 ) x Tv. ( 10 – 5 ) x Tv.
✓ Vb = (40 – 10 )+ ( 10 – 5)
, Va = (40 – 10 )+ ( 10 – 5)
30 x Tv. 5 x Tv.
✓ Vb = 35
, Va =
35
✓ Vb (D5W) = 0.85 (meaning 85%) x Tv (D10), Va (D40) = 0.15
(meaning 15%) x Tv (D10)
1) Hypokalaemia
Causes of Hypokalemia
Hypokalemia is either caused by loss from the body or entrance (shift) of
the plasma potassium in to the cell (intracellular compartment)
Causes due to potassium loss
✓ Renal loss:
▪ Diuretics, DKA, resolving AKI/obstructive uropathy, prolonged
vomiting or NG tube drainage
▪ Hypomagnesemia, renal tubular disorders due to drugs like
aminoglycosides, amphotericin, tenofovir, inherited tubular
diseases
▪ Hyperaldosteronism
✓ GI loss: diarrhea
Causes due to redistribution/shift into intracellular space
✓ Medicines: Insulin, beta-2 agonists
✓ Metabolic alkalosis
Clinical features
Unless it is severe, Mild to moderate hypokalemia is generally
asymptomatic.
If there are symptoms attributable to hypokalemia, it is considered to be
severe.
Symptoms of muscle weakness:
✓ Weakness of extremities
✓ Abdominal distention
Neuromuscular
✓ Generalized fatigue and malaise
✓ Muscle cramps, paresthesia
✓ Severe weakness (K <2.5 mEq/L)
✓ Paralysis if K <2.0 mEq/L and rapid development
CVS: ventricular or atrial arrythmia: the most feared manifestation of
hypokalemia is ventricular arrhythmia, as it is sudden onset there might not
be any signs during evaluation, cardiac arrest
GIT: Constipation, ileus, Gaseous abdominal distention with decreased to
absent bowel sounds and failure to pass feces due to paralytic ileus
GUS: Polyuria (hypokalemic nephropathy)
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Investigations
Electrolytes → Serum potassium, Serum magnesium, serum Ca
ECG
Further investigations to determine the underlying cause might be needed if
the cause is not obvious like Cr and BUN, serum osmolality, urine PH,
Urine K
Treatment
Pharmacologic treatment
Severe hypokalemia
Potassium chloride (KCl) IV infusion. 40-60 meq of elemental potassium, in
1000ml Normal saline, to run every 6-8 hours.
✓ Use non dextrose containing fluids
✓ Maximum concentration of potassium is 60meq in one liter of fluid.
✓ Maximum rate of infusion (in the presence of perfuser machine) is
10meq/hour
✓ Recommended if neuromuscular symptoms, cardiac arrhythmias, ongoing
GI loss or severe hypokalemia
✓ KCL 15-20 mEq/L in NS via peripheral vein. If > 40meq/L Kcl required,
central vein needed
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PLUS
Potassium chloride (KCl) tablet, 600mg (equivalent to 8meq of potassium),
2-3tabs, PO, TID to QID.
2) Hyperkalemia
Causes of hyperkalemia
I) Low renal excretion: AKI or CKD, spironolactone, ACE
inhibitors/ARBS, NASAIDS, adrenal insufficiency
* A decrease in renal K+ excretion due to AKI or CKD is the most
common underlying cause.
II) Excess intake: potassium tablets, potassium rich diet in patients
with AKI/CKD
III) Release from intracellular space: tumor lysis, rhabdomyolysis,
hemolysis
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Clinical features
Mild hyperkalemia is generally asymptomatic
Severe hyperkalemia results in muscle weakness or paralysis, Dyspnea,
Chest pain, palpitation or syncope, cardiac conduction abnormalities and
cardiac arrhythmias.
Investigations
RBS
Serum potassium
Serum creatinine and urea
ECG
Investigations for causes e.g. if adrenal insufficiency is suspected basal
serum cortisol level will be needed for screening purpose.
Treatment
3) Hyponatremia
Clinical features
➢ The symptoms directly attributable to hyponatremia primarily occur with
acute and marked reductions in the serum sodium concentration and
reflect neurologic dysfunction induced by cerebral edema, and possibly
adaptive responses of brain cells to osmotic swelling. In this setting, the
associated fall in serum osmolality creates an osmolal gradient that
favors water movement into the cells, leading to brain edema.
➢ Acute hyponatremia (duration known to be <48 hr.)
✓ Early: nausea, malaise, headache, muscle twitching, lethargy
✓ Late/Severe: obtundation Confusion and disorientation, seizures,
coma, Respiratory distress or arrest
➢ Chronic hyponatremia (duration known to be >48 hr.)
✓ Frequently mild or no symptoms
Investigation
➢ RBS
➢ Serum electrolytes
➢ Creatinine and BUN
➢ Serum osmolality to R/o pseudohyponatremia 1009
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𝐺𝑙𝑢𝑐𝑜𝑠𝑒 𝐵𝑈𝑁
✓ Plasma osmolality = (2 x plasma Na+) + +
18 2.8
✓ Patients with hyponatremia have low osmolality (<275mosm/kg)
➢ CXR → If pulmonary pathologies (pneumonia, lung cancer) suspected.
➢ Urine Na
➢ Urine osmolality
➢ TFT → In euvolemic hyponatremia
➢ Serum cortisol → basal or random (in critical patients)
➢ Investigation directed to the suspected underlying cause
Treatment
Pharmacologic treatment
➢ Hypovolemic hyponatremia
✓ Normal saline, IV infusion-volume depending on the estimated fluid
deficit
➢ Hypervolemia hyponatremia
✓ Furosemide, dose depending on the underlying disease and
previous response.
➢ Euvolemic hyponatremia: if it is severe/symptomatic acute hyponatremia
✓ 3% NaCl (513mmol of Na/L), IV, 1-2 ml/kg/hour
✓ Should elevate the serum Na approximately 1-2mmol per hour
✓ Raising the serum Na 4-6mmol/L over 2-3 hours is enough to
prevent serious neurologic complications
✓ Subsequently, the rate of correction should be less than 10mmol/L
per 24 hours.
4) Hypernatremia
Causes of hypernatremia
➢ Hypovolemic hypernatremia
✓ Renal water loss
▪ Loop diuretics
▪ post obstructive dieresis
▪ osmotic diuresis → glucosuria
▪ Hypercalcemia
▪ Hypokalemia
▪ Drugs like lithium
✓ Extra renal water loss:
▪ Burns
▪ GI Losses → Diarrhea, vomiting, etc.
▪ Insensible Loss (skin or lungs)
• Fever
• Hot Room
• Hyperventilation
o In association with deficit in water intake (coma,
stroke, immobility)
o Small volume hyperosmolar > 600mosm urine:
insensible loss
➢ Euvolemic hypernatremia: Diabetes insipidus, hypodipsia
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Clinical features
➢ Hypernatremia is basically a mirror image of hyponatremia. A rise in the serum
sodium concentration and osmolality causes water movement out of the brain
which leads to shrinkage of brain cell volume and secondary neurological
symptom
➢ Mild and chronic hypernatremia is usually asymptomatic
➢ If conscious most patients with hypernatremia will have excessive thirst
➢ Severe acute hypernatremia causes CNS symptoms-irritability, lethargy,
seizure and coma.
Treatment
Pharmacologic treatment
➢ The main stay of treatment for hypernatremia is water (free water) given
orally (preferred) or intravenously as 5%DW but the patients volume
status depends on the severity of hypernatremia and the patient’s
volume state.
➢ Hypovolemic Hypernatremia:
✓ Ringer’s lactate, IV, until hypovolemia improves.
✓ Once the hypovolemia improves shift the fluid to 5%DW after
calculating the water deficit.
➢ Euvolemic Hypernatremia:
✓ Correct water deficit using either oral free water or 5%DW
✓ Replace ongoing losses
✓ Consult specialist if Diabetes Insipidus is suspected.
➢ Hypervolemic Hypernatremia:
✓ Thiazide diuretics are preferred if the volume overload is mild
Alternative
✓ Furosemide IV or P.O., dose and route depending on severity of
hypervolemia.
5) Hypocalcemia
➢ Normal serum calcium level is 8.7 - 10.2 mg/dL (2.2 - 2.6 mmol/L) and
ionized serum calcium level is 4.5 - 5.3 mg/dL (1.12 - 1.32 mmol/L)
➢ Total calcium should always be corrected for serum albumin.
➢ Corrected calcium = measured calcium + [ 0.8 x (4.0- serum albumin)]
➢ Hypocalcemia is defined as a corrected total serum calcium level < 8.5
mg/dl (<2.12 mmol/l) or ionized serum calcium level < 4.5 mg/dL
(<1.13mmol/l)
➢ Hypocalcemia is a common problem in clinical practice, both in
ambulatory care and in hospitalized patients. More than 80% critically ill
patients develop hypocalcemia.
➢ The major factors that influence serum calcium concentration are
parathyroid hormone (PTH), vitamin D activity and their action on the
kidneys and the intestine.
➢ Hypocalcemia is mainly caused by disorders related the level or activity
of parathyroid hormone and/or vitamin D.
➢ The clinical presentation of hypocalcemia could vary from asymptomatic
(incidental finding) to a life threatening one depending on the rapidity of
development and severity.
✓ Autoimmune destruction
✓ Idiopathic hyperparathyroidism
➢ Miscellaneous
✓ “Hungry bone syndrome” following parathyroidectomy
✓ Extravascular deposition of calcium: hyperphosphatemia,
pancreatitis, tumor lysis syndrome
✓ Critical illness
✓ Drugs: IV bisphosphonate therapy
Clinical features
➢ Chronic hypocalcemia is generally asymptomatic or cause mild
symptoms.
➢ The hallmark of hypocalcemia is an irritable neuromuscular system which
shows spontaneous or induced hyperexcitability, called tetany.
➢ Mild symptoms: perioral numbness, paresthesia of the hands and feet,
muscle cramps, fatigue
➢ Severe clinical manifestations
✓ Tetany:
▪ Spams of hands and/or feet (carpopedal spasm): forced
inward movement (adduction) of the thumb, flexion of
metatarsophalangeal joints and wrists
▪ Laryngeal spams: stridor or change in voice, air hunger
▪ Induced tetany
• Trousseau’s sign: Carpal spasm induced but inflating
sphygmomanometer 20mmHg above the systolic BP and
keeping it for 3 minutes.
• Chvostek’s sign: elicited by tapping the facial nerve about
2cm in front of the ear (tragus) and observing contraction
of the facial muscles. Chvostek’s sign can also be seen in
normal individuals. It has poor sensitivity and specificity.
✓ CNS manifestations: Focal or generalized seizures, confusion,
delirium, papilledema
✓ Cardiac manifestations: hypotension, features of heart failure,
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Treatment
Non-pharmacologic
➢ Increase diet rich in calcium and vitamin D.
Pharmacologic
➢ Hypocalcemia with severe symptoms (tetany, seizure, change in mental
status, prolonged QT) or acute (postoperative) <7.5mg/dl: IV calcium
➢ Calcium gluconate (10%) 01 ampoule (10ml) IV over at least 10min
(rule of 10)
✓ If symptoms persist, repeat the above. Don’t repeat more than two
times.
✓ Give a continuous infusion (drip) of calcium in the following way
▪ Add 06 ampoules of 10% calcium gluconate in 1L of 5%DW
run 12 hours (80ml/hr or 28 drops/minute).
▪ This equivalent to 540mg of elemental calcium in 1000ml =
0.54mg/ml preparation running at about 45mg/hour)
✓ Do serum calcium every 12 hour and continue infusion until calcium
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6) Hypercalcemia
Clinical features
Diagnosis
➢ Once hypercalcemia is confirmed from serum total calcium or ionized
calcium, the next step important investigation is determination of serum
PTH.
➢ Low PTH: very likely hypercalcemia due to malignancy or vitamin D
related causes
➢ High or normal PTH: Hyperparathyroidism
➢ If serum PTH can’t be done and the patient has overt malignancy,
consider the hypercalcemia to be due to the malignancy.
Investigations
➢ Other investigation for patients with low serum PTH
✓ Investigate for malignancy based on clinical clues e.g. screening for
multiple myeloma
✓ Serum 25(OH) and 1,25(OH)Vitamin D
➢ Phosphorous: low in primary hyperparathyroidism, elevated in Vitamin D
related causes
➢ ECG: short QT interval
➢ X-rays: osteoporotic changes in cortical bone, typically in the wrist,
bone cysts (osteitis cystica fibrosa) in the long bones
➢ Ultrasound: Renal stones or evidence of nephrolithiasis
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Treatment
Non-pharmacologic treatment
➢ If the patient has severe hypercalcemia (>14mg/dl) or has severe
symptoms (features of dehydration, change mental status) urgent
admission is needed.
➢ Discontinue drugs which can cause hypercalcemia: thiazide, lithium
➢ Surgical management: in primary hyperparathyroidism, if there are
indications.
➢ Management at referral hospital level is strongly recommended.
Pharmacologic treatment
Severe hypercalcemia
➢ Aggressive hydration with normal saline for few days
✓ 4-6 liters of NS over 24 hours (1 liter over 4-6 hours), close monitoring
for fluid overload and fluid balance.
✓ Do not routinely use Furosemide unless the patient is fluid
overloaded (pulmonary crackles, raised JVP).
✓ If Fluid overloaded, Furosemide, 20-40mg IV, when needed. Similar
doses of can be repeated if fluid overload persists.
➢ Intravenous bisphosphonate
✓ Zoledronic acid, 4mg, diluted in 100ml of NS or D5W, given as infusion
over 15-30minutes.
➢ Corticosteroids
✓ Dexamethasone 4mg IV BID OR
✓ Hydrocortisone 100mg IV, BID OR
✓ Prednisolone 30-40mg/day.
7) Hypomagnesemia
➢ The normal range for serum magnesium is 1.7 to 2.1 mg/dl= 1.4 to
1.7 mEq/l= 0.70 to 0.85 mmol/L.
➢ Hypomagnesemia is defined as serum magnesium <1.6mg/dl or < 0.66
mmol/L (<1.3mEq/L).
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Clinical features
Diagnosis
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Treatment
Non-pharmacologic treatment
➢ Correction of the underlying cause: e.g. discontinuation of diuretics, nephrotoxic
medications, treating diarrhea, helping to decrease/quit alcohol.
➢ Increase dietary intake of magnesium: Food rich in magnesium: Green leafy
vegetables, nuts or peanuts, legumes (e.g. beans), soy milk, and whole grains
Pharmacologic treatment
Treatment of severe (<1.2mg/dl) and symptomatic
hypomagnesemia
➢ Life threatening (arrhythmia)
✓ IV Magnesium sulfate1- 2g, IV push over 3-5 minutes, Followed by
continuous infusion
➢ Emergent: No arrhythmia but severe symptoms (e.g. neuromuscular
manifestations)
✓ IV Magnesium sulfate, 1 to 2g diluted in 100mL D5W, run 15-30minutes,
Followed by continuous infusion.
➢ Non-emergent repletion in patients with severe hypomagnesemia
✓ Start with continuous infusion. Avoid the initial bolus.
✓ How to give continuous infusion?
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Oral magnesium
➢ Oral magnesium should be started along with or after IV magnesium sulfate.
➢ Most oral magnesium preparations are poorly absorbed and poorly tolerated
(due to diarrhea)
➢ 240 - 1000mg of elemental magnesium is needed in 24 hours.
➢ The most commonly available oral magnesium preparation available is
magnesium hydroxide.
✓ Magnesium hydroxide (liquid form), 400mg/5ml (168mg elemental Mg5ml)
give 10ml BID-TID.
✓ If it is combined with Aluminum, avoid prolonged use.
8) Hypermagnesemia
Clinical features
➢ Asymptomatic: serum magnesium level 2.5 -5mg/dL, though defined as
hypermagnesemia, is generally asymptomatic unless there is a concomitant
hypocalcemia.
➢ Symptomatic: The major symptoms and signs of hypermagnesemia are related
to neuromuscular or cardiovascular system.
➢ Neuromuscular: characterized by depressed neuromuscular conduction(activity)
✓ Mild: Nausea, vomiting, constipation, facial flushing, dizziness, depressed
deep tendon reflexes.
✓ Moderate: Absent deep tendon reflexes, drowsiness, paralytic ileus, urinary
retention, blurred vision, and hypotension.
✓ Severe (life threatening): flaccid paralysis, respiratory depression, coma,
apnea.
➢ Cardiovascular: characterized by delayed(depressed) cardiac conduction
✓ ECG abnormalities (every conduction is delayed): prolonged PR interval,
AV block, prolonged QRS duration, prolonged QT interval.
✓ Severe (Life threatening): bradycardia advanced AV-block, cardiac
arrest/asystole.
✓ Hypocalcemia: hypermagnesemia suppresses PTH secretion
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Treatment
Non-pharmacologic
➢ Stop magnesium infusion or oral magnesium containing drugs.
➢ Hemodialysis: In symptomatic hypermagnesemia with impaired kidney function
Pharmacologic
➢ Symptomatic hypermagnesemia:
✓ Intravenous calcium
▪ Calcium gluconate 10%, 10ml, diluted in 100ml D5W to run over 5-
10 minutes.
▪ In patients with cardiac arrest, give undiluted over 2-3 minutes.
▪ Repeat the dose, if symptoms persist.
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✓ Forced diuresis
▪ Normal saline 200ml/hour for 6 -12 hours, if the patient does not
have volume overload (edema, pulmonary congestion, and
hepatomegaly).
▪ Give Furosemide 40mg, IV, stat, in the middle of the NS infusion.
✓ Hemodialysis
▪ In patients with significantly impaired kidney function
(eGFR<30ml/min) and symptomatic hypermagnesemia, excretion of
the magnesium is unlikely to happen; hence urgent hemodialysis is
needed after giving.
➢ Asymptomatic hypermagnesemia
✓ No need for pharmacologic treatment.
✓ Stopping magnesium containing medications or magnesium sulfate
infusion, if being given, will suffice.
Prevention
➢ During parenteral magnesium sulfate administration
✓ Determine baseline serum creatinine and continuously monitor urine output
✓ Monitor serum magnesium regularly every 6 hours
✓ If possible, have ECG monitoring (bedside monitor)
➢ Avoid prolonged use of magnesium containing medications in patients with
impaired kidney function medications (antacids or magnesium containing
laxatives)
key features:
➢ It enables all trained first line health care providers to diagnose STI
syndromes and treat patients on the spot, without waiting for
laboratory results.
➢ It will help to offer treatment on the initial visit which is an important
step to stop the spread of the disease.
➢ It is problem oriented (it responds to the patient’s smx’s).
➢ It is highly sensitive and does not miss mixed infections.
➢ Uses flow charts that guide the health worker through logical steps.
✓ Each flowchart is made up of a series of steps:
▪ The clinical problem- the patient’s presenting symptoms at
the top; this is the starting point
▪ A decision to make, usually by answering “yes” or “no” to a
question
▪ An action to take: what you need to do
➢ Provides opportunity and time for education and counseling.
NB: A number of different organisms that cause STIs give rise to only a
limited number of syndromes.
➢ The aim of syndromic STI management is to identify one of the 7
syndromes and manage accordingly. These are
1) Vaginal discharge
2) Urethral discharges
3) genital ulcer
4) lower abdominal pain
5) scrotal swelling
6) inguinal bubo
7) neonatal conjunctivitis.
Risk Assessment
➢ Major risk factor for cervicitis using vaginal discharge as an entry point
to manage cervical infection is far from ideal.
➢ While vaginal discharge is highly indicative of vaginal infection, it is
poorly predictive of cervical infection with gonorrhea and/or chlamydia.
➢ The flowchart may become more predictive of cervical infection if a
number of risk factors indicative of cervical infection are included
➢ N.B. One or more of the following are risk factors for STI related
cevicitis in Ethiopia
✓ Multiple sexual partners in the last 3months.
✓ New sexual partner in the last 3 months
✓ Ever traded sex
✓ Age below 25 years
NB: The presences of one or more risk factor suggest cervicitis.
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Treatment
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➢ All sexually active women presenting with lower abdominal pain should
be carefully evaluated for the presence of upper genital tract infections
(tube, uterus, ovaries, and pelvic cavity).
➢ In addition, all women with presumptive STI should undergo thorough
bimanual and abdominal examination because some of the women with
PID may not complain of lower abdominal pain.
➢ Other suggestive symptoms include pain during intercourse, vaginal
discharge, abnormal vaginal bleeding (inter-menstrual), painful urination,
pain during menstruation, fever and sometimes nausea and vomiting.
➢ PID is difficult to diagnose because the clinical manifestations widely
vary.
➢ PID becomes highly probable when one or more of the above symptoms
are seen in a woman with adnexal tenderness, vaginal discharge and
cervical motion tenderness.
N.B. Many experts recommend that all patients with PID should be
admitted to hospital for treatment.
Etiology
Treatment
Complications of UDS
➢ Common acute complications
✓ Disseminated gonococci syndrome
✓ Perihepatitis
✓ Acute epididymoorchitis
➢ Common chronic complications
✓ Urethral stricture
✓ Infertility 1032
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Treatment of UDS
➢ UDS needs to be treated ASAP because if it is not treated on time it
can cause serious complication.
➢ Treatment should target gonorrhea and chlamydial infections.
➢ Look at the table below
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➢ Most cases of genital herpes are caused by HSV-2 in both males and
females constituting 44% and 76% of the cases respectively.Moreover,
dual infection with other genital ulcer pathogens is 52% of males and
78% of females.
Clinical presentations
➢ Clinical manifestation and patterns of GUS may vary with presence of
HIV infection.
➢ Genital ulcer has different kinds of clinical manifestations due to different
causatives.
➢ Common clinical manifestations of genital ulcer are:
✓ Constitutional symptoms such as fever, headache, malaise and
muscular pain
✓ Recurrent painful vesicles and irritations
✓ Shallow and non-indurated tender ulcers
✓ Common sites in male are glance penis, prepuce and penile shaft
✓ Common sites in women are vulva, perineum, vagina and cervix
and can cause occasionally severe vulvo-vaginitis and necrotizing
cervicitis
✓ Painless indurated ulcer (Chancre)
✓ Regional lymph adenopathy
➢ Genital herpes:
✓ HSV is the most common causes of genital ulcer worldwide.
✓ It produces lifelong infection after the primary infection (latency).
✓ The lesions are painful, erythematous macules which progressively
form vesicles, pustules, ulcer and crusts.
➢ Chancroid (ከርክር)
✓ Chancroid is also the common cause of genital ulcer in developing
countries.
✓ The lesion started as painful papules and pustules which ulcerate
with dirty base and soft edge.
✓ Inguinal fluctuant adenopathy (buboes) may occur following ulcer.
➢ Syphilis:
✓ Clinically has three stages (primary, secondary, tertiary).
✓ The ulcer starts during the primary stage of the disease as papules
& rapidly ulcerate.
✓ The ulcer is typically painless, clean base and raised boarder.
➢ Lymphogranuloma veneurum (LGV):
✓ The disease starts as painless papules that develops an ulcer.
✓ After a few days painful regional LAP develop and associated
systemic symptoms may occur.
➢ Granuloma inguinale (Donovanosis):
✓ It is chronically progressive ulcerative disease without systemic
symptoms.
✓ Presents with non-suppurative painless genital ulcer and beefy-red
appearance
Non-pharmacologic
Pharmacologic
5) Scrotal Swelling
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Treatment
➢ If quick and effective therapy is not given, the complications (Destruction
and scarring of testicular tissues, infertility, impotence, and prostatitis)
may occur.
➢ The treatment of scrotal swelling suspected of STI origin is similar to
that of urethral discharge
➢ In addition, analgesia and scrotal support may be indicated as required.
Non-pharmacologic:
➢ Scrotal support
Pharmacologic
6) Inguinal Bubo
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Treatment
Non pharmacologic:
Pharmacologic
7) Neonatal conjunctivitis.
Refer updated NICU guideline
Syphilis (ቂጥኝ)
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i. Early syphilis
B. Secondary syphilis:
✓ A systemic illness often including a rash (The rash is classically a
diffuse, symmetric macular or papular eruption involving the entire
trunk and extremities including the palms and soles), malaise, fever,
and other symptoms such as pharyngitis, mucous patches, hepatitis,
condyloma lata, alopecia.
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C. Early latent:
D. Tertiary syphilis:
➢ Late syphilis with symptomatic manifestations involving the CVS or
gummatous disease (granulomatous disease of skin and subcutaneous
tissues, viscera, or bones).
a. Early neurosyphilis:
➢ may have asymptomatic meningitis; symptomatic meningitis; or less
commonly meningovascular disease (ie, meningitis and stroke).
➢ Vision or hearing loss with or without concomitant meningitis may also
be present, and ocular/otologic syphilis is treated as neurosyphilis. 1044
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b. Late neurosyphilis:
➢ The most common forms involve brain and spinal cord (dementia -
general paresis and tabes dorsalis).
Complications of syphilis
➢ If untreated, Syphilis have a number of significant late manifestations or
complications, including cardiovascular, gummatous, and neurologic cxn.
DIAGNOSTIC TESTS
➢ Serologic tests
✓ Serologic tests provide a presumptive diagnosis of syphilis.
✓ There are two types of serologic tests for syphilis: nontreponemal
tests and treponemal-specific tests.
➢ Nontreponemal tests include:
✓ Rapid plasma reagin (RPR)
✓ Venereal Disease Research Laboratory (VDRL)
✓ Toluidine Red Unheated Serum Test (TRUST)
➢ Specific treponemal tests include:
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ii. PCR
Screening
Pre-treatment evaluation
Treatment
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Alternatives:
➢ Ceftriaxone 2 g IV daily for 10 to
14 days OR
➢ doxycycline 200 mg PO BID for 21
to 28 days (If no ceftriaxone or
allergic to it)
➢ After IV treatment completion, single dose of 2.4 million Units Benzathine
Penicillin G (for non-pregnant) and once/week for 3 weeks (pregnant) can be
used
Post-exposure See discussion below ➢ Penicillin G benzathine (Bicillin L-A)
prophylaxis 2.4 million units IM stat (administer
as 1.2 MU in each buttock)
*The National STI Guideline (2015) consider and manage a history of non-reactive RPR test within the
past 2 years as early syphilis and infections more than two years ago or no prior history of non-reactive
RPR test (unknown duration) as late syphilis.
Follow-up
➢ Monitor clinically and with serologic testing after treatment to ensure
response.
➢ Frequency of follow up and interpretation of nontreponemal titers;
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➢ The same test, preferably RPR, should be done each time and at the
same laboratory.
➢ A 4 times increase in nontreponemal titer after treatment is always
abnormal.
➢ A 4 times decrease in titer, equivalent to a change of two dilutions
(such as from 1:16 to 1:4 or 1:32 to 1:8), is considered as acceptable
response to therapy; but this may take months to attain.
➢ For pregnant a fall in maternal titers does not guarantee that fetal
treatment has been adequate.
➢ Over time, most successfully treated syphilis patients experience
seroreversion; but some may remain serofast.
Sexually partners:
Fetal treatment
Gonorrhea (ጨብጥ)
➢ Gonorrhea is an infection with the gram-negative coccus Neisseria
gonorrhoeae
➢ Gonorrhea is a major cause of urethritis in men and cervicitis in women;
the latter can result in PID, infertility, ectopic pregnancy, and chronic
pelvic pain.
➢ Gonococcal infections, including urethritis, cervicitis, epididymitis, and
proctitis, are a significant cause of morbidity among sexually active men
and women worldwide.
➢ Urogenital, anogenital, pharyngeal, and ocular gonococcal infections that
are not associated with bacteremia or ascending spread of the pathogen
to other organs are considered uncomplicated.
➢ Extragenital infections of the pharynx and rectum are prevalent in certain
groups, such as men who have sex with men (MSM).
➢ Invasive infections with N. gonorrhoeae, including disseminated
gonococcal infection, endocarditis, and meningitis, are uncommon but
can result in serious morbidity (complicated) 1051
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DIAGNOSTIC APPROACH
➢ Clinical syndrome approach (preferred in our setup) → which can
manifest as VDS, UDS, PID, conjunctivitis…
➢ nucleic acid amplification testing (NAAT) is the test of choice for the
initial microbiologic diagnosis of N. gonorrhoeae infection, although
culture remains an important diagnostic tool when antibiotic resistance is
suspected.
➢ If NAAT methods are unavailable, microscopy (for men), culture, antigen
detection, and genetic probe methods can be used with endocervical or
urethral swabs.
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Management
A. Syndromic approach is recommended (refer mgt of VDS, UDS, PID)
B. Mgt based on specific diagnosis
i. Uncomplicated gonorrhea: Cervicitis, proctitis, urethritis, pharyngitis:
First line
✓ Ceftriaxone 250mg IM stat plus
✓ azithromycin 1g po stat
Alternatives
Patients with severe cephalosporin allergy
✓ azithromycin 2 g PO stat
plus
✓ gentamicin 240mg IM stat or
✓ Gemifloxacin 320mg PO stat
If ceftriaxone unavailable
✓ Cefixime, 400 mg as a single dose in combination with oral
azithromycin
▪ Not recommended due to limited efficacy
ii. Conjunctivitis
v. Gonococcal Meningitis:
Note:
➢ To be used only for heterosexual partners with gonorrhea if health
department partner-management strategies are impractical/unavailable
and there is concern by the provider for the prompt evaluation and
treatment of the partner
➢ Provide written materials to educate partners about their exposure to
gonorrhea, importance of therapy, and when to seek clinical evaluation
for adverse reactions/complications
Treatment failure
➢ Note: Reinfections are more likely to occur than actual treatment
failures,
➢ Re-treatment with preferred dual-therapy regimen is recommended for re-
infection.
➢ Choice of agent (e.g. ceftriaxone, Gemifloxacin, or gentamicin) to
combine with azithromycin following treatment failure varies considerably
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Treatment
N.B For all STI, in addition to treatment, educate the patient on
Type of STI ➢ Abstinence from sex and avoiding alcohol intake till all symptoms
resolve and management completed
➢ Sex Partner notification and management based on type of STI and
indication
➢ Importance of HIV testing
➢ Proper and consistent use of condom
➢ Risk reduction
➢ Treatment compliance
Risk assessment +ve Risk assessment -ve
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NB:
➢ Patients should be advised to return if symptoms persist for 7 days
after the initiation of treatment.
➢ Single dose treatment is encouraged as much as possible
➢ Re-treat with initial regimen
✓ If non-compliant or re-exposure occurs, re-treat with the initial
regimen with due emphasis on drug compliance and/or partner
management.
Persistent/Recurrent ✓ Cover M. genitalium and T. vaginalis
Urethral Discharge ➢ If compliant with initial regimen and re-exposure can be excluded, the
recommended drug for persistent or recurrent urethral discharge
syndrome in Ethiopia is:
✓ Metronidazole 2 gm po. Stat or
✓ Tinidazole 1gm po once for 3 days (Avoid Alcohol!)
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PLUS
✓ Azithromycin 1g PO, stat (only if not used during the initial
episode to address doxycycline resistant M.genitalium)
➢ Despite all these treatments, if symptoms still persist to require
treatment with a new antibiotic regimen and a sexually transmitted
agent is the suspected cause, all partners in the past 3 months
before the initial diagnosis and any interim partners should be
consulted to a gynecologist for evaluation and appropriate treatment
of treatment failure.
A. Treatment for non- vesicular genital ulcer
➢ Benzathine penicillin, 2.4 million units IM stat or
➢ Doxycycline (in penicillin allergy) 100mg bid for 14 days
Genital Ulcer PLUS
Syndrome (GUS) ➢ Ciprofloxacin 500mg PO bid for 3 days or
➢ Erythromycin 500mg PO QID for 7 days
PLUS
➢ Acyclovir 400mg PO, TID for 10 days (or 200 mg 5 times per day of
10 day)
N.B. There is no medically proven role for topical acyclovir, its use is
discouraged.
Prevention of STIs
➢ Comprehensive approach to STI prevention includes
✓ Risk assessment with counseling
✓ Vaccination
✓ Identification of infected individuals and effective treatment with
follow-up
✓ Evaluation and treatment of sexual partners.
✓
tested for HIV infection.
Patient-centered risk reduction counseling:
▪ assess patient's understanding of STI transmission risk
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Vaccination
3.12.5 Sepsis
Sepsis is life-threatening organ dysfunction caused by a dysregulated
host response to infection.
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Sepsis and septic shock are the major causes of morbidity and mortality
worldwide.
The morbidity and mortality seems higher among extreme age groups
(neonates and elderly) than adults.
Cause
✓ Sepsis is caused by an immune response triggered by an infection.
✓ The infection is most commonly bacterial. Fungi, viruses, or parasites
can also cause sepsis.
✓ The most common primary sources that leads to sepsis was respiratory
tract, brain, urinary tract, skin, and abdominal organ infections.
✓ RF for sepsis
▪ Young or old age
▪ a weakened immune system from conditions such as cancer or
diabetes
▪ major trauma or burns
Clinical presentations
Common signs and symptoms of include
✓ Fever,
✓ Tachycardia
✓ Tachypnoea
✓ confusion.
✓ There may also be symptoms related to a specific infection, such as
a cough with pneumonia, or painful urination with a kidney infection.
✓ In the very young, old, and immunocompromised patients, symptoms
of a specific infection may not present and the body temperature
may be low or normal rather than high.
❖ However, they may need validation to the local contexts as they were
developed based on western patient data. 1061
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SOFA Score
4. Leucocytosis or leucopenia
▪Infection → either of the following (i.e. confirmed or
suspected infection)
☛ Bacteraemia (or viraemia /fungaemia/protozoan)
☛ Septic focus (abscess / cavity / tissue mass)
✓ Severe sepsis = Sepsis + Organ Dysfunction
✓ Septic Shock = Severe sepsis + Hypotension
Treatment
Earl measures
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Community acquired AND First choice antibiotic regimen Second line antibiotic
Immune-competent
Undifferentiated (no obvious Ceftriaxone,1 - 2g IV daily (usual dose is Ampicillin, 2-4g, IV, QID plus
source identified) 1g, IV, BID) Gentamicin, 5 mg/kg, IV, daily
Pneumonia Ceftriaxone,1 - 2g IV daily + Ceftriaxone + Doxycycline
Azithromycin, 500mg, po, daily for 3 days
Consecutive measures
☛ Glucocorticoids
☛ inotropics and
☛ blood transfusions (consider RBCs if hemoglobin <7 g/dl), can
be administered on an individual basis.
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8. Antibiotic stewardship.
o Sorting out the source of infection (preferably identifying the
specific pathogen) and optimizing antibiotic use is critical.
o De-escalation should be planned within 72 hours based on the
culture report and other criteria’s. Procalcitonin may help to guide
the de-escalation and deciding on the duration.
Prevention
o Vaccination
o Proper hand washing and other peculiar precautions
o Maintaining a clean environment
o Preventing aspiration etc.
Pregnant:
Additional considerations
other aspects of care for patients with sepsis and septic shock like
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Thyrotoxicosis
Clinical features
Symptoms
Weight loss despite increased appetite
Excessive sweating
Heat intolerance
Palpitations
Nervousness and irritability
Menstrual irregularity, mainly oligomenorrhea
Increased hair loss
In thyroiditis there could be neck pain and
Signs
Tachycardia with or without irregularity: Sinus tachycardia or atrial fibrillation
High blood pressure
Goiter often present but not always
Smooth and diffuse goiter in Grave's disease
Irregular goiter in toxic multi-nodular goiter
Single thyroid nodule in toxic adenoma 1071
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TFT
✓ 1st
determine TSH, then free T4 if TSH is abnormal
✓ TSH is the best initial diagnostic test. If the TSH is low, it suggests
hyperthyroidism
✓ A low TSH result should be followed by Free T4 and total T3
determinations. Rarely Free T3 determination may be needed.
o TSH normal = excludes hyperthyroidism
o TSH is low and high Free T4 or T3 = Primary hyperthyroidism
o If TSH is low, Free T4 and T3 normal= subclinical hyperthyroidism
ECG
Thyroid imaging and cytology are not generally necessary in the
work up of hyperthyroidism.
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Treatment
First line20
✓ Propylthiouracil (PTU)
o Initial dose: 100 - 150mg, PO, TID
o Max; 300mg, PO, TID
o Maintenance dose: Variable but commonly 100-200mg/day
20
according to UpToDate 2018, PTU is favored over methimazole because of PTU's effect to decrease T4-
to-T3 conversion. 2020 STG for general hospitals of Ethiopia, consider methimazole as first line and PTU as an
alternative.
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N.B
Propranolol has additional effects of blocking peripheral conversion
of T4 to T3
Betablockers are absolutely contraindicated in patients with;
o Asthma or COPD
o Severe peripheral vascular disease
o Bradycardia
o 2nd or 3rd degree heart block
o Hypoglycemia-prone diabetics in whom the early warning
symptoms of hypoglycemia may be masked and
o Raynaud phenomenon
In the absence of contraindications, beta blockers can be
administered as soon as the diagnosis of hyperthyroidism is made,
even before obtaining a definitive diagnosis as to the etiology of the
thyrotoxicosis.
21
if thyrotoxicosis is associated with goiter (e.g. toxic multinodular goiter) or if you
suspect thyroid malignancy, consult or link to surgery.
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Precipitants
◼ Infection
◼ Trauma
◼ DKA
◼ MI
◼ CVA
◼ PE
◼ Surgery
◼ Labor
◼ Withdrawal of thyroid medication
◼ Iodine administration
◼ Palpation of thyroid gland
◼ Ingestion of thyroid hormone
◼ Unknown etiology (20-25%)
Clinical features
Diagnosis
CVS dysfunction
130 to 139
≥140 25
1076
20
Atrial fibrillation 10
Heart failure Mild → Pedal edema 5
Moderate → Bibasilar rales 10
Severe → Pulmonary edema 15
Precipitant history Negative 0
Positive 10
* A score of 45 or more is highly suggestive of thyroid storm, a score of 25 to 44 supports the
diagnosis, and a score below 25 makes thyroid storm unlikely.
Laboratory findings
TFT
◼ All patients with overt primary hyperthyroidism have low TSH and high
free T4 and/or T3
◼ TSH should be assessed in all patients in whom there is A clinical
suspicion of thyroid storm;
A. hyperpyrexia with temperature > 39.4°C
B. Goiter
C. Cardiovascular dysfunction
D. Altered mentation
E. Atrial fibrillation
F. History of antithyroid drug therapy for hyperthyroidism
G. Recent thyroid or nonthyroidal surgery
H. Recent exposure to iodine-containing contrast.
◼ If the TSH is below normal, free T4 and T3 should be measured.
◼ The degree of hyperthyroidism (elevation of T4 and/or T3 and
suppression of TSH) in patients with thyroid storm is, in general,
comparable with that in patients with uncomplicated overt
hyperthyroidism. Thus, the degree of hyperthyroidism is not a criterion
for diagnosing thyroid storm.
➢ Other nonspecific laboratory findings may include;
➢ Mild hyperglycemia → secondary to a catecholamine-induced inhibition of
insulin release and increased glycogenolysis
➢ Mild hypercalcemia → may occur due to hemoconcentration and
enhanced bone resorption
➢ Abnormal LFT → elevated transaminase and elevated bilirubin
➢ Leukocytosis, or leukopenia.
➢ ECG features of arrythmia 1077
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N.B
◼ Propranolol has the additional effects of blocking peripheral conversion
of T4 to T3. But, this effect of propranolol is slow, occurring over 7 to
10 days, and contributes little to the therapeutic effects of the drug
◼ Look at contraindications of betablockers from thyrotoxicosis section
above.
➢ Decrease de novo synthesis:
PTU, 600-1000mg PO stat, followed by 200-250 mg, PO, q4 hrs
OR
Methimazole, 40 mg, PO stat, then 20 mg PO, every 4 - 6 hours
➢ Glucocorticoids
✓ Hydrocortisone, 100 mg, IV, TID or
✓ Dexamethasone, 2 mg, IV, QID
3.12.7 Hypothyroidism
❖ The body requires thyroid hormones for normal metabolism and growth.
❖ Hypothyroidism is a condition in which there is a reduction in thyroid hormone
production.
❖ In adults, it may be the cause of a slow metabolic rate, systemic problems
and dementia.
❖ The most common reason is decreased production by thyroid glands (called
primary hypothyroidism), rarely it could be caused by pituitary abnormalities
(secondary)
❖ Antibody-related thyroid gland destruction, surgical removal of the thyroid,
pituitary lesions or surgery, congenital, severe iodine deficiency are the major
causes.
❖ Myxedema coma describes the most severe state of hypothyroidism and is a
medical emergency.
Types of Hypothyroidism
Primary hypothyroidism
❖ From thyroid destruction
Central or secondary hypothyroidism
❖ From deficient TSH secretion, generally due to sellar lesions such as pituitary
tumor or craniopharyngioma
❖ Infrequently is congenital
Tertiary hypothyroidism
❖ From deficient TSH stimulation above level of pituitary→ i.e. lesions of
pituitary stalk or hypothalamus
❖ Is much less common than secondary hypothyroidism
Clinical features
Symptoms
❖ Patients could remain asymptomatic for several years or they might not
recognize the symptoms themselves.
❖ Intolerance to cold environments, constipation, weight gain, hair loss, dry skin
❖ Hoarse voice, lethargy, memory loss, depressed reflexes, dementia
❖ Abnormal menstrual periods and sub-fertility (in adult females)
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Signs
❖ Puffy face, pallor, slow pulse (usually <60 per minute)
❖ Goiter may be present
◼ TSH
◼ Free T4
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Treatment
Levothyroxine
❖ Starting dose → for patients with no cardiovascular disease
for patients with no cardiovascular disease
o Young patients → 100 µg/day
o Elderly patients → 50 µg/day
Patients with established cardiac disease → 25-50 µg/day
❖ Dose adjustment
Dose adjustment should be made after at least 2-3 months of therapy
Dose increments by 25-50 µg/day in 2- 3months
Achieving TSH is the target of treatments
After normalization of TSH, annual follow up of TSH suffices
Myxedema Coma
Precipitating factors
◼ Infection
◼ Surgery or trauma
◼ Myocardial infarction
◼ Stroke
◼ exposure to cold
◼ drugs → use of sedatives or opiates, Lithium, Amiodarone
Clinical features
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Treatment
Alternative
B. L-triiodothyronine 25 µg IV/PO, TID (12.5 µg in patients with cardiovascular
disease)
◼ Glucocorticoids → if there is concomitant adrenal insufficiency
A. Hydrocortisone 100 mg IV, TID
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◼ Immobility
◼ Previous VTE
◼ Major surgery, e.g. orthopedic, abdominal and pelvic surgery
◼ Trauma → especially involving the pelvis and lower limbs
◼ Pregnancy and postpartum state
◼ Contraceptive pill use, hormone replacement therapy (HRT)
◼ Cancer
◼ Obesity
◼ Medical conditions such as;
A. Heart Failure
B. Nephrotic syndrome or CKD
C. HTN
D. COPD
E. SLE
F. IBD
◼ Inherited disorders causing hypercoagulability
Pathogenesis
❖ A major theory described the pathogenesis of VTE is called Virchow's triad,
which occurs as a result of: mnemonic → EBC
✓
✓
✓
Endothelial Injury
Blood flow alterations (Stasis)
Coagulopathy → Alterations in the Constituents of Blood
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Clinical features
◼ VTE mimics other illnesses, and PE is known as "the Great Masquerader,"
making diagnosis difficult.
◼ Occult PE is especially hard to detect when it occurs concomitantly with overt
Heart Failure or Pneumonia.
◼ In evaluating patients with possible VTE, the initial task is to decide on the
clinical likelihood of the disorder.
◼ VTE can cause death from PE or, among survivors, Chronic Thromboembolic
Pulmonary Hypertension and Post thrombotic Syndrome/chronic venous
insufficiency/may occur.
DVT
PE
❖ For patients who have PE, the most common history is unexplained
breathlessness.
✓ Dyspnea is the most common symptom of PE, and Tachypnea is
the most common sign.
❖ Dyspnea, Syncope, Hypotension, or Cyanosis indicates a Massive PE, Whereas
Pleuritic Pain, Cough, or Hemoptysis often suggests a Small Embolism
situated distally near the pleura.
❖ On physical examination,
✓ Young and previously healthy individuals may appear anxious
✓ But otherwise seem well, even with an anatomically large PE.
❖ The presence of pulmonary infarction usually indicates a small PE
✓ But one that is exquisitely painful because it lodges peripherally,
near the innervation of pleural nerves.
❖ Pleuritic Chest Pain is more common with small, peripheral emboli. However,
larger, more central PEs can occur concomitantly with peripheral pulmonary
infarction.
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Classification
Interpretations and actions to be done in Wells score (for best setup, not applicable in
our setup)
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❖
❖ If the scan is positive, continue anticoagulation
Management of VTE
◼ The management of VTE is done in three different phases:
A. Initial Management
B. Primary Treatment
C. Secondary prevention
Pharmacologic
I. Acute treatment
First line
✓ UFH, 5000 Units, IV, bolus; then 250 Units/Kg/dose, Sc, BID or 17,500 Units
SC, BID (for an average adult) until two consecutive INR values become
therapeutic (2-3) or
✓ Enoxaparin 1mg/kg, SC, BID, until two consecutive INR values become
therapeutic (2-3)
o Enoxaparin dose should be reduced or it should be avoided in
patients with advanced CKD (GFR<30ml/min)
PLUS
✓ Warfarin (starting simultaneously with heparin)
o Starting dose: 5 mg, P.O., daily with regular dose adjustment and
monitoring of INR until target of 2 - 3 is attained.
o Add warfarin 5mg, PO, on day 1 or 2 of UFH, daily for 2 days, check
INR after 2 days and adjust based on the result
o Overlap warfarin and UFH for at least 5 days until desired INR/INR=2-
3/ maintained for 24hr then discontinue UFH.
N.B
➢ The full effect of warfarin requires at least 5 days, even if the prothrombin
time, used for monitoring, becomes elevated more rapidly.
➢ If warfarin is initiated as monotherapy during an acute thrombotic illness, a
paradoxical exacerbation of hypercoagulability increases the likelihood of
thrombosis.
➢ Overlapping UFH or LMWH with warfarin for at least 5 days will nullify the
early procoagulant effect of warfarin.
Alternatives
❖ At least half of the bleeding complications with warfarin occur When the
INR exceeds the therapeutic range (which is 2 to 3).
1. Pregnancy:
A. Cancer:
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◼ Risk assessment for VTE in surgical patients mainly depends on the type of
surgery and the bleeding risk associated with the procedure.
◼ The major risk factors for VTE among medical patients hospitalized for acute
care
A. ICU admission (critical care),
B. Stroke with lower limb paralysis
C. Active cancer
D. Known thrombophilia (inherited or acquired)
E. Prolonged immobilization ≥ 3days
F. Heart failure
G. Acute respiratory failure
H. Sepsis
I. Chronic inflammatory diseases.
◼ The presence of one or more risk factors puts the patient at increased risk.
◼ The higher the number of the risk factors, the higher the risk of developing
VTE.
◼ Although not widely validated, there are a few risk assessment models
designed to help clinicians make a better risk assessment and decide on the
provision of prophylaxis.
◼ We the use of one of the risk assessments tools: IMPROVE-VTE risk
assessment model (see the table below).
◼ Before starting prophylactic anticoagulation assessment of the risk of bleeding
is as important as assessing the risk of VTE. Use the IMPROVE-VTE
bleeding risk assessment tool given below.
◼ The major contraindications for pharmacologic prophylaxis
A. Active bleeding
B. Intracranial hemorrhage of any cause
C. Thrombocytopenia (<50,000 or <100,000 with additional risk factor)
D. Major surgery planned in the coming 12 hours.
◼ If a patient has a high risk of bleeding based on clinical evaluation or using
the IMPROVE VTE bleeding risk assessment, prophylactic anticoagulation
should be avoided.
◼ Options for pharmacologic prophylaxis
A. Enoxaparin 40mg, SC, daily for the time of hospitalization during acute illness
OR
B. UFH, 5,000 IU, SC, BID for the time of hospitalization during acute illness 3 -
4 weeks
✓ Penetrating injuries
✓ Superinfection by other bacteria
✓ Devitalized tissue
✓ Foreign body presence
✓ Tissue ischemia
➢ Clinical situations that may also predispose for tetanus:
✓ Infected umbilical stump in neonates
✓ Septic abortion
✓ Unhygienic circumcision
✓ Dental infections
✓ Infected diabetic foot ulcers
➢ In 10% of tetanus patients site of entry is not identified
Clinical
Features
➢ Incubation period:
✓ Ranges from a few days to a few weeks with an average of a week
✓ A short incubation period (time from injury to first symptom) of ≤4 days
generally indicates severe disease.
✓ The period between the first symptom and the development of muscular
spasms is termed the period of onset. Shorter periods of onset,
particularly <48hrs, are again associated with more severe forms of
tetanus
✓ Shorter in neonatal tetanus and with injuries close to the CNS
➢ Recovery from tetanus takes 4-6 weeks
➢ Generalized tetanus
✓ The commonest form
✓ The most common and important clinical features include trismus
(lockjaw) localized or generalized muscular rigidity and spasm.
✓ Lockjaw (or trismus) the cardinal symptom is characterized by: intense,
painful spasms of the masseter muscles, and an inability to open the
mouth
✓ Other symptoms: stiff neck, opisthotonos, risus sardonicus, board
abdomen, apnea during spasms, dysphagia, sweating, arrhythmia, fever,
labile BP
✓ Consciousness is not impaired in tetanus patients
✓ The presence of arrhythmia, extreme oscillation in blood pressure,
diaphoresis, laryngeal spasm and urinary retention may suggest
autonomic dysfunction.
➢ Local tetanus
✓ Rare
✓ Signs/ symptoms limited to one part of the body
✓ Difficult to diagnose early
✓ Less severe
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Investigations
Severity Scoring
➢ There are several severity scores used but the Ablett classification has
been used most commonly.
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Treatment
Non pharmacologic
Pharmacologic
➢ Patients with severe tetanus should be managed in the intensive care setting
where mechanical ventilator and appropriate medication are available. This
may necessitate referral of most patients to specialized centers.
A. Control of spasm
under.
✓ Magnesium is used in patients with severe tetanus for whom
tracheostomy has been done; it helps in reducing the need for other
muscle spasm controlling drugs and may reduce muscle spasms
and well-studied in reducing autonomic instabilities)
B. Neuromuscular blockade
C. Antimicrobial treatment
➢ Human Tetanus immunoglobulin (HTIG), 500 IU I.M. stat (at a different site to
the vaccine)
✓ the use of passive immunization to neutralize unbound toxin (bound toxin
is irreversible) is considered as the standard care as it is associated with
improved survival.
✓ Give immediately after the diagnosis, with part of the dose infiltrated
around the wound.
➢ Intravenous immune globulin may be administered as an alternative if HTIG is
not available.
E. Active immunization
➢ Tetanus Antitoxin (TAT) 10,000 IU IM. after a skin test:
✓ All patients with tetanus, particularly in those never immunized previously,
full series of active immunization with appropriate booster doses is
recommended immediately upon diagnosis, because tetanus infection do
not confer immunity.
✓ Administer vaccines at a different site than tetanus immune globulin.
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➢ If ICU services are not available, acute respiratory failure is a principal cause
of death from tetanus.
➢ In the absence of an ICU
✓ A separate ward or room should be designated for patients with tetanus,
and
✓ Keep sensory stimuli to a minimum because loud noises, physical contact,
and light can trigger tetanic spasms. Eye shades and ear plugs can also
be used to reduce stimuli.
✓ Nondepolarizing neuromuscular blockers (e.g. vecuronium and pancuronium)
are not safe in the absence of ventilatory support. Yet, benzodiazepines
and baclofen can be used with careful doses titration to avoid respiratory
depression. Magnesium sulfate can be used to adjunctive muscle spasm.
➢ Supportive care is the basic treatment for tetanus because the tetanus toxin
once bound to neurons cannot be displaced from the nervous system. Hence
patients with severe cases will remain immobile for a long (for weeks), most of
them in mechanical ventilation. As a result, they are predisposed to decubitus
ulcers, nosocomial infections, thromboembolic disease, tracheal stenosis, and
gastrointestinal hemorrhage.
➢ Bed sore prevention measures are important
➢ Early nutritional support may be required, enteral feeding is preferred, to meet
the increasing energy demands of tetanus patients.
➢ Prophylactic acid blockers or sucralfate may prevent gastroesophageal
hemorrhage from stress ulcer.
➢ Thromboembolism prophylaxis with heparin, or low molecular weight heparin
should be administered early.
➢ Physical therapy should be started as soon as spasms have ceased, to avoid
disability from prolonged muscle wasting and contractures.
Prevention
➢ Appropriate tetanus prophylaxis (human tetanus immune globulin and/or vaccine
(e.g. TT)) should be administered ASAP following a wound as well as up one
to two weeks of injury for previously vaccinated (not fully vaccinated or
vaccinated before 5-10 years) and up to 21 days of injury for previously
unvaccinated late care seekers.
➢ This is because the incubation period is quite variable; most cases occur
within 8 days, but the incubation period can be as short as 3 days or as long
as 21 days.
➢ For previously unvaccinated or partially vaccinated a human tetanus immune
globulin is concurrently (with the vaccine) recommended unlike the full
vaccinated individuals.
➢ Immunization of pregnant or childbearing age women reduces neonatal tetanus
mortality by more than 90 %.
➢ Improving hygiene during home births is also help to prevent neonatal tetanus.
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Etiology
➢ In 1873 Gerhard Armauer Hansen – identified M. leprae.
➢ Earliest description - from India
Microbiology
➢ M. leprae → acid-fast bacillus .
➢ A member of the family Mycobacteriacae.
➢ straight or slightly curved rod-shaped organism.
➢ Multiplies very slowly → generation time 14 days.
➢ An obligate intracellular parasite.
➢ It grows best at 27ºC to 33ºC→ predilection for affecting cooler areas of the
body
✓ the skin, nerve segments close to the skin, and the mucous
membranes of the upper respiratory tract ……..
➢ M. leprae has never been cultured in artificial media.
➢ Grows in armadillos extensively
➢ Armadillo and foot pad of mouse → core body temperature of 34ºC. ( M.
leprae grows best at 30-33ºC)
➢ It is a disease virtually confined to humans.
➢ Leprosy is found in wild armadillos in the south, central United States and in
Chimpanzee, Sooty Mangabey Monkeys, in Africa
Transmission
➢ uncertain.
➢ Nasal droplets from lepromatous patients. (believed to be the mode of
transmission by most authorities)
➢ skin-to-skin contact – not considered as an important route.
➢ Requirements for the spread of leprosy;Contagious patient (lepromatous
patient),Susceptible individual (genetic, poverty …)and Close or intimate contact.
➢ Contact with a tuberculoid case carries a very low risk.
Pathogenesis
➢ a little is known
Classification of leprosy
WHO’s classification
➢ Based on the number of skin lesions present, number of peripheral nerves
involved & presence or absence of bacilli on smears.
➢ Paucibacillary disease
✓ one to five skin lesions and no bacilli on smear testing.
✓ if only one nerve is involved, & nerve biopsy smear is negative (in case
of pure neural leprosy)
➢ Multibacillary disease
✓ six or more skin lesions with or without bacilli
✓ Less than six skin lesions, which have a positive slit skin smear result.
✓ if ≥ 2 nerves are involved or if one or more nerve involved with positive
smear (in case of pure neural leprosy)
Ridley-Jopling’s classification.
➢ Used to differentiate types of leprosy.
➢ helps in determining prognosis.
➢ It is based on clinical picture, histology, sometimes bacillary load.
➢ The granulomatous spectrum of disease described by Ridley&Jopling;
✓ Polar tuberculoid (TT)
✓ Border line tuberculoid (BT)
✓ Mid borderline (borderline) (BB)
✓ Borderline lepromatous (BL)
✓ Lepromatous leprosy (LLp)
✓ Polar tuberculoid leprosy ( TT )
➢ Immunity is strong.
➢ Solitary plaque having annular configuration, both border is sharply marginated,
indurated, erythematous, scaly, hypo pigmented hypesthetic, anhidrotic.
➢ Size is often less than 10cm.
➢ Resistance
✓ Is too low to restrain bacillary proliferation but still sufficient to induce
tissue destructive inflammation (nerve damage) thus, patients with BL
have the worst of both worlds.
➢ Highly variable in its clinical presentation.
➢ Diamorphic lesion can be seen in in 1/3rd of patients.
➢ Punched out lesions can also be seen
➢ Lesions range from solitary to wide spread.
➢ Poorly defined papules & nodules.
➢ Annular & plaque lesions are often asymmetric.
➢ Lepromatous like nodules are symmetric if numerous.
➢ Nerve trunk palsies have highest prevalence.
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➢ Leprosy should be considered in the setting of skin lesions that are chronic
and not responding to standard treatment for more common conditions or when
➢ sensory loss is observed within lesions or in extremities.
➢ Additional clues include presentation of cuts or burns in the absence of pain
and travel history including residence in endemic countries (foreign birth,
military experience, etc).
➢ 90% history of numbness first→ sometimes years before the skin lesions
appear
➢ Sensory loss: Temperature → light touch → pain → deep pressure.
➢ The skin lesions appear later during the course of the disease.
➢ Borderline patients may present in reaction with nerve pain, sudden palsy,
multiple new skin lesions, pain in the eye, or a systemic febrile illness.
➢ Patients commonly present with
✓ skin lesions
✓ weakness or numbness due to a peripheral nerve lesion
✓ a burn or ulcer in an an aesthetic hand or foot.
➢ Assess for physical signs in 3 general areas:
✓ For cutaneous lesions.
✓ Neuropathies.
✓ Eye damage.
➢ For cutaneous lesions
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✓ Always look at the face, ears, trunk, buttock and lateral aspect of the
limbs for cutaneous lesions.
✓ A hypo pigmented macule/plaque with a raised border is often the first
cutaneous lesion.
✓ Lesions may or may not be hypo esthetic.
➢ Neuropathies
✓ Assess for areas of hypoesthesia (light touch, pinprick, temperature) &
anhidrosis especially of peripheral nerve trunks and cutaneous nerves.
✓ commonly affected nerves include posterior tibial nerve, ulnar, median,
lateral popliteal, and facial nerves. (assess for enlargement, tenderness,
consistency, irregularities)
✓ sensory loss, motor loss, and autonomic loss should be assessed.
✓ Nerves commonly involved include
▪ the ulnar and median (claw hand)
▪ the common peroneal (foot drop)
▪ the posterior tibial (claw toes and plantar insensitivity)
▪ Facial, radial cutaneous,great auricular.
➢ Eye damage is most often seen with facial lesions.
✓ Lagophthalmos (inability to close the eye) due to involvement of facial
nerve.
✓ a late finding in LL
▪ reduced corneal reflex→ leaving dry eyes and reduced blinking are
due to ophthalmic division of trigeminal nerve involvement. (
corneal ulceration, scarring, blindness)
▪ Extraocular findings include madarosis , leonine facies..
Diagnosis
➢ the cardinal signs of leprosy
➢ The diagnosis of leprosy is primarily clinical.
➢ Diagnosis is based on one or more of 3 signs:
✓ Hypo pigmented or reddish patches with definite loss of sensation.
✓ Thickened peripheral nerves with loss of sensation & or weakness of
muscles supplied.
✓ Acid-fast bacilli on skin smears or biopsy material.
➢ Lab… Slit skin smear
✓ Lesions and cooler areas of the skin, such as the fore head, earlobes,
chin, elbows, knees, buttock and trunk are preferred sites for smear.
✓ An incision 5 mm long and 3 mm deep is made and blade is turned at
right angles to cut, and to take fluid, and pulp from the dermis.
✓ M. leprae are detected by modified Zeihl-Nelson staining.
➢ Skin biopsy
✓ To assess the extent and type of infiltrate and involvement of dermal
nerves, a full-thickness skin biopsy should be taken from the most active
margin of the most active lesion, entirely within a lesion.
✓ Skin smears, in which a small incision is made (on the ears,
elbows, and/or knees) to collect a dermal fluid sample, are no longer
widely used.
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Management
Goals
➢ Bacteriological cure.
➢ Detect and treat reactions.
➢ Prevent nerve damage and disabilities.
➢ Treat complications of nerve damage.
➢ Rehabilitation
✓ Physical
✓ Mental and
✓ Social
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Reactional states
Immunologically driven distinctive tissue destructive inflammatory processes that
appear suddenly in any form of leprosy.
Precipitating factors
- MDT, Pregnancy, Inter current infections ,BCG etc
Usually occur as complications during treatment but they may occur before
treatment or after treatment.
Two types of reactional states are known :-
- Type-1 (Reversal).
- Type-2 (Erythema nodosum leprosum, ENL).
Treatment of ENL
➢ General
➢ Lab investigation
➢ Grading of severity
➢ Mild
✓ Skin eruption without nerve tenderness or loss of function
➢ Severe
✓ Multiple and ulcerating lesion
✓ Iritis, orchitis, nephritis or hepatitis
✓ Nerve tenderness and loss of function
➢ What is a relapse?
✓ Return of active disease after completion of prescribed treatment
✓ When the BI at any site increases by at least 2+
✓ Detection of active disease 2 years after completion of treatment
✓ Relapse rate mono therapy era 20 -27%
✓ Relapse with combination treatment 4-20%
✓ Relapse after MDT less than 1% with the 2 years of MDT/ MB
✓ Relapse after 1year MDT/MB not yet known
➢ How to recognize relapse
✓ Active lesion
✓ Increase in BI
✓ New lesion
✓ Erythema
✓ Neuritis
✓ Deterioration of nerve functions
➢ Clinical features
✓ New lesions
✓ Extension of existing lesions
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(Elephantiasis)/ዝሆኔ/
3.12.14 COVID -19
Clinical features
Table; Toxidromes
Examples of
Toxidrome Mental status Pupil Vital signs Other toxic agents
Confusion Coma Miosis Bradycardia Salivation, urinary & fecal Organophosphate and
Cholinergic
Hypertension or incontinence, diarrhea, carbamate insecticides, nerve
Hypotension vomiting, lacrimation, agents,
bronchoconstrictio,
fasciculations, weakness,
seizures
Agitation, Mydriasis Hyperthermia, Dry skin & mucous Antihistamines, tricyclic
Anticholinergic
hallucinations, membranes, decreased antidepressants, antiparkin
delirium with tachycardia, bowel sounds, urinary son agents, antispasmodics,
mumbling speech, hypertension, retention, myoclonus, phenothiazines, atropine
coma tachypnea choreoathetosis
Investigations
✓ RBS
✓ CBC
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✓ U/A
✓ Electrolytes
✓ BUN and creatinine
✓ LFT
✓ Urine HCG → Routine urine pregnancy testing is strongly recommended in all women of
childbearing age
✓ ECG
✓ CXR → for possible aspiration pneumonia
✓ Toxicological analysis of identified substance (e.g. Gastric aspirate) or from serum → if
available
o Physiologic antagonism
☛ Prevention of re-exposure
o Child-proofing
o Psychiatric referral
☛ For Comatose pts…
o Search for Hypoxia, Opioid intoxication, hypoglycaemia, and Wernicke’s encephalopathy.
o Supplemental oxygen, Naloxone (for symptoms of opioid toxicity), 30ml of D50W
and 100mg of thiamine known as the ‘coma cocktail’ can be administered
Initial management
1. Hypoglycemia
o 40% Dextrose, IV, 40-60ml over 1-3 minutes PLUS
2. Hypotension
o NS, 1000ml, IV fast then according to response
3. Seizure management and medicine-associated agitated behavior
Activated charcoal
Catharsis
o Should be given only with the first dose of multiple dose charcoal in order to prevent
electrolyte abnormalities and osmotic diuresis.
o Magnesium sulphate, 250mg/kg or
o Sodium sulfate, 250mg/kg
Alkalization of urine
Decontamination
Skin decontamination
Remove contaminated clothing and flush exposed areas with copious quantities of tepid
(lukewarm) water or saline. Wash carefully behind ears, under nails, and in skin folds.
Use soap and shampoo for oily substances.
Always wear PPE to prevent secondary contamination to yourselves
Eye decontamination
irrigate with copious amounts of water or saline for 10 – 15 minutes
Ophthalmologic consultation is indicated for all ocular alkali injuries
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GI Decontamination Principles
A. Activated charcoal
B. Ipecac syrup
C. Gastric (Orogastric) lavage
D. Whole bowel irrigation
E. Urine alkalinisation
A. Activated Charcoal
Activated charcoal, 50 -100g (1- 1.5g/kg), P.O., or via NG tube, diluted in 400–800ml water
stat
✓ Activated charcoal may reduce systemic absorption of a variety of substances
(especially from GIT).
✓ The greatest benefit (indication) is achieved if activated charcoal is given within 1
hour after ingestion.
✓ Charcoal administration has become the decontamination strategy of choice to prevent
poisoning after toxicant ingestion
✓ When mixing, add a small amount of water to charcoal in a container cap and shake
container to make a slurry and then dilute further.
Complication: no systemic effects, but may induce vomiting, constipation, diarrhoea, Bowel
perforation or obstruction following multidose charcoal administration, aspiration of the
activated charcoal and impaired absorption of orally administered antidotes.
Avoid (no value): strong acids, alkali, corrosives, heavy metals, cyanides, lithium,
hydrocarbons (paraffin), methanol and ethylene glycol.
Contraindications:
✓ Known or suspected GI perforation
✓ GCS <8 (LOC) or declining rapidly (risk of aspiration)
✓ unprotected airway.
✓ Known ingestion of substance that charcoal does NOT adsorb.
❖ Dose: initial dose of 50 to 100 g (1 -1.5g/kg), PO or via NG tube, followed by 50g PO every 4hrs (in
case of intolerance 25 g every 2 hours) /0.5 - 1g/kg/, until clinical conditions and lab
parameters improves
❖ Multiple doses can enhance elimination of drugs already absorbed into the body by
interrupting enterohepatic circulation of drugs excreted into the bile.
❖ Indication: ingestion of large doses of Carbamazepine, dapsone, phenobarbitone,
quinine, theophylline, Salicylates, sustained release formulations.
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Indications
Contraindications
✓ Ingestion > 1 hr ago
✓ Toxin known to cause decreased LOC/seizure
✓ Caustics, hydrocarbons, TCAs
Indicated for ingestion of large amounts of tablets and capsules with a high inherent
toxicity within 2 hrs.
procedure:
✓ Place patient head tilted 20 degrees downward and in left lateral decubitus position
✓ Intubate patient, if they can’t protect their airway
✓ Insert a large bore orogastric tube (32-40 F)
✓ Aspirate fluid from stomach prior to fluid lavage
✓ Install warm tape water or saline into stomach: 200-300ml (10 mL/kg in children)
✓ Aspirate fluid back & repeat till aspirate clears
✓ Consider administration of activated charcoal via orogastric tube before removal.
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E. Urinary Alkalinisation
Universal Antidotes
➢ Thiamine
➢ Oxygen
➢ Naloxone
➢ Glucose
Benzodiazepines Flumazenil Initial dose: 0.1-0.2mg IV over 30-60 sec, repeat 0.1-0.2mg
IV every minute up to 1mg
Clinical features
☛ The killer signs are the 3B’s: Mnemonic for clinical features of Muscarinic
✓ Bradycardia overstimulation → DUMB BELL’S
✓ Bronchospasm
✓ Diarrhoea
✓ Bronchorrhea
✓ Urination
☛ Muscarinic overstimulation causes
✓ Miosis
✓ excessive salivation and sweating
✓ Bronchorrhea
➢ severe diaphoresis can actually lead to
dehydration with systemic hypovolemia
✓ Bronchospasm
✓ Lacrimation
✓ Emesis (Vomiting)
✓ Vomiting
✓ Lacrimation
✓ Diarrhea
Low or high HR (brady/tachycardia)
✓ Bronchorrhea or bronchospasm.
✓ abdominal cramping
✓
✓ Salivation and sweating 1118
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✓ miosis
✓ bradycardia or tachycardia
☛ Nicotinic overstimulation causes
✓ muscle fasciculations
✓ Paresis or paralysis.
✓ Death is usually caused by respiratory muscle paralysis.
✓ Blood pressure and pulse rate may be increased because of nicotinic effects or
decreased because of muscarinic effects.
Investigations
☛ Clinical
☛ Toxicological analysis
Treatment
☛ For all poisoning patients the principles of management are
o ABC’s of life comes first→ Pay careful attention to respiratory muscle weakness; sudden
respiratory arrest may occur.
o Give coma cocktail (Naloxone, thiamine, dextrose and oxygen),
o decontamination
o Antidote and
o Supportive care
Pharmacologic
➢ Atropine, 2 - 5 mg (0.05 to 0.1 mg/kg to children), IV, doubled every 5 min as needed
to obtain and maintain full atropinization, which is indicated by an end point of clearing
bronchial secretions and pulmonary rales.
✓ Do not stop atropine therapy abruptly. Wean the rate of administration slowly.
✓ During weaning monitor the patient for possible worsening.
✓ Our goal in atropinazation is chest clearance and not tachycardia.
✓ Therapy is continued until all absorbed organophosphate has been metabolized and
may require 2 mg to more than 2g of atropine over the course of a few hours to
several days. The most clinically important indication for continued atropine
administration is persistent wheezing or bronchorrhea.
✓ Note: Atropine will reverse muscarinic but not nicotinic effects.
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Atropinisation
➢ 1 ampule (1mg/ml) = 1ml
➢ Start with 2mg
➢ Escalate every 5min by doubling the dose (i.e. 2mg →4mg → 8mg → 16mg)
➢ Maximum until chest is clear
➢ If the chest is clear give 20% of the last dose as follows
✓ every 2hrs for 6hrs then
✓ every 4hrs for 24 hrs then
✓ QID → TID → BID →stop
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compounds that affect the uptake of acetylcholine and/or its release should be avoided in
the management of these patients. Specifically, aminophylline and phenothiazines are
contraindicated.
➢ Decontamination → activated charcoal, gastric lavage… Do not induce vomiting because of
the risk of abrupt onset of toxicity
➢ Observe patients for at least 6–8 hours to rule out delayed-onset symptoms resulting from
skin absorption.
❖ Corrosives are chemicals primarily acids and alkali that cause tissue injury to a burn.
❖ Acids cause coagulation necrosis with eschar formation that limits penetration and depth
of injury.
❖ Alkali cause liquefaction necrosis and penetrate more deeply. Alkali burns more common
and worse than acid.
❖ Some corrosives can cause severe systemic toxicity and profound electrolyte disturbance.
Clinical features
After ingestion of corrosive, hyper salivation, lethargy, polydipsia, vomiting, abdominal pain,
dysphagia, pharyngeal edema, oral pain, drooling, and oral, esophageal, and/or gastric
ulceration could occur.
Inhalation of corrosive gases may cause upper respiratory tract injury, with strider,
hoarseness, wheezing, and noncardiogenic pulmonary edema.
Eye or skin exposure to corrosive causes instant pain and redness, followed by blistering.
Conjunctivitis and lacrimation are common. Serious full-thickness burns and blindness can
occur.
Significant injury: airway compromise or gastrointestinal perforation complicated by
peritonitis, mediastinitis, sepsis and shock.
Diagnosis 1121
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Management
➢ Inhalation:
▪ Give oxygen, and
▪ follow closely for signs of airway obstruction or for non-cardiogenic pulmonary edema.
➢ Chemical ingestion:
▪ Pre-hospital: immediately give water or milk to drink.
▪ Gastric lavage & induction of vomiting are contraindicated.
▪ Give activated charcoal if the ingested agent can cause significant systemic toxicity.
▪ If there is esophageal perforation, avoid giving water as it may also enter to the
mediastinum.
▪ If esophageal or gastric perforation is suspected surgical consultation and repair
immediately.
➢ Chemical eye and skin burn:
▪ Remove all clothing, wash skin, and irrigate eyes with copious water or saline.
➢ Button batteries:
▪ Immediately lodged endoscopy guided removal should be done immediately.
➢ Antacids are used for subsequent ulcer treatment
➢ use of steroids & antibiotics has no benefit.
➢ For most agents, there is no specific antidote.
Herbicides are used as a weed killer which can cause human toxicity.
4.2.4 ChlorophenoxyHerbicides
The most common agent in this group are
✓ 2,4-dichlorophenoxyacetic acid (2,4-D)→ locally available also as Sura
✓ 2,4,5-trichlorophenoxyacetic acid (2,4,5-T);
✓ 4-chloro-2 Methyl chlorophenoxyacetic acid;
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Clinical feature
Eye and mucosal irritation after direct contact
Nausea, vomiting and diarrhoea after ingestion
Dyspnea, tachypnea and pulmonary edema after inhalational exposure
Systemic toxicity (If large exposure) result in:
✓ Neurologic toxicity (Mental status changes and seizures)
✓ Cardiac toxicity (hypotension, tachycardia, and dysrhythmias);
✓ Skeletal toxicity (muscle tenderness, fasciculation, rhabdomyolysis)
Diagnosis
Treatment
Supportive → Decontamination measures
✓ Administer activated charcoal, then Perform gastric lavage
✓ After lavage, give a dose of charcoal
✓ Skin decontamination if exposed
✓ Urinary alkalinization is recommended for severely poisoned patients,
✓ Hemodialysis can also be used
Respiratory support for myopathic-related respiratory failure,
No specific antidote
Patients should be monitored for rhabdomyolysis and treated as necessary.
Asymptomatic or minimally symptomatic discharged after 4 to 6 hours of observation;
Patients with muscle effects need Admission for Close observation and monitoring.
Plasma concentration peaks within minutes to 2 hours after ingestion, then distributed to most
organs, with the highest concentrations found in the kidneys and lungs;
In the lung paraquat accumulates and the high local oxygen tension generates a high levels
of toxic oxygen species and subsequent damage
In the kidney paraquat is concentrated during excretion, often leading to acute tubular
necrosis, which may occur soon after ingestion (within 24 hours)
Paraquat-induced renal dysfunction may decrease paraquat excretion, thereby enhancing
overall toxicity
A lethal oral dose of the 20% concentrate paraquat solution is about 10 to 20 mL in an adult
and 4 to 5 mL in a child;
Ingestion is responsible for the majority of paraquat deaths
Inhalation exposure to sprays can be very irritating to conjunctiva and the airway but are
unlikely to cause systemic toxicity
✓ Diquat
Has similar structure, mechanism and lethal dose as paraquat
Fewer occurrences of pulmonary injury and fibrosis because of diquat’s lower affinity for
pulmonary tissue
Caustic to the skin and GI tract, and exposure can result in renal and liver necrosis.
GI tract_ Ulceration of the lips, tongue, and pharynx within one to two days of ingestion,
esophageal ulceration may proceed to esophageal perforation
Skin —skin rashes (particularly on scrotal and intergluteal areas), cracked nails, and epistaxis
Lungs — Inhalation may cause local toxic effects on bronchi, possibly resulting in cough,
dyspnea, chest pain, pulmonary edema, epistaxis, and hemoptysis;
Eyes —corneal exposure can cause ulceration and scarring
Systemic toxicity
✓ Multisystem effects include acute renal failure, cardiac failure, hepatic failure, and
extensive pulmonary injury,
✓ Evident within a few hours following large ingestions, but more typical manifestations of
renal failure and hepatocellular necrosis develop between the second and fifth days,
with progressive pulmonary fibrosis leading to refractory hypoxemia 5 days to several
weeks later
✓ Metabolic (lactic) acidosis is common as a result of pulmonary effects (hypoxemia) and
multisystem failure;
Diagnosis
Exposure history
U/A
Organ function test
serum electrolyte
CXR → may show pneumomediastinum/pneumothorax due to corrosive rupture of the
esophagus
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Treatment
Admit any patient with Paraquat poisoning even if asymptomatic,
Supportive care:
✓ ABC of life
✓ Antipain
✓ Treatment of renal failure and complications
✓ Treatment of infection,
Do not administer supplemental oxygen unless the patient is severely hypoxic, because
added oxygen stimulates superoxide radical formation and promotes oxidative stress
Maintain intravascular volume and urine output to prevent pre-renal kidney injury,
Decontamination
✓ Remove clothing for splash
✓ Skin washing with mild detergent for dermal contact
✓ Irrigate eyes with saline/ copious water if conjunctivae exposure,
✓ Lavage not routinely recommended unless patient present early and for ingested
✓ Activated charcoal (1gm/kg up to 100 gm), and repeat dose in 1–2 hours
✓ Prolonged Hemoperfusion or Hemodialysis two to three weeks, 4-6 hours daily,
Repeated pulse doses of glucocorticoids and cyclophosphamide may improve survival in
severe cases
Treatment for diquat poisoning is similar to that for paraquat.
A. Non-anticoagulant Rodenticides
includes:
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Zinc/ Aluminum Phosphide, Arsenic, Barium carbonate/ hydroxide/ chloride/sulfide,
Phosphorus (elemental/ yellow), sodium fluroacetate, Strychnine, Tetramine, Thallium Sulfate ,
ANTU, Bromethalin, Dicaboximide, Vacor.
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Clinical feature
The onset of symptoms is usually rapid, although delayed onset of pulmonary edema has
been described;
If ingested; Immediate nausea, vomiting, epigastric pain, phosphorous or fishy breath, black
vomitus, and GI irritation or ulceration
Inhalation of phosphine gas is associated with cough, dyspnea, headache, dizziness, and
vomiting
Myocardial toxicity, shock unresponsive to pressers, and acute lung injury, agitation, coma,
seizures, hepato-renal injury, metabolic acidosis, hypocalcaemia tetany in both exposures has
been observed;
Diagnosis 1126
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Treatment
Emergency and Supportive care
Decontamination → Gastric lavage with potassium permanganate or combination coconut oil
and 3- 5%sodium bicarbonate (Reduce stomach acid and resulting production of phosphine
gas);
No specific antidote
✓ Magnesium sulphate IV with low dose of dopamine may be beneficial
✓ Consider acetylcysteine
Admit and observe for 48 - 72 hours for delayed onset of pulmonary edema,
B. Anti-coagulant rodenticides
First generation rodenticidal anticoagulants →
✓ They are less toxic than second generation agents.
✓ E.g. Warfarin (Coumadin) is used therapeutically and as rodenticides;
Second generation agents
✓ They are far more toxic than first generation.
✓ Lethal after a single ingestion of bait thus, they are sometimes referred to as "super
warfarin’s"
✓ Examples of Super warfarin: Brodifacoum, Diphacinone, Bromadiolone,
Chlorophacinone, Difenacoum, Pindone, and Valone;
✓ Have profound and prolonged anticoagulant effects.
✓ Locally available brands include Zara.
Toxic dose: most warfarin-based rodenticides produce little effect after a single dose (10-
20mg); While a single dose of super warfarin (as low as 1 mg) produce a significant clinical
effect,
Clinical feature
Seen as early as 8-12 hrs but mostly delayed by 1-2 days after ingestion and continue for
days, weeks or months after super warfarin ingestion
Sign and symptom of bleeding diathesis such as ecchymoses, subconjunctival hemorrhage,
bleeding gums, or evidence of internal hemorrhage (eg, hematemesis, melena, or hematuria)
the most immediately life-threatening complications are massive GI bleeding and ICH.
Diagnosis
Based on exposure history
Coagulation profile → Elevated levels of PT (INR) from admission level suggest poisoning
and a normal PT level after 48 hrs of exposure rules out significant exposure
CBC → Platelet count which may be used to rule out other causes of bleeding
BG &RH and cross-match, 1127
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Treatment
Emergency and supportive treatment
✓ Treat hypervolemia/ shock with crystalloids,
✓ Transfusion with whole blood or FFP
✓ Consult neurosurgeon if intracranial bleeding suspected
✓ Minimize or avoid invasive procedures like NGT insertion or endotracheal intubation if
possible
✓ Avoid drug, which may decrease metabolism of warfarin like cimetidine, sulfonamides,
NSAID;
Antidote → Vitamin K (phytonadione), effectively restores the production of clotting factors
✓ 5-10mg very slowly IV/SC, max; 200 mg/d
✓ Repeated may be required, especially in super warfarin product ingestion
✓ Titrate Vit. K dose based on PTT level,
✓ May require FFP/ whole blood transfusion for active bleeding as Vit. K take effect (6-
24hr later).
Decontamination: Activated charcoal can be used.
Enhanced elimination has no role.
Clinical features
The hallmark of ethanol toxicity is clinical inebriation.
Behavioural disinhibition may initially appear as euphoria or agitation and combativeness.
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As intoxication becomes more severe, slurred speech, nystagmus, ataxia, and decreased
motor coordination develop.
Severe intoxication may cause respiratory depression and coma.
Nausea and vomiting
Peripheral vasodilation promoting hypothermia and flushed, warm skin may also lead to
orthostatic hypotension (usually mild) and reflex tachycardia.
Hypoglycaemia
Lactic ketoacidosis.
Signs
Look evidence of infections and traumatic injuries
Depressed mental status
Diagnosis
RBS
serum alcohol levels in patients with altered mental status of unclear cause.
Treatment
Management is observation until sobriety.
Treat hypoglycaemia with IV glucose 0.5 to 1 grams/kg
long-term drinkers are sometimes treated with IV fluids containing magnesium, folate,
thiamine, and multivitamins, termed a banana bag because of the yellow color imparted by
the multivitamin mixture.
Wernicke’s encephalopathy (characterized by abnormal mental status, ataxia, and nystagmus)
requires daily treatment with thiamine, 100 mg, until normal diet is resumed.
Prior to discharge, reassess for an underlying mental health disorder, such as suicidal or
homicidal ideation, that requires further care or hospital admission.
Clinical judgment, rather than a serum ethanol level, determines the appropriateness of
discharge.
Discharge the patient in the care of a responsible companion.
Clinical presentation
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Nausea, vomiting, and diarrhoea, hematemesis may occur and as a result secondary
dehydration and electrolyte imbalance may develop.
Mild ocular irritation is possible.
Dermal contact generally causes a mild erythema or rash
Diagnosis:
Based on history of exposure.
IX; RBS, Electrolytes, glucose, calcium and Phosphate (after ingestion of phosphate-containing
products, Methaemoglobin (Cationic detergents)
Treatment
In patients with protracted vomiting or diarrhea, administer IV fluids to correct dehydration and
electrolyte imbalance.
If corrosive injury, use the management guideline for corrosive ingestion.
If hypocalcaemia occurs after ingestion of a phosphate-containing product, give IV calcium.
Decontamination:
✓ dilute orally with small amounts of water or milk.
✓ Do not induce vomiting because of the risk for corrosive injury.
✓ Consider gastric lavage only for massive ingestions.
✓ Activated charcoal is not effective.
✓ In severe cases anti-emetics may be required (e.g., metoclopramide, 1omg /0.2–0.4
mg/kg/, PO, SC, or IM, QID based).
Eyes and skin exposure→ irrigate with copious amounts of tepid water or saline. Consult an
ophthalmologist if eye pain persists or if there is significant corneal injury.
Clinical presentation
HEENT: exposure to the fumes can cause burning in the eyes, ears, and nose, pain in the
mouth, and pain in the throat
RS; chest tightness, coughing and difficulty of breathing. In more severe cases increased
breathing rate, wheezing, swelling of the airways and respiratory failure may occur, the onset
of which may take up to 36 h.
Skin: irritation of the exposed area. Burns and blistering have been reported.
GIT: abdominal pain, vomiting
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CVS: Rare cases of cardiovascular collapse and shock are presumed to consider secondary
to severe local injury.
Nervous system: Lethargy, delirium and coma can occur in patients with severe respiratory
effects.
laboratory studies
For ingestion → CBC, electrolytes, and chest and abdominal x-rays to look for mediastinal or
intraabdominal air, which suggests perforation.
For inhalation, arterial blood gases and pulse oximetry.
Treatment
Emergency and supportive measures
o Inhalation of chlorine gas:
✓ Immediately remove victim from exposure
✓ Give humidified supplemental oxygen.
✓ Observe for upper airway obstruction, and intubate if necessary.
✓ Use bronchodilators for wheezing and treat non-cardiogenic pulmonary edema if it
occurs.
Clinical presentation:
It causes CNS depression, corrosion of oral mucosa and gastrointestinal tract (upper GI
hemorrhage), laryngeal edema, upper airway obstruction, bronchospasm, nephrotoxicity,
hepatitis and cardiac arrhythmias.
The main risk of poisoning is aspiration with subsequent development of acute respiratory
distress syndrome (ARDS), pneumonia and sudden cardio-respiratory arrest.
Micro-aspiration has been hypothesized to be the reason for delayed upper airway obstruction
that may occur in totally asymptomatic patients up to 48 h after admission. 1131
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Treatment:
The mainstay of dettol poisoning is supportive management along with close observation in
hospital for stridor.
Emesis and gastric lavage should not normally be attempted. The only indication for gastric
lavage in the acute setting is a patient who has consumed other poison along with Dettol.
Patient should be started on IV fluids with regular monitoring of electrolytes.
Adolescents and adults who have consumed more than 200 to 300 ml and children who
have consumed lesser amounts should be kept NPO and watched carefully for signs and
symptoms of nephrotoxicity and CNS depression.
In case of severe poisoning or any evidence of hematuria or azotemia, do forced alkaline
diuresis
Exchange transfusion, and early dialysis for isopropyl alcohol can be attempted in rare
patients who are deteriorating steadily despite adequate supportive measures.
Even patients who arrive comatose to the ED frequently demonstrate a rapid and complete
recovery. It is, however, important to monitor closely in hospital for strider for a minimum of
48 hours after admission.
Clinical Presentation:
Pulmonary presents as coughing, gagging, or choking. This may progress within a few hours’ to tachypnea,
wheezing, and severe chemical pneumonitis.
Death may ensue from secondary bacterial infection and other respiratory complications.
Ingestion often causes abrupt nausea and vomiting, occasionally with hemorrhagic gastroenteritis.
Some compounds may be absorbed and produce systemic toxicity which includes confusion, ataxia, lethargy,
and headache.
With significant exposure, syncope, coma, and respiratory arrest may occur.
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Cardiac arrhythmias may occur owing to myocardial sensitization (with chlorinated and fluorinated compounds
Aspiration pneumonitis:
✓ If symptoms are not present within 6 h of exposure, it is very unlikely that chemical
pneumonitis will occur.
✓ Chest x-ray and arterial blood gases or oximetry may assist in the diagnosis.
Systemic intoxication:
✓ diagnosis is based on history of ingestion or inhalation, accompanied by the appropriate
systemic clinical manifestations.
Treatment
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such
as might occur with intentional overdose, may benefit from gastric
emptying. This is still a high-risk procedure that can result in further
aspiration.
Decontamination
✓ Inhalation: move the victim to fresh air and administer oxygen if available.
✓ Skin and eyes: remove contaminated clothing and wash exposed skin with water and soap. Irrigate
exposed eyes with copious tepid water or saline and perform fluorescein examination for corneal
injury.
✓ Ingestion: for agents with no known systemic toxicity, gut decontamination is neither necessary nor
desirable because any gut-emptying procedure may increase the risk of aspiration.
Clinical features
☛ Poisoning with carbon monoxide is common where there is incomplete combustion of
charcoal.
☛ Patients may manifest symptoms ranging from mild confusion to coma.
☛ Acute poisoning results in headache, nausea and vomiting, mental confusion and agitation.
☛ Severe toxicity causes confusion, impaired thinking, and may progress to coma, convulsions,
and death.
Investigations
Treatment
Non pharmacologic
☛ Supportive treatment
☛ Take the patient out to open air.
Pharmacologic
☛ The most important interventions in the management are removal from the CO source &
administer 100% oxygen by face mask
☛ Comatose patients should be intubated & mechanically ventilated using 100% oxygen.
☛ Hyperbaric oxygen
Clinical features
Local signs and symptoms
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Figure: Moderately severe envenomation. Note edema and early ecchymosis 2 h after a bite to the finger
Figure: left) Severe envenomation. Note extensive ecchymosis 5 days after a bite to the ankle. Right) Early
stages of severe, full-thickness necrosis 5 days after a viper bite
Figure; Severe necrosis 10 days after a pit viper bite in a young child
severity of envenomation:
Investigations
CBC
BG & RH
urinalysis for presence myoglobin or blood
BUN and Creatinine
LFT
PT/INR/PTT
Electrolytes
Whole blood clotting test (leave 2-5ml of blood in dried test tube. Failure to clot after 20
minutes implies in coagulable blood)
Treatment
Non pharmacologic
First Aid
☛ A significant proportion of snake bites do not result in envenomation……observe if no
clinical features of local/systemic sign and/ or symptoms;
☛ Move patient to a safe area
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☛ Remove anything tight around the bitten area (ankle bracelets, Rings)
☛ Splint the limb below the level of the heart to reduce movement and absorption of
venom if the limb is the affected organ; apply a firm bandage to affected limb from
fingers or toes to proximal site of bite.
☛ Do not move the limb
o Carry the person on a stretcher and tie the limb to a straight piece of wood.
o C lean the wound and reassure the patient.
At the hospital
Pharmacologic
If any evidence of neurologic dysfunction (e.g., any cranial nerve abnormalities such as ptosis
or inability to maintain upward gaze):
o Pre-treat with atropine: 0.6 mg IV (children, 0.02 mg/kg; min. of 0.1 mg) Followed by a
trial of anticholinesterase inhibitors
▪ Neostigmine: 1.5–2.0 mg IM (children, 0.025–0.08 mg/kg)
▪ If objective improvement is evident at 5 min, continue neostigmine at a dose of 0.5 mg
(children, 0.01 mg/kg) IV or SC every 30 min as needed, with continued administration of
atropine by continuous infusion of 0.6 mg over 8 h (children, 0.02 mg/kg over 8 h).
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Prophylactic antibiotics are unnecessary unless prehospital care included incisions or mouth
suction.
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N.B. The use of an NSAID is not recommended due to the potential danger of AKI in
a hypotensive patient.
Polyvalent antivenom
N.B.
☛ In most cases patients do not need and should not be given antivenom.
☛ The dose of antivenom is the same for adults and children.
☛ Serum sickness is a relatively common adverse event.
☛ Even after the administration of antivenom, patients with neurotoxic snakebites may need
ventilation.
slow IV infusion. Dilute 100 mL in 300ml of NS. Administer slowly for the first 15
minutes, as most allergic reactions will occur within this period. Increase the flow rate
gradually to complete the infusion within one hour.
o Prepare IM epinephrine (adrenaline) and IV chlorpheniramine, be ready if allergic
reaction occurs when antivenum given.
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o Before giving the anti-venom, perform skin test with 0.02 to 0.03 ml in 1:10 dilution,
subcutaneous, to test for anaphylaxis. If itching/urticarial rash, restlessness, fever,
cough or difficult breathing develop, then stop anti-venom and give epinephrine
(adrenaline).
o Start giving the antivenom with minimal dose for mild cases with a minimal dose of
22-40 ml and give a maximum of 200-400 ml. Blood transfusion should not be
required if anti-venom is given.
o Continue to observe for progression of edema and systemic signs of envenomation
during and after antivenom infusion.
✓ Measure limb circumference at several sites above and below the bite
✓ outline the advancing border of edema with a pen every 30 minutes.
✓ These measures serve as an index of the progression as well as a guide for
antivenom administration.
o More anti-venom should be given after 1–2 hr if the patient is continuing to bleed
briskly or has deteriorating neurotoxic or cardiovascular signs.
o Repeat laboratory determinations every 4 hours or after each course of antivenom
therapy, whichever is more frequent. Repeat if there is no clinical improvement after
the infusion.
o Clotting function returns to normal only after clotting factors are produced by the liver.
o Response of abnormal neurological signs to anti-venom is more variable and depends
on type of venom
o Neurotoxicity from elapid bites (cobra and mamba) may be harder to reverse with
antivenom. Once neurotoxicity is established and endotracheal intubation is required,
further doses of antivenom are unlikely to be beneficial. In such cases, the victim
must be maintained on mechanical ventilation until recovery, which may take days or
weeks.
o Mild hypersensitivity reactions should not be a reason not to give polyvalent.
o If acute reaction to antivenom develops and depending on severity of reaction:
▪ Stop infusion.
▪ Treat with standard doses of epinephrine (IM or IV; IV route only in the setting of
severe hypotension)
▪ Antihistamines (IV) e.g., Diphenhydramine, 1 mg/kg to a max. 100 mg, plus
Cimetidine, 5–10 mg/kg to a maximum of 300 mg
▪ IV glucocorticoids
▪ When reaction is controlled, restart antivenom ASAP if still indicated (may further
dilute in a larger volume of NS).
Surgical Management
Seek surgical opinion if there is severe swelling in a limb, it is pulseless or painful or there
is local necrosis
Surgical care will include:
o Intact serum-filled vesicles or hemorrhagic blebs should be left undisturbed. If ruptured,
they should be debrided with sterile technique.
o
o
Excision of dead tissue from wound 1140
Incision of fascial membranes to relieve pressure in limb compartments, if necessary
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Monitoring
Monitor very closely immediately after admission, then hourly for at least 24 hours as
envenomination can develop.
Any patient with signs of envenomation should be observed in the hospital for at least 24 h,
Patients whose condition is not stable should be admitted to an intensive care setting
Measure/record circumferences of the bitten extremity every 15 min until swelling has
stabilized; while monitoring, the extremity should be positioned at approximately heart level.
Admit to hospital. (If no evidence of envenomation, monitor for 8 h before discharge.)
Institute monitoring (cardiac and pulse oximetry)
Vital signs, cardiac rhythm, oxygen saturation, urine output.
At discharge, victims of venomous snakebite should be warned about possible recurrent
coagulopathy, signs and symptoms of wound infection, antivenom-related serum sickness
1141
✓ High-risk patients for toxicity include; If the patient is alcoholic, malnourished, or
fasting, or taking drugs that induce P-450 activity (e.g., anticonvulsants, INH)
Clinical Presentation
✓ Clinical manifestations depend on the time after ingestion.
✓ Early:
o usually no symptoms other than anorexia, nausea, or vomiting. Rarely, a massive
overdose may cause altered mental status and metabolic acidosis.
✓ After 24–48 hrs
o when AST and ALT level rise, hepatic necrosis becomes evident.
o If acute fulminant hepatic failure occurs, encephalopathy and death may ensue.
o Encephalopathy, metabolic acidosis, hypoglycaemia, and progressive rise in the
prothrombin time are indications of severe liver injury and has poor prognosis.
o Acute renal failure occasionally occurs, with or without concomitant liver failure.
Investigation
✓ RBS
✓ Electrolytes
✓ BUN and creatinine → the renal injury manifested after 2-3 days
✓ liver enzymes
✓ PT, INR
✓ Urine HCG→ because acetaminophen cross placenta by 14 weeks. So, antidote
should be considered in pregnancy ASAP.
✓ ECG → to exclude the presence of co-ingested cardiotoxic substances.
✓ Abdominal U/S → may reveal hepatic enlargement, renal abnormality, and
inflammatory changes.
✓ CT→ to see cerebral edema and encephalopathy in For patients with altered mental
status
✓ Interpretation of serum acetaminophen level lab result is based on Rumack-Matthew
nomogram (refer Poisoning and Drug Overdose Management Training for Health Care Professionals, FMOH,
Ethiopia, 2020)
Treatment
A. Emergency and supportive measures:
B. Decontamination:
✓ Prehospital. →
o activated charcoal, if available.
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NAC (N-Acetylcysteine)
✓ All patients requiring acetylcysteine therapy should be admitted to the hospital until
the
completion of the therapy. In general, admission to a hospital bed is adequate unless
the
co-ingestant is of concern, hepatotoxicity is severe, or the patient is suicidal, and 24-
hour
direct observation cannot be arranged.
✓ Patients who are not at risk for developing acetaminophen-induced hepatotoxicity
(e.g.,
acetaminophen concentration below the nomogram or unmeasurable acetaminophen
concentration with normal hepatic transaminase concentrations) should be observed in
the
ED for 4-6 hours to exclude potentially toxic coingestants before disposition.
Clinical presentation
✓ Generally, Asymptomatic or have mild GI upset (nausea, vomiting, abdominal pain,
and sometimes hematemesis).
✓ Occasionally, patients exhibit drowsiness, lethargy, ataxia, nystagmus, tinnitus, and
disorientation.
✓ With the more toxic agents and with massive ibuprofen overdose, seizure, coma,
renal failure, and cardiorespiratory arrest may occur.
✓ Rarely Hepatic dysfunction, hypoprothrombinaemia, and metabolic acidosis.
Investigation
✓ RBS
✓ U/A
✓ CBC
✓ Electrolytes
✓ BUN & creatinine
✓ liver transaminases
✓ PT, aPTT
Treatment 1144
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Clinical presentation
✓ Intoxication may occur after acute accidental or suicidal ingestion or with chronic
therapy.
✓ Signs and symptoms depend on chronicity of the intoxication.
✓ With acute over dose:
o vomiting, hyperkalaemia, sinus bradycardia, sinoatrial arrest, and 2nd or 3rd degree
AV block are common.
o Ventricular tachycardia or fibrillation may occur.
o Hyperkalaemia is a marker of severe acute toxicity and serum potassium is the best
predictor of cardiac glycoside toxicity after an acute overdose.
✓ With chronic intoxication:
o visual disturbances, weakness, sinus bradycardia, atrial fibrillation with slowed
ventricular response rate or junctional escape rhythm, and ventricular arrhythmias
(ventricular bigeminy or trigeminy, ventricular tachycardia, bidirectional tachycardia,
and ventricular fibrillation) are common.
o Accelerated junctional tachycardia and paroxysmal atrial tachycardia with block are
frequently seen.
o Hypokalemia and hypomagnesemia from chronic diuretic use may be evident and
appear to worsen the tachyarrhythmias.
Complications
✓ Hypoxic seizure
✓ Encephalopathy
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✓ Ischemic stroke
✓ MI
✓ ATN
Investigation
✓ Electrolytes → Serum potassium levels higher than 5.5 meq/L are associated with
severe poisoning, serum magnesium
✓ BUN & creatinine
✓ ECG monitoring
✓ Ix based on cxn (if there)
✓ Specific levels: stat serum digoxin or digitoxin levels are recommended, although they
may not correlate accurately with severity of intoxication. Therapeutic levels of digoxin
are 0.5-2 ng/mL; of digitoxin, 10-30 ng/mL.
Treatment
✓ Emergency and supportive measures:
o ABC of life
o Monitor the patient closely for at least 12–24 h after significant ingestion because of
delayed tissue distribution.
✓ Decontamination:
o Prehospital: activated charcoal, if there is no contraindication
o Hospital: activated charcoal. Gastric emptying is not necessary if activated charcoal
can be given promptly. Repeat-dose activated charcoal maybe useful for Digitoxin
toxicity and in patients with severe renal insufficiency, in which clearance of digoxin
is markedly diminished.
✓ Treat hyperkalemia (refer under short case of Nitsibin. click here → Hyperkalemia)
✓ Treat bradycardia or heart block:
o atropine is usually the drug of choice in this circumstance.
➢ For adults, give 0.5-1mg iv. For children, give 0.02 mg/kg iv up to a maximum of 0.5
mg and 1 mg in adolescents. Repeat as needed.
➢ Note that 3 mg is a fully vagolytic dose in adults. If response is not achieved at 3 mg,
the patient is unlikely to benefit from further treatment unless bradycardia is caused by
excessive cholinergic effects (e.g., carbamate or organophosphate overdose).
o A temporary pacemaker may be needed for persistent symptomatic bradycardia.
✓ Treat Ventricular tachyarrhythmias:
o may respond to lidocaine.
➢ Administer 1-1.5 mg/kg (usual adult dose 50-100 mg; children, 1 mg/kg) iv bolus at a
rate of 25-50 mg/min, followed by infusion of 1-4 mg/min (20-50 mcg/kg/min) to maintain
serum concentrations of 1.5-5 mg/L.
➢ If significant ectopy persists after the initial bolus, repeat doses of 0.5 mg/kg iv can be
given if needed at 10-min intervals (to a maximum 300 mg or 3 mg/kg total dose;
children may be given repeat 1 mg/kg doses every 5-10 min to a maximum of 5
mg/kg). 1146
o In patients with congestive heart failure or liver disease, use half the recommended
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Clinical presentation
✓ With mild or moderate overdose:
o lethargy is common. 1147
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Investigation
✓ RBS
✓ Electrolytes
✓ CXR
✓ arterial blood gases or oximetry
Treatment
✓ Emergency and supportive measures:
o ABC of life
o Administer supplemental oxygen.
o Treat coma, seizure, hypotension and non-cardiogenic pulmonary edema if they
occur.
✓ Decontamination:
o Prehospital:
▪ provide general supportive care.
▪ Activated charcoal is generally not indicated because of the risk of aspiration.
▪ Do not induce vomiting because of the potential for developing lethargy and
coma.
o Hospital:
▪ Administer activated charcoal if a patient presents soon after ingestion and is
not manifesting signs of toxicity. It is not recommended in patients showing
signs of toxicity because of the risk of aspiration.
▪ Gastric emptying is not necessary if activated charcoal can be given promptly.
o Naloxone, 0.4–2 mg, IV, repeat doses every 2–3 min, if there is no response, up
to a total dose of 10–20 mg
▪ It is a specific opioid antagonist
▪ large doses may be given safely.
▪ As little as 0.2–0.4 mg is usually effective for heroin overdose.
▪ Caution: the duration of effect of naloxone (1–2 h) is shorter than that of many
opioids. Therefore, do not release the patient who has awakened after naloxone
treatment until at least 3–4 h have passed since the last dose of naloxone.
▪ In general, if naloxone was required to reverse opioid-induced coma, it is safer
to admit the patient for at least 6– 12 h of observation.
o Sodium bicarbonate may be effective for QRS interval prolongation or hypotension
associated with propoxyphene poisoning.
✓ Phenothiazines, butyrophenones, and other related drugs are widely used to treat
psychosis and agitated depression.
✓ In addition, some of these drugs (e.g., prochlorperazine, promethazine, and triperidol)
are used as antiemetic agents.
✓ Suicidal overdoses are common, but because of the high toxic-therapeutic ratio,
acute overdose seldom results in death.
Clinical presentation
✓ Major toxicity is manifested in the cardiovascular and CNS.
o CVS toxicity: tachycardia, orthostatic hypotension.
o CNS toxicity: CNS depression, small pupils, Extrapyramidal dystonic reactions,
disturbed, Temperature regulation resulting in poikilothermia
✓ Mild intoxication:
o causes sedation, small pupils, and orthostatic hypotension.
o Anticholinergic manifestations include dry mouth, absence of sweating, tachycardia,
and urinary retention. Paradoxically, clozapine causes hypersalivation through an
unknown mechanism.
✓ Severe intoxication:
o may cause coma, seizures, and respiratory arrest.
o Hypothermia or hyperthermia may occur.
o Clozapine can cause a prolonged confusion state and rarely cardiac toxicity.
✓ Extrapyramidal dystonic side effects of therapeutic doses include torticollis, jaw
muscle spasm, oculogyric crisis, rigidity, bradykinesia, and pill-rolling tremor.
✓ Patients on chronic antipsychotic medication may develop the neuroleptic malignant
syndrome characterized by rigidity, hyperthermia, sweating, lactic acidosis, and
rhabdomyolysis.
✓ Clozapine use has been associated with agranulocytosis
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Investigation
✓ RBS
✓ Electrolytes
✓ BUN &creatinine
✓ CPK
✓ arterial blood gases or oximetry
✓ abdominal x-ray → to look for radiopaque pills, Phenothiazines are occasionally
visible on plain abdominal x-rays
✓ chest x-ray
✓ ECG → usually shows QT interval prolongation and occasionally QRS prolongation
(particularly with thioridazine and Risperidone).
Treatment
✓ Emergency and supportive measures:
o ABC life and supplemental oxygen.
o Treat coma, seizures, hypotension, and hyperthermia if they occur.
o Monitor vital signs and ECG for at least 6 h and admit the patient for at least 24 h
if there are signs of significant intoxication.
✓ Decontamination:
o Prehospital: general supportive measures. Administer activated charcoal if there is
no contra indication. Do not induce vomiting.
o Hospital: consider activated charcoal. Gastric emptying is not necessary if activated
charcoal can be given promptly
✓ There is no specific antidote.
✓ Dystonic reactions: give diphenhydramine, 0.5–1 mg/kg IV/IM or benztropine.
✓ QRS interval prolongation: treat quinidine-like cardiotoxic effects with bicarbonate, 1-2
mEq/kg IV.
✓ Deaths in seemingly isolated overdoses are more likely with short-acting derivatives
such as alprazolam, temazepam, and triazolam.
1150
✓ Death due solely to benzodiazepine overdose is rare in otherwise healthy individuals.
Clinical Features
✓ nonspecific
✓ The predominant manifestations are neurologic and are characterized by somnolence,
dizziness, slurred speech, confusion, ataxia, incoordination, and general impairment of
intellectual function.
✓ Coma, particularly if prolonged, is atypical and should prompt suspicion of intoxication
with other agents or a non-toxin–related medical condition.
✓ In the elderly, infants and children, protein-deficient persons, and those with hepatic
disease, the neurologic effects of benzodiazepines may be prolonged or enhanced.
✓ Paradoxical reactions, including excitement, anxiety, aggression, hostile behavior,
rage, and delirium, are quite uncommon.
✓ Other effects that have unclear aetiologies include headache, nausea, vomiting, chest
pain, joint pain, diarrhea, and incontinence.
✓ Some benzodiazepines may cause short-term anterograde amnesia.
✓ Uncommonly, respiratory depression and hypotension may occur
✓ Extrapyramidal reactions.
✓ Various allergic, hepatotoxic, and hematologic reactions are infrequent.
✓ In general, benzodiazepines have no long-term organ-system toxicity other than that
which can be ascribed to indirect effects from neurologic or cardiorespiratory
depression.
Investigations
✓ RBS →.to rule out hypoglycemia as the cause of chane in mentation.
✓ CBC
✓ RFT
✓ LFT with Liver enzymes
✓ Pregnancy test in women of childbearing age
✓ ECG → to rule out conduction system poisoning by drugs that effect the QRS or
QTc interval
✓ Arterial blood gas analysis
Management
✓ Initial treatment
o ABC of life → Endotracheal intubation if needed. Oxygen, secure IV line, continuous
cardiac monitoring.
o Check RBS immediately
o vast majority of benzodiazepine overdoses can be managed expectantly.
o Activated charcoal is generally not beneficial in overdose.
✓ Antidote → Flumazenil
o The initial adult dose of flumazenil is 0.2 mg (In children, 0.01 mg/kg, up to 0.2 mg),
IV over 30 seconds.
o A second dose of 0.3 mg may be given, followed by 0.5-mg doses at 1-minute
intervals, to a total of 3 mg.
o Most patients respond within 3 mg.
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Flumazenil
Indication Contraindications
Absolute Relative
✓ Isolated ✓ Known or suspected co-ingestant that lowers seizure ✓ Chronic
benzodiazepine threshold benzodiazepine user,
overdose in ✓ TCA, cocaine, lithium, methylxanthines, isoniazid, not taking for control
nonhabituated propoxyphene, monoamine oxidase inhibitors, of life-threatening
user (e.g., bupropion, diphenhydramine, carbamazepine, condition
accidental cyclosporine, chloral hydrate ✓ Known seizure
pediatric ✓ Patient taking benzodiazepine for control of a disorder not treated
exposure) potentially life-threatening condition (e.g., seizures) with
✓ Reversal of ✓ Concurrent sedative-hypnotic withdrawal benzodiazepines
conscious ✓ Seizure activity or myoclonus ✓ Head injury
sedation ✓ Hypersensitivity to flumazenil or benzodiazepines ✓ Panic attacks
✓ Patient with neuromuscular blockade ✓ Chronic alcoholism
✓ Disposition
o Patients remaining asymptomatic after 4 to 6 hours of ED observation may be
medically cleared.
o For cases of deliberate overdose, appropriate psychiatric consultation should be
obtained
o Indications for observation or hospital admission include significant alterations in
mental status, respiratory depression, and hypotension.
o If mental status depression persists or is profound, other agents or conditions must
be considered.
Clinical manifestations
✓ CNS Toxicity
o Nystagmus → The initial sign of toxicity, which is seen first on forced lateral gaze
and later becomes spontaneous. Vertical, bidirectional, or alternating nystagmus may
occur with severe intoxication. But, absence of nystagmus does not exclude severe
phenytoin toxicity.
o lethargy, ataxic gait, and dysarthria.
o confusion, coma, and even apnea in a large overdose.
o complete ophthalmoplegia and loss of corneal reflexes.
o Paradoxically, very high levels of phenytoin may be associated with seizures,
although this is a rare occurrence, and such phenytoin-induced seizures are usually
brief and generalized and almost always are preceded by other signs of toxicity,
especially in acute overdose.
o Dystonias and movement disorders, such as opisthotonos and choreoathetosis.
o Hyperactive deep tendon reflexes, clonus, and extensor toe responses also may be
elicited.
o Chronic neurologic toxicity includes peripheral neuropathy and cerebellar degeneration
with ataxia.
✓ CVS Toxicity
o CVS CXN have been almost entirely limited to cases of IV administration, or in rare
cases of chronic oral toxicity.
o CVS toxicity is more common in the elderly, those with underlying cardiac
disease, and the critically ill patients.
o hypotension
o bradycardia
✓ Vascular and Soft Tissue Toxicity
o IV extravasation may produce skin and soft tissue necrosis, compartment syndrome,
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✓ Hypersensitivity Reactions
o Hypersensitivity reactions usually occur within 1 to 6 weeks of beginning phenytoin
therapy and can present as a febrile illness with skin changes (erythema multiforme,
toxic epidermal necrolysis or Stevens-Johnson syndrome) and internal organ
involvement (hepatitis, rhabdomyolysis, acute interstitial pneumonitis, renal failure,
LAP, leukopenia and/or DIC).
o Patients with a history of previous hypersensitivity reactions should not receive
phenytoin
✓ Miscellaneous Effects
o Gingival hyperplasia is relatively common and is associated with poor dental hygiene
gingivitis and dental plaques.
Investigation
✓ RBS - To r/o hypoglycemia as the cause of any alteration in mental status.
✓ CBC- may have leucocytosis, eosinophilia
✓ Elevated liver enzymes.
✓ Serum albumin level- hypoalbuminemia patients with a therapeutic or mildly elevated
phenytoin concentration may exhibit significant toxicity.
✓ Pregnancy test- should be done in women of childbearing age.
✓ Serum Phenytoin level- The therapeutic phenytoin serum level is 10 to 20 µg/mL
which generally corresponds to a free phenytoin level of 1 to 2 µg/mL.
✓ ECG -reveals increased PR interval, widened QRS interval, and altered ST
segments and T waves, arrhythmias, ventricular tachycardia, primary ventricular
fibrillation, atrioventricular block, or sinus arrest with junctional or ventricular escape
that may occur after intravenous (or very rarely oral) exposure
Management
✓ ABC of life
o Endotracheal intubation if indicated
o Treat Hypotension with IV boluses of isotonic saline. Atropine, epinephrine, and
dopamine remain first line medical treatment for symptomatic brady dysrhythmias.
✓ Decontamination
o Activated charcoal (AC) may be useful in the setting of a recent ingestion.
o Multiple dose AC may remove some unbound phenytoin undergoing enterohepatic
circulation, even if the phenytoin was administered IV. It is not routinely use multiple
doses of activated charcoal.
✓ Seizures from phenytoin toxicity should be treated with benzodiazepines and
barbiturates as needed.
✓ There is no specific treatment or antidote for phenytoin toxicity
✓ Disposition and Follow-Up
o The decision to discharge or medically clear a patient for psychiatric evaluation
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Clinical manifestations
✓ Neurologic and possibly some CVS effects characterize acute carbamazepine toxicity.
✓ CNS effects;
o The initial neurologic disturbances include nystagmus, ataxia, and dysarthria. In
patients with large overdoses, fluctuations in level of consciousness and coma occur.
o Carbamazepine toxicity may cause seizures in both in epileptic and nonepileptic
patients by unknown mechanism.
o Chronic carbamazepine overdose can result in headaches, diplopia, or ataxia.
Idiosyncratic adverse events are common.
✓ Cardiovascular effects
o include sinus tachycardia, hypotension with myocardial depression, and cardiac
conduction abnormalities.
o These abnormalities can be delayed for as long as 20 hours and may occur with
chronic therapy but are not associated with life-threatening dysrhythmias or
permanent sequelae.
Investigation
✓ RBS
✓ U/A
✓ CBC
✓ Liver enzymes → elevated in acute toxicity
✓ serum electrolyte → hyponatremia
✓ Pregnancy test- should be done in women of childbearing age.
✓ ECG
o Carbamazepine can cause QRS prolongation and arrhythmia
o Sinus tachycardia is the most frequently observed cardiac effect of carbamazepine
o
ventricular tachycardia, and junctional escape rhythms
1155
Other effects include; bradycardia, AV block, premature ventricular contractions,
Management
✓ ABC of life
✓ Gastrointestinal decontamination
o Activated charcoal remains the most common method for acute carbamazepine
poisoning
o Multidose activated charcoal may be used in cases of severe carbamazepine
poisoning
✓ Extracorporeal elimination
o In patients with severe toxicity and multiorgan dysfunction, haemodialysis,
hemoperfusion, or hemodiafiltration is effective.
✓ QRS prolongation is treated with sodium bicarbonate. give boluses of 100 to 150
meq of sodium bicarbonate IV for QRS intervals longer than 110 milliseconds,
particularly in patients with hypotension.
✓ Seizures caused by carbamazepine overdose should be treated with GABA agonists,
such as benzodiazepines (eg, lorazepam). Propofol administered as a continuous
infusion for the sedation of intubated patients also functions as an effective
anticonvulsant. There is no role for phenytoin in the management of drug-induced
seizures.
✓ ECG monitoring may be necessary in some patients
✓ Patients can be medically cleared from the ED if at least two carbamazepine
measurements obtained a few hours apart show decreasing levels (preferably below
15 µg/mL) and the patient is awake, ambulatory, and free of cardiac conduction
Clinical features
✓ After acute toxicity, the most frequent sign is CNS depression, ranging from
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drowsiness to coma.
✓ Other findings include respiratory depression, hypotension, hypoglycaemia, and
electrolyte disturbances that may persist for days.
✓ Anion gap metabolic acidosis following overdose is a poor prognostic sign.
✓ Bone marrow suppression occurs 3–5 days following acute massive overdoses of
VPA and is characterized by pancytopenia. These hematopoietic disturbances usually
resolve spontaneously within a few days.
✓ Hepatotoxicity → Valproate-induced hepatotoxicity may be either intrinsic and benign
(reversible, reproducible, and dose dependent) or idiosyncratic and fatal
(unpredictable, not dose dependent, with a long latent period).
✓ Pancreatitis may occur, and thrombocytopenia may be clinically significant and
severe.
✓ Cerebral edema has been seen in acute overdose.
Investigations
✓ RBS → hypoglycaemia as cxn of toxicity or to rule out hypoglycaemia as the cause
of any alteration in mental status
✓ U/A-Valproate is eliminated partly as ketone bodies and may cause a positive test
result for ketones in the urine or blood.
✓ Urine HCG -in women of childbearing age
✓ CBC- as a baseline and to see complication of VPA toxicity (Pancytopenia,
thrombocytopenia)
✓ Serum electrolyte-hypernatremia, hypocalcaemia, hypophosphatemia, and anion gap
metabolic acidosis can be complication of valproate poisoning
✓ LFT and Enzyme tests- To see hepatotoxicity (elevated serum levels of
aminotransferases, ammonia, and lactate)
✓ ECG- to rule out conduction system impairment by drugs that prolong the QRS or
QTc intervals
✓ Lipase and amylase- To assess Acute pancreatitis
✓ Serum ammonia level → Hyperammonaemia in the absence of liver failure during
long-term therapy.
✓ Arterial blood gas analysis- To See anion gab metabolic acidosis and treat
accordingly
✓ Serum acetaminophen and Salicylates level-to rule out these common congestions
✓ Serum valproic acid concentration
o Therapeutic valproate concentrations are 50 to 100 µg/mL.
o Although serum concentration does not correlate well with either seizure control or
toxicity, adverse side effects increase as concentrations rise above 150 µg /mL, and
coma may occur with levels above 800 µg /mL.
o A consistent analytic methodology should be used when monitoring treatment.
Treatment
Clinical features
☛ Mild barbiturate toxicity mimics ethanol intoxication, presenting with drowsiness, slurred
speech, ataxia, unsteady gait, nystagmus, emotional liability, and impaired cognition.
☛ In severe acute intoxication, CNS depression progresses from stupor to deep coma and
respiratory arrest.
☛ The life threat of severe barbiturate toxicity is respiratory depression
1158
☛ A characteristic of a barbiturate overdose is the persistence of the pupillary light reflex even
with stage IV coma. Although pupils are usually normal or small and reactive, concomitant
Investigations
Treatment 1159
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Chapter 4; Poisoning, Drug Overdose, and Envenomation 1160
2. Decontamination
☛ With very large overdoses, antecedent gastric lavage may be considered.
☛ A single dose of activated charcoal should be given to cooperative, clinically stable patients
who present with in 1 hour of acute oral overdose. For patients who have a compromised
airway, endotracheal intubation is advised prior to giving charcoal
☛ Multi-dose activated charcoal is consider if a patient has ingested a life-threatening amount of
phenobarbital.
☛ monitor the airway is to decrease the risk of aspiration or bowel obstruction.
4. Extracorporeal Elimination
☛ Haemodialysis, hemoperfusion, and hemodiafiltration have all been used to enhance
elimination of phenobarbital; however, they are reserved for patients who are deteriorating
despite aggressive supportive care.
☛ These modalities are not useful for poisoning from barbiturates other than phenobarbital.
☛ Exchange transfusion has also been reported useful in neonatal phenobarbital toxicity
Clinical features:
ECG Features
Disposition
Patients with an alteration in mental status, hypotension, cardiac conduction abnormalities,
or seizures should be admitted to ICU.
Patients with mild symptoms, such as an isolated tachycardia without evidence of
conduction abnormalities (i.e., QRS <100 msec), could conceivably be admitted to a
monitored bed/ setting.
Asymptomatic patients who have no conduction abnormalities on ECG, may deteriorate
rapidly and should be monitored for at least 6 hours in an acute care setting can be
safely discharged or transferred to a psychiatric service for evaluation.
1162
Hospitalized patients can be cleared medically after 24 hours if they are asymptomatic,
with a normal or baseline ECG, normal mental status, and resolution of all antimuscarinic
symptoms.
The more X-rays reach an area of the film, the darker that area will be on the
radiograph. Therefore, if an object is very dense, less X-rays will reach the film
and consequently the image of the object will appear white on the radiograph.
If an object has little density, its image will appear black on the CXR because it
allows most of the X-ray beam to reach the film.
Difference in density and x ray attenuation…help outline anatomic
structures…allowing visualization of details
Image; Plain films have five basic radiographic densities in order of increasing brightness: 1 → Air (black),
2 → Fat (gray), 3 → Fluid (gray), 4 → Bone (white), 5 → Metal or x ray contrast agents (white).
CXR Projections
A) P-A projection
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Figure; PA CXR; Most CXRs are taken in a PA position; The x-ray beam passes through the patient from
back to front (i.e. PA) onto the film. The heart and mediastinum are thus closest to the film and therefore
not magnified.
Portable bedside CXR- “ward film”, Especially for critically ill / ICU pts
Important to;
o Look for new pathology after admission
o Assess C-P status & position of catheters, ETTs and other devices
o Detect complications related to these devices
Limitations:
o Often rotated films, poor quality
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C. lateral view
D. Lateral Decubitus
A B
Picture; A) Over penetrated/ over exposed film (Dark film). Easy to see thoracic spines behind the heart
shadow; but pulmonary vessels peripherally are not clearly seen. B) Under penetrated film (The image too
white); Fail to see vertebrae above T4 (and also behind the heart). Accentuates pulmonary vascularity,
which may be mistaken for generalized infiltrates.
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2.2 Assessment of adequacy of inspiratory effort (i.e. does the patient has taken
adequate inspiratory effort?)
By counting visible anterior or posterior ribs
Picture; Optimal: 6 anterior or 10 posterior ribs are visible above the diaphragm
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Picture; Two CXRs of the same patient taken on the same day. For the CXR on the left the patient has
made a poor inspiratory effort. Note the apparent bulkiness of the hila, increased density in the lower
zones and the enlarged cardiac silhouette. The CXR on the right taken in full inspiration demonstrates that
the patient’s CXR is normal and previous apparent abnormalities were due to poor inspiratory effort
If > 6 anterior or > 10 posterior ribs are visible above diaphragm, it implies
hyperexpanded lungs (eg. air trapping as in COPD with large lung volumes & flat
diaphragm)
Review areas:
o Apices
o Behind the heart
o CP angles
o Below the diaphragm
o Soft tissues (breast, surgical emphysema)
o Ribs & clavicle
o Vertebrae
Hidden areas: apices, mediastinum & hila, posterior sulcus
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3.3 Diaphragm
Elevation, flattening, C-P angle, air under the diaphragm
Normally the Right is higher (by 1-1.5cm) than the Left. A difference of > 3cm is
abnormal
The highest point of the hemidiaphragm should be at least 1.5cm above a line
drawn from cardio phrenic to costophrenic angle (< 1.5 cm suggests flat
diaphragm)
Air in the gastric fundus is normally seen below Left hemidiaphragm but air under
Right hemidiaphragm is pathological (as in perforated PUD).
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Picture; Air under the diaphragm, the normally air-filled gastric fundus lies beneath the diaphragm. If there
is free gas on the left, only the diaphragm, about 3–4 mm thick, separates the free gas from the lung.
Air in the gastric fundus is separated from the lung by the diaphragm and the gastric wall. Again, sharp
margins to the gas shadow increase the likelihood of free gas. If uncertainty remains, a lateral decubitus
AXR view should resolve the issue, as the free gas will travel to the least dependent area, i.e. the upper
most lateral margin of the abdomen.
3.4 Pleura
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Look for
Fluid or air in the pleural cavity; thickening, calcification
Normally the costophrenic angle is acute. Obliteration tells pleural
effusion/empyema
Meniscus sign (◡) is the typical obliteration of the costophrenic angle suggesting
fluid in the pleural cavity.
250ml fluid can be detected on a PA film; lateral decubitus film can detect 10 to
50 ml. The smallest amount visible on decubitus radiographs is 10 ml. With care,
as little as 175 mL of effusion can be detected on supine images.
Picture; Pleural effusions show homogeneous opacity without air bronchogram (as the pleura is extra
parenchymal). This helps to differentiate pleural fluid from consolidation.
In the supine position, a simple pleural effusion will accumulate posteriorly in the
chest and the above described meniscal effect is not seen.
On an upright PA film, fluid collects in the lateral costophrenic angle due to
gravity, giving it a blunted appearance. The posterior costophrenic angle is the
deepest, and fluid collects there first. This angle is hidden by the dome of the
diaphragm on a PA view. However, it is well seen on the lateral view. For this
reason, the upright lateral view is superior to the PA for demonstrating small
amounts of pleural fluid.
When in doubt of pleural effusion, order a decubitus view with the patient lying
down on the side of the suspected effusion. This will bring the fluid between the
lung and the chest wall where it is easy to see. Sometimes the parietal and
visceral pleura are stuck to each other (adhesion). In this situation, a pleural
effusion may not be able to move when the patient changes position. The fluid
may even be stuck in one of the fissures mimicking the appearance of a lung
mass (pseudo-tumor).
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Pictures; B) Lateral CXR: fluid around the left lower lobe. C) Left lateral decubitus view: fluid between the
chest wall and the left lung. A free fluid separating the lung from chest wall by > 10 mm on lateral film is
an indication for therapeutic thoracentesis.
Pleural fluid 1st spill out to posterior C-P angle, then to lateral & eventually
anterior; with further accumulation, it spreads up wards. Appear as Homogenous
opacity obscuring the basal lung field, Obliteration of the costophrenic and cardio
phrenic angle, Elevation of the ipsilateral hemidiaphragm
a. Empyema
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Picture; Frontal CXR of an adult with a right sided empyema. Note the pleural based opacity with a
vertical (white arrows) rather than meniscal contour indicating a complex collection in this case including
pockets of air (black arrows). The presence of pleural opacity that fails to conform to the meniscal
appearance characteristic of a simple pleural effusion should alert the reader to the possibility of an
empyema, or pleural tumor. Extension of an empyema outside the chest wall may mimic an invasive soft
tissue mass
b. Pneumothorax
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Picture; A) Chest radiograph of a pneumothorax. The pleural line has lucency on either side, representing
air in the pleural space on one side of the line and air in the lung on the other. The line is sharply
demarcated and can be traced along its course (lower arrow). No blood vessels can be seen beyond the
superior (upper arrow) and lateral (middle arrow) extent of the line. B) Chest radiograph of a skinfold
(arrows) that could be mistaken for a pneumothorax. The border is more of an edge, with lucency on only
one side. The edge is poorly defined and cannot be followed continuously (lower arrow). Blood vessels
can be traced beyond the border of the fold (arrowhead). A skin-fold line often is relatively straight,
whereas a pleural line follows the curve of the inner aspect of the chest wall
On a supine AP, the air rises to the anterior and lateral costophrenic angles
(sulci); since they are the highest region in the pleural cavity when pt is lying
down. This creates an abnormally dark and deep lateral sulcus (i.e. deep sulcus
sign).
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Picture; On P-A chest x-ray (A), the costophrenic angle is normally acute (arrow). In a supine patient, a
pneumothorax will often be anterior, medial, and basilar. On a subsequent supine film (B), the dark area
along the right cardiac border and lung base appeared larger (small arrows), and the costophrenic angle
much deeper and more acute than normal (large arrow). These findings were not recognized, and, as a
result, a tension pneumothorax developed in the same patient (C) with an extremely deep costophrenic
angle (large black arrow), an almost completely collapsed right lung (small white arrows), and shift of the
mediastinum to the left.
c. Tension pneumothorax
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Picture; PA CXR demonstrating an abnormally black right hemithorax. The right lung has been pushed
medially. The mediastinum is shifted to the left
d. Hydropneumothorax
Picture; Hydropneumothorax. When fluid and air are present in the pleural space on an upright chest x-
ray, a perfectly straight horizontal line will extend all the way from the spine to the edge of the pleural
cavity. In this patient, a loculated right basilar hydropneumothorax is present. The air/fluid interface is
1180
easily seen (arrows). If this were a lung abscess, the air/fluid level would be very unlikely to extend all the
way from the medial to the lateral aspect of the hemithorax
3.5 Trachea
Normally mid line or slightly shifted to the right
Diameter is 25mm in male, 21mm in female
Look for:
o Any narrowing, widening
o Displacement: away from the side of a pneumothorax or effusion; towards in
fibrosis or collapse
o Carinal angle – site of bifurcation of trachea, located at T6. Normal angle
is 600 - 750. Angle increased in Left Atrial enlargement or LAP
o Right paratracheal stripe: Normally the Right wall of the trachea should be
clearly seen (uniformly smooth and < 4mm in width)
o Any thickening or nodularity
The left lateral tracheal wall is surrounded by mediastinal vessels and fat is not
normally visible on CXR
The hilar point is formed by the outer margins of the upper lobe pulmonary veins
and the lower lobe pulmonary arteries as they cross. Note the left main pulmonary
artery loops over the left main bronchus therefore the left basal pulmonary artery
crosses the left upper lobe pulmonary vein higher on the left than on the right and
the hila point is also normally higher on the left.
3.6 Hilum
Picture; Sarcoidosis; Symmetrical hilar nodes, Paratracheal nodes, AP window nodes, Alveolar lung infiltrate
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Picture; Main Fissures; Right upper lobe (RUL) sits above horizontal fissure (HF), the Right lower lobe
(RLL) lies behind the oblique fissure (OF) and Right middle lobe (RML) is between the two. left lung has
an oblique fissure, separating it into left upper lobe (LUL) and left lower lobe (LLL).
Oblique Fissure
o Commence at T4 or T5 & end at anterior CPA on the Right & 5 cm behind
from Rt CPA for the Lt.
Horizontal Fissure
o Extend from hilum to 6th rib at anterior axillary Line
All fissures seen on Lateral film.
Horizontal fissure can be visible on a PA film.
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Lobar anatomy: Right lung has 3 lobes (upper, middle & lower), Left lung has 2
lobes (upper &lower lobes)
Causes of lung lucency
o Lung cysts & cavities
o Emphysema
o Bronchiectasis
o Pneumothorax
Causes of lung opacity
o Consolidation
o Atelectasis
o Infiltrations
o Nodule/ mass
o Fluid
Consolidation
Filling of alveoli with liquid like substance which causes silhouetting of adjacent
structures.
Common etiologies: Pneumonia, pulmonary hemorrhage, ARDS, pulmonary edema,
aspiration, neoplasm
Air bronchograms: patent air ways filled with air; creating faint luceny with in the
consolidated lung. It tells that the opacity is intrapulmonary (not a pleural
pathology)
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Picture; Silhouette sign: Ill-defined heart border due to consolidation on the para cardiac area. The CXR
appearances reflect the loss of air, hence the increase in opacity.
Atelectasis / Collapse:
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ii. Mass
Interstitial infiltrates:
Nodular
Reticular/ Reticulonodular
Milliary: DDx- TB, Hemosiderosis, sarcoidosis, fungal, pneumoconiosis
Honeycomb pattern
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If the lesion measures less than 3 cm, it is called a nodule. If it is larger than 3
cm, it is called a mass.
A nodule/mass is caused by either a malignant (e.g. lung cancer, metastasis) or
benign process (e.g. hamartoma, granuloma).
Primary lung cancers tend to have ill-defined, speculated borders, and grow over
time. Metastases tend to produce multiple smooth round lung nodules, often of
variable size. Benign lesions tend to be small, well defined, smooth, round and
maybe calcified. They usually are stable in size when compared to prior films
A doubling of volume in less than 3 months is unlikely to be a neoplasm but
more likely an infective or inflammatory process.
Doubling times from 3 to 18 months are within the window for malignant lesions
Lung mass
Picture; CXR of an adult male with metastatic renal cell carcinoma. Note the multiple well defined “cannon
ball” metastases.
Lung ca: Tumors < 1 cm in diameter may not be visible on CXR. Cavitation is
most likely to be found in SCC (squamous cell carcinoma)
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Picture; left) Milliary pattern. Right) Honeycomb pattern representing lung scarring.
iii. Fibrosis
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Chapter 5; Interpretation of Chest X - Ray (የደረት ራጅ ማንበብ) 1189
Picture; CXR of a pt with idiopathic pulmonary fibrosis. The magnified area demonstrates the interlacing
network of lines/ reticulation, which represent the visible pathologically thickened interstitium, in this case
due to fibrosis
PA CXR: left) typical batwing distribution of air space disease. Right) 1. Vascular redistribution:
Cephalization (blood vessels in the upper lung zones become larger than the ones in lower lung zones
/the inverse of normal/), 2. Interstitial pattern and Kerly B lines, 3. Peribrochial cuffing (bronchi seen head
on are surrounded by fluid Blood diversion), 4. Pleural effusions, 5. Batwing pattern (symmetrical air space
disease in the lung adjacent to the hila)
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Picture; Kerley B lines (black arrow); Tiny horizontal lines seen at the periphery of the basal lung area,
perpendicular to the pleura…represent fluid in the interlobular septa
v. Cavity
Gas filled space surrounded by complete wall. It has a thick, irregular wall, often
with a solid mural component.
Solitary cavity: most likely infection or primary lung cancer, post traumatic
Multiple cavitary lesions are typically vascular or spread through the vascular
system. DDX are: Aspiration lung abscess, TB, Septic emboli, Vasculitis (Wagner’s
granulomatosis), metastases
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Pictures; left) Right upper lobe large cavity. Middle) Multiple cavity: Bilateral thin walled cavities…cancer.
Right) Lung abscess: air–fluid level
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Cavity location:
o TB: Upper zone
o Lung abscess: Right lower zone
o Amoebic lung abscess: Right basal lung
o Pulmonary infarction: Basal
Cavity wall:
o Thick- neoplasm, acute abscess, wegner’s granulomatosis
o Thin wall- Usually benign e.g. bullae, pneumatocele, hydatid cyst, Chronic
inactive TB, traumatic lung cyst
o Shaggy inner wall – abscess
o Irregular & nodular – cancer
o Presence of air fluid level – lung abscess, empyema, TB, cavitating ca
o Presence of ball inside cavity- Aspergilloma in an old cavity
Note: A cyst may be confused with cavity.
Cyst is an air-containing lucency with a thin, nearly imperceptible wall. usually due
to a primary airway abnormality (e.g. Emphysema, bronchiectasis)
DDx for a single cyst:
o Bulla: an air-filled cyst measuring >1 cm
o Bleb: an air-filled cystic structure contiguous with the pleura measuring <1
cm.
N.B Rupture of a bleb is commonest cause of spontaneous pneumothorax.
Pneumatocele: is an air-filled space caused by prior lung trauma or as a
sequela of pneumonia, typically from A long-term sequel of S. aureus or PCP.
Pneumatoceles almost always resolve
The appearance is similar to that of a cavity, but thin walled with no adjacent lung
parenchymal opacity to suggest active inflammation
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Picture; A pneumatocele in a patient who had a staphylococcal pneumonia as a child. Note the thin wall,
the entirety of which is visible (white arrows), unlike the wall of a bulla. NO adjacent parenchymal opacity
to suggest active inflammation
Picture; CXR of a pt with bullous emphysema. Note the curvilinear lines (arrows) formed by the walls of
the bullae, but the entire wall is not visible.
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a. Heart
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𝐀+𝐁
Picture; cardiothoracic ratio = 𝐱 𝟏𝟎𝟎 % = 35-50%, If > 50 % - cardiomegaly
𝐂
Heart size will vary with body habitus making absolute lower limits meaningless,
but reasonable upper limits for adults are 15.5 cm for females and 16 cm for
males.
Look for evidences of chamber enlargement
o LA – splaying of carina, straightening of Left heart border, double Right
heart border, posterior displacement of esophagus
o RA – lateral bulging & clear outline of Rt heart border
o LVH – left & downwards displacement of the apex
o RVH – Narrowing of the anterior retrosternal clear space on lateral CXR.
Round apex with upward and lateral displacement. Obliteration of pulmonary
bay b/c of pulmonary artery enlargement
o LA or RA enlargement & LVH can be seen on P-A CXR; RVH is seen on
lateral CXR (causes narrowing of the anterior retrosternal clear space)
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Chapter 5; Interpretation of Chest X - Ray (የደረት ራጅ ማንበብ) 1195
Picture: CXR of A pt with early left heart failure. The magnified view demonstrates the double heart
border, right atrial wall (white arrow) and left atrial wall (black arrow). Double right heart border: caused by
the projection of the right wall of the left atrium behind the silhouette of the right atrium
Pericardial effusion
Pericardial effusions are difficult to appreciate on CXR. The most obvious signs
are a change in the shape of the heart to a more rounded contour (the globular
heart) and a rapid increase in size of the cardiac silhouette.
If pericardial fluid is >250 ml, it may be seen on CXR
o “Flask shaped’’ or ‘’water bottle heart’’ on erect PA film
o Globular when supine film
Pericardial calcifications: appear as curvilinear calcification on the surface of the
heart.
Causes of pericardial calcification
Pericarditis (TB, rheumatic fever, viruses)
Post-traumatic
b. Mediastinum:
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Picture; Components of the PA mediastinal shadow (A): SVC (1), Ascending aorta (2), RA (3), IVC (4),
aortic arch (5), pulmonary trunk (6), LA appendage (7) and, LV (8). Mediastinal compartments on the
lateral film (B) include: superior(S), anterior (A), middle (M) and posterior (P) compartments
Pneumonia
Lobar Pneumonia
Pictures; Left) Frontal CXR of an adult male with pneumonia confined to the anterior segment of the right
upper lobe. Note the inferior demarcation by the minor fissure (white arrows). Right) Atypical pneumonia;
Poorly-defined nodular opacities in RLL zone in a pt with Mycoplasma pneumoniae pneumonia.
Broncho Pneumonia
Picture; A frontal CXR of an adult female diagnosed with acute hypersensitivity pneumonitis. Note the
patchy ground grass opacity.
Pulmonary TB
Primary TB:
Consolidation, hilar LAP, effusion & milliary disease May occur in any lobe, but
most typical locations are the lower lobes or right middle lobe.
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Picture; The Primary complex (Ghon focus & ipsilateral hilar LAP) … Right lower lobe peripheral air space
opacity & Right hilar adenopathy
Because most inspired air is distributed to the middle and lower lung zones, these
areas of the lungs are most commonly involved in primary TB
Reactivation TB
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Pictures; left) Right upper lobe large cavity. Right) Upper lobe consolidation with cavitation
Bronchiectasis
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Picture; CXR of a pt with cylindrical bronchiectasis, on the magnified image are ring shadows (white
arrows) and tram tracks or lines (black arrows), representing dilated bronchi end on and lengthways
respectively
Picture; Chest CT; Airway dilation (detected as parallel "tram tracks" or as the "signet-ring sign"—a cross-
sectional area of the airway)
COPD
Emphysema
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Pictures; A) Hyperlucent, Hyperinflated lungs, Avascular zones. Sometimes, ball-shaped collections of air
develop, which are called bullae. On the radiograph, there is an overall decrease in lung density (too
black). This makes sense since the fluid density alveolar walls are being destroyed and air is trapped in
the lungs. Also, because of tissue destruction, there are fewer visible blood vessels. Ones that are seen
sometimes take an abnormal curved course because they are going around destroyed lung. B) Lateral
CXR: flattened hemidiaphragms and barrel chest deformity.
PCP
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Chapter 5; Interpretation of Chest X - Ray (የደረት ራጅ ማንበብ) 1202
ILD: Silicosis
Picture; A pt with silicosis: variably sized, poorly defined nodules (arrows) predominating in the upper lobes
ARDS
Picture; AP CXR of ARDS that shows diffuse interstitial and alveolar infiltrates, that can be difficult to
distinguish from LV failure. BUT the heart size is normal
Pulmonary edema
o Kerley A lines radiate outward from the hila and may represent dilation of
lymphatic channels.
Alveolar edema
o Bilateral perihilar opacifications
o Bat wing/ butterfly appearance when severe
o Pleural effusions and cardiomegaly are often present.
Acute PTE
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Chapter 5; Interpretation of Chest X - Ray (የደረት ራጅ ማንበብ) 1204
If the medial margin is visible, but the lateral margin is indistinct, the mass is
probably pleural based
picture; Left image demonstrates a pleural based mass, in this case mesothelioma. Note on the magnified
image the well-defined medial margin (white arrows) where the mass is adjacent to the lung and the
merging of the upper border with the chest wall (black arrow).
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Chapter 6; Basics of ECG and ECG interpretation 1205
6.1 ECG
❖ Electrocardiography (ECG/EKG) is the process of recording the electrical activity of
the heart over a period of time using electrodes placed on the skin through ECG
machine.
❖ The term Electrocardiography is derived from three Greek words. Electro = related
to electrical activity, Kardio = for heart and graph = to write
❖ The graph of voltage vs time produced by this noninvasive procedure is referred to
as electrocardiogram (ECG/EKG). That is a surface representation of the electrical
events of the cardiac cycle.
❖ The ECG is the most important test for interpretation of the cardiac rhythm,
conduction system abnormalities, and the detection of myocardial ischemia.
Cardiac impulse
Cardiac impulse originates in the SA node
Traverses the atria simultaneously – no special conduction wires in atria – so the
delay
Reaches AV node – the check post – so delay
Enters bundle of His and branches – through specialized conducting wires called
Purkinje network - activates both ventricles – quick QRS
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Chapter 6; Basics of ECG and ECG interpretation 1206
First the septum from L to R, then right ventricle and then the left ventricle and
finally the apex
Then the ventricles recover for next impulse
Electrode is a conductive pad in contact with the body that makes an electrical circuit
with the ECG.
✓ On a standard 12-lead ECG there are 10 electrodes (RA, LA, RL, LL, V1-V6)
A lead is usually more abstract and is the source of measurement of vector.
✓ 12 lead ECG has 3 sets of leads
a. 3 standard limb leads (I, II, III)
b. 3 augmented limb leads (aVR, aVF, aVL),
c. 6 precordial (chest) leads (V1- V6)
✓ Cardiac Monitors→ usually limb leads
In clinical practice the term lead and electrode are used interchangeably, although
this is not technically correct.
(aVR = lead augmented vector right, aVL = lead augmented vector left, aVF = lead
augmented vector foot, RA = right arm, LA = left arm, RL = right leg, LL = left leg, V1-
V6 = vector 1 – vector 6)
Summary of Leads
Limb Leads Precordial Leads
Bipolar I, II, III (standard limb leads)
Unipolar aVR, aVL, aVF (augmented V1-V6
limb leads)
Category of leads
Category Leads Activity
Inferior II, III, aVF Look at electrical activity from the
leads inferior (diaphragmatic) surface of
heart. E.g. inferior MI
Lateral
leads
I, aVL, aVR, V5, V6 Look at electrical activity from the
lateral wall of LV. E.g. LVH
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figure 1 Summary
▪ X-Axis represents time - Scale; X-Axis → 1 mm = 0.04 sec
▪ Y-Axis represents voltage - Scale; Y-Axis → 1 mm = 0.1 mV
▪ One big square on X-Axis = 0.2 sec (big box)
▪ Two big squares on Y-Axis = 1 milli volt (mV)
▪ Each small square is 0.04 sec (1 mm in size)
▪ Each big square on the ECG represents 5 small squares = 0.04 x 5 = 0.2 seconds
▪
▪
▪
5 such big squares = 0.2 x 5 = 1sec = 25 mm
One second is 25 mm or 5 big squares
One minute is 5 x 60 = 300 big squares
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T wave Ventricular repolarization 0.08 to 0.12 sec Tall peaked T waves indicate
Friend of ST (2-3 small boxes) hyperkalemia.
Inverted T waves are suggestive
of myocardial ischemia or a
ventricular conduction delay.
T waves that are larger or
smaller than normal may indicate
and electrolyte imbalance.
The electrical impulse is initiated in the sinus node and then activates the
right and left atria, generating the P wave. Impulse conduction through the
atrioventricular (AV) node and bundle of His, which are small structures,
does not generate any ECG activity; this period of "electrical silence" is
the PR interval. The first part of the ventricle to be depolarized is the left
side of the interventricular septum, producing a small septal Q wave,
followed by depolarization of the remainder of the ventricular myocardium,
generating the full QRS complex. The T wave represents ventricular
repolarization. A U wave may be present, representing repolarization of
the His Purkinje system.
❖ ECG waves are labeled alphabetically starting with the P wave, followed by the QRS
complex and the ST-T-U complex (ST segment, T wave, and U wave).
❖ The J point is the junction between the end of the QRS and the beginning of the ST
segment (waveform 1).
Figure 2
(waveform 1)
A. P wave
The P wave represents atrial depolarization.
The normal sinus P wave demonstrates depolarization from the right to left atrium
and is an initial low amplitude deflection preceding the QRS complex that is positive
in most leads.
The duration is generally <0.12 sec (3 small boxes) and the amplitude <0.25 mv (2.5
small boxes).
Since right atrial depolarization precedes that of the left atrium (as the sinus node is
in the high right atrium), the P wave is often notched in the limb leads and usually
biphasic in lead V1.
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The initial positive deflection in V1 is due to right atrial depolarization that is directed
anteriorly, while the second negative deflection represents left atrial depolarization that
is directed posteriorly.
The atrial repolarization sequence (atrial ST and T wave phases) occurs just before,
simultaneously, and just after depolarization of the ventricular myocardium.
The atrial "T wave" itself is usually hidden by the QRS complex and not observed on
the routine ECG.
In addition, the amplitude of the atrial T wave is often too small to be observed at
standard gain.
Clinically, atrial repolarization (the atrial ST phase) is most evident during acute
pericarditis, in which one often sees PR segment elevation in lead aVR and PR
segment depression in the infero-lateral leads, reflecting an atrial current of injury.
The low amplitude atrial T wave may also be unmasked in certain cases of high
degree AV block, especially when the atria are enlarged.
Finally, alterations in the atrial ST segment and T wave may occur with other
pathologies, such as atrial infarction or atrial tumor invasion.
B. QRS complex
✓ The QRS complex represents the time for ventricular depolarization.
✓ The entire QRS duration normally lasts for 0.06 to 0.10 seconds (1½ to 2½ small
boxes) and is not influenced by heart rate.
✓ If the initial deflection is negative, it is termed a Q wave.
✓ Small Q waves are often seen in leads I, aVL, and V4-V6 as a result of initial septal
depolarization and are considered normal.
✓ The first positive deflection of the QRS complex is called the R wave. It represents
depolarization of the left ventricular myocardium.
✓ Right ventricular depolarization is obscured because the left ventricular myocardial
mass is much greater than that of the right ventricle.
✓ The small R wave in lead V1 represents initial septal depolarization.
✓ The negative deflection following the R wave is the S wave, which represents
terminal depolarization of the high lateral wall.
✓ If there is a second positive deflection, it is known as an R'.
✓ Lower case letters (q, r, or s) are used for relatively small amplitude waves of less
than 0.5 mV (less than 5 mm with standard calibration).
✓ An entirely negative QRS complex is called a QS wave.
✓ The R wave should progress in size across the precordial leads V1-V6.
✓ Normally there is a small R wave in lead V1 with a deep S wave.
✓ The R wave amplitude should increase in size until V4-V6 while the S wave becomes
less deep. This is termed R wave progression across the precordium.
C. ST segment
❖ The ST segment occurs after ventricular depolarization has ended and before
repolarization has begun.
❖ It is a time of electrocardiographic silence.
❖ The intersection of the end of the QRS complex and the initial part of the ST
❖
segment is termed the J point (waveform 1 above).
Has a duration of 0.08 to 0.12 sec,
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❖ The normal ST segment is usually flat along the isoelectric line (i.e. zero potential as
identified by the T-P segment) and has a slight upward concavity. However, it may
have other configurations depending upon associated disease states (e.g. ischemia,
acute MI, or pericarditis). In these situations, the ST segment may be flattened,
depressed (below the isoelectric line) with an upsloping, horizontal, or down sloping
morphology, or elevated in a concave or convex direction (above the isoelectric line).
❖ ST elevation of greater than 2mm (> 2 small square) above the baseline or
depression of greater than 1 mm (> 1 small square) below the baseline may be
indicative of an MI
❖ In some normal cases (as with sinus tachycardia) the J point is depressed and the
ST segment is rapidly upsloping, becoming isoelectric within 0.08 seconds after the
end of the QRS complex.
❖ For more Look at ECG CRITERIA FOR MYOCARDIAL ISCHEMIA/INFARCT below
D. T wave
The T wave represents the period of ventricular repolarization.
Since the rate of repolarization is slower than depolarization, the T wave is broad,
has a slow upstroke, and rapidly returns to the isoelectric line following its peak (i.e.
slow upstroke, rapid downstroke). Thus, the T wave is asymmetric and the amplitude
is variable.
In addition, the T wave is usually smooth up and down.
The duration is 0.08 to 0.12 sec (2-3 small boxes)
If there is any irregularity on the T wave (bump, notch, rippled, etc) a superimposed
P wave should be considered.
the T wave vector on the ECG normally is in the same direction as the major
deflection of the QRS Since depolarization begins at the endocardial surface and
spreads to the epicardium, while repolarization begins at the epicardial surface and
spreads to the endocardium, the direction of ventricular depolarization is opposite to
that of ventricular repolarization.
Tall peaked T waves indicate hyperkalemia. Inverted T waves are suggestive of
myocardial ischemia or a ventricular conduction delay. T waves that are larger or
smaller than normal may indicate and electrolyte imbalance.
E. PR interval
✓ The PR interval includes the P wave as well as the PR segment.
✓ It is measured from the beginning of the P wave to the first part of the QRS
complex (which may be a Q wave or R wave).
✓ It includes time for atrial depolarization (the P wave) and conduction through the AV
node and the His-Purkinje system (which constitute the PR segment).
✓ The length of the PR interval changes with heart rate, but is normally 0.12 to 0.20
sec (3 – 5 small boxes).
✓ The PR interval is shorter at faster heart rates due to sympathetically mediated
enhancement of atrioventricular (AV) nodal conduction; it is longer when the rate is
slowed as a consequence of slower AV nodal conduction resulting from withdrawal of
sympathetic tone or an increase in vagal inputs.
F. QT interval
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❖ The QT interval consists of the QRS complex, the ST segment, and T wave. Thus,
the QT interval is primarily a measure of ventricular repolarization.
❖ The JT interval, which does not include the QRS complex, is a more accurate
measure of ventricular repolarization since it does not include ventricular
depolarization, but in most clinical situations, the QT interval is used.
❖ If the QRS complex duration is increased, this will lead to an increase in QT interval
but does not reflect a change in ventricular repolarization.
❖ A widened QRS, therefore, must be considered if a prolonged QT interval is being
evaluated.
❖ The time for ventricular repolarization and therefore the QT (or JT) interval is
dependent upon the heart rate; it is shorter at faster heart rates and longer when the
rate is slower.
❖ Thus, a QT interval that is corrected for heart rate (QTc) is often calculated as
follows (based on Bazett's formula):
𝐐𝐓 𝐢𝐧𝐭𝐞𝐫𝐯𝐚𝐥
QTc =
√𝐓𝐡𝐞 𝐑𝐑 𝐢𝐧𝐭𝐞𝐫𝐯𝐚𝐥 (𝐢𝐧 𝐬𝐞𝐜)
✓ Although this approach is simple, it is inaccurate at heart rate extremes and
results in overcorrecting at high rates and under correcting at low ones [1].
✓ The normal value for the QTc in men is ≤0.44 sec and in women is ≤0.45 to
0.46 sec.
✓ QTc values, however, are on a bell curve and normal patients may have longer
QTc values, while those with Long QT syndrome may have shorter QT values.
❖ Since the QRS widens in the setting of a bundle branch block, the QT interval will
widen.
❖ This increase in QT interval does not reflect an abnormality of ventricular
repolarization, since the increase is due to an abnormality of depolarization.
G. U wave
➢ U wave may be seen in some leads, especially the precordial leads V2 to V4.
➢ The exact cause of this wave is uncertain, though data suggest it may be from late
repolarization of the mid-myocardial M cells, due to a longer action potential duration
compared with the endocardium or epicardium, especially at slow heart rates.
➢ The amplitude of the U wave is typically less than 0.2 mV and is clearly separate
from the T wave. It is more evident in some circumstances such as hypokalemia and
bradycardia.
➢ The U wave may merge with the T wave when the QT interval is prolonged (a QT-U
wave), or may become very obvious when the QT or JT interval is shortened (eg,
with digoxin or hypercalcemia).
✓ Step 2: Rhythm
✓ Step 3: Axis determination
✓ Step 4: Intervals
✓ Step 5: P wave
✓ Step 6: QRS complex
✓ Step 7: ST segment-T wave
✓ Step 8: Overall interpretation
A. Rule of 300
❖ If the cardiac rhythm is regular, the interval between successive QRS complexes
determined from the electrocardiogram (ECG) grid can be used to determine heart
rate.
❖ The division of 300 by the number of large boxes calculates the heart rate/HR/.
𝟑𝟎𝟎
𝐇𝐑 =
𝐧𝐮𝐦𝐛𝐞𝐫 𝐨𝐟 𝐥𝐚𝐫𝐠𝐞 𝐛𝐨𝐱𝐞𝐬 (between successive QRS complexes)
For example;
interval between two successive heart rate
complexes
1 large box 300 ÷ 1 = 300 beats/min
2 large boxes 300 ÷ 2 = 150 beats/min
3 large boxes 300 ÷ 3 = 1o0 beats/min
4 large boxes etc 300 ÷ 4 = 75 beats/min
❖ Alternatively, the time between QRS complexes can be measured in seconds. This
number can be divided into 60 to derive the heart rate.
𝟔𝟎
𝐇𝐑 =
𝐭𝐢𝐦𝐞(𝐢𝐧 𝐬𝐞𝐜) 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐐𝐑𝐒 𝐜𝐨𝐦𝐩𝐥𝐞𝐱𝐞𝐬
✓ For instance, if the time between 2 QRS complexes is 0.75 seconds, the heart
rate is 80 beats/min (60 seconds/minute ÷ 0.75 seconds/beat = 80 beats/min).
❖ Although fast, this method only works for regular rhythms.
Example 1
Example 2
Example 3
B. 10 Second Rule
If the rhythm is irregular, the simplest way to determine the rate is by counting the
number of complexes on the ECG and multiplying by six, since the standard ECG
displays 10 seconds of time (As most EKGs record 10 seconds of rhythm per page).
✓ HR = 6 X total number of QRS complexes on the ECG
This method works well for irregular rhythms.
Example
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HR = 33 x 6 = 198 bpm
Do the QRS complexes occur with regular intervals or are they irregular?
Step 3: Establish the relationship between P waves and the QRS complex
Are the P waves associated with QRS complexes in a 1:1 fashion? Do the P waves
precede each QRS complex as is the case with most normal rhythms?
✓ If not, are there more or less P waves than QRS complexes and what are the
atrial and ventricular rates?
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✓ If there are more P waves than QRS complexes, then some form of AV block
is present, which may be physiologic if there is a concomitant atrial tachycardia
or flutter.
✓ If there are more QRS complexes than P waves, then the rhythm is an
accelerated ventricular or junctional rhythm.
Do P waves occur after each QRS complex (i.e. retrograde P waves) What is the
morphology? Are they upright or inverted? Are they all the same in shape and size?
Are the irregular P waves associated with ectopic beats?
upright and rounded in lead II the P Waves are usually originating from the SA
node, indicating a sinus rhythm.
A. Regular rhythm
Normal Sinus Rhythm
Implies normal sequence of conduction, originating in the sinus node and proceeding
to the ventricles via the AV node and His-Purkinje system.
ECG Characteristics:
✓ Rate 60-100 bpm
✓ Regular narrow-complex rhythm
✓ Each QRS complex is proceeded by a P wave
✓ Narrow QRS complex
✓ P wave is upright in lead II & down going in lead aVR
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B. Irregular Rhythm
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3. Axis determination
Axis
Axis is the electrical signal recorded on the ECG which contains information relative
to direction and magnitude of the various complexes.
The normal QRS electrical axis, as established in the frontal plane, is between -30
and 90º (directed downward or inferior and to the left) in adults. /figure 1/
An axis between -30º and -90º (directed superior and to the left) is termed left axis
deviation.
If the axis is between 90º and 180º (directed inferior and to the right), then right axis
deviation is present.
An axis between -90º and -180º (directed superior and to the right) is referred to as
extreme right or left axis.
If the QRS is equiphasic in all leads with no dominant QRS deflection, it is
indeterminate axis.
figure 1
Axis Determination
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The QRS axis can be determined by examining all of the limb leads, but the easiest
method involves looking at leads I, II, and aVF only (figure 2).
If the QRS complex is positive (upright) in both leads I and II, then the axis falls
between -30 and 90º, and the axis is normal.
If the QRS complex is positive in lead I but negative (down ward) in lead II, then the
axis is leftward (-30 to -90º).
If the complexes are negative in lead I and positive in aVF, then the axis is
rightward (90 to 180º).
If the complexes are negative in both I and aVF, then the axis is extreme (180 to -
90º).
❖ Another method of axis determination is to find the lead in which the complex is
most isoelectric; the axis is directed perpendicular to this lead. As an example, if the
QRS is isoelectric in lead III which is directed at 120º, then the electrical axis is
either 30º or -150º.
❖ A third method is to determine the frontal lead in which the QRS is of the greatest
positive amplitude. The axis is parallel to this lead.
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figure 2
Question 2
Question 3
4. Intervals
PR interval
Normal PR interval: 0.12 to 0.20 s (3 - 5 small squares)
A normal PR interval indicates the electrical impulse originated from the SA node or
in the atrium.
Short PR intervals are suggestive of Wolff-Parkinson-White syndrome.
Long PR intervals are usually seen in first degree AV block, but there may be other
causes.
QRS interval
Long QRS intervals represent a bundle branch block, ventricular pre-excitation,
ventricular pacing, or ventricular tachycardia.
QT interval
Short and long QT intervals may be present.
5. P wave
See rhythm analysis above
The normal sinus P wave is generally upright in leads I, II, aVF, and V4-V6 and
negative in lead aVR. It may be negative or biphasic in leads III and V1.
A negative P wave in the inferior leads or lead I suggests an ectopic rhythm (low
atrial or left atrial respectively). Similarly, a completely positive P wave in V1 suggests
a left atrial location.
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6. QRS complex
➢ It is essential to analyze the QRS in all 12 leads to be sure that it is normal.
Look for
✓ QRS Axis
✓ Wide or narrow- duration normally lasts for 0.06 to 0.10 seconds (1½ to 2½ small
boxes)
✓ Pathological Q waves
✓ Left or right ventricular hypertrophy
❖ If the QRS complexes are of normal duration (<0.10 sec) and morphology, then the
rhythm is supraventricular.
❖ If the QRS is wide (i.e. >0.10 sec)
✓ The rhythm is either supraventricular with aberrant conduction, pre-excitation, or
ventricular pacing, or it is of ventricular origin.
✓ Wide QRS with normal rate → bundle branch block (examination of the
morphology can determine if there is left or right bundle branch block or pre-
excitation present)
✓ Regular wide QRS with tachycardia →Ventricular tachycardia /hyperkalemia
✓ Wide QRS with increased voltage may indicate left or right ventricular
hypertrophy.
❖ A narrow QRS complex (<0.06 sec) reflects rapid activation of the ventricles via the
normal His-Purkinje system, which in turn suggests that the arrhythmia originates
above or within the atrioventricular (AV) node (i.e., a supraventricular tachycardia
[SVT]).
❖ Pathologic Q wave
✓ By definition, a Q wave is an initially negative deflection of the QRS complex
✓ 3 principles with respect to Q waves:
1. Not all Q waves are pathologic
2. Not all pathologic Q waves are due to myocardial infarction caused by
fixed coronary artery occlusion; and
3. There is no firm consensus on the criteria for the diagnosis of pathologic
Q waves
✓ Prominent Q waves are a characteristic finding in myocardial infarction, they
can also be seen in a number of Non infarct settings such as;
❖ Misplacement of chest lead electrodes
❖ Dextrocardia
❖ A rightward mediastinal shift in left pneumothorax
❖ Pectus excavatum 1228
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❖ COPD
❖ Rarely, congenitally corrected transposition of the great vessels or
congenital absence of the left pericardium
7. ST segment-T wave
The TP segment, between the T wave of one beat and the P wave of the next
beat, should be used as the baseline.
Normal ST segment: No elevation or depression
ST segment has a duration of 0.08 to 0.12 sec,
ST elevation greater than 2mm (>2 small squares) above the baseline or
depression of greater than 1 mm (>1 small square) below the baseline may be
indicative of an MI.
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T wave
Are the T waves inverted?
High peaked T waves can be indicative of hyperkalemia.
Inverted, elevated, or depressed T waves may indicate myocardial ischemia or
injury.
Inverted T waves are suggestive of MI or a ventricular conduction delay.
T wave inversions due to evolving or chronic ischemia are often associated with
QT prolongation.
8. Overall interpretation
Only after the prior steps have been completed should an overall description,
interpretation and possible diagnoses be determined.
This ensures assimilation of all information in the ECG and that no detail will be
overlooked.
Example 1
Interpret the following ECG
Answer;
Rate = 75 bpm
Regular sinus rhythm
No axis deviation
PR interval of 0.14 sec (3.5 small squares)
Normal QRS complex (0.10 sec)
No ST segment elevation or
Normal T wave (No T wave inversion or tall T wave)
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Answer;
Rate = 55 bpm
Regular sinus rhythm
No axis deviation
PR interval of 0.12 sec (3 small squares)
Loss of R waves in leads V1 to V3
ST segment elevation in v2 to v4
T wave inversion in leads I, aVL and V2 to V 5
Contiguous leads are defined as pairs or groups of leads that reflect the different
walls of the heart. These are the inferior (II, III, aVF), lateral (I, aVL), and anterior
leads (V1 to V6).
.
Prior MI
the following are the criteria for ECG changes associated with prior MI (in the
absence of LVH or LBBB)
Any Q wave in leads V2 to V3 ≥0.02 sec or QS complex in V2 and V3; or Q
wave ≥0.03 sec and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF; or V4
to V6 in any two leads of a contiguous lead grouping (I, aVL; V1 to V6; II, III,
aVF).
R wave ≥0.04 sec in V1 to V2 and R/S ≥1 with a concordant positive T wave in
the absence of a conduction defect.
LOCATION OF ISCHEMIA OR INFARCTION
Image; blood supply and MI leads, LAD =left anterior descending coronary artery, RCA = right coronary artery, LCX = left circumflex
coronary artery
The portion of the LV that is ischemic or infarcted may be predicted by which ECG
leads show ST-segment, T wave, or Q wave abnormalities.
waveform 1A-B
ST-segment shifts or Q waves in leads II, III, and aVF suggest inferior wall ischemia
or infarction (waveform 2).
If there is evidence of inferior wall ischemia, right-sided leads, especially V3R and
V4R, should be obtained to assess for a possible right ventricular ischemia/infarction
(waveform 2).
waveform 2
C. Posterior wall MI
Acute posterior wall MI induces ST elevations in leads placed over the back of
the heart, eg, leads V7 to V9 (waveform 3 and figure 1).
This is usually associated with reciprocal ST–segment depression in leads V1 to
V2 or V3.
Similar ST changes can also be the primary ECG manifestation of anterior
subendocardial ischemia that may occur in combination with inferior infarction.
Posterior inferior wall MI can usually be differentiated from anterior wall ischemia
by the presence of ST-segment elevation in the inferior leads (II, III, aVF) in
addition to posterior leads V7 to V9.
Relatively tall R waves may also appear in leads V1 to V3 (waveform 4),
corresponding to the appearance of pathologic Q waves (loss of depolarization
forces) in the posterior leads.
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waveform 3
figure 1
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waveform 4
D. Multiple regions
In some cases, ischemia affects more than one region of the myocardium.
In this setting, the ECG should show the characteristic findings of involvement in
each region (waveform 5). However, partial normalization may result from
cancellation of opposing vectorial forces.
waveform 5
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✓ ECG may also provide information about the site or arterial occlusion in patients
with STEMI.
Inferior MI on the ECG
An inferior wall MI generally have occlusion of either the right or the left
circumflex coronary artery.
The presence of ST-segment elevation in lead III exceeding that in lead II,
particularly when combined with ST-depression in leads I and aVL, is a very
useful predictor of an occlusion in the proximal or mid portion of the right coronary
artery
The presence of ST-segment elevation in lead II, which is equal to that of lead III,
especially when combined with ST-depression in leads V1 to V3 or ST-elevation in
leads I and aVL, is a useful but not absolute predictor of a left circumflex
coronary artery occlusion; these findings may also be seen in distal occlusion of a
dominant right coronary artery.
Some patients with an inferior MI have right-sided ST-elevation in leads V1 and
V4R; this finding is indicative of acute right ventricular injury and correlates closely
with occlusion of the proximal right coronary artery.
Anterior MI on the ECG
Anterior wall MI usually have occlusion of the left anterior descending coronary
artery (LAD).
The presence of ST-elevation in lead aVR, complete right bundle branch block,
ST-depression in lead V5, and/or ST elevation in V1 greater than 2.5 mm strongly
predicts a LAD artery occlusion proximal to the first septal perforator.
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Complete normalization of the ECG following STEMI is uncommon but can occur,
particularly with smaller infarcts and when left ventricular ejection fraction and
regional wall motion improve.
Normalization is usually associated with spontaneous recanalization or good
collateral circulation.
In contrast, persistent Q waves and ST elevations several weeks or more after an
infarct correlate strongly with a severe underlying wall motion disorder (akinetic or
dyskinetic zone), although not necessarily a frank ventricular aneurysm (waveform
6).
waveform 6
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6.6.2 Pericarditis
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ECG criteria →There have been multiple ECG criteria proposed for diagnosing LVH. The
most popular include:
Amplitude of S wave in lead V1 + amplitude of R wave in V5 or V6 (whichever is
the tallest) ≥35 mm.
Amplitude of R wave in aVL + amplitude of S wave in V3 >28 mm for men, or
>20 mm for women.
QRS voltage in all leads >175 to 225 mm.
R wave in I + S in 3 more than 25 mm
R in aVL more than 11 mm or >18 mm if left axis is present
R in aVF more than 20 mm
S in aVR more than 14 mm
S in V1 or V2 + R in V5 or V6 more than 35 mm
R in V5 or V6 more than 26 mm
R + S in any V lead more than 45 mm
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6.6.4 Arrhythmia
Mechanisms of Arrhythmias
Altered Automaticity (Increased or decreased Automaticity)
Reentry from ectopic foci
Triggered activity
Conduction Block
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Tachyarrhythmias
Supraventricular tachycardia (SVT)
Atrial fibrillation
Atrial flutter
Ventricular tachycardia
✓ Monomorphic
✓ Polymorphic (Torsade’s de pointe)
Ventricular fibrillation
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Atrioventricular block
Atrioventricular (AV) block may manifest as conduction delay in the AV node,
intermittent failure of conduction from the atria to the ventricles, or complete AV
block.
✓ MI
✓ Infiltrative CMP and DCMP
✓ Drugs that impair or slow nodal conduction including digoxin, beta blockers,
and non-dihydropyridine CCB
✓ Certain muscular dystrophies
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The QRS complexes are narrow unless AV conduction through the His Purkinje
system is abnormal due to functional (rate-related) aberration, pre-existing bundle
branch or fascicular block, or ventricular preexcitation with conduction down the
accessory pathway.
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Image; AF
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Ventricular arrhythmias
Ventricular arrhythmias are wide complex rhythms that may be regular or irregular.
These may be normal rate, bradycardic, or tachycardic, and may occur as single
beats or sustained.
Some ventricular arrhythmias may be present as sudden cardiac arrest.
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Intraventricular block
RIGHT BUNDLE BRANCH BLOCK
Incomplete RBBB
Complete RBBB
LEFT BUNDLE BRANCH BLOCK
Incomplete LBBB
Complete LBBB
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Hyperkalemia
Hypokalemia
Hypocalcemia
Hypercalcemia
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Phenytoin toxicity
✓ ECG -reveals increased PR interval, widened QRS interval, and altered ST
segments and T waves, arrhythmias, ventricular tachycardia, primary ventricular
fibrillation, atrioventricular block, or sinus arrest with junctional or ventricular escape
that may occur after intravenous (or very rarely oral) exposure
Phenothiazine toxicity
✓ ECG → usually shows QT interval prolongation and occasionally QRS prolongation
(particularly with thioridazine and Risperidone).
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Chapter 7; Basics about rational use of antibiotics 1272
WHO defines the rational use of antibiotics as the correct, proper and appropriate
use of antibiotics.
Rational use of antibiotics requires that the patient receives medications
appropriate to their clinical needs in doses that meet their own individual
requirements for an adequate period of time and lowest cost to them and their
community.
Antibiotics can be used as: Prophylaxis, Empirical or Definitive treatment
❖ ‘’Stat’’ means given as a ‘’single dose’’ only and there is no any other repeat dose.
E.g. Albendazole, 400mg, PO, stat
❖ QD (lat. Quaque in die) = daily, once per day, every 24 hours (q 24hr)
Don’t use the term ‘’QD’’, because the pharmacist may misinterpret as ‘’QID’’
❖ BID (lat. bis in die) = two times per day, every 12 hrs (2X/day or q12hr)
❖ TID (lat. ter in die) = three times per day, every 8 hrs (3X/day or q8hr)
❖ QID (lat. Quarter in die) = four times per day, every 6 hr (4X/day or q6hr)
❖ Dose more than 4x/day can be prescribed as → q4hr (6x/day), q3hr (8x/day), q1hr,
q5min….
❖ Suppository → drugs to be given per rectum. E.g. PCM suppository, bisacodyl
suppository
❖ Pessary → drugs to be inserted through vagina. E.g. clotrimazole vaginal pessary
Tapering dose
❖ Drugs to be tapered are those not to be stopped abruptly, rather you have to
discontinue the drug by decreasing the dose gradually. By how much to be tapered
depends on your target and patient’s clinical response
❖ Example
Prednisone, 1-2 mg/kg/day, PO, daily or BID, for 4-6 wks, followed by gradual tapering.
❖ Drugs can be given or written in ranges. So, maximum daily dose is the highest
total dose to be given per day. Taking the drug above the maximum level may
cause toxicity or intolerable side effects.
❖ Example
PCM, 500mg to 1g PRN; max 4g/day → in this case the patient can take a total of up to 4g/day
(i.e 500mg 8x/day or 1g 4x/day is the maximum limit)
Enalapril for hypertension; Initial: 5 mg, PO, daily (2.5 mg, PO, daily in patients
taking diuretics); titrate upward, usually at 1- to 2-week intervals; usual dose range:
10 to 40 mg daily. Target dose: 20 mg daily in 1 or 2 divided doses. Maximum: 40
mg/day.
6.6.6.2 Common scenarios in syrup and per body weight (per Kg) dosing
6.7 If a drug is prescribed as per day form (‘’x’’mg/kg/day), you have to divide the
final calculated amount to the frequency of dose (i.e divide by 2 for BID dose,
divide by 3 for TID dose)
6.8 But, if a drug is prescribed as per dose form (‘’x’’mg/kg/dose), you have to
give the total calculated amount per each dose (frequency of dose).
6.9 Per dose and per day have no effect on once daily dosage forms
6.10 Examples
o Gentamycin, 5mg/kg/day, IV, TID, for 3 weeks is the same as gentamycin
5mg/kg/day, in three divided doses, IV, for 3 weeks
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Lines of therapy
✓ Difference between 1st line, 2nd line, 3rd line and alternative
6.25 Treatment options can often be ranked or prioritized as 1st line, 2nd line, 3rd
line and so on.
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Picture; diagrammatic example on, how to search pregnancy risk factor of a specific drug from
UpToDate
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Picture; diagrammatic example on, how to search, a specific drug dose adjustment for renal or
hepatic impairment, from UpToDate
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Classification of antibiotics
6.26 There are four major classes of antibiotics
o Cell wall Synthesis inhibitors
o Protein synthesis inhibitors
o Nucleic acid synthesis Inhibitors
▪ Folate antagonists
▪ Direct enzyme inhibitors
o Miscellaneous
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#
turicatae (New World species),
B. duttonii (Old World species)
See the classification based on laboratory feature below
cephalosporins
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Chapter 8; Symptoms and signs in Amharic (የበሽታ ምልክቶች አማርኛ ትርጉም) 1283
HEENT related sign and symptoms STI and Gynaecology related sign and
❖ Buldged fontanelle = የእርግብግቢት እብጠት symptoms
❖ Epistaxis = ነስር ✓ Dyspareunia = በግብረ ስጋ ግንኙነት ወቅት
❖ Icteric sclera = የዓይን ቢጫ መሆን ህመም መሰማት
❖ Increased head circumference = የእራስ ቅል ✓ Vaginal bleeding (abnormal uterine
መጨመር bleeding) = በማህጸን ደም መፍሰስ
✓ Menstrual irregularitie = የወር አበባ መዛባት
Respiratory system related sign and symptoms ☛ Dysmenorrhea = በወር አበባ ወቅት
➢ Chest pain = የደረት ህመም (ደረት ውጋት) ከፍተኛ የሆነ ህመም ስሜት
➢ Cough = ሳል ☛ Menorrhagia/ metrorrhagia = መጠኑ
➢ Fast breathing (Tachypnea) = ከላይ ከላይ መተንፈስ፣ ብዙ የሆነ የወር አበባ መፍሰስ/ ለብዙ
ቃታ መንሳት ጊዜ መፍሰስ
➢ Hemoptysis = ደም የቀላቀለ አክታ ☛ Amenorrhea (10, 20) = አደፍ ቅሪት
➢ Rhinorrhoea = የንፍጥ መብዛት (ማናፈጥ) ✓ Vaginal discharge = የማህጸን ፈሳሽ ፣
➢ SOB (Dyspnoea) = ትንፋሽ ማጠር የብልት ፈሳሽ
➢ Sputum = አክታ ✓ Urethral discharge = የብልት ፈሳሽ
➢ Stridor = ኩርርታ ✓ Genital ulcer with/without inguinal
➢ Wheeze = ማቃተት፣ የሚአፏጭ ድምጽ swelling = የብልት (ሀፍረተ ስጋ) ቁስል
✓ chancre = ከርክር
CVS related sign and symptoms
Edema = ውሃ አዘል ገላ Haematology related sign and symptoms
Fatigue (easy fatigability) = ድካም ▪ Bleeding = ደም መፍሰስ፣ መድማት
Intermittent claudication = አልፎ አልፎ በጉዞ ▪ Blurring of vision = የእይታ መደብዘዝ
ወቅት የሚከሰት የእግር ሕመም ▪ Epistaxis’s = ነስር
Leg swelling = የእግር እብጠት ▪ Light headedness = የራስ መቅለል
Orthopnoea = ተንጋሎ ትንፋሽ ማጠር ▪ Pallor = መገርጣት
Palpitation = የልብ መደንከር ▪ Tinnitus = ህውታ፣ በጩኸት የሚፈጠር የጆሮ
Tachycardia = ፈጣን የልብ ምት ህመም
N.B vaccines
MMRV = Measles, mumps, rubella, and varicella virus vaccine
DPT = Diphtheria, tetanus toxoids, and acellular pertussis vaccine
Penta valent vaccine contains = DPT, HBV vaccine and Hib (Hemophilus influenza type b) vaccine
scabies = እከክ
o Itching = የማሳከክ ስሜት
Atopic Dermatitis (AD) = የቆዳ አስም
Contact dermatitis = በንክኪ የሚከሰት የቆዳ ብግነት/አለርጂ
Seborrhoeic dermatitis
Psoriasis = የሚያሳክክ የቆዳ በሽታ
Vitiligo
Albinism = ሻሾት
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Here we will discuss selected hematologic, chemistry, Hormone and Chemokine analysis,
serologic, and microbiological tests22
22
Sample for hematology and serology collected by CBC bottle, while sample for chemistry, hormone and chemokine analysis
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collected by organ bottle.
23
Sample for M.HCT collected with capillary tube and at least 2/3rd of the tube should be filled for better out come
24
If M.HCT is available no need of rapid Hgb test. It is used in peripheral setups where CBC machine or M.HCT are not
available. Hgb = 1/3rd of hematocrit
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25
Gram stain
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Samples from body fluids should be collected by sterile tubes (look at images in culture section below).
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Hematology
o Sample for hematology is taken by CBC bottle28. For ESR, collect adequate volume of
blood which is more than the volume of sample required for CBC. you can request
‘’CBC with ESR’’ in one request from one sample
o After taking sample mix gently and immediately to prevent coagulation
o ‘’CBC, BG & RH, Cross match’’ can be done from one sample of a patient. But, in
most setups CBC is done in hematology section of the laboratory while BG &RH done
at blood bank (or mini blood bank). So, the technician working in hematology may
discard the sample after doing CBC. To avoid this, request two papers like below
▪ Request #1 → ‘’CBC, please send sample to BG and RH’’
▪ Request #2 → ‘’BG & RH, Cross match’’
Chemistry
o Sample for chemistry is taken by Organ bottle
o Coagulation profile have its own bottle
o Don’t shake or mix the sample !!!
o During sample collection for serum electrolyte, after drawing venous blood, remove the
needle from the syringe then transfer sample from syringe into organ bottle. This is to
prevent hemolysis which significantly affect electrolyte determination
Sample for serology also collected by CBC bottle
For culture → look at specific topic below
Finally, unless you level the sample (at least by MRN and Pt’ name), all the above note will
be meaningless.
26
Blood culture is collected with specific blood culture bottles following possible sterile techniques. Culture
from other samples (e.g, CSF, Ascitic fluid, stool and urine) can by collected with sterile tubes (sterile
urine cup for urine sample) → look at images in culture section below
27
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This topic is included in this text, considering most setups of Ethiopia where job description is not applied, and majority of
work load given for medical interns. The note is also very essential for medical laboratory and other health science students.
28
we use the term CBC bottle to say EDTA tube)
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Picture; CBC bottles (EDTA blood tubes for Hematology test); These bottles are generally used for haematology tests where
whole blood is required for analysis. They have EDTA (Ethylene diamine tetra acetic Acid) as an additive which Removes
calcium, to prevent blood clotting.
Picture; Organ bottles (SST Tube with Gel and Clot Activator); SST Tube are used to collect blood for clinical biochemistry and
immunology. They can improve serum surface and prevent substance exchange between blood cell and serum. Guaranteeing
biochemical character and chemical components of serum unchanged evidently for a long time, which do not need to us
special tool to transport serum. SST = Serum separator tube
Picture; bottles for coagulation profile/PT, aPTT and INR/ sample collection (Blood PT Tube, Blood Collection PPT
Tube, Sodium Citrate Tube); these bottles have Sodium Citrate as an additive which Binds and Forms calcium salts to
remove calcium and finally prevent blood from clotting
Blood film is done after preparing blood smear and staining with Giemsa stain
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The term Giemsa stain originated from a name of German chemist and bacteriologist Gustav
Giemsa.
Reagents Required → Methanol, Giemsa powder, Glycerin, Water (Buffer)
Time of sample collection
o When the patients feels febrile
o Before anti-malaria drugs are given to the patients
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Thick film considered “gold standard” for detection of parasites due to being able to use
larger volume (10µl of blood)
Thin film considered “gold standard” in species identification
Smear examinations should be under oil immersion
Negatives should not be reported until 200 oil immersion fields have been examined
Additional specimens should be examined at 12-hour intervals for a subsequent 36 hours.
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Taking sample during febrile episodes of the patient increase positivity of the result
Mixed infections or low parasitemia usually difficult to diagnose.
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☛ Note: Avoid drying of smear by an incubator or by heat, because it may fix the blood smear
onto the slide and results in lysis of RBCs.
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* Identification of a schizont with >12 merozoites in the peripheral circulation is an important diagnostic clue for P. vivax. In general,
schizonts of P. falciparum are very rarely seen in blood films; they are generally absent from the peripheral circulation except in
cases of severe infection with overwhelming parasitemia.
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Blood smear and geimsa stain - Click on the link below and watch the video
https://youtu.be/uVaYuq6Jzk4
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Pictures; Hematocrit determination after centrifugation. Left) centrifuge machine. Right) In this particular
picture, HCT measured with hematocrit scale is ≅ 50% (a) and ≅ 45% (b)
This photo(left) shows two anticoagulated blood-filled Wintrobe hematocrit tubes following high speed centrifugation. The tube on the
left is from a normal subject, with a hematocrit of 38 percent (blue arrow). The tube on the right is from a 19-year-old female with
essential thrombocytosis, a normal white blood cell count, and a platelet count of 5,000,000/microL. The extreme degree of
thrombocytosis can be appreciated by the presence of a marked increase in the size of the "buffy coat" (white arrow). When the
Wintrobe tube is filled to near capacity (upper arrows), and the white blood cell count is not markedly elevated, the platelet count
can be estimated by the thickness of this layer, with each mm being equivalent to one million platelets/microL. In normal subjects,
the buffy coat, which is comprised of white blood cells and platelets, is only minimally visible.
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Picture; steps of Rapid hemoglobin determination using ‘’mission plus hemoglobin testing system’’
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A) Insert 4 batteries into the battery compartment, close the battery cover and make sure the snap is
shut down
B) Insert the correct ‘’code chip’’ into the ‘’code chip slat’’ on the meter. Compare the code number on
the code chip with the code number printed on test strips canister or the code device. Results will be
inaccurate if the two numbers are not identical.
C) Turn on the meter. ‘’Setting up the Meter’’ before testing is necessary which includes; correcting test
number setup incase to test up to 999 tests with one memory of the meter, setting 12h or 24h mode,
time setup (the date, month and year), setting units (g/dl, g/L or mmol/L) → download and watch the
video from the link attached below
D) Insert the test strip into the test channel in the same direction as the arrows indicate on the strip.
Make sure that, the test strip is inserted all the way to the end of the channel (insert the strip up to
the encircled black line in the picture)
E) The ‘’blood drop symbol’’ will flash when the meter is ready for the specimen to be applied
F) Collect capillary blood of 10 µl using a capillary transfer tube or pipette. The capillary transfer tube will
fill automatically
G) Make sure the blood covers the end of capillary transfer tube and never squeeze the tube
H) Apply the blood sample to the central region of specimen application area of the test strip
I) Results will be displayed in about 15 seconds with Hgb and HCT values as shown in the figure (Hgb
= 12.9g/dl, HCT = 38%)
Mission Plus Hb Hemoglobin testing system - Click on the link below and watch the video
https://youtu.be/WO7HApAUSME
Smear preparation for PM is the same as malarial thin smear preparation (look at the
section of BF above).
Review of the peripheral smear starts with choosing the best prepared and stained slide
for examination. Scanning the entire slide under low power enables selection of an optimal
area
Diagram; This schematic depicts a well-made peripheral blood smear. A drop of blood has been
placed on the left-hand side of a clean glass slide at point A, and has been pulled towards the right-
hand side using another glass slide, stopping at point B. The area near point A is too thick and too
darkly stained for interpretation, whereas the area at the very end of the smear, near point B (the
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"feather edge") is too thin, distorting the morphology of all cells in that area. The optimal area for
viewing is just behind point B (shown by the asterisk), in an area where the red blood cells are just
touching and demonstrate central pallor.
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There are various staining methods for PM, but most laboratories employ Wright-Giemsa
staining (look at BF section above)
For certain cases (e.g. Hematologic malignancy), pathologist evaluation of a well-prepared
smear is mandatory. Others (e.g anemia) can be evaluated by laboratory technologist or
experienced physicians.
Look at different morphologies of peripheral Blood smear from anemia section under
miscellaneous part of Nitsibin short cases. (click here →Anaemia (የደም ማነስ) )
10.1.5 Blood group and RH (BG & RH) determination, cross match
Figure; Landsteiner’s Rule; Reciprocal antibodies are present in the sera of normal people
whose RBCs lack the corresponding antigen(s)
slide grouping
Specimen
o Patient’s serum
o Patient’s cells
Reagents and equipments:
o Anti- A and anti-B serum
o Group O serum (anti-AB)
o Antigen A and antigen B (20% known RBC suspension)
o Group AB serum (Control)
o Tile or slide
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Interpretation
o Positive agglutination → antibodies specific for A/B antigen are present.
o Negative agglutination → no antibodies are present for antigens
Rh- typing
The importance of Rh typing
o Administration of Rh +ve blood to Rh -ve may sensitize the person to form anti-D
antibody.
o Donation of Rh +ve blood to recipient having anti D could be
fatal.
RBCs (D-Ag) + Anti -D (antisera) → ± agglutination (ag- ab rxn)
This can be performed on slide test, saline tube test, modified tube test
Interpretation
o If there is agglutination of RBCs -------- positive for D- antigen
(Rh positive)
o If there is no agglutination of RBCs -------- the D- antigen is not
ex pressed. This can be Rh negative or Du variant.
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Cross matching
➢ It is the last phase of pre transfusion testing
➢ It will detect ABO or Rh incompatibility
➢ There are two kinds of cross match.
1. Major cross match
2. Minor cross match
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❖ Detect antibodies in donor’s serum capable of affecting the RBC of the recipient.
❖ It has minor importance.
❖ Involves testing/mixing the donor’s serum with recipient’s red cells.
✓ Donor serum + recipient RBC → agglutination/ hemolysis.
❖ Result can be interpreted like major cross match.
❖ Called minor because:
✓ Any Ab in the donor’s serum will be diluted by the large volume of the recipient’s
blood.
✓ The Ab may also be neutralized by ABH substances present in a recipient’s tissues,
so is unlikely to cause a serious reaction.
✓ The destructed RBCs of the patient may be compensated by the transfused RBC of
the donors
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For more, refer under miscellaneous section of Nitsibin short case (click here → Blood
Transfusion)
10.1.6 ESR (Erythrocyte Sedimentation Rate) (Macro and micro /µ/ ESR)
Sample should be collected with CBC bottle (ESR needs much volume of blood than CBC)
When whole blood is placed in a vertical tube, red cells will tend to fall toward the bottom.
The length of fall of erythrocyte in a given interval of time is called ESR
ESR is used to follow up patients and supportive for some disease diagnosis. But it has no
specific diagnostic value
Has 3 stages
1. Roulaex formation = 1st 10 minutes
2. Sedimentation = next 40 minutes
3. Packing of sediments = last 10 minutes
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µESR is a routine investigation [especially for neonates} which can be done at bedside by any
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Put one drop of capillary prick blood sample over the tip of the strip, and read the
result (automatic numbers as shown in the picture). If RBS is > 600mg/dl, glucometer
failed to interpret and it displays ‘’H’’ instead of numbers meaning ‘’High’’
Picture; glucometers
Picture; finger prick for RBS sample collection (also for manual hematocrit sample collection in
adults), then draw sample with capillary tube to send for laboratory (only few sample is needed,
if glucometer is available in the ward/OPD, you can take directly from fingertip to the test strip
and no need of capillary tube.)
Pictures; left) The areas of the foot of a baby or infant that are suitable for obtaining capillary blood.
Right) Heel Prick
I. Immerse the reagent strip into the urine for up to 2 seconds then remove the
excess urine on the edge of the container
II. Compare the colors on the reagent area with corresponding color chart on the
container label
III. Report the result
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Protein Proteinuria
✓ Nephrotic sxx
✓ Edema
Ketone ✓ DKA
✓ Starvation ketoacidosis
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✓
be stored for not more than 24 hours (refrigeration). 1312
Note** If the urine sample is not analyzed within 2 hours after collection, it should
❖ For urine analysis, the sediment should first be observed under low power field (LPF)
when observing for crystals, casts, squamous cells or other larger objects. When making
a report, the number of casts seen under the microscope is usually reported as the
number of each type per low power field. Moreover, low power allows for a wider view,
which allows for clear observation of the number of casts seen.
❖ Note** - When observing the slide under low power, low light source should be used.
This is because of the fact that too much light would make it more difficult to see he
cellular and crystalline elements.
❖ To observe and identify cells, crystals and bacteria, high power field (HPF) is used. In
this case, the types of cells will also be described as the number of each type found per
the high-power field.
Abnormal findings in urine microscopic examinations (for normal reference values click here →
Chapter 11; Reference Intervals for Laboratory Tests)
➢ > 3 erythrocytes
➢ > 5 leukocytes
➢ > 2 renal tubular cells
➢ > 10 bacteria
Presence of:
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❖ For S/E, Collect the sample in a clean, water-tight dry urine free container with a tight lid.
❖ In the case of neonates and Infants, collect from the diaper.
✓ Put the cover glass on it and gently press it to get an evenly thin smear.
✓ See under 10x and 40x objective lenses.
Concentration methods
❖ The main aim of the concentration method is to remove the debris. Also, when the
parasite is low in number
❖ There are three methods used for the concentration of stool:
✓ Formalin-ethyl-acetate concentration method.
✓ Zinc-floatation method.
✓ Sheather sugar floatation method.
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◼ Some authors believe it a superior method for concentration and identifying eggs and
protozoan cyst.
◼ The parasites are lighter and float on the surface, while the debris settles at the bottom.
◼ Look at the procedure in the diagram below
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Picture; Common nematode eggs and larvae easily recognized on microscopy (wet mount) include: (A) Ascaris, (B) Trichuris
/wet mount with iodine/, (C) hookworm (wet mount with iodine), (D) Enterobius (pinworm), (E) Capillaria, (F) Strongyloides
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rhabditiform larvae.
Ascaris eggs are large with rough surfaces and a dark dense center (A). Trichuris eggs have distinctive mucus plugs at either end
as well as a "tea tray" appearance (B). Hookworm eggs are optically clear at the edges with a dense center composed of one or
more cells (C). Enterobius eggs have a distinctive oval shape with slight concavity (D). Capillaria eggs are similar to Trichuris but
are smaller with more flattened ends (E). Strongyloides larva may be distinguished from hookworm larva by the presence of
short buccal cavity and primordial genitalia midway down the body (F).
The measurements given represent the range seen for the black bar lengths for each organism.
Picture; Common trematode eggs seen on easily recognized on microscopy (wet mount with iodine) include: (A) Schistosoma
mansoni, (B) Schistosoma haematobium, (C) Schistosoma japonicum, (D) Clonorchis, (E) Fasciola, (F) Paragonimus
Schistosoma eggs are the largest of the helminths and can be distinguished by their spines which are lateral (S. mansoni, A),
terminal (S. haematobium and S. intercalatum, B), or vestigial (S. japonicum or S. mekongi, C). Clonorchis and Opisthorchis eggs
have an operculum and small remnant at the opposite end (D). Fasciola and Fasciolopsis are also operculated but smooth (E).
Paragonimus eggs are also operculated but have a thick, almost pointed opposite end (F).
The measurements given represent the length of the eggs along the long axis for each organism.
Picture; Common cestode eggs recognized on wet mount include: (A) Taenia solium, (B) Taenia saginata, (C) Hymenolepis
nana, (D) Diphyllobothrium latum, (E) Hymenolepis diminuta, (F) Dipylidium caninum.
The eggs can be useful for diagnosis, although the primary diagnostic forms are the mature (gravid) proglottids and the scolex.
The eggs of Taenia are indistinguishable (A and B).
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Picture; Common protozoa easily recognized on microscopy include: (A) Entamoeba histolytica (trichrome stain), (B) Giardia
lamblia (wet mount), (C) Cryptosporidium (acid-fast stain), (D) Cystoisospora (wet mount with exposure to ultraviolet light), (E)
Cyclospora (wet mount), (F) Balantidium coli (wet mount with iodine).
E. histolytica may appear as a cyst form with chromatid bar (A). Giardia lamblia has distinctive flagella (B). Cryptosporidium is
small with acid-fast staining (C). Cystoisospora (formerly Isospora) has an oblong shape, one or two nuclei, natural
fluorescence, and acid-fast positivity (D). Cyclospora is similar to but larger than Cryptosporidium, with natural fluorescence
and acid-fast positivity (E). Balantidium coli is the largest protozoan infecting humans and the only ciliate (F).
The measurements given represent the range seen for the black bar lengths for each organism.
For more images, look at investigation part of intestinal infection section of Nitsbin short cases
(click here → Amoeba (አሜባ), Giardia (ጃርዲያ), Intestinal Helminthic Infestations (የአንጀት ጥገኛ ተውሳክ ፣
የአንጀት ትላትል) and blood flukes)
Detect the presence of Human chorionic gonadotrophin (HCG) hormone, which is produced
by the trophoblastic tissue in the placenta
HCG has two sub units: The α sub unit & the β subunit
It has certain importance such as: To confirm pregnancy, to diagnose ectopic pregnancy and
GTD and trophoblastic tumors, testicular cancer in males.
Serum HCG reaches detectable level within 24 hours after implantation.
Methods of evaluation
9) Strip test → common in our set up
Principle:
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Urine HCG [strep test] is very simple test which can be performed at bedside (request ‘’urine HCG kit’’ and do it by yourself
instead of sending sample to lab, which decreases time wastage)
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oThe test reaction is between the HCG in the urine and gold coated antibody on the
strip.
o A positive control is also impregnated on the strip so that interpretation will be very
easy.
o The preferential sample for HCG test is first morning urine
Steps and Result interpretation → look at the images below
➢ Immerse the strip on the urine sample up to the maximum line (horizontal blue
line)
➢ Lay the strip flat (you can put on the top of urine cup)
➢ Read the result within 5 minutes
▪ Double lines (control and test) → positive for HCG.
▪ Control line only → Negative for HCG
▪ Invalid result → without having any line or appearance of test line only.
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Picures; Urine HCG strip test; A) negative urine HCG test in which only the control (C) line is visible; B) shows positive urine HCG
test in which both control (C) and test (T) line are visible. Picture taken, from two patient samples, at private clinic in Ethiopia.
Principle:
o Latex reagent coated with anti-HCG antibodies + urine
o Presence of visible agglutination positive for HCG.
o No visible agglutination indicates Negative for HCG
Principle:
o Urine + anti-HCG antibody + latex HCG
o Presence of visible agglutination negative for HCG.
o No visible agglutination indicates positive for HCG
10.5.2 PICT
A rapid test which was previously known as provider-initiated counselling and testing (PICT).
Current recommendation is test and then counsel, so the name changed as provider-initiated
testing and counselling.
An antigen is coated on the strip with positive control.
up on addition of serum /plasma or whole blood depending on the test procedure, there will
be reaction between antigen and antibody if present in the sample.
Reactive results: two colored bars (one for the control & the other for the patient)
Non- reactive: single colored bar (positive control only)
Invalid result: without having any line.
For final result interpretation look at investigation section of RVI from long case of Nitsibin (click
here → Chapter 5; RVI (ኤችአይቪ ኤዲስ))
Procedure (steps)
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Pictures; RDT for malaria test; pf = P. Falciparum, pv = P. vivax, CON = control, S = place for sample, A = place
for buffer. Picture taken, from a patient sample, at private clinic in Ethiopia.
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Pictures; widal test reagents; +ve control, negative control, ‘’H’’ antigen and ‘’O’’ antigen. Picture taken
from a private clinic in Ethiopia.
Pictures; widal test; right) reactive widal test with clear agglutination. Picture taken, from two patient samples, at
private clinic in Ethiopia.
Widal test - Click on the link below and watch the video
https://youtu.be/dflOQ8hXUbA
N.B Salmonella typhi stool antigen test is very specific and sensitive (up to
99%) than widal test
A Weil-Felix reaction is a type of agglutination test in which patients’ serum is tested for
agglutinins to O antigen of certain non-motile Proteus and rickettsial strains (OX19, OX2,
OXK) to determine the presence and type of rickettsial infection
OX19, OX2 are strains of Proteus vulgaris. OXK is the strain of Proteus mirabilis.
The blood serum of a patient with suspected rickettsial disease is tested against certain
strains of (OX-2, OX-19, OX-K).
In 1915, Weil and Felix showed that serum of patients infected with any member of the
typhus group of diseases contains agglutinins for one or more strains of O X Proteus.
In cases of typhus, the reaction usually appears before the 6th day and reaches its height in
the second week.
Procedure
The Weil-Felix Test can be done as either a slide or a tube test. Here we are going to
discuss slide test
The antigens necessary (OX2, OX19, and OXK) can be obtained commercially.
On a solid surface (glass slide, tile, card), a small amount (50- 100 μL) of the patient’s
serum is placed.
A single drop of the desired antigen is added, and the resulting suspension is mixed and
then rotated for one minute.
Visible agglutination is indicative of a positive result, and corresponds roughly to a titre of
1:20.
Positive results can be further titrated using the tube method, which is more labour- intensive.
Pictures; reagents for Weil - Felix test (OX 19, OX2 and OX K)
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Table; Interpretation of Weil - Felix result, RMSF = Rocky mountain spotted fever
Diagram; steps of H. pylori antigen stool (fecal) test with kit; Detects directly the presence of H. pylori antigen in a
stool sample. A stool test can detect traces of H. pylori in the feces. This test can be used to diagnose the infection
and confirm that it has been cured after treatment. One line = negative (control test), two line = positive, No line =
invalid. The absence of the control line, makes the result invalid. In this case, the sample must be retest.
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Diagram; H. pylori antigen stool (fecal) stripes test; Detects directly the presence of H. pylori antigen in a stool
sample. A stool test can detect traces of H. pylori in the feces. This test can be used to diagnose the infection and
confirm that it has been cured after treatment. One green line = negative (control test), One green line AND one
red line = positive, No line = invalid. The absence of the control line, which is the upper green line, makes the result
invalid. In this case, the sample must be retest.
Picture; H. pylori serum antibody test cassette/kit/; H. pylori serum antibody test cassette or strips detects
antibodies to the bacteria and will not distinguish previous infection from a current one. If test is negative, then it is
unlikely that a person has H. pylori infection. If ordered and positive, results should be confirmed using stool
antigen or breath test. As a result, blood tests cannot be used to see if the infection has been cured after
treatment. Picture taken from a private clinic in Ethiopia.
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HepBs Ag test procedure - Click on the link below and watch the video
https://youtu.be/h3iAL26d6SY
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Positive result: When both, control and test lines, appear, the sample tested has antibodies
against recombinant K39 antigen of Leishmania. Even a faint line should be considered
positive.
Negative result: When only the control line appears, there are no antibodies against
recombinant K39 antigen of Leishmania present in the patient’s sample.
Invalid result: When no control line appears, a fresh patient sample should be tested with a
new strip.
Advantages
o Simple to perform with minimal training.
o Does not require a laboratory.
o Can be performed with finger-prick whole blood, serum or plasma.
o Kits can be transported and stored at ambient temperature (up to 30 °C).
o Results are available within 10–20 minutes
Disadvantages
o Cannot distinguish between active cases and relapse in previously treated cases.
Therefore, interpretation must always be accompanied by clinical case definition.
o In patients with advanced HIV infection, a negative result does not rule out VL
diagnosis.
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Materials
Procedure
Negative result:
o The carbon particles remain in an even suspension = Non reactive
Positive result:
o The carbon particles clump together = Reactive
Procedure:
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Pipette 0.05ml or 1drop of inactivated serum into one ring of the ringed glass slide.
Add one-drop (1/60ml) antigen suspension onto each serum.
Rotate slide for 4 minutes. (If rotated by hand on a flat surface, this movement should
roughly circumscribed a 2 inch/5mm diameter circle).
Tests are read immediately after rotation microscopically with a 10x ocular and a 10x
objective.
Tests are read microscopically with low power objective at 10x magnification, which appears
short rod forms. Aggregation of these particles into large or small clumps is interpreted in
degrees of
Reporting system
o No clumping or very slight roughness: Non-reactive (NR)
o Small clumps: Weakly reactive (WR)
o Medium and large clumps: Reactive (R)
Interpretation
The detection of acid-fast bacilli (AFB) on microscopic examination of stained sputum smears
is the most rapid and inexpensive TB diagnostic tool.
A serious of at least 3 single specimens should be collected in 8 to 24 hours interval (with
at least one specimen obtained early in the morning) which should be submitted to the
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laboratory for AFB smear and mycobacterial culture, although the diagnosis often can be
made with 2 specimens
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The Ziehl-Neelsen staining technique is a differential staining technique that was initially
developed by Ziehl and modified later by Neelsen, hence the name Ziehl-Neelsen stain.
The Mycobacterial cell is difficult to stain by gram staining because they possess a
waxy envelope and a special method has to be used.
Besides being difficult to stain, once it is stained the organism is hard to decolorize.
Acid-fast bacteria can’t be affected by acid alcohol or 20% sulphuric acid, so named as acid
fast.
Required reagents → CAM
o Carbol-fuchsin → primary stain
o Acid-Alcohol → 20% sulphuric acid as Decolorizer
o Methylene blue/Malachite green → counterstain
Procedure
o Prepare the smear from the primary specimen and fix it by passing through the flame
and label clearly
o Place fixed slide on a staining rack and cover each slide with concentrated carbol
fuchsin solution.
o Heat the slide from underneath with sprit lamp until vapor rises (do not boil it) and wait
for 3-5 minutes.
o Wash off the stain with clean water.
o Cover the smear with 3% acid-alcohol solution until all color is removed (two minutes).
o Wash off the stain and cover the slide with 1% methylene
o Blue for one minute.
o Wash off the stain with clean water and let it air-dry.
o Examine the smear under the oil immersion objective to look for acid fast bacilli.
Results and Interpretation
o Acid-fast bacteria retain the primary dye, carbol-fuschin, and stain pink or Red
o Non-acid fast bacteria take up the methylene blue dye and appear Dark blue or Blue.
Applications of Ziehl-Neelsen Staining
o Used for examination and identification of Mycobacterium species including M.
tuberculosis and M. leprae.
o Used to differentiate between acid-fast and non-acid fast bacilli
o Used for the identification of some fungal species such as Cryptosporidium.
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How to do an acid fast- staining - Click on the link below and watch the video
https://youtu.be/faB_5STfZH8
Gram stain is a special stain for the diagnosis of the gram-positive or gram-negative
organism in various samples like sputum, pus, CSF, urine, tissue, sample from infected ulcer
or wound etc.
Gram stain divides bacteria in to two physiologic groups, gram positive &gram
negative
The name comes from its inventor, Hans Christian Gram. He published a gram stain method in
1884.
Indication
✓ To differentiate between gram-positive and gram-negative organisms 1339
✓ To diagnosis the presence of bacteria in sputum, pus, or any other tissue or fluids.
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* Look at culture section, below for each bacterial differentiation with examples
#
Gram +ve bacilli can be large, medium, small or branching
$
G -ve bacilli can be Medium to long[plump], Medium to long [thin], Short to long [pleomorphic], Tiny, Curved
Gram stain - Click on the link below and watch the video
https://youtu.be/ccMvyBcxvJc
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I. Blood culture
D2 → if D1 is not possible, draw blood directly from vein with 10 cc syringe, keeping possible
aseptic techniques to decreases contamination of sample with skin normal flora
E) Insert needle into a tube containing a culture medium and push the plunger into the barrel to
expel contents of the needle onto the side walls of the tube or directly into the liquid phase
of the medium (caution !!! → don’t open the cap /cover/ of culture bottle at any time of
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sample collection). Check that, correct volume was taken and send sample to lab immediately
after filling the culture request slip. Culture result usually expected after 05 days of
inoculation in culture media.
B) Urine culture
❖ Sample
➢ Early morning clean catch mid-stream urine which is collected aseptically by sterile
urine cup OR Supra pubic aspirates. For neonates and children urine is collected
by sterile plastic bags
➢ Foley catheter
o Urine should be aspirated from the distal end of the catheter with sterile syringe
after disinfecting the area (avoid sample taking from the urine bag)
o Urine specimen should be obtained aseptically without opening the catheter
collection junction
❖ Transport to the laboratory within 01 to 02 hours; if not, keep at 40C to avoid
multiplication of bacteria in urine
❖ 24hr urine cultures are not recommended
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Picture; left) suprapubic aspiration; The needle is inserted one to two centimeters above the pubic symphysis and angled 10 to 20 degrees
cephalad. right) urine culture sample collection from foley catheter system; Ideally urine samples for culture should be obtained by
removing the indwelling catheter and obtaining a midstream specimen. If ongoing catheterization is needed, ideally the catheter should be replaced prior to
collecting a urine sample for culture, to avoid culturing bacteria present in the biofilm of the catheter but not in the bladder. Many systems have a
"needleless" site that can be cleansed prior to specimen collection. If a sample is being collected without catheter removal, urine should be obtained from the
port in the drainage system. For circumstances in which the above approaches are not possible, the culture should be obtained by separating the catheter
from the drainage system. Although this approach is associated with some risk of introducing microbes into the closed system, culture results from urine
collected from the drainage bag cannot be used to guide treatment.
C) Stool culture
◼ Stool sample for culture can be collected by a clean, water-tight dry urine free container
with a tight lid
◼ Then place some amount of stool, from the container into sterile culture tube using
applicator stick. The stick is available together with sterile tube
◼ Mix well with the buffer [all sterile tubes of stool culture have buffer inside] inside the tube
and level the tube before sending to laboratory.
A) CSF Culture
❖ Culture from stool, CSF and other body sites collected by sterile tubes
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❖ Sterile Swab is needed [usually available together with sterile tube] to collect stool into
sterile tube
❖ Sterile swab also used to take sample from ulcer and wound discharge
Culture media
A) Blood agar
✓ Gamma /𝜸/ hemolysis (no hemolysis) → results in no change in the agar color
around and under the colony. Enterococcus faecalis (formerly group D
Streptococcus) displays gamma hemolysis.
✓ Hemolytic streptococci are further categorized by Lancefield grouping (see below)
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Selective medias
❖ Helps to detect specific pathogenic organisms growing concurrently with normal colonizing
bacteria in specimens collected from nonsterile sites.
❖ Pathogens that may be identified with selective media include Bordetella pertussis,
Salmonella species, Shigella species, N. gonorrhoeae, and Legionella pneumophila
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Chapter 10; Common Laboratory Investigations with practical points and procedures 1349
Coagulase test → used to differentiate S. aureus from other staphylococci (CoNS /S.
epidermidis/)
Oxidase test
❖ Used to differentiate gram-negative bacilli based on their production of certain cytochrome
c oxidases.
❖ A positive result is indicated by a purple color change that is detectable within a few
seconds.
❖ Oxidase-positive organisms include → P. aeruginosa, Pasteurella multocida, Vibrio, and
Aeromonas species.
❖ Oxidase-negative organisms include → Enterobacteriaceae (such as E. coli, K.
pneumoniae, Enterobacter cloacae, Serratia spp) and Acinetobacter species.
Lancefield grouping
❖ Lancefield grouping of hemolytic streptococci groups are based on specific carbohydrates
in the bacterial cell wall that allow agglutination with particular antisera. Not all
streptococci can be grouped; some species such as S. pneumoniae do not express
Lancefield antigens
❖ usually used to identify beta-hemolytic streptococci but may also be used to help identify
other streptococci and enterococci. For example, Enterococcus species are usually group
D; S. anginosus group are frequently group F but may be groups A, C, or G.
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For antibiotics sensitivity and antibiotic coverage of each bacteria click here → Chapter 7;
Basics about rational use of antibiotics
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Chapter 11; Reference Intervals for Laboratory Tests 1351
Further reading → UpToDate 2018 (Approach to Gram stain and culture results in the
microbiology laboratory, culture section)
LDL
Normal
Lower
≥ 1.55 mmol/L
< 1.03 mmol/L
1.8 - 4.9 mmol/L
≥ 60 mg/dL
< 40 mg/dL
70 -190 mg/dL
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Chapter 11; Reference Intervals for Laboratory Tests 1353
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Reading assignment 1357
Reading assignment
1. Respiratory system
o Upper respiratory tract infections
o Acute Bronchitis
2. GI system
o Hepatocellular carcinoma
o Diseases of the small intestine (malabsorption syndrome)
o Dysphagia and esophagitis
3. NS
o Brain abscess
o Headache
o Movement Disorders
o NMJ disorders
o Peripheral neuropathies
4. Hematology
o Hemostasis and bleeding disorders
6. Infectious disease
o Staphylococcal and Streptococcal Infections
o Anthrax/ቁርባ/, Clostridium Difficile Infection
o Shigellosis
o Brucellosis
o Virology → HSV, Influenza viruses, Ebola virus/ኢቦላ/
o Viral AFI → Dengue fever/ደንጉ/, Yellow fever/ቢጫ ወባ/, Chikungunya/ችጉንጉንያ/
o Rabies (የእብድ ውሻ በሽታ)
o Filariasis, Lymphatic (Elephantiasis)/ዝሆኔ/
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References (ዋቢ መጽሐፍት) 1358
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References (ዋቢ መጽሐፍት)
1
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