Rapid Review Clinical Medicine MRCP - 2
Rapid Review Clinical Medicine MRCP - 2
Rapid Review Clinical Medicine MRCP - 2
Clinical
Medicine
for MRCP Part 2
Second Edition
Sanjay Sharma
Rashmi Kaushal
MANSON
PUBLISHING
Dedication
For Ravi, Ashna, Anushka, Ishan, Shivani and Milan
Acknowledgements
We are grateful for the help of several colleagues who helped provide slides for the book:
Dr L Wilkinson, Ms S Gowrinath, Ms H Derry, Mr P Radomskij, Dr J Waktare, Ms A ODonoghue, Dr S Rosen,
Dr A Mehta, Dr L Shapiro, Professor M E Hodson, Dr G Rai, Dr A Ghuran, Professor C Oakley, Ms F Goulder,
Dr J Axford, Dr S Jain, Dr M Stodell, Dr B Harold, Dr D Seigler, Dr C Travill, Dr G Barrison, Dr D Hackett,
Dr J Bayliss, Dr R Lancaster, Dr R Foale, Dr W Davies, Professor D Sheridan, Professor W McKenna,
Professor G MacGregor, Dr A Belli, Dr Adams, Dr J Joseph, Dr M Impallomeni, Dr D Banerjee, Dr N Essex,
Dr S Nussey, Dr S Hyer, Dr A Rodin, Dr M Prentice, Dr N Mir, Mrs K Patel and Dr J Jacomb-Hood.
We are also grateful for the assistance of the Audiovisual Departments at Luton and Dunstable Hospital, St Marys
(Paddington) Hospital and St Georges Hospital Medical School and the ECG, Echocardiography and Radiology
Department at St Georges Hospital Medical School and University Hospital Lewisham.
Contents
Acknowledgements
Preface
Classification of Cases
Abbreviations
Clinical Cases
Data Interpretations Tutorials
Calcium Biochemistry
Genetics
Audiograms
Guidelines for the Interpretation of Cardiac Catheter Data
Respiratory Function Tests
Interpretation of Respiratory Flow Loop Curves
Echocardiography
Acidbase Disturbance
Normal Ranges
Index
2
3
4
5
7
415
415
415
416
418
419
420
421
426
427
429
Preface
Passing specialist examinations in internal medicine is a
difficult milestone for many doctors, but is a mandatory
requirement for career progression. Pass rates in these
examinations are generally low due to high standards
and stiff competition. Thorough preparation is essential
and requires a broad knowledge of internal medicine.
The pressures of a busy clinical job and nights on call
make it almost impossible for doctors to wade through
heaps of large text books to acquire all the knowledge
that is required to pass the examinations.
The aim of this book is to provide the busy doctor with
a comprehensive review of questions featured most
frequently in the MRCP (II) examination in internal
medicine. The MRCP (II) examination has a best of 5/n
from many answer format. The vast majority of the
questions in the book follow the same pattern; however,
we have chosen to include several scenarios with open
ended questions to stimulate the medical thought process.
The level of difficulty of each question is of the same
standard as MRCP (II) examination. However, some cases
are deliberately more difficult for teaching purposes.
A broad range of subjects is covered in over 400
questions ranging from metabolic medicine to infectious
diseases. Precise answers and detailed discussion follow
each question. Where appropriate, important differential
www.drmyothethan.blogspot.com
Sanjay Sharma
Professor of Clinical Cardiology
Consultant Cardiologist and Physician
Lecturer for Medibyte Intensive Courses
for the MRCP Part 2
Rashmi Kaushal
Consultant Physician and Endocrinologist
Classification of Cases
Cardiology
1, 10, 11, 13, 22, 25, 32, 40, 52, 53, 54, 62, 63, 66, 68,
74, 78, 80, 94, 95, 100, 121, 123, 125, 130132, 138,
144, 150, 160, 167, 178, 180, 184, 193, 197, 199, 202,
203, 207, 208, 223, 226, 229, 232, 235, 237, 243, 246,
259, 266, 270, 285, 287, 291, 296, 301, 305, 307, 309,
318, 323, 324, 327, 331, 332, 335, 342, 350, 353, 362,
368, 377, 387, 389, 391
Dermatology
116, 154, 173, 316
Endocrinology and diabetes
5, 9, 23, 39, 46, 76, 82, 89, 92, 101, 106, 107, 127,
134, 146, 159, 164, 168, 173, 181, 199, 218, 220, 238,
242, 254, 260, 261, 273, 281, 328, 334, 372, 373, 379,
397, 401
Metabolic medicine
9, 29, 34, 38, 50, 71, 74, 81, 82, 84, 90, 129, 134, 136,
147, 153, 161, 179, 189, 214, 215, 230, 248, 257, 271,
275, 283, 310, 321, 326, 329, 333, 334, 398
Nephrology
4, 17, 24, 29, 44, 53, 59, 60, 85, 92, 118, 119, 126, 135,
137, 141, 152, 185, 198, 228, 244, 245, 249, 250, 251,
278, 289, 294, 303, 304, 317, 328, 344, 354, 381, 382
Neurology
30, 65, 67, 93, 98, 103, 105, 108, 112, 128, 139, 145,
190, 192, 200, 239241, 247, 253, 255, 256, 268, 274,
288, 290, 292, 307, 314, 330, 345, 365, 390, 395, 399
Obstetric medicine
130132, 190, 193, 348
Environmental medicine
140
Oncology
117, 216, 258, 358, 359
Gastroenterology
3, 6, 19, 24, 33, 64, 72, 75, 104, 127, 133, 143, 148,
162, 169, 182, 188, 201, 231, 276, 293, 306, 338, 339,
347, 367, 369, 371, 383, 393, 394, 400
Ophthalmology
282, 345
Genetics
47, 85, 151, 170, 194, 195, 269, 315, 361
Haematology
12, 38, 49, 69, 70, 73, 86, 87, 102, 114, 115, 117, 120,
122, 142, 156, 163, 175, 191, 204, 211, 216, 219, 233,
258, 263, 265, 295, 297, 299, 308, 313, 336, 346, 351,
352, 358, 376, 385, 392, 394
Radiology
2, 18, 64, 88, 97, 99, 124, 183, 187, 222, 227, 252,
280, 300, 302, 311, 343, 349, 355, 357, 360, 363
Respiratory medicine
8, 14, 21, 35, 36, 37, 43, 45, 55, 56, 58, 61, 72, 79, 91,
99, 111, 113, 157, 164, 196, 217, 225, 272, 279, 298,
304, 327, 341, 349, 356, 370, 380, 384, 396
Immunology
15, 155, 374
Rheumatology
4, 15, 17, 31, 42, 71, 77, 87, 96, 109, 141, 171, 174,
177, 196, 198, 200, 210, 236, 264, 320, 324, 340, 364,
375, 401, 402
Infectious diseases
16, 18, 26, 41, 51, 83, 88, 93, 110, 128, 142, 143, 149,
152, 154, 158, 166, 176, 212, 221, 225, 234, 262, 267,
277, 280, 319, 322, 325, 337, 345, 351, 383, 386, 388
Therapeutics/toxicology
7, 8, 20, 27, 28, 36, 48, 57, 68, 77, 116, 118, 119, 165,
172, 175, 186, 205, 206, 209, 213, 224, 251, 284, 286,
312, 316, 317, 332, 339, 366, 378
Abbreviations
5-HIAA 5'-hydroxyindole acetic
acid
AIIRB angiotensin II receptor
blocker
AAFB acidalcohol fast bacilli
ACE
angiotensin-converting
enzyme
ACTH adrenocorticotrophic
hormone
ADH
antidiuretic hormone
AF
atrial fibrillation
AIDS
acquired immunedeficiency syndrome
AIN
acute interstitial nephritis
AIP
acute intermittent
porphyria
ALA
aminolaevulinic acid
ALT
alanine transaminase
(SGPT)
AML
acute myeloid leukaemia
AMP
adenosine 5'monophosphate
ANA
antinuclear antibody
ANCA antineutrophil cytoplasmic
antibodies
ANF
antinuclear factor
APCKD adult polycystic kidney
disease
APTT activated partial
thromboplastin time
AR
aortic regurgitation
ARDS adult respiratory distress
syndrome
ARVC arrhythmogenic right
ventricular cardiomyopathy
AS
aortic stenosis
ASD
atrial septal defect
ASO
antistreptolysin
AST
aspartate transaminase
(SGOT)
ATN
acute tubular necrosis
AZT
zidovudine
BCG
bacille CalmetteGurin
BIH
benign intracranial
hypertension
BP
blood pressure
BT
bleeding time
BTS
British Thoracic Society
CAH
chronic active hepatitis
CAP
community acquired
pneumonia
CCF
congestive cardiac failure
CFTR cystic fibrosis
transmembrane regulator
(protein)
CML
CMV
COPD
FVC
GBM
GCT
GFR
GH
GHRH
GI
GP
GPI
GT
GTN
Hb
HbSS
HC
HCC
HCM
HCV
HCG
HELLP
HHT
HIT
HIV
HONK
HR
HRT
HS
HSMN
HUS
ICD
ICP
INR
IPF
IVP
IVU
JVP
KCO
LBBB
LDH
LFT
liver function tests
LH
luteinizing hormone
LHON Lebers hereditary optic
neuropathy
LHRH luteinizing hormone
releasing hormone
LMWH low-molecular weight
heparin
LQTS long QT-syndrome
LVEDP left ventricular end-diastolic
pressure
LVH
left ventricular hypertrophy
MAHA microangiopathic
haemolytic anaemia
MAOI monoamine oxidase
inhibitor
MCH
mean cell haemoglobin
MCHC mean cell haemoglobin
content
MCV
mean cell volume
MELAS mitochondrial
encephalopathy, lactic
acidosis, stroke-like
syndrome
MEN
multiple endocrine
neoplasia
MERRF myoclonic epilepsy and red
ragged fibres
MGUS monoclonal gammopathy
of undetermined
significance
MPO
myeloperoxidase
MR
mitral regurgitation
MRA
magnetic resonance
angiography
MRCP magnetic resonance
cholangiopancreatogram
MRI
magnetic resonance
imaging
MRSA methicillin resistant
Staphylococcus aureus
MRV
magnetic resonance
venography
MSH
melanocyte stimulating
hormone
NADPH nicotinamide adenine
dinucleotide phosphate
(reduced)
NAPQI N-acetyl-pbenzoquinoneimine
NARP neuropathy, ataxia, retinitis
pigmentosa
NASH non-alcoholic
steatohepatitis
NIPPV non-invasive positive
pressure ventilation
NSAID non-steroidal antiinflammatory drug
TCAD
TIA
TIBC
TIPSS
TLC
TLCO
TOE
TPA
TPHA
TRH
TSAT
TSH
TT
TTP
U&E
URTI
US
UTI
VDRL
VF
VIP
VMA
VP
VR
VSD
VT
WCC
WPW
tricyclic antidepressant
overdose
transient ischaemic attack
total iron-binding capacity
transjugular intrahepatic
portosystemic shunt
total lung capacity
total lung carbon
monoxide transfer factor
transoesophageal
echocardiography
tissue plasminogen
activator
treponema pallidum
haemagglutination test
thyrotrophin releasing
hormone
transferrin saturation
thyroid stimulating
hormone
thrombin time
thrombotic
thrombocytopenic purpura
urea and electrolytes
upper respiratory tract
infection
ultrasound
urinary tract infection
Venereal Diseases Research
Laboratory test
ventricular fibrillation
vasointestinal polypeptide
vanilyl mandelic acid
variegate porphyria
ventricular rate
ventricular septal defect
ventricular tachycardia
white cell count
WolffParkinsonWhite
(syndrome)
Clinical Cases
Question 1
A 49-year-old male presented to the Accident and
Emergency Department with a one-hour history of severe
central chest pain. He smoked 30 cigarettes per day.
Physical examination was normal. The 12-lead ECG
revealed ST segment elevation in leads V1V4. There
were no contraindications to thrombolysis.
Question 2
A 68-year-old woman presented with pain and tingling in
the left arm when she raised her hands for prolonged
periods. On examination both pulses were palpable in the
upper limbs. The chest X-ray was abnormal. Aortography
was performed with the arms down (2a) and with the
arms up (2b).
2b
2a
Question 3
A 28-year-old male presented with a six-month history of
weight loss of 8 kg, generalized abdominal discomfort
and diarrhoea. On examination he was pale and slim, but
there were no other significant abnormalities.
Investigations are shown.
Hb
WCC
Platelets
MCV
ESR
Sodium
Potassium
Urea
Creatinine
Corrected calcium
phosphate
Alkaline phosphatase
Albumin
IgA
IgG
IgM
IgA anti-endomyosial
antibody
9 g/dl
4.6 ! 109/l
200 ! 109/l
76 fl
38 mm/h
141 mmol/l
4 mmol/l
3 mmol/l
68 "mol/l
2.02 mmol/l
0.8 mmol/l
190 iu/l
38 g/l
<0.1 g/l (NR 0.84.0 g/l)
9.0 g/l (NR 7.018.0 g/l)
0.6 g/l (NR 0.42.5 g/l)
Absent
8
Answer 1
e. Primary coronary angioplasty.
Coronary reperfusion may be achieved with thrombolytic
agents (which promote fibrinolysis) or by coronary
angioplasty. In the UK patients with ST elevation
myocardial infarction are conventionally treated with
thrombolytic agents. Early treatment is crucial to salvage
myocardium and reduce the risk of sudden death and
severe left ventricular dysfunction. Current goals for the
speed of treating with a thrombolytic agent include a
door-to-needle time of 20 minutes or a call-to-needle
time of 60 minutes.
Thrombolytic agents used commonly include
streptokinase, alteplase, tenectoplase and reteplase.
Streptokinase is less favoured compared with the other
thrombolytic agents because it is less effective at restoring
coronary perfusion and is associated with slightly worse
outcomes. The GUSTO I study compared front-loaded
alteplase therapy with streptokinase in patients with ST
EMI. Alteplase was superior to streptokinase in reducing
mortality (1% absolute reduction in mortality at 30 days
with alteplase) and was associated with greater coronary
patency rates. In the GUSTO trial the benefit was
greatest in patients aged under 75 years and those with
anterior myocardial infarction. However, streptokinase is
still used extensively in developing countries and in many
hospitals in the UK. Alteplase, tenectoplase and reteplase
appear to be equally effective. Tenectoplase and reteplase
are easier to administer (as a single bolus).
Answer 2
b. Left cervical rib.
There is mechanical occlusion of the left subclavian artery
on raising the left arm due to a left cervical rib. Cervical
Answer 3
c. Coeliac disease.
Diarrhoea, weight loss, abdominal discomfort and
isolated IgA deficiency are highly suggestive of coeliac
disease. Anti-endomyosial antibodies are highly sensitive
and specific for the diagnosis of coeliac disease. Anti-
Clinical Cases
Question 4
A 53-year-old male was admitted to hospital with a twoweek history of coughing and breathlessness. Apart from
a longstanding history of mild asthma he had been
relatively well with respect to the respiratory tract. He
had been on a skiing trip six weeks previously, without
any respiratory problems.
He had a past history of depression, for which he took
lithium five years ago, and suffered from occasional
tension headaches, for which he took simple analgesia.
On examination he appeared pale and unwell. His
heart rate was 90 beats/min and regular. His blood
pressure measured 160/94 mmHg. The JVP was not
raised. Both heart sounds were normal and the chest was
clear. Abdominal examination did not reveal any
abnormality. Urinalysis demonstrated blood ++ and
protein ++.
Investigations performed in hospital are shown.
Hb
WCC
7 g/dl
11 ! 109/1
(neutrophils 8 ! 109/l,
lymphocytes 2 ! 109/l,
eosinophils 1 ! 109/l)
38 mm/h
134 mmol/l
4.6 mmol/l
48 mmol/l
798 mmol /l
ESR
Sodium
Potassium
Urea
Creatinine
Renal ultrasound
Both kidneys measured 12 cm: there was no
evidence of ureteric obstruction.
Question 5
A 52-year-old male presented with impotence. He had a
four-year history of insulin-dependent diabetes mellitus.
There was no history of headaches or vomiting. The
patient was a non-smoker and did not consume alcohol.
Apart from insulin he took simple analgesia for joint
pains.
Investigations are shown.
What test would you perform to confirm the
diagnosis?
a. MRI scan of the brain.
b. Serum prolactin level.
c. Serum ferritin.
d. Dynamic pituitary function tests.
e. Liver ultrasound.
FBC
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alkaline phosphatase
Albumin
Thyroxine
TSH
Testosterone
Normal
135 mmol/l
4 mmol/l
6 mmol/l
100 mmol/l
12 mmol/l
200 iu/l
220 iu/l
128 iu/l
8 g/l
100 nmol/l
2.6 mu/l
7 nmol/l (NR 1035 nmol/l)
LH
FSH
LHRH test:
LH
FSH
10
Answer 4
d. ChurgStrauss syndrome.
The patient has a past history of asthma, eosinophilia and
rapidly progressive glomerulonephritis. The most probable
diagnosis is ChurgStrauss syndrome. The assumption that
he probably has rapidly progressive glomerulonephritis is
based on the fact that he was well enough to ski six weeks
ago, which would be highly unlikely in a patient with endstage renal disease. The identification of normal-sized
kidneys during renal ultrasonography supports acute rather
than chronic renal failure (Table A).
ChurgStrauss syndrome is a small-vessel multi-system
vasculitis characterized by cutaneous vasculitic lesions,
eosinophilia (usually <2.0 ! 10 9/l), asthma (usually
mild), mononeuritis or polyneuropathy and rarely
glomerulonephritis (10% of cases). Gastrointestinal and
cardiac involvement is recognized.
Pulmonary findings dominate the clinical presentation
with paroxysmal asthma attacks and presence of fleeting
pulmonary infiltrates. Asthma is the cardinal feature and may
be present for years before overt features of a multi-system
vasculitis become apparent. Skin lesions, which include
purpura and cutaneous and subcutaneous nodules, occur in
up to 70% of patients. Gastrointestinal complications include
mesenteric ischaemia or gastrointestinal haemorrhage.
Cardiac involvement is characterized by myo-pericarditis.
The diagnosis is usually clinical and supported by the
presence of a necrotizing granulomatous vasculitis with
extravascular eosinophilic infiltration on lung, renal or sural
biopsy. The American College or Rheumatology criteria
for the diagnosis of ChurgStrauss syndrome are tabulated
(Table B). Serum ANCA (MPO subset) are elevated but
this finding is also present in microscopic polyangitis.
The prognosis of untreated CSS is poor, with a
reported five-year survival rate of only 25%. Corticosteroid
therapy has been reported to increase the five-year
survival rate to more than 50%. In patients with acute
vasculitis the combination of cyclophosphamide and
prednisone is superior to prednisolone alone.
Although rapidly progressive glomerulonephritis also
features in the answer options section, the presence of
asthma and eosinophilia make ChurgStrauss syndrome
the best answer. It is worth noting however, that rapidly
progressive glomerulonephritis may also rarely be
Answer 5
c. Serum ferritin.
The clinical features and the data are consistent with the
diagnosis of idiopathic haemochromatosis. The insulindependent diabetes mellitus suggests pancreatic
Clinical Cases
common endocrine deficiency in hereditary haemo chromatosis. Primary hypogonadism due to testicular
iron deposition may occur with this disorder but is much
less common than secondary hypogonadism.
In the context of the question, a serum ferritin level
>500 mg/l would be diagnostic of primary haemo chromatosis. Alcohol-related liver disease, chronic viral
hepatitis, non-alcoholic steatohepatitis and porphyria
cutanea tarda also cause liver disease and increased serum
11
Question 6
A 38-year-old English male was investigated after he was
found to have an abnormal liver function test during a
health insurance medical check. He worked in an
information technology firm. Apart from occasional
fatigue he was well. He consumed less than 20 units of
alcohol per week. The patient had only travelled out of
Europe twice and on both occasions he had been to
North America. He took very infrequent paracetamol for
aches and pains in his ankles and knees. There was no
history of hepatitis or transfusion or blood products. He
had been married for 5 years. Systemic enquiry revealed
infrequent episodes of loose stool for almost 4 years.
On examination he appeared well. There were no
stigmata of chronic liver disease. Abdominal examination
revealed a palpable liver edge 3 cm below the costal
margin. There were no other masses. Examination of the
central nervous system was normal.
Investigations were as shown.
What is the most probable diagnosis?
a. Autoimmune hepatitis.
b. Primary sclerosing cholangitis.
c. Primary biliary cirrhosis.
d. Haemochromatosis.
e. Wilsons disease.
Question 7
A 17-year-old girl presented with jaundice three days
after having taken a paracetamol and alcohol overdose
during an argument with her boyfriend.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
AST
ALT
Alkaline phosphatase
Bilirubin
Albumin
Total cholesterol
Triglyceride
Blood glucose
Ferritin
Serum Fe
TIBC
Serum
caeruloplasmin
24-hr urine copper
IgG
IgA
IgM
Anti-nuclear
antibodies
Smooth muscle
antibodies
Antimitochondrial
antibodies
Hep B sAg
Hep C virus
antibodies
Abdominal ultrasound
12.6 g/dl
8 ! 109/l
210 ! 109/l
90 fl
136 mmol/l
4.1 mmol/l
6 mmol/l
100 mmol/l
60 iu/l (NR 1040 iu/l)
78 iu/l (NR 530 iu/l)
350 iu/l (NR 25100 iu/l)
22 mmol/l (NR 217 mol/l)
38 g/l (NR 3448 g/l)
5.2 mmol/l
3.1 mmol/l
6 mmol/l
256 mg/l (NR 15250 mg/l)
28 mmol/l
(NR 1432 mmol/l)
50 mmol/l
(NR 4080 mmol/l)
Slightly reduced
Slightly elevated
19 g/l (NR 718 g/l)
4.2 g/l (NR 0.84.0 g/l)
5.0 g/l (NR 0.42.5 g/l)
Positive 1/32
Not detected
Not detected
Not detected
Not detected
Normal
12
Answer 6
b. Primary sclerosing cholangitis.
This is a relatively difficult question. The history of loose
stool is crucial in making the diagnosis in this particular
case in the absence of data from the ERCP. Diarrhoea
and biochemical evidence of cholestasis (alkaline
phosphatase greater than transaminases) should lead to
the clinical suspicion of primary sclerosing cholangitis
(PSC). The aetiology of PSC is unknown but
immunological destruction of intra- and extra-hepatic
bile ducts is the main pathological feature. 90% of PSC is
associated with inflammatory bowel disease, particularly
ulcerative colitis, and hence the importance of the
intermittent diarrhoea. Ulcerative colitis is the most
frequent association with primary sclerosing cholangitis.
A raised alkaline phosphatase level in a patient with
ulcerative colitis (in the absence of bone disease) should
raise the possibility of PSC. The frequency of PSC is
inversely proportional to the severity of ulcerative colitis.
Other associations of PSC include coeliac disease.
Patients with PSC may be asymptomatic at pre sentation but can present with advanced liver disease.
Fatigue and pruritus are common complaints as with the
other cholestatic disorders. Approximately one-fifth of
the patients also complain of right upper quadrant pain.
The diagnosis is confirmed with ERCP that shows
strictures within biliary ducts. Complications are those of
chronic cholestasis, notably statorrhoea, fat-soluble
vitamin malabsorption, large biliary strictures, cholangitis,
cholangiocarcinoma and colonic carcinoma. There are no
effective pharmacological agents that greatly retard the
Answer 7
d. Prothrombin time.
Clinical Cases
13
Question 8
A 16-year-old girl presented with an 18-month history of
progressive breathlessness on exertion. On admission she
was breathless at rest. She had a past history of acute
myeloid leukaemia, for which she had been treated with
six courses of chemotherapy, followed by bone marrow
transplantation supplemented with radiotherapy and
cyclophosphamide treatment five years ago. She was
regularly followed up in the haematology clinic. Lung
function tests three years ago revealed an FEV1/FVC
ratio of 80%. On examination she was breathless at rest,
and cyanosed. There was no evidence of clubbing.
Auscultation of the lung fields revealed fine inspiratory
Question 9
A 21-year-old man was admitted to the intensive care
unit after a road traffic accident during which he suffered
Sodium
Potassium
Creatinine
Urea
Thyroxine
TSH
Serum cortisol
128 mmol/l
3.6 mmol/l
81 mmol/l
4 mmol/l
30 nmol/l
2 mu/l
1000 nmol/l
(NR 170700 nmol/l)
Question 10
A 40-year-old woman with dilated cardiomyopathy is
seen in the heart failure clinic complaining of a persistent
dry cough. Her exercise capacity is 1 mile while walking
on the flat. She can climb two flights of stairs without
difficulty. Her medication consists of ramipril 10 mg
daily, aspirin 75 mg daily, carvedilol 6.25 mg twice daily
and frusemide 40 mg daily. On examination her heart
rate is 70 beats/min and her blood pressure is
100/60 mmHg. Both heart sounds are normal and the
chest is clear.
14
Answer 8
d. Cyclophosphamide-induced lung fibrosis.
The patient presents with progressive symptoms
associated with a restrictive lung defect and a low
transfer factor. The findings are most consistent with
cyclophosphamide-induced pulmonary fibrosis.
Cyclophosphamide-induced lung fibrosis is rare and is
most likely to occur in patients who have had concomitant
pulmonary radiation therapy or have taken other drugs
associated with pulmonary toxicity. The disorder usually
occurs in patients who have been taking low doses for
relatively prolonged periods (over six months) and
presents several years after cessation of the drug and
hence the deterioration of symptoms with time. The
disorder has a relentless progression and inevitably results
in terminal respiratory failure. It is minimally responsive
to corticosteroids. Fine end-inspiratory crackles and
clubbing do not usually form part of the clinical
spectrum.
The diagnosis is clinical. Chest X-ray reveals reticulonodular shadowing of the upper zones. Lung function
tests demonstrate a restrictive lung defect. Lung biopsy is
not helpful.
Cyclophosphamide per se is not toxic to the lungs;
however, it is metabolized in the liver to toxic
metabolites such as hydroxycyclophosphamide, acrolein
and phosphoramide mustard, which are responsible for
pulmonary damage. Genetic factors may play a role in
determining which individuals develop pulmonary
fibrosis after exposure to the drug.
Cyclophosphamide
Busulphan
Methysergide
Methotrexate
Amiodarone
Nitrofurantoin
Minocycline
Ethambutol
Penicillamine
Answer 9
c. Syndrome of inappropriate ADH secretion.
The patient has a low sodium concentration in the
context of a head injury. The thyroid function tests
suggest the possibility of a secondary hypothyroidism, i.e.
a low TSH and a low thyroxine concentration, and hence
the possibility of damage to the pituitary. However, the
very high cortisol level indicates that pituitary function is
probably normal (high ACTH production secondary to
stress) and therefore the abnormal thyroid function tests
represent sick euthyroid syndrome. Low T4, T3 and TSH
levels are recognized in critically ill patients with nonthyroid illnesses. Originally such patients were thought to
Clinical Cases
15
Answer 10
b. Substitute ramipril with losartan.
The patient is in NYHA functional class II with respect to
her symptoms. She is on the correct dose of ramipril and
is appropriately being treated with a beta-blocker. The
dry cough that the patient is experiencing is almost
certainly the side-effect of ramipril. Angiotensinconverting enzyme inhibitors are associated with a dry
cough in 1520% of patients owing to increases in
circulating bradykinin levels. In such patients the ACE
inhibitor should be stopped and substituted with an
angiotensin receptor blocker such as losartan. The
efficacy of losartan compared with an ACE inhibitor
(captopril) was fully evaluated in the ELITE II study.
Question 11
A 60-year-old male was admitted to the coronary care unit
with central chest pain. Physical examination was normal.
The blood pressure measured 110/68 mmHg. The 12lead ECG was normal and the troponin T level was not
raised. The blood sugar was normal. The cholesterol level
on admission was 6.3 mmol/l. The patient underwent an
exercise stress test that was positive. A subsequent
coronary angiogram revealed an 80% stenosis in the
proximal aspect of the left anterior descending artery that
was successfully treated with a coronary artery stent.
Echocardiography revealed a normal-sized left ventricle
with good systolic function. The patient was discharged
home on aspirin 75 mg daily, clopidogrel 75 mg daily and
simvastatin 40 mg daily. He had been completely pain free
Question 12
A 62-year-old obese male with a known medical history
of hypertension presented with generalized headaches
and lethargy. He was taking bendroflumethiazide,
2.5 mg once daily for hypertension. The only other past
medical history included a left-sided deep vein
thrombosis six months previously. There was no history
of alcohol abuse or smoking.
What is the cause of his symptoms?
a. Obstructive sleep apnoea.
b. Gaissbocks syndrome.
c. Polycythaemia rubra vera.
d. Renal cell carcinoma.
e. Chronic hypoxaemia.
20 g/dl
88 fl
15 ! 109/l
500 ! 109/l
0.66 l/l
141 mmol/l
4.2 mmol/l
8 mmol/l
110 "mol/l
0.44 mmol/l
16
Answer 11
b. Ramipril.
The Heart Outcomes Prevention Evaluation Study
(HOPE) evaluated the role of angiotensin-converting
enzyme inhibitors (ramipril) in populations at high risk of
cardiovascular events without any evidence of left
ventricular dysfunction. The study assessed 9297 highrisk patients, defined as (1) aged >55 years; (2) history of
coronary artery disease, stroke or peripheral vascular
disease; or (3) diabetes mellitus and at least one risk
factor for coronary artery disease including hypertension,
increased total cholesterol, smoking and microalbuminuria. The patients were randomized to ramipril
10 mg daily or placebo. The primary outcome was a
combined endpoint of myocardial infarction, stroke or
cardiovascular death. The mean follow up was five years.
Patients treated with ramipril had a 14% event rate of
the combined morbidity and mortality endpoint whereas
placebo-treated patients had a 17.8% event rate. The 21%
decrease in events was seen in all pre-specified groups,
indicating that ACE inhibitor therapy with ramipril
significantly reduces morbidity and mortality in a high-
Answer 12
c. Polycythaemia rubra vera.
The high Hb is suggestive of polycythaemia. There is
nothing in the history to indicate a secondary cause, e.g.
hypoxia, renal carcinoma, adrenal tumour. Although he
was obese, there was nothing else in the history to allow
the diagnosis of obstructive sleep apnoea.
The high white cell count and platelet count favour
primary polycythaemia (polycythaemia rubra vera).
Headache and lethargy are common symptoms of
polycythaemia rubra vera. Polycythaemia rubra vera
causes lethargy due to hyperviscosity and raised
interleukin-6 levels. Other classic features include visual
disturbance, abdominal pain and pruritus.
Clinical Cases
17
Question 13
The ECG below was taken from a young boy who
experienced syncope. On examination he had a systolic
murmur.
13
Question 14
An 18-year-old male was admitted with sudden sharp
pain in the left infrascapular area. He was not breathless
on mild exertion. He was usually fit and well. He was an
occasional smoker. There was no history of respiratory
problems. On examination there was reduced air entry at
the left lung base. The oxygen saturation on air was 96%.
The CXR revealed a left-sided pneumothorax. There was
less than 2 cm rim of air between the edge of the lung
and the ribs.
18
Answer 13
c. Pulmonary stenosis.
The patient has a systolic murmur. The ECG shows
right axis deviation, a dominant R wave in V1 and
relatively prominent S waves in V5 and V6. The sum of
the R in V1 and in V6 is > 1.25 mV which indicates right
Answer 14
e. Allow home and repeat CXR after a week.
The question tests knowledge of the guidelines for the
management of pneumothorax set by the British
Thoracic Society.
The patient has a relatively small pneumothorax
(<2 cm rim of air between lung and ribs) with minimal
symptoms and can walk slowly without becoming
breathless. There is no history to suggest chronic lung
disease. In such a case no treatment is recommended and
the patient may be discharged. Patients are advised not to
over-exert themselves and to return if they develop
breathlessness. A repeat CXR is recommended after a
week to ensure that the pneumothorax has resolved.
If the patient has a pneumothorax >2 cm rim of air
between the lung and the chest wall on the CXR, or has
pain or dyspnoea at rest or on minimal exertion then
aspiration is recommended. If aspiration is successful the
patient is allowed home and reviewed with repeat CXR in
one week. If aspiration is unsuccessful a second attempt is
made at aspiration. If the lung still remains deflated then
insertion of a chest drain is recommended.
In patients with chronic lung disease the following
criteria should be used to decide whether aspiration or
insertion of a chest drain is the first procedure of choice.
Patients aged <50 years, who are relatively asymptomatic
and have a small pneumothorax, should be aspirated and
observed in hospital for 24 hours (assuming aspiration is
successful). If aspiration is unsuccessful in this group of
patients then insertion of a chest drain is advised. In
patients aged >50 years, with symptoms and with larger
pneumothoraces (>2 cm air between lung and chest wall)
a chest drain is necessary.
Management of pneumothorax
Spontaneous
pneumothorax
Yes
No
Allow home
Repeat CXR in
710 days
Aspirate
Successful
If unsuccessful,
repeat aspiration.
If still unsuccessful,
insert chest drain
Clinical Cases
19
Question 15
A 44-year-old was seen in the rheumatology clinic in
December complaining of malaise, joint pains and
tingling in the hands and feet. She had been diagnosed as
having Raynauds phenomenon several years ago. The
patient had consulted several doctors for intermittent
malaise and joint pains. There was no history of night
sweats, dyspnoea, or problems with swallowing. The
patient took paracetamol on a PRN basis for joint pains.
On examination she had palpable purpura on the
thighs and arms. There was no obvious evidence of joint
swelling. Abdominal examination revealed hepatomegaly
palpable 3 cm below the costal margin. Neurological
examination revealed decreased sensation in the hands
and feet. The blood pressure was 110/80 mmHg.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
Rheumatoid factor
C3
C4
Hep C Virus AB
Hep B sAg
Urinalysis
10 g/dl
9 ! 109/l
490 ! 109/l
90 mm/h
139 mmol/l
4.2 mmol/l
9 mol/l
140 "mol/l
15 mmol/l
90 iu/l
122 iu/l
33 g/l
IgM Positive (titre 1/640)
0.2 g/l (NR 0.551.2 g/l)
0.09 g/l (NR 0.20.5 g/l)
Positive
Negative
Blood +
Protein ++
Question 16
A 30-year-old businessman developed sudden onset of
fever, sore throat, diarrhoea and myalgia. Over the next
three days he noticed a widespread rash affecting his face,
trunk, palms and soles. He was usually fit and well and
had only consulted his GP once in the past 10 years for a
typhoid vaccine before travelling to India. Over the past
four months he had established business links with a
company in Thailand and had visited the country on
three occasions. His last visit to Thailand was eight weeks
previously. He was married with two young children. He
was not taking any medications and had no history of
drug allergy.
Hb
WCC
Platelets
Monspot test
Sodium
Potassium
Urea
Creatinine
Bilirubin
ALT
AST
13 g/dl
11 ! 109/l
(neutrophils 6 ! 109/l,
lymphocytes 4 ! 109/l)
130 ! 109/l
Negative
135 mmol/l
3.8 mmol/l
6 mmol/l
80 "mol/l
23 "mol/l
45 iu/l
49 iu/l
20
Answer 15
d. Pegylated interferon-# plus ribavarin.
This is a difficult question; however, the clue lies in the
fact that the patient has evidence of current or previous
infection with hepatitis virus and has Raynauds
phenomenon, palpable purpura (vasculitis), neuropathy
and hypocomplementaemia. The diagnosis is consistent
Types of cryoglobulinaemia
Type
I
Immunoglobulins
Monoclonal immunoglobulin
II
III
Associated condition(s)
Multiple myeloma
Waldenstroms macroglobulinaemia
Hepatitis C and hepatitis B
Chronic inflammation
Hepatitis C
Lymphoproliferative disease
Answer 16
a. Acute HIV infection.
The main differential diagnosis is between infectious
mononucleosis, CMV infection and acute HIV infection.
All three are associated with sore throat, rash, fever and
atypical lymphocytes. Mouth ulcers are usually absent in
Infections mononucleosis
Over a few days
Absent usually
Usually secondary to ampicillin
Unusual
Prominent
May be elevated
Frequent (90%) and numerous
Common
Common
HIV infection
Abrupt
Often present
Part of HIV seroconversion
Common
Mild
Elevated or suppressed
Present in 50%
Common
Common
Clinical Cases
21
Question 17
A 69-year-old woman with rheumatoid arthritis
presented with swollen ankles. She was diagnosed as
having rheumatoid arthritis over 18 years ago and had
been relatively well controlled on non-steroidal antiinflammatory drugs until six months ago, when her joint
pains and swelling required the addition of penicillamine
to control her symptoms. The patient had a past history
of hypertension, for which she took bendroflumethiazide.
On examination she had symmetrical joint deformities
consistent with rheumatoid arthritis. The heart rate was
90 beats/min and irregular. Her blood pressure
measured 140/90 mmHg. The JVP was not raised. Both
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Bilirubin
Alkaline phosphatase
Albumin
Urinalysis
11 g/dl
5 ! 109/l
190 !109/l
134 mmol/l
4.5 mmol/l
6 mmol/l
70 "mol/l
11"mol/l
100 iu/l
26 g/l
Protein $$$
Question 18
A 59-year-old female presented with weakness of both
legs. An MRI scan of the spine is shown (18).
What is the cause of her symptoms?
a. Syringomyelia.
b. Paravertebral abscess.
c. Thoracic disc prolapse.
d. Metastatic spinal cord compression.
e. Extradural meningioma.
18
22
Answer 17
a. Stop penicillamine.
The patient has heavy proteinuria and gives a relatively
recent history of onset of swollen ankles shortly after
starting penicillamine. The most likely diagnosis is
penicillamine-induced membranous nephropathy, which
usually occurs within 612 months of the initiation of
drug therapy. Proteinuria resolves in virtually all cases
after stopping the drug but this may take several months.
Other causes of heavy proteinuria secondary to
membranous nephropathy in rheumatoid arthritis include
gold therapy.
Renal amyloidosis is a recognized cause of heavy
proteinuria complicating chronic rheumatoid arthritis.
While it is possible that the patient may have renal
amyloidosis, the relationship of the proteinuria to the
Answer 18
d. Metastatic spinal cord compression.
This is a T2 weighted image that shows evidence of cord
compression from a collapsed thoracic vertebra. The
T1 weighted
T2 weighted
Water/vitreous/CSF
Fat
Muscle
Air
Fatty bone marrow
Brain white matter
Brain grey matter
black
white
grey
black
white
light grey
grey
T1 Weighted Imaging
T2 Weighted Imaging
Clinical Cases
23
Question 19
A 16-year-old girl presented with intermittent episodes of
lower colicky abdominal pain for six months. In the
interim she had lost almost 6.4 kg in weight. Her
appetite was not impaired. There was no history of
diarrhoea, although the patient had complained of
intermittent constipation and abdominal bloating. The
patient was English in origin. She had no family history
of note. She had last travelled abroad to Barbados on
holiday a year ago. The only other past medical history
included a short episode of painful ankles associated with
circular erythematous skin lesions.
On examination she was thin and mildly clubbed. The
heart rate was 90 beats/min and regular. The blood
pressure measured 100/55 mmHg. There was evidence
Hb
WCC
Platelets
ESR
U&E
AST
ALT
Bilirubin
Albumin
Stool culture
Chest X-ray
10 g/dl
11 ! 109/l
498 ! 109/l
55 mm/h
Normal
20 iu/l
22 iu/l
12 "mol/l
33 g/l
Negative
Minor calcification, a few
perihilar nodes
Question 20
A 24-year-old patient was admitted to hospital with acute
asthma for the fourth time in the past six years. The
asthma was usually precipitated by a coryzal illness or
exposure to allergens. There was no other past medical
history of note. The patient usually inhaled ventolin as
required, salmeterol inhaler twice daily, becotide inhaler
twice daily and had recently been prescribed
aminophylline 450 mg twice daily.
On admission she had a bilateral wheeze. The PEFR
was 200 l/min. The oxygen saturation on air was 86%
and on 28% oxygen it was 94%. The chest X-ray revealed
hyperinflated lungs. The patient was commenced on
nebulized bronchodilators, prednisolone 30 mg daily and
amoxycillin. The following day she developed a rash
therefore the amoxycillin was substituted with
erythromycin.
24
Answer 19
d. Crohns disease.
Abdominal cramps, weight loss, erythema nodosum
(raised circular skin lesions) and raised inflammatory
markers are highly suggestive of inflammatory bowel
disease. Tenderness in the right iliac fossa points to the
possibility of terminal ileal disease and hence Crohns
disease, although this is a non-specific feature since many
conditions may cause right iliac fossa tenderness.
Diarrhoea is not always a prominent feature in Crohns
disease.
Answer 20
d. Theophylline toxicity.
The question tests the candidates knowledge about
drugs interacting with aminophylline and inhibiting its
metabolism. With respect to the treatment of lower
respiratory tract infections, both quinolone and
macrolide antibiotics (e.g. ciprofloxacin, erythromycin
respectively) inhibit aminophylline metabolism.
Features of theophylline toxicity include nausea,
vomiting, hypotension, cardiac arrhythmias and seizures.
Other drugs that inhibit the metabolism of theophylline
include cimetidine, propranolol, allopurinol,
thiobendazole and the contraceptive pill. In the context
Clinical Cases
25
Question 21
A 64-year-old Asian man presented with a six-week
history of dyspnoea and wheeze. For two weeks he had
also developed a cough productive of yellow sputum and
fever. There was no history of night sweats. The patient
had not travelled abroad for over 20 years.
Investigations are shown.
Hb
WCC
Platelets
ESR
Biochemistry
Chest X-ray
Sputum culture
13 g/dl
11 ! 109/l
(neutrophils 8 ! 109/l,
lymphocytes 1 ! 10 9/l
eosinophils 2 ! 109/l)
258 ! 109/l
30 mm/h
Normal
Diffuse perihilar infiltrates
Negative
Question 22
A 78-year-old patient presented with sudden onset of
severe breathlessness. He had a history of ischaemic heart
disease and had suffered two myocardial infarctions in the
past three years. He had an 11-year history of
hypertension that had been well controlled. He was a
non-smoker. His medication consisted of aspirin,
ramipril, atenolol, bendroflumethiazide and simvastatin.
On examination he had a heart rate of 146 beats/min.
The pulse was irregular. The blood pressure was
100/68 mmHg. Both heart sounds were quiet.
Auscultation of the lungs revealed widespread inspiratory
crackle and expiratory wheeze. The ECG showed atrial
Question 23
An 81-year-old man with non-insulin-dependent diabetes
mellitus was found unconscious by his carer. Blood tests
performed on admission to hospital are shown.
Sodium
Potassium
Urea
Creatinine
Glucose
153 mmol/l
5.4 mmol/l
40 mmol/l
310 "mol/l
60 mmol/l
26
Answer 21
c. Allergic bronchopulmonary aspergillosis.
The history of cough sputum, eosinophilia and perihilar
infiltrates is most consistent with allergic broncho pulmonary aspergillosis in the context of the history
given. There is no drug history to indicate an
eosinophilic pneumonitis, nor a history of travel to the
tropics to suggest tropical pulmonary eosinophilia.
ChurgStrauss syndrome is unlikely in the absence of
vasculitis, neuropathy or renal involvement. Asthma does
not cause pulmonary infiltrates. Tuberculosis does not
usually cause eosinophilia.
The diagnosis of allergic bronchopulmonary
eosinophilia is made in patients with asthma, proximal
Answer 22
b. IV amiodarone.
The patient has rapid atrial fibrillation in the context of
ischaemic heart disease and has evidence of pulmonary
oedema. One has to assume that left ventricular function
is impaired to answer this question since it is highly
unlikely that a heart rate of 146 beats/min would cause
left ventricular failure in a patient with normal left
ventricular function. Amiodarone, dofetolide and
flecainide are capable of restoring sinus rhythm. Of these
amiodarone is the least negatively inotropic.
Flecainide is relatively contraindicated in patients with
known coronary artery disease. Dofetolide is a class III
Answer 23
b. IV saline (0.9%), IV insulin and subcutaneous
heparin.
The patient has a hyperosmolar non-ketotic diabetic
coma (HONK). The fluid of choice is saline. The
strength of saline used initially is always 0.9% since it is
effective at restoring volume and has a lower risk of
causing large drops in plasma osmolality, a risk factor for
Clinical Cases
27
Question 24
A 13-year-old girl was admitted with a two-day history of
lower abdominal pain and blood-stained diarrhoea. Three
days later, she developed pains in her ankles and right
elbow and felt nauseous. Positive findings on
examination were a purpuric rash affecting the arms and
legs, periorbital oedema and a blood pressure of
150/95 mmHg.
Investigations are shown.
Hb
WCC
Platelets
MCV
ESR
PT
APTT
Sodium
Potassium
Creatinine
Urinalysis
10 g/dl
12 ! 109/l
136 ! 109/l
70 fl
35 mm/h
13 s (control 13 s)
34 s (control 36 s)
138 mmol/l
5.9 mmol/l
130 "mol/l
Blood ++
Protein ++
Question 25
A 39-year-old African male was referred to the blood
pressure unit with persistent blood pressure readings of
140150/9095 mmHg over the past six months. He
was a non-smoker and consumed 4 units of alcohol per
week. The patient weighed 89 kg and measured 1.7 m.
Physical examination was normal with the exception of a
blood pressure reading of 150/92 mmHg.
Investigations are shown.
Sodium
Potassium
Urea
Glucose
Total cholesterol
Triglycerides
12-lead ECG
Urinalysis
136 mmol/l
4.2 mmol/l
5 mmol/l
4.1 mmol/l
4.1 mmol/l
1.2 mmol/l
Sinus rhythm
Right axis deviation
Protein
0
Blood
0
Cells
0
28
Answer 24
1: c. HenochSchnlein purpura.
2: a. Skin biopsy.
b. Renal biopsy.
The combination of lower abdominal pain, bloody
diarrhoea, purpuric rash and nephritis in a young girl
are highly suggestive of HenochSchnlein purpura.
The condition is a small-vessel vasculitis that occurs
most commonly in children aged 415 years. It is
characterized by gastrointestinal symptoms which
comprise abdominal pain, diarrhoea, and rectal
bleeding, flitting arthralgia affecting large joints, a
purpuric rash characteristically affecting the lower limbs
and buttocks and an acute nephritis. Complications
include intestinal perforation, haemorrhage and
intussusception and acute renal failure.
Answer 25
c. Low-salt diet, regular exercise.
The patient is young and has mild hypertension on
presentation. He does not have any other risk factors for
cardiovascular disease or evidence of secondary endorgan damage as a result of the raised blood pressure.
In this particular case the initial management plan
should include a low-salt diet, regular exercise and
weight loss. The patient should be observed carefully
for up to a year and should only be commenced on
pharmacological therapy if the blood pressure remains
above 140/85 mmHg.
If treatment is indicated after a year, the drugs of
choice are thiazide diuretics or calcium channel
blockers. Angiotensin-converting enzyme inhibitors and
beta-blockers are not particularly effective as
monotherapy because both drugs act by suppressing
renin levels, which are already relatively low in Afro-
Clinical Cases
29
Question 26
26b
26a
Hb
WCC
Platelets
Sodium
Potassium
Creatinine
PT
Fibrinogen degradation
products
11 g/dl
24 ! 109/l
30 ! 109/l
135 mmol/l
5 mmol/l
156 mol/l
48 s (control 13 s)
>25,000
On examination, he was confused. He had a widespread rash (26a). His left eye is shown (26b). The heart
rate was 120 beats/min; the blood pressure was
unrecordable. There was no evidence of nuchal rigidity,
and Kernigs sign was negative. There was no focal
neurological deficit. Examination of the cardiovascular,
respiratory and gastrointestinal tract was normal.
Investigations are shown.
Which single investigation would you perform next?
a. Blood cultures.
b. CT scan brain.
c. CSF for microscopy and culture.
d. Chest X-ray.
e. Throat swab for culture.
Question 27
A 36-year-old woman is seen in the Accident and
Emergency Department after having taken 40 paracetamol
tablets with a quarter-bottle of vodka six hours earlier,
following an argument with her husband. She was
nauseous, but had not vomited. There was no past medical
history of note. A physical examination was normal.
1. List two immediate management steps from the
following list:
a. Gastric lavage.
b. IV dextrose 5%.
c. Oral activated charcoal.
d. Fresh-frozen plasma.
e. IV sodium bicarbonate.
f. IV N-acetyl cysteine.
g. IV flumazenil.
h. IV vitamin K.
i. IV saline (0.9%).
j. IV prochlorperazine.
138 mmol/l
3.9 mmol/l
5.1 mmol/l
18 mmol/l
15 s (control 15 s)
200 mg/l
30
Answer 26
a. Blood cultures.
The eye demonstrates a conjunctival haemorrhage. The
rash is a necrotic purpuric rash, which is typical of
meningococcal septicaemia. The patient has septic shock
and requires immediate therapy. The recognition that he
has meningococcal septicaemia is important for the choice
of antibiotics that you will use. In medical emergencies, the
reader must be familiar with the drugs that are used in that
particular emergency, but not necessarily the dosage, as
this can be found in the British National Formulary or the
equivalent. Although most Neisseria meningitidis strains
are sensitive to benzyl penicillin, it is prudent to cover the
patient with additional cephalosporin or aminoglycoside
antibiotic therapy until the sensitivities of the organism are
known. The circulation must be restored to prevent
hypoperfusion of vital organs, particularly the kidneys. The
presence of low platelets, high fibrinogen degradation
products and abnormal clotting is suggestive of DIC,
which should be treated with fresh-frozen plasma to
prevent haemorrhage.
Neisseria meningitidis, the causal Gram-negative
diplococcus, can be cultured from the CSF in over 80% of
cases with evidence of neurological involvement. However,
Answer 27
1. c. Oral activated charcoal.
f. IV N-acetyl cysteine.
2. c. Arterial pH.
The drug should be given within 810 hours of ingestion
of the overdose, and continued while the liver function is
abnormal. It is useful because it replenishes cellular
glutathione stores and reduces oxidative damage caused
by the toxic metabolite, NAPQI. An alternative to this is
methionine. Gastric lavage is useful if performed within 1
hour of the overdose.
The patient has taken 20 g of paracetamol. An
ingestion of 15 g is considered potentially serious in most
patients. The toxicity of paracetamol is related to the
production of a toxic metabolite of paracetamol. This is
NAPQI, which usually is immediately conjugated with
glutathione and excreted. In paracetamol overdose, the
toxic metabolite is produced in excess and depletes
Clinical Cases
31
Question 28
A 52-year-old female was brought
into the Accident and Emergency
Department after being found
collapsed outside a public house.
There was no one accompanying
her, and there was no information
regarding her next of kin.
On examination, she was very
drowsy and had a Glasgow coma
score of 6 out of 15. Her pupils
were 10 mm each and reacted very
sluggishly to light. On attempting to
examine her fundi, she was noted to
have coarse nystagmus, but a clear
view of her fundi did not
demonstrate any abnormalities. The tone in all her limbs
was increased and her reflexes were brisk. The plantars
were both upgoing. The heart rate was 135 beats/min,
and regular. The blood pressure was 105/60 mmHg. The
respiratory rate was 20/min. Examination of the
precordium and lung fields was normal, but examination of
the abdomen revealed a firm palpable mass 4 cm above the
symphysis pubis. The patient was catheterized and drained
of 2 litres of urine. Investigations are shown.
Shortly after the lumbar puncture, the patient had a
generalized seizure which lasted 30 s. The attending nurse
raised concerns about an arrhythmia on the cardiac
monitor, and a 12-lead ECG was performed (28).
28
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
Calcium
Phosphate
Bilirubin
AST
Gamma GT
Alkaline phosphatase
Plasma osmolality
Urine osmolality
Blood glucose
Chest X-ray
Skull X-ray
Brain CT scan
Lumbar puncture:
CSF pressure
Cells
Protein
Glucose
ECG
14 g/dl
12 ! 109/l
221 ! 109/l
88 fl
144 mmol/l
4.0 mmol/l
13 mmol/l
100 mol/l
20 mmol/l
108 mmol/l
2.4 mmol/l
1.3 mmol/l
12 mol/l
33 iu/l
28 iu/l
120 iu/l
333 mOsm/l
120 mOsm/l
6 mmol/l
Normal-sized heart and
clear lung fields
Normal; no fractures seen
Normal
100 mmH2O
3/mm3
0.35 g/l
3 mmol/l
Sinus tachycardia; right
axis deviation
32
Answer 28
1. The plasma osmolality is calculated by the formula
2 ([Na] + [K]) + [Urea] + [Glucose]. In this case,
the calculated plasma osmolality is 315 mOsm/l.
2. The measured plasma osmolality is higher than the
calculated one, suggesting that the patient has
ingested something which has not been measured,
but has the effect of increasing the plasma
osmolality. The most likely possibility in this case is
alcohol ingestion. Although lithium contributes to
plasma osmolality, it would be very unusual for the
lithium concentration to be high enough to
increase the plasma osmolality by 18 mOsm/l,
considering that a serum lithium concentration of
2.5 mmol/l causes dangerous toxicity.
Clinical Cases
33
Question 29
29a
29b
29c
Hb
18 g/dl
WCC
10 ! 109/l
Platelets
300 ! 109/l
ESR
110 mm/h
Sodium
140 mmol/l
Potassium
3.1 mmol/l
Creatinine
120 mol/l
Calcium
2.6 mmol/l
Albumin
36 g/l
Chest X-ray (29b)
CT scan of abdomen (29c)
Urinalysis
Blood +++
Protein +
Bilirubin 0
34
Answer 29
1. i. Bone metastases.
ii. PTH-related peptide secretion from a right-sided
renal carcinoma.
2. Right-sided renal carcinoma.
3. i. Renal angiography.
ii. Renal venography and inferior vena cavogram.
iii. Bone scan to detect bony metastases.
4. Surgical removal of the right kidney if his general
health will allow.
This patient presents with anorexia, weight loss, and a
fever that may represent sepsis or malignancy. The right
loin tenderness and haematuria are suggestive of renal
involvement. The chest X-ray reveals multiple opacities in
both lungs which represents a cannon-ball metastases
from the right kidney. CT scan of the abdomen reveals a
carcinoma of the right kidney which is invading the
inferior vena cava; hence the scrotal and lower-limb
oedema. Hypernephroma characteristically presents with
a triad of haematuria, loin pain and swelling. Haematuria
is present in 50% of cases, but pain and swelling are less
frequent. Non-specific symptoms such as anorexia,
weight loss and fatigue may be present for several
Question 30
An 84-year-old female was referred to clinic with increasing
forgetfulness. Her GP had commenced her on a small dose
of haloperidol for agitation eight months ago. According to
the staff at the nursing home where she resided, she had
become increasingly confused over the past few months
and more recently had developed odd movements affecting
her face, arms and legs. Her GP had reviewed her two
weeks previously and stopped the haloperidol; however, she
remained confused and the movement disorder had
become much more pronounced. She was not taking any
other medication.
On examination, she had a mental test score of 4/10.
Her vital parameters were normal. She exhibited
intermittent yawning motions of the mouth, with
occasional tongue protrusion. There were semi-purposeful
Question 31
A 33-year-old Iranian male was investigated for a sixmonth history of general malaise, weight loss, fever, pain
in his knees, ankles and wrists and a sore mouth. On
systematic enquiry, he gave a two-year history of a
recurrent sore mouth that made it difficult for him to eat.
Just before the onset of all his symptoms he had
experienced an attack of abdominal pain and bloody
Clinical Cases
35
31a
31b
31c
31d
31e
Hb
WCC
Platelets
MCV
CRP
Rheumatoid factor
Antinuclear antibody
Radiology of painful joints
9.8 g/dl
13 ! 109/l
450 ! 109/l
82 fl
200 g/l
Absent
Absent
Normal
36
Answer 30
c. Extrapyramidal side-effects of haloperidol.
The woman has clinical evidence of dyskinesia and
parkinsonism. The most common cause of her neurological
signs is drug-induced extrapyramidal disease. Neuroleptic
drugs which include haloperidol are extensively used in
treating agitation in the elderly. By blocking dopamine
receptors in the basal ganglia, these drugs can offset
extrapyramidal side-effects which include tremor, dystonia,
akathisia, parkinsonism and tardive dyskinesia. Acute
dystonic reactions appear within the first few hours or days,
and consist of oculogyric crises, torticollis or trismus.
Fortunately, they are uncommon, and resolve as soon as the
drug is withdrawn. Chronic tardive dyskinesias are the most
serious complication and affect 20% of patients on chronic
neuroleptic therapy. They usually occur after a patient has
been on treatment for at least three months, and can be
made worse in the first few weeks after stopping the
offending drug. In 60% of cases the dyskinesia resolves over
three years after drug withdrawal; however, in the
remainder of patients the movement disorder persists and is
very difficult to treat. Characteristic features involve lip
smacking, tongue protrusion, orofacial mouthing, trunk
rocking and distal chorea of the hands and feet. A
combination of any of these features may be present.
Cerebral calcification is an incidental finding in 0.5% of
CT scans in the elderly. About 2030% of patients with
widespread calcification of the basal ganglia exhibit
30
Answer 31
d. Behets syndrome.
The patient has oral, genital and anal ulcers (31a, d and e,
respectively), conjunctivitis (31b), arthritis, erythema
nodosum (31c) and features of a systemic illness. There has
been a single episode of bloody diarrhoea and a previous
femoral vein thrombosis. The differential diagnoses include
Crohns disease, Reiters syndrome and Behets syndrome
(Table A). Reiters syndrome is classically a triad of
conjunctivitis, urethritis and arthritis 14 weeks after an
episode of bacterial dysentery or a sexually transmitted
urethritis. Other features include plantar fasciitis, Achilles
tendinitis, keratoderma blennorrhagica, circinate balanitis,
stomatitis, hepatitis, cardiac and neurological involvement,
and occasionally amyloidosis. It is possible that the
diarrhoeal illness may have been dysenteric and offset the
reactive features of Reiters disease. There is no history of
promiscuity or urethral discharge. Venous thrombosis
affects about 4% of patients with Reiters disease and occurs
early in the disease. Mouth ulcers are common in Reiters
disease and are painless. Erythema nodosum is not a feature
of Reiters syndrome. Arthritis is asymmetrical and usually
affects the knee and ankle joints. The most common joint
to be affected in the upper limb is the wrist, as in this case;
however, joint involvement occurs early, whereas in this
case the disease has been present for two years.
Crohns disease is a chronic granulomatous
inflammatory disease of the gastrointestinal tract of
unknown cause, and is a strong possibility in this case.
Bloody diarrhoea is a recognized feature of Crohns colitis.
Colonic disease is associated with perianal disease in just
over 30% of patients. A seronegative reactive arthritis is a
recognized complication of Crohns disease. Erythema
nodosum occurs in some cases. Genital ulcers are rare, as is
deep-vein thrombosis. Urethral involvement and dysuria
only occur when an inflammatory fistula develops between
the colon and the ureter. Recurrent urinary tract infections
due to faecaluria can cause urethral stricture.
Behets syndrome is the most probable diagnosis.
Behets syndrome is a recurrent multifocal disorder that
persists over many years. It is characterized by recurrent
mouth and genital ulcers, ocular lesions, and skin, joint
and neurological involvement. The incidence is high in
Japan and in countries bordering the Mediterranean.
Oral and genital ulcers are present in most patients.
Clinical Cases
37
Syphilis
Gonococcal infection
HIV
Pemphigus pemphigoid
StevensJohnson
syndrome
Ulcerative colitis
Reiters syndrome
Question 32
A 16-year-old female was admitted with a six-month
history of myalgia, loss of weight and night sweats. Over
the past six weeks she had started to become breathless on
exertion. On admission to hospital she had a temperature
of 38.1C (100.6F). On auscultation of the precordium,
there was an early diastolic murmur at the left lower
sternal edge. Examination of the chest, abdomen and
central nervous system was normal, with the exception of
her fundi, one of which is shown (32a). An echocardiogram was performed to investigate the murmur (32b).
32a
32b
38
Answer 32
1. c. Infective endocarditis.
2. d. Blood cultures.
Fever, diastolic murmur, presence of echogenic mass on
the aortic valve and a Roths spot in the retina
(haemorrhagic areas with a pale centre) are consistent
with the diagnosis of infective endocarditis. Clinical
features of infective endocarditis are tabulated (Table A).
Blood cultures are the single most important
investigation in the diagnosis of infective endocarditis,
and are positive in 90% of cases. Serial blood cultures
should be performed, because a single set of blood
cultures may not necessarily reveal the culprit organism.
Although transthoracic echocardiography is extremely
useful in confirming the presence of vegetations, the
absence of vegetations does not exclude endocarditis, as
Non-infective
SLE (LibmannSacs)
Marantic endocarditis
Clinical Cases
39
Question 33
A 51-year-old accountant presented with a six-month
history of persistent dull right upper quadrant pain and
fever. The pain did not radiate elsewhere, but was
exacerbated on lying on her right side. During this period
she had intermittent pale bulky stool which was difficult
to flush, and episodic dark urine. More recently, her
appetite was reduced and she had lost approximately 1 kg
in weight during the past month. Over the past week she
had difficulty sleeping due to itching all over her body,
and her colleague at work commented on a yellowish
pigmentation in her eyes. Six months before this, she had
been relatively well. She had a past history of a
cholecystectomy for cholesterol stones at the age of 32
and subsequently had an ERCP and removal of sludge
from the common bile duct six years ago. She consumed
10 units of alcohol per week. She was married with two
sons, aged 20 and 18. Three months ago she had been
on holiday in Scotland. She was not taking any regular
medication.
On examination, she was slightly icteric. Inspection of
her hands is shown (33).
There were spider naevi on her arms neck and face and
scratch marks around her trunk and lower limbs. She had
a temperature of 39C (102.2F). Her heart rate was
120 beats/min and blood pressure 140/80 mmHg.
There were a few inspiratory crackles on auscultation of
the right lung base. Abdominal examination demon strated firm, slightly tender hepatomegaly 4 cm below
the costal margin, and a moderately enlarged spleen.
There were no other abdominal masses, and there was no
evidence of shifting dullness. Rectal examination was
normal.
Investigations are shown.
33
AST
Alkaline phosphatase
Bilirubin
Albumin
Total protein
INR
Chest X-ray
60 iu/l
360 iu/l
82 mol/l
25 g/l
93 g/l
1.49
Normal
Question 34
A 75-year-old male was seen by his GP with a five-day
history of wheeze and ankle swelling. He was prescribed
some medication, but continued to deteriorate and was
admitted to hospital.
Investigations are shown.
1. What is the acid-base disturbance?
2. Suggest two possible causes for this metabolic
picture.
7.33
7 kPa
6.5 kPa
20 mmol/l
133 mmol/l
5 mmol/l
28 mmol/l
200 mol/l
40
Answer 33
1. a. Blood cultures.
2. e. Recurrent cholangitis.
The key in this question is a prior history of cholelithiasis
affecting the gallbladder and the biliary tree. Stones in the
bile duct are a nidus for infections, particularly when there
has been instrumentation, as in this case. Cholangitis is
characterized by the triad of right upper quadrant pain,
jaundice and fever. This patient has had previous episodes
suggestive of cholangitis, and the best answer for the
presenting complaint is recurrent cholangitis. She also has
evidence of cirrhosis, which is almost certainly secondary to
chronic cholestasis. Although cholangiocarcinoma may
rarely complicate biliary cholestasis, this is unlikely given
the mode of presentation. Cholangiocarcinoma
characteristically presents with intermittent jaundice, and
causes duct obstruction before the onset of biliary cirrhosis.
Primary sclerosing cholangitis is very uncommon. The
aetiology is thought to be auto-immune, but the trigger
factor is unknown. More usually, it is associated with
Answer 34
1. Combined respiratory and metabolic acidosis.
2.i. Acute cardiac failure.
ii. Severe exacerbation of obstructive airways disease
and pre-renal failure from diuretics.
The patient has a respiratory acidosis that is characterized
by a PaCO2 of 6.5 kPa or more, and a pH below 7.35, and
is hypoxic. In the acute situation, respiratory acidosis is not
compensated by the kidney, but after 35 days the kidneys
retain bicarbonate ions to compensate, which results in
normalization of the pH at the expense of a relative
metabolic alkalosis. In this patient the bicarbonate is
slightly low, suggesting a metabolic acidosis. This may be
Aspirin poisoning
Severe pneumonia with renal failure due to septicaemia or interstitial nephritis (Legionnaires disease)
Septicaemia from any cause complicated by ARDS
Malaria complicated by pneumonia
Acute renal failure and fluid overload
Renal pulmonary syndromes: anti-GBM disease, Wegeners granulomatosis, microscopic polyarteritis nodosa
Acute massive pulmonary embolism
Cardiac arrest (before ventilation)
Clinical Cases
41
Question 35
A 14-year-old male presented with joint pains, polydipsia
and polyuria.
Respiratory function tests are shown.
FEV1 (l)
FVC (l)
FEV1/FVC
TLC (l)
Residual volume (l)
KCO (mmol/l/kPa)
Actual
2.0
4.0
50%
4.9
1.7
5.0
Predicted
4.5
5.6
80%
7.0
2.2
10
Question 36
A 64-year-old patient who had been attending the
cardiology clinic for 15 years presented with increasing
breathlessness on exertion and a reduced appetite.
Examination of the face is shown (36a, b).
Investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
Thyroxine
TSH
ECG
Echocardiogram
13 g/dl
7 ! 109/l
190 ! 109/l
80 fl
135 mmol/l
4.1 mmol/l
8 mmol/l
100 mol/l
48 mol/l
160 iu/l
180 iu/l
39 g/l
190 nmol/l
<0.1 mu/l
Atrial fibrillation
Ventricular rate 80/min
Enlarged left atrium
Normal-sized left ventricle
with good function
Normal valves
36a
36b
42
Answer 35
1. A mixed obstructive and restrictive defect with a
reduced KCO. The low FEV1/FVC ratio is in
keeping with an obstructive defect; however, the
low residual volume also suggests a restrictive
pattern.
2. The combination of polydipsia and polyuria with
respiratory involvement is suggestive of diabetes
insipidus. In a young patient with a mixed
restrictive and obstructive defect the most likely
diagnosis is histiocytosis X.
3. Transbronchial lung biopsy/liver biopsy/trephine
aspirate may all show histiocytes and small round
cells.
4. Cystic fibrosis.
Histiocytosis X is a benign disorder of unknown aetiology.
It generally affects many systems, but in up to 25% of
cases only one system may be involved. The peak age of
presentation is between 2 and 4 years, and the condition
affects males more than females. The skin, bones, ears,
lungs, eyes, and the reticuloendothelial and central
nervous systems are most often affected. A skin rash is
Answer 36
1. Amiodarone toxicity.
2. Formal lung function tests including a KCO
estimation.
The patient has biochemical evidence of hepatitis and
hyperthyroidism. In a patient who has been attending the
cardiology clinic for several years, and has underlying atrial
fibrillation, it is highly likely that these abnormalities are
due to the toxicity of amiodarone which was prescribed to
control the AF. Amiodarone is a class III anti-arrhythmic
agent which is very effective in the management of
ventricular and supraventricular arrhythmias; however, it is
associated with several side-effects and complications
(Table). Lung fibrosis is an important complication and
almost certainly accounts for the patients breathlessness.
Early interstitial fibrosis may not be apparent on chest Xray, but is suggested by a low KCO on respiratory function
tests. Both hyperthyroidism and hypothyroidism are
recognized due to the iodine content of the drug.
Asymptomatic biochemical hepatitis may occur and some
patients may progress to cirrhosis of the liver. Patients on
amiodarone should have an annual thyroid test, an LFT
Complications
Optic neuritis
Peripheral neuropathy
Myopathy
Hepatitis/cirrhosis
Alveolitis
Hyper/hypothyroidism
Epididymitis
Conduction tissue
disturbances
Clinical Cases
43
Question 37
37a
37b
37c
10
8
Expiration
6
4
Flow (l/s)
Normal
0
2
4
Patient
Inspiration
6
8
10
0
2
4
6
Change in lung volume (l)
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Glucose
Urinalysis
Blood film (37b)
Flow loop curve (37c)
10.8 g/dl
14.2 ! 109/l
80 ! 109/l
91 fl
133 mmol/l
3.9 mmol/l
18 mmol/l
179 mol/l
8.1 mmol/l
Glucose 0
Ketones +
44
Answer 37
1. Bronchial carcinoma affecting the left lung.
2. i. Severely reduced expiratory flow consistent with
obstructive airways disease.
ii. Reduced inspiratory flow limb consistent with
upper airways obstruction. In this case it is
probably due to a laryngeal nerve palsy causing
vocal cord paralysis. (See Interpretation of
Respiratory Flow Loop Curves, page 420.)
3. i. Hypercalcaemia.
ii. Cerebral metastases.
iii. Hypoxia.
iv. Concurrent respiratory tract infection.
v. Dehydration.
4. i. Hypercalcaemia.
ii. Cranial diabetes insipidus.
5. i. Local and distant metastases (recurrent laryngeal
nerve, bone and brain).
ii. Poor respiratory reserve.
Question 38
A 76-year-old Polish male was found collapsed in the toilet
by the home help. He had been generally unwell for the
past five months and was easily fatigued. His appetite was
reduced because he felt constantly nauseous. He was seen
in the Accident and Emergency Department one month
ago with abdominal pain, and was diagnosed as having
constipation, for which he was prescribed senna. He had
not been out of bed for four days. He had a past history of
hypertension and osteoarthritis. He lived alone and was
becoming increasingly dependent on the social services as
his health deteriorated. He smoked ten cigarettes per day.
On examination, he was confused and agitated, and
appeared pale. He was malnourished and clinically
dehydrated. There was no evidence of cyanosis or
lymphadenopathy. His temperature was 39C (102.2F).
The heart rate was 110 beats/min and blood pressure
105/50 mmHg. The JVP was not raised. Examination of
his tongue is shown (38a). On examination of the
cardiovascular system, he had a fourth heart sound.
Respiratory examination revealed a respiratory rate of
30/min. Movement of the right hemithorax was reduced.
Percussion note was dull from the right mid-zone to the
base. The abdomen was thin. A liver edge was palpable
38a
Clinical Cases
45
38b
Hb
8 g/dl
WCC
25 ! 109/l
Platelets
90 ! 109/l
Blood film (38d)
ESR
148 mm/h
Sodium
130 mmol/l
Potassium
4 mmol/l
Urea
16 mmol/l
Total protein
50 g/l
Albumin
18 g/l
Alkaline phosphatase
220 iu/l
AST
26 iu/l
Bilirubin
13 mol/l
Arterial blood gases (40% O2):
pH
7.4
PaO2
9 kPa
PaCO2
5 kPa
Bicarbonate
18 mmol/l
Chest X-ray (38e)
X-ray, right arm (38f)
Bone marrow aspirate
Dry tap
Urinalysis
Protein +++
No organisms
38c
38d
38e
38f
46
Answer 38
1. Multiple myeloma.
2. Branch retinal vein occlusion.
3. He has a pathological fracture affecting his right
radius.
4. i. Oedema due to nephrotic syndrome.
ii. Bruising secondary to thrombocytopenia or
amyloid related capillary fragility.
5. i. Sepsis affecting the right lung as a result of
immunoparesis. Bronchopneumonia and renal
failure are the most common causes of death in
multiple myeloma.
ii. Amyloidosis. The tongue is enlarged owing to
amyloid infiltration. The patient is oedematous
and hypoalbuminaemic and has marked
proteinuria, suggesting nephrotic syndrome,
which is a manifestation of renal amyloid.
Amyloid often affects the heart in myeloma, and
is an important cause of death. Skin deposits, a
peripheral neuropathy and massive hepatic
infiltration are all recognized features of
amyloidosis associated with multiple myeloma.
38g
Clinical Cases
47
Question 39
A 60-year-old female presented with a four-month history
of headaches and general malaise. Over the past three
weeks she had developed nausea and epigastric pain after
meals. She was restless at night and had noticed occasional
palpitations, but attributed these symptoms to fear of
illness. She also had of episodic diarrhoea. On examination,
she appeared anxious. She had an irregular swelling in her
neck, which moved vertically with swallowing. Her heart
rate was 120 beats/min, and regular; blood pressure was
180/105 mmHg. Examination of all the major systems
was normal. Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Blood glucose
TSH
17 g/dl
9 ! 109/l
300 ! 109/l
135 mmol/l
3.4 mmol/l
10 mmol/l
120 mol/l
2.8 mmol/l
0.6 mmol/l
10 mmol/l
3 mu/l
Question 40
M-mode echocardiograms of two
women (A and B), who were
investigated for breathlessness in a
busy cardiology clinic, are shown
(40a, b).
40a
40b
48
Answer 39
1. Hypercalcaemia (peptic ulcer disease, pancreatitis).
2. i. Raised calcitonin levels.
ii. Phaeochromocytoma.
3. Phaeochromocytoma.
4. Secondary polycythaemia in association with
phaeochromocytoma.
5. Multiple endocrine neoplasia type 2 (MEN 2).
6. i. Fine-needle aspiration of the thyroid.
ii. Serum calcitonin.
The patient has hypercalcaemia and hypertension
associated with palpitations. She has an irregular swelling
in the neck, which is consistent with a thyroid goitre. The
TSH is normal, indicating that she is euthyroid. The low
serum phosphate and high calcium levels indicate
that primary hyperparathyroidism is the most likely
cause of the raised calcium. Although primary
hyperparathyroidism by itself is a recognized cause of
hypertension, it does not account for the palpitations and
restlessness, which are best explained by a coexisting
phaeochromocytoma. The combination of primary
hyperparathyroidism and phaeochromocytoma should
lead one to consider the possibility of MEN 2. In the
context of this question it is very probable that the
thyroid goitre represents a medullary cell carcinoma.
MEN 2 consists of tumours arising from thyroid C cell
carcinoma, the parathyroid gland and the adrenal
Answer 40
1. a. Mitral valve prolapse.
2. b. Atrial myxoma.
Female A (40a): the mitral valve has a normal appearance
in diastole. In systole, both the anterior and posterior
leaflets appose normally in the beginning; however, in
mid systole there is posterior movement (prolapse) of
both leaflets, but predominantly the posterior leaflet.
This is characteristic of mitral valve prolapse and is
responsible for the mid-systolic clicks and/or the midsystolic murmur of mitral regurgitation. Mitral valve
prolapse is present in 25% of the general population. It
is generally benign but may be associated with symptoms
of sharp inframammary chest pain, breathlessness even
with normal ventricular function, palpitation and odd
neurological symptoms. There is a risk of infective
endocarditis in patients with consequent mitral
Clinical Cases
49
Question 41
A 45-year-old woman presented with a three-week
history of fever, persistent dry cough, headache and
photophobia. She lived with her son, who owned two
greyhounds and several racing pigeons. The patient had
not travelled abroad.
On examination she had a temperature of 38.2C
(100.8F) and was slightly confused. She had a
generalized macular rash but there was no obvious
evidence of lymphadenopathy.
Examination of the respiratory system was normal,
with the exception of a respiratory rate of 18 per min.
Both heart sounds were normal; there were no added
heart sounds or murmurs. Abdominal examination
revealed hepatomegaly palpable three finger-breadths
from the costal margin and a palpable spleen 2 cm below
the costal margin.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alkaline phosphatase
Albumin
11 g/dl
12 ! 109/l
380 ! 109/l
130 mmol/l
3.7 mmol/l
8 mmol/l
70 "mol/l
12 "mol/l
46 iu/l
52 iu/l
100 iu/l
34 g/l
Question 42
A 42-year-old woman with a past medical history of
systemic lupus erythematosus that was well-controlled on
methotrexate, presented with a four-day history of right
lower chest pain that was sharp in character and worse on
Hb
WCC
Platelets
ESR
CRP
Sodium
Potassium
Urea
Creatinine
C3
C4
Chest X-ray
Oxygen saturation on air
11.2 g/dl
6 ! 109/l
260 ! 109/l
23 mm/h
3 g/l
134 mmol/l
4.1 mmol/l
9 mmol/l
130 "mol/l
0.35 g/l (NR 0.551.20 g/l)
0.26 g/l (NR 0.20.5 g/l)
Normal
98%
50
Answer 41
b. Tetracycline.
A history of dry cough, fever, headache and photophobia
in a patient who is in contact with racing pigeons is
consistent with the diagnosis of psittacosis, which is
caused by the Gram-negative bacterium Chlamydia
psittaci. Psittacine birds are the primary reservoir and
man is an incidental host. The organism is transmitted to
man via aerosol inhalation of faecal and urinary products
on bird feathers. Chlamydia psittaci infection is an
occupational hazard in pet-shop employees, veterinary
doctors and nurses, zoo personnel and workers in poultry
processing plants. Chlamydia psittaci infection is rare and
accounts for 1% of all atypical pneumonias.
Clinical presentation includes a dry cough and fever,
which may be abrupt in onset. Headache is a prominent
feature and may be accompanied by photophobia;
however, genuine meningitis is a rare complication of the
infection. Malaise, night sweats, anorexia, diarrhoea and
delirium are recognized. The respiratory features may be
mild but fulminant respiratory failure may occur in a few
cases.
Extrapulmonary complications do occur but with a
much lower frequency than in Mycoplasma pneumonia
infection (Table A). Jaundice is rare.
Respiratory examination reveals evidence of pleurisy,
consolidation or effusion. Splenomegaly and hepatomegaly
are present in 10% of cases.
Rapid diagnosis is not possible. The diagnostic
investigation of choice is the complement fixation test.
First-line therapy is tetracycline or doxycycline.
Erythromycin is a second-line drug.
Other chlamydial infections (Table B)
Infection due to Chlamydia pneumoniae causes
pneumonia that is indistinguishable from pneumonia
secondary to Streptococcus pneumoniae infection. Unlike
Mycoplasma infection, which affects young individuals,
Chlamydia pneumoniae infection affects patients in the
seventh and eighth decades. Hoarseness, pharyngitis and
sinusitis are common. The white cell count is normal and
Glomerulonephritis
Pancreatitis
Haemolysis
Thyroiditis
Dermatological
Erythema nodosum
Chlamydia
pneumoniae
Chlamydia psittaci
Males
Non-gonococcal urethritis
Lymphogranuloma venerum
Epididymitis
Prostatitis
Proctitis (homosexuals)
Reactive arthritis
(Reiter syndrome)
Females
Non-gonococcal urethritis
Cervicitis
Pelvic inflammatory disease
Peri-hepatitis (Fitzhugh
Curtis syndrome)
Newborns (born to infected mothers)
Conjunctivitis
Pneumonia
Pneumonia
Psittacosis
Answer 42
c. Relapse of systemic lupus erythematosus.
This is a difficult question since there is a very limited
amount of data provided. However, the combination of
Clinical Cases
51
Question 43
A 72-year-old male with a known history of chronic
obstructive airway disease had eight admissions to
hospital with a cough and breathlessness over a
12-month period. He had stopped smoking two years
previously. His normal exercise capacity was limited to
27.5 metres on the flat before stopping. He was taking
salmeterol, pulmicort and oxivent inhalers, and had
received several courses of steroids in the past year.
On examination he was cyanosed. His heart rate was
100 beats/min and regular. His blood pressure measured
110/70 mmHg. The JVP was raised 4 cm above the
costal margin at 45. The trachea was central. Chest
expansion was generally reduced. Percussion note was
19 g/dl
0.56 l/l
8 ! 109/l
340 ! 109/l
82 fl
Hyper-inflated lung fields
7.35
7.5 kPa
6.1 kPa
34 mmol/l
Normal left ventricle.
Right ventricular
hypertrophy and dilatation
Pulmonary artery
pressure of 42 mmHg
Question 44
A 35-year-old type 1 diabetic presented eight months
following a renal transplant with fever, night sweats and
malaise. He had experienced two episodes of transplant
rejection, which were successfully reversed with
corticosteroids. He was currently maintained on
prednisolone and ciclosporin. On examination he had a
temperature of 39C (102.2F). The heart rate was
120 beats/min and blood pressure was 140/60 mmHg.
The respiratory rate was 40/min. Precordial examination
revealed an early diastolic murmur at the left lower
sternal edge. The chest was clear. The abdomen
including the graft was non-tender.
Investigations are shown.
What is the most likely diagnosis?
a. Acute renal transplant rejection.
b. CMV infection.
c. Infective endocarditis.
d. Gram-negative sepsis.
e. Ciclosporin nephrotoxicity.
Hb
WCC
Neutrophils
Lymphocytes
Eosinophils
Basophils
Monocytes
Platelets
ESR
Sodium
Potassium
Chloride
Bicarbonate
Urea
Creatinine
Glucose
Urine output
Urinary microscopy
ECG
10 g/dl
10 ! 109/l
7 ! 109/l
2.5 ! 109/l
0.04 ! 109/l
0.1 ! 109/l
0.4 ! 109/l
300 ! 109/l
100
130 mmol/l
5.5 mmol/l
87 mmol/l
22 mmol/l
9 mmol/l
130 "mol/l
6 mmol/l
45 ml/hr
Red blood cells and no
white cell casts
Sinus tachycardia
52
Answer 43
e. Long-term oxygen therapy.
Indications for long-term oxygen therapy are a PO2 of
7.38 kPa once stable and either secondary polycy thaemia, nocturnal hypoxaemia, peripheral oedema or
Answer 44
c. Infective endocarditis.
Infection is the commonest life-threatening complication
of long-term immunosuppressive therapy (Table). More
than 6 months post-transplant most patients have stable
allografts and are maintained on minimal
immunosuppressive therapy. Infection in the majority of
these patients is usually similar to that seen in the general
population. The patient in question has a murmur of
aortic regurgitation and a high fever, raising the
possibility of infective endocarditis.
The overall incidence of bacterial endocarditis is much
greater in renal transplant recipients than in the general
population. Independent risk factors for bacterial
endocarditis include a history of hospitalization for
valvular heart disease, graft loss and increased duration of
dialysis before transplantation. The mean time from
transplantation to diagnosis of endocarditis is estimated
to be three and a half years (range two months to 15
years), with an overall mortality of 50%.
The increased susceptibility of renal transplant
recipients to infective endocarditis can probably be
explained by a combination of necessary invasive
procedures (e.g. intravascular line placement) during the
immediate post-transplant period as well as
immunosuppression for prevention of organ rejection.
Pre-existing valvular abnormality in renal transplant
patients may also be conducive to endocarditis similar to
that in non-transplant patients. Immunosuppression plays
an important role in the development of fungal
endocarditis, but may also be important in the clearance
Infection
Usual post-surgical infections (as seen in immunocompetent patients)
CMV and other opportunistic infections
Community acquired infections (viral and bacterial) and recurrence of
inadequately treated opportunistic infections
Clinical Cases
53
Question 45
A 52-year-old woman was referred to a chest physician
with a six-month history of dyspnoea associated with a
non-productive cough, intermittent fever and night
sweats. At the onset of the illness her symptoms were
intermittent, usually worse in the evenings, but over the
past few weeks they had become more persistent. The
patient also complained of reduced appetite and loss of
weight. She had worked on a farm with her husband for
the past four years. She smoked ten cigarettes per day.
There was no previous history of breathlessness.
On examination she was thin. There was evidence of
peripheral cyanosis but no clubbing. Auscultation of the
lungs was normal. The chest X-ray showed reticulonodular shadowing affecting the upper and mid zones.
Question 46
A 19-year-old man was admitted for further investigation
for a six-month history of lethargy and depression. 11
months previously he had collapsed while on holiday in
San Francisco when walking on a very hot day and was
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
Alkaline phosphatase
Bicarbonate
TSH
Thyroxine
24-h urinary calcium excretion
Chest X-ray
13 g/dl
4.5 ! 109/l
259 ! 109/l
137 mmol/l
3.9 mmol/l
4 mmol/l
70 "mol/l
1.8 mmol/l
1.9 mmol/l
42 g/l
100 iu/l
24 mmol/l
18 iu/l
40 iu/l
Increased
Normal
Question 47
A 28-year-old woman who is eight weeks pregnant
attends a genetic counselling service with her husband,
who is a lawyer. His brother is heterozygous for the 508
mutation for cystic fibrosis. The husband agrees to be
screened and is also found to be heterozygous for the
mutation. The pregnant woman in question declines the
screening test.
54
Answer 45
d. Extrinsic allergic alveolitis.
The patient is a farmers wife and her original symptoms
were consistent with an allergic (hypersensitivity)
pneumonitis; however, more recently she has developed
persistent breathlessness, suggesting advanced paren chymal lung disease. Repeated episodes of pneumonitis
Answer 46
c. Pseudohypoparathyroidism.
The patient has low calcium and high phosphate levels in
the absence of abnormal renal function. The differential
diagnosis is between hypoparathyroidism and
pseudohypoparathyroidism. Pseudohyoparathyroidism is
due to the end-organ resistance to the effects of PTH,
Answer 47
b. 1 in 80.
The gene frequency of the mutation in question is 1/20,
hence the chances of the pregnant woman carrying the
mutation is 1 in 20. Her husband has been screened and
is a definite carrier. Therefore, the chances of them both
having a heterozygous genetic mutation is
1/20 ! 1/1 = 1/20.
Clinical Cases
55
Question 48
An alcoholic vagrant was admitted to the Accident and
Emergency Department after being found collapsed on
the street. Four hours previously he had been spotted
wandering outside the hospital and appeared well.
On examination he had a Glasgow coma scale of 5.
His heart rate was 120 beats/min and regular. The blood
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
Glucose
Amylase
Plasma osmolality
ECG
Arterial blood gases:
pH
PaO2
PaCO2
Bicarbonate
Blood lactate
Urinalysis
131 mmol/l
5.4 mmol/l
5 mmol/l
110 "mol/l
12 mmol/l
96 mmol/l
6 mmo/l
120 iu/l
(NR <220 iu/l)
320 mOsm/l
Sinus tachycardia, left axis deviation
7.21
9 kPa
2.1 kPa
12 mmol/l
6 mmol/l
Protein
0
Glucose 0
Ketones +
Question 49
A 29-year-old woman presented with sudden onset of
weakness affecting the left side of the body. There was no
history of headaches or head injury. She had previously
been well with the exception of having mild Raynauds
disease. The patient had a history of two previous
miscarriages four years ago but had had a successful
pregnancy six months previously that was complicated by
a below-knee deep vein thrombosis. She worked as a
clerk in a large business firm prior to her pregnancy. Her
appetite was good and her weight was stable.
On examination she had a left facial palsy and obvious
left-sided weakness. Her heart rate was 80 beats/min and
regular. The blood pressure was 150/88 mmHg. The
temperature was 36.8C (98.2F). Both heart sounds
were normal; there was a soft systolic murmur in the
pulmonary area. The chest was clear. Investigations are
shown.
Hb
WCC
Platelets
ESR
CT scan brain
Trans-thoracic
echocardiogram
11 g/dl
11 ! 109/l
152 ! 109/l
11 mm/h
Infarct in right middle cerebral
artery territory
Normal.
56
Answer 48
b. Methanol toxicity.
The main differential diagnoses of severe metabolic
acidosis and collapse specific to an individual who abuses
alcohol includes methanol toxicity, ethylene glycol
poisoning, acute severe pancreatitis and acute hepatic
failure. The patient has a normal amylase therefore acute
pancreatitis is unlikely. The actual plasma osmolality is
higher than the calculated plasma osmolality
(approximately 284 mOsm/l) suggesting the presence of
a large concentration of an osmotically active substance.
The most probable candidates include methanol or
ethylene glycol (anti-freeze). Both conditions present
with drunkenness, acidosis and coma and in untreated
cases the mortality is high. Methanol and ethylene glycol
are relatively toxic; however, once ingested they are
metabolized to formic acid (methanoic acid) and glycolic
acid, respectively, by the enzyme alcohol dehydrogenase,
both of which are very toxic.
Patients with methanol toxicity may complain of
headache, nausea, fatigue or reduced visual acuity if not
Step 4
Step 5
Answer 49
d. Lupus anticoagulant syndrome.
The patient has a predisposition to arterial and venous
thromboses. She has had miscarriages in the second
trimester. She also has Raynauds phenomenon and
thrombocytopenia, all of which are characteristic of lupus
anticoagulant syndrome. The normal echocardiogram in
this context rules out an atrial septal defect and hence a
paradoxical embolus as a cause of the stroke.
Echocardiography may show evidence of verrucous
(LibmannSack) endocarditis. The manifestations of
antiphospholipid syndrome are tabulated.
Clinical Cases
57
Question 50
A 70-year-old male presented with a one-week history of
increasing confusion. According to his wife his general
health had been deteriorating for about three months.
His appetite was reduced. He complained of abdominal
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
11 g/dl
11 ! 109/l
100 ! 109/l
139 mmol/l
5 mmol/l
20 mmol/l
190 "mol/l
3.2 mmol/l
1.4 mmol/l
32 g/l
Question 51
A 40-year-old woman presented at the Accident and
Emergency Department with a 48-hour history of headache
and neck stiffness. She had returned from a holiday in the
CT scan of brain
CSF analysis:
WCC
Protein
Glucose
Gram stain
Normal
Appearance clear
20 per mm3
(80% lymphocytes)
0.48 g/l
2.3 mmol/l (simultaneous
blood glucose 4.5 mmol/l)
No organism identified
Question 52
52a
58
Answer 50
c. IV saline (0.9%).
The patient has symptomatic hypercalcaemia. In general
patients with hypercalcaemia rarely exhibit symptoms if
the serum calcium is below 3 mmol/l. Treatment of
symptomatic hypercalcaemia has to be instituted before
the underlying cause is identified (Table). The most
important aspect of management is vigorous rehydration.
Most patients are dehydrated owing to fluid loss from the
kidneys resulting from nephrogenic diabetes insipidus.
Fluid loss may also occur from the gastrointestinal tract
owing to vomiting. The general recommendation is to
treat with 4 litres of saline over 24 hours and review
hydration status. Some guidelines recommend the
concomitant use of furosemide, as this promotes hypercalcuria; however, in diuresis it may worsen dehydration
and is best reserved for patients who exhibit fluid
overload after rehydration.
Answer 51
c. Viral meningitis.
The patient has a lymphocytic meningitis with a normal
CSF protein and a very slight reduction in CSF glucose
(Table). The differential diagnosis is between viral
meningitis (and some cases of viral meningitis do cause a
very slight reduction in glucose) or meningitis due to
brucellosis, lyme disease, listeria monocytogenes, and
partially treated bacterial meningitis. The patient has been
to the south of France and one could infer that she may
have indulged in soft cheeses and developed listerosis;
however, listerosis usually affects immunocompromised
Opening pressure
Protein content
Glucose
White cell count
Red cells
IgG
Answer 52
b. Left axis deviation.
c. Voltage for left atrial enlargement.
f. Voltage criteria for right ventricular hypertrophy.
g. RBBB.
h. Voltage criteria for right atrial enlargement.
The criteria for left and right atrial and ventricular
hypertrophy are discussed in Answer 259. Bundle branch
block is characterized by a wider QRS complex (more
than 120 ms; three small squares on the ECG). In RBBB
the QRS complex in lead VI has an rsR pattern and in
LBBB the QRS complex in lead VI has a qS pattern
(52b)
RBBB
52b
LBBB
R
Lead VI
r
S
s
Clinical Cases
59
Question 53
A 63-year-old male with a known history of myocardial
infarction, hypertension and peripheral vascular disease is
Sodium
137 mmol/l
Potassium
4.5 mmol/l
Urea
11 mmol/l
Creatinine
130 mmol/l
Troponin T
<0.1ng/l (NR <0.1 ng/l)
Arterial gases (room air):
pH
7.31
PaCO2
6.4 kPa
PaO2
7.1 kPa
Bicarbonate
16 mmol/l
Chest X-ray
Severe pulmonary oedema
ECG
LBBB
Urinalysis
Protein 0
Blood 0
Question 54
A 74-year-old woman presented with a transient syncopal
episode. There was a previous history of paroxysmal atrial
fibrillation and congestive cardiac failure. Medications on
admission included amiodarone 200 mg od, furosemide
40 mg od, enalapril 20 mg od and warfarin. The ECG on
admission is shown (54a). Electrolytes were as follows:
Sodium
Potassium
Urea
Creatinine
Magnesium
138 mmol/l
4.2 mmol/l
11 mmol/l
128 "mol/l
0.8 mmol/l (NR)
54a
54b
60
Answer 53
c. Renal artery stenosis.
The patient presents with acute pulmonary oedema. He
has a background history of ischaemic heart disease,
peripheral vascular disease and hypertension. The
differential diagnosis is between heart failure secondary to
hypertensive heart disease, myocardial infarction or flash
pulmonary oedema secondary to renal artery stenosis.
The possibility of renal artery stenosis should always be
considered in a patient with peripheral vascular disease
and impaired renal function. The serum cardiac troponin
is not raised, excluding myocardial infarction. The left
ventricular function is only mildly impaired and should
not cause such severe pulmonary oedema unless the
patient suffered an episode of myocardial stunning due to
Chronic hypertension
Diabetes mellitus
Generalized atherosclerosis (coronary and reno-vascular disease)
Polyarteritis nodosa and other vasculitides
Systemic sclerosis
Antiphospholipid syndrome
Infective endocarditis
Amyloidosis
Ethylene glycol poisoning
Answer 54
d. IV magnesium bolus (8 mmol/l).
The initial ECG shows a nodal bradycardia with marked
prolongation of the QT interval and U waves. The serum
potassium and magnesium are normal. The most
probable cause of the bradyarrhythmia and the
prolongation of the QT is amiodarone toxicity.
Prolonged QT is usually associated with polymorphic VT
(torsades de pointes) but monomorphic ventricular
Clinical Cases
61
Questions 55 and 56
A 69-year-old male consulted his GP with pleuritic chest
pain and had reduced air entry at the left lung base. He
had experienced a dry cough, fever and myalgia for 48
hours prior to the onset of the chest pain. He was a nonsmoker. On examination he was alert and orientated with
a mini-mental score test of 10/10. The blood pressure
was 100/66 mmHg. The respiratory rate was 32/min.
Investigations are shown.
Hb
WCC
Platelets
CRP
Sodium
Potassium
Urea
Creatinine
Chest X-ray
Oxygen saturation on air
14 g/dl
9 ! 109/l
480 ! 109/l
60 g/l
133 mmol/l
4.1 mmol/l
7.5 mmol/l
110 "mol/l
Left lower lobe
consolidation
94%
Aspiration:
Appearance
Gram stain
Culture
pH
Pleural fluid LDH
Purulent
Negative
Sterile
7.1
1000 iu/l
(Plasma LDH 200 iu/l)
Pleural fluid protein 40 g/l
(Total plasma protein 72 g/l)
Question 55
Question 56
Question 57
A 19-year-old girl was seen by her GP complaining of a
24-hour history of nausea and vomiting. She was
prescribed some medication. Later that evening her
boyfriend brought her into the Accident and Emergency
Department stating that she had been unable to speak
and had a very stiff neck.
On examination she appeared well. She was alert and
orientated without any difficulty with her speech. She was
unable to account for the episode encountered by her
boyfriend but denied any previous similar attacks. While
being examined she was seen to become rigid. Her jaw
was fixed open and her eyes were deviated up and to
the left.
62
Answers 55 and 56
Answer 55
d. Admit to hospital and treat with IV cefuroxime and
oral clarythromycin.
The patient has a community-acquired pneumonia (CAP)
as evidenced by symptoms and signs of a lower respiratory
tract infection and consolidation on the chest X-ray.
CURB-65
score
0 or 1
CURB-65
score
2
GROUP 3
Mortality
high (22%)
GROUP 1
Mortality low
(1.5%)
Home
treatment
GROUP 2
Mortality
intermediate
(9.2%)
CURB-65
score
3 or more
Consider hospital
supervised
treatment either
Short stay in
hospital or
hospital
supervised outpatient
Manage in
hospital as
severe CAP
Assess for
ICU if
CURB is
4 or 5
Answer 56
e. Drain effusion using an intercostal drain and
continue with aggressive antibiotic therapy.
The pneumonia has been complicated by an empyema,
which is characterized by frank pus in the pleural space.
Organisms may be seen on Gram stain or isolated during
culture. Biochemical investigation of the purulent fluid
will reveal high protein and LDH concentrations and low
pH and glucose concentration. The treatment of
empyema involves drainage with an intercostal drain
followed by a prolonged course of antibiotic therapy,
including anaerobic cover.
Hospital
treated
(not
severe)
Hospital
treated
(severe)
Preferred
Oral amoxycillin
Alternative
Oral erythromycin
or
Oral clarythromycin
Oral levofloxacin
or
Oral moxifloxacin
Oral amoxycillin
+
Oral erythromycin
or
Oral clarythromycin
IV co-amoxiclav
Oral levofloxacin
or
+
IV cefuroxime
IV benzylpenicillin
or
IV cefotaxime
+
Oral erythromycin
or
Oral clarythromycin
Clinical Cases
63
Answer 57
b. Intravenous procyclidine.
The description is typical of acute dystonia following
treatment for vomiting. The culprit agent is a neuroleptic
agent used to treat vomiting, classically metoclopramide
or prochlorperazine. Both drugs work by blocking
dopaminergic type 2 receptors in the mid-brain. Sideeffects include acute dystonia. Chronic use is associated
with tardive dyskinesia. Treatment is with intravenous
procyclidine or benzotropine, which are both anti cholinergic agents, or intramuscular diphenhydramine,
which is an anti-histamine.
Question 58
A 72-year-old male presented with a two-month history
of right-sided chest discomfort and weight loss. The
Hb
WCC
Platelets
Sodium
Potassium
Urea
Glucose
Protein
LDH
Chest X-ray
Pleural fluid:
Protein
LDH
Glucose
Gram stain
Cytology
11 g/dl
12 ! 109/l
300 ! 109/l
131 mmol/l
3.6 mmol/l
7 mmol/l
4.8 mmol/l
60 g/l
180 iu/l
Hyperinflated left lung
Moderate pleural
effusion right lung
29 g/l
180 iu/l
3 mmol/l
Negative
Mesothelial cells only
Question 59
A 10-year-old boy presented with a three-week history of
swollen ankles. On examination his blood pressure
Hb
WCC
Platelets
Blood film
Sodium
Potassium
Urea
Creatinine
Albumin
24-hour urine protein
12 g/dl
5 ! 109/l
200 ! 109/l
Normal
134 mmol/l
3.7 mmol/l
6 mmol/l
90 "mol/l
21g/l
3.6 g/l
64
Answer 58
b. Contrast enhanced thoracic CT scan.
The patient is a smoker and presents with right-sided
chest discomfort and has a pleural effusion. The pleural
fluid protein concentration is <30 g/l. Sole reliance on
the pleural fluid protein content would result in an
erroneous misinterpretation of a transudative effusion.
However, pleural fluid protein measurements should be
interpreted in the context of the serum protein
concentration. In patients with abnormal serum protein
or pleural fluid protein concentrations close to 30 g/l
more stringent criteria are required to differentiate a
pleural transudate from an exudate (Table A).
According to the Lights criteria, the effusion has the
biochemical features of an exudate. The pleural glucose
Answer 59
a. Oral high dose prednisolone therapy.
The patient has nephrotic syndrome. The commonest
cause of nephrotic syndrome in children is minimal change
glomerulonephritis, accounting for 90% of all cases of
nephrotic syndrome in children aged below 10 years, and
50% of children aged above 10 years. The causes of
nephrotic syndrome are tabulated below (Table A).
A trial of high-dose prednisolone (1 mg/kg per day) is
the first-line management step in children presenting
with pure heavy proteinuria and peripheral oedema. Most
children achieve remission within two weeks and almost
Immune
Non-steroidal anti-inflammatory drugs
Hodgkin's lumphoma
Food allergy (cows milk)
Bee-sting reaction
Lithium
Pamidronate
Clinical Cases
65
Question 60
A 68-year-old man presented with a cholestatic blood
picture, and hepatobiliary ultrasound revealed dilated
extra-hepatic ducts. He underwent an ERCP which was
complicated by E. coli septicaemia. One week following
the procedure the renal function was as follows:
Sodium
Potassium
Urea
Creatinine
131 mmol/l
4.9 mmol/l
28 mmol/l
430 "mol/l
Question 61
A 50-year-old shipyard worker presented with a single
episode of haemoptysis comprising approximately one
egg cup-full of fresh blood. He gave a two-year history of
progressively increasing breathlessness and a persistent
cough. He had never experienced any chest pain. He
stopped smoking two months previously after a chest
infection which took several weeks to resolve, but before
that was smoking 2030 cigarettes/day. He kept pigeons
in his teenage years, but had not had any direct contact
with birds since. The only other past medical history of
note was a four-year history of mild hypertension, for
which he was taking propranolol 80 mg three times daily.
On examination, he was centrally cyanosed and had early
finger clubbing. The respiratory rate was 23/min. On
examination of the respiratory system the chest expansion
was symmetrical, but generally reduced. The trachea was
central. On auscultation of the lung fields there were fine
end-inspiratory crackles at both lung bases. Precordial
examination was normal, with the exception of a loud
pulmonary component to the second heart sound.
Flow
(l/sec)
10
8
6
4
61
Normal
Patient
2
0
2
4
6
8
10
0 1 2 3 4 5 6 7 8
Change in lung volume (l)
14 g/dl
9 ! 109/l
190 ! 109/l
91 fl
64 mm/h
132 mmol/l
3.7 mmol/l
7 mmol/l
91 "mol/l
7.44
7.1
3.4
21
75%
Irregular, linear shadowing
at both lung bases
No abnormalities
66
Answer 60
e. None of the above.
The patient has probably developed renal failure
secondary to acute tubular necrosis arising from E. coli
septicaemia. Acute tubular necrosis generally lasts
between one and three weeks. Most patients make a
recovery and return to their normal or near normal renal
function. The management of acute renal failure due to
acute tubular necrosis is supportive.
Nephrotoxic agents are stopped or avoided.
Hypovolaemia is corrected with intravenous saline whilst
monitoring central venous pressure. Urine output is
monitored with a urinary catheter in situ. Once the
patient is euvolaemic, the quantitative daily fluid
replacement is equal to the volume of urine output plus
an additional 500 ml to allow for insensible losses. The
patient is carefully monitored for signs of fluid overload
Answer 61
1: b. Carcinoma of the bronchus.
2: e. Asbestosis.
The main features of this case are a long-term smoker who
presents with haemoptysis. He has worked in the shipyard,
an occupation which was historically associated with
asbestos exposure. He has objective evidence of lung
fibrosis; he is hypoxic, his chest X-ray shows linear
shadowing in the lower zones and the flow loop is
consistent with shrunken lungs. In the context of this case
the most likely cause for lung fibrosis and breathlessness is
asbestosis. The history of keeping pigeons may implicate
extrinsic allergic alveolitis as a possible cause; however, it
has been a long time since he was exposed to avian
antigens. Furthermore, EAA classically causes upper zone
reticulo-nodular shadowing on the chest X-ray, whereas
asbestosis is associated with shadowing in the lower zones.
Clinical Cases
67
Questions 62 and 63
A 62-year-old male presented with fever and
breathlessness four weeks after a prosthetic aortic valve
replacement for aortic stenosis. On examination he
appeared pale and had a temperature of 38C (100.4F).
Auscultation of the heart revealed a prosthetic second
heart sound and a long early diastolic murmur.
Auscultation of the lungs revealed inspiratory crackles at
both lung bases.
Initial investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
12-lead ECG
Chest X-ray
Question 62
Which two of the following investigations will
provide the most diagnostic information?
a. C-reactive protein.
b. Renal ultrasound.
c. ASO titres.
d. Serial blood cultures.
e. Transthoracic echocardiography.
f. Urinalysis for blood.
g. Complement fixation tests for Coxiella burnetii.
h. Transoesophageal echocardiography.
11 g/dl
15 ! 109/l
400 ! 109/l
70 mm/h
140 mmol/l
4.2 mmol/l
8 mmol/l
130 "mol/l
Left bundle branch block (old)
Cardiomegaly and pulmonary
oedema
Question 63
Which organism is most likely to be present in the
blood culture?
a. Streptococcus viridans.
b. Staphylococcus aureus.
c. Staphylococcus epidermidis.
d. Organism from the HACEK group.
e. Enterococci.
Question 64
A 38-year-old male was investigated for abnormal liver
function tests following investigation of intermittent
episodes of diarrhoea. He was generally fit and well. He
consumed no more than 10 units of alcohol per week.
He did not take any medications. He had a past history
64
Hb
WCC
Platelets
CRP
Bilirubin
ALT
Alkaline phosphatase
Albumin
Thyroxine
TSH
Hepatobiliary ultrasound
ERCP (64)
11 g/dl
7 ! 109/l
190 ! 109/l
12 g/l
19 mol/l
32 iu/l
178 iu/l
33 g/l
102 nmol/l
1.2 nmol/l
Normal
68
Answers 62 and 63
Answer 62
d. Serial blood cultures.
h. Transoesophageal echocardiography.
Answer 63
c. Staphylococcus epidermidis.
The patient has developed a fever and murmur of aortic
regurgitation only four weeks after a prosthetic aortic
valve replacement, indicating early prosthetic valve
endocarditis. In early PVE, micro-organisms usually reach
the prosthesis by direct contamination during the intraoperative period or via haematogenous spread several
days or weeks after surgery. The consequences of early
PVE are grave as the organisms have direct access to the
prosthesis annulus-interface and to perivalvular tissue
around the sutures lines since the valve is not
endothelialized. Patients with early PVE commonly
develop valve dehiscence and annular abscesses. The risk
of embolic phenomena is also greater with PVE. The
clinical features are similar to native valve endocarditis.
Answer 64
a. Primary sclerosing cholangitis.
The ERCP shows multiple strictures and dilatations in
the intrahepatic ducts and in the left and right hepatic
ducts. The finding is characteristic of primary sclerosing
cholangitis, which is a chronic progressive inflammatory
Clinical Cases
69
Question 65
A 52-year-old man was admitted to the intensive care
unit with difficulty in breathing after a coryzal illness. He
had a six-week history of rapidly progressive muscular
fatigue which was worse at the end of the day. More
recently he had had difficulty with speech and chewing
food while eating.
15 g/dl
9 ! 109/l
200 ! 109/l
Normal
Elevation of both hemidiaphragms
Lungs normal
Arterial blood gases:
pH
7.1
PaCO2
9 kPa
PaO2
7 kPa
FVC (baseline)
0.8 l
FVC (after 2 mg
1.2 l
edrophonium)
Hb
WCC
Platelets
Electrolytes
Chest X-ray
Question 66
66
70
Answer 65
d. Plasmapheresis.
The patient presents with acute generalized muscle
weakness and respiratory failure. There is a six-week
history of muscle fatigue, which is a cardinal feature of
myasthenia gravis. Response to edrophonium (Tensilon),
a short-acting anti-cholinesterase agent, supports the
diagnosis of myasthenia gravis, although false-positive
results are common.
Patients with myasthenia gravis may present with
myasthenic crises, which comprise severe muscle
weakness including respiratory and bulbar muscles. Such
Elective ventilation
Withdrawal of anti-cholinesterase drugs
(if applicable)
Plasmapheresis or intravenous
immunoglobulin
Indications
Mild symptoms
Ocular myasthenia
Immunosuppressive drugs
Corticosteroids
Azathioprine
Cyclosporin
Thymectomy*
* Some neurologists recommend thymectomy even in the absence of thymoma in all patients between puberty
and 60 years of age since most patients have abnormalities of the thymus gland.
Answer 66
b. Dextrocardia.
The patient has a dominant R wave in V1 which would
be consistent with all five choices provided in the
question. There is a rightward QRS and P wave axis, a
deep S wave in lead I and dominant R wave in aVr which
Clinical Cases
71
Question 67
An 18-year-old girl presented with a six-month history of
daytime somnolence that was causing embarrassment
during lecture theatres and while talking to friends. She
was apprehensive about driving because she did not have
any recollection about how she had driven from one
destination to another and felt that she may have fallen
asleep while driving on a few occasions. She had vivid
frightening dreams just as she fell asleep, which would
wake her frequently. On waking she was unable to move
for a few minutes. Three months previously the patient
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
12-lead ECG
Chest X-ray
11 g/dl
15 ! 109/l
400 ! 109/l
70 mm/h
140 mmol/l
4.2 mmol/l
8 mmol/l
130 "mol/l
Left bundle branch block (old)
Cardiomegaly and pulmonary
oedema
Question 68
A 70-year-old man with a known history of ischaemic
heart disease and congestive cardiac failure presented
with nausea and abdominal discomfort. He was taking
digoxin 250 g , frusemide 40 mg and lisinopril 20 mg.
The patient had been recently commenced on
amiodarone for atrial fibrillation. On examination the
JVP was raised 4 cm above the sternal angle. There was a
third heart sound. The liver edge was palpable 3 cm
below the costal margin and there was mild ankle
oedema. The digoxin level was 3 iu (NR 12 iu).
72
Answer 67
d. Narcolepsy.
The patient has excessive daytime somnolence,
hypnagogic hallucinations, cataplexy and sleep paralysis.
This combination is consistent with the diagnosis of
narcolepsy. Spontaneous recovery of the events is
inconsistent with hypoglycaemic episodes. Torsades de
pointes due to long QT syndrome may present with
episodic collapse during intense emotion; however,
consciousness is impaired in collapse associated with long
QT syndrome. (See Question 266.)
Excessive daytime somnolence is a cardinal feature of
narcolepsy. The symptoms are improved after a brief nap.
Hypnagogic hallucinations are vivid and often
frightening hallucinations just after falling asleep or just
before waking. They are effectively a mixture of REM
sleep and wakefulness.
Cataplexy is defined as sudden episodes of bilateral
muscle weakness leading to partial or complete collapse. It
is usually triggered by strong emotions such as anger,
laughter or intense excitement. Weakness is present for 12
minutes. Consciousness is not impaired. Almost two-thirds
of patients with narcolepsy go on to develop cataplexy.
Sleep paralysis is a complete inability to move 1 or 2
minutes after waking and is often accompanied by
hypnagogic hallucinations.
Answer 68
d. Halve the dose of digoxin.
The patient has abdominal discomfort and nausea. The
differential diagnosis for his symptoms includes hepatic
congestion secondary to heart failure, digoxin toxicity or
gastro-intestinal side-effects of amiodarone (usually occur
within a few days of starting the drug). In this particular
situation the plasma digoxin level is raised and hence
digoxin toxicity is the most likely cause (Tables A and B).
Amiodarone may promote digoxin toxicity by competing
for digoxin binding sites hence increasing plasma digoxin
Clinical Cases
73
Question 69
A 15-year-old Nigerian female was admitted with right
upper quadrant abdominal pain. She had a history of
sickle cell anaemia, and had several admissions with hand
and foot crises. During the last two admissions she
complained of abdominal pain. She was born in England.
She was the only child of a middle-class family.
On examination, she was distressed with pain. The
temperature was 37.6C (99.7F). She was mildly
jaundiced. The pulse was 105 beats/min, and blood
pressure 100/75 mmHg. On examination of the
respiratory system there was dullness to percussion on the
anterior aspect of the right lung. Abdominal examination
revealed tenderness in the right upper quadrant. The liver
was palpable 3 cm below the costal margin.
Investigations are shown.
Hb
WCC
Platelets
U&E
AST
Alkaline phosphatase
Albumin
Urine osmolality
Urinalysis
Chest X-ray
6 g/dl
12 ! 109/l
200 ! 109/l
Normal
50 iu/l
150 iu/l
34 g/l
120 mOsm/kg
Urobilinogen +++
Blood
0
Protein 0
Bilirubin 0
Opacification in the right
upper zone
Question 70
A 25-year-old female presented with a right calf deepvein thrombosis.
Blood results are shown.
Hb
WCC
Platelets
PT
APTT
Antinuclear
antibody factor
Double-stranded
DNA
12 g/dl
7 ! 109/l
140 ! 109/l
13 s (control 12 s)
59 s (control 40 s)
Not detected
Not detected
74
Answer 69
1. Acute cholecystitis.
2. Ultrasound examination of the liver.
3. Right upper lobe pneumonia.
4. Chronic tubulo-interstitial nephritis or renal papillary
necrosis leading to impaired concentrating ability.
Sickle cell anaemia is discussed in detail in Answer 263.
This question tests the readers knowledge of
complications secondary to sickle cell anaemia.
The story is typical of cholecystitis which, in this case, is
secondary to pigment gallstones. Hepatic infarction due to
a sickling crisis in the liver is unlikely because it would be
associated with a higher AST. Sequestration is unlikely
because it is very rare in older patients with sickle cell
anaemia. The shadowing on the chest X-ray is probably
secondary to streptococcal pneumonia. Patients with sickle
cell anaemia are hyposplenic as a result of autosplenic
infarction. As a result, they are predisposed to bacterial
infections by capsulated organisms such as Streptococcus
pneumoniae, Neisseria meningitidis and Haemophilus
influenzae. Pulmonary infarction may also cause
pulmonary shadowing on the chest X-ray but is less likely
in the absence of pleurisy and severe breathlessness.
Answer 70
1. Antiphospholipid syndrome.
2 . i. Antiphospholipid antibodies (these may result in
a false positive VDRL test).
ii. Failure of APTT to improve after addition of
normal plasma.
iii. Lupus anticoagulant.
3. Any of the following:
i. Recurrent abortions.
ii. Livedo reticularis.
iii. Pulmonary hypertension.
iv. Transient ischaemic attacks.
v. Chorea.
vi. Migraines.
vii. Valvular heart disease.
viii. Thrombocytopenia.
The antiphospholipid syndrome usually affects young
women and is characterized by arterial and venous
thromboses and recurrent abortions (Table). There may
be evidence of thrombocytopenia. It is caused by
circulating antiphospholipid antibodies, which are IgG
and IgM immunoglobulins directed against phospholipid
molecules. They were first described in SLE, but may be
present in a wide variety of autoimmune conditions and
have been associated with multiple sclerosis, acquired
immunodeficiency syndrome (AIDS) and carcinomatosis.
Clinical Cases
75
Question 71
71a
15 g/dl
10 ! 109/l
230 ! 109/l
30 mm/h
2.3 mmol/l
0.8 mmol/l
90 iu/l
40 g/l
Glucose ++
Protein 0
71b
71c
76
Answer 71
1. Alkaptonuria.
2. Urinary homogentisic acid level. Urine becomes
dark on standing.
3. Homogentisic acid is a reducing substance and
therefore gives a positive reaction to glucostix
(Clinistix). Other substances that produce a falsepositive glucostix test are shown (Table). Glucose
oxidase (Clinitest) sticks do not give this falsepositive reaction.
Alkaptonuria is inherited as an autosomal recessive trait.
There is a deficiency in the enzyme homogentisic acid
oxidase, leading to accumulation of homogentisic acid in
the urine and increased pigmentation (ochronosis) in
cartilage and connective tissue. Urine becomes dark on
standing owing to oxidation and polymerization of
homogentisic acid. Freshly voided urine appears normal
in colour, so these patients do not often report dark
urine. Abnormal pigmentation is found in the ear and
sclerae (71a, b) as well as articular cartilage (at surgery).
Premature arthritis predominantly affecting the back, and
Fructose
Pentose
Lactose
Salicylates
Ascorbic acid
Homogentisic acid
Question 72
An 18-year-old male was referred to the respiratory outpatient clinic with a three-year history of progressively
increasing breathlessness. Until the age of 15 years he was
able to participate in school sports, but since then he had
noticed increasing fatigue and breathlessness on exertion.
He was diagnosed as having exercise-induced asthma and
was prescribed salbutamol and beclomethasone inhalers,
with initial relief of his symptoms until he was 16 years of
age, when his symptoms started to deteriorate. At this
stage he was seen by a hospital specialist, who felt that he
had resistant asthma and started him on a two-week trial of
oral steroids, which proved to be successful. Subsequently,
the dose of inhaled steroid was increased. Three months
before coming to clinic his symptoms had deteriorated
considerably. He was breathless on walking less than 200
metres on the flat at a slow pace. His appetite was reduced,
and he had noticed that his ankles were swollen towards
the end of the day. He was a non-smoker, and had never
consumed alcohol. He was currently at a college
attempting to do his GCSE examinations, but was having
Clinical Cases
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Total protein
Albumin
Bilirubin
AST
Alkaline phosphatase
77
17 g/dl
9 ! 109/l
130 ! 109/l
100 fl
135 mmol/l
4.1 mmol/l
3 mmol/l
60 mol/l
2.1 mmol/l
1.0 mmol/l
66 g/l
31 g/l
58 mol/l
49 iu/l
600 u/l
72
Question 73
A 48-year-old baker presented with a right deep-vein
thrombosis affecting the right calf. Apart from a swollen
right calf, physical examination did not demonstrate any
other abnormality.
Hb
PCV
MCV
WCC
Neutrophils
Lymphocytes
Monocytes
Platelets
Blood film
18 g/dl
0.57 l/l
89 fl
9 ! 109/l
92%
8%
4%
388 ! 109/l
Normal
78
Answer 72
e. Measurement of the serum -1 antitrypsin and
its electrophoretic mobility.
The patient has hyperinflated lung fields, an obstructive
lung defect with reduced transfer factor and evidence of
cirrhosis of the liver. The combination of chronic lung
disease and cirrhosis of the liver in a young patient should
raise suspicion of two important diagnoses: -1
antitrypsin deficiency; and cystic fibrosis. In this case, the
chest X-ray is against the diagnosis of cystic fibrosis (72).
Patients with cystic fibrosis often have cystic
bronchiectasis, patchy consolidation and fibrotic changes.
Furthermore, the absence of cough productive of sputum
is also against the diagnosis of cystic fibrosis.
-1 antitrypsin deficiency is a rare autosomal recessive
disorder due to a genetic abnormality on chromosome
14. The absence or reduced levels of this protease
inhibitor leads to alveolar and liver damage. There are
several different abnormal alleles for the gene. M is the
normal allele, and Z and S are the most frequently
encountered abnormal alleles. The expression of each
phenotype is suffixed by the letters Pi, which stand for
Answer 73
1. b. Secondary polycythaemia.
2. i. Red cell mass estimation.
ii. Arterial blood gases.
iii. Abdominal ultrasound scan with particular
reference to the kidneys and the liver.
iv. -fetoprotein.
v. Erythropoietin level.
The patient has an elevated haemoglobin and a raised
PCV. The differential diagnosis is between
pseudopolycythaemia, primary polycythaemia
(polycythaemia rubra vera) or a secondary polycythaemia.
In pseudopolycythaemia, the Hb and the PCV are raised
owing to haemoconcentration resulting from any cause
of reduced extracellular volume (dehydration, diuretics).
Pseudopolycythaemia can be differentiated from true
polycythaemia by red cell mass estimation, which will
reveal a normal red cell volume to extracellular fluid
volume ratio in pseudopolycythaemia, and a raised ratio
in true polycythaemia. A popular cause of
pseudopolycythaemia in the MRCP and similar
examinations is Gaissbocks syndrome, which occurs in
middle-aged men who are usually obese and have a
smoking history. In this case, the red cell volume is
normal, but the plasma volume is reduced. True
polycythaemia is divided into primary polycythaemia and
secondary polycythaemia. The former is a result of a
Genotype
-1 antitrypsin levels
PiMM
PiSS
PiZZ
PiSZ
Pi null null
Normal
>50%
<10%
20%
Nil
Clinical Cases
79
Causes of polycythaemia
Pseudopolycythaemia
Dehydration
Gaissbocks syndrome
Primary
Polycythaemia rubra vera
Secondary
1. Physiological increase in erythropoietin (due to chronic hypoxaemia):
Chronic lung disease
Living at high altitudes
Cyanotic heart disease
Smoking (carboxyhaemoglobin)
Familial (HbM)
2. Inappropriate increase in erythropoietin:
Renal cell carcinoma, polycystic kidneys, transplant kidney
Adrenal tumours (phaeochromocytoma)
Hepatocellular carcinoma
Ovarian fibroma
Cerebellar haemangioblastoma (part of Von HippelLindau)
73
Pseudopolycythaemia
Important investigations
Normal
Normal WCC
Normal platelets
No splenomegaly
High
O2 saturation >90%
True erythrocytosis
Dehydration
Diuretics
Gaissbocks syndrome
Renal ultrasound
Hepatic ultrasound/-fetoprotein
O2 saturation <90%
Chronic obstructive
pulmonary disease
Cyanotic heart disease
High altitude
Pickwickian
80
Question 74
A 62-year-old former insurance broker presented to the
cardiology out-patient clinic with a five-week history of
increasing breathlessness and ankle swelling that started
while on a three-week holiday in Spain. Over the past three
days he had become breathless at rest, and was having to
sleep propped up on four pillows to help his symptoms.
His GP had commenced him on a small dose of diuretic,
which had not made any difference. There was no history
of chest pain and no coryzal illness over the past few
months. Eight months previously he was diagnosed as
having diabetes mellitus, which was not well controlled on
oral hypoglycaemic agents, and he had recently started
insulin injections. The only other past medical history of
note was intermittent pain and swelling in both knees that
was helped by taking an NSAID. He was married and had
three sons. He had never smoked, and consumed a very
occasional glass of wine. There was a strong family history
of diabetes and ischaemic heart disease. His father had died
from heart failure.
On examination, he was slightly tanned. He was
breathless on mild exertion. His heart rate was 110
beats/min and regular. His blood pressure was
100/60 mmHg. Examination of the neck is shown (74a).
The apex was displaced in the 6th intercostal space and
anterior axillary line. On auscultation of the precordium
there was a loud third heart sound, and a soft systolic
murmur in the mitral area. Auscultation of the lung fields
demonstrated basal inspiratory crackles bilaterally. The
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
AST
ALT
Alkaline phosphatase
Albumin
Blood glucose
ECG (74b)
Chest X-ray (74c)
Echocardiogram
14 g/dl
10 ! 109/l
158 ! 109/l
90 fl
134 mmol/l
3.5 mmol/l
11 mmol/l
110 mol/l
100 iu/l
110 iu/l
130 u/l
38 g/l
6 mmol/l
Clinical Cases
74a
74b
74c
74d
74e
74g
81
74f
74h
74i
82
Answer 74
1. Congestive cardiac failure.
2. Cardiomegaly and pulmonary oedema.
3. LBBB (Table A).
4. Dilated left ventricle. The upper limit of normal
size for the left ventricular end-diastolic dimension
is 54 mm. Each white line on the scan represents
10 mm.
5. Coronary angiography, which demonstrates a
normal left and right coronary artery. See
diagrammatic representation of the coronary
anatomy (74J).
6. Chondrocalcinosis (Table B).
7. Cirrhosis of the liver complicated by portal
hypertension.
8. Enlarged spleen which, in the presence of ascites,
would be consistent with the diagnosis of portal
hypertension in the context of this history.
9. Perls stain, which is used to demonstrate the
presence of iron. In the presence of iron, Perls
stain produces a dark blue/black colour.
10. Idiopathic haemochromatosis.
11. Weekly venesection until the serum ferritin is
normal.
12. Screen his sons for the genetic disorder. This
could be done genetically, or with iron studies.
Affected asymptomatic relatives can thus be
treated before there is any tissue damage.
In the absence of alcohol abuse, the combination of a
dilated cardiomyopathy with normal coronary arteries,
diabetes mellitus, arthropathy, and cirrhosis of the liver in
a pigmented individual can all be explained by idiopathic
haemochromatosis, an autosomal recessive genetic
disorder characterized by increased iron absorption from
the gastrointestinal tract with subsequent deposition in
the skin, liver, heart, pancreas, gonads and the pituitary
gland. The genetic defect is a point mutation on the
gene HLA FE, which is the short arm of chromosome 6.
The mutation results in the substitution of the amino
acid cysteine by tyrosine at position 282. The actual
function of the gene is unknown. There is also an
association with HLA-A3, B7 and HLA-A3, B14. The
most common presentation in homozygotes is with
lethargy and malaise, although joint pains, particularly in
the knee, symptoms of diabetes mellitus and skin
pigmentation may also be the initial presenting
complaints. Males are more susceptible than females who
are protected by menstruation. Alcohol abuse may
cause the same clinical picture in heterozygotes.
Cardiac involvement leads to dilated or restrictive
cardiomyopathy and an abnormal ECG, but
haemochromatosis is a rare cause of cardiomyopathy.
Deposition of excess iron in the liver leads to cirrhosis and
an increased predisposition to hepatocellular carcinoma.
Chondrocalcinosis is a recognized complication, most
74j
LMS
RCA
proximal
RCA
mid
LAD proximal
CX
OM1
LAD
mid
OM2
RCA
distal
Intermediate
PD
LAD
distal
Key:
CX Circumflex artery
LAD Left anterior descending artery
LMS Left main stem
OM Obtuse marginal
PD Posterior descending artery
RCA Right coronary artery
Clinical Cases
83
Table C Differential diagnosis of conditions causing simultaneous cardiac and liver disease
Alcohol abuse
Haemochromatosis
Pericardial constriction
Chronic tricuspid regurgitation
Carcinoid tumour with hepatic metastases
Sarcoidosis
HIV
Neoplasia
Storage disorders
Liver
Cirrhosis
Cirrhosis
Cirrhosis
Hepatic congestion
Metastases
Granulomas
Hepatitis
Metastases
Hepatic dysfunction
Heart
Dilated cardiomyopathy
Dilated cardiomyopathy
Cardiac failure
Cardiac failure
Pulmonary/tricuspid stenosis
Restrictive cardiomyopathy
Myopericarditis
Pericardial effusion
Cardiomyopathy
Question 75
75
84
Answer 75
1. b. Mesenteric ischaemia. The differential diagnosis
includes carcinoma of the pancreas or chronic
pancreatitis.
2. d. Mesenteric angiography.
The patient has chronic abdominal pain after meals,
steatorrhoea and weight loss. All three differential
diagnoses could account for this picture. He has stigmata
of hyperlipidaemia (the eyes reveal xanthelasma and
corneal arcus) and peripheral vascular disease (carotid
bruit). He is diabetic, and a long-term smoker. All these
factors favour atherosclerosis, making the diagnosis of
intestinal ischaemia more likely in the examination
situation, although there is no reason why a patient with
generalized arteriosclerosis should not develop carcinoma
of the pancreas or chronic pancreatitis, which is
idiopathic in almost 50% of cases. Severe atheroma
affecting the coeliac axis would account for the
symptoms. Increased intestinal motility after a meal
exacerbates ischaemia, causing pain. The ischaemic small
bowel loses functional capacity and therefore a
Question 76
A 34-year-old female presented with a six-week history of
epigastric pain that radiated to her back and that was
precipitated by meals. There was no accompanying
nausea or vomiting. Her GP prescribed ranitidine and
antacid solution, which relieved the discomfort to some
extent. Just one month previously she had requested a
blood sugar check because she had developed nocturia,
but the test was normal. According to her husband, she
had started to become miserable and spoke very little.
She attributed this to fear of having an abdominal
malignancy because her maternal aunt had just died from
carcinoma of the stomach. The only other family history
of significance was that her father had undergone an
operation on his neck 20 years ago to treat kidney stones.
She did not consume alcohol and was a non-smoker. She
worked in a confectioners shop near the house. She had
two daughters, aged eight and six.
On examination, the patient had mild tenderness on
palpation of the epigastrum, but all other physical
examination was normal.
Investigations are shown.
The patient underwent surgery shortly afterwards,
which improved all her symptoms, and she remained well
for six years; following this, the abdominal pain returned.
The pain was associated with dyspepsia. She also
complained of intermittent episodes of foul-smelling
diarrhoea. She was prescribed ranitidine once again;
however, on this occasion it proved to be ineffective. She
12 g/dl
7 ! 109/l
380 ! 109/l
88 fl
11 mm/h
135 mmol/l
4 mmol/l
7.1 mmol/l
89 mol/l
118 mmol/l
19 mmol/l
3.0 mmol/l
0.7 mmol/l
345 iu/l
4.6 mmol/l
Faecal loading, but no
bowel obstruction
20 mmol/l
Clinical Cases
76a
76b
Hb
WCC
Platelets
MCV
ESR
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Alkaline phosphatase
Thyroxine
TSH
FSH
LH
PRL
Skull X-ray (76b)
10 g/dl
6 ! 109/l
300 ! 109/l
81 fl
25 mm/h
129 mmol/l
4 mmol/l
4 mmol/l
89 mol/l
2.1 mmol/l
1.2 mmol/l
92 iu/l
4 nmol/l
0.1 mu/l
0.3 iu/l
0.3 iu/l
4,500 mu/l
85
86
Answer 76
1.
2.
3.
4.
Hyperparathyroidism.
Parathyroidectomy.
Peptic ulceration resulting from a gastrinoma.
Assessment of serum gastrin after intravenous
secretin or measurement of gastric acid output after
the administration of pentagastrin. In normal
individuals, secretin causes suppression of serum
gastrin levels; however, in patients with gastrinomas,
gastrin secretion is not suppressed and may even
demonstrate a paradoxical rise. Pentagastrin reduces
gastric acid production in normal individuals, but
not in patients with gastrinomas.
5. The patient has a bitemporal hemianopia, suggesting
a lesion compressing the optic chiasm. This could be
a meningioma, an aneurysm, a pituitary tumour or a
cerebral metastasis.
6. There is enlargement of the pituitary fossa, a double
floor to the sella turcica and erosion of the posterior
clinoid process. The findings are consistent with a
pituitary tumour.
Causes of hyperprolactinaemia
Prolactinoma
Hypothalamic or pituitary stalk lesions
Hypothyroidism
Coitus
Pregnancy
Nipple suckling
Stress
Oral contraceptive pill
Dopamine antagonist drugs, e.g. phenothiazines
PCOS
Chronic renal failure
Chest wall damage/trauma
Clinical Cases
Question 77
A 48-year-old male with rheumatoid arthritis presented
with a cough, high fever and painless jaundice. He had a
seven-year history of rheumatoid arthritis affecting his
shoulders, elbows, wrists, hands and feet, and which was
refractory to therapy with NSAIDs. Over the past 16
months his symptoms had progressed, and he had been
switched to immunosuppressant drugs, which had
controlled his symptoms. He was a non-smoker and
consumed less than 2 units of alcohol per week.
On examination he was unwell, jaundiced and had a
temperature of 39C (102.2F). Examination of the oral
cavity revealed candidal infection and palatal petechiae.
On auscultation of the lung fields there were coarse
crackles at the right lung base. On abdominal
examination there was evidence of a palpable spleen 3 cm
below the costal margin.
Investigations are shown.
Hb
WCC
Platelets
MCV
Reticulocyte count
INR
ESR
CRP
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
7.1 g/dl
1.4 ! 109/l
33 ! 109/l
103 fl
<1%
1.9
70 mm/h
190 g/l
136 mmol/l
4 mmol/l
6 mmol/l
110 mol/l
180 mol/l
180 iu/l
450 iu/l
29 g/l
Question 78
The following cardiac catheter data is from a 10-year-old
male after a murmur was heard during a school medical.
Chamber
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left ventricle
Aorta
Pressure (mmHg)
5
20/6
32/12
3
100/8
90/65
Oxygen saturation(%)
74
74
92
96
96
87
88
Answer 77
1. i. Septicaemia secondary to respiratory infection
precipitated by methotrexate-induced
neutropenia.
ii. Septicaemia secondary to respiratory infection
precipitated by azathioprine-induced neutropenia.
iii. Septicaemia secondary to respiratory tract
infection due to Feltys syndrome.
2. i. Chest X-ray.
ii. Oxygen saturation.
iii. Blood cultures.
iv. Urine culture.
v. Throat swab for culture.
vi. Hepatobiliary ultrasound scan.
3. i. Megaloblastic anaemia due to methotrexate or
azathioprine.
ii. Megaloblastic anaemia due to folate deficiency
(methotrexate inhibits dihydrofolate reductase).
iii. Liver cirrhosis.
4. i. Stop immunosuppressant drug.
ii. Broad-spectrum intravenous antibiotics following
a septic screen. Usually the combination of a
penicillin and aminoglycoside or a third-line
cephalosporin is used.
This patient with rheumatoid arthritis presents with a
respiratory tract infection and high fever. The blood tests
reveal a profound neutropenia, which has almost certainly
predisposed him to the respiratory and oral Candida
infection. In the context of rheumatoid arthritis, the
neutropenia is either drug-induced or secondary to
hypersplenism (part of Feltys syndrome). Feltys
Answer 78
1. i. Elevated pulmonary artery pressure.
ii. Step up in oxygen saturation in the pulmonary
artery.
2. The findings are consistent with a patent ductus
arteriosus with a left-to-right shunt.
Clinical Cases
89
Question 79
A 25-year-old male presented to the Accident and
Emergency Department with a three-day history of
pleuritic, left-sided chest pain and increasing breathlessness.
The symptoms started suddenly while he was playing
football. He denied any chest trauma. Until then he had
been fit and well, and there was no past medical history of
note. His father died suddenly at the age of 32 years.
On examination he was thin and tall and distressed
with pain. There was no pallor or cyanosis. He had a
wide arm span. The heart rate was 100 beats/min and
blood pressure 150/80 mmHg. The respiratory rate was
32/min. The trachea was deviated to the right.
Percussion appeared to be reduced on the right side and
was loud on the left side. The left lung base was dull to
percussion. On auscultation of the lung fields breath
Question 80
80a
80b
80d
80c
90
Answer 79
1. Chest radiography.
2. A large, left-sided pneumothorax.
3. Insertion of a chest drain.
4. Marfans syndrome.
A large pneumothorax in a symptomatic patient receives
relief with chest drain insertion rather than simple needle
aspiration. Pleuritic chest pain and increasing
breathlessness occur in pleurisy with or without pleural
effusion, pneumonia, pulmonary embolism and lung
malignancy. The physical signs are suggestive of a large
left pneumothorax. The trachea is deviated to the right,
and there are no breath sounds on auscultation of the left
lung. The right lung sounds comparatively dull to
percussion when compared with the left lung, which is
hyper-resonant. There also appears to be a small effusion
at the base of the left lung, which is not uncommon with
pneumothoraces and represents either blood or an
inflammatory exudate.
Causes of pneumothorax include asthma, emphysema,
stab wound to the lung or following a fractured rib,
fibrotic lung disease, suppurative lung disease (rupture of
a lung abscess into a bronchus, staphylococcal
pneumonia), pneumoconiosis, neurofibromatosis,
Answer 80
1. An enlarged cardiothoracic ratio and evidence of an
enlarged left atrium. Features of an enlarged left
atrium include a prominent left heart border, a
double shadow behind the heart and splaying of the
carinae, with elevation of the left hilum.
2. Atrial fibrillation (for causes, see Table, Answer
138). There is a complete absence of P-waves
and a beat-to-beat variation of the RR-interval. This
patient also has voltage criteria for left ventricular
hypertrophy, presumably secondary to the
hypertension or coexisting mitral regurgitation.
3. i. Enlarged left atrium.
ii. A thickened dome-shaped appearance of the
mitral valve in diastole, which is consistent with
mitral stenosis.
Clinical Cases
91
Question 81
A 47-year-old businessman was referred to the
dermatology clinic with a rash over his hands, scalp and
face. He had been generally well. He smoked 20 cigarettes
per day and drank 810 units of alcohol on a daily basis.
There was no other significant medical history of note. The
patient had not taken any medication, with the exception
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Blood glucose
Bilirubin
AST
Alkaline phosphatase
Albumin
Globulins
Gamma GT
Serum ferritin
Skin biopsy
18.5 g/dl
7 ! 109/l
149 ! 109/l
101 fl
135 mmol/l
3.9 mmol/l
4 mmol/l
80 mol/l
10 mmol/l
25 mol/l
52 iu/l
450 iu/l
37 g/l
30 g/l
52 iu/l
550 g/l
Subepidermal blisters with perivascular
deposition of PAS-staining material
81
Question 82
A 13-year-old female was admitted under the surgeons
with acute abdominal pain. The blood pressure was
100/60 mmHg.
Investigations are shown.
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
Abdominal X-ray
Urinalysis
131 mmol/l
7.2 mmol/l
13 mmol/l
121 mol/l
8 mmol/l
96 mmol/l
Normal
Glucose +++
92
Answer 81
1. PCT.
2. i. Urinary uroporphyrin level.
ii. Uroporphyrin decarboxylase assay on red blood
cells.
3. i. Sunlight.
ii. Alcohol.
4. i. Venesection.
ii. Chloroquine.
The blistering skin rash in a patient with a history of
excess alcohol consumption and biochemical evidence of
liver disease is suggestive of the diagnosis of PCT.
PCT is a rare disorder of haem synthesis that is
inherited as an autosomal dominant trait. It is one of the
most commonly tested porphyrias in higher medical
examinations, and is caused by a reduced activity or
complete absence of the enzyme uroporphyrin
decarboxylase, which catalyses the conversion of
uroporphyrin to coproporphyrin. This leads to an excess
of uroporphyrins in the blood and urine. The result is a
pruritic photosensitive blistering rash that affects areas
exposed to sunlight, and cirrhosis of the liver. Blisters on
the skin lesion contain PAS-positive material. The clinical
Answer 82
1. Metabolic acidosis with a high anion gap.
2. Diabetic ketoacidosis.
3. i. Intravenous calcium gluconate to prevent
hyperkalaemic cardiac arrest.
ii. Intravenous insulin infusion to halt further
ketoacidosis.
iii. Intravenous saline to rehydrate patient and
correct acidosis.
The patient has a very low serum bicarbonate, which is
indicative of a metabolic acidosis. The heavy glycosuria is
the clue to the cause of the acidosis. Diabetic ketoacidosis
is the result of insulin deficiency. It may occur in
previously undiagnosed insulin-dependent diabetes
mellitus, established insulin-dependent diabetics who are
Clinical Cases
93
Question 83
A 14-year-old male was admitted with a headache and
drowsiness. Three days previously he had complained of a
sore throat.
Investigations are shown.
CT scan of brain
CSF:
Opening pressure
Cells
Protein
Glucose
Gram stain (83a)
83a
Normal
160 mmH2O
200 neutrophils/mm3
20 red cells/mm3
1.2 g/l
2.4 mmol/l
Question 84
A 64-year-old West Indian male was admitted after his
daughter noted that he had become increasingly drowsy
over the past 48 hours. He had a 10-year history of
diabetes mellitus for which he was taking
chlorpropamide. Before the deterioration, he had
complained of increasing urinary frequency and excessive
thirst. He recently saw his GP, and was noted to have a
blood pressure of 170/100 mmHg for which he had
been commenced on a thiazide diuretic.
On examination he was drowsy and apyrexial, but
answered questions appropriately. There was reduced
skin turgor. The heart rate was 110 beats/min and
regular, and the blood pressure was 115/60 mmHg. The
heart sounds were normal, and the chest was clear.
Examination of the abdomen did not reveal any
abnormality, and there was no focal neurological deficit.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Urinalysis
15 g/dl
13 ! 109/l
179 ! 109/l
151 mmol/l
5 mmol/
17 mmol/l
140 mol/l
Glucose +++
Protein +
94
Answer 83
1. a. Streptococcal meningitis.
2. Intravenous cefotaxime on admission. The
antibiotic can be switched to benzylpenicillin if the
organism is sensitive to penicillin.
The CSF neutrophil count is consistent with a bacterial
meningitis (see Answer 267). The three commonest
bacterial meningitides worldwide include those due to
Streptococcus pneumoniae, Neisseria meningitidis, and
Haemophilus influenzae. The Gram stain reveals Grampositive (stain bluepurple) cocci, therefore the most
likely diagnosis is S. pneumoniae.
N. menigitidis is a Gram-negative (stains pink)
diploccocus (83b). H. influenzae is a Gram-negative
bacillus (pink rods in 83c).
All three present with fever, headache, neck stiffness
and photophobia. A necrotic purpuric rash is characteristic of menigitis due to N. meningitidis, but may
occur with all three types.
83b
83c
Answer 84
1. Hyperosmolar non-ketotic diabetic coma (HONK).
2. i. Plasma osmolality.
ii. Blood glucose.
iii. Blood cultures.
iv. Urine culture.
v. Chest X-ray.
vi. ECG.
3. i. Rehydration with 0.9% saline.
ii. Insulin infusion of 13 units/h.
iii. Anticoagulation.
iv. Treat underlying cause.
Hyperosmolar non-ketotic diabetic coma usually
complicates middle-aged or elderly patients with noninsulin-dependent diabetes mellitus and is characterized
by a marked increase in blood glucose (usually higher than
50 mmol/l) and a consequent increase in plasma
osmolality. Ketonuria is absent and acidosis is mild or
absent. The actual pathogenesis of the condition is
unclear, but possible triggers include consumption of
large amounts of sugary drinks, infection, recent
prescription of thiazide diuretics or steroids and
myocardial infarction. Patients present with thirst,
polyuria, impaired level of consciousness and sometimes
evidence of the precipitating disorder.
Clinical Cases
95
Question 85
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
85a
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
Affected male
Unaffected male*
Affected female
Unaffected female*
85b
AC
Right
Left
BC
Right
Left
Unmasked
125
250
500
1000
2000
4000
8000
Frequency HZ
125
250
500
1000
2000
4000
8000
Frequency HZ
The chart above (85a) is the pedigree of a family with a rare condition. All
members are affected by the same condition. Patient A is dead, but he had a
history of progressive renal failure, and had a renal transplant which was
affected by a separate renal disease causing haematuria and rapid deterioration
of renal function. An audiogram and a picture of his fundus have been
removed from his case notes and are shown (85b, c). His sister (patient C),
aged 70 years, was deaf and had intermittent haematuria, but her creatinine
was 89 mol/l. His brother (patient B), aged 65 years, had a renal transplant
14 years previously and was also deaf. Patients D, F, G, H, I and J all had a
history of intermittent haematuria, but serum creatinine was within the
normal range in each case. Patients D and H had premature cataracts, and
patient J was blind, but did not have cataracts. Patient E was aged 38 and was
on the transplant list for renal failure. He had been fitted with a hearing aid
aged 26 years, and had had intermittent haematuria since he was aged 7 years.
1. What is the mode of transmission of the disorder?
2. What is shown on the audiogram?
3. Why may patient J have been blind?
85c
Question 86
A 45-year-old male attended to become a blood donor.
Blood results were as follows (0 = no agglutination,
+ = agglutination):
1. What is the patients blood group?
2. Give at least two possible underlying diagnoses.
96
Answer 85
1. The mode of inheritance is X-linked dominant.
2. There is progressive and severe hearing loss at
higher frequencies which is typical of
sensorineuronal deafness. (See Audiograms,
page 416.)
3. It is possible that she had retinitis pigmentosa just
like her great uncle (patient A).
4. The condition is Alports syndrome.
5. Anti-GBM disease.
There is no male-to-male transmission which is characteristic of X-linked conditions. Affected males transmit
the disease to all female offspring in conditions inherited
by an X-linked dominant trait, whereas affected females
pass the disease to 50% of all their offspring.
Alportss syndrome is an X-linked hereditary nephritis
characterized by progressive glomerular disease, ocular
and auditory abnormalities. The renal manifestations
begin early in childhood, comprising asymptomatic
haematuria and proteinuria. Progressive renal deterioration has a bimodal age distribution, presenting between
1635 years and 4560 years. Only males develop progressive renal failure. Affected females develop asymptomatic haematuria, but progression to renal failure does
not occur. Sensorineuronal loss occurs in 3050% of
patients, and many patients have ocular abnormalities
which include myopia, retinitis pigmentosa (85c) and
cataracts. Renal biopsy reveals thinning of the GBM, but
as the disease progresses the membranes become thin and
start to split. The genetic defect is in the -5 chain of type
IV collagen which is located on the X chromosome, but
collagen defects in the -3 and -4 chains of type IV
collagen on chromosome 2 have also been described in
some families. All three types of chains combine to form
the collagen network in the GBM. Some patients with
Alports syndrome develop anti-GBM antibodies after
renal transplantation. The risk is greatest in patients with a
large deletion in the gene encoding the -3 chain of type
IV collagen, in which case the Goodpasture antigen is not
expressed and therefore the Goodpasture antigen in the
transplanted organ is recognized as foreign. Some 5% of
patients with transplants for Alports syndrome will
develop anti-GBM disease.
Answer 86
1. Blood group O rhesus-positive (absent anti-A and
anti-B).
2. Hypogammaglobulinaemia due to:
i. Thymoma.
ii. Chronic lymphatic leukaemia.
iii. Myeloma.
iv. Lymphoma.
v. Drugs.
vi. Common variable hypogammaglobulinaemia.
vii. HIV infection.
The patients red cells fail to agglutinate with sera
containing anti-A and anti-B, suggesting that the patient
is blood group O, i.e. the cells do not express the antigens A or B on the cell surface. His cells agglutinate with
serum containing anti-D, indicating that his cells express
the rhesus D antigen. Patients with blood group O have
anti-A and anti-B antibodies which are of the IgG, IgM
and the IgA class. The serum from an O-positive
individual should normally agglutinate blood cells
Clinical Cases
97
Question 87
A 35-year-old woman presented with an epileptic seizure
five days after having a baby by Caesarean section. There
was no previous history of epilepsy. She had been well
throughout her pregnancy. She had had two normal
pregnancies without any complication.
On examination her heart rate was 90 beats/min and
regular and her temperature was 37.9C (100.2F). The
blood pressure was 180/102 mmHg. She had a Glasgow
coma score of 13/15. There was no evidence of a focal
neurological deficit. Investigations are shown.
Hb
WCC
Platelets
Blood film
10 g/dl
11 ! 109/l
45 ! 109/l
Normochromic normocytic anaemia
Fragmented red cells;
microspherocytes
PT
14 s (control 14 s)
APTT
45 s (control 44 s)
Factor V level Normal
Factor VII level Normal
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
LDH
Alkaline phosphatase
Albumin
Urinalysis
CT scan brain
137 mmol/l
4.6 mmol/l
10 mmol/l
130 "mol/l
11 "mol/l
34 iu/l
1530 iu/l (NR 252525 iu/l)
80 iu/l
30 g/l
Protein ++
Normal
Question 88
A 68-year-old Sri Lankan woman presented with a threeweek history of lower back pain and progressive weakness
of the lower limbs. She had a temperature of 37.9C
(100.2F). Investigationsare shown.
88a
88b
Hb
WCC
Platelets
ESR
CRP
Blood cultures
Lumbar spine X-ray
MRI scan lumbar
spine
10 g/dl
13 ! 109/l
460 ! 109/l
120 mm/h
200 g/l
Sterile
(88a)
(88b)
98
Answer 87
d. Plasma exchange with fresh frozen plasma.
The patient is post-partum and presents with an epileptic
seizure (Table A). She has a fever, thrombocytopenia,
microangiopathic haemolytic anaemia and impaired renal
function, raising the possibility of either haemolytic
uraemic syndrome or thrombotic thrombo cytopenic
purpura. The two conditions are probably part of the
same disorder. Classically TTP is characterized by
neurological manifestation and more subtle deterioration
in renal function compared with HUS, where
neurological dysfunction is relatively infrequent. In TTP
neurological manifestations include headache, seizures
and coma. Objective localizing signs are rare. Diagnosis
of TTP is based on the pentad below (Table B).
Cerebral neoplasm
Cerebral haemorrhage
Eclampsia
Haemolysis, elevated liver enzymes and low
platelets
Thrombotic thrombocytopenic purpura
Cerebral vein thrombosis secondary to
hyperviscocity
MAHA
Thrombocytopenia
Fever
Renal involvement
Neurological involvement
Clinical Cases
99
Answer 88
d. Organize CT-guided aspiration/biopsy of the
lower lumbar spine.
The presentation of back pain associated with weakness
of the lower limbs is consistent with cord compression.
The accompanying fever, night sweats and raised
inflammatory markers are highly suggestive of infection
of the lower spine or a involvement of bone with
haematological malignancy. The plain lumbar spine film
shows minor destruction of the third lumbar vertebra and
reduced joint space between the third and fourth lumbar
vertebrae to indicate a discitis. The MRI scan shows
destruction of the third and fourth lumbar vertebrae and
marked discitis (reduced joint space). There is a
collection of pus around the anterior and posterior
aspects of the third and fourth lumbar vertebrae. The
anterior collection is pressing on the spinal cord. The
most probable diagnosis is tuberculous osteomyelitis of
the lumbar spine in a female of her ethnicity.
Spinal TB usually occurs in immunocompromised
adults and is due to reactivation of TB acquired from a
Question 89
A 23-year-old woman with insulin-dependent diabetes
mellitus had experienced recurrent episodes of cystitis for
which she was taking trimethoprim. She smoked 1520
cigarettes per day. Her blood pressure measured
120/80 mmHg. Urinalysis did not reveal any evidence of
micralbuminuria.
Question 90
A 35-year-old woman presented with vomiting and
epigastric discomfort after a weekend of binge drinking.
On examination she was alert. She had several spider
naevi on the face and chest wall. The heart rate was
100 beats/min and regular. The blood pressure was
160/96 mmHg. The respiratory rate was 20/min. Both
heart sounds were normal. The abdomen was soft.
Inspection of the fundi was normal.
Initial investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
Bilirubin
AST
Gamma GT
Plasma osmolality
Blood glucose
Urinalysis
12 g/dl
12 ! 109/l
100 ! 109/l
102 fl
132 mmol/l
3.3 mmol/l
7 mmol/l
80 "mol/l
11 mmol/l
98 mmol/l
18 "mol/l
160 iu/l
100 iu/l
290 mOsm/l
5 mmol/l
Ketones ++++
No crystals
100
Answer 89
b. Strict glycaemic control.
The patient does not have hypertension or micro albuminuria, therefore the best treatment for preventing
nephropathy is meticulous glycaemic control. Glycaemic
control and blood pressure are the main predictors for the
development of microalbuminuria (the earliest marker of
diabetic nephropathy) in both type 1 and type 2 diabetes.
Data from the DCCT trial in type 1 diabetes and UKPDS
trial in type 2 diabetes have shown that meticulous
glycaemic control alone delays the onset of diabetic
nephropathy in patients who do not have coexistent
hypertension. In patients with diabetes and hypertension
prevention of diabetic nephropathy requires both
meticulous glycaemic control and maintaining a normal
blood pressure. Better glycaemic control reduces glomerular
basement membrane thickening and microalbuminuria.
Once microalbuminuria has developed there is little
evidence that improving glycaemic control alone delays
progression of nephropathy. In these circumstances,
No microalbuminuria
Yes
Meticulous glycaemic
control and aggressive
BP control
Target BP
130/75 mmHg
No
Meticulous glycaemic
control Hblc 7%
Answer 90
c. Euglycaemic ketoacidosis.
The patient is admitted after an episode of alcohol
bingeing. Apart from the history, her investigations raise
the suspicion of alcohol abuse (macrocytosis, low
platelets and abnormal liver function tests). Patients who
abuse alcohol may present with ketoacidosis in the
absence of insulin deficiency. There are several factors
that contribute to ketoacidosis. Firstly, alcohol inhibits
gluconeogenesis, which offsets glucagon-mediated
lipolysis and ketone generation. Secondly, alcohol itself
may be metabolized to ketones. Thirdly, patients who
abuse alcohol generally have a low calorie intake and are
effectively starving on a chronic basis. Patients usually
Clinical Cases
101
Question 91
A 27-year-old female artist was seen in the chest clinic
with a three-day history of worsening dyspnoea requiring
the use of an inhaled short-acting &2-agonist every 34
hours. Over the past few months she had been using the
bronchodilator with increasing frequency. She had also
experienced a non-productive cough particularly at night
and after exercise. She was diagnosed with asthma since
the age of 14 years and was hospitalized on two
occasions more than 10 years ago for infective
exacerbations of asthma. Her only other medication was
a low-dose inhaled steroid, which she takes twice daily.
On examination she was afebrile. She was 1.52 m tall.
The peak expiratory flow rate was 365 l/min, with her
normal best at 470 l/min. She could complete sentences
in one breath. Her respiratory rate was 20/min, pulse
rate 80 beats/min and blood pressure 110/70 mmHg.
Auscultation of the lungs revealed mild generalized
polyphonic wheeze.
Blood gases (air):
PaCO2
PaO2
pH
5 kPa
12 kPa
7.34
Question 92
A 52-year-old male with non-insulin-dependent diabetes
mellitus has a blood pressure of 148/94 mmHg.
Fundoscopy reveals evidence of background diabetic
retinopathy.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Glucose
Cholesterol
Triglycerides
12-lead ECG
24-hour urine protein
13.1 g/dl
5 ! 109/l
290 ! 109/l
138 mmol/l
4.1 mmol/l
9 mmol/l
138 mol/l
8 mmol/l
5.8 mmol/l
3.2 mmol/l
Normal
1g
102
Answer 91
b. Continue short-acting &2-agonist as required and
substitute high-dose inhaled steroid twice daily.
e. Continue short-acting &2-agonist as required and
continue on low-dose inhaled steroid, add longacting inhaled &2-agonist twice daily.
The British Thoracic Society (BTS) published guidelines
for the management of asthma in 1990, which have since
been updated (1997), in response to concerns over the
increasing prevalence, morbidity, admissions and deaths
from asthma. Supported by randomized controlled trials,
steroids have since been established as the mainstay of
preventative treatment in all but the mildest cases of
asthma. This question tests the candidates knowledge of
the BTS guidelines of the stepwise approach to the
management of chronic asthma with the introduction of
inhaled steroids early in the treatment (Table A).
Clinical Cases
103
Answer 92
a. Losartan.
The patient has moderate proteinuria and abnormal renal
function. The question specifically relates to the
treatment of diabetic nephropathy in a patient with type
2 diabetes mellitus. While ACE inhibitors have been
clearly shown to attenuate micro-albuminuria in patients
without overt nephropathy and retard progression of
nephropathy in those patients with established diabetic
nephropathy in type 1 diabetes, the management of
nephropathy in type 2 diabetes is still evolving.
It is clear that tight glycaemic control is effective in
retarding nephropathy in both type 1 and type 2 diabetes
mellitus and that control of hypertension is also necessary
in both conditions. In contrast with type 1 diabetes
mellitus, there is much less information on the effects of
Question 93
A 45-year-old man with HIV syndrome presented with
weakness affecting the left upper and lower limbs. On
examination he was confused and had a temperature of
38C (100.4F). He had recently been treated for a
Pneumocystis carinii infection. The CD4 count was 150.
CT scan of the brain with contrast revealed subcortical
atrophy and multiple contrast-enhancing ring lesions in
the cortex and subcortical areas.
Question 94
A 60-year-old male was noted to have an irregular pulse.
A subsequent 12-lead ECG showed atrial fibrillation with
a ventricular rate of 80 beats/min. The patient was
asymptomatic. There was no past medical history of note.
The patient consumed 10 units of alcohol per week. His
Hb
Blood glucose
Total cholesterol
TSH
Total thyroxine
Chest X-ray
12-lead ECG
Echocardiography
12 g/dl
4.2 mmol/l
5.4 mmol/l
1.3 mu/l
170 nmol/l
Normal
Atrial fibrillation
Normal QRS complexes
Left atrial diameter 40 mm
Normal left ventricle
Normal systolic function
Normal valves
104
Answer 93
d. Cerebral toxoplasmosis.
The most probable diagnosis is cerebral toxoplasmosis.
The CT scan is consistent with the diagnosis; the subcortical atrophy probably represents HIV encephalopathy.
The exact cause of CNS involvement in HIV infection
is largely influenced by the CD4 count. Patients with
CD4 counts >500 have benign and malignant brain
tumours similar to those seen in immunocompetent
patients. Patients with a CD4 count of between 200 and
500 often have cognitive disorders associated with HIV
such as HIV dementia and progressive leucoence phalopathy, which are not mass lesions. Patients with a
CD4 count <200 have either opportunistic CNS
infections or HIV-related cerebral tumours.
Opportunistic infections include toxoplasmosis, TB,
CMV and cryptococcal meningitis (see Question 277).
Toxoplasmosis is by far the commonest cerebral mass
lesion seen in HIV patients and is usually associated with
multiple ring-enhancing lesions either in the cortico-
Answer 94
d. Aspirin.
The patient has atrial fibrillation which is associated with
a five-fold increase in stroke secondary to systemic
thromboembolism. The two main pharmacological
treatments available for preventing systemic thromboembolism in AF are antithrombotic agents and oral
anticoagulant drugs. Aspirin is the only antithrombotic
agent recommended for preventing systemic thromoboembolism in AF. Warfarin is the most commonly used
oral anticoagulant drug used in this particular situation.
Studies have shown that in high-risk patients (see
below) warfarin is superior to aspirin in preventing
systemic thromboembolism. However, there is no
conclusive evidence that warfarin is superior to aspirin in
this regard in low-risk patients. In patients at moderate
risk both aspirin and warfarin appear to be equally
effective in reducing systemic thromboembolism.
Patients' age above 75 years of age, rheumatic mitral
valve disease and prior embolic events are the greatest risk
factors for systemic thromboembolism in AF (Table).
The patient in question is at low risk of systemic
thromboembolism, therefore he should be treated with
aspirin instead of warfarin.
An alternative method of determining who will benefit
from warfarin is to use the CHADS score (right): a score
>2 is an indication of anticoagulation therapy; patients
with a score of 12 could be considered for aspirin or
warfarin; and patients with a score of 0 are deemed at
relatively low risk and suitable for aspirin (150300 mg).
Risk
Treatment
High
Warfarin
Moderate
Warfarin
or
aspirin
All of
Age <65 years
Low
Normal left
ventricular function
No evidence of
rheumatic heart disease
No hypertension
C = coronary artery disease
H = hypertension
A = age >75
D = diabetes mellitus
S = previous stroke
Aspirin
1 point
1 point
1 point
1 point
2 points
Clinical Cases
105
Question 95
An 84-year-old fully independent male was admitted with
very transient episodes of dizziness. The 12-lead ECG
showed first degree AV block and left bundle branch
block. A subsequent 24-hour ECG revealed episodic
third degree AV block.
Question 96
Hb
WCC
10 g/dl
3.1 ! 109/l
(neutrophils, 1.5;
lymphocytes, 0.7;
eosinophils, 0.9)
Platelets
108 ! 109/l
MCV
80 fl
Bone marrow: Erythroid hyperplasia,
myeloid hyperplasia but lack of
mature forms
Multiple megakaryocytes
Question 97
A 50-year-old woman presented with pain in her right
shoulder and weight loss of 4 kg over the past four
weeks. She had been taking non-steroidal antiinflammatory drugs with only mild relief of her pain. She
smoked 1520 cigarettes per day.
Investigations are shown.
Hb
11.2 g/dl
WCC
8.2 ! 109/l
Platelets
500 ! 109/l
ESR
72 mm/h
Chest X-ray (97)
97
106
Answer 95
c. DDDR Pacemaker.
The patient has third degree AV block. The condition is
associated with an annual mortality exceeding 15% in the
Choice of pacemaker
Condition
Pure sustained AF
Pure sinus node dysfunction without AF or
evidence of AV block at rapid heart rates
(>150/min)
Second or third degree AVB or other
bradyarrhythmias with visible P waves
Pacemaker of choice
VVI or VVIR
AAIR (or DDDR)*
DDD or DDDR
*Most cardiologists in the UK implant DDD (DDDR) pacemakers in patients with sick sinus syndrome as many
patients go on to develop atrioventricular block. First letter, chamber(s) paced; second letter, chamber(s)
sensed; third letter, mode of sensing (I = inhibition and D = triggering and inhibition); fourth letter (R), rate
response facility.
Answer 96
d. Feltys syndrome.
In a patient with chronic rheumatoid arthritis,
neutropaenia and splenomegaly, the most probable
diagnosis is Feltys syndrome. However, other conditions
associated with a low white cell count in rheumatoid
arthritis include drugs such as penicillamine, gold and
methotrexate, which are associated with bone marrow
aplasia. Folate deficiency may also cause pancytopenia.
The bone marrow does not reveal hypoplasia, therefore
drug-induced marrow aplasia is unlikely here. The
absence of megaloblasts is against the diagnosis of folate
deficiency.
Answer 97
d. Metastatic bone disease.
There are small lucencies in the head of the humerus and
a large lucency in the lateral border of the scapula. There
is only one breast shadow present (on the right). The left
breast shadow is absent, indicating that the patient has
Clinical Cases
107
Question 98
A 22-year-old medical student developed sudden
dysphasia and right-sided weakness while on holiday in
Australia. She was afebrile. Apart from the neurological
abnormality described, there were no other abnormal
physical signs.
Investigations are shown.
Hb
WCC
Platelets
ESR
Autoantibody screen
12-lead ECG
2-D echocardiogram
Carotid Doppler study
15 g/dl
10 ! 109/l
200 ! 109/l
8 mm/h
Normal
Normal
Normal
Normal
Question 99
A 50-year-old Jamaican male was admitted with discomfort in the right shoulder. On examination he had weakness of abduction of the right upper limb.
Investigations are shown.
Hb
11 g/dl
WCC
11.5 ! 109/l
Platelets
200 ! 109/l
Sodium
133 mmol/l
Potassium
4.6 mmol/l
Urea
7.4 mmol/l
Calcium
2.76 mmol/l
Albumin
36 g/l
Chest X-ray (99a)
99a
108
Answer 98
d. Paradoxical embolus via patent foramen ovale.
A young patient presenting with stroke with a normal
cardiac examination, 2-D echocardiogram, carotid
Doppler study, autoantibody screen and inflammatory
markers is highly consistent with the diagnosis of
paradoxical embolism via a patent foramen ovale.
A PFO occurs when the primum and secundum septa
fail to fuse completely leaving a small flap-like
communication allowing the possibility of a shunt. She
has been on a long flight from Australia and therefore it
is possible that she had deep-vein thrombi, which have
traversed the PFO and passed into the systemic
circulation. PFOs are relatively common and may be
present in up to 30% of the general population. PFOs
Notes
Sudden onset severe headache and vomiting
Fever, confusion, meningism, seizures
Headache, focal neurology, seizures
Trauma/pain/unilateral lower cranial nerve palsies
Usually female; may be precipitated by typical aura
Systemic features, raised inflammatory markers,
positive autoantibody screen
Involves carotid artery; associated intracranial
aneurysms; renal artery commonly affected
Hyperviscocity, pregnancy, contraceptive pill, ear,
sinus or facial skin infection; headache, focal
neurology, seizures
Previous arterial or venous thrombosis
Irregular pulse; murmur
Thrombophilic states
Cardiac causes (severe hypertension, AF,
rheumatic heart disease, mechanical valves,
cardiomyopathy, septal defects, PFOs)
Haematological (polycythaemia, thrombocythaemia,
paroxysmal nocturnal haemaglobinuria, sickle cell anaemia)
Mitochondrial disease, e.g. MELAS
(see Question 315)
Answer 99
d. Bronchial carcinoma.
There is opacification of the right upper lobe consistent
with a mass lesion. The first rib is eroded on the right
side indicating involvement of bone. The findings are
typical of a Pancoast tumour. The raised calcium may be
secondary to bone metastases or secretion of PTHrelated peptide by the carcinoma. Patients with Pancoast
tumour present with symptoms and signs of pressure on
the brachial plexus, the sympathetic trunk (Horners
syndrome) and bone metastases (99b, arrows).
99b
Clinical Cases
109
Question 100
A 67-year-old male with dilated cardiomyopathy is
admitted for the third time in four months with
increasing breathlessness and swollen ankles. He
consumed 2 units of alcohol per week. His medications
consisted of furosemide 80 mg daily, ramipril 10 mg
daily, candesartan 6 mg daily, spironolactone 25 mg
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
ECG
Chest X-ray
11 g/dl
7 ! 109/l
200 ! 109/l
90 fl
129 mmol/l
5.9 mmol/l
17 mmol/l
Sinus rhythm; LBBB
Enlarged heart; bilateral
pleural effusions
Echocardiography:
Dilated left and right ventricles.
Ejection fraction 20%.
Severe functional mitral regurgitation
Question 101
A 21-year-old woman presented with a painless swelling
in her neck. There was no history of a recent viral illness.
The patient did not have symptoms of hyper- or
hypothyroidism. She was not taking any medications. On
Hb
ESR
TSH
Chest X-ray
14 g/dl
5 mm/h
2 iu/l
Normal
Question 102
Hb
WCC
Platelets
MCV
MCHC
Ferritin
Bilirubin
AST
LDH
Alkaline phosphatase
Albumin
6.1 g/dl
3.0 ! 109/l
115 ! 109/l
116 fl
37 pg
710 "mol/l
35 "mol/l
40 iu/l
1500 iu/l
100 iu/l
37 g/l
110
Answer 100
d. Implant biventricular pacemaker.
The patient has severe symptoms despite adequate doses
of an ACE inhibitor, beta-blocker and spironolactone.
His low systolic blood pressure does not allow additional
pharmacological therapy such as an angiotensin II
receptor blocker. He has poor left ventricular function
and an interventricular conduction defect suggesting that
he may benefit symptomatically from biventricular pacing
(Table A). The mitral regurgitation is a consequence of
the left ventricular dilatation rather than the cause of it.
An internal cardiac defibrillator prevents sudden death in
patients at risk of malignant ventricular arrhythmias but
does not improve functional capacity.
Improves
Quality of life
Exercise capacity
NYHA functional class
LV ejection fraction
LV dimensions
Reduces
Total and heart failure
related hospitalizations
Heart rate
Answer 101
c. Fine-needle aspiration of the thyroid gland.
Thyroid lumps may represent simple or multinodular
goitres, toxic nodules, neoplastic lesions, inflammatory
masses or thyroid cysts. Thyroid carcinomas account for
56% of all lumps in the thyroid. Thyroid cancer is most
common in patients aged under 30 years or over 60
years. Prior radiation to the head and neck is a recognized risk factor for thyroid carcinoma. Patients with a
family history of thyroid carcinoma are at a higher risk of
thyroid malignancy than the general population.
A painless swelling in the neck associated with cervical
lymphadenopathy is highly suggestive of papillary
carcinoma of the thyroid gland. Papillary carcinoma of
the thyroid invades local structures quickly and usually
presents early as a result. The diagnosis of thyroid
carcinoma is usually made by histological sampling of a
fine-needle thyroid aspirate. Prior thyroid ultrasound is
not necessary. Indeed in patients with a normal TSH,
fine-needle aspiration is the investigation of choice to
investigate thyroid lumps. In patients with a low TSH a
radio-iodine uptake scan is performed to confirm the
Clinical Cases
111
Answer 102
b. Pernicious anaemia.
This patient with lethargy has a markedly raised MCV
and pancytopenia. The best answer is pernicious anaemia.
Although paroxysmal nocturnal haemoglobinuria can
also be associated with pancytopenia and raised MCV,
the actual MCV in PNH is less than in pernicious
anaemia. The raised MCV in PNH is due to reticulocytes
(newly formed red cell) arising from rapid red cell
turnover secondary to haemolysis, whereas in pernicious
anaemia the raised MCV is due to large immature red
cells (erythroid precursors) secondary to immature
nuclear development. Remember hydroxycobalamin is
required for thymidine synthesis, an important DNA
Question 103
A 64-year-old man presented immediately after
recovering from a 20-minute episode of dysphasia and
weakness of the right side of the face and arm. He had
experienced two episodes of transient loss of vision in the
left eye in the past three weeks. There was a past medical
history of a myocardial infarction two years ago. His
medication comprised 75 mg of aspirin daily. He did not
smoke.
On examination there was no evidence of residual
neurological deficit. Fundoscopy was normal. The pulse
rate was 80 beats/min and regular in nature. His blood
pressure measured 138/86 mmHg in both arms. Both
heart sounds were normal. Auscultation over the carotid
arteries revealed a bruit over the left carotid artery.
Investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Glucose
Total cholesterol
CT scan brain
Carotid Doppler
15 g/dl
8 ! 109/l
300 ! 109/l
20 mm/h
138 mmol/l
4.1 mmol/l
6 mmol/l
100 mmol/l
4.7 mmol/l
6 mmol/l
Normal
Stenosis (40%) in left
internal carotid artery.
Stenosis (80%) in right
external carotid artery
112
Answer 103
b. Add dipyridamole to current therapy.
g. Start ACE inhibitor after three days.
i. Start therapy with a statin drug.
Yes
No
Consider carotid
endarterectomy
Consider
medical therapy
Clinical Cases
113
Question 104
A 36-year-old woman presented with a four-week history
of intermittent upper abdominal pain and vomiting. Her
bowel movements were unaffected and were normal.
There was no blood or mucus in the stool. Her appetite
was reduced. She had lost 2 kg in weight. She had a past
medical history of ulcerative colitis which was diagnosed
at the age of 14 years, and was stable on sulphasalazine.
In the past she had received several courses of steroids for
acute exacerbation of her colitis. Her only other drug
history was that she was currently on the contraceptive
pill. She had been married for 10 years and had two
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alkaline phosphatase
Albumin
Chest X-ray
13 g/dl
8 ! 109/l
190 ! 109/l
131 mmol/l
3.1 mmol/l
7.2 mmol/l
100 "mol/l
20 mol/l
24 iu/l
21 iu/l
150 iu/l
29 g/l
Normal heart size
Clear lung fields
114
Answer 104
1. i. Liver ultrasound and Doppler studies.
ii. Liver biopsy via internal jugular vein.
2. c. Hepatic vein thrombosis.
The patient has a long history of relatively quiescent
ulcerative colitis and presents with a short history of
intermittent upper abdominal pain, vomiting, tender
hepatomegaly and ascites. There is no history of weight
loss preceding the illness. However, she is a smoker and
on the oral contraceptive pill, both of which are recognized risk factors for venous thrombosis. Ulcerative
colitis itself is associated with an increased risk of venous
thrombosis owing to increased fibrinogen levels and the
elevated plasma viscosity. The most likely diagnosis in
this patient is hepatic vein thrombosis. Although portal
Complications of ulcerative colitis
Gastrointestinal
Haemorrhage
Toxic dilatation
Perforation
Carcinoma of the colon
Oral and anal ulcers
Hepatobiliary
Fatty infiltration of the liver
CAH
Cirrhosis of the liver
Sclerosing cholangitis
Dermatological
Erythema nodosum
Pyoderma gangrenosum
Ophthalmic
Episcleritis
Scleritis
Anterior uveitis
Rheumatological
Seronegative arthritis of the small joints
Ankylosing spondylitis
Haematological
Predisposition to venous thromboses
Clinical Cases
115
Question 105
A 40-year-old woman presented with a five-day history of
recurrent falls and an unsteady gait. She had a past
history of a stroke causing a right-sided hemiparesis,
which resolved spontaneously after a few days. The
patient underwent intensive investigation following
presentation with the stroke including carotid Doppler
studies, transoesophageal echocardiography and CT scan
of the brain, which were normal.
On examination she had a broad-based gait. There was
evidence of dysdiadochokinesia in both upper limbs and
abnormal heelshin testing. The lower limb reflexes were
brisk and the plantar response was extensor. The heart rate
Hb
WCC
Platelets
Sodium
Potassium
Urea
Albumin
Alkaline phosphatase
Alpha-fetoprotein
Human chorionic
gonadotrophin
TSH
Thyroxine
Testosterone
Oestradiol
14 g/dl
6 ! 109/l
180 ! 109/l
135 mmol/l
4.3 mmol/l
5 mmol/l
38 g/l
190 iu/l (NR 25115 iu/l)
8 ku/l (NR <10 ku/l)
1250 iu/l
Question 106
<0.01 mu/l
300 nmol/l
(NR 60160 nmol/l)
60 nmol/l
(NR 1035 nmol/l)
1300 pmol/l
(NR 5001100 pmol/l)
Question 107
Question 108
A 42-year-old man required ventilation for a prolonged
period during an episode of septicaemia. Following this
he developed difficulty with walking and required the aid
of an assistant to mobilize. On neurological examination
there was weakness on dorsiflexion of the toes, as well as
ankle eversion. The patient also had reduced sensation,
affecting the anterior lateral aspects below the knee and
the dorsum of the foot.
116
Answer 105
b. Multiple sclerosis.
The patient has had a previous right hemiparesis and now
presents with ataxia. Neurological examination reveals
findings consistent with a cerebellar syndrome and bilateral
pyramidal tract involvement. The differential diagnosis of
cerebellar and pyramidal tract involvement includes
multiple sclerosis, subacute combined degeneration of the
spinal cord, Friedreichs ataxia, multiple cerebral metastases
and multiple cerebral infarcts.
The most probable diagnosis is multiple sclerosis, a
demyelinating disorder characterized by involvement of
the optic tracts, pyramidal tracts, cerebellar peduncle and
the posterior columns of the spinal cord.
Answer 108
c. Common peroneal nerve palsy.
Weakness of dorsiflexion and eversion of the foot and
reduced sensation over the antero-lateral aspects of the
lower leg and dorsum of the foot are typical features of
common peroneal nerve palsy. The common peroneal
nerve crosses over the fibula, where it may become
Clinical Cases
117
Question 109
A 53-year-old male was investigated for recurrent
episodes of sinusitis and earache that did not respond to
conventional antibiotics. He had experienced several
Hb
WCC
Platelets
MCV
ESR
CRP
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alkaline phosphatase
Albumin
Immunology:
pANCA
(myeloperoxidase)
cANCA
ANF
C3
C4
Chest X-ray
Urinalysis
11 g/dl
15 ! 109/l
(neutrophils 12 ! 109/l,
lymphocytes 2 ! 109/l,
eosinophils 0.35 ! 109/l)
490 ! 109/l
80 fl
60 mm/h
90 g/l
138 mmol/l
4.1 mmol/l
7 mmol/l
110 "mol/l
11 "mol/l
23 iu/l
25 iu/l
156 iu/l (NR <115 iu/l)
31 g/l
Positive
Negative
Negative
0.9 g/l (NR 0.551.2 g/l)
0.3 g/l (NR 0.20.5 g/l)
Right middle lobe
consolidation
24-hour protein 0.8g
Blood ++
Casts absent
Question 110
A 40-year-old homosexual male presented to the
Accident and Emergency Department with a four-day
history of sore throat and fever. On examination he had
cervical and axillary lymphadenopathy and widespread
maculopapular rash. An HIV antibody test was negative.
118
Answer 109
c. Microscopic polyangiitis.
The patient presents with specific symptoms of upper and
lower respiratory tract involvement. Additionally, he has
malaise, arthralgia, weight loss and raised inflammatory
markers suggestive of a systemic illness. The presence of
blood and protein in the urine indicates renal involvement. A normal creatinine concentration does not
preclude renal involvement. The differential diagnosis is
that of a multi-system disease capable of involving the
upper and lower respiratory tract as well as the kidneys.
The presence of a positive ANCA test is suggestive of a
small-vessel vasculitis. Possibilities include Wegeners
granulomatosis, microscopic polyangiitis and
ChurgStrauss syndrome.
Wegeners granulomatosis and microscopic
polyangiitis are both small-vessel vasculitides associated
with ANCA. Both are characterized by upper and lower
tract involvement (sinusitis, epistaxis, otitis media,
haemoptysis) and renal involvement. Other features
common to both include episcleritis, peripheral/central
nervous system involvement and effects on the
gastrointestinal tract. While manifestations of the upper
and lower respiratory tract involvement may be identical
in both of these small-vessel vasculitides, the presence of
granulomata in small vessels in biopsy specimens is
specific for Wegeners granulomatosis. The ANCA
subtype may also aid differentiation between Wegeners
granulomatosis and microscopic polyangiitis. Wegeners
granulomatosis is characterized by the presence of
Answer 110
c. HIV viral RNA load.
The presentation is consistent with HIV seroconversion.
Most patients can be diagnosed by conventional ELISA
tests, which identify the presence of HIV antibodies by
the time the patient has features of HIV seroconversion.
However, if HIV antibody testing proves negative, then
Clinical Cases
119
Question 111
A 68-year-old male complained of dyspnoea on minimal
exertion. Respiratory function tests are shown.
FEV1
FVC
TLC
TLCO
2.1 l (predicted 23 l)
2.5 l (predicted 2.84.4 l)
4.2 l (predicted 57 l)
90% predicted value
Question 112
A 66-year-old female patient presented with transient
bilateral loss of vision lasting a few seconds. A few days
later she developed a right-sided hemiparesis. There was
no history of head injury or headaches. She had a fouryear history of hypertension. The patient had smoked for
12-lead ECG
Normal
2-D echocardiogram
with colour flow
Normal
CT scan brain
Question 113
A 79-year-old man was admitted with sudden onset of
chest pain and breathlessness. On examination he was
cyanosed. He had had a total hip replacement ten days
previously. The patient smoked ten cigarettes per day and
had hypertension for which he took nifedipine. On
examination the heart sounds were normal and auscultation of the lungs revealed a clear chest.
Investigations are shown.
Hb
13 g/dl
WCC
13 ! 109/l
Platelets
250 ! 109/l
CRP
28 g/l
ECG
Sinus tachycardia and LBBB
Arterial blood gases (air):
pH
7.49
PaCO2
3.1 kPa
PaO2
8.8 kPa
HCO3
28 mmol/l
120
Answer 111
d. Ankylosing spondylitis.
The patient has a restrictive lung defect (FEV1/FVC
ratio approx. 80%), a low total lung capacity and a
relatively normal transfer factor. These findings are
consistent with either a thoracic cage deformity, a
Answer 112
a. Carotid Doppler studies.
The patient has evidence of multiple transient ischaemic
episodes followed by a right-sided hemiparesis. CT scan
of the brain reveals a left middle cerebral artery
infarction, which is consistent with the final presentation.
There is no evidence of any other abnormality in the
brain. Possible causes of multiple cerebral emboli in this
particular case include thrombi from the carotid arteries,
calcific plaques from a degenerative aortic valve, and
paradoxical emboli from a patent foramen ovale. In the
absence of atrial fibrillation, the commonest cause of
thromboembolism to the brain is atheromatous carotid
artery disease, particularly in patients with hypertension.
Answer 113
a. Pulmonary embolism.
The presentation with sudden chest pain, dyspnoea,
hypoxia and hypocarbia ten days after a hip replacement
is highly suggestive of pulmonary embolism. The ECG
reveals LBBB, which may be due to silent coronary
disease or long-standing hypertension. The ECG in
massive pulmonary embolism classically reveals right
ventricular strain pattern or RBBB. Although it is
possible that the presentation may represent acute
Clinical Cases
121
10 g/dl
12 ! 109/l
30 ! 109/l
94 s (control 45 s)
3.8
Absent
Question 114
Question 115
Question 116
A patient with psoriasis was referred to the psychiatrist
and found to have manic depression. He was started on
medication that resulted in severe exacerbation of the
rash shown (116).
116
122
Answers 114 and 115
Answer 114
d. Heparin-induced thrombocytopenia type II.
Answer 115
a. Stop warfarin and switch to danaparoid.
The diagnosis is heparin-induced thrombocytopenia type
II, also known as heparin-induced thrombocytopenic
thrombosis. In contrast with HIT type I, which is a
transient isolated thrombocytopenia usually occurring
after 48 hours of therapy with unfractionated heparin,
HIT type II is an immune-mediated disorder resulting in
the formation of antibodies against the heparin-platelet
factor 4 complex. HIT type II has a prevalence of
between 0.3 and 3% of patients who have been on
heparin for between 4 and 10 days. The condition rarely
occurs after 10 days of treatment.
HIT II is characterized by an increased level of IgG
and IgM antibodies to heparin, which results in both
platelet activation causing venous and arterial thromboses
and thrombocytopenia due to immune-mediated
destruction of platelets. Venous thromboses are more
common than arterial ones. Manifestations include deep-
Answer 116
d. Lithium.
The patient has developed severe psoriasis. Psoriasis may
be exacerbated by drugs and infections. With respect to
drugs, the commonest culprits are beta-blockers, lithium
Clinical Cases
123
Question 117
A 69-year-old woman presented with pain in her
shoulders and upper back, polydipsia and polyuria.
Investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Total protein
Albumin
9 g/dl
14 ! 109/l
140 ! 109/l
89 fl
129 mmol/l
3.4 mmol/l
26 mmol/l
290 "mol/l
2.8 mmol/l
1.9 mmol/l
98 g/l
34 g/l
24-hour urinalysis
14 g/dl
12 ! 109/l
7 ! 109/l
2.5 ! 109/l
4 ! 109/l
0.1 ! 109/l
0.4 ! 109/l
300 ! 109/l
120 mm/h
130 mmol/l
6.5 mmol/l
87 mmol/l
26 mmol/l
300 "mol/l
9 mmol/l
White blood cells,
red blood cells and white
cell casts
Sodium
60 mmol/l
Protein
0.8 g
Question 118
What is the cause of this patients renal dysfunction?
a. Renal tuberculosis.
b. Acute tubular necrosis.
c. Acute interstitial nephritis.
d. Acute post-infectious glomerulonephritis.
e. Rhabdomyolysis.
Question 119
What is the most important initial step in his
management?
a. Renal biopsy.
b. Haemodialysis.
c. Corticosteroids.
d. Discontinuation of isoniazid.
e. Discontinuation of rifampicin.
124
Answer 117
1. a. Multiple myeloma.
2. c. Tubular obstruction by light chain.
3. d. Proximal renal tubular acidosis.
The diagnosis of myeloma is based on the very high
globulin count (albumin subtracted from total protein
content), anaemia, renal failure and hypercalcaemia.
Clinical Cases
125
Question 120
A 56-year-old male was admitted with weight loss and
fatigue. He consumed 40 units of alcohol per week. On
examination he was pale and had a palpable spleen 10 cm
below the costal margin.
Investigations are shown.
Hb
WCC
Platelets
MCV
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Neutrophil alkaline
phosphatase
8 g/dl
23 ! 109/l
500 ! 109/l
90 fl
58%
2%
1%
1%
2%
25 iu/l
(NR 35100 iu/l)
Question 121
A 67-year-old man presented with central chest pain
associated with ST segment depression in the inferior and
lateral leads. He had smoked 2030 cigarettes per day for
over 40 years. Troponin T 12 hours after admission was
0.4 ng/l (NR <0.05 ng/l). The patient remained pain
free for three days and the ECG changes resolved. He
was treated with antiplatelet agents, a statin, ACE
inhibitor and a beta-blocker.
Question 122
A 24-year-old woman presented with a swollen left lower
limb when she was eight weeks pregnant. Lower limb
vein Doppler studies confirmed a femoral vein deep-vein
thrombosis. There was no family history of
thrombophilia.
126
Answer 120
d. Chronic myeloid leukaemia.
The patient has large splenomegaly and a high white cell
count consisting predominantly of neutrophils. The
differential diagnosis is between CML and myelofibrosis.
Both conditions may be associated with much higher
white cell counts; however, CML can be differentiated
Answer 121
b. Coronary angiography prior to discharge.
The patient has chest pain and raised troponin in the
absence of ST elevation. By definition this patient has
suffered a non-ST elevation myocardial infarction. Such
patients have a relatively low risk of in-hospital mortality
compared with ST segment elevation myocardial
infarction; however, six-month mortality exceeds that of
patients with STEMI and is around 20%. Therefore, it is
prudent that all appropriate patients with NSTEMI have
coronary angiography and revascularization (if required)
prior to discharge from hospital. The same applies to
patients who present with chest pain and marked ST
segment depression even if the serum cardiac troponin is
not elevated (Table A).
In the interim the management of both groups of
patients is essentially the same and consists of antithrombotic agents (aspirin and clopidogrel together),
fractionated heparin, and IIb/IIIa platelet receptor
blocking agents (Table B). High-dose statins may play a
role in plaque pacification in the peri-infarction period.
In addition beta-blockers may reduce myocardial oxygen
demand. GTN infusion is useful in reducing symptoms of
acute myocardial ischaemia.
The benefits of aspirin in myocardial infarction are
well established. Over the past few years the CURE study
demonstrated that the addition of clopidogrel to aspirin
Clinical Cases
127
Answer 122
b. Start subcutaneous fractionated heparin and
continue for the entire pregnancy, maintaining an
antifactor Xa >1.0 four hours after injection of
heparin. After pregnancy give warfarin for six
weeks.
The patient requires anticoagulation but warfarin is
contraindicated in the first 13 weeks of pregnancy as it is
teratogenic (skeletal, cartilage and foetal CNS
abnormalities). Heparin, on the other hand, does not
cross the placenta and has not been associated with
teratogenic effects. The recommendation is to use either
unfractionated or low-molecular weight heparin, at least
in the first 13 weeks.
Following this there are three options, as follows:
1. Continue dose-adjusted unfractionated heparin
throughout pregnancy, maintaining an APPT twice
that of the normal range. However, treatment with
unfractionated heparin requires daily monitoring of
the APTT, which is inconvenient and impractical.
Long-term unfractionated heparin injections are
associated with a high risk of osteoporosis.
Question 123
A 70-year-old obese male saw his GP and was noted to
have a blood pressure of 170/98 mmHg. The fundi were
normal. Urinalysis was normal. Urea, electrolytes and
blood sugar were normal. The total cholesterol measured
6 mmol/l. The patient was advised to lose weight and
adhere to a low-salt diet. Blood pressure readings over
the next six months were 170/96 mmHg, 168/96
mmHg and 166/96 mmHg.
128
Answer 123
b. Bendroflumethiazide (bendroflumethazide).
The patient has moderate to severe hypertension and
requires lifestyle modification advice as well as
pharmacological therapy to help control his blood
pressure. Hypertension in the elderly is best treated with
calcium channel blockers or a thiazide diuretic. The use
of thiazide diuretics as first line in most elderly patients
with hypertension is supported by the recently published
ALLHAT study, which was the largest study ever in the
hypertensive population. The study showed that thiazide
diuretics were more effective than beta-blockers, calcium
channel blockers and angiotensin-converting enzyme
inhibitors at reducing cardiovascular mortality in
diabetics and non-diabetics.
All patients should receive advice regarding lifestyle
modification to help reduce the blood pressure (Table A).
Lifestyle modification alone without antihyper tensive
drug therapy for a period of six months to one year is
reserved for patients with mild hypertension (BP
140159/ 9099 mmHg) who do not have any evidence
of end-organ damage such as retinopathy, abnormal renal
function, proteinuria, or any history of diabetes,
nephropathy, stroke, coronary artery disease or heart
failure (Table A). Most patients with hypertension
require antihypertensive drug therapy.
The British Hypertension Society recommends that
any one of the five major classes of antihypertensive drugs
(thiazides, beta-blockers, calcium channel blockers, ACE
inhibitors and angiotensin II receptor blockers) may be
used as first-line monotherapy, although most patients
Table A Lifestyle
modification
Lose weight to bring
BMI down below 30
Reduce alcohol
consumption
Regular exercise for
3045 min three times
per week
Reduce salt intake to
6 g/day
Increase potassium to
90 mmol/day
Smoking cessation
Age 55 years
Black patients
Step 1
A or B
C or D
Step 2
A or B
C or D
Step 3
Step 4
C
D
+
Spironolactone or doxazocin
Clinical Cases
129
Question 124
A 70-year-old male presented with a four-week history of
increasing dyspnoea and swollen ankles. There was no
evidence of ischaemic heart disease, diabetes or alcohol
abuse. On examination he had clinical and radiological
evidence of pulmonary oedema. The blood pressure
measured 180/100 mmHg. He was treated with
intravenous furosemide with good results.
Investigations are shown.
Hb
10 g/dl
WCC
10 ! 109/l
Platelets
200 ! 109/l
Sodium
139 mmol/l
Potassium
5.1 mmol/l
Urea
14.9 mmol/l
Creatinine
250 "mol/l
Albumin
29 g/l
Chest X-ray after diuretic treatment (124)
ECG
Sinus rhythm;
small complexes;
Q waves inferior and
lateral leads
Urinalysis
Protein ++
Renal ultrasound
Normal kidneys
124
Question 125
A 54-year-old non-insulin-dependent diabetic patient
was referred to the blood pressure clinic for assessment
and control of blood pressure. He was a non-smoker.
He had a body mass index of 28. The blood pressure in
clinic measured 180/98 mmHg on three successive
occasions. His medication comprised metformin 1 g
twice daily, simvastatin 40 mg od, aspirin 75 mg and
amlodipine 10 mg od. Renal function was normal but
urinalysis revealed proteinuria +. The HbA1c was 7%.
The total cholesterol was 5.2 mmol/l. The 12-lead
ECG revealed voltage criteria for left ventricular
hypertrophy.
130
Answer 124
d. Cardiac amyloid.
The commonest causes of heart failure in the UK are
ischaemic heart disease and hypertension. However, the
clue to the answer in this question is in the interpretation
of the chest X-ray, which shows expansile lytic lesions in
the ribs consistent with the diagnosis of multiple
myeloma. A significant proportion of patients with
multiple myeloma develop amyloidosis. Cardiac amyloid
is associated with restrictive dilated cardiomyopathy,
conduction disturbance and angina due to amyloid
deposits in the coronary arteries. The characteristic
features of cardiac amyloid on the 12-lead ECG include
small complexes, pseudo-infarcts (q-waves) and heart
block (see Question 389). Amyloidosis commonly causes
renal failure in multiple myeloma as in this case (see
Question 38).
Almost 80% of patients have evidence of bone
involvement from myeloma at the time of diagnosis.
Answer 125
e. Start losartan.
The most effective method of reducing cardiovascular
mortality in this patient with non-insulin-dependent
diabetes would be to control the blood pressure
effectively. Weight loss alone in a patient with this
magnitude of hypertension would not be enough to
reduce blood pressure.
While all groups of antihypertensive drugs listed have
been shown to be equally efficacious in bringing the
blood pressure down in 4060% of patients when used as
monotherapy, there are clinical settings in which certain
groups of drugs may have additional benefits on
cardiovascular mortality. In patients with non-insulindependent diabetes mellitus, both angiotensin II receptor
blockers and angiotensin-converting enzyme inhibitors
have been particularly effective in reducing cardiovascular
mortality, as shown in the HOPE study and LIFE
studies, respectively.
The LIFE trial evaluated the specific cardiovascular
benefits of losartan in high-risk patients with moderate
to severe hypertension (resting BP 160200/
95115 mmHg) and electrocardiographic evidence of
left ventricular hypertrophy.
Patients were randomly assigned to either losartan or
atenolol therapy, with dose increases and the addition of
hydrochlorthiazide (as well as other agents) to attain the
Clinical Cases
131
Question 126
A 69-year-old male was seen in the renal clinic
complaining of fatigue and dyspnoea. He had chronic
renal impairment secondary to focal segmental
glomerulonephritis and had been on haemodialysis for six
months. The patient was noted to have been anaemic
three months ago for which he was commenced on oral
iron supplements. He had controlled hypertension but
no other medical history. Medication comprised
amlodipine 10 mg od, ferrous sulphate 200 mg bd and
simvastatin 40 mg od.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
Glucose
Iron
TIBC
Ferritin
ECG
Chest X-ray
9.9 g/dl
5 ! 109/l
200 ! 109/l
88 fl
138 mmol/l
5.1 mmol/l
20 mmol/l
340 "mol/l
2.0 mmol/l
1.3 mmol/l
38 g/l
4 mmol/l
9 mmol/l (NR 1432 mmol/l)
50 mmol/l (NR 4080 mmol/l)
36 mg/l (NR 15250 mg/l)
Left ventricular hypertrophy
Slight cardiac enlargement;
clear lung fields
Question 127
A 17-year-old boy was referred to the local paediatrician
because he had not grown very much in the past four years.
Apart from feeling more lethargic than his school friends,
he gave no other history of note. He measured 1.53 m. He
had never needed to shave. His younger brother, aged 16,
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Calcium
Phosphate
Albumin
Glucose
10 g/dl
7 ! 109/l
200 ! 109/l
102 fl
138 mmol/l
4.3 mmol/l
4 mmol/l
2.1 mmol/l
1.1 mmol/l
38 g/l
4.3 mmol/l
132
Answer 126
chronic renal failure. The patient in question has
evidence of absolute iron deficiency and requires iron
supplements before considering the need for EPO.
Patients with iron deficiency usually require intravenous
iron supplements to replenish iron stores, particularly
patients receiving haemodialysis. A treatment algorithm
for anaemia in chronic renal failure is shown below.
Patients who are not iron deficient generally respond to
erythropoietin.
Erythropoietin deficiency
Chronic blood loss (iron deficiency)
Hypothyroidism
Vitamin B12 or folate deficiency
Chronic infection or inflammation
Aluminium toxicity
Malignancy
Haemolysis
Myeloma
Bone marrow infiltration
Marrow aplasia
Yes
No
Start EPO
300 iu/week
No
Check monthly
response
Achieve and
maintain target Hb
Yes
Hb <11 g/dl
Commence EPO
Clinical Cases
133
Answer 127
a. Coeliac disease.
This is a difficult question. There is evidence of short
stature, delayed puberty and a macrocytosis. These three
features can be best explained by malabsorption. The
commonest cause of malabsorption in the Western world
is coeliac disease. The macrocytosis in this respect is due
to folate deficiency. It is unusual, however, not to also
have biochemical evidence of osteomalacia. The
differential diagnosis here is hypothyroidism, which may
Question 128
A 15-year-old male presented with a four-day history of
severe right-sided headaches affecting the orbit and right
maxillary area. On examination he had acneform lesions
around the nose and cheeks. Shortly after admission he
became drowsy and developed a high temperature. He
complained of diplopia. Subsequent physical examination
revealed swelling of the right eye, a partial ptosis of the
right eye and a lateral gaze palsy affecting the same eye.
Fundoscopy revealed papilloedema. There was no
evidence of nuchal rigidity.
Question 129
A 60-year-old man presents with general malaise and
drowsiness. On examination, the blood pressure was
120/70 mmHg. Investigations are shown.
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Random blood sugar
Urine glucose
Urine ketones
108 mmol/l
4 mmol/l
3 mmol/l
56 "mol/l
23 mmol/l
4.2 mmol/l
Not detected
Not detected
134
Answer 128
a. Septic cavernous sinus thrombosis.
The patient has septic dural sinus thrombosis syndrome.
Three main types of dural sinus thrombosis are
recognized, notably cavernous sinus thrombosis, lateral
sinus thrombosis and superior saggital sinus thrombosis.
The commonest variety is the cavernous sinus
thrombosis syndrome, possibly because the facial veins drain
into the sinus and the most common source of infection is
due to squeezing of nasal furuncles without antibiotic
cover. Other sources of infection include otitis media,
sinusitis and dental infections (Table). The commonest
organism implicated is Staphylococcus aureus. Patients with
cavernous sinus thrombosis present with severe peri-orbital
headache, which also affects areas innervated by the
ophthalmic and maxillary branches of the trigeminal nerve.
Fever and peri-orbital oedema usually develop afterwards.
Ocular swelling, chemosis, ophthalmoplegia and drowsiness
are recognized complications. Ophthalmoplegia is due to
compression of the third, fourth and sixth cranial nerves.
Headache and associated ophthalmoplegia should always
alert the clinician to the possible diagnosis of cavernous
sinus thrombosis.
The diagnosis of cavernous sinus thrombosis is either
with high resolution CT scan of the orbit with contrast or
a gadolinium-enhanced MRI scan of the orbit.
Management comprises intravenous flucloxacillin and
Answer 129
c. SIADH secretion.
Syndrome of inappropriate ADH secretion (see Table for
causes) is the most likely diagnosis when the serum
sodium is <115 mmol/l. Hypothyroidism can cause
failure to excrete water, and produce a similar
biochemical picture to SIADH. The diagnosis is
confirmed by demonstrating a low plasma osmolality and
an inappropriately high urine osmolality.
Causes of SIADH
Central nervous system
Head injury
Encephalitis/meningitis
Cerebral abscess
Cerebral neoplasm
Cerebral haemorrhage
Respiratory system
Bronchial carcinoma (particularly oat cell)
TB
Pneumonia (Legionnaires is the college favourite)
Empyema
Drugs
Chlorpropamide
Chlorpromazine
Carbamazepine
Opiates
Vincristine
Miscellaneous
GuillainBarr syndrome
Acute intermittent porphyria
Carcinoma pancreas/thymoma
Clinical Cases
135
Questions 130132
A 32-year-old woman who was 12 weeks into her first
pregnancy presented with headache and malaise. Her
blood pressure in the antenatal clinic four weeks
previously was 120/70 mmHg. The current blood
pressure reading was 220/112 mmHg.
Investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Autoantibody screen
ECG
Urinalysis
Renal ultrasound
13 g/dl
7 ! 109/l
180 ! 109/l
12 mm/h
140 mmol/l
4 mmol/l
6 mmol/l
110 "mol/l
Normal
Normal
Normal
12 cm kidney on the
right and a 7 cm
kidney on the left
Question 130
What is the most probable cause for the hypertension?
a. Atheromatous left-sided renal artery stenosis.
b. Fibromuscular dysplasia of the left renal artery.
c. Unilateral reflux nephropathy affecting left
kidney.
d. Congenital atrophic kidney.
e. Pre-eclampsia.
Question 131
If the patient has papilloedema what is the drug
treatment of choice?
a. IV labetolol.
b. Oral methyldopa.
c. Oral bendroflumethiazide.
d. Oral nifedipine.
e. IV nitroprusside.
Question 132
Which one of the following drugs should not be used
to treat hypertension in pregnancy?
a. Labetolol.
b. Methyldopa.
c. Lisinopril.
d. Nifedipine.
e. Hydralazine.
Question 133
A 22-year-old male was admitted to hospital after an
episode of haematemesis preceded by profuse vomiting.
The patient had been on an alcoholic binge drinking
session 12 hours previously. On examination his heart
rate was 90 beats/min. The blood pressure was
100/60 mmHg. The Hb was 15 g/dl. An upper
gastrointestinal endoscopy performed 24 hours after
admission was normal.
136
Answers 130132
Answer 130
b. Fibromuscular dysplasia of the left renal artery.
Answer 131
a. IV labetolol.
Answer 132
c. Lisinopril.
The onset of severe hypertension within a few weeks of
pregnancy in the setting of unilateral kidney disease is
highly suggestive of renal artery stenosis. Two distinct
forms of renal artery stenosis are recognized, notably
atheromatous renal artery disease, which is more common
in middle-aged males with risk factors for atherosclerosis,
and fibromuscular dysplasia, which usually occurs in
younger females and is characterized by narrowing of the
distal main renal artery or the intrarenal arteries.
The most probable diagnosis in this particular case is
fibromuscular dysplasia affecting the left renal artery.
Affected patients may present with severe exacerbations
of an otherwise relatively stable (normal or slightly
elevated) blood pressure. In pregnancy, for example, the
increase in blood volume results in increased vascular
oxidative stress in the kidney in patients with renal artery
stenosis, which is a stimulus for increased production of
angiotensin II, a potent vasoconstrictor. Increased
angiotensin II levels have the effect of large increases in
blood pressure and precipitation of left ventricular failure
or encephalopathy.
While unilateral pyelonephritis is a recognized cause of
unilateral small kidney, it does not usually result in
disturbed renal function unless there is an intrinsic
abnormality affecting the contralateral kidney.
Pre-eclampsia usually occurs after 20 weeks gestation,
complicates 56% of all pregnancies and is much more
common in women with pre-existing hypertension. It is
defined as hypertension and proteinuria (>0.3 g/
24 hours). Up to 2% of patients with pre-eclampsia
develop seizures and the condition is then termed
Answer 133
c. Allow home.
Patients with a bleeding MalloryWeiss tear, but without
risk factors for re-bleeding, clinical features indicating
severe bleeding, or active bleeding at endoscopy will
almost always heal spontaneously. They can be managed
medically with a brief hospitalization of 24 hours.
Clinical Cases
137
Question 134
A 48-year-old post-menopausal woman with asthma was
taking hormone replacement therapy to prevent
progression of osteoporosis, which was thought to be
due to steroid therapy. While on hormone replacement
therapy she developed a deep-vein thrombosis.
Question 135
A 38-year-old man was recently diagnosed with
polycystic kidney disease after being investigated for
hypertension. His father and brother also had
hypertension but had never been screened for polycystic
kidney disease. His paternal uncle had died from heart
failure. There was no family history of sudden death or
cerebral haemorrhage. His blood pressure measured
150/94 mmHg.
Question 136
A 20-year-old male was admitted with hypertension and
malaise. His blood pressure on admission was
210/124 mmHg. The mini-mental test score was
10/10. Both heart sounds were normal and the chest
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Glucose
24-hour urinalysis
11 g/dl
12 ! 109/l
120 ! 109/l
60 mm/h
138 mmol/l
7.4 mmol/l
28 mmol/l
500 "mol/l
4 mmol/l
Volume 400 ml
Protein 1.4 g
Blood ++
138
Answer 134
c. Alendronate.
All patients with or at risk of osteoporosis should have a
diet containing 800 iu of vitamin D and take
supplemental calcium 1.2 g per day. Regular exercise (30
minutes three times per week) and cessation of smoking
are also recommended.
Drug treatment of choice in established osteoporosis
is a bisphosphonate, of which alendronate has been used
most successfully. Other drugs include selective
oestrogen receptor modulators such as raloxifene,
oestrogen itself, calcitonin and vitamin D. The selective
receptor modulator raloxifene has been shown to be
effective in the treatment of osteoporosis, and unlike
Answer 135
b. There is a high chance that the patient will be
dialysis-dependent by the age of 60 years.
The features of polycystic kidney disease are covered in
Question 382. Hypertension is common in patients with
PKD, and patients with hypertension have a faster decline
in renal function than patients who are normotensive.
However, there is no conclusive trial demonstrating that
treatment of hypertension reduces the rate of decline of
renal function. ACE inhibitors and AIIRBs do not have
an effect on renal function but may improve prognosis by
preventing left ventricular hypertrophy.
Answer 136
d. IV calcium gluconate.
The patient has life-threatening hyperkalaemia, which is
defined as a serum potassium level 7 mmol/l or
hyperkalaemia <7 mmol/l that is associated with typical
electrocardiographic changes or muscle weakness, the
latter occur owing to antagonistic effects of potassium on
the membrane potential. In these circumstances the
immediate treatment is to stabilize the membrane
potential with intravenous calcium gluconate. Intravenous
calcium acts within minutes. Its effects last for up to 60
minutes, which allows definitive treatment with
intravenous dextrose and insulin to take effect (Table).
Management of hyperkalaemia
Method
Antagonism of
membrane actions
of potassium
Drive extra-cellular
potassium into cells
Agent
Calcium gluconate
Clinical Cases
139
Question 137
A 5-year-old male was admitted for investigation of ankle
swelling and abdominal distension that had occurred over
three months. His appetite was satisfactory, and there was
no history of diarrhoea, breathlessness, arthralgia or
syncope. He was born by a normal vaginal delivery and
weighed 3.6 kg at birth. He was well as a neonate and had
achieved his milestones normally thus far. Apart from
having mild eczema there was no past medical history of
note. His father was a solicitor, and his mother had just
returned to full-time teaching after giving birth to his
16-month-old brother, who was the only other sibling.
There was no history of travel abroad or any drug history.
On examination, he had facial swelling. There was no
pallor or cyanosis. The most striking feature was pitting
oedema of the lower limbs from the ankles to the thighs.
The heart rate was 100 beats/min and regular. The blood
pressure was 95/55 mmHg. The JVP was not raised.
Palpation of the precordium was normal. On auscultation,
heart sounds I and II were normal, but there was an
additional third heart sound. Examination of the
respiratory system revealed dullness to percussion at the
right lung base and reduced air entry on auscultation.
Abdominal examination demonstrated a non-tender,
distended abdomen with shifting dullness. There was no
palpable organomegaly.
Investigations are shown.
The patient was treated with 60 mg prednisolone and
40 mg furosemide. The oedema started improving after
one week, and renal function remained normal. After two
weeks he was discharged and seen at weekly intervals. In
the sixth week the oedema had completely subsided, and
his abdomen was soft and non-distended. A 24-hour
urinary protein estimation was 0.7 g. The furosemide was
stopped and plans were made to review the patient again
in two weeks, but three days later he was admitted with
right upper quadrant pain and abdominal distension. On
examination, the JVP was not raised. There was palpable
tender hepatomegaly and shifting dullness. There was no
lower-limb oedema.
Further investigations are shown.
Hb
WCC
Platelets
MCV
Urinalysis
10 g/dl
5 ! 109/l
166 ! 109/l
80 fl
Microscopy revealed
occasional transitional cells
24-hour urinary protein 5.2 g
Selective protein clearance
ratio was low
Ascitic fluid
Protein 8 g/l
Chest X-ray
Normal
Sodium
135 mmol/l
Potassium
3.7 mmol/l
Urea
2.1 mmol/l
Creatinine
65 mol/l
Bilirubin
10 mol/l
AST
19 iu/l
Alkaline phosphatase 80 iu/l
Total protein
36 g/l
Albumin
13 g/l
Glucose
4 mmol/l
Bilirubin
AST
Alkaline phosphatase
Albumin
15 mol/l
90 iu/l
89 iu/l
35 g/l
Question 138
What is the rhythm disturbance in this rhythm strip
(138)?
138
140
Answer 137
1. Nephrotic syndrome.
2. Hepatic vein thrombosis.
3. i. Ultrasound or CT scan of the liver looking
particularly at the hepatic and portal veins.
ii. Liver biopsy.
4. Thrombolysis to prevent severe hepatic congestion.
The combination of hypoalbuminaemia, heavy
proteinuria and oedema is strongly suggestive of the
diagnosis of nephrotic syndrome, which in young
children is most often due to minimal change
glomerulonephritis. Minimal change glomerulonephritis
is thought to be an auto-immune disorder, and usually
responds extremely well to steroids and other
immunosuppressants such as cyclophosphamide and
chlorambucil. There is a well-recognized association of
the disorder with Hodgkins lymphoma, bee stings, cows
milk allergy and ingestion of NSAIDs. Minimal change
nephropathy is found in 80% of children with nephrotic
syndrome. Treatment is with high-dose steroids, and
diuretics are often necessary to treat the oedema.
Relapses are common and are treated with steroids until
the urine is completely free of protein for three days.
Steroids are prescribed for a maximum of four weeks.
Recurrent relapses are managed with cyclophosphamide
Answer 138
Atrial flutter with 2:1/3:1 atrioventricular block.
There is an irregular narrow complex tachycardia, and the
differential diagnosis is between atrial fibrillation, atrial
flutter with varying atrioventricular block, and an atrial
tachycardia with varying atrioventricular block. The clue
is in the rhythm strip which reveals a saw-tooth pattern
to the ECG complexes, indicating flutter. The RRinterval is not constant, therefore there is flutter with
varying block. In this case there are between two and
three flutter waves between each RR-interval, and hence
the diagnosis is atrial flutter with 2:1/3:1 atrioventricular
block. The causes of atrial flutter are the same as those
for AF. The most effective treatment for atrial flutter is
DC cardioversion, delivering small energy shocks of
between 50 and 100 J. Chemical cardioversion is
difficult, but the most effective drugs for this purpose are
flecainide and amiodarone. Like AF, patients with atrial
flutter should be anticoagulated to prevent the risk of
thromboembolism.
Clinical Cases
141
Question 139
A 66-year-old retired school teacher presented with a sixmonth history of progressive weakness, fatigue and
breathlessness which was accompanied by weight loss of
5 kg. He had difficulty climbing stairs because his legs
would not carry him, and had noticed that he had
difficulty holding light objects with his left hand without
dropping them. Over the past week his wife had noticed
that his speech appeared slurred and nasal, and he was
having difficulty swallowing his meals. He had a past
history of pernicious anaemia for which he was taking
regular intramuscular B12 injections. On examination, he
was thin. There was no evidence of pallor or clubbing.
The patient had dysarthria. Examination of the cranial
nerves revealed normal eye movements, but tongue
movement was sluggish and there was reduced palatal
movement. The jaw jerk was brisk. On examination of his
limbs there was wasting and fasciculation of the small
muscles of the left hand. The tone and power in the left
upper limb was generally reduced. The upper-limb
reflexes were brisk. There was wasting and fasciculation in
both thigh muscles. The tone was increased and the
power was reduced. The ankle and knee jerks were brisk,
and there was obvious clonus at the ankle joint. Sensation
was normal and Rombergs test was negative. Examination of the fundi revealed bitemporal pallor.
Investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Chest X-ray
12 g/dl
5 ! 109/l
180 ! 109/l
86 fl
137 mmol/l
4.1 mmol/l
6 mmol/l
110 mol/l
Normal
Question 140
An 86-year-old male was found collapsed in his home by
his neighbour after his son raised concern about not
being able to contact him by telephone. There was no
significant past medical history. He was independent. He
was last seen two days earlier when he joined his
neighbour for Christmas dinner.
On examination, he was unconscious and had a
Glasgow coma scale of 5 out of 15. There was no nuchal
rigidity. Pupillary reflexes were sluggish, but examination
of the fundi was normal. Tone was slightly increased in
all the limbs. The peripheral reflexes were present and
both plantar reflexes were flexor. The heart rate was
40 beats/min, and blood pressure was 80/40 mmHg.
Heart sounds were normal, and the chest was clear.
An ECG was performed in the Accident and Emergency Department (140).
140
142
Answer 139
1. d. Motor neurone disease.
2. e. Nerve conduction studies.
j. Electromyography.
There is evidence of combined lower motor neurone and
upper motor neurone lesions and a pseudobulbar palsy.
There is no sensory abnormality, and ocular movements are
normal. These findings are characteristic of motor neurone
disease, which is characterized by a progressive
degeneration of the motor neurones in the cortex, spinal
cord and motor nuclei of the cranial nerves. The breathlessness is probably due to involvement of the respiratory
muscles. The bitemporal pallor is a red herring, and although it may have led some readers to diagnose multiple
sclerosis, it is important to note that bitemporal pallor is a
normal finding in some individuals. Moreover, wasting and
fasciculation are not features of multiple sclerosis because it
does not affect lower motor neurones. Although the patient
has a history of pernicious anaemia, his blood count does
not suggest B 12 deficiency and therefore subacute
degeneration of the spinal cord is unlikely. The absence of a
sensory neuropathy is also against the diagnosis.
The cause of motor neurone disease is unknown. In
approximately 15% of cases the disease is familial and is
due to mutations in the copper/zinc superoxide dis mutase gene on chromosome 21. The incidence is
1/50,000, and the male-to-female ratio is 1.5:1. There
are three distinct patterns known as progressive muscular
atrophy, amyotrophic lateral sclerosis and progressive
bulbar palsy which are characterized by predominantly
lower motor lesions, predominantly upper motor neurone
lesions, and bulbar and pseudobulbar palsy, respectively.
Usually, a combination of all three is present. Female sex,
bulbar onset and old age are poor prognostic markers.
The disease usually progresses inexorably and death is
usually from bronchopneumonia within five years of onset
of symptoms.
The diagnosis is clinical, but electromyography characteristically reveals a reduced number of action potentials
in the muscles which have an increased amplitude and
duration. Nerve conduction studies reveal normal motor
conduction and exclude an underlying neuropathy,
particularly in patients with the progressive muscular
atrophy variety of the disorder.
There are no curative therapies, but glutamate antagonists such as riluzole appear promising, as does ciliary
neurotrophic factor, which has been shown to promote
survival of cultured rat and human motor neurones. Both
agents are currently being tested on affected humans.
Answer 140
1. i. Bradycardia.
ii. Tremor artefact.
iii. J-waves.
iv. Prolonged QT-interval.
2. Rectal (core) temperature with a low-reading
thermometer.
3. Gradual rewarming using space blankets and
possibly warmed intravenous fluids, depending on
the severity of hypothermia.
Hypothermia is common among the elderly. It is usually
attributable to cold environment (no heating at home),
inadequate clothing, poor nutrition, neuroleptic drugs,
alcohol and hypothyroidism. Hypothermia is defined as
a fall in the core temperature to below 35C (95F).
Severe hypothermia causes impaired consciousness and
cardiac embarrassment. Bradycardia, hypotension,
Clinical Cases
143
Question 141
141a
Hb
WCC
Platelets
ESR
CRP
Sodium
Potassium
Urea
Creatinine
Urinalysis
11 g/dl
14 ! 109/l (neutrophil leucocytosis)
480 ! 109/l
110 mm/h
209 g/l
134 mmol/l
4.1 mmol/l
6 mmol/l
89 mol/l
Protein +1
Blood not detected
Chest X-ray (141a)
144
Answer 141
1. The chest X-ray demonstrates alveolar shadowing
affecting the right middle and lower lobes and in
the left lower lobe. In addition, there is a round
cavitating lesion in the left lower lobe. The findings
are consistent with either a purulent pneumonia
with left lower lobe abscess formation, or
pulmonary haemorrhage and a cavitating
granuloma due to Wegeners granulomatosis.
2. The Rinnes test reveals reduced bone and air
hearing conduction, suggesting sensorineuronal
deafness on the left side. The Webers test does not
normally lateralize to either ear, but in this case it
lateralized to the right. This is in keeping with
sensorineuronal hearing loss in the left ear. Because
both air and bone conduction are impaired in
sensorineuronal deafness, the sound from the
tuning fork (which is conducted via bone in the
Webers test) is heard loudest in the ear which is
not affected. In the case of pure conduction
deafness, the Webers test lateralizes to the affected
ear. Wegeners granulomatosis can produce
conduction and sensorineuronal deafness by
blockage of the Eustachian tube when it involves
the upper respiratory tract and 8th cranial nerve,
respectively.
3. i. Nasal or transbronchial lung biopsy.
ii. c-ANCA (antiproteinase 3).
4. Wegeners granulomatosis.
Wegeners granulomatosis is a necrotizing granulomatous
vasculitis affecting the upper and lower respiratory tracts
and the kidneys, although several other organs can be
affected. Granulomas occur in small arterioles. The
diagnosis should be suspected when two of these systems
are involved in the presence of systemic features such as
malaise, night sweats, fever and weight loss. This patient
has features of upper and lower respiratory tract
involvement which include frontal sinusitis, purulent nasal
discharge and nasal septal crusting, dry cough and evidence
of gross respiratory involvement on the chest X-ray. The
deafness in the left ear is indicative of 8th nerve
ANCA
c-ANCA
(PF3)
Wegeners granulomatosis
141b
p-ANCA
Anti-MPO subset
Non-specific subset
Microscopic polyarteritis
nodosa
Idiopathic crescentic
glomerulonephritis
Clinical Cases
145
Question 142
A 28-year-old male presented with a three-day history of
rigors and pleuritic pain affecting the left lung, where
there were signs of consolidation. There was no evidence
of lymphadenopathy or hepatosplenomegaly.
Investigations are shown.
Hb
WCC
Platelets
Neutrophils
Normoblasts
Myeloblasts
Myelocytes
Lymphocytes
12 g/dl
24 ! 109/l
149 ! 109/l
85%
7%
3%
2%
3%
Question 143
The following are serial LFT on a 51-year-old married
schoolteacher who had a partial gastrectomy for a
perforated peptic ulcer ten years previously. He was
asymptomatic. He was currently taking ranitidine.
1987
30
42
100
17
1988
36
65
112
20
1990
40
69
118
24
1992
44
73
125
29
1993
49
78
135
36
Question 144
The following are cardiac catheter data on a 4-year-old male with cyanosis and failure to thrive:
Chamber
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left ventricle
Aorta
Pressure
(mmHg)
8
90/30
22/12
4
80/20
77/50
Oxygen saturation
(%) (on air)
52
53
53
82
66
146
Answer 142
1. Leukaemoid reaction.
2. i. The presence of toxic granulations or Dohle
bodies in the white cells.
ii. Neutrophils exhibiting a toxic shift to the left,
i.e. three or fewer segments of the nucleus.
Answer 143
1. Chronic active hepatitis due to hepatitis B or
hepatitis C.
2. i. Hepatitis B and C serology.
ii. Liver biopsy.
3. Interferon therapy.
The patient has had major surgery in the past that almost
certainly required blood transfusion. Both hepatitis B and C
are readily contracted from blood transfusions. Since
screening donated blood for hepatitis B was initiated in the
1980s, hepatitis C has become the most common cause of
post-transfusion hepatitis in the Western world.
Almost 20% of patients with hepatitis B infection will
develop CAH. The cause is unknown, but is thought to be
a defective T-cell immune response. Most patients affected
are male. The condition is usually asymptomatic, or may
present as very slowly progressive hepatitis. About 50% of
those affected present with established chronic liver disease.
CAH may also occur following hepatitis C infection.
The acute hepatitic event is usually very mild, and often
goes unnoticed. The sequelae are similar to those of hepatitis B infection; however the incidence of CAH is almost
50%. Other causes of CAH are given (Table). There is
nothing in the patients history to suggest any of these
other causes.
The aminotransferases and bilirubin are usually modestly
raised and the alkaline phosphatase is very slightly raised.
The blood transaminase level bears no correlation with the
Answer 144
(See Interpretation of Cardiac Catheter Data, page 418.)
1. i. Elevated right ventricular pressure.
ii. Pressure drop across the pulmonary valve,
suggesting pulmonary stenosis.
iii. Low oxygen saturation in the left ventricle,
suggestive of a VSD with a right-to-left shunt.
iv. Saturation in the ascending aorta much lower
than the left ventricle, indicating an overriding
aorta.
2. Fallots tetralogy.
3. The right-to-left shunt means that the majority of
the blood does not pass through the lungs to be
oxygenated.
Clinical Cases
147
Question 145
145b
145a
-10
AC
0
10
Right
20
Left
30
40
BC
50
Right
60
70
Left
80
Unmasked
90
100
110
120
130
140
125
250
500
1000
2000
4000
8000
Frequency (Hz)
-10
0
20
30
Hearing level (dB)
10
40
50
60
70
80
90
100
110
120
130
140
125
250
500
1000
2000
4000
8000
Frequency (Hz)
Question 146
A 17-year-old male was referred with poorly developed
secondary sexual characteristics. He was a slow developer,
and had been to a special school for his entire education.
He had a brother who was severely handicapped and
wheelchair-bound who had died at the age of 17 years.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine kinase
Testosterone
LH
FSH
12 g/dl
5 ! 109/l
190 ! 109/l
137 mmol/l
3.7 mmol/l
5 mmol/l
350 iu/l
4 nmol/l
35 iu/l (normal range 110 iu/l)
30 iu/l (normal range 17 iu/l)
148
Answer 145
145c
Bilateral
Degenerative (presbycusis)
Aminoglycosides
Amphotericin
High-dose loop diuretics
Mumps
Rubella
Answer 146
1. Primary hypogonadism (hypergonadotrophic
hypogonadism).
2. Kleinfelters syndrome.
3. Demonstration of Barr body on buccal smear or
karyotyping.
4. Carrier for Duchenne muscular dystrophy.
The most common cause of primary hypogonadism is
Kleinfelters syndrome, which has an incidence of
1/1,000 births. Patients are tall, lack secondary sexual
characteristics, have gynaecomastia, and are often mentally subnormal. The condition is characterized by failure
of development of Leydig cells and seminiferous tubules.
Other causes of primary hypogonadism include Prader
Willi syndrome, LawrenceMoonBiedel syndrome,
Clinical Cases
149
Question 147
A 17-year-old female was admitted with a seven-hour
history of severe central abdominal pain radiating to her
back, which was accompanied by bilious vomiting. She
had been constipated for 72 hours. There was no
significant past medical history; in particular there was no
history of abdominal surgery. She was a non-smoker and
had a very occasional glass of wine. She was an only child.
Her father died when she was aged two. She was not
certain about the cause of death, but mentioned that he
had a history of psychosis and epilepsy. Her mother had
gallstones, but was otherwise well. She took paracetamol
for infrequent period pains. The only other drug history
was that of the contraceptive pill, which had been
commenced 10 days previously.
On examination she was unwell and distressed with pain.
She was sweating profusely. Her heart rate was
130 beats/min and blood pressure 190/110 mmHg.
Examination of the precordium revealed normal heart
sounds. Peripheral pulses were easily palpable. The chest
was clear. The abdomen was generally very tender, with
guarding around the umbilical area. The hernial orifice was
normal. There was a positive succussion splash and the
bowel sounds were present. Rectal examination revealed an
empty rectum. Neurological examination was normal.
The patient was prescribed pethidine for her pain and
metoclopramide for the vomiting. She received
intravenous saline. A few hours later she complained of
weakness affecting her left shoulder. She was unable to
abduct or adduct the shoulder. Shortly afterwards she
developed weakness in both her legs, in addition to
urinary retention. She was due to be catheterized when
she had a grand mal epileptic seizure.
Investigations are shown.
Question 148
A 68-year-old male presented with a 48-hour history of
right upper quadrant pain, dark urine and pale stools.
Shortly after admission he had an investigation (148).
1. What investigation has been performed?
2. What does it reveal?
3. What is the diagnosis?
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Calcium
Albumin
Bilirubin
AST
Blood glucose
Abdominal X-ray
Chest X-ray
CT scan brain
Lumbar puncture
13 g/dl
19 ! 109/l
400 ! 109/l
12 mm/h
121 mmol/l
3 mmol/l
5 mmol/l
2.5 mmol/l
44 g/l
15 mol/l
44 iu/l
4 mmol/l
Normal
Normal
Normal
1 lymphocyte/mm3
No red cells
Protein 0.3 g/l
Glucose 3.3 mmol/l
148
150
Answer 147
1. Acute intermittent porphyria (AIP). The
combination of abdominal pain, neurological
features, hypertension and tachycardia in a young
person should raise the suspicion of AIP.
2. i. Urinary PBG.
ii. Assay red cells for the enzyme PBG deaminase.
3. The oral contraceptive pill.
4. i. Stop oral contraceptive pill.
ii. High calorie intake with intravenous infusion
500 ml of 50% dextrose per 24 hours via a large
central vein in this case. The normal regime is 2
litres of 20% dextrose per 24 hours; however, in
the case of syndrome of inappropriate ADH
secretion, fluid restriction demands the use of
smaller volumes of high-concentration dextrose.
iii. Start intravenous haematin.
iv. Intravenous beta-blocker to control tachycardia
and hypertension.
5. Intravenous diazepam or chlormethiazole.
Acute intermittent porphyria is the most common type of
acute porphyria. It is a rare condition caused by a genetic
mutation in the gene encoding the enzyme PBG deaminase
on chromosome 11, and is inherited as an autosomal
dominant trait. A family history is usually present, but in up
to one-third of cases this may be absent, either because the
condition has not been diagnosed in first-degree relatives,
or because the condition is running a latent course. It is five
times more common in females than males, and usually
presents between the ages of 14 and 30 years. The absence
of PBG deaminase leads to elevated -ALA and PBG in the
blood stream (147), both of which are responsible for the
clinical manifestations of the condition. AIP is characterized
mainly by gastrointestinal and neurological symptoms.
Unlike the chronic porphyrias, skin photosensitivity is
extremely unusual in AIP. Attacks are usually precipitated
by drugs, alcohol, fasting and sepsis. Several drugs, particularly barbiturates and other anticonvulsants, have been
implicated. The oral contraceptive pill has also been
associated with acute attacks of porphyria and is the most
likely precipitating factor in this case. The most common
symptoms are acute abdominal pain which can simulate a
surgical emergency, nausea, vomiting and constipation.
Abdominal guarding may be present, but bowel sounds are
usually present. There is often evidence of delayed gastric
emptying, and it is not unusual to elicit a succussion splash
due to a stomach full of gastric contents. The abdominal
X-ray is normal. Neurological manifestations of the disease
include a peripheral and autonomic neuropathy. Autonomic
neuropathy most commonly manifests as tachycardia which
is out of proportion to the extent of abdominal pain, hypertension and excess sweating. In approximately 50% of cases
there is evidence of a motor neuropathy which often affects
the proximal muscles. Both bulbar palsy and quadriplegia
are recognized manifestations. Respiratory muscle paralysis
147
ALA synthetase
ALA
ALA dehydratase*
PBG
PBG deaminase
Deficient
in AIP
Uroporphyrinogen
Uroporphyrin
decarboxylase
Deficient
in PCT
Coproporphyrin
Coproporphyrin oxidase*
Protoporphyrin
Ferrochelatase*
Haem
*Inhibited by lead
Clinical Cases
151
Answer 148
1. The investigation is a percutaneous transhepatic cholangiogram.
2. Both the common bile duct and the internal hepatic ducts are dilated. There is a large filling defect at the distal
end of the common bile duct.
3. A gall stone in the common bile duct causing obstructive jaundice.
Question 149
149a
149b
149c
152
Answer 149
1. Left facial nerve palsy.
2. Erythema chronicum migrans.
3. i. Borrelia lymphocytoma.
ii. Acrodermatitis chronica atrophicans.
4. Complete heart block. (Third-degree
atrioventricular block.)
5. Lyme disease.
6. i. Therapy with doxycycline, benzyl penicillin,
azithromycin, or cefotaxime.
ii. Temporary cardiac pacing.
The patient presented with a facial palsy and has ECG
evidence of third-degree atrioventricular block. In addition, she had a macular rash which appears to be fading
in the centre (149b) and is characteristic of erythema
chronicum migrans. While there are several medical
conditions which may involve the cardiovascular and
central nervous system simultaneously (Table), the rash
makes Lyme disease the most likely diagnosis.
Lyme disease is caused by the spirochaete, Borrelia
burgdorferi. It is transmitted by hard-bodied ticks (Ixodes
species). The disease has a wide clinical spectrum, ranging
from asymptomatic infection to multi-system
involvement. The first presentation is a characteristic skin
lesion at the site of the tick bite, which begins as a macule
between 240 days after exposure, and expands with
central clearing. This is termed erythema chronicum
migrans and may be associated with fever and regional
Drugs
Amphetamines
Tricyclic antidepressant drugs
Lithium
Neuroectodermal syndromes
Neurofibromatosis
Tuberose sclerosis
Hereditary neuropathies
Friedreichs ataxia
Dystrophia myotonica
Duchenne muscular dystrophy
Miscellaneous
AIP
GuillainBarr syndrome
Clinical Cases
153
Question 150
A 69-year-old male was admitted to the Coronary Care
Unit after presenting with a three-hour history of chest
pain, palpitations and breathlessness. He had a past
history of hypertension and three myocardial infarctions.
His regular medication comprised aspirin 150 mg once
daily, captopril 50 mg three times daily, furosemide
150a
Question 151
A deaf couple both have a hereditary form of deafness.
They have recently married, and want advice on the
chances of their children being affected. The family tree
of both parents is shown (151).
Affected male
Unaffected male*
Affected female
Unaffected female*
151
154
Answer 150
150b
Answer 151
1. b. Autosomal recessive.
2. b. Autosomal recessive.
3. d. 100%.
In both families neither parent is affected, which excludes
an autosomal dominant or an X-linked dominant condition
in any of the parents and an X-linked recessive condition in
both fathers (the presence of a defective
X-linked gene in the fathers would manifest as abnormal
phenotype). This leaves the possibility of an autosomal
recessive condition, or that the mothers are carriers of an
X-linked condition. However, an X-linked recessive mode
Clinical Cases
155
Question 152
A 5-year-old male was admitted with a two-day history of
blood-stained diarrhoea. Three days after, he felt
nauseous and generally unwell. On examination he had
Hb
WCC
Platelets
PT
APTT
Blood film (152)
Sodium
Potassium
Creatinine
Urea
8 g/dl
13 ! 109/l
36 ! 109/l
13 s (control 13 s)
34 s (control 36 s)
152
138 mmol/l
5.9 mmol/l
130 mol/l
11 mmol/l
Question 153
Hb
WCC
Platelets
MCV
Clotting
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Calcium
Phosphate
Bilirubin
AST
Alkaline phosphatase
Albumin
Glucose
Urinalysis
Chest X-ray
X-ray of left hip
ECG
9.8 g/dl
14 ! 109/l
350 ! 109/l
84 fl
Normal
135 mmol/l
6.8 mmol/l
16 mmol/l
670 mmol/l
15 mmol/l
2.0 mmol/l
2.8 mmol/l
14 mol/l
26 iu/l
100 iu/l
40 g/l
9 mmol/l
Blood +++
Protein +
Normal
Fracture and dislocation of
the neck of femur
Minor T-wave abnormalities
in the lateral leads
156
Answer 152
1.c. Haemolytic uraemic syndrome.
2.c. Stool culture for Escherichia coli 0157:H7.
E. coli 0157:H7 is most commonly transmitted by eating
under-cooked beef. The bacterium produces a toxin that
is responsible for the gastrointestinal effects, which include
colicky pain and diarrhoea, which may be blood-stained.
Fever is very mild or completely absent. Symptoms of
infection usually subside after about a week; however, the
HUS develops in approximately 6% of patients. This is
characterized by an MAHA, which is a result of
endothelial damage by the toxin, leading to adherence of
fibrin strands which trap and fragment red cells and
platelets. This produces a characteristic blood picture of
anaemia, red cell fragments, thrombocytopenia and
increased reticulocytes. Small vessel fibrin deposition and
thrombosis resulting from MAHA lead to renal damage
and oliguric renal failure. Bleeding and bruising are
common. In pure MAHA clotting is usually normal;
however, MAHA often coexists with disseminated
intravascular coagulation, where clotting is impaired and
the serum fibrinogen degradation product level is
elevated. Treatment of HUS complicated by MAHA and
renal failure is supportive. Blood transfusions are often
HUS
Thrombotic thrombocytopenic purpura
Accelerated hypertension
Septicaemia
Vasculitides
Connective tissue diseases
Mucinous adenocarcinoma
Burns
Prosthetic valve-induced haemolysis
Drugs (cyclosporin, mitomycin)
Answer 153
1. Rhabdomyolysis.
2. i. Measuring creatinine kinase levels, which are
elevated due to skeletal muscle damage
ii. Detection of myoglobin in the urine.
There are two important clues for diagnosing rhabdomyolysis. Firstly, the patient has had a fall. Secondly,
there is renal failure with a disproportionately raised
creatinine level. Other causes of rhabdomyolysis are
tabulated below (Table A). The common pathology is
Muscle trauma/infarction
Electrocution
Hypothermia
Status epilepticus
Neuroleptic malignant syndrome
Ecstasy/amphetamine abuse
Burns
Septicaemia
Therapy with statins
Very strenuous exercise (e.g. marathon running)
Clinical Cases
157
Question 154
154
Hb
WCC
Platelets
Blood film
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alkaline phosphatase
Albumin
Chest X-ray
9 g/dl
5 ! 109/l
150 ! 109/l
Red cell agglutination
131 mmol/l
4.0 mmol/l
4.0 mmol/l
70 mol/l
26 mol/l
60 iu/l
83 iu/l
110 iu/l
36 g/l
Right middle lobe
consolidation
Question 155
A 14-year-old female was admitted for investigation of
intermittent colicky abdominal pain associated with
vomiting. She had experienced several episodes in the
past six months requiring hospital admissions. Physical
examination during these episodes revealed a distended
abdomen which was tympanic to percussion. Bowel
sounds were tinkling. Hernial orifice examination was
normal. The patient usually developed two painful 4 cm
raised lesions on her left hand and forearm respectively
which were only present while she was symptomatic. She
was never in hospital for more than 48 hours, during
which time she was managed with intravenous fluids and
resting the bowel. She always made a spontaneous
recovery. In between episodes of abdominal pain she was
perfectly well. She had a 5-year-old cousin who had also
recently been admitted to hospital on three occasions
with the same symptoms.
These investigations were performed while the patient
was symptomatic.
The patient had a small bowel meal when her symptoms had recovered, which was also normal.
Hb
WCC
Platelets
U&E
LFT
Thyroid function tests
Bone biochemistry
Blood glucose
Serum amylase
Serum lead
Urinary -ALA
Urinary PBG
Serum immunoglobulins
12 g/dl
6 ! 109/l
390 ! 109/l
Normal
Normal
Normal
Normal
5 mmol/l
Normal
Undetectable
Undetectable
Undetectable
Normal
158
Answer 154
1. Erythema multiforme.
2. Syndrome of inappropriate ADH secretion.
3. Autoimmune haemolytic anaemia.
4. Direct Coombs test at 4C (39.2F).
5. Mycoplasma pneumonia.
6. i. Mycoplasma serology.
ii. Cold agglutinin estimation.
Infections
Mycoplasma pneumonias
Herpes simplex virus
Orf
TB
Neurological
Aseptic meningitis
Encephalitis
Transverse myelitis
GuillainBarr syndrome
Peripheral neuropathy
Drugs
Penicillins
Sulphonamides
Barbiturates
NSAID
Cardiac
Myocarditis
Pericarditis
Miscellaneous
Connective tissue diseases
Vasculitides
Internal malignancy
Haematological Thrombocytopenia
Cold autoimmune haemolytic
anaemia
Locomotor
Myositis
Arthritis
Skin
Erythema multiforme
Gastrointestinal Diarrhoea/vomiting
Endocrine
SIADH
Miscellaneous
Bullous myringitis
Answer 155
1. Hereditary angio-oedema.
2. Use fresh-frozen plasma or C1 esterase inhibitor
concentrates.
Hereditary angio-oedema is inherited as an autosomal
dominant trait. It is associated with C1 esterase inhibitor
deficiency, resulting in high C1 esterase levels. Deficiency
of C1 esterase inhibitor (which modulates complement)
can lead to angio-oedema. A positive family history is
very common, although there is a similar condition
associated with an acquired lymphoproliferative disorder
in which C1 esterase inhibitor levels are also low. Clinical
features can occur late in adult life. Attacks are preceded
Clinical Cases
159
Question 156
A 30-year-old male presented with a four-day history of
passing dark urine. He had passed dark urine intermittently
for six months, though such passage had never exceeded
24 hours, except on this occasion. More recently, he
complained of malaise, lethargy and weakness. His GP
thought he appeared pale, and prescribed iron tablets. Two
days before coming to the hospital, the patient developed
sharp right lower chest pain which was worsened on
inspiration, and a cough productive of bright red sputum.
On further questioning, he volunteered a six-month
history of intermittent abdominal pain and episodes of
abdominal distension.
He had never taken any regular medication and had
not travelled abroad for a year. He consumed 57 litres
of lager on weekends, and occasionally had a glass of
wine with a meal.
On examination, he was pale and slightly jaundiced. He
had a temperature of 37.5C (99.5F). There was no
lymphadenopathy. The JVP was not raised. Examination of
the respiratory system revealed dullness of the right base
associated with reduction of air entry. Abdominal examination demonstrated firm, palpable hepatomegaly 4 cm below
the costal margin. There were no other palpable masses.
There was no clinical evidence of peripheral oedema.
Investigations are shown.
Hb
WCC
Platelets
MCV
Reticulocyte count
Direct Coombs test
Chest radiograph
Urinalysis
Sodium
Potassium
Urea
Bilirubin
AST
Alkaline phosphatase
Albumin
7.3 g/dl
2.8 ! 109/l
200 ! 109/l
93 fl
15%
Negative
Atelectasis at the right
lung base
Urobilinogen +++
Haemosiderin ++
Cell 0
136 mmol/l
4.8 mmol/l
5.3 mmol/l
33 mol/l
40 iu/l
94 iu/l
36 g/l
Question 157
An 18-year-old male developed sharp left-sided chest
pain on running up a flight of stairs, followed by slight
breathlessness on exertion. On examination, he appeared
relatively well. His heart rate was 90 beats/min, and the
respiratory rate was 18/min. On auscultation of the heart
there was a clicking sound synchronous with the heart
sounds.
160
Answer 156
1. d. Haemoglobinuria.
2. a. Haemolysis.
Bilirubinuria does not occur in haemolytic anaemia
because bilirubin is in the unconjugated form and
therefore is not water-soluble and cannot be excreted in
the urine. Urobilinogen does stain urine, but not enough
to give it the red colour of haemoglobinuria. Myoglobin is
produced in large amounts in rhabdomyolysis, and while it
may produce red discoloration of urine, there is no
evidence for rhabdomyolysis in this case. Haemosiderinuria
occurs in intravascular haemolyis, but can only be detected
on staining the urine with Prussian blue.
Hepatitis, gallstones and pancreatitis do not account
for the severity of the anaemia. Although haemolyis and
thrombotic episodes can be present in a patient with
malignancy, it does not account for the dark urine that is
present in the absence of red cells in the urine.
The diagnosis is PNH. This is an acquired disorder of
the haematopoietic cells which usually occurs after an
episode of aplastic anaemia, leading to increased
susceptibility of red cells to complement lysis. White cells
and platelets are also affected. The onset of the disease is
often insidious. The disorder is characterized by nonimmune haemolytic anaemia, variable pancytopenia and
thrombotic episodes. The MCV may be normal,
depending on the extent of reticulocytosis. The
molecular basis of the membrane defect has recently been
unfolded and attributed to abnormalities in the synthesis
of the phospholipid GPI, which serves an anchoring
function for important cell surface proteins such as CD59
on red cells, which is a complement lysis inhibitor. Lack
of GPI does not permit red cells to express the antigen
CD59 on their cell surface, leading to complement lysis.
The thrombotic tendency results from inappropriate
activation of platelets that are abnormally sensitive to
complement. Intravascular haemolysis is reflected by an
Answer 157
1. c. Left-sided apical pneumothorax.
2. e. Chest X-ray in end expiration.
A systolic click that is synchronous with heart sounds is a
rare but recognized sign of a small left apical
pneumothorax. It is often referred to as Hammans sign.
A differential diagnosis of this sign is the systolic click of
Clinical Cases
161
Question 158
158a
Question 159
A 15-year-old female was investigated for short stature.
She measured 1.22 m tall. Her sister aged 14 was 1.53 m
tall. She was born three weeks prematurely, and was
noted to have a divergent squint affecting her left eye in
childhood. She had achieved her milestones in a normal
manner, but school performance had been below
average. On examination, the patient weighed 42 kg. She
had a left-sided divergent squint. Her neck was short and
her hands were small. Breast development had just begun
and there was scanty pubic and axillary hair growth. The
heart rate was 90 beats/min and regular, and the blood
pressure was 110/70 mmHg. The heart sounds were
normal and the chest was clear. Abdominal and neurological examination was also normal.
Initial investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Glucose
Calcium
Phosphate
Alkaline phosphatase
Albumin
TSH
Thyroxine
LH
FSH
GH
X-ray
13 g/dl
4.2 ! 109/l
410 ! 109/l
136 mmol/l
3.8 mmol/l
5.1 mmol/l
90 mol/l
5.2 mmol/l
1.96 mmol/l
1.3 mmol/l
90 iu/l
39 g/l
2 mu/l
87 nmol/l
(normal 60160 nmol/l)
4 iu/l (normal 112 iu/l)
6 iu/l (normal 19 iu/l)
2 mu/l
Left wrist, lateral skull
normal bone age
162
Answer 158
158b
158c
Answer 159
1. i. Pseudohypoparathyroidism.
ii. Idiopathic hypoparathyroidism.
2. Serum PTH level.
A low serum calcium, raised phosphate and normal
alkaline phosphatase are suggestive of either idiopathic
hypoparathyroidism or pseudohypoparathyroidism. The
short stature, short neck and squint are characteristic of
pseudohypoparathyroidism. In addition, the patient has
small hands presumably secondary to short metacarpals
which are also associated with pseudohypoparathyroidism. However, these morphological changes are also
infrequently present in idiopathic hypoparathyroidism.
Pseudohypoparathyroidism results from resistance of
some target tissues to the actions of PTH. The disorder
may be asymptomatic, present with lethargy, neuromuscular irritability or psychosis. Neuromuscular irritability is
Clinical Cases
163
Question 160
160a
160b
Question 161
A 70-year-old male presents to the Accident and
Emergency Department in the morning with a painful
swelling on the anterior aspect of his left thigh which he
had noticed on the previous evening. The swelling had
become bigger and he was having difficulty walking due
to the pain. He denied any recent trauma to the leg.
Apart from a past history of TB 30 years ago, there was
no other history of note. He was widowed three years
ago and lived alone. He took paracetamol infrequently
for aches and pains in his limbs.
On examination, he appeared unkempt and was thin.
There was no pallor or oedema. Vital parameters were
normal and he was apyrexial. There was a 6 cm, tender
swelling on the anterior aspect of the left thigh. There
was also evidence of widespread bruising on his forearms
and legs.
Investigations are shown.
Hb
WCC
Platelets
MCV
PT
APTT
BT
11 g/dl
5 ! 109/l
170 ! 109/l
90 fl
14 s (control 14 s)
45 s (control 45 s)
12 min (control <10 min)
164
Answer 160
1. Acute inferior myocardial infarction with complete
heart block complicating an acute proximal aortic
dissection. The echocardiogram demonstrates an
enlarged aortic root with an obvious dissection flap.
(See Echocardiography, page 421.)
2. Immediate referral to the cardiothoracic surgeons.
Patients with proximal dissections should undergo urgent
surgical repair, but those with distal dissection are treated
conservatively. Repair is by resection of the ascending
aorta and replacement with dacron. In the interim, it
would be important to relieve the severe pain with
opiates and insert a temporary pacing wire to treat the
complete heart block and help maintain circulation as he
is hypotensive. In acute dissection, hypotension is due to
rupture of the proximal dissection into the pericardial
space, which is not present in this case; therefore,
complete heart block is contributing to the hypotension
in this case. In contrast with this case, most patients
presenting with acute dissection are hypertensive and in
these circumstances it is prudent to treat the hypertension
aggressively to obtain a systolic blood pressure equal to
or less than 100 mmHg. Drugs most commonly used
include intravenous beta-blockers, for example, labetolol,
or intravenous nitroprusside. It is very important to
recognize that the cause of myocardial infarction is a
proximal dissection, and not coronary thrombosis. While
thrombolytic therapy has revolutionized the management
of acute coronary thrombosis, it is an absolute
contraindication in a patient who has sustained a
myocardial infarction secondary to aortic dissection.
Answer 161
a. Vitamin C deficiency (scurvy).
The normocytic anaemia, bruising and abnormal
bleeding time in an elderly patient point to the diagnosis
of vitamin C (ascorbic acid) deficiency, or scurvy.
Vitamin C is abundant in fresh greens, citrus fruits, liver
and kidney. Nutritional deficiency is relatively common in
the elderly, who eat predominantly tinned foods. Vitamin
C is required for the hydroxylation of proline in collagen
synthesis. Deficiency results in abnormal connective
tissue, resulting in easy bruising, bleeding gums,
periosteal haemorrhage and muscle haematomas. The
characteristic signs of vitamin C deficiency are
Clinical Cases
165
Question 162
A 48-year-old female had an 11-month history of
abdominal cramps and diarrhoea. She moved her bowels
twice daily; the stool was loose and foul-smelling. There
was no history of bleeding per rectum or tenesmus. Her
appetite was unchanged, but she had lost 8 kg in weight.
Two years ago she had a total abdominal hysterectomy
and salpingo-oophorectomy for carcinoma of the cervix,
followed by a course of external radiotherapy. She had
been followed up regularly by her gynaecologist, and was
free from recurrence of the malignancy. She was married
with two sons, aged 10 and 12. She worked as a
secretary. She consumed 1 unit of alcohol daily and was a
non-smoker. There was no history of travel abroad. She
had a long history of Raynauds phenomenon. She took
paracetamol for very infrequent headaches.
On examination she was thin. There was no pallor,
clubbing, lymphadenopathy or oedema. The temperature
was normal. Inspection of the oral cavity revealed two
small, non-tender, shallow ulcers. The abdomen was thin.
There was a lower, midline scar. Mild tenderness was
elicited on palpation of the right iliac fossa. Rectal
examination was normal. Investigations are shown.
1. What is the diagnosis?
a. Crohns disease.
b. Coeliac disease.
c. Small bowel lymphoma.
d. Radiation enteritis.
e. Tuberculous ileitis.
Hb
WCC
Platelets
MCV
ESR
Serum B12
Serum folate
Calcium
Phosphate
Alkaline phosphatase
Albumin
U&E
Total thyroxine
TSH
Abdominal X-ray
Chest X-ray
10g/dl
8 ! 109/l
199 ! 109/l
106 fl
16 mm/h
98 pmol/l
18 g/l
2.12 mmol/l
0.9 mmol/l
112 u/l
38 g/l
Normal
110 nmol/l
1.9 mu/l
Normal
Normal
Question 163
An 18-year-old female had blood tests as part of a routine
medical (below).
Hb
WCC
Platelets
MCV
MCHC
MCH
Red cell count
Blood film
Sodium
Potassium
Urea
Creatinine
10.5 g/dl
6 ! 109/l
300 ! 109/l
61 fl
28 g/l
19 pg
6.8 ! 1012/l
Hypochromia, anisocytosis,
poikilocytosis, target cells
136 mmol/l
4.1 mmol/l
4 mmol/l
72 mol/l
166
Answer 162
1. d. Radiation enteritis.
2. c. Small bowel meal.
The patient has a malabsorption syndrome. The B12 level
is low in the presence of a normal folate level. This
suggests either selective B 12 malabsorption due to
terminal ileal disease (Crohns disease, terminal ileal
resection, ileal TB), pernicious anaemia or excess
utilization of B 12 within the gut itself (bacterial
overgrowth which occurs in the presence of a structural
abnormality of the small bowel, e.g. after Billroth II
gastric surgery, jejunal diverticula, Crohns disease,
intestinal fistulae, radiation enteritis and small bowel
involvement in systemic sclerosis, amyloidosis and
diabetic autonomic neuropathy).
Symptoms of malabsorption are absent in pernicious
anaemia. The differential diagnosis is, therefore, between
terminal ileal disease or bacterial overgrowth. There is no
mention of small bowel surgery in the question. Ileal TB
is unlikely in the absence of a febrile illness, night sweats,
only slightly elevated ESR, absent past history or contact
Answer 163
1. c. -thalassaemia minor.
d.Iron-deficiency anaemia.
2. c. Serum ferritin.
g. Haemoglobin electrophoresis.
The best answer is -thalassaemia minor. The clue lies in
the fact that the MCV is disproportionately low compared with the Hb. In -thalassaemia trait (minor), the
cells are small due to defective globin synthesis and are
removed relatively rapidly from the circulation by the
spleen. As a consequence, the marrow produces large
amounts of red cells and, provided that iron and folate
stores remain replenished, the Hb is only modestly
reduced but the cells are relatively small. The red cell
count itself, however, may be high. In iron deficiency,
the marrow is unable to produce red cells to maintain a
normal Hb because haem synthesis is incomplete without
iron. Therefore, the number of cells produced (and hence
the red cell count) is small compared with -thalassaemia
trait; however, the size is similar. By the time the iron
deficiency has become severe enough to cause a reduction in the MCV as low as 61 fl, the Hb is much lower
than in -thalassaemia trait.
In -thalassaemia major the Hb, red cell count and
MCV are all very low, and such patients require life-long
blood transfusions to maintain a Hb around 10 g/dl.
-thalassaemia trait may present with a similar picture as
-thalassaemia trait if two of the four genes which code
Clinical Cases
167
Question 164
164a
164b
10
8
6
Expiration
4
Flow (l/s)
2
0
2
4
6
8
10
A 76-year-old female developed gradual onset of breathlessness over the past three weeks. On admission, she had
stridor. Her respiratory rate was 30/min, and she was not
cyanosed. Her trachea was slightly deviated to the right,
and there was a mass just palpable in front of it, which
moved slightly with swallowing. The lower margins of
the mass could not be defined. Auscultation of the lungs
revealed stridor-type sounds transmitted from the upper
airways. She was managed with oxygen and saline nebulizers in the Accident and Emergency Department, and
felt considerably better. She mentioned having a problem
with her thyroid gland, and over 20 years ago was told
she did not need any treatment. She had lost 5 kg in
weight over the past two months.
She had a chest radiograph (164a) in the Accident
and Emergency Department.
Lung function tests and a thyroid scan were per formed the following day. Results of the flow loop curve
(164b) and thyroid scan (164c) are shown.
Inspiration
0
2
4
6
Change in lung volume (l)
164c
Question 165
The blood results shown were performed two months
apart in a patient with HIV infection.
Hb (g/dl)
WCC (! 109/l)
Platelets (! 109/l)
MCV (fl)
Reticulocyte count (%)
CD4
October
11.8
3.0
160
86
1.5
24
December
7.6
3.1
90
110
4
120
168
Answer 164
1. The lateral chest X-ray reveals a mass in the superior
mediastinum. Possible causes of a superior
mediastinal mass include (i) retrosternal goitre,
(ii) thymoma, (iii) lymphoma, (iv) malignant
lymphadenopathy, (v) teratoma, and (vi) aneurysm
of the aortic arch. The most likely cause of the mass
in this situation is a retrosternal goitre.
2. There is evidence of reduced airflow rate which is
more pronounced in the inspiratory phase of
respiration. This is suggestive of extrathoracic large
airways obstruction. Typical examples include
retrosternal goitre and its complications,
compression by malignant lymph nodes and bilateral
vocal cord paralysis.
3. i. Compression from a retrosternal multinodular
goitre which has undergone malignant change.
ii. Compression from a retrosternal multinodular
goitre due to spontaneous haemorrhage within
the gland.
iii. Compression from locally metastasized lymphatic
deposits from carcinoma of the thyroid.
4. A large cold nodule in the left lobe of the thyroid
gland.
5. i. CT scan of the neck and upper thorax.
ii. Fine-needle aspirate of the thyroid gland for
histology.
There is a history of a chronic thyroid disorder in this elderly
woman. She is clinically and biochemically euthyroid, and
has a palpable mass in the suprasternal area which moves
with swallowing. The most probable cause for the mass in
the superior mediastinum is a retrosternal extension of a
goitre. The reason for sudden deterioration is tracheal
compression due to rapid enlargement of the goitre. This
Answer 165
e. Zidovudine toxicity.
The patient has become more anaemic, has developed a
macrocytosis, thrombocytopenia and an increase in the
CD4 count. The most likely cause of these abnormalities is
treatment with AZT. AZT is a nucleoside analogue that
inhibits the viral enzyme reverse transcriptase and is a DNA
chain terminator. It is widely used in symptomatic HIV
infection. In such patients it has been shown to reduce
mortality by reducing the incidence of opportunistic
infections owing to a significant but transient improvement
in the CD4 count. The drug has important haematological
side-effects, which include a reduction in all cell lines and a
megaloblastic change in the marrow. The general sideeffects of the drug include nausea, vomiting, myalgia,
headaches, neuropathy and myopathy.
Clinical Cases
169
Question 166
166a
166b
Hb
11 g/dl
WCC
10 ! 109/l
Platelets
180 ! 109/l
MCV
85 fl
ESR
80 mm/h
Sodium
129 mmol/l
Potassium
4.3 mmol/l
Urea
8 mmol/l
Creatinine
90 mol/l
Glucose
5 mmol/l
Echocardiogram (166a)
Sputum microscopy (166b)
Question 167
The data are from cardiac catheter traces of a 14-year-old
male, taken five years apart.
5 years ago
Pressure Satn (%)
(mmHg)
68
8
68
40/5
94
40/18
94
Present
Pressure Satn (%)
(mmHg)
49
12
50
120/20
50
115/55
50
6
110/4
115/60
8
115/15
100/50
95
95
57
50
170
Answer 166
1. The echocardiogram demonstrates a large
pericardial effusion. (See Table for causes.) (See
Echocardiography, page 421.)
2. Tuberculous pericardial effusion.
3. i. Pericardiocentesis.
ii. Empirical antituberculous therapy with
rifampicin, isoniazid and ethambutol. In patients
of ethnic origin, or where multi-resistant bacilli
are suspected, there is a case for adding
pyrazinamide.
4. Contact tracing.
The most likely underlying cause is TB, considering that the
woman has a productive cough and the sputum, which is
stained with the ZiehlNeelsen stain, reveals acid-fast bacilli.
In the UK, the incidence of TB in immigrants from the
Asian subcontinent is 40 times higher than in the native
white population. Primary TB is usually without symptoms
in the majority of individuals, although in a few cases there
may be a cough, wheeze and fever. The primary complex
heals with calcification; however, there may be reactivation
of infection several years later due to malnourishment or
conditions predisposing to immunosuppression resulting in
pulmonary TB and possible dissemination to other organs
via the lymphatics and the bloodstream.
The diagnosis is based on identifying the organism
from pericardial fluid. In the simplest form this may be
done by staining the fluid with ZiehlNeelsen to reveal
acid-fast bacilli; however, the yield is only 25% with this
method. The organism may be cultured on LowensteinJensen medium but this can take over eight weeks. The
quickest method of making the diagnosis in the event of
a negative acid-fast stain is by PCR to tuberculous
protein or by demonstrating evidence of the disease
elsewhere, for example in the patients sputum.
Answer 167
1. i. Elevated right ventricular pressure.
ii. Elevated pulmonary artery pressure.
iii. Increase in oxygen saturation in the right
ventricle, suggesting a left-to-right shunt at the
level of the ventricle.
2. i. Huge increase in right ventricular pressure in the
following five years.
ii. Huge increase in pulmonary artery pressure in the
following five years.
iii. Reduction in oxygen saturation in the left
ventricle, suggesting a right-to-left shunt at the
level of the ventricles.
(See Interpretation of Cardiac Catheter Data, page 418.)
Clinical Cases
171
Question 168
A 45-year-old male was referred to the local psychiatrist
by his GP with a three-month history of lethargy, loss of
appetite, nausea, early morning wakening and loss of
libido. He had recently lost his job as a clerk for making
three serious errors in the space of a fortnight. There was
no history of headaches or weight loss. He had
experienced intermittent abdominal pain after meals
which was investigated with upper gastrointestinal
endoscopy four weeks earlier and attributed to a small
gastric ulcer. Biopsy from the ulcer demonstrated an inflammatory infiltrate but there was no evidence of
malignancy or Helicobacter pyloris. He had a long history
of constipation which had not caused him any concern,
and more recently complained of pains in his hands and
feet. He was not sleeping well and awoke between two
and three times a night to pass urine, which was extremely unusual for him. His wife was concerned that he
was worried about loss of earnings and had become very
depressed. He had no other significant past medical
history. He was a non-smoker and consumed half a bottle
of wine daily.
On examination, he had a reduced affect. There was
no pallor, clubbing or lymphadenopathy. He was apyrexial. The heart rate was 96 beats/min and blood pressure 160/95 mmHg. Examination of his eye is shown
(168a). On abdominal examination, a mass was
identified in the right iliac fossa which was indentible.
There was no tenderness and the bowel sounds were
audible. A rectal examination was not performed. The
examination of the cardiovascular and respiratory system
was normal. He had painful hands, but there was no
evidence of joint swelling or restriction of movements.
Examination of his central nervous system, including his
higher mental function was entirely normal.
Investigations are shown.
1. List two tests you would perform to come to a
rapid diagnosis.
2. What is the definitive treatment?
3. How would you manage the patient after he has
had the definitive treatment?
168a
168b
Hb
WCC
Platelets
ESR
Sodium
Potassium
Bicarbonate
Chloride
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Total protein
Albumin
X-ray of hands (168b)
15 g/dl
5 ! 109/l
306 ! 109/l
18 mm/h
136 mmol/l
4.2 mmol/l
19 mmol/l
115 mmol/l
7 mmol/l
89 mol/l
12 mol/l
24 iu/l
300 iu/l
78 g/l
44 g/l
172
Answer 168
1. i. Serum calcium.
ii. PTH level.
2. Parathyroidectomy.
3. Vitamin D supplements.
The symptoms of hypercalcaemia are rather non-specific,
and include nausea, anorexia, weight loss, abdominal pain,
bone pain, polyuria, polydipsia, lack of concentration,
depression and occasionally acute psychosis. The
abdominal pain may be non-specific or due to constipation, peptic ulcer disease, pancreatitis and renal colic, all of
which are recognized complications of hyperparathyroidism. It is worth remembering that while nephrocalcinosis
is also a complication of hyperparathyroidism, it is not
associated with abdominal pain. This man has several of
these symptoms, as well as recent peptic ulcer disease. The
eye in 168a reveals corneal calcification which occurs in
hypercalcaemic states. The calcification is usually seen at
the 3 and 9 oclock positions. The hand X-ray (168b)
demonstrates periosteal bone resorption which is characteristic of hyperparathyroidism. Hyperparathyroid-related
bone disease is further supported by the raised alkaline
phosphatase level. Bone changes are seen in 2% of cases of
hyperparathyroidism. Cystic lesions may be present, and
can result in pathological fractures. Extensive bone resorption affecting the skull gives it a characteristic salt-andpepper appearance on the skull X-ray.
Hyperparathyroidism is diagnosed by demonstrating
elevated or normal levels of PTH in the presence of a high
serum calcium. Primary hyperparathyroidism is usually
secondary to a single, benign parathyroid adenoma.
Hyperparathyroidism due to carcinoma of the parathyroid
glands is extremely rare. Hyperparathyroidism can be part
of MEN syndromes. Secondary hyperparathyroidism results
from chronic calcium deficiency, and is a compensating
mechanism whereby all four parathyroid glands undergo
hyperplasia. In this situation, the calcium may be low or
normal, but the PTH level is elevated. The condition is
treated with vitamin D and calcium supplements. Tertiary
hyperparathyroidism complicates some cases of secondary
hyperparathyroidism where autonomous production of
PTH occurs, leading to hypercalcaemia which is not
controlled with vitamin D or calcium supplements. In this
case, there is no underlying disorder to predispose to
secondary or tertiary hyperparathyroidism, and so the most
likely answer is primary hyperparathyroidism.
Other causes of hypercalcaemia are given below
(Table). Myeloma is unlikely in the presence of a normal
full blood count, ESR and globulin level. Sarcoidosis is
associated with hypercalcaemia and band keratopathy, but
is less likely in the presence of a normal chest X-ray. Moreover, it would not explain the X-ray changes in the hands.
This patient is not taking regular antacids, which excludes
the milk-alkali syndrome, a condition caused by chronic
ingestion of calcium-based antacids and milk for the relief
of dyspepsia or peptic ulcer disease. Metastatic bone
disease is a possibility, but the majority of patients with
bony metastases have overt metastatic deposits, particularly in areas where pain is experienced. In such cases, the
albumin level is also low due to cachexia and the plasma
bicarbonate is normal or high because bony destruction
often releases bicarbonate from the bone. In hyperparathyroidism in the absence of renal disease, a mild metabolic acidosis is common. It is due to RTA and is reflected
by a slightly low bicarbonate and a high chloride level.
In the past, other causes of hypercalcaemia particularly malignancy could be differentiated from hyperparathyroidism by the hydrocortisone suppression test,
where high doses of hydrocortisone given daily for a week
would fail to reduce the serum calcium level in hyperparathyroidism but not in other cases; however, the more
sensitive PTH assays used nowadays have made this test
obsolete.
Treatment of primary hyperparathyroidism is with total
parathyroidectomy following transplantation of a small
amount of parathyroid tissue into the forearm muscles.
Following surgery, calcium levels have to be monitored
because they fall rapidly and tetany can be precipitated.
Hypocalcaemia can persist for several months during which
time it is important to continue vitamin D supplements.
(See Calcium Biochemistry, page 415.)
Causes of hypercalcaemia
1 hyperparathyroidism
3 hyperparathyroidism
Sarcoidosis
Multiple myeloma
Thiazide diuretics
Milk-alkali syndrome
Addisons disease
Acromegaly
Phaeochromocytoma
Thyrotoxicosis
Vitamin D intoxication
Pagets disease
(immobility)
Familial hypocalcuric
hypercalcaemia
Clinical Cases
173
Question 169
A 44-year-old female was persuaded to come into hospital after she was seen in the out-patient clinic with
jaundice. She was diagnosed as having auto-immune
CAH five months ago and was successfully treated with
high-dose steroids, which had gradually been withdrawn.
She had not been taking any medication before admission
and denied alcohol consumption. On examination, she
was thin and deeply jaundiced. She was alert and
orientated, and did not demonstrate any signs of
cognitive impairment. Abdominal examina tion was
essentially normal. Investigations on admission are
shown. Two days following admission, the patient
became suddenly very aggressive, and soon after
collapsed and was comatosed.
Hb
WCC
Platelets
MCV
PT
APTT
Bilirubin
AST
Alkaline phosphatase
Albumin
12.3 g/dl
8 ! 109/l
45 ! 109/l
109 fl
59 s (control 13 s)
90 s (control 45 s)
300 mol/l
350 iu/l
340 iu/l
26 g/l
Question 170
This pedigree chart (170) is from a family with a very
rare condition.
170
C
Affected male
Unaffected male*
Affected female
Unaffected female*
174
Answer 169
e. Blood glucose.
The patient was admitted with gross hepatic dysfunction.
She had previously been successfully treated with corticosteroids, and had a relapse after they were gradually
withdrawn. She became aggressive and then comatosed.
The most probable diagnosis is hepatic encephalopathy.
Precipitating factors include gastrointestinal haemorrhage, sepsis, hypokalaemia, drugs promoting catabolism,
sedatives and hypoglycaemia. In hepatic encephalopathy
it is possible for both hypoglycaemia and hyperglycaemia
to occur because glucose homeostasis is disturbed. Glycogen is neither efficiently stored nor mobilized and
gluconeogenesis is impaired. Early features of encephalopathy include confusion, irritation, aggressiveness or
psychosis. Coma can ensue rapidly. The test which would
be most useful in determining the cause of collapse is the
serum blood glucose, because its correction and therapeutic effect are almost immediate. There is nothing in
the history or examination to suggest sepsis, although it
must be noted that patients with chronic liver disease do
not always have a pyrexia. There is no history of sedative
drug ingestion, and in practice screening for sedative
drugs is unhelpful because it seldom influences the
management. A cerebral haemorrhage is possible in the
presence of a raised PT and low platelets. If the blood
glucose is normal, a cerebral haemorrhage should be
excluded by CT scanning of the head. If this is normal,
the diagnosis is encephalopathy. An EEG is not necessary
to diagnose encephalopathy, but at the onset of encephalopathy the EEG shows an alpha rhythm and as drowsiness worsens this is replaced by lower frequency theta
activity. In deep coma, high-amplitude delta waves are
present.
Answer 170
1. c. X-linked dominant.
2. a. None.
3. b. 100%.
4. d. 50%.
In X-linked conditions there is no male-to-male transmission. In X-linked dominant conditions, the female
offspring of affected males have an abnormal phenotype,
and in X-linked recessive conditions all female offspring
Question 171
A 65-year-old male was admitted with a six-week history of
progressive dyspnoea. One week before admission he had
developed dyspnoea at rest, orthopnoea and paroxysmal
nocturnal dyspnoea. He had lost his appetite, and had lost
over 3 kg in weight in six weeks. He had a cough
productive of yellow sputum initially which was treated
with antibiotics; however, the cough persisted and three
days before admission he had an episode of frank haemoptysis. The patient had enjoyed a very active and independent life and, apart from a truncal vagotomy and drainage
procedure for a perforated duodenal ulcer 20 years ago, he
had been very well. He was a non-smoker.
Clinical Cases
175
5.3 g/dl
17 ! 109/l
249 ! 109/l
89 fl
34 g/dl
102 mm/h
131 mmol/l
5.7 mmol/l
29 mmol/l
560 mol/l
2.1 mmol/l
1.5 mmol/l
33 g/l
14 mol/l
19 iu/l
113 iu/l
1320 iu/l
Normal
316 mg/l
12 s (control 12 s)
43 s (control 41 s)
Normal-sized kidneys with
echogenic renal parenchyma
No evidence of obstruction
Sodium
Potassium
Urea
Creatinine
131 mmol/l
6.0 mmol/l
35 mmol/l
780 mol/l
171
176
Answer 171
1. The chest X-ray reveals bilateral, widespread
alveolar shadowing with sparing of the apices.
Possible causes of alveolar shadowing on the chest
X-ray include:
i. Pulmonary oedema.
ii. Pulmonary haemorrhage.
iii. Pulmonary consolidation.
In this case, pulmonary oedema is unlikely if the
apices are spared, and this could only be explained
if there was pre-existing, severe bilateral apical
emphysema.
2. The patient has a relatively acute illness involving
the respiratory and renal system. Possible cause of a
systemic illness causing respiratory and renal
impairment include:
The vasculitides (in order of decreasing frequency):
Anti-GBM disease or Goodpastures syndrome.
Polyarteritis nodosa.
Wegeners granulomatosis.
Systemic lupus erythematosus.
The history of continuing haemoptysis and failure of the
haemoglobin to rise sufficiently after blood transfusion
strongly suggest that the chest X-ray appearances are
secondary to pulmonary haemorrhage rather than any
other cause. The presence of normal-sized kidneys is suggestive of an acute renal process. In chronic renal disease,
the kidney size is usually small, although there are a few
exceptions (Table A). Pulmonary haemorrhage and acute
renal failure are best explained by a systemic vasculitis.
The best answers are, therefore, anti-GBM, polyarteritis
nodosa or Wegeners granulomatosis in decreas ing
frequency. Anti-GBM disease is a rare condition where
antibodies to the basement membrane of the glomeruli
and alveoli lead to acute nephritis and pulmonary
haemorrhage, respectively. The disease presents with
cough, fatigue, dyspnoea or haemoptysis followed days,
weeks or months later, by glomerulonephritis.
Wegeners granulomatosis would be the best answer if
there was additional upper respiratory tract involvement.
Although it is also possible, involvement of the upper
respiratory tract is much more common in Wegeners
than in any of the other vasculitides. SLE is rare in males
and in this age group. Pulmonary haemorrhage is much
less common in SLE than in the other vasculitides
mentioned above. Although Legionnaires disease is
possible, there is no history of travel abroad or being in
an environment with air conditioning, and it does not
easily explain the pulmonary haemorrhage. Fever is a
recognized feature of both infection and the vasculitides.
The initial cough productive of yellow-brown sputum
may have been secondary to a respiratory tract infection
which is of interest because pulmonary haemorrhage is
more common in anti-GBM disease if there has been a
recent respiratory infection. Other factors predisposing to
Infection:
Legionnaires disease and secondary interstitial
nephritis.
Pneumococcal pneumonia with mycotic emboli
to the kidneys.
3. i. Anti-GBM antibodies.
ii. ANCA.
iii. Renal biopsy with immunofluoresence studies.
iv. Transbronchial lung biopsy if the patients
respiratory status permits.
v. Antinuclear factor.
vi. Legionella antigen in the urine or Legionella
RMAT on the serum.
vii. TLCO.
4. Haemodialysis.
Myeloma
Diabetes mellitus
Amyloidosis
Polycystic kidney disease (kidneys are usually
huge by the time renal impairment becomes
apparent)
Clinical Cases
177
creatinine, and has developed hyperkalaemia. Haemodialysis is indicated in all of these situations and when the
patient shows evidence of fluid overload. It allows the
opportunity for plasmapheresis, which is successful in
some patients with anti-GBM disease, particularly with
respect to pulmonary haemorrhage. However, results on
the renal system are not very satisfactory if plasmapheresis
is initiated after significant renal impairment has occurred. Subsequent management will be with high-dose
steroids and cyclophosphamide.
Pulmonary haemorrhage
Polycythaemia
Left-to-right shunts
Asthma
Question 172
An 18-year-old male was admitted following a collapse at
a local night club. On examination he was drowsy. His
temperature was 40C (104F), and he was sweating
profusely. His heart rate was 120 beats/min, and regular.
The blood pressure was 160/110 mmHg. His pupils
were dilated and reacted poorly to light.
Investigations are shown.
Hb
WCC
Platelets
PT
APTT
TT
Sodium
Potassium
Urea
Creatinine
Phosphate
Urine
11 g/dl
11 ! 109/l
100 ! 109/l
20 s
70 s
16 s
125 mmol/l
7.4 mmol/l
10 mmol/l
123 mol/l
1.7 mmol/l
Blood +++
178
Answer 172
1. Ecstasy (3, 4-methylenedioxymetamphetamine;
MDMA) abuse.
2. Rhabdomyolysis.
3. DIC.
4. i. Cooling/tepid sponging.
ii. Intravenous dantrolene.
5. i. Syndrome of inappropriate antidiuretic hormone.
ii. Excess sodium loss from skin during profuse
perspiration.
The history is of collapse at a local night club, and on
examination the patient has a very high temperature, is
sweating profusely, has dilated pupils, and is hypertensive.
The blood tests reveal evidence of renal failure with a
disproportionately high potassium and phosphate, hinting that the patient may have rhabdomyolysis; the
haematological tests suggest underlying DIC. In this
case, the most probable diagnosis is Ecstasy abuse. The
case would have been more difficult if he was hypotensive
because then the differential diagnosis would have
included septicaemia, encephalitis or meningitis, all of
which must also be borne in mind when attending to a
young patient with any of these features.
Ecstasy abuse has become an increasingly common
problem over the past few years, and therefore knowledge of its recognition and management have become
almost mandatory. The clinical features are basically those
of a large concentration of circulating catecholamines in
the blood. In the acute situation it may present as
collapse, convulsions and hyperpyrexia, i.e. a core temperature of 3942C (102.2107.6F) (see Table for
causes of hyperpyrexia). Other features comprise profuse
sweating, tachycardia, hypertension and dilated pupils.
The blood pressure may also be low due to shock
from excessive fluid loss secondary to perspiration.
Complications of Ecstasy abuse include rhabdomyolysis,
acute renal failure (either from reduced renal perfusion or
myoglobin-induced tubular damage), DIC, acute hepatitis, myocardial infarction and cerebrovascular accident.
Hyponatraemia is a common problem and may be due
to excess sodium loss from the skin during perspiration.
The problem is compounded because most Ecstasy
abusers are advised to drink large amounts of water which
may replenish fluid, but not the actual salt loss. Furthermore, Ecstasy is thought to cause SIADH which may
Causes of hyperpyrexia
Septicaemia
Viral infections
Malaria
Neuroleptic malignant syndrome
Malignant hyperpyrexia
Ecstasy or other amphetamine abuse
Cocaine abuse
Malignancy
Aspirin toxicity
Prostaglandins
Clinical Cases
179
Question 173
173a
173b
Hb
WCC
Platelets
Sodium
Potassium
Urea
Bicarbonate
Glucose
14 g/dl
12 ! 109/l
230 ! 109/l
139 mmol/l
3.2 mmol/l
7 mmol/l
30 mmol/l
16 mmol/l
9.00 a.m.
940
900
After dexamethasone
2 mg q.i.d. for 48 h
Midnight
1,000
800
Chest X-ray
Normal
CT scan abdomen (173b)
180
Answer 173
1. The arm pit demonstrates acanthosis nigricans.
2. The high dose of dexamethasone fails to suppress the
elevated cortisol down to normal.
3. The differential diagnosis is between ectopic ACTH
and an autonomous glucocorticoid-secreting adrenal
tumour (173d).
4. Plasma ACTH level, which will be elevated in ectopic
ACTH secretion and suppressed in a cortisolsecreting tumour.
5. The CT scan demonstrates an adrenal tumour on the
left side (see also detail, 173c, arrowed).
6. Diabetes mellitus.
7. Surgical excision of the affected adrenal gland.
Acanthosis nigricans is characterized by velvety hyperpigmentation and overgrowth of skin affecting the neck, axilla, groin
or the face. The condition may be a normal variant in the
Asian race. It is associated with internal malig nancy,
particularly carcinoma of the stomach and the lung and
lymphoma. It is also associated with a variety of endocrine
disorders causing insulin resistance and hyperandrogenic
states (Table A). In this case, it is due to Cushings syndrome
(Table B). Complications are shown in Table C.
The high-dose dexamethasone test suppresses the
serum cortisol in over 60% of patients with Cushings
173c
Low dose
dexamethasone
0.5 mg four times
daily for 2 days
Suppression of cortisol to
normal levels
Pituitary Cushings disease
Suppression of cortisol to
normal levels
Obesity
Alcohol abuse
Anxiety
Depression
Pregnancy
PCOS
Ectopic ACTH
Check
serum
ACTH
Suppressed
Cortisol-secreting adrenal tumour
173d
Clinical Cases
Obesity
Diabetes mellitus
Hypertension
Premature coronary
artery disease
Osteoporosis
Myopathy
Psychosis
Immunosuppression
Poor wound healing
Hypokalaemia
181
Question 174
174
Hb
WCC
Platelets
MCV
ESR
CRP
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
Bilirubin
AST
Gamma GT
Alkaline phosphatase
Total protein
Glucose
ANF
Rheumatoid factor
Immunoelectrophoresis
Blood cultures ! 6
Urinalysis
Urine culture
Chest X-ray
9.5 g/dl
15.1 ! 109/l
591 ! 109/l
90 fl
104 mm/h
82 g/l
136 mmol/l
5.3 mmol/l
6.5 mmol/l
99 mol/l
2.31 mmol/l
0.9 mmol/l
35 g/l
7 mol/l
22 iu/l
43 iu/l
162 iu/l
77 g/l
5.4 mmol/l
Negative
Not detected
Polyclonal increase in
gamma-globulin region
No paraprotein
No growth
Blood ++
24 hour urine protein 2.4g
Negative. AAFB not
detected on early morning
urine specimens
Normal
182
Answer 174
1. i. Polyarteritis nodosa.
ii. Polymyalgia rheumatica.
iii. Lymphoma.
iv. Testicular seminoma.
v. Post-primary TB.
2. i. Renal biopsy.
ii. Skin biopsy.
iii. Muscle biopsy may help in the differentiation of
vasculitis from polymyalgia rheumatica.
iv. Renal or hepatic angiography to demonstrate
micro-aneurysms.
v. Serum ANCA lends support to a vasculitic
process.
vi. CT scan thorax/abdomen to check for intraabdominal malignancy, splenomegaly and paraaortic lymphadenopathy.
vii. Ultrasound of the testes.
viii. Bone marrow examination/culture for AAFB.
ix. Mantoux test.
This is a case where several diagnoses are possible. The
patient is in his seventh decade and has evidence of general
malaise, night sweats, weight loss and myalgia, associated
with a very high ESR (Table C). There is clinical evidence
of peripheral neuropathy. The inflammatory markers are
elevated and the possible differential diagnoses in an elderly
patient includes PAN, malignancy (including lymphoma),
PMR and sepsis. TB is a possibility; however, a completely
PMR
7th decade onwards
Male
As above
Absent
Absent
Absent
Common
Common
Absent
PAN
Middle age onwards
Male
As above
Present
Recognized
Present
Common
Common
Uncommon
Clinical Cases
183
Question 175
A 45-year-old female on treatment for ulcerative colitis
complained of increasing tiredness, while her bowel
problems seemed well controlled.
Some of her results are shown.
Hb
MCV
MCHC
WCC
Neutrophils
Platelets
Reticulocytes
Blood film (175)
175
7.5 g/dl
95 fl
34%
10.5 ! 109/l
8.4 ! 109/l
290 ! 109/l
9.8%
Question 176
A 26-year-old male presented to the Accident and
Emergency Department with a stiff jaw and being unable
to open his mouth. Three days previously he was
immunized with tetanus toxin after lacerating his finger
at work. On examination, he had evidence of lock jaw.
His injured finger was swollen, painful and exuding pus.
184
Answer 175
1. c. Oxidative haemolytic anaemia.
2. e. Sulphasalazine-induced anaemia.
The patient has a low Hb and a high reticulocyte count,
suggesting either haemolysis or recent blood loss. The
blood film is diagnostic. It is stained with methyl violet to
reveal small inclusions within red cells termed Heinz
bodies, which are essentially precipitated Hb. These
inclusion bodies are visualized with methyl violet stain.
They occur in patients with genetic Hb abnormalities
(unstable Hb), or when the iron within the haem
molecule is oxidized from the ferrous state (Fe2+) to the
ferric state (Fe3+) to produce methaemoglobin. Causes of
methaemoglobinaemia are discussed in Answer 316. In
this case, therapy for ulcerative colitis with sulphasalazine
Answer 176
1. d. Intramuscular human tetanus immunoglobulin.
Tetanus is caused by the anaerobic, Gram-positive
bacillus Clostridium tetani. The organism produces
spores that are commonly found in soil and faeces of
domestic animals. Soil is the natural habitat for C. tetani.
The organism gains entry into the body through
traumatic wounds, where it multiplies under anaerobic
conditions and produces tetanospasmin, a potent
neurotoxin. The toxin reaches the spinal cord via the
blood or by retrograde axon transport and increases
excitability in motor neurones by interfering with the
function of inhibitory neurones. The toxin may also
produce overactivity of the sympathetic nervous system.
The incubation period after injury is less than 14 days
and can be as early as 2 days.
The dominant features of tetanus are rigidity and
reflex spasms. Rigidity may affect any muscle, including
the jaw muscles, so the mouth cannot be fully opened, as
in this case. This is known as trismus or lock jaw.
Stiffness may affect the facial muscles, altering facial
appearance. Risus sardonicus (pursing of the lips with
retraction of the angles of the mouth) is a characteristic
feature of this phenomenon. Pharyngeal involvement may
produce dysphagia early in the disease. Rigidity of the
muscles of the back causes the body to curve back
excessively with the head fully retracted (ophisthotonus).
Reflex spasms are a sudden exacerbation of underlying
rigidity which last 12 seconds. The time of onset of
spasms from the first symptoms of rigidity is known as
Clinical Cases
185
Question 177
A 33-year-old Indian male presented with a four-week
history of a painful swollen knee, which he attributed to a
fall during a game of tennis. The knee was painful after
the fall, but over the next two weeks he developed
swelling and increasing pain which was only partially
relieved by paracetamol. He had never had a similar
problem in the past. Apart from feeling slightly more
breathless than usual while playing tennis over the past
three months, he had no other complaints. There was no
significant family history except that his grandparents had
both had TB. He could not ever recall having had a BCG
vaccine, but did have several chest X-rays in his early
teenage years. On examination, he appeared well. He had
a temperature of 37.5C (99.5F). Examination of his
upper arms did not reveal a BCG scar. Examination of the
left knee demonstrated a painful erythematous joint with
a large synovial effusion. On examination of the
respiratory system there were some harsh breath sounds in
anterior aspect of the chest. The attending rheumatologist
requested some investigations, which are shown.
On the basis of these investigations, the patient was
commenced on empirical antituberculous therapy. He was
reviewed four months later and had an ESR check, which
measured 57 mm/h. The swelling in the left knee had
subsided, but the changes on the chest X-ray persisted.
Six months later he presented to the Accident and
Emergency Department with swelling in his right knee
and both ankles. In addition, he complained of pain in
the cervical area and lower back pain that radiated into
the buttocks and was worse in the mornings.
1. What is the diagnosis?
2. How would you explain the changes on the
chest X-ray?
3. Give two diagnostic tests.
4. Apart from diagnostic tests, which other
investigation would you perform to help his further
management?
5. What is the management of his condition?
177a
Hb
WCC
Platelets
ESR
Chest X-ray (177a)
Rheumatoid factor
X-ray of left knee
Aspirate of
knee joint
Synovial biopsy
12 g/dl
7 ! 109/l
308 ! 109/l
107 mm/h
Negative
Soft-tissue swelling
No bony involvement
Yellow fluid; low viscosity;
WCC 50/mm3; culture
sterile
Thickened synovium
macroscopically with
histological evidence
ofincreased inflammatory
infiltrate
186
Answer 177
1. Ankylosing spondylitis.
2. Bilateral apical fibrosis.
3. i. X-ray of the sacroiliac joints, which will
demonstrate sacroiliitis and may demonstrate
squaring of the lumbar vertebrae with thickening
and calcification of the interspinous ligaments.
ii. HLA typing for B27; however, one must
remember that this is found in 5% of the general
population.
4. Respiratory function tests given the history of
breathlessness on exertion and the lung fibrosis.
5. NSAID and physiotherapy.
While the inflamed knee joint in association with the
abnormal chest X-ray may be highly suggestive of TB in
an Asian patient, the failure to improve with antituberculous therapy is against this diagnosis. In a young
male with a synovitis of the knee joint followed by pain in
the ankle joints and in the lumbar and cervical area, the
differential diagnosis is between rheumatoid arthritis,
adult Stills disease and a seronegative arthropathy,
particularly ankylosing spondylitis. The absence of the
rheumatoid factor is against the diagnosis of rheumatoid
arthritis. Stills disease is not sufficient to explain the
chest X-ray abnormalities, which in this case are due to
TB
Extrinsic allergic alveolitis
Ankylosing spondylitis
Allergic bronchopulmonary
aspergillosis
Radiation
Sarcoidosis
Histiocytosis X
Table C Causes of
sacroiliitis
Ankylosing spondylitis
Reiters syndrome
Psoriatic arthropathy
Enteropathic arthritis
(inflammatory bowel
disease)
Whipples disease
Osteoarthritis
apical fibrosis (177a) (Table A lists other causes), a wellrecognized complication of ankylosing spondylitis. Other
complications of ankylosing spondylitis are listed below
(Table B). In addition, there is an increased incidence of
scleritis and scleromalacia.
Ankylosing spondylitis is a chronic inflammatory
disorder that predominantly affects the spinal joints. It is
strongly associated with the presence of HLA B27, which
is present in 95% of all cases, and the disease is more
prevalent in males in their second and third decades. The
exact aetiology of the disorder is unknown. Most patients
present with a sacroiliitis causing back pain and stiffness,
which is worse in the mornings (Table C). There is a
characteristic loss of lumbar lordosis and a reduced ability
to flex the spine. An asymmetric peripheral large joint
arthropathy may be the presenting feature in some
patients as in this case. Enthesopathy causes pain in the
tendons, particularly the Achilles tendon. Weight loss,
low-grade fever and high inflammatory markers in the
blood are recognized. Extra-articular complications occur
in approximately 15% of patients. The diagnosis is a
clinical one, but is helped by the demonstration of
sacroiliitis on the X-ray of the pelvis and the
demonstration of thickening and calcification of the
interspinous ligament, which may give the appearance of
a bamboo spine (177b).
Table B Ankylosing
spondylitis is easily
remembered as the A
disease
Arthritis
Atlano axial subluxation
Arachnoiditis (spinal)
Apical fibrosis
Anterior uveitis
Aortitis
Aortic regurgitation
Atrioventricular block
Amyloidosis
IgA nephropathy
Achilles tendinitis
Plantar fAsciitis
177b
Clinical Cases
187
Question 178
178a
10 g/dl
8 ! 109/l
360 ! 109/l
90 mm/h
135 mmol/l
4.1 mmol/l
8 mmol/l
5 mmol/l
Cardiac silhouette slightly enlarged
Upper lobe vein distension and
bibasal interstitial lung shadowing
178b
2. What investigation is
required to confirm
the diagnosis?
a. Serial blood
cultures.
b. Serum ANCA.
c. Double stranded
DNA antibodies.
d. Coronary
angiography.
e. Echocardiography.
Question 179
A 15-year-old male is admitted for parathyroidectomy.
His father had a parathyroidectomy 20 years previously.
Pre-operative:
Post-operative:
Calcium
Phosphate
Albumin
PTH
Calcium
Phosphate
Albumin
PTH
2.8 mmol/l
0.8 mmol/l
44 g/l
40 ng/l
2.9 mmol/l
0.9 mmol/l
43 g/l
Undetectable
188
Answer 178
178c
Answer 179
1. Familial benign hypocalcuric hypercalcaemia.
2. 24-hour urinary calcium estimation or a urinary
calcium clearance to creatinine clearance
(CaCl/CrCl) ratio.
Familial benign hypocalcuric hypercalcaemia is an
autosomal dominant disorder which is characterized by
life-long, asymptomatic hypercalcaemia. However, some
patients develop acute pancreatitis, gallstones and
chondrocalcinosis. The abnormality is in the calciumsensing receptor, a G-protein-coupled receptor. It may be
difficult to distinguish from primary hyperparathyroidism,
and in 20% of cases the PTH is mildly elevated. The serum
phosphate values are usually normal or slightly reduced. In
contrast to other causes of hypercalcaemia, the 24-hour
Clinical Cases
189
Question 180
A 43-year-old male was admitted with a 2-hour history
of malaise and nausea. A 12-lead ECG revealed an acute
inferior myocardial infarction and third degree AV block.
He had type 1 diabetes mellitus. The heart rate at rest
was 34 beats/min. The blood pressure was
80/50 mmHg. Both heart sounds were normal. A
temporary pacing wire was inserted via the right
superficial femoral vein and the patient was successfully
paced. The BP improved to 90/60 mmHg.
Blood results were as follows:
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Glucose
13 g/dl
17 ! 109/l
380 ! 109/l
140 mmol/l
4.2 mmol/l
8 mmol/l
126 "mol/l
17 mmol/l
Question 181
A 16-year-old female was investigated for lethargy and
polyuria. Her blood pressure measured 116/70 mmHg.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Calcium
Phosphate
Albumin
Glucose
24-hour urinalysis:
Sodium
Potassium
Calcium
Chloride
Serum renin
13 g/dl
7 ! 109/l
300 ! 109/l
129 mmol/l
3.0 mmol/l
7 mmol/l
80 "mol/l
33 mol/l
2.0 mmol/l
1.3 mmol/l
40 g/l
4 mmol/l
30 mmol/l (<20 mmol/l in hyponatraemia)
40 mmol/l (<10 mmo/l in presence of hypokalaemia)
10.6 mmol (NR <7.5 mmol/24h)
42 mmol/l (NR <25 mmol/l)
960 pmol/l (NR 100500 pmol/l)
190
Answer 180
b. IV recombinant tissue plasminogen activator.
There is good evidence that the patient should either
undergo primary coronary angioplasty or receive
thrombolysis to reduce his immediate risk of sudden
death. The angioplasty option is not provided, therefore
the candidate is left to decide between streptokinase and
Answer 181
E. Bartters syndrome.
The patient has hypokalaemia and metabolic alkalosis
associated with a normal blood pressure. The differential
diagnosis is between self-induced vomiting, chronic
thiazide diuretic use (or abuse) and Bartters syndrome.
Although laxative abuse can also be associated with
hyponatraemia and hypokalaemia, most patients who
abuse laxatives have a metabolic acidosis rather than
alkalosis (loss of bicarbonate via the gastrointestinal
tract). Addisons disease is usually associated with
hypotension, hyperkalaemia, reduced potassium
excretion in the urine and metabolic acidosis.
The differentiation between thiazide drug abuse, selfinduced vomiting and Bartters syndrome is dependent
upon the history and the urinary electrolytes. Patients
who lose sodium or potassium via the gastrointestinal
tract usually have low urinary sodium (<10 mmol/l) and
potassium (<20 mmol/l) levels. The patient in question
has inappropriately high urinary sodium and potassium,
indicating primary renal tubular dysfunction or lack of
mineralocorticoid. Mineralocorticoid deficiency is
characterized by low serum sodium, high serum
potassium and metabolic acidosis.
The remaining differential diagnosis is between
thiazide diuretic abuse and Bartters syndrome. Thiazides
may cause all of the biochemical abnormalities in the
blood shown in the question. Raised plasma renin is due
to hypovolaemia or hyponatraemia. Furthermore
thiazides are also associated with high urine sodium,
potassium and chloride levels. However, urinary calcium
is low in patients taking thiazide diuretics since thiazides
increase absorption of calcium in the distal convoluted
Clinical Cases
191
Question 182
A 60-year-old obese male was referred to a
gastroenterologist with a 4-month history of right upper
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
AST
ALT
Alkaline phosphatase
Bilirubin
Albumin
Total cholesterol
Triglyceride
Blood glucose
Serum ferritin
Serum iron
TIBC
IgG
IgA
IgM
Hep B sAg
HCV antibodies
14 g/dl
6 ! 109/l
200 ! 109/l
136 mmol/l
4.1 mmol/l
6 mmol/l
100 "mol/l
60 iu/l
78 iu/l
180 iu/l
12 mol/l
38 g/l
7.2 mmol/l
6.1 mmol/l
13 mmol/l
400 "g/l
20 "mol/l
60 "mol/l
22 g/l
4.8 g/l
3.1 g/l
Not detected
Not detected
Question 183
This is a chest X-ray (183) of a 70-year-old Indian female
who presented with dyspnoea and a low-grade fever.
183
192
Answer 182
b. Non-alcoholic steatohepatitis.
The patient is obese. He has non-insulin-dependent
diabetes mellitus, hypertension and mixed hyper lipidaemia. The findings are compatible with insulin
resistance or metabolic syndrome. Additionally, the
patient has right upper quadrant pain, hepatomegaly and
a transaminitis in the absence of alcohol abuse, specific
drug therapy or hepatitis B or C infection. The most
probable diagnosis is non-alcoholic steatohepatitis.
NASH is associated with obesity and the metabolic
syndrome. It is characterized by fatty infiltration of the
liver associated with hepatitis or even cirrhosis in the
absence of alcohol abuse, specific drug therapy
(amiodarone, tamoxifen, oestrogens) or chronic viral
hepatitis. Liver biopsy is identical to alcoholic hepatitis.
Both AST and ALT are raised. The AST/ALT ratio is
usually <1, unlike in alcohol abuse where the ratio is
usually >2. Alkaline phosphatase is only modestly raised
Drugs
Differentiating features*
History of alcohol abuse/AST:ALT >2
Virology
Autoantibody screen shows raised SMA or ANA
Hypergammaglobulinaemia is also a feature
Predominant cholestasis on blood tests and positive antimitochondrial
antibodies
Serum TIBC >90%; ferritin >300
History of inflammatory bowel disease
Predominantly cholestatic
picture
Hypergammaglobulinaemia
History
Answer 183
d. Aspirate left-sided pleural effusion and send fluid
for microscopy and culture.
There is a large area of opacification affecting the left
lung without any visible lung markings, and marked
mediastinal shift to the right. The diagnosis is consistent
Clinical Cases
193
Question 184
A 24-year-old man presented with sudden onset of
palpitations while walking to work. He had no past
medical history of note. He consumed two units of
alcohol per day. He did not smoke or abuse illicit drugs.
Hb
WCC
Sodium
Potassium
Blood glucose
Serum TSH
ECG
Chest X-ray
Echocardiogram
15 g/dl
5 ! 109/l
138 mmol/l
3.8 mmol/l
4.2 mmol/l
2 mu/l
Atrial fibrillation with
a ventricular rate of
132 beats/min but no
other abnormality
Normal
Normal study
Question 185
An 18-year-old male navy cadet presented with a 2-day
history of headache, fever and sore throat. On examination he was noted to have cervical lymphadenopathy.
His heart rate was 80 beats/min and BP was
170/100 mmHg. There was a soft systolic murmur at
the left lower sternal edge, which did not radiate. All
other examination was normal.
Investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Blood cultures
Throat swab culture
Urinalysis
13.6 g/dl
12.0 ! 109/l
180 ! 109/l
36 mm/h
136 mmol/l
4.8 mmol/l
7.3mmol/l
143 "mol/l
No growth
No growth
1020 rbc ++,
granular casts,
no growth
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
ANA and ds DNA binding
Urinalysis
14.1 g/dl
8.2 ! 109/l
191 ! 109/l
136 mmol/l
4.1 mmol/l
5.1 mmol/l
92 "mol/l
Negative
Blood ++
Protein ++
194
Answer 184
b. IV flecanide infusion.
The patient has atrial fibrillation (AF) that is definitely less
than 48 hours in duration. In such patients sinus rhythm
can be safely restored immediately without prior
anticoagulation if the patient does not have left ventricular
dysfunction or rheumatic mitral valve disease (see below).
In patients with haemodynamic embarrassment due to
atrial fibrillation with a rapid ventricular rate the
treatment of choice is urgent electrical cardioversion, as it
is more effective than pharmacological therapy at
restoring sinus rhythm.
In patients who are haemodynamically stable and do
not have dilated cardiomyopathy or suspicion of
rheumatic mitral valve disease, either electrical
cardioversion or anti-arrhythmic drugs may be used to
restore sinus rhythm. The drugs commonly used are class
I and class III anti-arrhythmic agents. The class III antiarrhythmic agents commonly used are sotalol and
amiodarone. Recent evidence suggests that sotalol is not
superior to conventional beta-blockers at restoring sinus
rhythm. Amiodarone is not as effective as some of the
class I anti-arrhythmic drugs and should be reserved for
use in patients with underlying cardiomyopathy.
Commonly used class I anti-arrhythmic agents used to
restore sinus rhythm in atrial fibrillation include flecanide,
propafenone and dofetilide. Of these, flecanide is the
most effective agent at restoring sinus rhythm early and is
effective in 7295% of cases. Flecanide is avoided in
patients who have any form of cardiomyopathy or have
atrial fibrillation in the context of a myocardial infarction.
Digoxin is not effective at restoring sinus rhythm, but
plays an important role in controlling ventricular rate
when given with beta-blockers or calcium antagonists
Answer 185
b. Bergers nephritis.
There is a short history of upper respiratory tract infection
with transient deterioration in renal function and persistent
proteinuria and microscopic haematuria. The most probable
diagnosis is Bergers nephritis (IgA nephritis). The history is
not long enough for classic post-streptococcal
glomerulonephritis, which usually occurs 1014 days after
the initial respiratory infection. Apart from the nephritis
there is nothing to suggest HenochSchnlein vasculitis
such as a rash, arthralgia or abdominal symptoms. Although
there is a soft murmur at the lower sternal edge, the
preceding symptoms of an upper respiratory tract infection
favour IgA nephritis rather than nephritis complicating
infective endocarditis. Treatment is not usually required.
www.drmyothethan.blogspot.com
Clinical Cases
195
Question 186
A 45-year-old man was involved in a motorbike accident
resulting in a fractured femur. He underwent internal
Arterial blood gases:
pH
PCO2
PO2
Bicarbonate
Sodium
Potassium
Urea
Creatinine
7.3
6.2 kPa
12 kPa
18 mmo/l
136 mmol/l
7.1 mmol/l
7 mmol/l
130 "mol/l
Question 187
187
Question 188
A 69-year-old woman attended her GP complaining of
lethargy and pruritus. She also complained of difficulty
on climbing stairs because she felt her thighs could not
carry her. She had always led a very healthy lifestyle and
was not taking any medications. On examination she
appeared slightly icteric and had xanthelasma. There were
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Total protein
Albumin
11 g/dl
6 ! 109/l
120 ! 109/l
133 mmol/l
4.1 mmol/l
3 mmol/l
110 "mol/l
56 mmol/l
58 iu/l
230 iu/l
70 g/l
32 g/l
196
Answer 186
a. Stop anaesthesia.
Hyperpyrexia, hypertonia and hyperkalaemia during
anaesthesia raise the possibility of malignant hyper pyrexia.
Malignant hyperthermia is a rare genetic disorder,
which manifests following treatment with anaesthetic
agents, most commonly succinylcholine and halothane.
The onset of malignant hyperthermia is usually within
one hour of the administration of general anaesthesia but
rarely may be delayed as long as 11 hours. 50% of cases
are inherited in an autosomal dominant fashion.
Susceptible patients with autosomal dominant disease
have any one of eight distinct mutations in the ryanodine
receptor calcium channel receptor found in the
sarcoplasmic reticulum of skeletal muscle.
In the presence of anaesthetic agents, alterations in the
hydrophilic, amino-terminal portion of the ryanodine
receptor result in uncontrolled efflux of calcium from the
sarcoplasmic reticulum with subsequent tetany, increased
skeletal muscle metabolism, and heat production.
Early clinical findings in malignant hyperthermia
include muscle rigidity (especially masseter stiffness),
sinus tachycardia, increased CO2 production, and skin
cyanosis with mottling. Marked hyperthermia (up to
45C [113F]) occurs minutes to hours later; core body
temperature tends to rise 1C every 5 to 60 minutes.
Hypotension, complex dysrhythmias, rhabdomyolysis,
electrolyte abnormalities, disseminated intravascular
coagulation, and mixed acidosis commonly accompany
the elevated temperature. Rectal temperature should be
determined in all patients. Abnormalities of vital signs in
severe hyperthermia include sinus tachycardia,
tachypnoea, a widened pulse pressure, and hypotension.
Answer 187
c. Bony metastases.
Answer 188
a. Cholestasis.
e. Osteomalacia.
Clinical Cases
197
Question 189
A 66-year-old white female slipped and fell on an icy
walkway. When seen in the Accident and Emergency
Department she complained of pain in the left hip. Her
left leg was shortened and externally rotated. X-rays
confirmed a diagnosis of fractured neck of the femur, for
which she underwent arthroplasty. Two days after
surgery, she complained of difficulty breathing. On
Arterial blood gases:
PaO2
PaCO2
pH
Haemoglobin
MCV
WCC
Platelets
Fibrinogen
8 kPa
4 kPa
7.55
8.0 g/dl
80 fl
11 ! 109/l
100 ! 109/l
0.95 g/l (NR 24 g/l)
Question 190
A 30-year-old woman with a history of epilepsy since
childhood was 12 weeks pregnant. Her epilepsy had been
very well controlled on carbamazepine 200 mg tds and
she had been completely free from epileptic seizures for
eight years.
Question 191
A 26-year-old female patient developed severe abdominal
pain and vomiting. The haemoglobin on admission was
9.6 g/dl. A blood film is shown (191).
191
198
Answer 189
c. Fat embolism.
Fat embolism is a clinical diagnosis. In many patients the
diagnosis is missed owing to subclinical illness or
confounding injury or illness. Mortality rate is 1020%. It is
usually caused by trauma to a long bone or the pelvis,
including orthopaedic procedures, as well as parenteral lipid
infusion or recent corticosteroid administration (Table).
Early persistent tachycardia may herald the onset of the
syndrome. Patients become tachypnoeic, dyspnoeic and
hypoxic owing to ventilationperfusion abnormalities
1272 hours after the initial injury. A high fever is
common. Between 20 and 50% of patients develop reddishbrown non-palpable petechiae over the upper body,
particularly in the maxillae, within 2436 hours of insult or
injury; these resolve quickly. The presence of petechiae in
this setting is virtually diagnostic of fat embolism.
Subconjunctival and oral haemorrhages are also recognized.
Central nervous system dysfunction initially manifests
as agitated delirium but may progress to stupor, seizures,
or coma and frequently is unresponsive to correction of
hypoxia. Retinal haemorrhages with intra-arterial fat
globules are visible upon fundoscopic examination.
Arterial blood gas shows an otherwise unexplained
increase in pulmonary shunt fraction alveolar-to-arterial
oxygen tension difference.
Answer 190
a. Continue with the current dose of carbamazepine.
Most anticonvulsant drugs have teratogenic properties.
However, in patients with epilepsy the benefits of
treatment with anticonvulsant drugs outweigh the risks
of teratogenicity, and anticonvulsant therapy is
continued. The risk of teratogenicity is reduced if the
treatment of epilepsy is limited to a single drug in
pregnancy.
Neural tube defects are probably the most serious
teratogenic effect of anticonvulsants and are particularly
Answer 191
a. Biliary colic.
The blood film shows numerous spherocytes (red cells
without the central punched out doughnut ring). The
presence of more than 50% spherocytes on the blood film
Clinical Cases
199
Question 192
A 20-year-old woman gave birth to a full term baby who
was floppy at birth and required resuscitation followed by
assisted ventilation. The mother had ptosis, muscle
weakness and bilateral cataracts. Her father also had
premature cataracts.
Question 193
A 29-year-old Tanzanian woman presented with a oneweek history of increasing dyspnoea, orthopnoea and
paroxysmal nocturnal dyspnoea. She had undergone a
Caesarean section for an uncomplicated twin pregnancy
two weeks previously. This was her first pregnancy. The
blood pressure throughout the pregnancy was normal. The
first trimester was complicated by hyperemesis, which
resolved spontaneously. The patient had noticed increasing
dyspnoea and swollen ankles just prior to delivery but
attributed this to her advanced pregnant state.
A murmur was heard on routine examination in the
second trimester, which was investigated with a 12-lead
ECG and echocardiogram that were both reported as
normal. There was no family history of cardiac disease.
On examination the pulse was 120/min and regular.
The temperature was 37.2C (99.0F). The blood
pressure measured 100/60 mmHg. The JVP was raised.
Palpation of the precordium revealed a displaced and
prominent apex. On auscultation both heart sounds were
normal. In addition there was a systolic murmur of mitral
193a
Hb
10.8 g/dl
WCC
13 ! 109/l
Platelets
368 ! 109/l
ESR
38 mm/h
CRP
13 g/l
CXR
Pulmonary oedema
12-lead ECG (193a)
Echocardiogram
Dilated left ventricle with
globally impaired systolic
function
Ejection fraction 35%
Mitral regurgitation
No obvious vegetations on
the valves
Blood cultures
Awaited
Arterial blood gases:
pH
7.38
PaCO2
4.3 kPa
PaO2
7.3 kPa
Bicarbonate
25 mmol/l
200
Answer 192
e. Myotonic dystrophy.
The mother has ptosis, muscle weakness and bilateral
cataracts indicating that she has myotonic dystrophy. Her
baby is also affected. Whereas the classical form of dystrophia
myotonica presents in adolescence or young adulthood,
babies born to mothers with dystrophia myotonica may have
the manifesting features of myotonic dystrophy at birth, i.e.
hypotonia and respiratory muscle weakness.
Dystrophia myotonica is inherited as an autosomal
dominant trait. The condition is due to mutation
comprising a triple nucleotide repeat (CTG) expansion in
the gene encoding a serine threonine protein kinase on
chromosome 19. Another locus on chromosome 3
comprising a CCGT repeat has also been identified.
Answer 193
e. Peri-partum cardiomyopathy.
The patient presents with pulmonary oedema in the
puerperium associated with systolic heart failure. She had
previously documented normal LV function and there is
no obvious cause for her heart failure other than
pregnancy. Although she has a low-grade fever and a
murmur of mitral regurgitation, the CRP is not high
enough to indicate overwhelming sepsis, and the
echocardiogram does not show any vegetations or valve
dysfunction as would be expected in this situation.
Peri-partum cardiomyopathy affects 1 in 3,000 livebirth pregnancies. The aetiology is unknown but the
condition is much more common in African women.
Other predisposing factors include advanced age, multiple
pregnancy, multi-parity and a history of hypertension in
pregnancy. The condition presents in the last month of
pregnancy or within five months post delivery, whereas
females with idiopathic dilated cardiomyopathy present in
the second trimester when the burden of volume overload
is greatest (193b).
Diagnosis requires the following four criteria:
1. Presentation in the last month or within five months
of delivery.
2. Absence of an obvious cause for heart failure.
3. Previously normal cardiac status.
4. Echocardiographic evidence of systolic left ventricular
dysfunction.
The patient fulfils all four criteria. The ECG may show
multiple abnormalities that include voltage criteria for left
ventricular hypertrophy and ST/T wave abnormalities, as
in this case. There are no symptoms of myocardial
More
common in
West Africans
? Viral
myocarditis
Lake salt
Selenium
deficiency
Treat with
conventional
heart failure
therapy and
anticoagulation
? IV immunoglobulin
193b
1/3,000
live births
Advanced
age >30
Peripartum
cardiomyopathy
Increased
parity
Diagnosis based
on echo and
the absence of
an alternative
cause
Rare before
36/52
50% recover
10% die
within
2 years
4% require
transplant
Clinical Cases
201
Possibly affected
?
A
?
B
Question 194
Question 195
Question 196
A 60-year-old female, who was diagnosed as having
rheumatoid arthritis eight years previously, presented
with a two-month history of progressive dyspnoea. She
was on a non-steroidal agent and methotrexate for
control of her rheumatoid arthritis. There was no history
of cough productive of sputum.
On examination her heart rate was 80 beats/min and
regular. Her blood pressure measured 106/68 mmHg.
The JVP was not raised. Both heart sounds were normal
and the chest was clear. The oxygen saturation on air was
96% but desaturated to 85% after walking for two
minutes. The chest X-ray was normal.
202
Answers 194 and 195
Answer 194
c. 50%.
Answer 195
d. 25%.
This is a family pedigree with an X-linked recessive
condition. The mother of A in generation 2 is a definite
carrier as his brother is affected. Since females pass the
Symbol definitions
Clear
Affected
?
Generation 1
Possibly affected
Generation 2
Generation 3
A
Generation 4
B
Answer 196
b. Ventilation/perfusion scan.
This is a difficult question. Progressive dyspnoea and
oxygen desaturation during exercise in patients with
rheumatoid arthritis are suggestive of pulmonary fibrosis.
However multiple pulmonary emboli may also present in
a similar fashion. The presence of sharp chest pains does
not differentiate small pulmonary emboli from pulmonary
fibrosis due to rheumatoid arthritis because sharp chest
pain is common to both. The absence of inspiratory
crackles and a normal chest X-ray are not characteristic of
Clinical Cases
203
Question 197
A 57-year-old woman presented with a six-hour history
of severe central chest pain. The 12-lead ECG revealed
ST elevation in the antero-lateral leads. Apart from a
history of a perforated duodenal ulcer requiring surgery
five weeks previously, there was no other past medical
history of significance.
Question 198
A 50-year-old West African woman was admitted to
hospital with a 48-hour history of generalized headache
and dyspnoea at rest. The patient had a cough productive
of white frothy sputum. There was no history of fever,
haemoptysis or drowsiness. The patient had been treated
for hypertension for five years; blood pressure control
over the past two years had been satisfactory. She was
known to have mild asthma that was usually precipitated
by cold weather. She had Raynauds disease that was
controlled with nifedipine and had recently been referred
to a gastroenterologist for investigation of difficulty in
swallowing. Current medications included nifedipine SR
20 mg bd and ranitidine 150 mg bd.
On examination she appeared unwell. Her
temperature was 36.8C (98.2F) and her heart rate was
110 beats/min and regular. The blood pressure was
220/130 mmHg. The JVP was not raised. On
examination of the precordium, the apex was not
displaced. Auscultation revealed normal heart sounds and
an added fourth heart sound at the apex. The respiratory
rate was 28/min. Auscultation of the lungs revealed
bibasal inspiratory crackles. The ankles were mildly
Hb
WCC
Platelets
Blood film
Sodium
Potassium
Urea
Creatinine
ECG
Chest X-ray
Urinalysis
11 g/dl
11 ! 109/l
100 ! 109/l
Shistocytes
Microspherocytes
138 mmol/l
4.8 mmol/l
28 mmol/l
490 mol/l
Left ventricular hypertrophy
Bilateral basal alveolar shadows
and small pleural effusions
Protein ++
Blood 0
204
Answer 197
e. Primary coronary angioplasty.
The patients chest pain and ST elevation in the anterior
leads are consistent with the diagnosis of acute anterior
myocardial infarction. The usual treatment would be to
thrombolyse the patient. However, the patient does have
a major contraindication as she had major surgery only
five weeks previously (Table). The safest and most
effective therapy in this situation would be to perform
coronary angiography with a view to primary angioplasty.
Patients who undergo primary angioplasty are usually
given intravenous abciximab (which itself may promote
haemorrhage) to reduce the risk of acute stent occlusion;
however, the drug would be used with great caution in a
patient who had recently had major surgery.
While aspirin and heparin have been shown to reduce
mortality in acute myocardial infarction, they are not as
effective as thrombolysis or angioplasty.
Answer 198
d. ACE inhibitor.
The patient has a history of well-controlled hypertension
and then presents with headache and breathlessness. The
presence of grade III hypertensive retinopathy and
pulmonary oedema in association with severe
hypertension is consistent with the development of
accelerated or malignant hypertension.
While there are potentially several conditions
associated with malignant hypertension such as renal
artery stenosis, hypertensive nephrosclerosis, haemolytic
uraemic syndrome, anti-phospholipid syndrome the
presence of Raynauds syndrome and possible
oesophageal problems is highly suggestive of systemic
sclerosis. In the context of this history the microangiopathic haemolytic blood picture reflects malignant
hypertension rather than haemolytic uraemic syndrome
or a vasculitis.
Renal disease is frequently present in patients with
scleroderma. Up to 80% of patients have renal disease and
50% actually have signs of renal problems, e.g. abnormal
electrolytes, hypertension and proteinuria. Around 10% of
Clinical Cases
205
Question 199
A 70-year-old man was awoken with retrosternal chest pain
radiating into his left arm in the early hours of the morning.
The pain was persistent for 5 hours, and unrelieved by taking
antacids before finally subsiding. The following day he
consulted his daughter over the telephone, who persuaded
him to make an urgent appointment with his GP. There was
a past history of mild hypertension and hypothyroidism. The
latter was diagnosed over a year ago after the patient
presented with lethargy and was treated with 25 mg of
thyroxine; however, the drug was stopped by the patient
within three months because he felt well again. He was a
non-smoker and consumed alcohol on a very infrequent
basis. Over the past two months he had felt lethargic and
saw another doctor, who diagnosed depression. He lived
alone. He had been widowed three years previously. He
took antacids for infrequent indigestion.
199
9.6 g/dl
4 ! 109/l
150 ! 109/l
108 fl
132 mmol/l
3.8 mmol/l
3 mmol/l
300 iu/l
5.3 ng /l (NR < 0.1 ng/l)
21 mu/l
30 nmol/l
Positive 1/3,000
800 ng/l
8 iu/l (normal, 110 iu/l)
5 iu/l (normal, 17 iu/l)
550 mu/l
Question 200
A 50-year-old woman presented with a two-day history
of increasing difficulty with swallowing and regurgitation
of food. Over the preceding two to three months she had
also experienced difficulty climbing stairs, raising her
arms above her head, and arising from a sitting or lying
position, with some associated lower back pain. On
examination she was found to have symmetrical proximal
muscle weakness with normal tone, sensation and deep
tendon reflexes. Cranial nerve examination revealed
weakness of the bulbar muscles.
206
Answer 199
1. b. Non-ST elevation anterolateral infarction.
2. c. Auto-immune hypothyroidism.
3. a. Serum B12 level.
The patient presents with a non-ST elevation anterolateral
myocardial infarction as evidenced by the ST depression
and elevated troponin level. The blood results suggest that
he has primary hypothyroidism. The very high titre of antimicrosomal antibodies indicates atrophic auto-immune
hypothyroidism or Hashimotos hypothyroidism.
Hypothyroidism is a well-recognized cause of secondary
hypercholesterolaemia (Table A for other causes) and
ischaemic heart disease. Other cardiac manifestations of the
condition include pericarditis, dilated cardiomyopathy and
pericardial effusion. In this case, the raised creatinine kinase
level could be explained by myocardial infarction and by
hypothyroid induced myositis. Other causes of raised
creatinine kinase are listed (Table B). Kleinfelters
Alcohol abuse
Diabetes mellitus
Hypothyroidism
Primary biliary cirrhosis
Obesity
Chronic liver disease
Myeloma
Nephrotic syndrome
Answer 200
d. Polymyositis.
The patient has symmetrical distribution of proximal muscle
weakness as well as weakness of the bulbar muscles. The
most probable diagnosis is polymyositis. Muscle weakness is
the most common presenting feature of polymyositis. The
onset is usually insidious, with gradual worsening over a
period of several months before medical attention is sought.
Occasionally, however, it shows acute onset of symptoms.
Diagnostic criteria:
Symmetric proximal muscle weakness.
Elevated plasma muscle enzymes.
Myopathic changes on electromyography.
Characteristic muscle biopsy abnormalities and the
absence of histopathologic signs of other myopathies.
There is a female to male predominance of about 2:1
and, in adults, the peak incidence occurs in the fifth
decade, although all age groups may be affected.
Muscle atrophy may occur in severe, long-standing
disease. 30% develop weakness of the oropharyngeal
muscles or the striated muscle of the upper one-third of
the oesophagus, leading to dysphagia, nasal regurgitation
or aspiration.
Clinical Cases
207
Question 201
A 29-year-old male presented with a three-hour history
of severe epigastric pain and profuse vomiting. The pain
radiated into his back, and was not relieved by any of the
antacid therapies which he had tried at home. There was
no previous history of abdominal pain. He was a nonsmoker and consumed 12 units of alcohol on an
infrequent basis.
On examination, he was distressed with pain. On
inspection of the trunk there were several raised lesions
(201). There was no pallor. His heart rate was 100
beats/min and blood pressure 140/80 mmHg. On
examination of the abdomen, he was very tender in the
epigastrum but there was no abdominal rigidity. Bowel
sounds were reduced.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Chloride
Potassium
Urea
Creatinine
Calcium
Albumin
Glucose
Chest X-ray
Abdominal X-ray
15 g/dl
16 ! 109/l
200 ! 109/l
128 mmol/l
98 mmol/l
3.6 mmol/l
6 mmol/l
100 mol/l
2.1 mmol/l
42 g/l
6 mmol/l
Normal
Normal
201
Question 202
A patient collapsed during an ECG (202a).
1. What is the cause of collapse?
2. What is the immediate management?
202a
208
Answer 201
Causes of acute pancreatitis
1. Serum amylase.
2. i. Arterial blood gases.
ii. Clotting studies.
3. Acute pancreatitis secondary to hypertriglyceridaemia.
4. i. Vomiting.
ii. Pseudohyponatraemia secondary to hyperlipidaemia.
The history of acute abdominal pain radiating to the back
and associated with profuse vomiting is consistent with
acute pancreatitis, although a perforated duodenal ulcer
and cholecystitis may present similarly. The slightly low
serum calcium supports the diagnosis of acute pancreatitis
because the associated rise in serum lipase resulting from
pancreatic damage leads to an increase in the free fatty
acid concentration in the blood, which has the effect of
binding calcium and thus reducing the free calcium in
the serum.
A very high serum amylase is usually diagnostic of
acute pancreatitis, but acute parotitis may cause similarly
high levels. However, in the latter case the history is of
painful parotid glands. A modestly elevated level is seen
in perforated duodenal ulcer, cholecystitis and aortic
aneurysm.
A neutrophil leucocytosis is common. The serum
calcium may be low for reasons explained above. It is
mandatory to check urea, electrolytes, glucose, arterial
blood gases, chest X-ray and clotting. The most common
cause of mortality is renal failure and respiratory failure
Alcohol abuse
Cholelithiasis
Coxsackie and mumps virus
Hypercalcaemia
Hypertriglyceridaemia
Drugs: thiazides, steroids, azathioprine
ERCP
Trauma
Answer 202
1. Ventricular fibrillation precipitated by the R on T
phenomenon.
2. DC cardioversion using 200 J.
The rhythm is broad complex, and the QRS-complexes
are very irregular and are of varying amplitude and duration. This is typical of ventricular fibrillation.
There is only one effective method of reverting ventricular fibrillation to sinus rhythm, and that is DC cardioversion using a high-energy shock. The quicker this is
given, the higher the chance of reverting to sinus rhythm.
The window for success is around 2 minutes, following
which reversion becomes increasingly difficult. The most
common cause of ventricular fibrillation is myocardial
infarction; however, the cardiomyopathies, ventricular
aneurysms, electrolyte imbalances (particularly hypo kalaemia) and certain drug overdoses (e.g. cocaine or
tricyclic antidepressant drugs) are also recognized causes.
Following myocardial infarction, multiple ventricular
ectopics occurring on the preceding T-wave may cause
202b
2
1
monomorphic ventricular tachycardia which can degenerate into ventricular fibrillation. Post-myocardial infarction
patients with R on T ventricular ectopics are treated
prophylactically with a lignocaine infusion to reduce the
frequency of the ectopics.
In this case (202b), there is clear evidence of the Rwave of an ectopic beat (1) on the T-wave of the
preceding sinus beat (2).
Clinical Cases
209
Question 203
203a
203b
203c
203d
210
Answer 203
1. A double apical impulse is the result of a palpable
fourth heart sound which occurs when there is
forceful left atrial contraction against a noncompliant left ventricle. This sign is often present in
conditions which produce significant left ventricular
hypertrophy. Examples include aortic stenosis,
hypertrophic cardiomyopathy and occasionally
severe left ventricular hypertrophy due to
hypertension.
2. In the absence of hypertension, the differential
diagnosis is between aortic stenosis and
hypertrophic cardiomyopathy. In hypertrophic
cardiomyopathy, an obstructive element is present
in approximately 30% of patients. The obstruction is
variable and thought to be due to anterior motion
of the mitral valve towards the hypertrophied
interventricular septum in systole, thus narrowing
the left ventricular outflow tract. The exact
mechanism for this is not clearly understood. The
obstruction is worsened by manoeuvres which
reduce LVEDP, and in these circumstances the
murmur is louder. The Valsalva manoeuvre
(blowing against a closed glottis) increases
intrathoracic pressure and therefore reduces venous
return to the heart, reducing LVEDP. Standing
from a squatting position has similar consequences.
In aortic stenosis these manoeuvres reduce the
intensity of the systolic murmur.
3. The ECG reveals sinus rhythm with voltage criteria
for left ventricular hypertrophy and deep S-waves in
the septal (V2V3) leads. In addition, there is Twave inversion in the inferior leads. Regular physical
training can also produce left ventricular
hypertrophy; however, the extent of hypertrophy
4.
5.
6.
7.
Gene affected
-myosin heavy chain
Troponin T
Troponin I
-tropomyosin
Chromosome
11
7
3
12
Gene affected
Myosin-binding protein C
?
Myosin essential light chain
Myosin regulatory light chain
Clinical Cases
211
Question 204
204
10.1 g/dl
60 ! 109/l
190 ! 109/l
12%
101 fl
39 mol/l
20 iu/l
70 iu/l
36 g/l
56 g/l
Normal
Urobilinogen ++
Bilirubin 0
Question 205
A 19-year-old medical student was admitted to the
Accident and Emergency Department with headache and
drowsiness on a cold winters morning. He shared a
house with three fellow students, who found him in bed
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Arterial blood gases:
pH
PaO2
PaCO2
Bicarbonate
O2 saturation
Chest X-ray
ECG
14 g/dl
9 ! 109/l
370 ! 109/l
135 mmol/l
4.4 mmol/l
4 mmol/l
80 "mol/l
7.37
7.2 kPa
3.8 kPa
23 mmol/l
98%
Normal
Sinus tachycardia
212
Answer 204
1. i. Numerous mature lymphocytes.
ii. Smudge or smear cell.
iii. Red cell agglutination.
2. Smudge or smear cells are an artefact phenomenon
which arises during blood film preparation due to the
fragility of lymphocytes in chronic lymphatic
leukaemia.
3. Warm auto-immune haemolytic anaemia (see Table
for other causes).
4. i. Reticulocytosis secondary to haemolysis.
ii. Megaloblastic anaemia due to folate deficiency
from increased cell turnover.
5. Direct Coombs test.
Chronic lymphatic leukaemia usually affects the middleaged and the elderly. It is a malignancy of B-cell
lymphocytes. The clinical features are insidious, and the
diagnosis may be made incidentally on a blood film. The
main features are lethargy, night sweats, weight loss and
recurrent infections due to hypogammaglobulinaemia.
Physical examination reveals generalized lymphadenopathy
and hepatosplenomegaly. The characteristic blood picture
is of a lymphocytosis and a mild normochromic
normocytic anaemia. Smudge or smear cells are common.
As disease progresses, the anaemia becomes more severe,
partly owing to marrow suppression and partly owing to an
Answer 205
d. Carbon monoxide poisoning.
The clue for the diagnosis of carbon monoxide poisoning
comes from the arterial blood gases, which reveal hypoxia
but a normal oxygen saturation. Carbon monoxide
displaces oxygen from Hb and displaces the oxygen
dissociation curve to the left. It also inhibits cellular
respiration by inhibiting the cytochrome oxidase system.
This results in tissue hypoxia, which may manifest as
headaches, dizziness, convulsions, nausea and vomiting.
On examination, patients may have tachycardia,
tachypnoea, ataxia and cherry red discoloration of the
lips; however, the latter is a relatively rare and late
manifestation of the condition. Retinal haemorrhages are
a recognized complication of carbon monoxide
poisoning. Late complications include basal ganglia
infarction and parkinsonism, and sometimes
neuropsychiatric symptoms. Oxygen saturation is normal
because automated biochemical and pulse oximeter
analysers cannot differentiate between oxyhaemoglobin
and carboxyhaemoglobin; however, PaO2 is low when
there is significant carbon monoxide poisoning. It is
worth noting that arterial PaO 2 is often normal in
Clinical Cases
213
Question 206
A 38-year-old businessman was admitted to hospital with
nausea, vomiting and drowsiness. He had been in
Thailand for 10 days and returned back to England two
days previously. He was well in Thailand, but on arrival
to England developed general malaise and a headache.
He attributed his symptoms to excess alcohol ingestion
while abroad, and attempted to relieve his symptoms with
two paracetamol tablets. He continued to have a
headache the following morning, and took another two
tablets of paracetamol, without much relief of his
symptoms. Following this, he took two paracetamol
tablets every four hours. He gradually became more
unwell, nauseous and started vomiting. There was no
neck stiffness, photophobia or diarrhoea. He normally
consumed two bottles of wine and occasional spirits per
day and smoked 30 cigarettes a day. While abroad, he
had drunk more alcohol than usual. There was no
significant past medical history.
On examination, he was tanned and had a flushed
face. He was mildly icteric. He had a fever of 39C
(102.2F). He was slightly drowsy, but could hold a
normal, coherent conversation. There was no evidence of
asterixis. Examination of the fundi was normal. The heart
rate was 110 beats/min and blood pressure 105/70
mmHg. Examination of the precordium revealed a very
soft third heart sound. His chest was clear. Abdominal
examination revealed a slightly tender palpable liver edge
4 cm below the costal margin. The spleen was not
palpable.
Investigations are shown.
Hb
WCC
Platelets
MCV
PT
Malaria parasite
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Serum ferritin
Chest X-ray
15.8 g/dl
9 ! 109/l
105 ! 109/l
102 fl
20 s (control 14 s)
Not detected
133 mmol/l
3.5 mmol/l
5 mmol/l
98 mol/l
30 mol/l
1500 iu/l
110 iu/l
500 g/l
Normal
Question 207
A 42-year-old female presented with
increasing dyspnoea on exertion. She
had a past history of rheumatic fever.
Left and right cardiac catheter data
were as follows:
Chamber
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left ventricle
Aorta
Pressure (mmHg)
10
40/10
40/22
16
160/10
110/70
214
Answer 206
1. d. Serum paracetamol level.
2. b. Paracetamol poisoning/alcohol abuse.
There is a history of alcohol abuse and consumption of
67 g of paracetamol in 24 hours. Ingestion of 15 g of
paracetamol is regarded as a significant overdose in normal
healthy individuals; however, the dose of paracetamol
required to cause hepatotoxicity in individuals with chronic,
heavy alcohol ingestion is much lower. This is explained by
the ability of alcohol to induce hepatic microsomal enzymes
and to deplete hepatic intracellular levels of glutathione.
Paracetamol itself is not hepatotoxic, but it is usually
metabolized to NAPQI, a potent oxidative agent with
potential to cause massive hepatic necrosis. The metabolite
is normally rapidly conjugated with glutathione, which
renders it inactive and it is excreted. In patients with heavy
alcohol ingestion the detoxifying microsomal enzyme
concentration is increased to metabolize alcohol. Although
this is a beneficial effect when dealing with alcohol, it can
have serious consequences when large amounts of
paracetamol are ingested because it leads to rapid
metabolism of the drug to NAPQI. The hepatocytes are
relatively depleted of glutathione owing to hepatic damage
from alcohol and soon become completely depleted in an
attempt to conjugate NAPQI. The result is an excess of
NAPQI, causing hepatic necrosis, which can have profound
effects if hepatic reserve has already been severely affected
by alcohol abuse. Alcohol abusers are more likely to develop
massive hepatic necrosis and have a worse prognosis from
paracetamol overdose.
Answer 207
a. Mitral stenosis, aortic stenosis and pulmonary
hypertension.
The right ventricular pressure and pulmonary artery
pressures exceed 35mmHg, indicating pulmonary
hypertension. The PCWP exceeds the LVEDP by
6 mmHg, indicating significant mitral stenosis. There is a
pressure drop of 50 mmHg across the aortic valve,
indicating moderate to severe aortic stenosis.
There is no evidence of step-up in oxygen saturation in
the right heart to indicate a left-to-right intracardiac shunt.
(See Interpretation of Cardiac Catheter Data, page 418.)
Clinical Cases
215
Question 208
208a
208b
Question 209
A 33-year-old male with recently diagnosed acute schizophrenia was referred to the Accident and Emergency
Department after he was found collapsed on the
psychiatric ward. On examination, the patient was very
drowsy and appeared rigid. The heart rate was
120 beats/min, and regular; blood pres sure was
110/60 mmHg.
The temperature was 40C (104F). Examination of
the cardiovascular, respiratory and abdominal system was
normal. Neurological examination demonstrated generalized rigidity of all muscle groups.
Investigations are shown.
Hb
WCC
Platelets
Urinalysis
Sodium
Potassium
Urea
Creatinine
15 g/dl
10 ! 109/l
300 ! 109/l
Protein +
138 mmol/l
4 mmol/l
10 mmol/l
160 mol/l
216
Answer 208
1. An atrioventricular tachycardia with LBBB.
2. i. Vagotonic manoeuvres such as carotid sinus
massage, Valsalva manoeuvre, compression of the
eyeball.
ii. Intravenous adenosine.
3. WolffParkinsonWhite syndrome (type A).
4. i. Sotalol.
ii. Flecanide.
iii. Disopyramide.
iv. Amiodarone.
5. Radiofrequency ablation of the accessory pathway.
WolffParkinsonWhite syndrome (WPW), a congenital
illness with a prevalence of 1 in 1,500, is characterized by
an accessory conduction pathway between atria and
ventricles (bundle of Kent) which predisposes to an
electrical re-entrant circuit and tachycardia. During sinus
rhythm the electrical impulse conducts rapidly over the
accessory conduction pathway and depolarizes the
ventricles prematurely, resulting in a short PR-interval
and a wide QRS-complex with slurred upstroke, often
called a delta wave. Anterograde conduction through the
accessory pathway and retrograde conduction via the
atrioventricular node may predispose to two types of
tachyarrhythmias which are atrioventricular re-entrant
tachycardia or atrial fibrillation. Two variants of WPW are
recognized: type A (left-sided pathway), with an upright
(positive) delta wave in V1, as in this case; and type B
(right-sided pathway), with negative delta wave in V1
(208c). The former is more common.
208c
Answer 209
1. Neuroleptic malignant syndrome secondary to the
use of phenothiazines.
2. Serum creatinine kinase.
3. i. Stop drug.
ii. Intravenous diazepam.
iii. Adequate hydration to prevent renal failure.
The neuroleptic malignant syndrome is a rare but lifethreatening condition that can occur with any antipsychotic drug, irrespective of dose. It is most common
when starting treatment or increasing the dose. Symptoms
include fever, muscle rigidity, confusion and impaired
consciousness. Autonomic instability is well recognized and
is associated with excessive sweating, labile blood pressure
and tachycardia. The diagnosis is made by demonstrating a
grossly elevated creatinine kinase. Rhabdomyolysis may
precipitate renal failure, which can be avoided by adequate
hydration. Other complications include aspiration
pneumonia and respiratory failure. The management of this
Clinical Cases
217
Question 210
A 59-year-old male presented with a three-week history of
cough and progressive breathlessness and three episodes
of haemoptysis in 24 hours. At the onset of the initial
symptoms he visited his GP, who diagnosed a respiratory
tract infection and prescribed a course of broad-spectrum
antibiotics. The cough persisted and the patient remained
breathless. His effort tolerance had become significantly
reduced from walking two miles daily to being breathless
at rest. He had felt increasingly lethargic and nauseous for
a week before being seen in the Accident and Emergency
Department. Twenty-four hours previously he had
coughed an egg-cup-full of fresh clots of blood on three
separate occasions. There was no history of sore throat or
night sweats. Prior to a week previously, his appetite was
good. There was no history of weight loss. He had a past
history of haemorrhoids which were surgically ligated two
years ago.
The patient was married with one son and worked as a
mechanic. He smoked 10 cigarettes per day and
consumed 23 units of alcohol per week. There was no
history of travel abroad. There was no family history of
note, with the exception that his mother had been
treated for pulmonary TB 16 years ago.
On examination, he appeared pale and centrally
cyanosed. There was no evidence of clubbing or lymphadenopathy. There was bilateral pitting ankle oedema. The
heart rate was 110 beats/min, and regular, and blood
pressure was 176/105 mmHg. The JVP was raised 4 cm
above the sternal angle. On examination of the respiratory system chest expansion was symmetrically reduced.
The trachea was central. Percussion note was dull at both
bases, and on auscultation there was widespread bronchial breathing at both mid-zones and bases. Precordial
and abdominal examination was normal.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
ECG
Chest X-ray
Urinalysis
Lung function:
FEV1
FVC
TLC
RV
TLCO
7.2 g/dl
12 ! 109/l
500 ! 109/l
137 mmol/l
5.2 mmol/l
19 mmol/l
400 mol/l
2.1 mmol/l
2 mmol/l
40 g/l
Sinus tachycardia. Partial RBBB
Alveolar shadowing affecting both
lower zones
Blood +++
Protein ++
Numerous blood cells and red cell
casts
65% predicted
60% predicted
68% predicted
66% predicted
110% predicted
Question 211
Red cell count
Hb
PCV
MCV
MCH
WCC
Neutrophils
Lymphocytes
Monocytes
Platelets
Blood film
8 ! 1012/l
14.2 g/dl
0.55
69 fl
18.2 pg
15 ! 109/l
88%
8%
4%
475 ! 109/l
Hypochromia ++
218
Answer 210
1. Restrictive lung defect with a raised TLCO. (See
Respiratory Function Tests, page 419.)
2. Goodpastures syndrome. Other possible diagnoses
include microscopic polyarteritis nodosa and
Wegeners granulomatosis.
3. i. Renal biopsy.
ii. Anti-GBM disease.
4. i. Smoking.
ii. Lower respiratory tract infection.
iii. Pulmonary oedema.
iv. Inhalation of organic solvents.
The patient has evidence of acute glomerulonephritis. The
breathlessness, haemoptysis, raised TLCO and bilateral
alveolar shadows on the chest X-ray are highly suggestive
of pulmonary haemorrhage. The combination of acute
nephritis and pulmonary haemorrhage may occur in antiGBM disease, Wegeners granulomatosis, microscopic
polyarteritis nodosa and SLE. In anti-GBM disease,
patients who are smokers are more predisposed to lung
haemorrhage, as are patients who are exposed to hydrocarbons. The patient is both a smoker and has been
exposed to hydrocarbons from his occupation as a garage
mechanic. The most probable diagnosis is anti-GBM
disease.
Anti-GBM disease is rare, with prevalence 1 case per
million. The male to female ratio is 2:1. The age of onset
has two peaks which are the third and the seventh
Answer 211
c. Primary polycythaemia (polycythaemia rubra vera).
The patient has a normal Hb but the PCV and the red cell
count are elevated. Furthermore, he has associated leucocytosis, thrombocytosis and splenomegaly, which should
raise the suspicion of PRV. The normal (as opposed to
high Hb) is due to coexisting iron deficiency. The diagnosis of iron deficiency is supported by the low MCV.
PRV has an insidious onset. It rarely occurs before the
fifth decade. Symptoms include lethargy, depression,
Clinical Cases
219
Question 212
A 54-year-old Turkish male was admitted to hospital with
a three-week history of malaise, headaches, pain in his
arms, legs and lower back and night sweats. His appetite
was poor, and he had lost almost 3 kilograms in three
weeks. He worked as a butcher. He had returned from a
holiday in Turkey six weeks ago where he lived on his
brothers farm for two weeks.
On examination, he was unwell. He had generalized
cervical lymphadenopathy. His temperature was 38.5C
(101.3F). The blood pressure was 120/60 mmHg.
Cardiovascular examination revealed a soft systolic murmur
at the apex. Examination of the respiratory system was
normal. On examination of his abdomen he had a palpable
spleen 4 cm below the costal margin. The liver edge was also
palpable 3 cm below the costal margin. Genital examination
demonstrated an erythematous scrotum with a swollen,
tender left testicle. Examination of the central nervous
system, including the fundi, was normal. His lower back was
tender, but movements were not restricted. Similarly, his
limbs were tender but there was no fasciculation and power
was preserved. He had tender, red, macular lesions on his
11.8 g/dl
2 ! 109/l (neutropenia)
440 ! 109/l
66 mm/h
210 mg/l
Normal
Normal
Few calcified paratracheal lymph
nodes
Question 213
A 24-year-old Jamaican painter and decorator was
admitted with acute colicky central abdominal pain
associated with vomiting. The only past history was that
of a viral illness associated with a rash two weeks
previously. On examination, he appeared pale. The heart
rate was 110 beats/min and the blood pressure
Hb
WCC
Platelets
MCV
MCHC
Blood film (213)
Urinary d-ALA
Sodium
Potassium
Bicarbonate
Chloride
Urea
Creatinine
Calcium
Albumin
Glucose
CT of brain
213
10 g/dl
7 ! 109/l
170 ! 109/l
63 fl
28 g/dl
100 mmol/day (normal range
1157 mmol/day)
134 mmol/l
3.2 mmol/l
15 mmol/l
115 mmol/l
7 mmol/l
80 "mol/l
2.32 mmol/l
40g/l
4 mmol/l
Normal
220
Answer 212
1. Brucellosis.
2. i. Blood culture.
ii. Marrow culture.
iii. Brucella agglutination test or Brucella
immunoglobulins (ELISA).
3. Tetracycline and rifampicin; co-trimoxazole.
The history of malaise, myalgia, headaches and weight loss
in association with neutropenia, hepatosplenomegaly and
erythema nodosum is highly suggestive of brucellosis.
Brucellosis is caused by Brucella, a Gram-negative
bacillus, which may be contracted from cows, goats, pigs
or sheep. It has a wide animal reservoir. Three main
species cause infection in man: B. abortus (cattle),
B. melitensis (goats/sheep), and B. suis (pigs). The
organism usually gains access into the human body
through the gastrointestinal tract as a result of consuming
unpasteurized milk; however, contact with animal
carcasses may also increase risk of oral ingestion of the
bacterium. Brucellosis is virtually eliminated in the UK
due to the strict policy of pasteurization of milk. Once in
the gastro intestinal tract, the bacilli travel to the
Answer 213
c. Lead poisoning.
In a young man with abdominal pain, vomiting,
neuropathy and anaemia, the most likely diagnosis is lead
poisoning, although several other conditions may also cause
the same symptoms (Table). The diagnosis is confirmed by
measuring the serum lead concentration. A lead
concentration above 4 mmol/l is toxic. Treatment is with
D-penicillamine therapy.
Acute lead poisoning is rare, but chronic poisoning may
occur in scrap-metal workers or plumbers, in individuals
ingesting water from lead pipes, in children ingesting old
lead-based paint in the house, and painters and decorators.
Lead interferes with haem and globin synthesis (see Answer
147). The effects are a microcytic anaemia and raised
precursors of haem synthesis. The latter cause abdominal
symptoms, autonomic and motor neuropathy which are
identical to those seen in AIP. In both lead poisoning and
AIP the '-ALA is elevated; however, lead poisoning is
differentiated from AIP by the relatively severe anaemia,
basophilic stippling affecting the red cells and the elevated
proto- and coproporphyrins. Basophilic stippling is caused
by aggregates of RNA resulting from inhibition of the
enzyme pyrimidine-5-nucleotidase. Other features include
haemolytic anaemia, lead encephalopathy (which is
characterized by a high CSF protein), a blue line on the
gums, and dense metaphyseal bands at the end of long
AIP
Lead poisoning
Arsenic poisoning
GuillainBarr syndrome
Polyarteritis nodosa
Diabetic ketoacidosis
Intra-abdominal malignancy
Sarcoidosis
Alcohol abuse
Clinical Cases
Question 214
214
134 mmol/l
4.3 mmol/l
120 mol/l
8 mmol/l
Sinus tachycardia
Question 215
A 25-year-old Malaysian male was admitted to hospital as
an emergency when he noticed that he was completely
paralysed for two hours after waking from his sleep in the
early hours of the morning. He had experienced this type of
severe weakness on four occasions over the past few
months, and remarked how they always occurred during
sleep and on waking he could not move. He drank four
units of alcohol every night. He had recently seen his GP
for anxiety attacks and was being counselled. He emigrated
to England in 1994 and worked as a chef. He was single.
All his family members were in Malaysia and were well.
On examination, he was thin; otherwise, physical
examination was normal. Investigations are shown.
FBC
Sodium
Potassium
Urea
Bicarbonate
TSH
Thyroxine
221
Normal
136 mmol/l
2 mmol/l
5 mmol/l
23 mmol/l
<0.1 mu/l
190 nmol/
7.5
1.8 kPa
15 kPa
19.3 mmol/l
+7
222
Answer 214
1. The blood gases demonstrate a partially
compensated respiratory alkalosis.
2. Hyperventilation.
Respiratory alkalosis is characterized by a low PaCO2 and
a high pH. Respiratory alkalosis may be seen in hyperventilation and artificial ventilation. In these situations it
is associated with a high or normal PaO2. It is also seen
in conditions predisposing to ventilation/perfusion mismatch such as pneumonia, pulmonary oedema, pul monary embolus and parenchymal lung disease. In this
particular case, the patient has a normal PaO2 and clear
lung fields on the chest X-ray, suggesting that she is
hyperventilating (see Table for causes of respiratory
alkalosis).
In all chronic respiratory alkalotic states the kidneys
compensate by excreting excess bicarbonate to produce a
relative metabolic acidosis in an attempt to normalize the
blood pH. Therefore, in compensated respiratory alkalosis the plasma bicarbonate is low.
Acute salicylate poisoning also produces a combined
respiratory alkalosis and metabolic acidosis. In toxic
Answer 215
1. b. Periodic paralysis.
2. c. Treat hypokalaemia.
e. Start carbimazole.
Hypokalaemic periodic paralysis is a rare condition that is
often inherited as an autosomal dominant trait. It is
characterized by episodic paralysis, which classically
occurs at night while the patient is asleep. The cause of
hypokalaemia is not clear, but shifts in potassium from
the extracellular fluid to the intracellular fluid are
thought to be responsible. Symptoms can be precipitated
by administering intravenous glucose and insulin into
such patients, which would lend support to the potassium
shift theory. Other precipitating factors include alcohol,
large carbohydrate meals, anxiety and tension. Recovery
is usually rapid, but can be expedited by intravenous
Clinical Cases
223
Question 216
216
4 g/dl
70 ! 109/l (predominantly blasts)
26 ! 109/l
137 mmol/l
3.7 mmol/l
4 mmol/l
74 mol/l
136 mmol/l
7.2 mmol/l
23 mmol/l
300 mol/l
1.2 mmol/l
3 mmol/l
Question 217
A 59-year-old headmaster was referred to a chest unit
with a six-month history of progressive breathlessness.
His effort tolerance one year previously was very good,
allowing him to jog 10 km, twice a week. Since then he
has had to give up running due to fatigue and breathlessness. His condition had continued to deteriorate, despite
the use of steroid and salbutamol inhalers prescribed by
his GP. He was now breathless after walking just 200 m.
He was a non-smoker. He had been a headmaster in a
London public school for nearly 25 years. There was no
family history of lung disease. He had never worked with
asbestos, and did not keep pets.
On examination, the patient was cyanosed and tachypnoeic. His hands and feet were clubbed. The JVP was
not raised, and heart sounds were normal. On ausculFEV1 (% predicted) 50
Blood gases on air:
FVC (% predicted) 52
pH
7.45
FEV1/FVC (%)
89
PaCO2
3.5 kPa
TLC (% predicted) 56
PaO2
6.4 kPa
KCO (% predicted) 60
Bicarbonate 22 mmol/l
Bronchoalveolar lavage revealed increased number
of cells which were predominantly neutrophils
Chest X-ray (217)
tation of the lung fields there were bilateral fine endinspiratory crackles at both lung bases.
Investigations are shown.
217
224
Answer 216
1. Acute myeloid leukaemia. Myeloblasts are large round cells with a round nucleus
and prominent nucleoli. In addition, they may contain cytoplasmic inclusions
known as Auer rods, which are almost pathognomonic of the condition.
2. Tumour lysis syndrome. The large numbers of blasts destroyed by chemotherapy
liberate large amounts of intracellular contents into the bloodstream, as evidenced
by the high potassium and phosphate concentrations. The nucleic acid from the
cell nuclei is metabolized to produce urate, which is excreted by the kidney.
3. Hyperuricaemic nephropathy. High concentrations of urate may cause
crystallization within renal tubules and acute renal failure.
4. i. Pre-hydration with intravenous fluids.
ii. Allopurinol, a xanthine oxidase inhibitor that inhibits the synthesis of urate.
iii. Rasburicase, a recombinant urate oxidase inhibitor.
Answer 217
1. i. Restrictive lung defect with reduced KCO.
ii. Cryptogenic fibrosing alveolitis.
2. i. High-resolution CT scan.
ii. Transbronchial lung biopsy.
In the absence of an obvious underlying cause (occupational, drugs, connective tissue disorder) for the symptoms and signs, the most likely diagnosis is CFA, which is
a disorder of unknown aetiology which usually occurs in
middle age. It is characterized by progressively worsening
dyspnoea, eventually leading to respiratory failure and cor
pulmonale from pulmonary hypertension. The cardinal
signs include cyanosis, clubbing and fine inspiratory
crackles at both lung bases. The chest X-ray demonstrates
a ground-glass appearance in the mid-zones and bases of
the lung which progresses to nodular shadows and streaky
fibrosis. The end result is a honeycomb appearance of the
lung on the chest X-ray.
Lung function tests demonstrate a restrictive lung
defect and a low KCO.
Blood gases demonstrate a low arterial oxygen content
and a normal CO2 content unless the patient develops
end-stage respiratory failure. The quality of high-resolution CT scans obviate the need for lung biopsy to
diagnose the condition in the majority of patients, but in
younger patients biopsy may be useful in differentiating
the condition from other causes of a similar chest X-ray
appearance. Bronchoalveolar lavage reveals large numbers
of neutrophils, and transbronchial biopsy will demonstrate cellular infiltration and thickening and fibrosis of
the alveolar walls.
Clinical Cases
225
Question 218
A 76-year-old female was admitted after being found on the
floor by the home help. She complained of frequent dizzy
spells, particularly after standing from a recumbent position.
She had experienced several falls at home, but never
required hospital admission. She had become housebound
due to the dizzy spells and falls and was increasingly
dependent on the social services. She also complained of
lethargy, hoarse voice, intermittent confusion, and weight
gain of almost 7 kg over the past seven months. She had a
history of arthritis for which she took paracetamol when in
pain. She was not taking any other regular medications.
On examination, she was pale and frail. The heart rate
was 60 beats/min and regular. The blood pressure was
200/60 mmHg when lying, and 90/50 mmHg when
standing. The JVP was not raised. The apex was displaced
slightly. Auscultation of the heart revealed soft first and
second heart sounds. There were no added sounds or
murmurs. Auscultation of the lungs was normal, as was
examination of the abdomen. Central nervous system
examination was essentially normal, with the exception of
bilateral absence of the ankle jerks.
Investigations are shown.
218
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
Total protein
Chest X-ray (218)
ECG
10 g/dl
6 ! 109/l
149 ! 109/l
87 fl
118 mmol/l
5.3 mmol/l
3 mmol/l
69 mol/l
12 mol/l
20 iu/l
100 iu/l
36 g/l
63 g/l
Normal rhythm and
complexes
Question 219
A 69-year-old male was seen by his GP with pain in his
wrist after a fall. He complained of generalized weakness
and pains in his lower limbs over the past few months.
Several investigations were ordered, the results of which
are as follows:
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Calcium
13 g/dl
7 ! 109/l
350 ! 109/l
55 mm/h
136 mmol/l
4 mmol/l
6 mmol/l
90 mol/l
2.0 mmol/l
Phosphate
Alkaline phosphatase
IgG
IgM
IgA
Paraprotein
X-ray of wrist
0.7 mmol/l
240 iu/l
23 g/l
2 g/l
2.4 g/l
6 g/l
Fracture radius, small
radiolucent area adjacent
to fracture
226
Answer 218
1. Postural hypotension.
2. Addisons disease.
3. Short synacthen test.
4. Polyendocrine deficiency type 2 (Schmidts
syndrome).
The postural hypotension and hyponatraemia suggest the
diagnosis of Addisons disease. For causes and further
details on Addisons disease, see Answer 273. The
additional history of weight gain, croaky voice, and
enlarged heart on the chest X-ray suggests coexistent
hypothyroidism. (Note: in pure Addisons disease the
heart is characteristically small owing to chronic
hypovolaemia; however, if hypothyroidism is also present
the heart may be enlarged owing to a consequent
cardiomyopathy or a pericardial effusion.) Approximately
10% of cases of Addisons disease due to auto-immune
adrenalitis are associated with other endocrine
deficiencies (Table). The association of auto-immune
adrenalitis with auto-immune hypothyroidism or insulindependent diabetes mellitus is termed Schmidts
syndrome or polyendocrine deficiency type 2.
The patients confusion could be explained by either
Addisons disease or hypothyroidism. Absent ankle jerks
Answer 219
1. i. Osteomalacia.
ii. Monoclonal gammopathy of undetermined
significance.
2. i. Not anaemic.
ii. No evidence of immune paresis.
iii. Paraprotein level below 20 g/l.
The diagnosis of osteomalacia is relatively straightforward
on the bone biochemistry, which classically reveals hypocalcaemia, hypophosphataemia and a raised alkaline phosphatase, the latter being secondary to an increase in PTH
release in response to hypocalcaemia. Skeletal mani festations of osteomalacia include Loosers zones, which
are linear radiolucent areas seen most commonly in the
bones of the forearms, scapulae, femurs and the pelvis.
The raised ESR and IgG level associated with a very mild
paraproteinaemia will confuse some readers, and commit
Clinical Cases
227
Question 220
220a
220b
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
ECG (220a)
142 mmol/l
3.3 mmol/l
4.0 mmol/l
100 mol/l
36 mmol/l
107 mmol/l
228
Answer 220
220c
1. Hypokalaemic alkalosis (see Answer 275).
2. i. First-degree atrioventricular block. The PRinterval is much greater than 200 ms. There are
many causes of first-degree atrioventricular block
(Table A); however, in this case the most likely
cause is hypokalaemia.
ii. There is voltage criteria of left ventricular
hypertrophy. The sum of the S-wave in V1 and
the R-wave in V5 or V6 exceeds 0.35 mV (each
small square on the ECG is 0.1 mV), which
conforms with the Sokolow criteria for left
ventricular hypertrophy.
iii. There is ST-segment depression in the lateral
leads which may be secondary to left ventricular
hypertrophy or to hypokalaemia. Although
myocardial ischaemia is also a recognized cause of
ST-segment depression, it is unlikely in the
context of this question.
iv. There are prominent U-waves (upright waves
immediately following the T-wave, 220c
arrowed) which are suggestive of hypokalaemia.
Other ECG changes in relation to metabolic
abnormalities are tabulated below (Table B).
3. Primary hyperaldosteronism or Conns syndrome
secondary to an adrenal adenoma. Conns tumours
are bright yellow as opposed to phaeochromocytomas, which are a greyish-purple colour
(220d).
4. i. Lying and standing plasma renin and aldosterone
levels.
ii. High-resolution abdominal CT scan.
5. High doses of spironolactone, an aldosterone
antagonist.
220d
Clinical Cases
Conns syndrome
Cushings syndrome
Phaeochromocytoma
Acromegaly
Thyrotoxicosis
Hyperparathyroidism
11-- and 17--hydroxylase deficiency
229
Question 221
A 15-year-old farmers daughter was admitted to the
infectious diseases unit with a five-day history of right
Hb
WCC
Platelets
Reticulocyte count
Blood film
PT
APTT
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
Hepatitis B sAg
HCV Ab
CMV serology
Monospot test
8 g/dl
18.8 ! 109/l
140 ! 109/l
20%
No fragmented red cells
seen
36 s (control 12 s)
59 s (control 45 s)
136 mmol/l
4.9 mmol/l
26 mmol/l
400 "mol/l
50 mmol/l
900 iu/l
300 iu/l
33 g/l
Absent
Absent
Absent
Negative
230
Answer 221
1. i. Leptospirosis (Weils disease).
ii. Acute hepatitis A infection.
iii. Paracetamol overdose.
iv. Iron overdose.
2. i. Blood loss from endothelial damage resulting in
haemorrhage.
ii. Haemolysis.
iii. Disseminated intravascular coagulation causing
blood loss.
The patient has evidence of hepatitis together with renal
failure and a coagulation disorder. The clinical scenario
which would fit this triad is fulminant hepatic failure
complicated by the hepatorenal syndrome. The majority
of cases are due to viral hepatitis (hepatitis A, B, C and
D, although EBV, CMV, Coxsackie and herpes simplex
virus have been implicated; Lassa fever, Ebola virus and
Marburg virus should be considered in a patient who has
recently returned from Africa), and drugs (paracetamol,
iron, tetracycline, isoniazid, rifampicin, halothane). Other
recognized causes include toxins (alcohol, carbon
tetrachloride), leptospirosis (Weils disease), Wilsons
disease, and pregnancy. In a farmers daughter
leptospirosis causing hepatic and renal failure (Weils
disease) is a distinct possibility, but hepatitis A and drug
overdose should also be borne in mind.
Leptospirosis is caused by the spirochaete Leptospira
icterohaemorrhagica. Rodents, particularly rats, are the
most important reservoir of infection. Other hosts
include cattle, pigs, goats, hamsters, mice, hedgehogs,
foxes and skunks. The organism is excreted in the urine
and may survive in the soil for several weeks. Entry into
the human host is through cuts and abrasions on the
skin, or through intact mucous membranes. Occupations
most susceptible are sewage workers, fishermen, vets and
farmers. Replication occurs in the blood and tissue and
multi-system involvement may occur. The kidneys and
liver are most affected. Glomerular injury occurs first
causing an acute interstitial nephritis and tubular
necrosis. In the liver there is evidence of centrilobular
necrosis in severe cases.
Clinical Cases
Question 222
231
222a
Hb
WCC
Platelets
MCV
Sodium
Urea
Calcium
Albumin
Bilirubin
Alkaline phosphatase
AST
Chest X-ray (222a)
CT Thorax (222b)
16 g/dl
6.9 ! 109/l
412 ! 109/l
98 fl
138 mmol/l
6 mmol/l
2.31 mmol/l
35 g/l
18 mmol/l
190 iu/l
30 iu/l
222b
Question 223
A 70-year-old male developed atrial fibrillation 12 hours
after thrombolysis for an anterior myocardial infarction.
He did not have chest pain. He had a history of
hypertension and chronic obstructive airways disease. The
heart rate measured 122 beats/min. The blood pressure
measured 130/80 mmHg and the chest was clear.
Question 224
A 44-year-old male was admitted to the Coronary Care
Unit following an inferior myocardial infarction. He was
a smoker and consumed up to 20 units of alcohol per
day. On the third day of admission he became gradually
clammy. He was aggressive towards the nursing staff. His
heart rate was 130 beats/min. The blood pressure was
160/100 mmHg. Oxygen saturation on air was 96%.
232
Answer 222
d. Emphysema.
In a patient with rheumatoid arthritis, a history of heavy
smoking and an occupational history of mining there are
several potential causes of dyspnoea, which include
rheumatoid lung disease (see Answer 320), occupational
dust induced fibrosis and obstructive airways disease. The
Answer 223
a. IV digoxin.
The patient has developed rapid atrial fibrillation shortly
after myocardial infarction. He is surprisingly
asymptomatic. DC cardioversion is only indicated if there
is ongoing myocardial ischaemia or heamodynamic
compromise. In the absence of these features the aim is
to control the ventricular rate to reduce myocardial
oxygen consumption and to prevent systemic
thromboembolism.
The most effective drugs to slow ventricular rate are
beta-blockers, but these are relatively contraindicated in
this patient, who also has COPD. Although diltiazem is
effective, there have been recent reports suggesting that
calcium channel antagonists may be associated with an
increased mortality following myocardial infarction.
Answer 224
c. Oral diazepam.
The patient presents with features of delirium tremens
(aggressive behaviour, sweating, tachycardia and
hypertension), the best treatment for which is therapy with
benzodiazepines. Short-acting agents such as lorazepam
are usually not recommended because they have to be
given relatively frequently. Chlormethiazole was commonly
used in the 1980s but there have been adverse effects with
respiratory suppression, therefore the drug is no longer
recommended for alcohol withdrawal. Diazepam is
Clinical Cases
233
Question 225
A 23-year-old male was admitted with a 24-hour history
of cough, fever and confusion. He had a history of
epilepsy that was well controlled on carbamazepine.
Looking through his records there were several transient
admissions for deliberate self-harm, including a history of
Ecstasy abuse. According to a friend he consumed up to
70 units of alcohol per week.
On examination he was pale. The heart rate was
110/min and regular. The blood pressure measured
96/60 mmHg. There was reduced air entry over the
anterior aspect of the right chest.
Investigations are shown.
Which antibiotic regime would you prescribe for the
patient?
a. IV cefuroxime.
b. IV amoxycillin.
c. IV clarithromycin.
d. IV cefuroxime and clarithromycin.
e. IV amoxycillin and metronidazole.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Gamma GT
12 g/dl
14 ! 109/l
200 ! 109/l
90 fl
134 mmol/l
3.8 mmol/l
7 mmol/l
120 "mol/l
15 mmol/l
140 iu/l
182 iu/l
312 iu/l
225b
225a
Question 226
A 16-year-old girl was admitted with a 3-hour history of
vomiting followed by collapse. She had recently split up
from her boyfriend and was thought to have taken an
overdose of digoxin that her father had been prescribed
for atrial fibrillation.
What is the immediate management of her condition?
a. Activated charcoal via nasogastric tube.
b. IV atropine.
c. IV isoprenaline.
d. IV dextrose 50% (50 ml).
e. IV digoxin specific antibody fragments (Digibind).
133 mmol/l
4.8 mmol/l
5.6 mmol/l
100 "mol/l
5 nmol/l
High second degree AV block;
VR 36/min
234
Answer 225
e. IV amoxycillin and metronidazole.
The patient has evidence of a right upper lobe
consolidation, which would usually be treated
conventionally with IV cefuroxime and IV clarithromycin
in accordance with the guidelines set by the British
Thoracic Society. However, he has several risk factors for
aspiration, notably alcohol and recreational drug abuse.
Aspiration pneumonia is caused by anaerobic bacteria
that are not effectively treated with cephalosporins,
macrolides, aminoglycosides or the quinolones.
Answer 226
b. IV atropine.
Digoxin toxicity is characterized by gastrointestinal
disturbance such as anorexia, nausea, vomiting and
diarrhoea, blurred vision, xanthopsia, dizziness,
confusion and delirium. Cardiac arrhythmias are usually
the most serious complication and are the commonest
cause of mortality in digoxin toxicity. Almost any
arrhythmia is possible. Ventricular extra-systoles are the
commonest rhythm disturbance. The presence of
supraventricular tachyarrhythmias and atrioventricular
block in a patient taking digoxin are highly suggestive of
digoxin toxicity.
The management of digoxin therapy includes
prevention of absorption of the drug, correction of
electrolyte disturbances that promote digoxin toxicity or
occur as a result of digoxin toxicity, and management of
arrhythmias. A small proportion of patients may require
digoxin specific antibody fragments (Table).
In severe digoxin toxicity, the inhibition of the
Na+/K+ ATPase can result in hyperkalaemia that should
be treated conventionally with 50 ml of 50% dextrose
and 1618 units of short-acting insulin. Severe
bradyarrhythmias (HR <40 beats/min), as in this
situation, should be treated with IV atropine. Temporary
cardiac pacing is necessary in patients unresponsive to
atropine. Isoprenaline is contraindicated, as it may
precipitate tachyarrhythmias.
Verapamil is the drug of choice in patients with
supraventricular arrhythmias. Lignocaine and phenytoin
are effective in the management of ventricular
tachycardia. Electrical cardioversion is indicated in
patients with haemodynamic compromise but with
relatively low voltage DC shocks, e.g. 50 J, as there is a
risk of asystole.
Correct electrolytes
Manage bradyarrhythmias
Temporary cardiac pacing
Manage SVTs
Manage VT
In very severe cases
Technique/drug
Gastric lavage or
ipecacuanha
Activated charcoal
if ingestion
<68 hours
Correct K+ and Mg2+
Atropine
Verapamil
Lignocaine
Phenytoin
Digoxin binding
antibody fragments
(see above)
Clinical Cases
235
Question 227
227
Question 228
A 30-year-old male with a family history of adult
polycystic kidney disease wished to be screened for the
condition. His mother was affected and a paternal aunt
had recently suffered a subarachnoid haemorrhage as a
result of a ruptured berry aneurysm.
Question 229
Below is an ECG (229) from a patient presenting with
syncope.
229
236
Answer 227
b. Left upper lobe collapse.
There are three main features that are related to loss of
lung volume: elevation of the left hemidiaphragm;
Answer 228
b. Renal ultrasound.
The patient has adult polycystic kidney disease. 86% of
patients with APCKD have an abnormality in a gene
adjacent to the alpha globin gene in chromosome 16
(PKD-1 gene). The other patients with APCKD (PCKD-2)
have an abnormal gene on chromosome 4. In PCKD-2
cysts and end-stage renal failure occur late (in the sixth or
seventh decade), thus screening with ultrasound may miss
young PCKD-2 patients. However, this is not felt to be
particularly important since most patients with this
genotype remain well throughout life.
With respect to APCKD-1, screening is based on the
demonstration of cysts in one or both kidneys (depending
upon age) using CT scan or renal ultrasound. In children
CT scan of the abdomen is the screening test of choice as
small cysts may be missed using ultrasound. By the age of
3035 years all patients with APCKD-1 have visible cysts
on renal ultrasound; therefore, for adults in or above this
age group renal ultrasound is the screening test of choice.
Even in patients aged 20, the false-negative rate with renal
ultrasound is only 4%. See Table for ultrasound criteria for
diagnosis of polycystic kidney disease.
Genetic testing for APCKD-1 is 99% accurate but is not
widely available, and is currently reserved for screening
children in whom CT scan may be normal and those who
are potential transplant donors for their families.
APCKD is associated with intracranial aneurysms.
Approximately 8% of patients with APCKD have
intracranial aneurysms, which is four to five times higher
than the general population. Ruptured aneurysms are
responsible for around 6% of all deaths due to APCKD.
Patients with APCKD and a family history of cerebral
Criterion
at least two cysts (unilateral or bilateral)
at least two cysts in each kidney
at least four cysts in each kidney
No
Screening not
indicated
MRA brain or
spiral CT brain
scan
No
Intercerebral
aneurysms?
Yes
Repeat every
5 years
Answer 229
a. Complete heart block.
The patient has a bifascicular block (left anterior
hemiblock and RBBB) and a prolonged PR interval.
Clinical Cases
237
Question 230
A 48-year-old male, psychiatric patient, living in an
institution, was witnessed to have a fit for the first time.
He had been treated with chlorpromazine for the past
Sodium
Potassium
Urea
Creatinine
Glucose
POsm
Renin
Aldosterone
TSH
Urine sodium
Urine osmolality
115 mmol/l
3.4 mmol/l
1.1 mmol/l
60 "mol/l
4.1 mmol/l
248 mOsm/l
90 pmol/l (NR 100500 pmol/l)
50 pmol/l (NR 100500)
3 mu/l (NR 0.55.0 mu/l)
10 mmol/l
90 mOsm/l
Question 231
A 56-year-old woman presented with a four-day history
of breathlessness, cough and a high fever. She gave a long
history of indigestion and intermittent dysphagia to solids
and fluids. On several occasions undigested food would
be regurgitated back shortly after she had eaten. She
would often wake at night with episodes of coughing and
spluttering. There was no history of weight loss.
238
Answer 230
e. Compulsive water drinking.
The patient has a very low serum sodium and low plasma
osmolality (calculated 242 mOsm/l). The main
differential diagnoses are SIADH and primary polydipsia,
although hypothyroidism and cortisol deficiency may also
present with similar plasma biochemistry. In compulsive
water drinking (primary polydipsia), ADH production is
completely inhibited and urine osmolality is very low
(<100 mOsm/l). In this particular case the very low
urine osmolality is consistent with the diagnosis of
compulsive water drinking. This is a relatively common
problem in patients with schizophrenia.
Although chlorpromazine can cause SIADH, the low
urine osmolality is against the diagnosis. Patients with
P Na/Osm
Normal/high
Low
Low
Low
Low/normal
Low
U Na
Low
High
High
High
Low
Low
U Osm
Low
High
High
High
High
Low
*Includes dehydration from GI loss, excess perspiration, water loss, CCF, hypoalbuminaemic states.
Exceptions include renal failure due to interstitial nephritis, where sodium excretion is increased even in
dehydration.
Answer 231
1. c. Achalasia.
2. b. Barium swallow.
A history of dyspepsia, dysphagia, oesophageal reflux and
a possible aspiration pneumonia is consistent with the
diagnosis of achalasia. Hiatus hernia may cause reflux and
occasionally nocturnal cough and aspiration pneumonia;
however, dysphagia is not a feature unless recurrent
reflux has caused a peptic stricture. Peptic stricture may
cause all the symptoms of achalasia; however, there is
usually a long history of indigestion before the onset of
dysphagia. Pharyngeal pouch does not cause retrosternal
pain, although dysphagia and regurgitation are common.
A barium swallow is the best method of differentiating
between achalasia, peptic stricture, hiatus hernia and
pharyngeal pouch. Although it is relatively clear that the
diagnosis is achalasia, oesophageal manometry scores
fewer marks than barium swallow or oesophagoscopy
because other causes of dysphagia particularly
Clinical Cases
239
Question 232
A 16-year-old girl who had undergone previous surgery
for congenital heart disease presented with fatigue. On
examination she had a heart rate of 40 beats/min. The
blood pressure was 110/70 mmHg. There was no
evidence of heart failure. The ECG showed complete
heart block with a ventricular rate of 40/min.
Question 233
A 38-year-old man was investigated for lethargy and
severe lower back pain. He had a past medical history of
Hodgkins lymphoma (stage 1A) which had been treated
Hb
WCC
Platelets
MCV
Reticulocyte count
Blood film
9 g/dl
14 ! 109/l
80 ! 109/l
88 fl
0.4%
Nucleated red cells;
metamyelocytes and
myeloblasts
Question 234
A 15-year-old boy was admitted to the intensive care unit
for the second time with meningococcal septicaemia.
Investigations on admission were as follows:
Hb
WCC
Platelets
14.8 g/dl
18 ! 109/l (neutrophils 80%)
190 ! 109/l
Question 235
Below is an ECG (235) from a 78-year-old patient with a slow pulse rate.
235
240
Answer 232
a. Dual chamber permanent pacemaker.
The patient has had prior cardiac surgery and presents
with symptoms of fatigue and a heart rate of
40 beats/min secondary to third degree AV block. All
forms of acquired third degree AV block should be
paced. The annual mortality from acquired third degree
block is 15% in the absence of cardiac pacing.
Answer 233
Causes of a leucoerythroblastic blood picture
d. Marrow infiltration.
The patient has a past history of Hodgkins lymphoma
and presents with back pain. There is evidence of a
normochromic, normocytic anaemia. The blood film
shows evidence of immature red and white cells, i.e. a
leucoerythroblastic blood picture. In the context of this
question, the most likely cause of the leucoerythroblastic
blood picture is marrow infiltration (Table).
Answer 234
c. Serum complement level.
Patients with C5 to C9 complement deficiency are prone
to recurrent Neisseria infections.
Hypocomplementaemia may be inherited or acquired.
Inherited hypocomplementaemia is associated with a
Disorder
Auto-immune diseases e.g. SLE
SLE
Severe recurrent infections with encapsulated bacteria shortly
after birth
Auto-immune disorders such as HenochSchnlein
syndrome, membranous glomerulonephritis, scleroderma
Predisposition to Neisseria spp. infections (manifests in late teens usually)
Answer 235
d. 2:1 second degree AV block.
e. Left ventricular hypertrophy.
Clinical Cases
241
Question 236
A 41-year-old schoolteacher was seen by a
rheumatologist for intermittent painful blue fingers
during exposure to the cold weather. She had also
recently developed fixed flexion deformities of her fingers
bilaterally and thickening on the dorsal aspects of the
hands. She was subsequently commenced on
penicillamine and a non-steroidal anti-inflammatory
drug. Two months later she complained of breathlessness
on exertion and retrosternal burning pain on stooping
forward. On auscultation of the lung fields there were
fine end-inspiratory crackles at both lung bases. Lung
function tests revealed a restrictive defect with reduced
transfer factor.
Question 237
An 83-year-old woman was admitted with central chest
pain radiating to her left arm while out shopping. She
had never experienced chest pain previously. There was
no history of smoking, hypertension or diabetes. The
serum cholesterol was 8 mmol/l.
Physical examination was normal. The 12-lead ECG
showed flattening of the T waves in leads I, V5 and V6.
The troponin level 12 hours after the pain was not
elevated. A diagnosis of angina was made. The patient
remained stable and pain free over the next 48 hours. An
exercise test performed on the third day of admission
revealed ST segment depression >2 mm in leads V4V6
after 4 minutes of exercise (HR 120 beats/min). The
patient did not experience chest pain on the treadmill.
Question 238
A 16-year-old female was referred with primary
amenorrhoea and hirsutism. The patient had noticed
excessive hair on her face, arms and legs since the age of
8 years. She had a past history of measles but had been
well otherwise. She lived in a mountain hut with her
father and aunt. She had two older siblings who were
well. Her father was 1.8 m tall. On examination she had
excessive acne and facial hair. The blood pressure was
105/65 mmHg. On inspection of the genitalia, there
was evidence of pubic hair up to the umbilical region and
moderate cliteromegaly.
242
Answer 236
d. Systemic sclerosis.
The patient has scleroderma and associated Raynauds
phenomenon as well as other organ involvement, notably
the lungs (pulmonary fibrosis) and the oesophagus
(dysmotility/lower oesophageal sphincter dysfunction).
The best diagnosis is systemic sclerosis. 90% of patients
with systemic sclerosis have gut involvement (50% are
symptomatic). Oesophageal dysmotility is the most
frequent visceral complication of systemic sclerosis. 70%
have pulmonary involvement. Renal, cardiac and
musculoskeletal involvement is well recognized. Renal
involvement is characterized by hypertension that may be
acute and severe; cardiac involvement comprises
pericarditis and its complications, restrictive cardio myopathy and myocardial fibrosis. Myocardial fibrosis is
Answer 237
b. Nifedipine.
All patients with angina should be prescribed an antithrombotic drug. The antithrombotic drug of choice is
aspirin, which has been shown to significantly reduce
mortality following myocardial infarction (ISIS 2 trial).
No other antithrombotic drug has been shown to be
superior to aspirin, although clopidogrel is equally
effective. Beta-blockers reduce myocardial oxygen
demand and are prognostically useful in the event of
myocardial infarction (ISIS 1). In patients with coronary
Answer 238
a. Congenital adrenal hyperplasia secondary to 21hydroxylase deficiency.
The differential diagnosis of hirsutism and virilism
includes congenital adrenal hyperplasia, polycystic ovary
syndrome, androgen secreting adrenal tumour,
Cushings syndrome, arrhenoblastoma (ovarian tumour
secreting androgens) and anabolic drug abuse. The
patient has presented with primary amenorrhoea and had
evidence of virilism at a relatively young age, which
would be consistent with 21-hydroxylase deficiency
congenital adrenal hyperplasia. PCOS rarely presents
Clinical Cases
243
ESR
8 mm/h
CT scan of the brain without contrast
Normal
Lumbar puncture and CSF analysis:
Opening pressure
29 cmH2O
Protein
0.4 g/l
Glucose
4.5 mmol/l
Microscopy
Lymphocytes 4/mm3
Question 239
Question 241
Question 240
What would your next management step be?
a. Anticoagulation.
b. Corticosteriods.
c. Stop the oral contraceptive pill.
d. Neurosurgical referral.
e. Nimodipine.
Question 242
A 46-year-old obese woman was recently diagnosed as
having diabetes mellitus. Investigations on presentation
are shown.
Sodium
Potassium
Urea
Creatinine
Fasting glucose
Fasting cholesterol
Fasting triglycerides
HbA1c
Urinalysis
132 mmol/l
4.6 mmol/l
12 mmol/l
190 "mol/l
13 mmol/l
8.2 mmol/l
8 mmol/l
9.4%
Protein ++
Glucose ++
Microscopy normal
244
Answers 239, 240 and 241
Answer 239
b. MRI scan of the brain with MR venography.
Answer 240
c. Stop the oral contraceptive pill.
Answer 241
d. Neurosurgical referral for optic nerve fenestration.
The presentation of benign intracranial hypertension may
simulate that of a cerebral tumour, hence it is also known
as pseudotumour cerebri. Patients present with
symptoms of raised intracranial pressure, which comprise
headache, transient visual obscurations and diplopia. The
most signifi cant physical finding in these patients is
bilateral disc oedema. The diplopia is due to unilateral or
bilateral sixth nerve palsies and resolves on lowering the
intracranial pressure.
The diagnostic criteria include the following:
Symptoms and signs restricted to those of elevated
intracranial pressure.
Normal neuroimaging studies (excluding nonspecific findings of raised intracranial pressure).
Increased cerebrospinal fluid pressure with a normal
composition.
The pathophysiology of this disorder is unclear. It is widely
presumed that a relative resistance to the absorption of
cerebrospinal fluid across the arachnoid villi is present. The
disease commonly occurs in individuals who are
Clinical Cases
245
239a
Malignant
hypertension?
No
Urgent neuroimaging
(preferably MRI)
Space-occupying
lesion or a dural sinus
thrombosis?
No
Lumbar puncture
Raised opening
pressure?
Yes
BIH
No
246
Clinical Medicine
No visual loss
Visual loss
1. Weight loss
2. Symptomatic
headache treatment
1. Weight loss
2. Acetazolamide or
furosemide
RESOLUTION
Progression
Progression or
intractable headache
Steroids or nerve
sheath fenestration
Lumbar shunt
Answer 242
b. Insulin.
The three main goals in the management of diabetes are:
1. Good glycaemic control, which has been shown to
reduce microvascular complications.
2. Treatment of nephropathy, retinopathy and diabetic
foot disease.
3. Aggressive treatment of risk factors for atherosclerosis
to reduce morbidity and mortality from macro-vascular
disease (Table).
This particular question tests the candidate on
management of hyperglycaemia. Glycaemic control
involves dietary modification, weight loss, regular exercise
and pharmacological therapy.
The patient in question has evidence of nephropathy and
has a mixed hyperlipidaemia. There is good evidence that
meticulous glycaemic control will retard progression of
renal impairment and have a beneficial effect on lipid
profile. Weight loss and stringent diabetic diet should
always be implemented in overweight diabetics as increased
body mass index is linked with insulin resistance. However,
this patient has nephropathy, an unsatisfactory HbA1c and
Achieve BMI 28
Cessation of smoking
Regular exercise*
HbA1c 7%
BP 130/80 mmHg
Total cholesterol 5 mmol/l
LDL cholesterol 2.2 mmol/l
247
Question 243
A 60-year-old woman attended the Accident and
Emergency Department with central chest pain radiating
to the jaw. Risk factors for coronary artery disease
included hypercholesterolaemia and a family history of
ischaemic heart disease. The 12-lead ECG revealed ST
segment depression in leads V2V6. Troponin T 12
hours after admission was 0.4 ng/l (NR <0.1ng/l).
Sodium
Potassium
Urea
Creatinine
137 mmol/l
3.6 mmol/l
8.2 mmol/l
137 "mol/l
135 mmol/l
4.6 mmol/l
15 mmol/l
220 "mol/l
Question 244
What is the most likely cause for the patients
deterioration?
a. Initiation of furosemide.
b. Initiation of an ACE inhibitor.
c. Hypertensive nephropathy.
d. Relative hypotension.
e. Left ventricular dysfunction.
Question 245
What is the next best investigation to ascertain the
cause of the abnormal renal function?
a. Renal biopsy.
b. Renal angiography.
c. Renal isotope scan.
d. Captopril renogram.
e. Echocardiogram.
248
Answer 243
d. Non-ST elevation myocardial infarction.
The patient presents with chest pain, non-ST elevation
ECG changes and a raised troponin level (specific for
myocardial damage). The triad is consistent with the
diagnosis of NSTEMI. Since the widespread use of
troponin in the investigation of chest pain, there has
been some confusion with respect to the diagnosis of
myocardial infarction. As a result, acute coronary
syndromes have been divided into three categories:
1. Classic ST elevation myocardial infarction.
2. NSTEMI (where patient may or may not have classic
chest pain associated with ST segment depression or T
wave inversion and raised troponin*).
3. Unstable angina (troponin-negative chest pain with or
without non-ST elevation ECG changes).
*Troponin T >0.05 mg/l; troponin I >0.3 mg/l.
STEMI is managed with urgent thrombolysis or primary
angioplasty if the patient presents within 12 hours and
had no contraindications to thrombolysis. Patients who
have failed thrombolysis, or have on-going myocardial
ischaemia, should have in--patient coronary angiography.
Patients with a positive exercise stress test following
STEMI should also have early coronary angiography.
The immediate prognosis in STEMI is worse than that
in NSTEMI; nevertheless over the following six months
patients with NSTEMI have a 16% mortality. Therefore
patients presenting with NSTEMI should undergo early
coronary angiography with a view to revascularization (comorbidities, quality of life and cognitive state allowing).
The differentiation between NSTEMI and unstable
angina is retrospective and based on a troponin result
performed 12 hours after admission. The management is
essentially the same, comprising of aspirin, clopidogrel,
heparin, glycoprotein IIb/IIIa receptor inhibitor, GTN
and beta-blocker therapy. Aggressive management of risk
factors for coronary artery disease is important. In
unstable angina early angiography is recommended in
patients with chest pain associated with ST segment
depression or T wave inversion.
Myocardial infarction
Myopericarditis
Dilated and hypertrophic cardiomyopathy
DC cardioversion
Tachyarrhythmias
Pulmonary embolus
Exacerbation of chronic obstructive airways disease
Chemotherapy
Chronic renal impairment
Septicaemia
Subarachnoid haemorrhage
Marathon running
Clinical Cases
249
Question 246
The following are cardiac catheter data on a 40-year-old
male with heart failure.
Chamber
Pressure
(mmHg)
15
105/40
102/50
98/36
98/60
98/60
Oxygen saturation
(%)
60
61
65
64
68
95
95
80
Question 247
A 31-year-old pregnant woman in her third trimester
complained of pain and tingling affecting her right hand,
forearm and shoulder. The symptoms were worse at
night but were relieved by shaking the hand. Her hand
felt weaker than usual. On examination there was no
wasting of the hand muscles. Abduction of the right
thumb was difficult. There was impaired touch sensation
affecting the palmar aspects of the first three digits in the
right hand. The biceps, triceps and supinator reflexes
were intact.
Question 248
A 19-year-old woman presented with lethargy and
constipation. Her appetite had increased. On
examination the heart rate was 100 beats/min and there
was a soft systolic murmur at the left lower sternal edge.
Haemoglobin
WCC
Platelets
MCV
Sodium
Potassium
Urea
Total T4
Total T3
Free T4
Free T3
TSH
11.4 g/dl
4 ! 109/l
179 ! 109/l
80 fl
138 mmol/l
3.6 mmol/l
6 mmol/l
190 nmol/l (NR 60160 nmol/l)
3.5 nmol/l (NR 1.23.1 nmol/l)
20 pmol/l (NR 2030 pmol/l)
Normal
3.5 mu/l
(NR 0.55.0 mu/l)
250
Answer 246
e. Patent ductus arteriosus.
g. Eisenmengers syndrome.
There is evidence of a right-to-left shunt after the
ascending aorta. The most likely diagnosis is a patent
ductus arteriosus allowing communication between the
aorta (just distal to the left subclavian artery usually) and
Answer 247
a. Carpal tunnel syndrome.
The patient has the classic symptoms of carpal tunnel
syndrome, which is caused by compression of the
median nerve beneath the transverse carpal ligament. It
is usually bilateral and more common in females than
males (Table).
Pregnancy is a recognized cause, presumably owing to
fluid retention. Symptoms include pain in the first three
digits of the hand that may also affect the arm and
shoulder. There is tingling and pain in the palmar aspects
of the first three digits that may be relieved by shaking
the hand. The symptoms are worse at night but may be
present in the day when carrying out actions that involve
repetitive flexion of the hand.
Clinical examination reveals reduced sensation affecting
the first three digits. There is weakness affecting the first
lumbrical muscle, opponens pollicis and abduction pollicis
brevis. Wasting of abductor pollicis brevis causes wasting
of the thenar eminence. Tinels sign (precipitation of
Pregnancy
Oral contraceptive pill
Acromegaly
Amyloidosis
Hypothyroidism
Rheumatoid arthritis
Tight plaster casts
Repetitive wrist movements
Answer 248
c. Pregnancy.
Lethargy, weight gain, constipation and increased
appetite are consistent with pregnancy in a young
woman. Raised total T3 and T4 but normal free T3 and
T 4 suggest high concentrations of thyroid binding
globulin, which are present in pregnancy. It is important
to note that high concentrations of HCG in early
pregnancy may result in subclinical hyperthyroidism since
HCG has a common beta subunit to TSH.
Clinical Cases
251
Question 249
Question 250
Question 251
A 63-year-old patient who had a cadaveric renal
transplant six months ago was admitted to the dialysis
unit with nausea, vomiting and deteriorating renal
function. He also complained of headache.
On examination he was tremulous. The heart rate was
90 beats/min and regular. The blood pressure measured
200/110 mmHg. The temperature was 37C (98.6F).
The JVP was not raised. Both heart sounds were normal.
Inspection of the fundi revealed grade II hypertensive
retinopathy. There were no focal neurological signs. The
renal graft was non-tender.
Investigations are shown.
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Chloride
131 mmol/l
5.6 mmol/l
20 mmol/l
400 "mol/l
15 mmol/l
111 mmol/l
252
Answers 249 and 250
Answer 249
b. Calcium oxalate.
Answer 250
c. High fluid intake.
Patients with Crohns disease are prone to
nephrolithiasis. The renal stones in Crohns disease are
most commonly composed of calcium oxalate, primarily
owing to enteropathic hyperoxaluria. Terminal ileal
disease is associated with reduced free fatty acid
absorption. The free fatty acids bind intraluminal free
calcium, allowing increased oxalate reabsorption.
Furthermore, the presence of bile salts in the colon
increases colonic permeability to small molecules such as
Specific management
Thiazide diuretics
Potassium citrate/thiazide diuretics (if hypercalcuria)
Thiazide diuretic
Calcium carbonate
Potassium citrate
Allopurinol or potassium citrate
Surgical removal
Penicillamine
Captopril
Tiopronin
Answer 251
b. Ciclosporin toxicity.
Deteriorating renal function (usually due to interstitial
fibrosis with chronic therapy or arteriolar vasoconstriction
in the early treatment), headache, rising BP and an
epileptic seizure are all in keeping with ciclosporin
Clinical Cases
253
Question 252
This 40-year-old male had a long history of recurrent
lower respiratory chest infection that required aggressive
treatment with intravenous antibiotics. He had a recent
appendicectomy that proved to be technically difficult.
He was a non-smoker and married with three children. A
chest X-ray performed after surgery is shown.
Question 253
A 32-year-old woman, who had recently seen her GP for
a chest infection, visited her GP again complaining of
being clumsy and dropping things. Her husband had also
noticed that her speech was slurred in the evening when
he saw her after work. There was no previous medical
history or family history of note. She was on no
medication. She appeared well and there was nothing to
find on general examination. Her pupillary reflexes, visual
fields and fundoscopy were normal. She had diplopia on
looking left and upwards to the right. All cranial nerves
were normal. Tone, power and reflexes were all normal as
were coordination and sensation.
Question 254
A 54-year-old non-insulin-dependent diabetic is seen in
the diabetic control clinic. His blood pressure is
130/80 mmHg. HbA1c measures 9.6%. The creatinine is
160 "mol/l. Urinalysis reveals protein ++ and glucose ++.
252
254
Answer 252
c. Kartageners syndrome.
The chest X-ray reveals thickened and dilated bibasal
bronchioles, consistent with bronchiectasis, which are
most prominent in the right lower lobe. Looking
carefully at the left/right annotation on the chest X-ray
one notices that the X-ray has been switched the wrong
way round (left side is on the right side). Therefore, the
patient also has dextrocardia. The difficulty with the
appendicectomy suggests that the appendix must have
been in the left iliac fossa. The combination of situs
inversus and bronchiectasis is consistent with a diagnosis
of Kartageners syndrome.
Answer 253
b. Myasthenia gravis.
The patient has evidence of fatiguability (slurred speech
in the evenings and extraocular muscle weakness) which
helps make the diagnosis. There are no neurological signs
on examining the limbs, therefore all the other options
provided are excluded. Weakness is exacerbated by
pregnancy, hypokalaemia, infection, over-treatment of
myasthenia gravis, a change in climate, emotion, exercise
and certain drugs, for example aminoglycosides.
The incidence of myasthenia gravis has two age peaks:
the second and third decades (F > M) and the sixth and
seventh decades (M > F). Acetylcholine receptor
antibodies are detectable in 90% of patients. A thymoma
Answer 254
c. Irbesartan.
The patient has evidence of overt diabetic nephropathy,
i.e. impaired renal function and frank proteinuria. Urine
dipsticks only become positive for protein once urine
protein concentration is between 0.3 and 0.5 g/day.
The UKPDS study showed that aggressive glycaemic
control prevented microvascular complications. However,
the vast majority of patients studied had either no
Clinical Cases
255
Question 255
Question 256
Question 257
A 14-year-old girl was investigated for abdominal pain.
Abdominal examination was normal.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Amylase
Serum Iron
TIBC
Urinary
coproporphyrins
10.8 g/dl
8 ! 109/l
(normal differential)
200 ! 109/l
75 fl
136 mmol/l
3.8 mmol/l
6 mmol/l
100 "mol/l
100 iu/l (NR <220 iu/l)
33 "mol/l (NR 1332 mol/l)
49 "mol/l (NR 4280 mol/l)
640 nmol/24h
(NR 50350 nmol/24h)
Question 258
A 24-year-old woman presented with severe menorrhagia.
There were several bruises on her arms and legs.
Hb
WCC
Platelets
Marrow aspirate
D-dimer
6.2 g/dl
29 ! 109/l
32 ! 109/l
Metamyelocytes
Promyelocytes ++++
Myelomonocytes and
myeloblasts
Massively elevated
256
Answers 255 and 256
Answer 255
c. Multiple sclerosis.
Answer 256
d. IV methylprednisolone.
The patient presents with sudden onset of reduced visual
acuity in one eye and fundoscopy suggests the possibility
of optic neuritis. The preceding history of transient ataxia
six months previously is highly suggestive of an underlying diagnosis of multiple sclerosis.
The diagnosis of multiple sclerosis is usually clinical
and should be considered in any patient who has
neurological episodes that are scattered in time (two or
more separate episodes) and space (two or more separate
locations) (Table). There is no single test that can
confirm the diagnosis, although the use of MRI scanning
in conjunction with clinical findings has improved
diagnostic accuracy. CSF analysis for oligoclonal bands
continues to remain useful.
Optic neuritis and all other acute episodes in multiple
sclerosis that are serious enough to cause distress or
increase limitation of activities should be treated with a
course of high-dose steroids as soon as possible after the
onset of symptoms. The therapy of choice is intravenous
or oral methyprednisolone for 35 days.
Answer 257
d. Lead poisoning.
Abdominal pain and raised serum coproporphyrin levels
are indicative of either lead poisoning or hereditary
coproporphyria. The most probable answer is lead
poisoning since lead poisoning is much more common
than hereditary coproporphyria and there is a history of
patient exposure to lead through his occupation.
Hereditary coproporphyria is inherited as an autosomal
dominant trait and is due to a partial deficiency in the
Answer 258
c. Translocation (15,17).
The blood film and coagulation profiles are consistent with
AML type 3 (promyelocytic leukaemia). AML 3 is
associated with disseminated intravascular coagulation. The
genetics of AML 3 are understood. Reciprocal translocation
of the long arms of chromosomes 15 and 17 is the basic
genetic defect. The break point on chromosome 17 has
been mapped to the retinoic acid receptor alpha (RAR-
Clinical Cases
257
Question 259
259a
259b
Question 259a
1. What information does the ECG give you with
respect to cardiac morphology?
2. Give four acquired causes and three inherited causes
for the ECG abnormalities.
Question 259b
1. List two abnormalities.
2. Suggest two possible diagnoses.
Question 260
facial hair. There was scanty pubic hair in the genital
region and his testes were small. His father and mother
were 1.83 m and 1.68 m tall, respectively.
Results of dynamic pituitary function testing with
0.2 units/kg insulin, 100 "g of LHRH and 200 mg of
TRH were as follows:
Time
(min)
Glucose
(mmol/l)
GH
mu/l
Cortisol
(nmol/l)
TSH
(mu/l)
LH
(iu/l)
FSH
(iu/l)
Testosterone
(nmol/l)
4.0
1.4
400
2.0
29
16
34
20
2.8
12.0
860
5.2
40
24
60
30
1.6
28
1270
40
1.5
32
1450
60
2.2
20
1120
34
20
60
258
Answer 259
Answer 259b
1. i. Voltage criteria for left atrial enlargement.
ii. Left ventricular hypertrophy (see explanation).
2. i. Aortic stenosis.
ii. Hypertrophic cardiomyopathy.
259c
Right atrial enlargement
Lead I
0.25 mV
0.25 mV
120 ms
Lead VI
0.1mV
Answer 259a
1. The ECG demonstrates voltage criteria for right
atrial enlargement and right ventricular hypertrophy.
2. Acquired causes include:
i. Fibrotic lung disease.
ii. Bronchiectasis.
iii. Thromboembolic pulmonary disease.
iv. Chronic obstructive airways disease.
Inherited causes:
i. Cystic fibrosis.
ii. -1 antitrypsin deficiency.
iii. Ostium secundum atrial septal defect (may be
inherited as an autosomal dominant trait).
40 ms
Answer 260
c. Recent onset of puberty.
The findings are consistent with recent onset of puberty.
The basal gonadotrophin and testosterone levels are
generally high during puberty. The patient has scanty
pubic hair and gynaecomastia, both markers of puberty.
PraderWilli and Kleinfelters syndrome are recognized
causes of primary hypogonadism; however, the high
testosterone level is against this. Testicular feminization
syndrome would be associated with a similar testosterone
and gonadotrophin level; however, patients affected with
the testicular feminization syndrome are phenotypically
female (see Answer 397). Kallmans syndrome is rare and
often inherited as an X-linked recessive trait. It is
characterized by deficient gonadotrophin production by
the pituitary, anosmia, cleft palate and colour blindness.
These patients may also have congenital renal
Clinical Cases
259
Question 261
261
Calcium
2.5 mmol/l
13 g/dl
Phosphate
1 mmol/l
9 ! 10 9/l
Albumin
40 g/l
210 ! 10 9/l
Alkaline phosphatase
100 iu/l
89 fl
Bilirubin
10 mol/l
135 mmol/l
AST
20 iu/l
4 mmol/l
ALT
25 iu/l
6 mmol/l
Chest X-ray (261)
98 mol/l
Bulky mediastinum due to lymphadenopathy (mediastinal views)
Normal
3 mu/l (normal range 0.55.0 mu/l)
110 nmol/l
60 iu/l
30 iu/l
30
4
260
Serum calcitonin
Serum glucagon
Serum VIP
Serum PTH
Serum noradrenaline
Urinary VMA
Normal
Normal
Normal
45
1.8
700
60
3
620
90
8
500
Normal
Normal
Normal
1. List two inferences you can make from the oral glucose tolerance test.
2. Comment on the insulin tolerance test.
3. Comment on the abnormal gonadotrophin levels, and give the most likely explanation.
4. Comment on the chest X-ray.
5. What is the connection between the chest X-ray and the endocrine abnormality?
120
11
400
260
Answer 261
1. The patient has diabetes mellitus and acromegaly.
The fasting blood glucose is over 6.7 mmol/l and
the 2-hour blood glucose level is 10.5 mmol/l.
Impaired glucose tolerance is diagnosed when
fasting blood glucose is above 6.7 mmol/l and the
2-hour blood glucose is under 10 mmol/l. The
resting growth hormone level of above 4 mu/l is
highly suggestive of acromegaly. In normal people,
growth hormone secretion is suppressed to below
2 mu/l with hyperglycaemia; however, in
acromegaly there is failure of growth hormone
secretion suppression and there may be a
paradoxical rise in growth hormone levels with
hyperglycaemia.
2. There is adequate hypoglycaemia (blood glucose
falls to under 2.2 mmol/l after 45 min) and there is
an appropriate rise in serum cortisol (>550 nmol/l),
suggesting adequate pituitary ACTH reserve.
3. The patient is aged 47 and has amenorrhoea. The
grossly elevated gonadotrophin reflects menopause.
The low circulating oestrogen level (lack of negative
feedback of oestrogen on the pituitary) is the
stimulus for hypersecretion of the gonadotrophins.
Question 262
A 29-year-old male living in a hostel presented with a
three-week history of reduced visual acuity and a six-week
history of watery diarrhoea. There was no history of
headaches or abdominal pain. On further questioning, he
mentioned he had a sore mouth and throat, and found it
difficult to swallow. He had not been on any medications
in the past six months.
Hb
10 g/dl
WCC
4 ! 109/l
Platelets
170 ! 109/l
Sodium
134 mmol/
Potassium
4.1 mmol/l
Urea
4 mmol/l
Creatinine
67 mol/l
Glucose
4 mmol/l
Chest X-ray
Clear
Upper gastrointestinal Oesophagitis endoscopy
Oesophageal washings (262d)
Stool microscopy (262e)
Rectal biopsy (262f)
Clinical Cases
262a
261
262b
262c
262d
262e
262f
262
Answer 262
1. CMV retinitis.
2. Oesophageal candidiasis.
3. Oral hairy leukoplakia.
4. i. Cryptosporidial infection.
ii. CMV colitis.
5. i. Ganciclovir.
ii. Paromomycin.
The patient has evidence of several AIDS-defining
conditions. The fundal appearance is consistent with
CMV retinitis, which is the most common cause of visual
impairment in these patients. The diagnosis is clinical.
Early retinal changes include narrowing of the lumen of
the retinal vessels. This is followed by vascular occlusion
and perivascular haemorrhages (red areas), resulting in
retinal ischaemia (white areas). Without therapy, the
condition progresses to bilateral blindness. Treatment is
with intravenous ganciclovir, followed by oral
maintenance therapy. CMV may also cause encephalitis,
colitis and cholangitis, all of which are best treated by the
same drug. In the gastrointestinal tract CMV is
diagnosed histologically by the demonstration of round
intranuclear inclusion bodies within epithelial cells of the
intestinal mucosa, as shown in the rectal biopsy (262f).
Oral candidiasis is common in patients with HIV and
is treated with nystatin or fluconazole. Gastric washings
in this patient reveal Candida hyphae. Oesophageal
Candida may cause severe dysphagia, but responds to the
same treatment. Hairy leukoplakia affects the lateral
borders of the tongue. Unlike Candida, it cannot be
scraped off the tongue with ease. The condition is
painless and is due to infection with EBV. Its presence is
highly suggestive of HIV infection. Acyclovir may be of
some benefit in its management.
The stool reveals evidence of Cryptosporidium, which
is the most common cause of diarrhoea in patients with
HIV infection. The diarrhoea may be transient or
persistent, and may be mild or profuse. The diagnosis is
made by staining stool with modified ZiehlNeelsen stain
(262e) to demonstrate red cysts of Cryptosporidium.
Treatment may be difficult and usually involves antidiarrhoeal agents and fluid replacement. Definitive drugs
in the management of cryptosporidial infection include
spiramycin and paromomycin.
Complications of HIV
Respiratory
Pneumocystis carinii pneumonia
CMV pneumonia
Cryptococcal pneumonia
TB (including Mycobacterium avium
intracellulare)
Histoplasmosis
Lymphoma
Kaposis sarcoma
Skin
Seborrhoeic dermatitis
Molluscum contagiosum
Folliculitis
TB
Candida infection
Tinea infection
Pityriasis versicolor
Kaposis sarcoma
Gastrointestinal
HIV enteritis
CMV colitis
Giardiasis
Cryptosporidium
Isospora belli
Salmonella enteritidis
Shigella dysentery
Candida infection
Mouth
Herpetic stomatitis
Aphthous ulcers
Kaposis sarcoma
Clinical Cases
263
Question 263
A 16-year-old Nigerian male presented to hospital with
severe pain affecting his left knee and right elbow. He
required admission to another hospital with similar pain
three years ago, and was treated with painkillers. He had
experienced milder pains at home for which he had
required paracetamol. He was one of four siblings and
had an older sister who was known to have a form of
anaemia.
Hb
WCC
Platelets
MCV
MCHC
Reticulocyte count
Blood film
10.2 g/dl
11 ! 109/l
190 ! 109/l
69 fl
29 g/dl
7.7%
Numerous target cells
and polychromasia
Sodium
135 mmol/l
Potassium
3.7 mmol/l
Urea
6 mmol/l
Aspartate aminotransferase 48 iu/l
Bilirubin
40 mol/l
Alkaline phosphatase
130 iu/l
Question 264
A 35-year-old Irish nurse returns from Baltimore and is
admitted with sharp right lower chest pain which is worse
on inspiration. The following day she develops similar
pain in the left lower chest. On examination, she has a
Hb
WCC
Platelets
ESR
Chest X-ray
Arterial gases:
pH
PaO2
PaCO2
Bicarbonate
12 g/dl
3.5 ! 109/l
300 ! 109/l
33 mm/h
Normal lung fields and
cardiac size
7.4
11.5 kPa
4.5 kPa
25 mmol/l
264
Answer 263
1. Bone infarction.
2. i. Hb electrophoresis.
ii. Family screening.
3. Sickle cell anaemia. It is also possible that he may
have another sickle syndrome such as HbSC disease
or HbS/-thalassaemia trait.
Sickle cell anaemia (HbSS) is the most common sickling
disorder and it is inherited as an autosomal recessive trait. It
is due to a point mutation in both &-globin genes, which
results in the substitution of the amino acid glutamine for
valine at position 6. Other sickling disorders include HbSC
disease (where one &-globin chain is similar to that seen in
HbSS and the other &-globin chain is similar to that seen in
HbC, another haemoglobin variant), and HbS/&thalassaemia trait. Patients with HbSC make equal quantities
of HbS and HbC, whereas those with HbS/&-thalassaemia
trait make predominantly HbS. The amino acid substitution
in HbS causes red cell sickling during deoxygenation,
leading to increased rigidity and aggregation in the microcirculation. This results in a haemolytic anaemia and episodic
tissue infarction the sickle cell crises (Table).
The sickle cell gene is spread widely throughout Africa,
some Mediterranean countries, the Middle East and parts of
India. It confers protection to malaria.
Patients with sickle cell anaemia are anaemic (Hb
610 g/dl) and have a high reticulocyte count (1020%).
The blood film demonstrates polychromasia, target cells and
variable numbers of sickle cells. In general, patients with
HbSC disease have a less severe form of anaemia, more
target cells and fewer sickle cells. They have fewer crises;
however, retinal damage, aseptic necrosis of neck of femur
and recurrent haematuria are important complications.
Pulmonary emboli may occur, particularly during and after
Answer 264
1. i. Systemic lupus erythematosus.
ii. Bornholms disease (Coxsackie virus).
2. i. Double-stranded DNA antibody.
ii. Antinuclear antibody.
iii. CRP.
iv. Serum complement.
The patient has symptoms suggestive of polyserositis
(pleurisy and pericarditis), a high temperature, a slightly
elevated ESR and a relative leucopenia. The most probable
diagnosis is SLE, although epidemic myalgia or Bornholms
syndrome due to Coxsackie virus (A or B) infection may
present in a similar fashion. The patient has returned from
Baltimore, where there may have been an epidemic of
Coxsackie virus infection. Familial Mediterranean fever is
Clinical Cases
265
Question 265
An 8-year-old male with a known history of haemophilia
A presented with a ten-hour history of pain in the left
groin, which radiated to the back. He described this as a
dull pain which was constant in nature. He was given
Factor VIII concentrate and admitted for observation;
however, the pain persisted and a few hours later was
radiating into the anterior aspect of the left thigh.
266
Answer 265
with root pain and gradual paraplegia. Muscle
haematomas may cause necrosis, but in this case the
muscle at risk is the psoas, not the quadriceps muscle.
Femoral artery thrombosis would be most unusual in a
haemophiliac, and the presentation would consist of
sudden onset of pain and paralysis of the left lower limb.
Failure to manage the bleed may be owing to a variety
of reasons, which have been listed in the items in the first
part of the question. Patients with Factor VIII antibodies
are those who are completely deficient in Factor VIII, or
have very low (<5%) levels. In this case, possible
therapeutic remedies are very high doses of Factor VIII,
purified porcine Factor VIII, Factor IX concentrates or
activated prothrombin complex (contains activated X).
An inadequate dose of Factor VIII is a very important
cause of continued bleeding. Factor VIII which has been
held at a temperature exceeding 4C (39.2F) for more
than a couple of hours is not very effective. In the past,
up to 50% of patients had CAH, and it is possible that
underlying chronic liver disease may prevent early
haemostasis owing to several other clotting factor
deficiencies.
Further useful investigations should consist of a CT
scan of the abdomen to confirm the psoas haematoma.
The APTT is an indicator of the severity of the clotting
abnormality and a good guide to adequate replacement
of Factor VIII levels. Factor VIII levels are useful in
determining the amount of Factor VIII which should be
replaced to correct the APTT. Estimation of Factor VIII
antibodies is very useful because it calls for other
therapeutic applications which have been mentioned
above. The BT is of no use because it is unchanged in
haemophilia, but is elevated in von Willebrands disease
(Table).
Clotting abnormalities
Haemophilia A
Haemophilia B
Von Willebrands disease
Vitamin K deficiency
Heparin therapy
DIC
PT
APTT
TT
BT
N
N
N
N
N
N
N
N
N*
N
()**
()**
* Can be differentiated from haemophilia A, by measuring Factor VIII and IX levels. In haemophilia A, Factor
VIII is low, and in haemophilia B, Factor IX is low.
** Increased if the platelet count is low.
Clinical Cases
Question 266
266
Question 267
A 37-year-old man was admitted to hospital with a threeday history of a generalized headache and photophobia.
He gave a five-day history of a dry cough before the onset
of headache. On examination, he was unwell. The
temperature was 37.7C (99.9F). Kernigs sign was
absent. There was no evidence of papilloedema or any
neurological deficit. There was no history of travel abroad.
He was married with two children. He was a non-smoker
and consumed 48 units of alcohol per week. The
following day his condition deteriorated. He became
drowsy and developed weakness in his lower limbs.
On examination, he was drowsy and his temperature
was 38C (100.4F). He had a left facial nerve palsy and
had failure of lateral gaze on the same side. The upper
limbs were normal. The lower limbs had diminished
power. Lower-limb reflexes were brisk. The left plantar
was upgoing and the right plantar was equivocal.
Abdominal reflexes were diminished.
Investigations are shown.
CSF analysis:
Cells
Protein
Glucose
Gram stain
EEG
267
268
Answer 266
c. Long QT syndrome (see Question 368). Brugadas
syndrome is discussed in Answer 353 and ARVC in
Answer 362.
Answer 267
a. Viral encephalomyelitis.
The most likely diagnosis is viral encephalomyelitis. There
is a prodrome of dry cough in an otherwise fit, relatively
young healthy male with no past history or history of
travel, followed by drowsiness and signs consistent with
brainstem involvement. Most cases of viral encephalitis are
self-limiting and may present as a febrile illness associated
with headache and photophobia. In a small proportion of
patients the illness is more severe and is accompanied by
progressive drowsiness, coma, seizures and focal
neurological signs, particularly affecting the brain and
spinal cord. Demyelination of the spinal cord and
brainstem is characteristic. The patient has left-sided 6th
and 7th cranial nerve palsies, which are suggestive of
pontine involvement. In addition, he has brisk lower-limb
reflexes, upgoing plantars, and absent abdominal reflexes
suggestive of spinal cord involvement. The CSF reveals a
modestly elevated WCC with a significant number of
lymphocytes and a modestly elevated protein count. The
CSF sugar content is normal, which excludes tuberculous
and bacterial meningitis. Other causes of high lymphocyte
count and elevated protein are shown in Table A. The
EEG demonstrates the characteristic slow waves seen in
viral encephalitis, although this appearance may also be
seen in metabolic encephalopathies and cortical vein
thrombosis. The most commonly implicated viruses in viral
encephalitis are measles, herpes, and influenza.
Lyme disease may also cause neurological involvement.
It is caused by the spirochaete Borrelia burghdorferi,
which is transmitted by tick bites. The initial illness (stage
1) is characterized by a fever and a typical erythematous
indurating rash at the site of the tick bite, known as
erythema chronicum migrans. The second stage of the
disease occurs between two and three weeks afterwards,
and is characterized by cardiac and neurological
involvement. Cardiac manifestations include pericarditis,
myocarditis and heart block of varying degrees.
Neurological involvement is characterized by symptoms of
meningitis, focal neurological signs including cranial nerve
palsies and a radiculopathy. There is no history of tick
bites or travel to North America; however, the history of
tick bites is not always elicited. It is only remotely possible
that the patient may have been in contact with ticks. CSF
findings include lymphocytosis and a modestly elevated
protein count (Table B). The CSF sugar is normal. The
Clinical Cases
269
Protein g/l
0.40.8
Sugar
>1/2 blood glucose
2003,000 (neutrophils)
0.52.0
TB meningitis
Raised
50500 (lymphocytes)
0.53.0
Lyme disease
Normal
Slightly raised
50500 (lymphocytes)
0.40.8
Cryptococcal
meningitis
Normal
Slightly raised
50300 (lymphocytes)
0.53.0
Usually low
Viral meningitis
or encephalitis*
Pressure
Normal
Slightly raised
* Similar findings may be seen in cerebral toxoplasmosis, leptospiral meningitis, brucellosis, Listeria meningitis.
** In partially treated bacterial meningitis there may be evidence of a pleiocytosis (presence of both lymphocytes
and neutrophils) where the predominant cells are lymphocytes. The sugar content of the CSF may be only
slightly reduced.
contraceptive pill. There is a possibility that the sudden
deterioration in the patients condition may be due to this
complication. However, CSF features are not in keeping
with bacterial or tuberculous meningitis, the prodromal
illness was short and did not seem severe, and his past
good health is against a coexisting disorder that may have
predisposed to cortical vein thrombosis.
Question 268
A 20-year-old female is admitted to hospital with a 12hour history of weakness in her arms and legs. This was
accompanied by paraesthesia in her hands and feet. Five
days before admission she experienced severe pain
between her shoulder blades, and shortly afterwards
developed blurred vision. The back pain had persisted
but was less severe on admission. There was no history of
headaches or nausea, but she had been constipated for
two days and had intermittent lower abdominal pain. At
the age of eight years she suffered a bout of viral
meningitis for which she was in hospital for a week. At
the age of 15 years she took an overdose of sleeping
tablets while her parents were undergoing a divorce. She
had enjoyed good health otherwise.
On examination, the patient was not distressed but
had an expressionless face and found it difficult to close
13 g/dl
7 ! 109/l
300 ! 109/l
Normal
270
Answer 268
1. a. Forced vital capacity.
h. Arterial blood gases.
2. e. GuillainBarr syndrome.
The patient presents with generalized muscle weakness
following severe pain in the mid-thoracic area. She also
complained of diplopia before the weakness, and has
evidence of papilloedema and generalized motor
neuropathy on examination. The patient has no sensory
level to suggest spinal cord compression, therefore the
constipation and the palpable bladder indicate an
underlying autonomic neuropathy. The diagnosis which fits
best with the symptoms and signs is GuillainBarr
syndrome or post-infectious polyneuropathy.
GuillainBarr syndrome is a polyneuropathy which may
develop over a few days or even a few weeks after an
infectious illness, usually involving the respiratory tract.
Enterovirus, EBV, Mycoplasma, Campylobacter jejuni and
Chlamydia have been implicated, but the condition may
occur following surgical conditions. In the majority of cases
the underlying cause is never identified. The onset is often
heralded by severe lumbar or interscapular pain, as in this
case, and is followed by proximal, distal or generalized
muscle weakness due to a motor neuropathy; however,
some sensory loss is also present. Sensory loss commonly
manifests as distal paraesthesiae and loss of vibration and
positional sensation. The latter results in a sensory ataxia.
GuillainBarr syndrome
Spinal cord tumour causing spinal block (Froins
syndrome)
Acoustic neuroma
Lead encephalopathy
Subacute sclerosing panencephalopathy
Clinical Cases
Question 269
271
269a
F
Affected male
Unaffected male*
Affected female
Unaffected female*
Question 270
The following are cardiac catheter data from an 18-yearold female with breathlessness on exertion.
Chamber
Superior vena cava
Inferior vena cava
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left ventricle
Aorta
Pressure
(mmHg)
a = 14
v = 20
92/20
94/42
a = 14
v = 22
106/20
100/70
Oxygen saturation
(%)
68
67
(high) 68
(mid) 69
(low) 83
83
82
96
96
272
Answer 269
1. a. X-linked
recessive.
2. b. Haemophilia A.
3. e. 100%.
4. a. 0%.
269b
5. a. 0%.
6. e. 100%.
7. b. 25%.
8. a. 0%.
9. b. 25%.
II
III
100% chance of
being a carrier because
her sons are affected
Answer 270
270
2. i. Partial RBBB.
ii. Right ventricular hypertrophy.
iii. Left atrial enlargement.
iv. Right atrial enlargement.
v. Left axis deviation. The ECG in ostium primum
defects characteristically reveals partial or
complete RBBB and left axis deviation (270). In
contrast, patients with ostium secundum defects
have partial RBBB and right axis deviation.
3. There is a step up in the oxygen saturation in the
low right atrium, suggesting an ostium primum
ASD. The defect is associated with mitral and
tricuspid ring defects, causing both mitral and
tricuspid regurgitation.
Clinical Cases
273
Question 271
271a
271b
271c
271d
Hb
AST
WCC
Bilirubin
Platelets
Alkaline phosphatase
MCV
Albumin
U&E
Chest X-ray
ECG
Gastroscopy
11 g/dl
60 iu/l
5 ! 109/l
11 mol/l
160 ! 109/l
112 iu/l
105 fl
43 g/l
Normal
Kyphoscoliosis
Clear lung fields
Normal heart size
Normal
Gastro-oesophagitis
274
Answer 271
1. Homocystinuria.
2. i. Phenytoin therapy. Phenytoin is thought to
interfere with folate absorption. Other
anticonvulsants causing folate deficiency include
primidone and barbiturate therapy.
ii. The conversion of homocystine to methionine
requires large amounts of the enzyme 5-methyl
tetrahydrofolate methyltransferase, which utilizes
folate as a cofactor. During the enzyme reaction
some of the folate is degraded, and folate
deficiency can occur.
3. The urine gives a positive nitroprusside test. Raised
levels of plasma methionine and homocystine are
more reliable because the nitroprusside test is also
positive in cystinuria.
4. Autosomal recessive inheritance. The gene is
located on chromosome 21.
The chest pain due to oesophagitis has no connection
with the underlying diagnosis. The examiner expects the
reader to pick up on the skeletal, ocular and neurological
abnormalities to come to a diagnosis of homocystinuria.
Homocystinuria is due to cystathionine deficiency. As
a result, there is accumulation of homocysteine which in
turn is oxidized to homocystine. There is no production
of cystine. Plasma and urinary levels of homocystine are
elevated. Homocystine is thought to affect cross-linking
of collagen, leading to skeletal, ocular, neurological and
vascular abnormalities.
Skeletal: The patients have the same skeletal
abnormalities as in Marfans syndrome. These include
tallness, kyphoscoliosis, arachnodactyly, high-arched
palate, pectus excavatum and flat feet. The ligaments are
lax, and muscular development weak. Osteoporosis is a
Clinical Cases
275
Question 272
A 59-year-old farmer was referred to a chest unit with an 18month history of progressive breathlessness. Over the past
four years, he had noticed a dry cough in the afternoons and
evenings. His effort tolerance three years previously was very
good, allowing him to work on the farm for almost 12 hours
per day. Since then he had resolved to work only two days a
week owing to fatigue and breathlessness, and had asked
both his sons to take over his farm.
His GP diagnosed asthma, but his condition had
continued to deteriorate despite the use of steroid and
salbutamol inhalers. He was now breathless after walking
just 200 metres. He was a non-smoker. There was no
family history of lung disease. He had never worked with
asbestos, and did not keep pets.
On examination, he was cyanosed and tachypnoeic.
He had evidence of early clubbing. The JVP was not
raised, and heart sounds were normal. On auscultation of
the lung fields there were bilateral fine end-inspiratory
crackles in both lungs.
Investigations are shown.
Hb
WCC
Platelets
ESR
Chest X-ray
FEV1 (%)
FVC (%)
FEV1/FVC (%)
TLC (%)
KCO (%)
12 g/dl
5 ! 109/l
400 ! 109/l
54 mm/h
Diffuse reticulonodular
shadowing in both apices and
midzones
50
Blood gases on air:
52
pH
7.45
89
PaCO2
3.5 kPa
56
pO2
6.4 kPa
60
Bicarbonate 22 mmol/l
Question 273
A 78-year-old male presented with a several weeks
history of weakness, lethargy, weight loss and vomiting.
On examination, the blood pressure (standing) was
80/50 mmHg.
Blood results are shown.
Sodium
Potassium
Urea
Bicarbonate
Blood glucose
124 mmol/l
4.9 mmol/l
15 mmol/l
15 mmol/l
4.0 mmol/l
Question 274
A 51-year-old dentist presented to his GP because he had
difficulty lifting his right arm for over one week. For the
past few days he could not hold the razor to his face with
his right arm while shaving. About two weeks previously
he received a hepatitis B booster vaccine which was
associated with pain over his deltoid and shoulder region
for almost 48 hours.
On examination there was wasting over the deltoid
region. There was reduced power on abduction, flexion
and internal rotation of the right arm and flexion of the
right elbow. The right biceps and supinator reflexes were
absent. All other examinations were normal.
What is the diagnosis?
a. Radiculopathy secondary to Lyme disease.
b. Neuralgic amyotrophy.
Hb
WCC
Platelets
ESR
Biochemistry
X-rays of chest and
cervical spine
14.3 g/dl
5 ! 109/l
199 ! 109/l
11 mm/h
Normal
Normal
c. Syringomyelia.
d. Cervical myelopathy.
e. Motor neurone disease.
276
Answer 272
1. Extrinsic allergic alveolitis.
2. i. Precipitins from Micropolyspora faenii.
ii. High-resolution CT scan.
iii. Bronchoalveolar lavage.
iv. Bronchoscopy with transbronchial lung biopsy.
Extrinsic allergic alveolitis is a cell-mediated allergic
reaction that occurs in response to inhalation of a variety
of agents. It is characterized by interstitial inflammation
and progressive lung fibrosis. Patients typically present
with fever and dyspnoea several hours after inhaling the
antigen. In this case, the farmer who has been working in
the morning will not develop symptoms until late
afternoon. During the reaction the patient will be
tachypnoeic, febrile and have widespread coarse crackles
throughout the lung. Continuing exposure and
inflammation results in interstitial fibrosis, leading to
progressive dyspnoea and functional limitation. The chest
X-ray reveals nodular shadows in the upper zones that
eventually involve the mid-zones. In severe cases the lung
Answer 273
i. Addisons disease/primary hypoadrenalism.
ii. Diuretic therapy.
iii. Salt-losing nephritis.
The combination of lethargy, weight loss, vomiting,
hypotension, hyponatraemia and hyperkalaemia is
suggestive of Addisons disease. Addisons disease is caused
by destruction of the adrenal glands, resulting in deficiency
of glucocorticoid and mineralocorticoid hormones. The
most common cause of Addisons disease is auto-immune
adrenalitis. Other causes are listed (Table). The condition
has an insidious presentation in the majority of cases, but
may present as a crisis. Lethargy, anorexia, nausea,
vomiting, abdominal pain and symptoms of postural
hypotension are common. Some patients are misdiagnosed
as having depression. In the elderly, the condition may
present as a confusional state. On examination, there may
be evidence of pigmentation which is prominent in skin
creases, scars and the buccal mucosa. The supine blood
pressure may be normal, but there is a marked drop in
systolic pressure on standing (>25 mmHg).
Acute Addisonian crisis is characterized by coma,
profound hypotension and hypoglycaemia. The
electrolytes are usually abnormal (as above) but may also
be normal. Acute adrenal failure or Addisonian crisis is a
medical emergency which should be aggressively treated
with intravenous hydrocortisone and saline. Dextrose is
used in hypoglycaemic cases.
Clinical Cases
277
Answer 274
b. Neuralgic amyotrophy.
The diagnosis is neuralgic amyotrophy. This is an
inflammatory process affecting the roots of C5 and C6
and occasionally C7. It usually follows an infective illness
or trauma to the deltoid region. It is preceded by pain
over the shoulder and arm followed by weakness and
wasting of the muscles supplied by the affected roots.
Spontaneous recovery is usual but may take several
months. The differential diagnosis is cervical cord
Question 275
A 28-year-old obese female was admitted to the ward for
further investigation after presenting with lethargy. She
did not give any further history of significance. Her blood
pressure in clinic was 128/85 mmHg. Blood results are
shown.
After these blood results, the patient was questioned
further about her bowel habit and medication. She denied
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Renin
135 mmol/l
2.2 mmol/l
7.3 mmol/l
60 mol/l
36 mmol/l
1,500 pg/ml/h
(NR [lying supine]
3001,300 pg/ml/h)
24-h urine output
500 ml
24-h urine potassium 10 mmol/l
278
Answer 275
1. The patient has a hypokalaemic alkalosis and an
appropriate hypokaluria. Patients with a serum
potassium of <3.5 mmol/l conserve potassium and
excrete <20 mmol/l of potassium in the urine. The
urea is modestly elevated, as is her serum renin,
both of which suggest hypoperfusion of the afferent
glomerular vessels. This may occur in dehydration,
shock, glomerular and renal parenchymal disease.
However, in primary renal disease the serum
creatinine is also elevated, and in this history the
blood pressure is not suggestive of shock.
275
Malignant hypertension
Renal artery stenosis
Diuretic therapy
Increased
Decreased
?Renin concentration
Yes
?Hypertensive
>20 mmol/l
Serum
potassium
<3.5mmol/l
Check
urinary
potassium
Conns syndrome
Cushings syndrome
Liddles syndrome
No
Check bicarbonate
<20 mmol/l
RTA
Gastrointestinal
losses:
diarrhoea
vomiting
reduced intake (starvation)
Diuretics
Carbenoloxone
Aminoglycosides
Barrters syndrome
Clinical Cases
279
*In 11--hydroxylase deficiency, the aldosterone levels are low; however, there is excessive production of
deoxycorticosterone which has strong mineralocorticoid effects and causes both hypertension and hypokalaemia.
Question 276
A 17-year-old female was referred to the gynaecologist
with primary amenorrhoea. She had been relatively well
throughout her life. Her mother was concerned that she
was not gaining any weight, despite eating well. She had
been investigated for diabetes by the GP and was found
to have a normal blood glucose. Apart from complaining
9.8 g/dl
5 ! 109/l
190 ! 109/l
104 fl
Target cells, anisocytosis,
macrocytes, poikilocytosis
Sodium
137 mmol/l
Potassium
4.1 mmol/l
Urea
3 mmol/l
Creatinine
78 mol/l
Calcium
2.0 mmol/l
Phosphate
0.75 mmol/l
Albumin
37 g/l
AST
20 iu/l
Alkaline phosphatase 300 iu/l
Bilirubin
11 mol/l
Thyroxine
100 nmol/l
TSH
2.0 mu/l
Hb
WCC
Platelets
MCV
Blood film
280
Answer 276
1. Underweight owing to malabsorption
(malabsorption syndrome).
2. Coeliac disease.
3. i. Osteomalacia.
ii. Patient in a growth spurt.
4. i. Duodenal biopsy or jejunal biopsy.
ii. Antiendomyosium, antigliadin or antireticulin
antibodies.
The patient is short for her age. She has a macrocytic
anaemia. The blood film reveals hypochromasia,
macrocytosis and target cells, suggesting either isolated
folate (or possibly B12) deficiency or combined iron and
folate deficiency. The bone biochemistry is in keeping
with vitamin D deficiency. The slightly low albumin level
is indicative of poor nutritional status in this context.
Failure to grow, or weight loss despite a normal appetite,
plus a combination of nutritional deficiencies should
always raise the question of a malabsorption syndrome.
The lack of secondary sexual characteristics and delayed
menstruation in this patient may be explained by the fact
that she has yet to reach puberty, either because of a
constitutional delay or because puberty has been delayed
owing to a malabsorption syndrome.
Malabsorption syndromes are a recognized cause of
primary and secondary amenorrhoea in girls and young
women, predominantly as a result of poor nutrition
causing profound weight loss. Readers may fall into the
trap of diagnosing hypopituitarism in this case, given the
short stature and absent secondary sexual characteristics.
However, the diagnosis of hypopituitarism fails to explain
the normal thyroid function tests and the abnormal bone
biochemistry. Anaemia is a recognized feature of
hypopituitarism. It is usually normochromic normocytic,
but may be macro- or microcytic.
A variety of conditions produce malabsorption
syndromes (Table), but the most common cause by far in
the Western world is coeliac disease. This affects 1 in
2,000 patients in the UK, and is even more common in
Ireland, affecting 1 in 300. The disorder is characterized
by total villous atrophy in the small intestine as a result of
ingestion of gluten-containing food. The majority (80%)
of patients have the haplotype HLA A1, B8, DR7 or
DQW2, suggesting a genetic basis. There is 30%
disconcordance among identical twins, which suggests
that non-genetic factors may also be involved. Small
bowel injury occurs as a result of gluten ingestion. Gluten
is a high-molecular weight compound which contains
various gliadins. #-gliadin damages small bowel mucosa
276
Clinical Cases
281
Additional comments
Coeliac disease
Dermatitis herpetiformis
Bacterial overgrowth
Low B12 but normal or high serum folate. Previous gastric surgery (Billroth
II), jejunal diverticuli
Giardiasis
Whipples disease
Tropical sprue
Radiation enteritis
Crohns disease
Hypogammaglobulinaemia
ZollingerEllison syndrome
Intestinal lymphangiectasia
Question 277
A 30-year-old sailor was admitted to the navy hospital
with a seven-day history of increasing confusion, malaise,
fever and reduced visual acuity in his left eye. Two weeks
previously he had developed weakness affecting his left
arm and left lower limb. He had a past history of
Hodgkins lymphoma which was successfully treated with
chemotherapy five years ago.
On examination, he was confused. His temperature
was 40C (104F). There was evidence of cervical
lymphadenopathy on palpation of the neck. On
examination of the fundi, there was widespread retinal
scarring in both eyes, the right eye being more affected
than the left. There was no obvious papilloedema. The
left-sided limbs demonstrated marked weakness.
Investigations are shown.
Hb
WCC
Platelets
ESR
EEG
11 g/dl
6 ! 109/l
190 ! 109/l
80 mm/h
Diffuse slow wave activity
282
Answer 277
1. i. Cerebral toxoplasmosis.
ii. Tuberculous meningitis.
iii. Cryptococcal meningitis.
iv. Cerebral lymphoma.
2. i. CT scan brain (277). Multiple ring-enhancing
lesions may suggest cerebral toxoplasmosis, TB
abscesses or lymphoma.
ii. CSF IgM levels or SabinFeldman dye test for
Toxoplasma gondii.
iii. CSF staining with auramine or ZiehlNeelsen
stain may detect TB and staining with Indian ink
will identify cryptococcal meningitis.
iv. Brain biopsy.
3. i. Pyrimethamine and sulphadiazine for
toxoplasmosis.
ii. Ansamycin and clofazimine for TB (particularly
effective for atypical TB).
iii. Amphotericin for cryptococcal meningitis.
iv. Radiotherapy to the skull for cerebral lymphoma.
The patient is a sailor. In MRCP and similar
examinations questions, sailors are associated with a high
level of promiscuity and high risk for HIV infection. This
patient is confused, has focal neurological signs, and
evidence of bilateral scarring of the retina. The confusion
may be the manifestation of an encephalitis, meningitis,
cerebral abscess or cerebral metastases in the context of
the question.
Focal neurological signs may be caused by all of the
above. The presence of chorioretinitis and focal
neurological signs favours the diagnosis of cerebral
toxoplasmosis, TB or cryptococcal meningitis. Cerebral
lymphoma per se does not cause chorioretinitis; however,
it is possible that the patient has both cerebral lymphoma
and a CSF infection causing chorioretinitis. Other
recognized causes of chorioretinitis in patients with HIV
include CMV and syphilitic infection. The slow waves on
the EEG are suggestive of an encephalitic process, which
may be part of the cerebral effect of the HIV itself, or as a
result of opportunistic infections such as CMV, herpes
virus, toxoplasmosis, atypical mycobacteria or
lymphomatous infiltration.
The diagnosis and management for each condition are
outlined above. It may be difficult to differentiate
between cerebral lymphoma and toxoplasmosis in this
277
HIV dementia
Progressive multifocal leucoencephalopathy
Tuberculous meningitis/tuberculoma
Toxoplasmosis
Lymphoma
Herpes encephalitis
Peripheral neuropathy
Clinical Cases
283
Question 278
A 15-year-old girl presented with a 48-hour history of a
sore throat and dark urine. On examination she appeared
relatively well at rest. The blood pressure was
100/60 mmHg.
HB
WCC
Platelets
Sodium
Potassium
Urea
Serum creatinine
Urinalysis
12.5 g/dl
11 ! 109/l
240 ! 109/l
136 mmol/l
4.1 mmol/l
4.2 mmol/l
80 "mol/l
Microscopic haematuria
Question 279
A 55-year-old man was seen by a respiratory physician for
daytime somnolence. According to his wife he snored
loudly in his sleep. He was a life-long heavy smoker. He
7.35
7.0 kPa
8.2 kPa
35 mmol/l
85%
45% predicted
55% predicted
50%
O2 sat (%)
100%
80%
60%
4
Time (h)
284
Answer 278
e. None of the above.
Causes of haematuria after an upper respiratory
tract infection include IgA nephropathy, poststreptococcal glomerulonephritis and non-specific
mesangioproliferative glomerulonephritis. IgA
nephropathy is probably the most common cause of
glomerulonephritis after a URTI. Patients present with
recurrent episodes of gross haematuria one to three days
after a URTI. The haematuria resolves within a few days.
Some patients develop acute renal failure. The serum IgA
may be raised in 50% of cases but there are no other
specific auto-antibodies to help make the diagnosis.
Post-streptococcal glomerulonephritis is induced by
infection with specific strains of group A, -haemolytic
streptococci (such as type 12 and type 49). This can
occur in sporadic cases or during an epidemic. The
clinical presentation can vary from asymptomatic,
microscopic haematuria to the full-blown acute nephritic
Post Strep
GMN
IgA
nephropathy
Onset of
haematuria
10 days after
sore throat
Recurrent
haematuria
Rare
Common
Throat culture
Positive
Negative
ASO titre
Positive
Negative
Haematuria after
6 months
Rare
Common
Answer 279
c. Nocturnal continuous positive-pressure airway
ventilation.
The patient has features of obstructive sleep apnoea. He
snores and has daytime somnolence. He also appears to
be overweight. The sleep study shows marked oxygen
desaturations throughout the night. These desaturations
represent apnoeic episodes due to airway obstruction.
The fact that he also has respiratory failure suggests that
he must also have underlying parenchymal lung disease,
since pure obstructive sleep apnoea syndrome does not
usually cause respiratory failure unless the patient has low
tidal volumes due to gross obesity, as seen in the
Pickwickian syndrome.
Obstructive sleep apnoea is usually due to an
abnormality in the size or collapsibility of the pharynx.
During sleep there is a combination of factors (reduced
tone input into the upper airways, diminished reflexes to
Clinical Cases
285
Question 280
280
Question 281
A 62-year-old asymptomatic female had the following
thyroid function tests as part of a health screen. She was
not taking any medication and had always enjoyed good
health:
Serum T4 20 iu/l
Serum TSH 8 iu/l
Antithyroid myoperoxidase antibodies: absent
Question 282
A 64-year-old male presented with reduced visual acuity.
He had a long history of hypertension.
282
286
Answer 280
c. IV acyclovir.
Herpes simplex encephalitis is most usually due to HSV 1
and presents with headache, fever and drowsiness. The
virus may complicate HSV infecting the oropharyngeal
area or may be due to reactivation of latent virus in the
CNS. It affects the inferior aspects of the frontal lobes and
the medial aspects of the temporal lobes. Olfactory and
gustatory hallucinations and impairment of memory are
Answer 281
b. No treatment. Repeat thyroid function tests in
six months.
Yes
No
Treat
TSH >14
Yes
No
Treat
Thyroid MPO
Antibodies
Yes
No
Treat
Observe
Answer 282
e. Papilloedema.
The patient had blurred disc margins with a few
haemorrhages around the disc. The diagnosis is
papilloedema, which is a feature of raised intracranial
pressure. Causes of papilloedema are tabulated.
Causes of papilloedema
Clinical Cases
287
Question 283
A 62-year-old female with a two-year history of noninsulin-dependent diabetes mellitus was admitted with
nausea and vomiting. Her diabetes was usually well
controlled on a combination of chlorpropamide 500 mg
and metformin 500 mg bd. One week previously she was
seen by her GP with general malaise and noted to have a
BM stix reading of 19 mmol/l, and the dose of
metformin was doubled.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Chloride
Blood sugar
Arterial blood gases:
pH
PaCO2
PaO2
HCO3
Urinalysis:
Protein + 1
Glucose + 1
15.2 g/dl
16.4 ! 109/l
284 ! 109/l
134 mmol/l
5.0 mmol/l
30.5 mmol/l
160 "mol/l
106 mmol/l
9 mmol/
7.3
2.6 kPa
9.6 kPa
11 mmol/l
Blood negative
Ketones negative
Question 284
A 39-year-old woman with depression presented with
nausea, vomiting, tremor and convulsions.
Sodium
Potassium
Urea
TSH
149 mmol/l
3.9 mmol/l
18 mmol/l
14 mu/l
Question 285
A 32-year-old woman had had persistently raised BP
measurements over the past six months. Her systolic blood
pressure readings had ranged from 158 to 170 mmHg and
the diastolic blood pressure readings had ranged between
90 and 98 mmHg. She was asymptomatic. She was not on
any medications (including the oral contraceptive pill).
There was no past medical history of note or any family
history of hypertension. Physical examination did not reveal
any abnormalities other than a BP reading of
160/96 mmHg. Blood urea and electrolytes were normal.
288
Answer 283
c. Lactic acidosis secondary to sepsis.
The patient has features of septicaemia and a metabolic
acidosis. Overproduction of lactic acid secondary to
diminished organ perfusion as a result of hypotension is
the most probable cause of the acidosis. Lactic acidosis
usually occurs in states where there is increased pyruvate
production due to excessive anaerobic metabolism, for
example in shock states, excessive exercise, grand mal
seizures, cyanide toxicity, and carbon monoxide
poisoning. Renal failure and liver disease cause lactic
acidosis primarily owing to decreased utilization of the
substrate. Biguanide drugs and malignancy cause lactic
acidosis but the mechanisms by which acidosis occurs are
unclear (Table).
The diagnosis can be confirmed by measuring the
plasma lactate concentration. Concurrent treatment with
metformin is probably contributing to the lactic acidosis.
Answer 284
a. Lithium toxicity.
The patient has a history of depression therefore it is
possible that her presentation is secondary to drug
overdose. Overdose with neuroleptic agents, tricyclic
antidepressant drugs or lithium may present with a
reduced conscious level and convulsions. However, the
biochemistry in this case is highly suggestive of lithium
overdose. The raised serum sodium and urea indicate
severe water loss, as may occur in diabetes insipidus.
Lithium is a recognized cause of nephrogenic diabetes
insipidus. The patient also has biochemical evidence of
hypothyroidism. Chronic use also interferes with iodine
uptake in the thyroid and may result in hypothyroidism.
Answer 285
a. Essential hypertension.
The patient is relatively young but does not have
symptoms to suggest a secondary cause such as
headaches, hyperhidrosis, palpitation or nocturia. She has
not been described to be cushingoid and the absence of
Clinical Cases
289
Question 286
A 29-year-old male with Marfans syndrome had a
prolonged stay in hospital following a subarachnoid
haemorrhage, which rendered him with a residual left
hemiparesis. A right posterior communicating artery
aneurysm was clipped. On discharge the patient had
normal speech and was able to carry out basic domestic
tasks. During his hospital stay he had been made
redundant from his job as a postman. Following
discharge he had been placed in a warden-controlled flat.
His friends had seen very little of him for the past month.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
HCO3
Glucose
ECG
CXR
CT scan brain
14 g/dl
12 ! 109/l
175 ! 109/l
136 mmol/l
4.6 mmol/l
6.0 mmol/l
107 "mol/l
18 mmol/l
6.1 mmol/l
Sinus tachycardia;
QRS duration 110 msec
Cardiac size normal.
Normal lung fields
Old left-sided infarction
Question 287
A 75-year-old woman was admitted with an anterior
myocardial infarction for which she received
thrombolysis. Within 6 hours of admission she became
confused. The blood pressure was 80/36 mmHg. The
JVP was raised. Both heart sounds were normal and there
was an added third heart sound; there were no audible
murmurs. Auscultation of the chest revealed fine crackles
in the mid- and lower-zones in both lungs.
Subsequent investigations were as follows:
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Glucose
Chest X-ray
ECG
Echocardiography
12 g/dl
15 ! 109/l
200 ! 109/l
136 mmol/l
3.9 mmol/l
17 mmol/l
140 "mol/l
16 mmol/l
Bilateral alveolar shadows and small bilateral pleural effusions
Sinus tachycardia; ST elevation and q waves in V1V6
Dilated left ventricle with akinetic anterior wall and apex. No evidence of VSD.
Functional mitral regurgitation. No pericardial effusion
290
Answer 286
d. Ventricular arrhythmias.
The patient has features consistent with the diagnosis of
tricyclic antidepressant overdose. Ventricular
arrhythmias are the most common cause of death in
TCAD overdose.
Intravenous sodium bicarbonate is the single most
effective intervention for the management of TCAD
cardiovascular toxicity. This agent can reverse QRS
prolongation, ventricular arrhythmias and hypotension.
Because acidosis aggravates TCAD toxicity, the
beneficial action of sodium bicarbonate may be partly
due to correction of acidosis. It is clear, however, that
sodium bicarbonate administration is effective even
when the arterial pH is normal.
Answer 287
e. Early invasive coronary revascularization.
The patient has hypotension, oliguria, raised JVP and
pulmonary oedema following an extensive anterior
myocardial infarction. Clinically she has evidence of
cardiogenic shock, which is associated with a poor
prognosis (5080% mortality within 48 hours). In the
context of the clinical circumstances, the differential
diagnosis is between severe left ventricular dysfunction
due to loss of a large amount of myocardium, acute
VSD, papillary muscle rupture causing severe mitral
regurgitation or cardiac tamponade. The patient does
not have any obvious murmurs but the echocardiogram
proves useful in resolving the cause of cardiogenic
shock. Echocardiography is an important investigative
tool in a patient with cardiogenic shock and should be
employed whenever possible.
Clinical Cases
291
Question 288
A 17-year-old male presented with blurring of vision
followed by total loss of vision in the left eye. A few days
later he developed total blindness in the other eye. There
were no other neurological symptoms. There was no past
medical history of significance or any history of alcohol
abuse. The patient was not taking any medications. He
had a maternal uncle who had become blind before the
age of 18 years. On examination there was evidence of
bilateral optic atrophy and a mild tremor.
Investigations are shown.
FBC
U&E
Liver function
Vitamin B screen
Serum lead
CT scan brain
CSF analysis
Normal
Normal
Normal
Normal
Not elevated
Normal
Normal
Question 289
A patient was brought into the Accident and Emergency
Department in ventricular fibrillation. After prolonged
resuscitation he was admitted to the Intensive Care Unit
and developed oliguric renal failure. Serum and urine
electrolytes were as follows:
Serum electrolytes
Urine electrolytes
Sodium
Potassium
Urea
Creatinine
Osmolality
Sodium
Potassium
Urea
Creatinine
Osmolality
132 mmol/l
5 mmol/l
30 mmol/l
400 "mol/l
320 mOsmol
90 mmol/l
30 mmol/l
120 mmol/l
7 "mol/l
300 mOsmol
Question 290
A 70-year-old patient was admitted in a drowsy state after
being found collapsed by his neighbour. On admission
the Glasgow coma score was 9. A CT scan (290) of the
brain was performed as an emergency.
290
292
Answer 288
d. Lebers hereditary optic neuropathy.
This young male presents with bilateral blindness in a
relatively short space of time. There are no obvious
acquired precipitating factors such as drugs or toxins.
The patient does not have diabetes and has normal B12
levels. He does not have any symptoms or other
indications to suggest an ischaemic optic neuropathy.
Optic neuropathy is a common feature of multiple
sclerosis but it is usually unilateral. The presence of
bilateral optic neuropathy should raise the possibility of a
toxic neuropathy or the rarer Lebers hereditary optic
neuropathy.
The family history of premature blindness in a
maternal uncle indicates a hereditary aetiology and
provides a vital clue to the underlying diagnosis. Lebers
hereditary optic neuropathy is an inherited disorder of
mitochondrial DNA encoding the electron transport
Answer 289
e. Increased urinary sodium excretion.
g. Urine osmolality:plasma osmolality 1:1.1.
Acute tubular necrosis is caused by renal ischaemia and
may be precipitated by a variety of insults including
hypovolaemia and septicaemia (causing reduced renal
Pre-renal failure
Low
>500
1.5:1
>20:1
<20 mmol/l
ATN
Low
<350
1.1:1
<20:1
>50 mmol/l
Answer 290
d. Subdural haematoma.
Clinical Cases
293
Question 291
A 68-year-old male was brought into the Accident and
Emergency Department with severe chest pain and an
ECG consistent with a recent anterior myocardial
infarction. According to his wife he had been
experiencing pain for three days but over the previous
three hours the pain had become very intense. He was
diabetic. On arrival at hospital he received IV
tenectoplase. Two hours after thrombolysis he dropped
his blood pressure and became very breathless. On
examination the heart rate was 120 beats/min and
regular. The blood pressure was 80 mmHg systolic.
Auscultation over the precordium revealed a pansystolic
Question 292
A 44-year-old male presented to his GP with a two-day
history of severe boring intermittent pain just below the
supraorbital ridge of the right eye. The pain had awoken
the patient from his sleep in the early hours of the
morning and lasted 3 hours before subsiding. The pain
recurred again in the afternoon and persisted for 4 hours
despite the patient having taken paracetamol. In 48
hours he had experienced five episodes of similar pain.
The patient had also noticed that he had a blocked nose
and therefore made a self-diagnosis of sinusitis. He
recalled having two similar episodes of pain two and four
months previously that he attributed to sinusitis and
treated himself with steam inhalations for four days. On
examination the patient was distressed with pain. His
right eye was red and watering. He had a partial ptosis
and miosis affecting the right eye. His blood pressure was
160/90 mmHg. All other physical examination was
normal.
Question 293
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
AST
Alkaline phosphatase
Albumin
Calcium
Phosphate
Glucose
HbA1c
10 g/dl
5 ! 109/l
200 ! 109/l
12 mm/h
135 mmol/l
3.6 mmol/l
2 mmol/l
21 iu/l
160 iu/l
37 g/l
2.0 mmo/l
0.7 mmol/
8 mmol/l
7.2%
294
Answer 291
b. Transthoracic echocardiogram.
The patient has developed severe pulmonary oedema after
a myocardial infarction. He also has a pansystolic murmur,
indicating that he may have mitral regurgitation due to
papillary muscle rupture or a ventricular septal defect.
Echocardiography would be the most practical
method of differentiating between the possibilities. As
the patient is so unstable, a transthoracic echocardiogram
is preferable to transoesophageal echocardiogram. In
general, transthoracic echo is better at visualizing a VSD
than transoesophageal echocardiogram; however, the
latter is superior in the diagnosis of papillary muscle
rupture. The indications for transoesophagel echo cardiography in routine clinical practice are listed in the
table below. SwanGanz right heart catheterization may
Answer 292
1. c. Migrainous neuralgia.
2. d. IM sumatriptan.
e. High-concentration inhaled oxygen.
The features are typical of migrainous neuralgia (Table).
High-concentration inhaled oxygen (1012 l/min) and
the triptan drugs are very effective at aborting an acute
attack. Verapamil is the drug of choice at preventing
frequent recurrence, although lithium, methysergide,
sodium valproate, ergotamine and prednisolone are all
useful therapies in this respect. Methysergide is no longer
used owing to its association with retroperitoneal
fibrosis.
Answer 293
c. Coeliac disease.
The commonest cause of weight loss in a patient with
insulin-dependent diabetes is poor glycaemic control.
The HbA1c of 7.2% is not suggestive of recent poor
control. Furthermore the calcium level is at the lower
limit of normal, the phosphate is low and the alkaline
Clinical Cases
295
Question 294
Hb
WCC
Neutrophils
Lymphocytes
Eosinophils
Basophils
Monocytes
Platelets
ESR
Sodium
Potassium
Chloride
Bicarbonate
Urea
Creatinine
AST
ALT
Alkaline phosphatase
Glucose
Urine output
Urinary microscopy
ECG
10 g/dl
3.5 ! 109/l
1.1 ! 109/l
2.4 ! 109/l
0.03 ! 109/l
0 ! 109/l
0.1 ! 109/l
140 ! 109/l
100 mm/h
130 mmol/l
5.5 mmol/l
87 mmol/l
24 mmol/l
9 mmol/l
133 "mol/l
60 iu/l
90 iu/l
110 iu/l
6 mmol/l
45 ml/h
NAD
Sinus tachycardia
Question 295
A 36-year-old nurse with two children, aged 8 and 14 years
of age, went to see her GP, concerned that her maternal
aunt had recently had a pulmonary embolus and was
heterozygous for the Factor V Leiden mutation. The patient
was taking the combined oral contraceptive pill and was
adamant that she did not want any more children. Her own
mother had never had thrombotic tendencies and had
normal pregnancies except for varicose veins during her
second pregnancy. The patient herself had never experienced
any thrombotic episodes and was a non-smoker.
Question 296
A 62-year-old male presented with acute dyspnoea. He
had clinical and radiological evidence of pulmonary
oedema that responded well to intravenous nitrates and
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Echocardiography
Coronary angiography
13 g/dl
8 ! 109/l
200 ! 109/l
138 mmol/l
4.2 mmol/l
6 mmol/l
100 "mol/l
Dilated left ventricle
with poor left
ventricular function
Normal coronary
arteries
296
Answer 294
b. CMV infection.
The neutropenia and mild hepatitis in a patient a few
months after renal transplantation favour CMV infection.
The raised creatinine level may reflect dehydration; if
acute, however, concomitant allograft rejection (a feature
of CMV infection) and ciclosporin toxicity could also
explain the raised creatinine level.
Infections are the leading cause of morbidity and
mortality in the early post-transplant period, as more than
80% of recipients suffer at least one episode of infection
in the first year. Infection and allograft dysfunction
caused by rejection are closely interrelated through the
use of immunosuppressive therapy (see below).
CMV is the most important infection in renal
transplant recipients. More than two-thirds of donors and
recipients have detectable IgG anti-CMV antibodies in
the plasma prior to transplantation. It is therefore
common for the donor and/or recipient to be CMVpositive at the time of transplantation. The virus can be
transmitted from the donor either by blood transfusion
or by the transplanted kidney; the concurrent
administration of immunosuppressive drugs to prevent
rejection further increases the risk of clinically relevant
CMV disease.
Symptomatic CMV infections typically occur one to four
months after transplantation, but can develop later.
Typically, the onset of disease usually follows the period of
maximal immunosuppression (associated with neutropenia)
for the prevention and treatment of acute rejection. Clinical
features include fever, deteriorating renal function and a
tender graft. However, the latter feature is rarely present as
it is masked by immunosuppressive therapy. CMV infection
in transplant patients may affect other organs causing
hepatitis, pneumonitis, pancreatitis, gastroenteritis,
meningo-encephalitis and rarely myocarditis.
Answer 295
e. Screen her blood for Factor V Leiden mutation.
Stop pill if positive.
The risk of venous thromboembolism is approximately
34 times higher in patients who are heterozygous for
the Factor V Leiden mutation. The risk is increased to
3040 fold in women who are smokers or on the
contraceptive pill. Even though population screening for
Factor V Leiden mutation is not cost effective, since only
a small proportion of patients with it will suffer from
Clinical Cases
297
Answer 296
d. Bisoprolol.
The patient has a dilated, poorly contracting left ventricle
and therefore has dilated cardiomyopathy. There are no
obvious reversible causes in this case such as B 12
deficiency, anaemia, haemochromatosis, thyroid
dysfunction or coronary artery disease. The treatment of
dilated cardiomyopathy aims to improve symptoms and
prognosis.
The low cardiac output resulting from dilated
cardiomyopathy offsets the reninangiotensin
aldosterone system and the sympathetic nervous system
in an attempt to restore circulation. Unfortunately
activation of both systems has a detrimental effect on the
heart, causing volume overload, progressive deterioration
of cardiac function owing to adverse remodelling, cardiac
arrhythmias and sudden death.
The goals in the management of heart failure are to
improve symptoms and prognosis. Therapeutic
modalities in chronic heart failure include lifestyle
modification, pharmacotherapy, device therapy and
surgery (Table A).
Loop diuretics are very effective at improving symptoms of pulmonary and peripheral congestion rapidly but
do not have an impact on prognosis. Digoxin is
particularly effective at providing symptomatic relief in
patients with atrial fibrillation, but has also been shown
to be effective in patients in sinus rhythm through its
weakly inotropic effects. Interestingly it is the only
inotropic agent used in heart failure that has not been
shown to cause sudden death. Like loop diuretics,
digoxin does not have an impact on prognosis.
The prognosis of dilated cardiomyopathy has been
improved significantly by the use of pharmacological
agents that inhibit the reninangiotensinaldosterone
system and beta-blockers. ACE inhibitors improve
Pharmacological therapy
Device therapy
Surgery
298
Initiation dose
1.25 mg od
3.125 mg od
6.25 mg tds
1.25 mg od
NYHA
class?
NYHA III
Start beta-blocker
NYHA IIIIV
Start
spironolactone
NYHA
class?
Clinical Cases
299
Question 297
A 75-year-old woman with a long history of atrial fibrillation
was seen in the anticoagulant clinic and noted to have an
INR of 8.2. She had been on warfarin for three years
without any complications. One week previously she had
received a course of erythromycin for a lower respiratory
tract infection. There was no history of blood loss from the
respiratory and gastrointestinal tracts or the genito-urinary
system. There was no history of alcohol abuse. The INR
two weeks previously was 2.3. On examination she appeared
well but had multiple bruises on her arms.
Investigations are shown.
Hb
WCC
Platelets
Urea
Creatinine
AST
Alkaline phosphatase
Albumin
12 g/dl
5.2 ! 109/l
180 ! 109/l
6 mmol/l
92 "mol/l
20 iu/l
30 iu/l
39 g/l
Question 298
A 40-year-old male consulted his GP at the end of the
year for wheeze and dyspnoea. He was given a
bronchodilator with good effect. Two weeks later he had
an exacerbation of his symptoms, which responded well
to a one-week course of steroids. Follow ing this his
symptoms were stable and completely resolved when he
went to the Caribbean for a two-week holiday, only to
return within a few days when he came back to England.
He had no history of atopy and did not keep any pets.
He did not smoke. He was married with two children
and had been working as a solderer for a car
manufacturing company for the past 14 months. Apart
from a bronchodilator inhaler, the patient was not taking
any other medications.
Question 299
Hb
WCC
Platelets
PCV
MCV
Blood film
Bilirubin
AST
Alkaline phosphatase
Albumin
11 g/dl
30 ! 109/l
160 ! 109/l
44 l/l
100 fl
Spherocytes, red cell
agglutination
78 mol/l
40 iu/l
100 iu/l
39 g/l
300
Answer 297
a. Stop warfarin and repeat the INR in three days.
The answer to this question is based upon guidelines
provided by the British Society of Haematology for
anticoagulation reversal with warfarin, which are as
follows:
In the event of major bleeding stop warfarin and give
5 mg IV vitamin K slowly and IV fresh-frozen plasma
or prothrombin concentrate.
Answer 298
1. b. Occupational asthma.
2. a. Peak flow monitoring at work and at home.
The patient has been complaining of cough and wheeze
for the past year that has responded to a bronchodilator
inhaler and then a steroid trial. The history would be
consistent with reversible bronchospasm. While adultonset asthma can occur at this age, there appears to be a
relationship between the onset of his symptoms and the
time he has worked as a car solderer. Further evidence
for this comes from the fact that his symptoms resolved
while he was away on holiday only to return a few days
after he arrived back to the country (and presumably
returned to work). These findings indicate that the
patient is exposed to an allergen at work that causes
bronchospasm. Soldering material contains colophony,
which is a large molecular weight allergen that induces
bronchospasm by hypersensitivity immune reactions.
Answer 299
b. Auto-immune haemolytic anaemia.
Clinical Cases
Question 300
301
300
Question 301
A 67-year-old Afro-Caribbean patient was being followed
up in clinic for hypertension. He had been adhering to a
low-salt diet. He was currently taking bendroflumetha-
Sodium
Potassium
Urea
Creatinine
Glucose (fasting)
12-lead ECG
Urinalysis
138 mmol/l
3.3 mmol/l
6 mmol/l
150 "mol/l
13 mmol/l
Left ventricular hypertrophy
No blood pre protein
Glucose +
Question 302
302a
302
Answer 300
a. Hiatus hernia.
Answer 301
c. Add losartan.
Hypertension is very common among black patients and
affects 1 in 2 individuals aged >40 years. Hypertension in
black patients usually occurs at a younger age, is more
severe and associated with a higher rate of stroke, heart
failure and renal failure than in white patients.
Hypertension in black patients is salt-sensitive and
associated with an expanded vascular volume. It responds
well to low salt intake and to pharmacological agents that
promote urinary sodium excretion and to vasodilators.
Thiazide diuretics or calcium channel blockers are the firstline drugs of choice. Since plasma renin levels are generally
low in black patients, agents affecting the
reninangiotensinaldosterone system (i.e. ACE inhibitors,
angiotensin II receptor blockers and beta-blockers) are not
particularly effective when used as first-line agents (see
Answer 123). However any of these three drugs is effective
Answer 302
a. Right middle lobe consolidation.
There is loss of the contour of the right heart border on
the PA film. There is also evidence of a slight increase in
the opacification of the right lower lung and a slight
reduction in overall lung volume compared with the left
lung. These features are consistent with right middle lobe
collapse/consolidation.
The right middle lobe accounts for just 10% of the total
lung volume and is more prone to collapse than the other
lung lobes because of decreased collateral ventilation.
Owing to its small size, collapse of the right middle lobe
has little impact on the appearance of the surrounding
structures. In the PA film there may be a triangular opacity
pointing laterally. In some patients an absent contour of
the right heart border is the only indicator of right middle
lobe collapse/consolidation. The diagnosis can be
confirmed on a lateral film, which demonstrates an oblique
triangular opacity with its apex pointing towards the hilum
(302b, arrows). This appearance results from the anterosuperior displacement of the major fissure and the posteroinferior displacement of the minor fissure.
302b
Clinical Cases
303
Question 303
Hb
WCC
Neutrophils
Lymphocytes
Eosinophils
Platelets
ESR
CRP
Urea
Creatinine
ANA
ANCA
C3
C4
Blood culture
Urinalysis
15 g/dl
11 ! 109/l
8 ! 109/l
1.5 ! 109/l
1.5 ! 109/l
200 ! 109/l
80 mm/h
100 g/l
13 mmol/l
178 "mol/l
Negative
Negative
Low
Low
Sterile
White cells ++
Protein ++
Question 304
Hb
MCV
WCC
MCH
Urea
Creatinine
Chest X-ray
Renal ultrasound
Urinalysis
Lung function:
FEV1 (l)
FVC (l)
TLC (l)
KCO
Question 305
7.5 g/dl
76 fl
8 ! 109/l
28 pg
15 mmol/l
136 "mol/l
Bilateral alveolar shadowing
Normal-sized echogenic
kidneys
>50 rbc, red cell casts
seen
Actual
Predicted
2.6
3.0
2.9
4.2
5.1
6.5
2.8
2.2
A 30-year-old garage mechanic presented with a oneweek history of generalized malaise, fever, cough and
intermittent haemoptysis.
Investigations are shown.
What are the two best investigations that would
establish the diagnosis?
a. Serum IgE specific for Aspergillus.
b. Serum angiotensin-converting enzyme level.
c. Antistreptococcal antibodies.
d. Lupus anticoagulant.
e. Serum cryoglobulin.
f. Antiglomerular basement membrane antibodies.
g. Antineutrophil cytoplasmic antibodies.
h. Serum IgA.
i. Serum complement.
j. Urinary Legionella antigen.
304
Answer 303
b. Cholesterol atheroemboli.
The history of renal failure and cutaneous manifestations
after coronary angiography is most consistent with
cholesterol atheroemboli.
Cholesterol atheroemboli may complicate manipulation
of atheromatous arteries, such as during angiography,
angioplasty or vascular surgery. Embolization of cholesterol
crystals results in fever, raised inflammatory markers,
eosinophilia, hypocomplementaemia, cutaneous
manifestations and renal failure. Cholesterol atheroemboli
lodge in small capillaries in the skin, producing livedo
reticularis and occasionally a vasculitic rash. The distal
extremities may appear blue. The emboli may also cause
ischaemia of the renal cortex leading to cortical atrophy and
a progressive decline in renal function that persists for over
two weeks. Urinalysis usually reveals white cells in the urine
and mild proteinuria; however, proteinuria in the nephritic
range and haematuria have also been described. Baseline
renal function may never return to normal in severe cases.
Answer 304
f. Antiglomerular basement membrane antibodies.
g. Antineutrophil cytoplasmic antibodies.
The patient presents with an acute renalpulmonary
syndrome characterized by pulmonary haemorrhage and
an acute nephritis. The differential diagnosis (in decreasing
frequency) is between antiglomerular basement membrane
(anti-GBM) disease (Goodpasteurs syndrome), Wegeners
granulomatosis, microscopic polyangiitis, polyarteritis
nodosa, SLE and post-streptococcal glomerulonephritis.
In individuals with a coexistent purpuric rash the diagnosis
of HenochSchnlein purpura may also be considered,
although pulmonary vasculitis is a very rare complication
of the disorder.
Answer 305
d. Carvedilol.
Prognostically useful drugs in heart failure are tabulated
below. In Afro-Caribbean patients the combination of
isosorbide dinitrate or mononitrate and hydralazine has
been shown to improve prognosis in symptomatic
patients when added to conventional heart failure therapy
that includes ACE inhibitors, beta-blockers and
spironolactone (see Answer 296).
Clinical Cases
305
Question 306
A 49-year-old male with alcohol-related liver disease
presented with burning epigastric pain and loss of
appetite. An upper gastrointestinal endoscopy revealed
gastritis and he had very small oesophageal varices that
had not bled. There was no previous history of
haematemesis or malena. The patient was haemo dynamically stable.
Question 307
A 70-year-old female presented with sudden onset of
expressive dysphasia and a right hemiparesis. She had a
long-standing history of hypertension and had been
investigated for an episode of amurosis fugax five years
ago. There was no history of diabetes mellitus and the
patient was a non-smoker. The patient was taking
bendroflumethiazide 2.5 mg for hypertension. She was
not on any other medication.
12-lead ECG
CT scan brain
Atrial fibrillation
Cerebral infarction affecting
the territory supplied by
the left middle cerebral
artery
Question 308
308
Question 309
A 67-year-old male with a mechanical aortic valve is
admitted with a dense left hemiparesis. CT scan of the
brain reveals evidence of cerebral infarction but no
haemorrhage. The INR on admission is 2.1.
306
Answer 306
d. Propranolol.
All patients with cirrhosis of the liver should undergo upper
gastrointestinal endoscopy to evaluate the presence of
varices. Prevention of bleeding of varices reduces mortality.
There is good evidence from large trials that betablockers, particularly propranolol and nadolol, are highly
effective agents at controlling portal hypertension and
preventing variceal bleeds. Beta-blockers are recommended
as prophylactic therapy in patients with mild to moderate
oesophageal or gastric varices to prevent bleeding.
Sclerotherapy is not recommended for primary prophylaxis,
Answer 307
a. Aspirin.
The patient has suffered a recent cerebrovascular accident.
In this particular case the CVA may be secondary to
thrombosis of the middle cerebral artery due to
atherosclerotic plaque rupture or due to an embolus arising
from the carotid arteries or the left atrium. The probability
of embolism from left atrial thrombus is high since the
patient is in atrial fibrillation. A cerebral haemorrhage has
been excluded by CT scan; therefore, treatment with an
antithrombotic agent such as aspirin or clopidogrel is
Answer 308
d. Sickle cell anaemia.
The blood film reveals multiple sickle cells and target
cells. Bone crisis is the most common type of sickle-
Answer 309
e. Stop warfarin and switch to intravenous heparin.
It is very difficult to stop anticoagulation completely in
this situation and there is a high risk of prosthetic valve
obstruction with thrombus. Furthermore, it is likely that
the embolic cerebrovascular accident in this patient was
due to under anticoagulation for the mechanical valve.
Patients with mechanical valve prostheses are usually
maintained on an INR of 34.
Clinical Cases
Question 310
A 20-year-old male was investigated for a six-year history
of blistering of the forehead and the hands that was
worse during the summer. He was not on any
medications. He had been investigated for several
episodes of severe central abdominal pain over the past
two years for which no obvious cause had been
identified. He admitted to binge drinking and consumed
up to 100 units of alcohol per week. Abdominal
examination was normal. Investigations are shown.
What is the diagnosis?
a. Acute intermittent porphyria.
b. Porphyria cutanea tarda.
c. Haemochromatosis.
d. Variegate porphyria.
e. Hereditary coproporphyria.
Hb
WCC
Platelets
Blood film
Amylase
Serum iron
TIBC
Serum ferritin
Urinary coproporphyrins
Faecal coproporphyrin
Urinary protoporphyrin
CT scan abdomen
307
13.8 g/dl
8 ! 109/l
(normal differential)
200 ! 109/l
Normal
100 iu/l
(NR <220 iu/l)
33 mmol/l
(NR 1332 mmol/l)
49 mmol/l
(NR 4280 mmol/l)
300 iu/l
1640 nmol/24h
(NR 50350 nmol/24h)
1900 nmol/24h
400 nmol/24h
(slightly raised)
Normal
Question 311
311a
Question 312
An alcohol-dependent patient was admitted with asterixis
and jaundice. Blood results are shown.
Hb
MCV
WCC
Platelets
Sodium
Potassium
Urea
Glucose
10g/dl
102 fl
14 ! 109/l
80 ! 109/l
131 mmol/l
3.2 mmo/l
2 mmol/l
4.2 mmol/l
308
Answer 310
e. Hereditary coproporphyria.
Hereditary coproporphyria is an autosomal dominant
porphyria caused by deficiency of the enzyme
coproporphyrinogen oxidase. The disorder results in
increased excretion of coproporphyrin in the urine and
faeces and is characterized by a combination of neurovisceral
features that are similar to but less severe than those seen in
acute intermittent porphyria, and photosensitivity. Patients
experience blistering, scarring and hypertrichosis of the skin
exposed to sunlight that is identical to that seen in porphyria
cutanea tarda. HC has been reported mainly in the UK,
Europe and North America. HC is precipitated by the same
factors that precipitate acute intermittent porphyria.
The disorder can be differentiated clinically from acute
intermittent porphyria by the fact that photosensitivity is
not a feature of acute intermittent porphyria. In patients
who do not have photosensitivity, the differentiation
from acute intermittent porphyria is based on the
Answer 311
a. Chest X-ray.
311b
Answer 312
a. IV flumazenil.
The patient has become encephalopathic owing to
diazepam. Patients with advanced cirrhosis may be
309
Clinical Cases
Question 313
313a
313b
313c
313d
Hb
WCC
Platelets
Blood film (313c)
Barium study (313d)
8.8 g/dl
6 ! 109/l
170 ! 109/l
Question 314
A 14-year-old female was referred to a specialist because
she had difficulty in walking over the past eight months.
She tripped easily. Her feet had adopted a strange shape
and she had problems fitting her shoes. Her father had
weakness affecting his legs and was under regular review by
a neurologist.
On examination, she appeared well and a general
examination was normal. There was wasting of the small
muscles of the hand, but upper-limb tone was normal and
the reflexes were preserved. On examination of the lower
limbs she had bilateral pes cavus. The calf muscles were
wasted and exhibited fasciculation. There was mild
310
Answer 313
1. The woman has koilonychia and glossitis, which are
features of iron-deficiency anaemia.
2. Anaemia with microcytosis, anisocytosis,
poikilocytosis and hypochromia. The features are
consistent with iron-deficiency anaemia.
3. Stricture in the upper oesophagus consistent with
an oesophageal web (PatersonBrownKelly or
PlummerVinson syndrome).
4. The differential diagnosis is between oesophageal
web and carcinoma of the upper oesophagus.
5. Oesophagoscopy and biopsy of stricture for
histological analysis.
Answer 314
1. CharcotMarieTooth disease (hereditary
sensorimotor neuropathy (HSMN)/peroneal
muscular atrophy).
2. i. Nerve conduction studies.
ii. Sural biopsy.
iii. Family screening.
The patient presents with difficulty in walking. On
physical examination, she has pes cavus, weakness of the
distal aspects of the upper and lower limbs. The lowerlimb reflexes are absent and proprioception and twopoint discrimination sense are impaired. These are the
features of HSMN. A family history is not given, but this
should be an important part of the investigation.
HSMN is divided into Types I, II and III. Type I is
the classic, familial type in which there is a diffuse
demyelinating neuropathy which usually presents in the
first two decades. Distal wasting of the lower limbs
produces peroneal muscular atrophy and the
characteristic inverted champagne bottle appearance.
Deformities of the feet and scoliosis are common. The
sensory fibres of proprioception are affected, producing a
sensory ataxia. Linkage studies on families with this
neuropathy have localized the condition to a genetic
Clinical Cases
311
Question 315
315
Affected male
Unaffected male*
Affected female
Unaffected female*
Question 316
A 59-year-old female was referred to the out-patient
clinic with lethargy and chest pain consistent with angina.
She was on a gluten-free diet and on long-standing
treatment for a skin rash (316). On examination, she was
thin and had pale conjunctivae. She appeared cyanosed.
The heart rate was 110 beats/min, with good volume;
the blood pressure was 130/75 mmHg. The heart
sounds were normal and the chest was clear.
Investigations are shown.
Hb
WCC
Platelets
MCV
PCV
Reticulocytes
Blood film
Serum B12
Red cell folate
Serum folate
8 g/dl
11 ! 109/l
240 ! 109/l
110 fl
0.34
10%
Polychromasia, macrocytosis,
target cells, a few fragmented
red cells
470 ng/l
65 g/l
1.8 g/l
316
312
Answer 315
1. Inheritance of maternal mitochondrial genetic
abnormality.
2. Conditions inherited in this way are listed (Table).
During conception, all the mitochondria inherited by the
zygote come from the ovum because the spermatozoon is
relatively depleted of mitochondria by the time it reaches
the ovum; therefore, abnormalities in mitochondrial DNA
can only be transmitted by a female. An affected female will
transfer the abnormal gene and the abnormal phenotype to
all offspring; however, a male does not transfer the disease.
Mitochondrial DNA contains a limited number of genes
that may be subject to point mutations, deletions or
duplications. Abnormalities in mitochondrial DNA result in
a variety of abnormalities, including easy fatigue, myopathy,
epilepsy, diabetes, optic atrophy, deafness, retinitis
pigmentosa and cardiomyopathy. Calcification of basal
ganglia is well recognized with mitochondrial disease. The
most common mutation is an A to G mutation at
nucleotide 3243. Most recognized mutations occur in
transfer RNA or genes encoding the proteins involved in
the oxidative phosphorylation pathway. The serum
lactate/pyruvate ratio is elevated, indicating impaired
aerobic glycolysis. CSF lactate may be elevated even when
Answer 316
1. i. Malabsorption.
ii. Dapsone-induced haemolysis.
2. Dapsone-induced haemolytic anaemia.
3. The presence of Heinz bodies (oxidative
haemolysis).
4. Serum methaemoglobin level.
5. i. Anaemia.
ii. Reduced delivery of oxygen to the heart due to
leftward shift of the oxygen dissociation curve
resulting from methaemoglobinaemia.
iii. Tachycardia.
The patient is on a gluten-free diet, suggesting that she
has a gluten-sensitive enteropathy. She is on treatment
for a long-standing rash (316) which is characteristic of
dermatitis herpetiformis. The association between
dermatitis herpetiformis and gluten-sensitive enteropathy
is well recognized. Dermatitis herpetiformis is effectively
treated with dapsone. An important side-effect of
dapsone is haemolytic anaemia because of its oxidant
effect on Hb. This effect is severe in patients with
glucose-6-phosphate dehydrogenase deficiency, but may
also occur in some individuals as an idiosyncratic
Clinical Cases
313
Methaemoglobinaemia
Sulphaemoglobinaemia
Fetal Hb
2,3 diphosphoglycerate deficiency
Alkalosis
Hypocapnia
Hypothermia
Question 317
A 76-year-old female was admitted to hospital with
malaise, weakness, nausea and anorexia. She had been
relatively well until two weeks previously when she
developed a painful left calf for which she was prescribed
some tablets by her GP. On examination, she appeared
dehydrated and her blood pressure was 90/50 mmHg.
She had clinical evidence of a deep-vein thrombosis in
her left calf. All other physical examination was normal.
Investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Chloride
Bicarbonate
Urea
Creatinine
Blood glucose
Urinalysis
13 g/dl
8 ! 109/l
300 ! 109/l
88 fl
128 mmol/l
6.2 mmol/l
88 mmol/l
13 mmol/l
24 mmol/l
297 mol/l
10 mmol/l
24-hour sodium
68 mmol/l
314
Answer 317
c. Acute tubulointerstitial nephritis secondary to
NSAIDs.
All five suggested answers can be responsible for
hyponatraemia, but in a woman who has recently been
treated for a painful calf it is most likely that she was
prescribed some form of pain killer. She has subsequently
presented with anorexia, malaise and vomiting and has
deranged renal function. Urinalysis reveals a 24-hour
urine of over 20 mmol/l sodium, which suggests a saltlosing state when one considers her low serum sodium.
The most probable cause of her presentation is an acute
nephritis secondary to prescription of an NSAID.
The biochemistry is partly consistent with Addisons
disease; however, the diagnosis is less likely in the context
of the history and the presence of a raised blood sugar.
Diuretic excess is also possible. One could assume that she
was prescribed a diuretic; this has resulted in dehydration
and pre-renal failure, but the serum bicarbonate and the
potassium levels suggest that this is unlikely. Diuretics
used to treat ankle swelling alone comprise thiazides or
loop diuretics, which result in a hypokalaemic alkalosis.
Potassium-sparing drugs such as amiloride alone or
spironolactone are not the drugs of choice to treat ankle
swelling. Vomiting is also a recognized cause of
hyponatraemia, but there is no mention of it in the
history, and the raised potassium is unlikely to explain
profuse vomiting, which usually results in low sodium,
potassium and chloride levels because gastric fluid
contains high concentrations of all these ions.
Diabetic ketoacidosis would be lowest in the
differential diagnosis because the blood sugar is relatively
low. The hyponatraemia resulting from ketoacidosis is a
result of osmotic diuresis from the very high blood sugar.
A random blood sugar of 10 mmol/l could represent
impaired glucose tolerance or mild non-insulindependent diabetes, but is against diabetic ketoacidosis.
NSAIDs may cause acute tubular necrosis or an acute
tubulointerstitial nephritis (Table). Acute tubular necrosis
is an increasing problem with NSAID prescription.
NSAIDs inhibit cyclo-oxygenase activity and decrease
Penicillins
NSAIDs
Sulphonamides
Allopurinol
Phenindione
Acute pyelonephritis
Sickle cell crisis
Lead poisoning
Clinical Cases
Question 318
318a
318b
Question 319
A 40-year-old dentist presented with a five-month history
of weight loss. He had recently become jaundiced.
Blood results are shown.
AST
Alkaline phosphatase
Bilirubin
Albumin
-fetoprotein
Serum ferritin
Hepatitis serology
40 iu/l
165 iu/l
80 mol/l
32 g/l
40 ng/l
450 g/l
Hep B sAg positive
Hep B eAg positive
Hep B cAb positive
315
316
Answer 318
1. Sick sinus syndrome. Rhythm strip 318a reveals
sinus tachycardia followed by sinus arrest or sinus
pause of 2.5 seconds. Rhythm strip 318b reveals
atrial fibrillation with a rapid ventricular rate.
2. Symptomatic patients should be paced.
The diagnosis is consistent with sick sinus syndrome,
which is a degenerative condition affecting the sino-atrial
node and the atrial myocardium. It is characterized by
Answer 319
1. Chronic active hepatitis B infection.
2. i. Hepatitis B e antibody (Hep B eAb)/hepatitis s
antibody (Hep B sAb).
ii. Liver ultrasound.
iii. Liver biopsy (if platelets and clotting not
severely deranged).
iv. HIV antigen.
3. #-interferon.
The differential diagnosis of weight loss and jaundice is
wide, but the presence of Hep B eAg and Hep B sAg
narrows this down to active hepatitis B infection. (Note:
dentistry is a high-risk occupation for hepatitis B.)
The symptoms have been present for five months,
suggesting that there is a chronic active infection.
Investigations should be based on confirming the extent
of hepatic damage and determining the patients
infectivity and immune status. The #-fetoprotein is
modestly elevated in severe viral hepatitis and active
cirrhosis. Levels exceeding 1,000 ng/l are strongly
suggestive of hepatocellular carcinoma. Liver biopsy will
reveal a ground-glass appearance of infected hepatocytes
and evidence of balloon degeneration. Serological
markers such as Hep B eAb and Hep B sAb will
determine infectivity and immune response. Liver
ultrasound may be useful in determining the extent of
liver damage when clotting and platelets are very
abnormal. Hepatitis B-positive patients in high-risk
occupations should also be offered HIV testing, because
both conditions are acquired in the same manner from
the same type of patients. There is evidence that
treatment with #-interferon in patients with circulating
Hep B sAg and Hep B eAg will reduce viral replication
and infectivity.
Some 2% of patients with hepatitis B infection develop
fulminant hepatitis, while 10% of patients become carriers
after the initial infection. Some carriers are positive for
Clinical Cases
317
Question 320
A 62-year-old female with rheumatoid arthritis was
referred to an ophthalmologist with a three-day history of
a painful left eye. The visual acuity was normal. She had a
similar problem three years ago which required therapy
with oral steroids. She was diagnosed with rheumatoid
arthritis 21 years ago after presenting with pain in her
hands, feet and elbows. Initial treatment comprised
NSAIDs, then chloroquine, but over the past five years
she was successfully managed on a combination of
NSAIDs and penicillamine. On further questioning, she
complained of a slightly reduced appetite, lethargy and
breathlessness on trying to negotiate inclines, and swollen
ankles. There was no other past medical history. She was
a non-smoker. She was married and her husband worked
as an architect.
On examination, the appearance of the eye was as
shown (320a). The anterior chamber was clear and the
pupils reacted normally to light. Visual acuity was 6/6 in
the left eye, and 6/12 in the right eye. Examination of
the fundi was normal. Examination of her hands and feet
revealed evidence of a generalized, symmetrical deforming arthropathy. The heart rate was 90 beats/min and
regular. The blood pressure was 140/90 mmHg. The
jugular veins were not distended. The heart sounds were
normal. Auscultation of the lung fields revealed fine
inspiratory crackles at both bases, which persisted after
coughing. On examination of the abdomen, there was a
palpable spleen 3 cm below the costal margin. The liver
was not palpable, and there was no ascites. Examination
of the lower limbs revealed multiple bruises and pitting
ankle oedema to the shins.
Investigations are shown.
320a
Hb
WCC
Platelets
MCV
ESR
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Alkaline phosphatase
Albumin
IgM
IgG
IgA
Immunoelectrophoresis
Chest X-ray
Urine dipstick
7.4 g/dl
3 ! 109/l
45 ! 109/l
78 fl
56 mm/h
134 mmol/l
4.4 mmol/l
13 mmol/l
168 mol/l
2.0 mmol/l
1.2 mmol/l
200 iu/l
29 g/l
2.0 g/l
19 g/l
1.9 g/l
Increased gammaglobulin band
No paraproteinaemia
Rheumatoid factor positive
1 in 460
Normal
Protein ++
Blood 0
318
Answer 320
1. Scleritis.
2. i. Penicillamine-induced marrow suppression.
ii. Hypersplenism (Feltys syndrome).
3. i. Bone marrow aspirate/trephine.
ii. Red cell sequestration study.
4. i. Penicillamine-induced membranous
glomerulonephritis and secondary nephrotic
syndrome.
ii. Renal amyloidosis.
5. Interstitial lung fibrosis or fibrotic lung disease.
6. Formal spirometry and transfer factor.
This woman with long-standing rheumatoid arthritis
presents with a second attack of unilateral painful red eye,
which has previously required systemic steroids. The
most probable diagnosis is scleritis. Other causes of a red
eye in rheumatoid arthritis include episcleritis and
keratitis secondary to Sjgrens syndrome. The former is
painless, and the latter is bilateral. It is important to note
that the only definitive method of differentiating scleritis
from episcleritis without a history is by slit-lamp
examination of the eye. Recurrent episodes of scleritis
may result in perforation of the sclera (scleromalacia
perforans) (320b).
In addition to the scleritis, she has other problems
commonly seen in patients with rheumatoid arthritis which
include anaemia, Feltys syndrome (which itself may be
responsible for the anaemia), renal and respiratory
involvement. Drugs used in the treatment of rheumatoid
arthritis may themselves cause many of the complications
seen in rheumatoid arthritis, and a knowledge of the drugs
used and their complications is essential in the
management of a patient with rheumatoid arthritis.
320b
Episcleritis/scleritis/scleromalacia
Sjgrens syndrome
Cataracts secondary to steroid therapy
Retinopathy secondary to chloroquine
Extraocular muscle tendon synovitis
Extraocular muscle paralysis secondary to
penicillamine-induced myaesthenia
Extraocular muscle paralysis secondary to a
mononeuritis multiplex
Clinical Cases
319
Cricoarytenitis
Pleural effusion
Pulmonary fibrosis
Bronchiolitis obliterans
Pneumonitis
Pulmonary nodules
Caplans syndrome (nodules plus progressive
massive fibrosis in coal workers disease)
Question 321
An 11-year-old male was referred to the local
paediatrician after his mother complained that he was
unusually short for his age. His appetite was normal, and
there was no history of recent diarrhoea or weight loss.
He was performing well at school and enjoyed a relatively
active life. His mother was short, measuring 1.48 m, but
his father measured 1.81 m. There were no siblings.
On examination, the boy measured 0.97 m. There was
no evidence of pallor, cyanosis or oedema. The heart
sounds were normal and the chest was clear. The
abdomen was soft, and there was no palpable
organomegaly. The lower limbs appeared bowed.
Neurological examination was normal.
Investigations are shown.
Hb
WCC
Platelets
Sodium
Potassium
Urea
Calcium
Phosphate
Albumin
Alkaline phosphatase
X-ray of knees (321)
11 g/dl
5 ! 109/l
180 ! 109/l
135 mmol/l
4 mmol/l
4 mmol/l
2.2 mmol/l
0.3 mmol/l
39 g/l
500 iu/l
321
320
Answer 321
1. Splaying of the metaphyses and widening of the
epiphyseal plate, indicating rickets.
2. Hypophosphataemic rickets; X-linked dominant
hypophophataemic rickets; vitamin D resistant
rickets.
3. i. Urinary phosphate excretion (elevated).
ii. Renal tubular reabsorption rate of phosphate.
4. High-dose vitamin D and oral phosphate
supplements.
Both the boy and his mother are short. There is
radiological
evidence
of
rickets
and
a
hypophosphataemia, but the serum calcium level is
normal. The findings are consistent with the diagnosis of
hypophosphataemic rickets or vitamin D resistant rickets.
The condition is inherited as an X-linked dominant
condition. The fundamental abnormality is failure of
Type 2
Mode of inheritance
Autosomal recessive
Autosomal recessive
Defect
Reduced
1-hydroxycholecalciferol
Resistance to
1,25-dihydroxycholecalciferol
1,25-dihydroxycholecalciferol level
Reduced
Elevated
Myopathy
Present
Present
Associations
Treatment
Alopecia
Very high doses of
1,25-dihydroxycholecalciferol
Clinical Cases
321
Question 322
CD4 count
Viral load
CT scan
CSF pressure
CSF analysis:
White cells
Red cells
Protein
Glucose
Gram stain
ZiehlNeelsen
stain
Blood glucose
300 ! 106/l
1,000 copies/ml
Normal
10 cmH2O
580/mm3 (90% lymphocytes)
3/mm3
0.9 g/l
1.5 mmol/l
Negative
Negative
5 mmol/l
Question 323
323
Sodium
Potassium
Urea
Creatinine
Glucose
136 mmol/l
4.0 mmol/l
8 mmol/l
90 mol/l
6 mmol/l
Hb
WCC
Platelets
Chest X-ray
13 g/dl
17 ! 109/l
159 ! 109/l
Normal
322
Answer 322
1. i. Tuberculous meningitis.
ii. Cryptococcal meningitis.
iii. Listeria meningitis.
iv. Cerebral lymphoma or leukaemia.
v. Brucellosis.
2. i. ZiehlNeelsen stain or PCR on the CSF for
tuberculous meningitis.
ii. Indian ink stain on CSF to identify Cryptococcus
neoformans.
iii. CSF analysis by the cytology department to look
for malignant cells.
This homosexual male with a low CD4 count presents
with an epileptic seizure. The CD4 count suggests that
he has advanced HIV infection. The CSF reveals a
lymphocytosis, high protein and a sugar concentration
less than half of the blood sugar. The differential
diagnosis of these CSF findings is listed (Table). The
Tuberculous meningitis
Brucellosis*
Fungal meningitis
Cerebral lymphoma
Leukaemic infiltration into the brain
Metastatic brain disease
Cerebral abscess
Answer 323
1. e. Acute posterolateral myocardial infarction.
2. e. Right ventricular hypokinesia.
The ECG on admission reveals ST-segment elevation of
more than 2 mm in leads I and aVl. This is consistent
with a limited lateral myocardial infarction. The J-point
in leads II and V3V6 is elevated, but there is no
pathological ST-segment elevation in these leads. There
is also evidence of a dominant R-wave in leads V1V3
which, in the context of the history, represents posterior
extension of the infarct. Posterior infarction gives the
opposite appearance of an acute anterior infarction;
therefore instead of Q-waves (which would be seen in the
case of an anterior infarction) there are prominent Rwaves. The full diagnosis is acute posterolateral
myocardial infarction.
There are several possible causes of hypotension in this
man; however the only real possibility in this clinical
scenario is right ventricular infarction and secondary right
ventricular hypokinesia. This is a recognized complication
of inferior and posterior myocardial infarction, and is
characterized by a reduced cardiac output from the right
heart causing hypotension and a raised JVP. Treatment is
Clinical Cases
323
Question 324
A 5-year-old male was admitted with a one-week history
of fever, general malaise and pain in his hands and feet.
Two weeks previously he had had a bout of tonsillitis
which required a course of antibiotics. On the day of
admission he complained of intermittent chest pain
radiating into his back and his arms. He was born at 41
weeks gestation via a normal vaginal delivery. He had
achieved his milestones normally. He was the only child.
His father was a businessman, and his mother a teacher.
He had been seen by the GP two days earlier and
diagnosed as having a viral illness for which he was
prescribed paracetamol syrup.
On examination, he appeared unwell. He had a fever
of 40C (104F). His heart rate was 140 beats/min and
regular. His lips appeared oedematous, and examination
of his mouth revealed a white-coated tongue with
prominent papillae. On examination of the neck there
was widespread, tender, cervical lymphadenopathy.
Examination of the pharynx and tonsillar area was
normal. The palms of his hands and feet were red, and
there was evidence of early desquamation of the skin on
the palmar surface of both hands. There was tenderness
over the metacarpophalangeal joints of both hands. The
Hb
WCC
Platelets
ESR
CRP
Biochemistry
Blood cultures
Chest X-ray
ECG
10.5 g/dl
15 ! 109/l
490 ! 109/l
90 mm/h
80 g/l
Normal
Normal
Normal
Sinus tachycardia
Inverted T- waves V1V6
Question 325
A 33-year-old single male was admitted with a one-week
history of fever, sore throat, a maculopapular rash on the
trunk and cervical lymphadenopathy. His only past
medical history consisted of treatment for urethritis one
year previously following a trip abroad. His most recent
325
Hb
WCC
Platelets
Blood film (325)
Paul Bunnell test
CMV titre
Toxoplasma titres
VDRL
FTA IgG
Hep B sAg
HCV Ab
11 g/dl
6 ! 109/l
180 ! 109/l
Negative
Increased IgG at a titre of 1/16
Negative
Negative
Positive
Absent
Absent
324
Answer 324
1. Kawasakis disease.
2. Transthoracic echocardiography to visualize
the coronary arteries on the short-axis views
of the aorta.
3. i. Oral aspirin.
ii. Intravenous human immunoglobulin.
324
Answer 325
1. The diagnosis is HIV seroconversion.
2. Repeat HIV antibody test.
HIV seroconversion occurs 26 weeks after HIV
infection. The illness resembles infectious mononucleosis,
comprising fever, pharyngitis, lymphadenopathy and a
Clinical Cases
325
Question 326
A 39-year-old male presents with a three-month history
of lower back pain. Over the past two years he has
experienced three episodes of severe right lower quadrant
pain.
Investigations are shown.
Sodium
Potassium
Chloride
Bicarbonate
Urea
Creatinine
Calcium
Phosphate
138 mmol/l
3.5 mmol/l
119 mmol/l
13 mmol/l
7 mmol/l
112 mol/l
2.1 mmol/l
0.7 mmol/l
326
Answer 326
1. Distal (type I) RTA.
2. Early morning urinary pH measurement or
measurement of urine pH after ammonium
chloride infusion.
3. Osteomalacia.
4. i. X-ray of the lumbar spine may reveal osteopenia
or Loosers zones in osteomalacia.
ii. Serum alkaline phosphatase level, which is
characteristically raised in osteomalacia.
5. Renal colic.
6. i. Plain abdominal X-ray may identify a radioopaque renal stone.
ii. Intravenous urography is the investigation of
choice to identify stones in the renal tract.
The biochemical results reveal a hypokalaemic,
hyperchloraemic acidosis. In addition, there are low
calcium and phosphate levels. These are features of RTA,
which is characterized by abnormalities in urinary
acidification. RTA may be divided into type 1 (distal
RTA) and type 2 (proximal RTA). The causes and
associations of renal tubular acidosis are tabulated below.
Distal RTA is due to defective excretion of H+ in the
distal convoluted tubule, and proximal RTA is due to
failure of H+ secretion by the proximal convoluted tubule.
In both cases there is hypokalaemia and hypercalcuria.
Hypokalaemia can be explained as follows.
Causes of RTA
Distal (Type 1)
Inherited
Proximal (Type 2)
Inherited
Part of Fanconis syndrome
Acquired
Primary biliary cirrhosis
CAH
Obstructive nephropathy
Vitamin D intoxication
Tetracycline
Acquired
Hyperparathyroidism
Heavy metal poisoning (lead, arsenic)
Myeloma
Acetazolamide
Clinical Cases
327
Question 327
A 64-year-old female was admitted to hospital with a
three-month history of increasing breathlessness and
swollen ankles. She had been well until two-and-a-half
years ago, when she experienced sudden onset of
breathlessness while walking. She was observed in hospital
overnight but was much improved the following day and
allowed home. She had a further similar episode four
months later, and then again a year later. On each occasion
she improved within 2448 hours. In between the two
most recent episodes she had noticed that she was unable
to exert herself as much without becoming breathless.
There was no history of chest pain or a cough. Physical
examination performed by the senior house officers during
each hospital admission had been normal, with the
exception of a sinus tachycardia of 110 beats/min. A chest
X-ray performed on the admission one year ago is shown
(327a). The patient had a past medical history of
hysterectomy aged 43 years for menorrhagia due to uterine
fibroids. Three years ago she had surgery for varicose veins
of the lower limbs. She was a non-smoker. She was not
taking any medication. She was a receptionist in a doctors
surgery for 20 years before retiring 20 years ago. She was
married and lived with her husband. The couple had a dog
and a parrot as pets.
On examination, she was breathless at rest and
cyanosed. There was no clubbing. She had marked pitting
lower-limb oedema up to her thighs. The heart rate was
102 beats/min and blood pressure 105/60 mmHg. The
JVP was elevated to the level of the mastoid. Closer
inspection revealed prominent c-v waves. On examination
of the precordium, the apex was displaced to the anterior
axillary line. There was a marked left parasternal heave. On
auscultation of the precordium there was a soft systolic
murmur and a loud fourth heart sound at the left lower
sternal edge. The chest was clear. Abdominal examination
demonstrated ascites and a pulsatile liver edge 5 cm below
the costal margin. The ECG performed on admission is
shown (327b).
Respiratory function tests performed on this admission
are shown.
327a
327b
FEV1 (l/min)
FVC (l/min)
TLC (l)
Transfer factor
Corrected transfer factor
Actual
0.94
1.12
2.1
3.4
0.4
Predicted
1.262.94
1.823.81
4.386.8
4.28.8
0.71.62
328
Answer 327
e. Right heart catheter plus pulmonary angiography.
The patient has a history of progressive breathlessness,
and now presents with ECG evidence of right ventricular
hypertrophy and a clinical picture of severe right heart
failure. Lung function tests demonstrate a restrictive
defect and a low transfer factor. She has cor pulmonale
complicating multiple pulmonary emboli, extrinsic
allergic alveolitis, or CFA. The latter two diagnoses are
unlikely in the absence of chest signs on three hospital
admissions and the normal chest X-ray one year
previously. In contrast the chest X-ray in multiple
pulmonary emboli may appear relatively normal, the only
evidence of pulmonary emboli being oligaemic lung
fields. Another possible diagnosis is right heart failure due
to chronic pulmonary hypertension from an ostium
secundum ASD; however, the chest X-ray in this
Question 328
A 42-year-old, insulin-dependent diabetic was
investigated further after he was noted to have a positive
dipstick for protein on urine analysis. He was diagnosed
with diabetes at the age of 23 years after presenting with
ketoacidosis. Initial management with porcine insulin was
good; however, he was switched to human insulin 10
years ago because of severe lipoatrophy at sites of
injection. Over the past three years blood glucose control
had been suboptimal, and the dose of insulin had been
increased on five occasions. He was married with two
children. He owned a grocers shop which was open
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Glucose
12.8 g/dl
6 ! 109/l
212 ! 109/l
89 fl
136 mmol/l
3.4 mmol/l
6.8 mmol/l
117 mol/l
11 mmol/l
seven days a week and was staffed by the patient and his
wife at all times. He smoked five cigarettes per day. He
did not consume alcohol.
On examination, he had bilateral corneal arcus. His
heart rate was 80 beats/min and regular; blood pressure
was 150/90 mmHg. There was no evidence of cardiac
enlargement or cardiac failure. The peripheral pulses were
all palpable, and there were no audible bruits over the
carotid arteries or in the abdomen. Examination of his
fundi is shown (328a).
Investigations are shown below.
Glycosylated Hb
Cholesterol
Triglycerides
24-hour urinalysis
Clinical Cases
328a
329
328b
328c
133 mmol/l
6.4 mmol/l
32 mmol/l
500 mol/l
10 mmol/l
Question 329
A 16-year-old female was brought into the Accident and
Emergency Department with shortness of breath.
Blood gases on inspiring room air are shown.
pH
PaCO2
PaO2
Bicarbonate
O2 saturation
7.49
2.4 kPa
15.5 kPa
12 mmol/l
96%
330
Answer 328
1. Small retinal haemorrhages, and micro-aneurysms
consistent with background diabetic retinopathy.
2. There is evidence of eosin staining (pink) fibrotic
(hyaline) nodules characteristic of diabetic
glomerulosclerosis, sometimes known as
KimmelsteilWilson nodules.
3. Diabetic nephropathy. Other causes of protein in
the urine in diabetics include a urinary tract
infection.
4. Angiotensin-converting enzyme inhibitor-induced
glomerular hypoperfusion in a patient with bilateral
renal artery stenosis.
5. i. Stop ACE inhibitor.
ii. Bilateral renal angioplasty.
iii. Improve diabetic control.
iv. Control hyperlipidaemia.
v. Ensure blood pressure below 140/85 mmHg.
vi. Advise against smoking.
Overt diabetic nephropathy is based on the
demonstration of over 0.5 mg of protein on a 24-hour
urinary collection. A protein content of this level is easily
detected on a urine dipstick. More recently, it has been
noted that some patients pass small amounts of albumin
in the urine (0.020.3 mg/24 h) before the development
of a positive dipstick test. Such patients are said to have
micro-albuminuria or incipient diabetic nephropathy.
Answer 329
1. There is a respiratory alkalosis and a metabolic
acidosis.
2. Aspirin toxicity (see also Answer 172).
3. The management is dependent on the serum
salicylate level. Levels below 500 mg/l are treated
with intravenous saline to promote renal clearance.
Levels between 500 and 750 mg/l are treated with
intravenous bicarbonate but may require forced
alkaline diuresis on a high-dependency unit. Levels
between 750 and 1,000 mg/l are best treated with
haemodialysis.
Clinical Cases
331
Question 330
A 46-year-old garage mechanic was investigated in a
medical clinic for weight loss. Six months previously he
had commenced a voluntary diet to reduce weight. He
lost 4 kg over two months, following which he stopped
his diet. Despite a normal appetite he continued to lose
another 4 kg in weight over the next four months. He
had also noticed that he tired easily, and was finding it
difficult to perform heavy manual work as part of his
profession. His arms felt weak. He was breathless on
strenuous effort and found heavy lifting increasingly
difficult. More recently, he had developed lower back
pain which was worse when he sat upright and was
associated with pain and numbness of his left calf and left
foot. The pain was worsened by movement and he was
forced to stop working. His appetite remained good. He
had moved his bowels twice daily ever since he could
remember. The stool was of normal consistency and did
not contain blood. He was married with three children.
He stopped smoking 15 years ago after an attack of
bronchitis. He consumed 23 units of alcohol per week.
On examination, he was of relative heavy build. There
was no evidence of pallor or clubbing. The heart rate was
102 beats/min and irregularly irregular. The blood
pressure was 130/80 mmHg. The JVP was not raised.
On examination of the upper limbs there was no muscle
tenderness, but there was wasting of the proximal
muscles of the upper limb with weakness of abduction
and adduction. The upper limb reflexes were brisk.
Sensory testing was normal. On examination of the lower
limbs, there was wasting of the muscles of the thighs.
Power testing demonstrated weakness of plantar flexion
on the left side. Reflexes were brisk with the exception of
the left ankle jerk, which was absent. Plantar responses
were normal. Sensory testing demonstrated reduced pinprick sensation affecting the anterolateral aspect of the
left foot.
Investigations are shown.
Hb
WCC
Platelets
ESR
Chest X-ray
Sodium
Potassium
Urea
Calcium
Phosphate
Albumin
14 g/dl
6 ! 109/l
210 ! 109/l
10 mm/h
Normal
135 mmol/l
3.4 mmol/l
5 mmol/l
2.4 mmol/l
1 mmol/l
40 g/l
Question 331
This ECG (331) is from a 35-year-old male with
sudden onset of expressive dysphasia and right
upper-limb weakness. On examination, he was
apyrexial. The heart rate was 100 beats/min and
regular; blood pressure was 110/80 mmHg. He
had a soft systolic murmur. There were no
carotid bruits. He had been well and
asymptomatic all his life, and was a non-smoker.
331
332
Answer 330
1. c. Prolapsed intervertebral disc between L5/S1.
2. c. Thyrotoxic myopathy.
The patient has weight loss, despite a normal appetite.
The differential diagnosis for this scenario is
malabsorption, diabetes mellitus, phaeochromocytoma
and thyrotoxicosis. He has atrial fibrillation, which is
most consistent with thyrotoxicosis. He also has proximal
muscle wasting of his limbs, a well-known feature of
thyrotoxic myopathy. A paraneoplastic syndrome is
unlikely because there is no immediate evidence of an
underlying neoplastic process. For similar reasons, he is
unlikely to have EatonLambert syndrome, which is a
myasthenic syndrome associated with malignancy.
Proximal myopathy is a feature, but reflexes are absent.
In contrast to myasthenia, weakness improves with
repetitive muscular stimulation. Both polymyalgia
Answer 331
1. i. Right axis deviation.
ii. RBBB.
iii. Voltage criteria for right ventricular hypertrophy.
2. Ostium secundum ASD.
3. Paradoxical embolus from the systemic veins.
The combination of right axis deviation and RBBB in a
young, previously asymptomatic man with a soft systolic
murmur is suggestive of an underlying ostium secundum
ASD. Ostium primum defects are associated with left axis
deviation and RBBB. Although both pulmonary stenosis
and VSDs can produce similar ECG changes, a soft
murmur in a patient with a VSD is suggestive of a large
defect which would almost certainly cause symptoms of
cardiovascular dysfunction before the third decade. Mild
pulmonary stenosis is characterized by lack of symptoms
Clinical Cases
333
Question 332
A 22-year-old basketball player presented with
sudden onset of severe left-sided chest pain
radiating into his neck four hours before he
was due to play in a large tournament. He had
never experienced any previous chest pain,
and was extremely fit, according to his team
coach.
On examination, he was distressed with
chest pain. His heart rate was 70 beats/min
and blood pressure 190/110 mmHg.
Examination of the precordium and the chest
was normal. An ECG was performed
immediately (332), and he was subsequently admitted to
the Coronary Care Unit. The following day he was
asymptomatic and his blood pressure was normal.
Examination of his fundi did not demonstrate any fundal
changes of hypertension, and general examination did
not reveal any peripheral stigmata of hyperlipidaemia. He
denied any previous history of hypertension, diabetes
mellitus or a family history of coronary artery disease. He
had never smoked previously.
Investigations following admission are shown.
An echocardiogram performed three days later
demonstrated minor apical hypokinesia, but satisfactory
overall systolic function. Coronary angiography before
discharge was entirely normal.
332
Hb
WCC
Platelets
Sodium
Potassium
Glucose
Creatinine kinase
13 g/dl
12 ! 109/l
204 ! 109/l
139 mmol/l
3.9 mmol/l
4.2 mmol/l
560 iu/l
Question 333
A 66-year-old male with a long history of breathlessness
presented with a three-day history of profound
breathlessness and a cough productive of yellow sputum.
Arterial blood gases are shown.
pH
PaCO2
PaO2
Bicarbonate
Base excess
7.33
8.8kPa
6.5kPa
36 mmol/l
+11
334
Answer 332
1. A history of amphetamine abuse.
2. A calcium channel blocker such as amlodipine or
verapamil.
The clinical scenario is that of an elite athlete presenting
with an acute myocardial infarction but subsequently he
has normal coronary arteries, although the
echocardiogram is indicative of myocardial damage. While
there are several causes of myocardial ischaemia despite
normal coronary arteries (Table A), the possibility of
cocaine (an amphetamine) abuse should be considered.
Cocaine abuse has reached epidemic proportions in
some groups of elite athletes; however, the incidence of
cardiac complications remains low. Cocaine inhibits reuptake of the catecholamine neurotransmitter
noradrenaline, which is a potent vasoconstrictor. By this
mechanism it may induce coronary artery spasm and
myocardial infarction. The drug has also been implicated
in causing myocarditis through direct effects on the
heart. In addition, its local anaesthetic properties block
the fast inward sodium and slow calcium currents within
myocardial cells, thereby predisposing to lethal
ventricular arrhythmias. Cocaine also prolongs the QTinterval and increases the risk of torsades de pointes-type
polymorphic ventricular tachycardia. Arrhythmias are best
treated by antiarrhythmic agents which do not prolong
the QT-interval. Beta-blockers are contraindicated in the
management of cocaine-induced cardiac problems
because they would result in unopposed alpha activity,
causing profound vasoconstriction. Cocaine is a relatively
rare cause of sudden death in young elite athletes.
Relatively more common causes are shown (Table B).
Non-cardiac causes of mortality from cocaine include
CVA, status epilepticus and rhabdomyolysis.
HCM
Aortic stenosis
Hypertensive heart disease
Coronary arteritis, particularly polyarteritis
nodosa
Coronary artery embolus secondary to
intramural thrombus or vegetation
Severe anaemia
Thyrotoxicosis
Phaeochromocytoma
Cocaine
Amphetamines
Answer 333
c. Partially compensated respiratory acidosis.
The high PaCO2 and low pH is diagnostic of respiratory
acidosis. The arterial bicarbonate is high, indicating that
Clinical Cases
335
Question 334
A 16-year-old Turkish female was referred to the
gynaecological outpatient clinic with a 14-month history
of amenorrhoea. She started menstruating at the age of 13
years. She had almost regular periods until the age of 14
and after this had three scanty periods and none for the
past year. She was born in Turkey and had only recently
come to England. At the age of nine years she had been
commenced on hydrocortisone 15 mg in the morning and
10 mg in the evening for an illness about which both
parents were very vague. Apart from occasional dizziness
Hb
WCC
Platelets
Sodium
Potassium
Urea
Creatinine
Blood sugar
Calcium
Phosphate
AST
Alkaline phosphatase
Thyroxine
TSH
FSH
LH
Oestradiol
Testosterone
17-hydroxyprogesterone
23 nmol/l
(NR <5 nmol/l)
Androstenedione
16 nmol/l
(NR 512 nmol/l)
Dihydroepiandrostenedione 21 nmol/l
(NR <12 nmol/l)
Recumbent plasma renin 9 pmol/l/ml/h
(NR 0.22.2 pmol/l/ml/h)
Ambulant plasma renin
12 pmol/l
(NR 1.24.4 pmol/l)
Prolactin
385 mu/l
(NR <450 mu/l)
Urinary pregnantetriol
Elevated +++
US ovaries
Normal-sized ovaries
containing multiple
cysts
Small uterus
13 g/dl
7 ! 109/l
200 ! 109/l
138 mmol/l
4.0 mmol/l
4 mmol/l
60 mol/l
5 mmol/l
2.4 mmol/l
1.0 mmol/l
22 iu/l
179 iu/l
18 pmol/l
3.1 mu/l
5 u/l (NR 17 iu/l)
8 u/l (NR 220 iu/l)
90 pmol/l
(NR 4092 pmol/l)
9 nmol/l (NR 13 nmol/l)
Question 335
A 75-year-old male was investigated for increasing
dyspnoea.
Results of investigations are shown.
Chamber
Right atrium
Right ventricle
Pulmonary artery pressure
PCWP (mean)
Left ventricle
Aorta
Pressure
(cmH2O)
6
25/6
25/18
16
210/18
210/55
Oxygen
saturation (%)
65
67
67
98
98
336
Answer 334
Polycystic ovaries
Androgen-secreting adrenal tumour
Arrhenoblastoma
Cushings syndrome
17- hydroxylase
Pregnenolone
3-HSD
Progesterone
21-hydroxylase
Deoxycorticosterone
11- hydroxylase
Corticosterone
18-hydroxylase
180H-corticosterone
18-oxidase
Aldosterone
334
C-17 lyase
Dehydroepiandrostenedione
170H-pregnenolone
3-HSD
170H-progesterone
21-hydroxylase
11-deoxycortisol
11- hydroxylase
Cortisol
3-HSD
Androstenedione
Peripheral tissues
Testosterone
Clinical Cases
337
Answer 335
d. Long early diastolic murmur at left lower sternal
edge and in the aortic area.
Question 336
A 58-year-old male presented with nausea and pain in his
right upper quadrant. On examination he had tender
hepatomegaly with an irregular edge.
Investigations are shown.
Hb
WCC
Platelets
Neutrophils
Normoblasts
Myeloblasts
Myelocytes
Metamyelocytes
Lymphocytes
8 g/dl
18 ! 109/l
100 ! 109/l
68%
8%
8%
4%
6%
15%
Question 337
A 13-year-old male was admitted to hospital with
complete loss of vision in his right eye. He had been
placed in a juvenile offenders residential home six
months ago for stealing on several occasions. His parents
had separated a few months previously, and before that
he had been living with his father, who was an alcohol
abuser, and had three dogs. Two weeks before admission
he had complained of reduced visual acuity in his right
eye, which had progressively become worse.
On examination, he appeared well. He had
generalized lymphadenopathy, and was clinically blind in
the right eye. Examination of the fundus in the right eye
revealed two large, raised white lesions situated adjacent
to the optic disc and in the macular region. He was
apyrexial and all other physical examinations were
normal.
Investigations are shown.
Hb
WCC
Platelets
Neutrophils
Lymphocytes
Eosinophils
Monocytes
Basophils
ESR
Biochemistry
11.4 g/dl
6.6 ! 109/l (differential below)
180 ! 109/l
4.1 ! 109/l
1.2 ! 109/l
1.1 ! 109/l
0.11 ! 109/l
0.09 ! 109/l
25 mm/h
Normal
338
Answer 336
1. b. Marrow infiltration by malignant cells.
2. a. Bone marrow trephine.
The patient has a leucoerythroblastic anaemia (Table),
which is characterized by immature granulocytes and red
cells (normoblasts) in the peripheral blood film. This
characteristically occurs when the marrow is replaced by
malignant cells, cells containing metabolic products of
storage disorders, fibrous tissue and bone. Leukaemias,
lymphoma,
adenocarcinoma,
myeloma
and
myeloproliferative disease are all capable of malignant
infiltration. In this case, the patient has a knobbly liver,
suggesting liver metastases most probably from a primary
lung carcinoma. Carcinoma of the lung also metastasizes
to the bone and may result in marrow infiltration by
Answer 337
1. Ocular Toxocara infection or ocular larva
migrans.
2. i. IgM antibodies to Toxocara in the aqueous or
vitreous humour of the eye.
ii. IgM antibodies to Toxocara in the blood.
The patient has contracted Toxocara infection from the
dogs. Toxocariasis is due to migrating larvae of the
parasite T. canis. The disease occurs where there is a large
dog or cat population. It is well-recognized in the
Western world, and it is estimated that approximately
23% of the population carry antibodies to the parasite.
The parasite is carried in dogs (T. canis) and cats
(T. cati). Embryonated eggs are passed into faeces and
may be ingested by humans, particularly children in close
contact with cats and dogs (ingestion of contaminated fur
or soil). The larvae from the eggs hatch out into the
small intestine and migrate to liver, lungs and brain,
where they stimulate local granuloma formation by the
immune system. They do not mature into adult worms.
Toxocariasis can produce two distinct clinical patterns;
the classical visceral larva migrans syndrome, and ocular
toxocariasis. Most children who develop the classical larva
migrans remain asymptomatic. The minority develop
Clinical Cases
339
Question 338
A 58-year-old man presented with recent onset of
epigastric burning that was precipitated by hunger or
after a heavy meal. His appetite was unchanged and his
weight was stable. He was a non-smoker and did not
consume alcohol. The patient took paracetamol only for
a painful left hip.
Investigations are shown.
Hb
11 g/dl
MCV
70 fl
Ferritin
20 iu/l
Colonoscopy
Normal
H. pylori urease test Positive
Upper gastrointestinal endoscopy showed small
duodenal ulcer
Question 339
A 72-year-old woman underwent upper gastrointestinal
endoscopy for epigastric discomfort, which revealed mild
antral gastritis. She had a history of transient ischaemic
attacks for which she was taking aspirin 75 mg daily. The
patient also took regular diclofenac for arthritis. The
urease breath test for H. pylori was negative.
Question 340
A 68-year-old woman presented with lethargy, mild
weight loss, weakness, and progressive pain and stiffness
of her shoulders and thighs. On examination, she had
tender shoulder and thigh muscles and a fever of 38C
(100.4F).
Investigations are shown.
Hb
WCC
Platelets
ESR
Rheumatoid factor
AST
ALT
Alkaline phosphatase
Bilirubin
LDH
11 g/dl
13 ! 109/l
160 ! 109/l
85 mm/h
1/640
86 iu/l
296 iu/l
100 iu/l
12 "mol/l
1500 iu/l
340
Answer 338
a. Reassure and discharge. Review again if he
becomes symptomatic.
This patient with dyspepsia had iron deficiency anaemia,
which is an indication for upper gastrointestinal
endoscopy. He has a duodenal ulcer and has evidence of
Answer 339
e. Start misoprostil.
Gastroduodenal toxicity secondary to non-steroidal antiinflammatory drugs (NSAIDs) is relatively common. The
patient takes two NSAIDs, namely diclofenac and aspirin.
The best treatment would be to stop both drugs, but she
needs diclofenac for the treatment of her arthritis and
aspirin to reduce the risk of transient ischaemic attacks.
Until recently patients experiencing intolerable
gastroduodenal side-effects from NSAIDs used for
arthritis were switched from NSAIDs to COX II
inhibitors such as rofecoxib; however, the latter group of
drugs have been associated with an increased frequency
of adverse cardiovascular events and have been
withdrawn from the market.
Answer 340
a. Polymyositis.
The differential diagnosis is between polymyalgia
rheumatica and polymyositis (Table). Both present with
Polymyositis
Common
Common
Present
Absent
Present (30%)
Present (usually)
Present (30%)
Present
Present (20%)
Polymyalgia rheumatica
Common
May occur
Recognized
May be present
Absent
Absent
Absent
Absent
Absent
Clinical Cases
341
Question 341
A 74-year-old male presented with sudden onset of
dyspnoea. There was no preceding history of a cough or
chest trauma. He was a smoker. Four weeks previously he
had had a right knee replacement. There was a past
history of prostatic carcinoma, which was being
Arterial blood gases (air):
pH
7.45
PaCO2
3.4 kPa
PaO2
9.1 kPa
HCO3
21 mmol/l
Chest X-ray Left lower lobe shadowing
ECG
Non-specific T wave flattening in
leads V5 and V6
Inverted T waves in III and aVf
Question 342
A 70-year-old patient presented with dizziness (342).
342
342
Answer 341
d. CT pulmonary angiography.
The patient presents with sudden onset of dyspnoea in the
absence of a lower respiratory tract infection or pulmonary
oedema. He has a major risk factor for venous
thromboembolism, having had a recent knee replacement.
A coexisting history of prostatic carcinoma may also
contribute to his risk of venous thrombo embolism.
Therefore the clinical probability of the presentation being
secondary to pulmonary embolism is high. The probability
of PE is calculated by (a) demonstrating the absence of
another reasonable clinical explanation of the presentation
and (b) the presence of a major risk factor (Table). If both
(a) and (b) are present the probability of PE is high; if
either (a) or (b) is present the probability is intermediate;
and if neither (a) nor (b) is present the probability is low.
In patients where the clinical probability of PE is high,
the investigation of choice is CT pulmonary angiography,
(341) which has superseded ventilationperfusion
scanning in the investigation of PE. It is superior to
ventilationperfusion scanning in diagnosing and
excluding PE. It is quicker to perform, easier to arrange
urgently out of hours, and rarely needs to be followed up
by further imaging. Furthermore, CT pulmonary
Examples
Major abdominal,
pelvic, hip or knee
Late pregnancy,
Caesarean section,
puerperium
Fracture, varicose veins
Abdominal/pelvic,
advanced metastatic
Investigation of PE
Assess clinical probability
High
341
D-dimer N/A
Intermediate
SimpliRED
Start LMWH
CT Pulmonary angiogram
PE
Warfarin
No PE
Low
Vidas/MDA
Any D-dimer
D-dimer assay
Positive
Negative
Another
diagnosis
Clinical Cases
343
Answer 342
e. Mobitz type I second degree AV block.
There is failure of some P-waves to conduct that is preceded
by progressive prolongation of the PR interval, which is
Question 343
343
13 g/dl
6 !109/l
200 !109/l
28 mm/h
32 g/l
7.4
4.3 kPa
8.3 kPa
26 mmol/l
Question 344
A 44-year-old male who was receiving haemodialysis
three times weekly complained of fatigue, night sweats
and a dry cough and was found to have a haemoglobin of
Hb
MCV
WCC
Serum ferritin
Serum B12
Serum folate
Serum aluminium
Plasma PTH
C-reactive protein
8.5 g/l
87 fl
11 ! 109/l
580 mg/l
260 ng/l
7 mg/l
6 mg/l
15 pmol/l (NR 0.95.4 pmol/l)
110 mg/l (NR <10 mg/l )
344
Answer 343
c. Cryptogenic fibrosing alveolitis.
There is no obvious cause for the increasing
breathlessness in the history. Although the patient has
been taking an ACE inhibitor for six months, there is no
association between ACE inhibitors and pulmonary
fibrosis. The physical findings and the chest X-ray are
consistent with cryptogenic fibrosing alveolitis. There is
reticulonodular shadowing of both lung bases. The
differential diagnosis for bibasal lung shadowing is shown
(Table). Although sarcoidosis is listed in the potential
choices, there is no previous history of acute sarcoid nor
any evidence of multi-system involvement.
Answer 344
c. Chronic sepsis.
The patient has resistance to erythropoietin despite
satisfactory iron stores the causes of which are tabulated
below. Iron deficiency is by far the commonest cause of
anaemia despite erythropoietin. Erythropoeitin should
not be started until iron stores are replenished as
evidenced by a serum ferritin 150 mg/l, or the
transferrin saturation is 20%.
The data provided in the question are against folate or
B12 deficiency or aluminium toxicity. The patient has a
mildly raised serum PTH, as one would expect in a
patient with chronic renal failure. In general
erythropoietin resistance is only seen in bone disease due
to severe hyperparathyroidism. The history of malaise and
night sweats together with the raised serum CRP,
indicates that the most probable cause for failure to
respond to erythropoietin is chronic sepsis. The
identification and treatment of the source of sepsis should
help resolve the anaemia.
Clinical Cases
345
Question 345
A 38-year-old male with HIV presented with confusion
and ataxia and reduced visual acuity in the left eye. A
brain MRI scan is shown (345a).
345a
Question 346
A 72-year-old male presented with anorexia, nausea and
intermittent falls secondary to dizziness. The BP
measured 110/60 mmHg when lying and 70/30 mmHg
on standing (accompanying dizziness). The JVP was
raised. Cardiac auscultation revealed a loud third heart
sound. There was mild pitting ankle oedema.
Investigations were as follows:
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Calcium
Phosphate
AST
Alkaline phosphatase
Albumin
Total protein
24-hour urinalysis:
Protein
Sodium
8.9 g/dl
9 ! 109/l
170 ! 109/l
89 mm/h
131 mmol/l
3.8 mmol/l
14 mmol/l
2.8 mmol/l
1.9 mmol/l
26 iu/l
140 iu/l
19 g/l
70 g/l
5 g/l
7 mmol/l
346
Answer 345
b. Progressive multifocal leucoencephalopathy.
The MRI scan reveals multiple bilateral, asymmetrical
confluent high intensity signals without any evidence of
raised intracranial pressure or mass effect. This is the
characteristic finding in progressive multifocal
leucoencephalopathy. The lesions usually involve the
periventricular areas and subcortical white matter. The
spinal cord is rarely affected in PMLE.
In contrast, most patients with HIV syndrome
develop cerebral disorders associated with cerebral
oedema and mass effect on CT scan or MR scan of the
brain (345b).
Multiple sclerosis may have similar findings on the
MRI scan; however, confusion and multifocal
abnormalities occurring simultaneously in an immunocompromised patient are more consistent with the
diagnosis of PMLE.
PMLE is characterized by rapidly progressive focal
neurological deficit without evidence of raised
intracranial pressure. The disorder affects
immunocompromised patients who become infected with
345b
Mass effect
No mass effect
Cerebral toxoplasmosis
Cerebral lymphoma
Cryptococcal meningitis
TB meningitis or tuberculoma
Nocardia infection
Bacterial abscess
CMV encephalitis
PMLE
HIV encephalitis
Answer 346
c. Autonomic neuropathy secondary to amyloidosis.
The patient has anaemia, a raised ESR, and
hypercalcaemia, which are all consistent with the
diagnosis of multiple myeloma. The heart failure and
nephrotic syndrome in a patient with myeloma is highly
suggestive of primary amyloidosis complicating the
multiple myeloma. Primary amyloidosis is a recognized
Clinical Cases
347
Question 347
A 78-year-old female patient presented with acute
abdominal pain and vomiting. A plain abdominal film is
shown (347a).
347a
Question 348
A 30-year-old female presented with malaise, nausea,
vomiting and right upper quadrant pain in the last week
of her pregnancy. She had tolerated the pregnancy very
well prior to the event. Her blood pressure control
throughout the pregnancy had been good, with the last
Hb
WCC
Platelets
PT
APTT
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
ALT
Alk Phos
LDH
Albumin
Amylase
Urinalysis
Hepatobiliary ultrasound
10 g/dl
12 ! 109/l
33 ! 109/l
12 sec
43 sec
137 mmol/l
3.4 mmol/l
12 mmol/l
223 "mol/l
20 mol/l
250 iu/l
298 iu/l
200 iu/l
800 iu/l
33 g/l
150 iu/l (NR <220 iu/l)
Protein +
Normal
348
Answer 347
c. Gallstone ileus.
347b
Answer 348
c. Deliver the baby urgently.
The patient presents with nausea, vomiting and right
upper quadrant discomfort towards the end of her
pregnancy. Her blood pressure is at the upper limit of
normal and considerably higher than it was two weeks
previously. The patient also has proteinuria, a microangiopathy as characterized by the fragmented red cells
on the blood film, abnormal liver enzymes and low
platelets. The diagnosis is consistent with the HELLP
syndrome (haemolysis, elevated liver enzymes and low
platelets. The condition affects approximately 1 per 1000
pregnancies. It is more common in multiparous women.
Some authorities believe that it is a manifestation of
severe pre-eclampsia; however, approximately 15% of
affected females do not have hypertension and
proteinuria, which are the classical hallmarks of preeclampsia, causing other authorities to postulate that it
may be a completely separate disorder.
HELLP syndrome usually occurs in the last trimester
of pregnancy or within the first week of parturition. A
few cases may have been reported to occur in the second
trimester. Patients often present with malaise, nausea,
vomiting and right upper quadrant tenderness. The
condition may mimic several other medical conditions
such as viral hepatitis and cholecystitis. Hypertension and
proteinuria are often present. The blood film shows
Management of HELLP
1. Deliver the foetus as soon as possible.
2. Intravenous corticosteroids in females <34
weeks gestation to defer early delivery.
3. Treat hypertension.
4. Platelet and blood transfusion if there is
bleeding.
5. Magnesium sulphate for epileptic seizures.
6. Dialysis for rapidly deteriorating renal function.
Clinical Cases
349
Question 349
A 30-year-old male presented with sudden onset of leftsided weakness. The was no history of headache. He had
experienced transient weakness of his right arm three
years previously, which resolved spontaneously after
5 hours and did not receive medical attention. He had a
past history of multiple episodes of epistaxis which had
not been investigated. Eight months previously he had
experienced a cough associated with fever and
intermittent haemoptysis, which improved after a course
of amoxicillin, but he had been more breathless than
usual since the episode. There was no family history of
premature atherosclerosis. His father was fit and well but
his mother was anaemic and had been investigated on
numerous occasions for gastrointestinal haemorrhage.
The patient smoked 20 cigarettes per day.
On examination he had a left-sided hemiparesis. The
pulse was regular. The blood pressure measured
Hb
WCC
Platelets
PCV
CRP
Total cholesterol
Blood glucose
12-lead ECG
Echocardiogram
CT scan brain
Carotid Doppler studies
Chest X-ray (349a)
18 g/dl
11 ! 109/l
206 ! 109/l
0.58
9 g/l
5.2 mmol/l
4.1 mmol/l
Normal
Normal
Normal
Normal
349a
Question 350
A 75-year-old male presented with exertional chest pain.
On examination he had an ejection systolic murmur
consistent with aortic stenosis. The 12-lead ECG
revealed voltage criteria for left ventricular hypertrophy.
Echocardiography confirmed calcific aortic stenosis with
a pressure gradient of 68 mmHg across the aortic valve.
350
Answer 349
d. Hereditary haemorrhagic telangiectasia.
This young patient presents with a stroke in the absence of
any of the conventional risk factors for atherosclerosis. He
has a long history of epistaxis. He also has haemoptysis,
and his chest X-ray reveals a well-defined round opacity
adjacent to the right heart border that has a linear shadow
at the 1 oclock position, consistent with a feeding vessel
indicating a pulmonary arterio-venous mal formation.
There is a family history of anaemia and gastrointestinal
haemorrhage and visible telangiectasia in the left nostril.
The most likely underlying diagnosis is hereditary
haemorrhagic telangiectasia. The increased haemoglobin
concentration in this patient reflects physiological
polycythaemia due to chronic hypoxaemia.
HHT, also known as OslerWeberRendu syndrome,
is a genetic disorder resulting in arterio-venous
malformations in various parts of the body including the
skin, liver, respiratory system, GI tract and the brain.
Abnormalities in the genes encoding the angiogenesis
factors endoglin and activin receptor-like kinase 1 have
been identified on chromosome 9 and 12 respectively.
Complications of HHT
349b
Migraines
Seizures
TIA/CVA
Cerebral abscess
Cerebral haemorrhage due to cerebral arteriovenous malformation
Haemothorax
Massive haemoptysis
Pulmonary hypertension
Central cyanosis
GI haemorrhage
Anaemia due to blood loss
Polycythaemia due to chronic hypoxia
Answer 350
d. Presence of symptoms.
Indications for surgery in severe aortic stenosis include:
Presence of symptoms.
Patients with severe AS undergoing coronary artery
bypass surgery.
Patients with severe AS undergoing surgery on the
aorta or other heart valve(s).
Clinical Cases
351
Question 351
A 36-year-old woman presented with fever and malaise.
She had been commenced on carbimazole for
symptomatic thyrotoxicosis four weeks previously. On
examination her temperature was 39.2C (102.5F) and
her mouth was red. Examination of all the major systems
was normal.
Investigations are shown.
Hb
WCC
Platelets
CRP
Chest X-ray
B cultures
Mouth swabs
Urine culture
Stool culture
12 g/dl
0.8 ! 109/l (neutrophils 0.3)
190 ! 109/l
240 mg/l
Normal
No growth
No growth
No growth
No pathological organisms
Question 352
A 16-year-old Spanish boy was admitted to hospital with
a three-day history of abdominal pain and jaundice. One
week before admission he had developed a sore throat,
accompanied by fever and myalgia. He had experienced
three similar episodes of jaundice and abdominal pain
preceded by a sore throat and fever at the ages of 6, 12
and 14, and on each occasion he made an uncomplicated
recovery. There was no history of recent travel abroad.
He was the only child in the family.
Hb
WCC
Platelets
Monospot test
Bilirubin
ALT
Alkaline phosphatase
Urinalysis
9.1 g/dl
6 ! 109/l
100 ! 109/l
Negative
33 mmol/l
23 iu/l
120 iu/l
Urobilinogen ++++
Nil else
352
Answer 351
carbapenem such as meropenem, or a third generation
cephalosporin such as ceftazidime, together with an
351
Duration of antibiotics
Antithyroid (carbimazole)
Sulphonamides
Anticonvulsants
Non-steroidal anti-inflammatory
drugs (phenylbutazone)
Antibiotics (chloramphenicol)
Phenothiazines
Any drugs used for chemotherapy
Afebrile on day 3
Yes
Neutrophil count
0.5 after 48 h
Stop antibiotics if no
obvious focus of
infection
No
Neutrophil count
< 0.5 after 48 h
Low risk
Neutrophil count
0.5 after 48 h
High risk
Neutrophil count
<0.5 after 48 h
Continue antibiotics
Stop when afebrile for 57 days
Clinical Cases
353
Answer 352
352
a. Hereditary spherocytosis.
The history of recurrent episodes of abdominal pain and
jaundice precipitated by a sore throat in a young boy with
anaemia, splenomegaly and a raised urinary urobilinogen is
suggestive of an inherited haemolytic anaemia. There is a
family history of splenectomy to treat anaemia in a firstdegree relative to support a hereditary anaemia. The most
likely diagnosis is HS, although other possible causes of this
picture include hereditary elliptocytosis, glucose-6phosphate dehydrogenase deficiency, pyruvate kinase
deficiency. Sickle cell anaemia may be associated with
haemolytic crises during infection, however the spleen is
impalpable because it has atrophied owing to multiple
infarcts. The history of a purulent sore throat and haemolysis
could be explained entirely by infectious mononucleosis;
however, it would be unusual for a young boy to have three
episodes of EBV infection. In this case, the sore throat has
been the precipitant for increased haemolysis in an individual
with a red cells which are vulnerable to haemolysis. Gilberts
disease is associated with mild jaundice during illness but
does not explain the anaemia or haemolysis.
Hereditary spherocytosis (352) is an autosomal dominant
disorder of red cells. It is due to a defect in the membrane
protein spectrin, which results in membrane loss as the cell
passes through the spleen. The surface-to-volume ratio is
reduced and the cells become spherocytic. Spherocytes are
eventually destroyed by the spleen. The disorder may present
as neonatal jaundice; however, most patients have a low-
Question 353
A 16-year-old boy was found dead in bed by his mother.
A detailed post-mortem failed to reveal any obvious
cause of death. His father died suddenly aged 30. He had
a paternal aunt who was being investigated for syncopal
episodes. His sister was diagnosed as having epilepsy
aged 11.
354
Answer 353
e. Long QT syndrome.
The patient has died suddenly in the absence of previous ill
health and the postmortem has failed to reveal any
abnormality. By definition this individual is a victim of the
sudden adult death syndrome. There are approximately 500
such cases in the UK each year. Most deaths are thought to
be secondary to fatal cardiac arrhythmias. Many conditions
may be identifiable on 12-lead ECG during life and many
may be familial. It is now recommended that all first-degree
relatives of victims of SADS undergo cardiovascular
evaluation to identify conditions that could potentially cause
sudden cardiac death.
In this particular case there is reason to believe that
the patient may have died from a familial cardiac disorder
since there is a family history of premature sudden death
and syncope. Long QT syndrome is a well recognized
cause of sudden death in young patients where the postmortem is normal. The diagnosis can be made antemortem with 12-lead ECG. Patients with long QT
syndrome may be entirely asymptomatic or experience
syncope/sudden death or epileptic seizures due to
malignant ventricular arrhythmias. Patients with long QT
syndrome are often misdiagnosed as having epilepsy.
Most sudden non-traumatic deaths in young
individuals are due to cardiac disease. The causes of
sudden cardiac death with normal post-mortem findings
are shown below (Table).
Brugadas syndrome is a genetic disorder caused by
mutations within the sodium ion channel SCN5A. The
disorder is inherited as an autosomal dominant trait and
characterized by a propensity to fatal ventricular arrhythmias
and sudden death in patients with structurally normal hearts.
The resting ECG shows a characteristic peculiar pattern
consisting of a pseudo-right bundle branch block and
persistent ST elevation in leads V1 to V3 (353). The
widened S-wave in the left lateral leads that usually
characterizes RBBB is absent in most patients with Brugadas
syndrome, suggesting that there is a high take off of the ST
segment in the right precordium (J-wave) rather than true
353
Clinical Cases
355
Question 354
A 63-year-old male with end-stage renal failure and a
12-month history of dialysis had been on an active renal
transplant list for over six months. Over the past few
months dialysis therapy had been incomplete owing to
poor tolerance, and his general health had started to
deteriorate. He had made enquiries about renal
transplants and had heard that he could travel to some
third-world countries and purchase a kidney at a cheap
price. He was married with one son aged 16 years old.
He did not have any siblings and both parents had died.
His wife was not keen to donate her kidney, however his
son was eager to donate to help his father.
Question 355
A 60-year-old female presented with a dry cough and
haemoptysis. She had a past history of tuberculosis. A
chest X-ray and CT scan of the thorax are shown in
figures 355a and b, respectively.
355a
355b
356
Answer 354
d. Advise him to take his sons kidney.
This question relates to ethical issues around organ
donation for transplantation. Availability or renal donors
for transplants is a major problem in all developed
countries. Most patients receive transplants from
cadavers; however, success from live donor transplants is
superior to cadaveric transplants even in non-related
donors. A blood group match in essential. A HLA match
is desirable but not mandatory.
In this particular situation, a first-degree relative is
prepared to donate his kidney. The individual in question
is above the age of 16 and in a situation where he may
sign his own consent to donate his kidney. Absolute
contra-indications to organ donation for renal
transplantation are tabulated below. The son should
undergo routine blood tests, urinalysis, 24-hour urine
assessment of protein estimation and creatinine clearance,
HLA typing, serology for viral antibodies including CMV
and HIV, IVU and renal angiography or equivalent.
Answer 355
d. Aspergilloma.
The plain X-ray reveals a scarring in the left apex
consistent with previous tuberculosis. In the right apex
there is an opacity surrounded by a crescent of air
(Monods sign). This finding is typical of an aspergilloma
(mycetomoa) in an old tuberculous cavity. The CT scan
of the thorax demonstrates the mass lesion within the
lung cavity (the air around the aspergilloma is black).
Aspergilloma is due to colonization by the species
Aspergillus fumigatus rather than direct tissue invasion,
and is usually not an indicator of an immuno compromised state. It arises most commonly in old
tuberculous cavities but may occur in cavities created by
neoplasms, sarcoidosis and other fungal infections such as
histoplasmosis (causes of pulmonary cavities are
tabulated). The aspergilloma comprises fungal hyphae,
inflammatory cells and fibrin. Patients may be asymptomatic but the vast majority experience haemoptysis. Some
patients complain of chest pain, wheeze and a fever. The
diagnosis is made with radiological tests. The chest X-ray
is usually diagnostic but confirmation of the aspergilloma
may require a CT scan or MRI scan of the thorax. The
identification of Aspergillus in the sputum in such
patients is highly suggestive of the diagnosis.
Primary
Secondary
Vascular
Pulmonary emboli
Vasculitides
Granulomatous disease
Sarcoidosis
Clinical Cases
357
Question 356
A 26-year-old female with cystic fibrosis wishes to become
pregnant. She has never had any previous pregnancies. She
was menstruating once or twice every three months. She
had been with her partner for six years. She was diagnosed
with cystic fibrosis as a neonate after presenting with rectal
prolapse. Her condition was relatively satisfactory in
childhood. During adolescence she experienced three to
Question 357
357
Question 358
Hb
WCC
Platelets
MCV
ESR
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
Total protein
X-ray lumbar spine
10 g/dl
10!109/l
180!109/l
84 fl
96 mm/h
133 mmol/l
4.6 mmol/l
11 mmol/l
180 "mol/l
3.2 mmol/l
1.4 mmol/l
30 g/l
74 g/l
Wedge fracture 4th lumbar
vertebra
358
Answer 356
d. To go ahead and become pregnant but explain the
risk of her offspring being affected.
The patient has stable pulmonary function and normal
pulmonary artery pressures, which is the main medical
concern with respect to the risk of pregnancy for the
female. Females with poor lung reserve may develop
respiratory failure once the diaphragm is splinted by the
gravid uterus. Patients with pulmonary hypertension are
at risk of cardiac failure.
Approximately 20% of females with cystic fibrosis are
infertile owing either to malnourishment or to viscid
cervical secretions. However, most women are capable of
falling pregnant, and advice regarding conception is
mainly based on the clinical risk of cardiac or heart failure
during gestation. Patients with severe lung disease or
significant pulmonary hypertension (50 mmHg) should
be discouraged from becoming pregnant owing to the
high risk of cardio-respiratory failure.
Most women with stable pulmonary function and FEV1
values 60% predicted usually tolerate pregnancy without
complication. Patients with unstable respiratory function
Answer 357
b. Avascular necrosis of the femora.
The patient has increased lucency in both femoral heads
below the articular surfaces. The femoral heads have lost
their smooth spherical shape, indicating advanced disease.
These findings are consistent with the diagnosis of
avascular necrosis affecting both femoral heads. Avascular
necrosis is a frequent complication following renal
transplantation. The aetiology is multi-factorial but
steroid therapy for immunosuppression plays an
important role. The prevalence of avascular necrosis of
bone following transplantation has reduced significantly
since the use of ciclosporin. Other causes of avascular
necrosis of bone are tabulated below. Patients present
with groin or buttock pain that is worse on movement.
Treatment may involve conservative measures such as
analgesia and reduced movement of the joint concerned,
but generally core decompression, osteotomy or joint
replacement is required to treat the condition.
Answer 358
d. Bone marrow biopsy.
Clinical Cases
359
Question 359
A 76-year-old man was seen in the Accident and
Emergency Department after an episode of loss of
consciousness. He had become increasingly confused and
suffered several falls over the past two months. Over the
past six months his family had noticed a gradual
deterioration in his health. He had a constant nonproductive cough. He appeared apathetic and
uninterested in his surroundings. His appetite was
reduced, but according to his wife he was constantly
thirsty and had recently become incontinent of large
volumes of urine. His GP had commenced
antidepressants three weeks previously. He smoked 40
cigarettes per day until two weeks previously but did not
Question 360
An 18-year-old female suffers from epilepsy and mental
retardation. Her mother was similarly affected. A CT scan
of the brain is shown (360).
360
Question 361
361
Affected male
Unaffected male*
Affected female
Unaffected female*
360
Answer 359
c. Chest X-ray.
In a life-long heavy smoker, the symptoms of persistent
cough, weight loss, polydipsia and polyuria in the
presence of a normal blood glucose are indicative of
bronchial carcinoma complicated by hypercalcaemia.
Hypercalcaemia is associated with nephrogenic diabetes
inspidus. The hypercalcaemia may be secondary to bony
Answer 360
b. Adenoma sebaceum (facial angiofibromas).
The patient has a history of mental retardation and
epilepsy. Her mother also has epilepsy, raising the
possibility of a familial condition. The CT scan of the brain
shows subependymal calcified nodules which represent
calcified hamartomas. This finding is almost pathog nomonic of tuberous sclerosis in a patient who has epilepsy.
Tuberous sclerosis is a neurocutaneous disorder that
is inherited as an autosomal dominant trait with variable
phenotypic expression. It is characterized by epilepsy,
mental retardation and facial angiofibromas (Vogts triad)
and benign tumour in the brain, heart and kidneys. The
prevalence ranges from 1/5000 to 1/10,000 births.
Mutations in two genes are responsible for the disease
process. The first gene, TSC1, is on chromosome 9 and
encodes the protein hamartin. The second gene, TSC2, is
on chromosome 16 and encodes the protein tuberin. The
precise functions of hamartin and tuberin are unknown,
but animal studies suggest that both play an important
role in brain development.
Only 50% of patients present with the classic Vogts
triad, therefore the diagnosis relies on the demonstration
of two major and one minor criteria or one major and
two or more minor criteria from Table A. Other features
include shagreen patches, hypomelanotic lesions and
periungual fibromas.
Short metacarpals are a feature of pseudohypoparathyroidism (see Question 159) and are associated
with calcification of the basal ganglia. Bilateral ptosis has a
large differential diagnosis, but mitochondrial disorders are
a recognized cause of bilateral facial weakness and
calcification of the basal ganglia. Retinitis pigmentosa is
Answer 361
e. Autosomal dominant with incomplete penetrance.
Clinical Cases
361
Question 362
A 20-year-old cyclist was seen by a cardiologist after
experiencing a sudden syncopal episode while training for
a major race. For the past six months he had complained
of deteriorating fitness despite strenuous training and
higher heart rates during training sessions. There was no
history of chest pain, palpitation or breathlessness during
normal exertion. He was a non-smoker and drank a
maximum of 6 units of alcohol per week. He denied all
forms of drug abuse.
His father died suddenly at the age of 33 years. The
cause of death was not entirely clear but was attributed to
a form of heart disorder. His sister had recently seen a
362a
362b
d. Dilated cardiomyopathy.
e. Multiple pulmonary emboli.
362
Answer 362
c. Arrhythmogenic right ventricular cardiomyopathy.
The combination of T wave inversion in the right
ventricular leads (V1V3), dilated and hypokinetic right
ventricle, ventricular tachycardia with left bundle branch
morphology and more than 1000 ventricular ectopics
with left bundle branch morphology in the context of a
family history of premature sudden cardiac death is
consistent with the diagnosis of arrhythmogenic right
ventricular cardiomyopathy (Table).
ARVC is characterized by fibrofatty replacement of
the right ventricle, resulting in right ventricular
dysfunction and arrhythmias of right ventricular origin
(LBBB morphology). The disorder is due to mutations in
genes encoding cell adhesion proteins. The two main
proteins identified thus far are desmoplakin and
plakoglobin. The disorder has a prevalence of 1 in 5000.
Over one-third of cases are familial, with an autosomal
dominant inheritance pattern. Patients often experience
palpitation, presyncope or syncope. Sudden death from
ventricular fibrillation may be the first presentation and
occurs most commonly during physical exercise.
The ECG is abnormal in 90% of cases with symptoms
and usually shows T-wave inversion in the right
ventricular leads and depolarization abnormalities after
the QRS complex (often termed epsilon waves).
Echocardiography may be normal but in gross cases
demonstrates aneurysms of the right ventricular wall.
The MRI scan is more diagnostic, revealing fatty
infiltration of the right ventricle.
Question 363
363
This is a chest X-ray from an asymptomatic 50-year-old
banker (363).
What is the diagnosis?
a. Cryptogenic fibrosing alveolitis.
b. Miliary tuberculosis.
c. Healed chicken pox pneumonia.
d. Pulmonary metastases.
e. Histoplasmosis.
Clinical Cases
363
Question 364
A 54-year-old male presented with an acute painful
swollen left knee. There was no history of trauma or any
systemic features. There was a past history of a bleeding
Hb
WCC
Platelets
ESR
CRP
Blood cultures
Joint aspirate
16 g/dl
13 ! 109/l
359 ! 109/l
78 mm/h
92 g/l
Normal
Needle-shaped crystals with
strong negative
birefringence under
polarized light
Question 365
A 77-year-old male was seen in the memory clinic owing
to progressive deterioration of cognitive function.
According to his daughter he had been diagnosed with
Parkinsons disease two years previously, for which he
was commenced on L-dopa. Over the past few months
FBC
ESR
Serum B12
Serum folate
U&E
Blood sugar
Thyroid function
12-lead ECG
Chest X-ray
Urinalysis
CT scan brain
Normal
33 mm/h
Normal
Normal
Normal
Normal
Normal
SR; left axis deviation
Normal
Normal
Mild global cerebral
atrophy
364
Answer 363
c. Healed chicken pox pneumonia.
There are multiple calcified nodules throughout both lung
fields in an otherwise asymptomatic patient. The differential
diagnosis of multiple nodular opacities in the lungs is
tabulated below. Patients with miliary TB are systemically
unwell and complain of fever, cough and night sweats.
Although histoplasmosis may present with multiple calcified
nodules in the lung, the patient is completely well whereas
patients with miliary histoplasmosis usually experience
profound respiratory symptoms. Cryptogenic fibrosing
alveolitis is associated with diffuse reticulonodular
Occupational dusts
Pulmonary metastases
Alvelolar microlithiasis
TB
Histoplasmosis
Coccidiocomycosis
Chicken pox in adulthood
Silicosis
Caplans syndrome
Answer 364
e. Inject joint with steroid.
The treatment options for acute gout include the use of
non-steroidal anti-inflammatory agents, colchicine or
injection of the joint with steroids. The most effective
method of treating monoarticular gout is aspiration of the
joint with intra-articular steroid injection. This method
provides rapid relief of symptoms and produces no systemic
side-effects. NSAIDs are relatively contraindicated in a
Answer 365
d. Lewy body dementia.
The presence of hallucinations, falls and syncope in a
patient with Parkinsons disease is suggestive of dementia
with Lewy bodies, which is the most common form of
dementia associated with Parkinsons disease. It is
characterized by the presence of Lewy bodies in the
brainstem and the cortex. Lewy bodies are intracytoplasmic
inclusions composed of alpha-synuclein and ubiquitin. The
dementia is slowly progressive. There are fluctuations in
cognition in relation to alertness and attentiveness. Memory
impairment is mild in the early stages. Patients experience
recurrent visual hallucinations of people and animals.
Features of parkinsonism are generally mild. Daytime
drowsiness and sleepiness, falls, syncope and delusions are
well recognized. Patients with Lewy body dementia are
particularly sensitive to neuroleptic agents. There is
considerable overlap between Parkinsons disease, Lewy
body dementia and Alzheimers disease. Daytime sleepiness
or drowsiness appears to be more common in Lewy body
dementia than the other two entities.
Pickss disease is a subtype of fronto-temporal dementia
that is characterized by Pick bodies in the neocortex and
Clinical Cases
365
Question 366
A 68-year-old male with disseminated colonic carcinoma
was admitted to hospital having collapsed at home. He had
been complaining of severe back pain for 48 hours, for
which he was taking two different analgesic agents. He was
also taking bronchodilator inhalers for chronic asthma.
On examination he was drowsy and had a Glasgow
coma score of 8. The pupils were small and equal and
Sodium
133 mmol/l
Potassium
3.7 mmol/l
Urea
8 mmol/l
Calcium
2.7 mmol/l
Albumin
29 g/l
Arterial blood gases on 60% oxygen:
pH
7.2
PaCO2
9.6 kPa
PaO2
28 kPa
HCO3
28 mmol/l
CT scan brain
Multiple cerebral
metastases
Question 367
A 64-year-old male presented with a three-month history
of copious diarrhoea associated with lower abdominal
cramps and weight loss. The patient moved his bowel up
to 20 times per day. There was no blood in the stools.
He had a past history of gallstones, for which he
underwent a cholecystectomy five years ago. He had not
experienced any episodes of biliary colic since surgery.
The patient was also in the process of being investigated
for intermittent dizziness that usually occurred after
meals and was preceded by a burning sensation over the
face, neck and chest. According to his wife he developed
a red complexion during these episodes, which lasted for
3060 seconds at a time. On two occasions he had
almost lost consciousness when he stood suddenly during
these episodes. The patient had not travelled abroad for
over eight months. He was not taking any medication.
His father had ulcerative colitis and his paternal nephew
had gluten sensitive enteropathy.
On examination he had several telangiectasiae on his
face, neck and upper trunk. The JVP was raised with
prominent V waves. On auscultation of the precordium,
there was a soft systolic murmur. The chest was clear.
Abdominal examination revealed a palpable liver edge
5 cm below the costal margin that had a firm and
irregular consistency. Rectal examination was normal.
11 g/dl
80 fl
12 ! 109/l
200 ! 109/l
68 mm/h
130 mmol/l
3.4 mmol/l
9 mmol/l
40 iu/l
320 iu/l
16 mol/l
29 g/l
366
Answer 366
b. Intravenous naloxone.
The patient takes analgesia for chronic pain, presumably
related to the disseminated carcinoma. He presents with
drowsiness, miosis, reduced respiratory rate and a
respiratory acidosis. The patient has tachycardia, which is
probably due to vasodilatation from the acidosis. The most
probable cause of the presentation is opiate overdose, which
may be accidental or deliberate. The immediate treatment
to reverse the effects is intravenous naloxone. Although
benzodiazepine overdose can present in identical fashion,
the patient is more likely to have taken excess opiate for his
pain rather than a benzodiazepine. Flumazenil, the antidote
for benzodiazepine overdose, should be considered only if
respiratory depression is not reversed with naloxone.
The patient also has cerebral metastases, which may be
causing raised intracranial pressure and may be
Answer 367
e. Carcinoid syndrome.
The patient has copious diarrhoea and weight loss as well
as intermittent dizziness associated with a red
complexion, which would be consistent with carcinoid
syndrome. The presence of a firm and irregular liver edge
is highly suggestive of metastases to the liver which is
usually required for the clinical manifestation of carcinoid
tumours arising from the gastrointestinal tract.
Crohns disease and coeliac disease rarely cause
copious diarrhoea and would not explain the flushing. In
ulcerative colitis loose stool is often blood-stained.
Carcinoid syndrome is caused by tumours that have
the ability to store and synthesize polypeptides and
biogenic amines and prostaglandins. The tumours
commonly arise from the gut, notably the small bowel,
appendix and rectum, and may arise from the lungs and
pancreas. The tumours commonly produce serotonin, a
metabolite of the amino acid tryptophan, histamine and
kallikrein. These biogenic compounds are inactivated by
the liver. After metastasis to the liver, the amines are
secreted into hepatic veins and enter the systemic
circulation to cause symptoms.
In the vast majority of cases, the symptoms depend
largely on the proportion of serotonin, histamine or
kallikrein produced by the tumour. In general, hindgut
tumours such as those arising from the rectum lack the
decarboxylase enzyme that catalyses the conversion of
tryptophan to 5-hydroxytryptamine, therefore these
tumours are unable to cause the carcinoid syndrome.
Clinical Cases
367
Question 368
A 16-year-old girl collapsed at school while playing
hockey. According to the physical training tutor, she was
unconscious for a few seconds and then was completely
rousable and did not realize what had happened. The
episode occurred without any warning symptoms. There
was no history of trauma or head injury during the game,
or any ill health before the game. There was no history of
epilepsy. She had experienced two previous syncopal
episodes at the ages of 8 and 11 years. On the first
occasion she had witnessed a road traffic accident, and on
the second occasion she collapsed after receiving a hoax
telephone call. She had been completely well since the
last syncopal episode. She was not taking any medication.
She had a younger brother, aged 14, who was well. Her
parents were well. Her mother had a past history of
syncopal episodes during her adolescence, for which no
cause had been found. Her maternal aunt was found
dead in her bed at the age of 15, for which no cause was
found at post-mortem.
On examination, the patient was 1.55 m tall and
weighed 48 kg. Her heart rate was 65 beats/min and
irregular. The blood pressure was 110/65 mmHg.
Examination of the precordium was completely normal.
There were no carotid bruits, and all peripheral pulses
were palpable. The chest was clear and abdominal
examination was normal. Examination of the central
nervous system, including the fundi, was completely
normal
Investigations are shown.
The following day, the patient was being seen by the
consultant cardiologist and his team on the ward when
she had a syncopal episode. The tracing from the ECG
monitor is shown (368b).
368a
368b
Hb
WCC
Platelets
Blood glucose
ECG (368a)
Sodium
Potassium
Urea
14 g/dl
12 ! 109/l
300 ! 109/l
5 mmol/l
136 mmol/l
3.5 mmol/l
4 mmol/l
368
Answer 368
1. d. Congenital LQTS.
2. c. Abnormal sodium/potassium channels in cardiac
myocytes.
3. d. A beta-blocker.
4. d. Family screening.
The combination of a family history of premature sudden
death, long QT and polymorphic ventricular tachycardia
associated with syncope is diagnostic of idiopathic LQTS.
The condition is familial in up to 90% of cases, and can
be inherited both as an autosomal dominant and recessive
trait. The rarer variant (autosomal recessive) is associated
with congenital nerve deafness and known as the
JarvellLangeNeilsen syndrome. The more common
autosomal dominant form is often known as the
RomanoWard syndrome.
In congenital LQTS defects within transmembrane
ion channels produce abnormalities in cardiac
repolarization, leading to an increased propensity for
syncope due to fatal ventricular arrhythmias in situations
causing increased sympathetic activity. Syncope may be
precipitated by physical exertion, intense emotion and
sudden loud auditory stimuli. The classic arrhythmia is a
form of polymorphic ventricular tachycardia termed
torsades de pointes, which may degenerate to
ventricular fibrillation, causing sudden death. Thus far,
abnormalities have been demonstrated in genes encoding
both potassium and sodium ion transport channel
proteins which are located on chromosomes 11, 3, 4 and
7 (see below).
Myocardial disarray is a feature of HCM; an accessory
conduction pathway would indicate Wolff
ParkinsonWhite or LownGanongLevine syndrome;
fibrofatty replacement of the myocardium would indicate
arrhythmogenic right ventricular cardiomyopathy; and
myocardial fibrosis is a finding common to all
cardiomyopathies and ischaemic heart disease.
Treatment is aimed at reducing the effects of the
sympathetic nervous system on the conduction tissue.
The immediate treatment of choice to prevent further
ventricular tachycardia is beta-blockers, which may be
given intravenously in the first instance. In situations
where this produces a profound bradycardia a permanent
pacemaker is also implanted. There is some evidence that
intravenous magnesium may arrest ventricular
arrhythmias in the acute state, even when the serum
magnesium level is normal. Patients who continue to
have ventricular arrhythmias despite heavy beta-blockade
are implanted with an automatic cardioverter
defibrillator. It is worth noting that therapy with
isoprenaline, a sympathomimetic agent which is useful in
acquired LQTS, is contraindicated in congenital LQTS.
Screening of first-degree relatives is very important in
this condition. In approximately 60% of cases the
diagnosis of idiopathic LQTS is made during screening of
Drugs
Class Ia and Ic antiarrhythmic agents
Tricyclic antidepressants, neuroleptic agents
Erythromycin
Ketoconazole
Certain antihistamines
Cisapride
Electrolyte disturbances
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
Cardiovascular diseases
Myocardial infarction
Complete heart block
Sick sinus syndrome
Mitral valve prolapse
Others
Subarachnoid haemorrhage
Liquid protein diet
www.drmyothethan.blogspot.com
Clinical Cases
369
Question 369
A 44-year-old man presented with recent onset of epigastric
burning that was precipitated by hunger or after a heavy
meal. His appetite was unchanged and his weight was
stable. He consumed 21 units of alcohol per week but was
Question 370
A 72-year-old patient with previous admissions for
exacerbation of chronic obstructive airways disease was
admitted to hospital with a six-day history of cough
productive of yellow sputum and dyspnoea. He smoked
five cigarettes per day but had previously been a heavy
smoker. He had a past medical history of ischaemic heart
disease and had had a stent to the right coronary artery
following a myocardial infarction two years ago. His
medications included inhaled iprotropium bromide, inhaled
salbutamol and inhaled pulmicort. His GP had commenced
amoxycillin five days previously.
On examination he was cyanosed. The respiratory rate
was 30/min. The heart rate was 120 beats/min and
regular. The blood pressure measured 150/90 mmHg.
Both heart sounds were soft. Auscultation of the lung
fields revealed coarse crackles throughout the lungs.
16 g/dl
17 ! 109/l
400 ! 109/l
138 mmol/l
4.0 mmol/l
7 mmol/l
120 "mol/l
Hyperinflated lung
markings with reduced
vascular markings.
Arterial blood gases (2 l oxygen/min):
pH
7.1
PaCO2
8.2 kPa
PaO2
6 kPa
HCO3
30 mmol/l
12-lead ECG
Atrial fibrillation/RBBB
(ventricular rate 120)
Urinalysis
Blood +
370
Answer 369
b. Start omeprazole, amoxycillin and clarithromycin
for 710 days.
The patient has dyspepsia and a positive urease breath
test suggestive of Helicobacter infection. Such patients
should receive eradication therapy. Recommended
eradication therapy for H. pylori infection includes a fulldose proton pump inhibitor twice daily, amoxycillin 1 g
twice daily and clarithromycin 500 mg twice daily for one
week. An alternative regime is full-dose proton pump
inhibitor twice daily, metronidazole 400 mg twice daily
and clarithromycin 250 mg twice daily for 710 days.
The therapeutic recommendations in patients with
uncomplicated dyspepsia are as follows:
1. Ensure all ulcerogenic medications have been stopped.
2. Treat dyspepsia with a proton pump inhibitor for a
month.
3. If symptoms persist the patient should be tested for
H.pylori infection with the intent to treat. The most
useful test for H. pylori is the urease breath test. Firstline treatment regimes are described in the first
paragraph above. Most duodenal ulcers (more than
90%) respond to eradication therapy.
4. Patients who develop recurrence of symptoms after
eradication therapy, particularly those aged over 55
years of age, should be referred for upper gastrointestinal endoscopy.
5. Upper gastrointestinal endoscopy should also be
performed on patients presenting with features of
chronic gastrointestinal bleeding, progressive unintentional weight loss, dysphagia, persistent vomiting, iron
deficiency anaemia, epigastric mass or suspicious barium
meal to exclude a malignant peptic ulcer.
6. In patients noted to have a duodenal ulcer at endoscopy, a
urease breath test is performed to check for persistence of
H. pylori infection (assuming that the patient has already
received eradication therapy at initial presentation). In
patients with evidence of H. pylori infection, second-line
eradication therapy is offered (assuming the patient has
relapsed on first-line eradication therapy). If the patient
becomes asymptomatic after this, no further investigation
is necessary. Patients with evidence of persistent H. pylori
infection on eradication therapy are treated with longterm, low-dose antisecretory therapy with either proton
pump inhibitors or H2 receptor blockers. Some patients
(5%) have duodenal ulcers in the absence of H. pylori
infection. These patients are also managed with long-term
antisecretory drugs.
7. Patients with gastric ulcers at endoscopy should be
biopsed to exclude malignancy. Gastric ulcer patients are
treated similarly to patients with duodenal ulcers.
Treatment with eradication therapy leads to healing of
the vast majority of gastric ulcers. Unlike patients with
duodenal ulcers, patients with gastric ulcers should have
repeat endoscopy at six weeks, even in the absence of
symptoms, to ensure healing of the ulcer, as gastric ulcers
are associated with higher complication rates and are
often malignant. Failure of a gastric ulcer to heal may be
an indication of malignancy and warrants repeat biopsies.
Answer 370
b. Non-invasive positive pressure ventilation.
The patient has a severe infective exacerbation of chronic
obstructive pulmonary disease as evidenced by the marked
hypoxia and respiratory acidosis. Early NIPPV is required
and has been shown to be as effective as invasive ventilation
(without the problems associated with invasive ventilation)
in terms of expediting recovery and reducing mortality.
Patients who should be considered for NIPPV include those
who have a moderate to severe dyspnoea, a respiratory rate
of >25/min, an arterial pH <7.35 and a PaCO2 >6 kPa.
There is no place for IV aminophylline in the
management of acute exacerbations of COPD. It is not
effective and increases the risk of arrhythmias in the
hypoxic patient. Similarly doxapram, a respiratory
stimulant, is no longer used in the management of acute
exacerbations of COPD.
Short-term high-dose steroids (two-week course) have
been shown to be effective in the management of
exacerbations of COPD (NEJM 1999; 340 (25);
194147) (Table). Steroids cause a modest increase in
Clinical Cases
371
Question 371
A 50-year-old man presented with a 24-hour history of
heamatemesis and malena. There was no preceding
history of abdominal discomfort. He consumed
80100 units of alcohol per week.
On examination he was pale. His heart rate was
110 beats/min and blood pressure measured
90/60 mmHg.
Investigations are shown.
Hb
WCC
Platelets
PT
Sodium
Potassium
Urea
Creatinine
AST
Bilirubin
Albumin
10 g/dl
16 ! 109/l
80 ! 109/l
22 s
131 mmol/l
3.2 mmol/l
14 mmol/l
90 "mol/l
160 iu/l
32 mol/l
28 g/l
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Glucose
TSH
Chlolesterol
Chest X-ray
ECG
10 g/dl
7 ! 109/l
200 ! 109/l
86 fl
130 mmol/l
4 mmol/l
5 mmol/l
4 mmol/l
0.3 mu/l
(NR 0.43.6 mu/l)
6.9 mmol/l
Normal
Sinus bradycardia rate
60 beats/min
372
Answer 371
ligation of the bleeding varices (see algorithm [371] and
Table for management).
No
Oesophageal varices
Band ligation or
sclerotherapy
Gastric varices
Isolated
gastric
varices
Gastrooesphageal
varices
Treat as oesphageal
varices
Uncontrolled
Controlled
Balloon
tamponade
Band eradication
programme
TIPSS/surgery
Eradication
Injection
with
fibrin
glue or
TIPSS
Recurrent
bleed
Clinical Cases
373
Notes
Tumours, cysts
Craniopharyngioma
Infarction after massive
haemorrhage,
e.g. during child birth
Haemochromatosis,
lymphocytic hypophysitis
Mutation in PROP-1 or
Pit-1
Addisons
disease
Common
Lassitude, malaise,
depression
Loss of body hair
Recognized
Hyperpigmentation Common
Panhypopituitarism
Common
Common
Not part of
disorder
Ocular signs
Not present
Dependent
on cause*
Collapse
Recognized
Only occurs
in severe ACTH
depletion
Low sodium
Common
Common
High potassium
Characteristic Not part of
disorder
*Present secondary to tumour
Question 374
A 31-year-old female presented with acute onset of
swelling of the neck after attending the funeral of a close
friend. On examination she had well-demarcated oedema
of the lips, eyes and ear lobes. The heart rate was
100 beats/min. The blood pressure was 90/50 mmHg.
The respiratory rate was 24 /min. The chest was clear.
She had previously attended the Accident and
Emergency Department with intermittent ankle swelling
and abdominal pain. Her father had suffered with similar
episodes for many years but had never had to seek medical
attention.
374
Answer 374
d. C1 esterase inhibitor concentrate
Hereditary angio-oedema is a genetic disorder inherited
as an autosomal dominant trait that results in a deficiency
of C1 esterase inhibitor. Deficiencies in this protein allow
unchecked activation of the classic complement pathway
and other biochemical systems.
Patients can present with any combination of cutaneous
angio-oedema, abdominal pain, or acute airway
obstruction. Prior to the development of effective therapy,
the mortality rate was 2030%. Typically, presentation is in
late childhood or early adolescence following trauma,
infection, dental procedures, or emotional stress. There is
an increasing frequency and severity of episodes during
puberty, menstruation and ovulation. The acquired form
typically occurs at an older age and may not be associated
with trauma. The symptoms of C1 esterase inhibitor
deficiency range in severity from a minor inconvenience to
life-threatening oedema.
Although preventable and treatable, the
complications of this disease do not respond well to
the usual therapies for angio-oedema and are more
refractory to the use of intramuscular adrenaline,
antihistamines and steroids. Therefore, establishment
of the correct diagnosis is critical. The management
of hereditary angio-oedema is outlined in Table.
Question 375
A 17-year-old female was admitted with a six-week history
of malaise and joint pains. She had pain affecting her neck,
left shoulder and the small joints of both her hands. She
had intermittent fever associated with profuse sweating. She
was born in Kenya and travelled to England for further
studies two years ago. She had not travelled abroad since.
She was well while in Kenya, although she had had two
mild attacks of malaria at the ages of 5 years and 12 years.
She was a non-smoker and a teetotaller. Two days before
coming into hospital she developed some sharp inframammary chest pain, which was worsened by movement,
deep inspiration and on lying flat. There was no history of
cough or sputum production. Her appetite was slightly
reduced and she had lost 2 kg in weight.
On examination, she appeared unwell. She had a
temperature of 39.2C (102.6F) and a widespread rash,
Clinical Cases
375a
375
375b
375c
Hb
10 g/dl
WCC
17 ! 109/l
Platelets
470 ! 109/l
MCV
82 fl
Malaria parasite
Absent
ESR
86 mm/h
CRP
54 g/l
Sodium
134 mmol/l
Potassium
3.8 mmol/l
Urea
5 mmol/l
Creatinine
70 "mol/l
Blood cultures 3
Negative
Thyroxine
98 nmol/l
TSH
1.1 mu/l
ECG (375b)
Chest X-ray
Normal
Echocardiogram (375c)
Rhesus factor
Absent
Urinalysis
Trace of protein
No blood
Question 376
An obese woman was diagnosed as having pernicious anaemia when she presented with lethargy and was found to have
a raised MCV, low B12 level and intrinsic factor antibodies.
A blood count performed at the time was as follows:
Hb
WCC
Platelets
MCV
9.1 g/dl
7 ! 109/l
250 ! 109/l
110 fl
Hb
WCC
Platelets
MCV
11 g/dl
7.4 ! 109/l
260 ! 109/l
105 fl
d. Orotic aciduria.
e. Carcinoma of the stomach.
f. Hypothyroidism.
g. Chronic renal failure.
h. Myeloma.
i. Crohns disease.
j. Iron deficiency.
376
Answer 375
a. Adult-onset Stills disease.
The characteristics of the chest pain are consistent with
acute pericarditis, which is confirmed on the ECG.
The patient has malaise, fever, arthralgia, a rash,
lymphadenopathy, arthritis and splenomegaly.
The differential diagnosis is between adult-onset
juvenile chronic arthritis or Stills disease, SLE, and
lymphoma. The high CRP is against the diagnosis of SLE.
While lymphoma is quite possible, the seronegative
arthritis, neutrophil leucocytosis, high fever and
maculopapular rash are best explained by Stills disease.
Adult Stills disease is rare. It affects young adults aged
between 16 and 35 years. The characteristics are identical
to those of juvenile chronic arthritis in younger patients.
The diagnosis is essentially clinical, and the clinical criteria
are outlined below (Table). Antinuclear factor is negative
in Stills disease. Generalized lymphadenopathy is relatively
common, and lymph node biopsy shows only reactive
changes. If both these tests are negative, then adult Stills
disease is the most likely diagnosis.
Infective endocarditis is unlikely with three negative
blood cultures. The echocardiogram (375c) reveals a
normal aortic and mitral valve, and right-sided endocarditis
is most unusual in young, previously healthy individuals
unless there is a history of intravenous drug abuse.
Rheumatic fever may be suspected in a woman living in
East Africa with a murmur, fever, arthritis and pericarditis;
however, there is no history of streptococcal infection, and
her symptoms are relatively long-standing for rheumatic
fever. In this case, the murmur is likely to represent
Answer 376
c. Folate deficiency.
f. Hypothyroidism.
The patient was diagnosed as having pernicious anaemia
on the basis of a large MCV, low B12 levels and intrinsic
factor antibodies. Indeed, an MCV >110 fl is highly
suggestive of a megaloblastic marrow (i.e. B12, folate
deficiency or treatment with cytotoxic drugs). The
patient has responded partly to B 12 injections as
evidenced by the increased haemoglobin and partial
improvement in the MCV. However, she continues to
remain symptomatic and has subnormal Hb and MCV.
Clinical Cases
377
Causes of macrocytosis
Cause
B12 or folate
deficiency
Cytotoxic drugs
Inherited disorders
of DNA synthesis
Hypothyroidism
Liver disease
Alcoholism
Myelodysplastic
syndrome
Haemolysis
Drugs
Myeloma
Hyperlipidaemia
Notes
MCV >110 fl
MCV >110 fl
Orotic aciduria
Question 377
A 58-year-old patient was noted to be in atrial fibrillation
prior to ENT surgery. He was asymptomatic. An elective
cardioversion was planned to try and restore sinus
rhythm. There was no history of hypertension or valve
disease. The patient had never experienced a transient
ischaemic attack or stroke. On examination the heart rate
was 80 beats/min. Both heart sounds were normal and
there were no murmurs.
Question 378
A 42-year-old woman was rescued from a house fire
where she had become unconscious. On admission she
was drowsy and had a marked wheeze.
Blood results were as follows:
378
Answer 377
c. Warfarin for 34 weeks prior to cardioversion
and 4 weeks afterwards.
The three main goals in the management of atrial
fibrillation include restoration to sinus rhythm (if possible),
control of ventricular rate (if restoration of sinus rhythm is
not possible or desirable), and the prevention of systemic
thromboembolism. Stagnation of blood in the atrial
appendage promotes thrombus formation. Restoration to
sinus rhythm from atrial fibrillation increases the probability
of thromboembolism (dislodging of the thrombus) since
Answer 378
c. 100% oxygen.
e. Intravenous sodium thiosulphate.
Smoke inhalation is associated with four major
consequences (see Table).
This question tests the candidates knowledge of the
consequences of inhalation of systemic toxins, which
include carbon monoxide and hydrogen cyanide. These
substances impair the delivery and/or utilization of oxygen
and may result in systemic tissue hypoxia and rapid death.
Carbon monoxide is the main cause of smoke-related
fatalities and causes almost 80% of all smoke inhalation
deaths. Symptoms and signs include headache, nausea,
malaise, altered cognition, dyspnoea, angina, seizures,
cardiac arrhythmias, congestive heart failure and/or coma.
Hydrogen cyanide is a highly toxic compound that
can be formed in the high temperature combustion of a
number of common materials such as polyurethane,
nylon, wool and cotton. Cyanide binds to a variety of
iron-containing enzymes, the most important of which is
the cytochrome a-a3 complex, which is critical for
electron transport during oxidative phosphorylation. By
binding to this molecule, minute amounts of cyanide can
inhibit aerobic metabolism and rapidly result in death.
The typical clinical syndrome due to cyanide
poisoning is one of rapidly developing coma, apnoea,
cardiac dysfunction and severe lactic acidosis in
Question 379
A 58-year-old man presented with a three-month history of
lower back pain. He had also noticed weakness in his legs
when climbing stairs, and had considerable difficulty in
raising himself from a chair. More recently, he was excessively
thirsty and was waking frequently at night to pass urine. He
had lost over 4 kg in weight since the onset of his illness.
Before this he was well. He was married with two children.
Clinical Cases
379
Question 380
A 70-year-old female presented with sudden onset of
dyspnoea. There was no preceding history of a cough or
chest trauma. She was a smoker. Four weeks previously
she had had a right hip replacement.
On examination she was cyanosed. The heart rate was
140 beats/min and irregular. The blood pressure was
380
Answer 379
1. b. Steroid-induced myopathy.
2. a. Bone metastases.
3. d. Ectopic ACTH production from a bronchial
carcinoma.
f. Cortisol secreting adenocarcinoma.
4. a. Serum ACTH.
b. Chest X-ray.
The patient presented with lower back pain and clinical
symptoms of a proximal lower limb myopathy. The latter
is confirmed clinically. He is diabetic and hypertensive.
Routine blood results demonstrate a low potassium and
elevated bicarbonate. The differential diagnosis at this
point is between Cushings disease (ACTH-secreting
basophil adenoma from the pituitary), cortisol-secreting
adrenal adenoma or ectopic ACTH production. The
diagnosis is narrowed down to a cortisol-secreting
adrenal adenoma and ectopic ACTH by the failure of
suppression of cortisol following high-dose
dexamethasone. (See Answer 173.)
The short history of the presenting complaint and
history of smoking favour ectopic ACTH production by
carcinoma of the bronchus. These patients produce large
amounts of ACTH and present primarily with weakness
and myopathy associated with hypokalaemia, rather than
a Cushingoid appearance.
The proximal myopathy is due to steroid excess, and
the accompanying muscle weakness is compounded by
the hypokalaemia. The hypokalaemia per se does not
cause myopathy unless it is very long standing. The
diabetes would account for the polydipsia and polyuria,
Answer 380
b. Intravenous alteplase 50 mg.
The patient presents with acute dyspnoea associated with
severe circulatory collapse, hypoxia, hypocarbia and
metabolic acidosis. In addition her JVP is raised,
indicating right heart strain. The ECG shows ST segment
depression, which may be part of right heart strain or
myocardial ischaemia secondary to severe hypoxia.
Patients with massive pulmonary embolism judged
clinically by cardiac arrest, circulatory collapse, severe
hypoxia, acidosis or signs of right heart strain are treated
with early thrombolysis. The usual treatment is a 50 mg
bolus of alteplase followed by a heparin infusion. The
diagnosis of massive pulmonary embolism can be
confirmed by echocardiography or CT pulmonary
angiography; however, the seriousness of the circulatory
collapse may not allow time for investigation until
thrombolysis has been instituted.
Patients with intermediate or high probability of nonmassive pulmonary embolus are treated with heparin
until imaging. Low-molecular weight heparin is
preferable to unfractionated heparin, as it is equally
effective and easier to use. Unfractionated heparin is only
considered in situations where rapid reversal of
anticoagulation is required.
Once the diagnosis has been confirmed all patients are
commenced on warfarin and the heparin is stopped once
the INR exceeds 2. Patients remain on warfarin for six
weeks if the pulmonary embolus was secondary to a
temporary risk factor such as recent lower-limb
orthopaedic surgery. In patients with idiopathic
pulmonary embolus warfarin is continued for three
months. Patients with recurrent pulmonary emboli or
permanent risk factor for pulmonary emboli are
anticoagulated indefinitely if the risks of pulmonary
embolism outweigh the dangers of haemorrhage.
381
Clinical Cases
Question 381
381a
381b
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Alkaline phosphatase
Albumin
Chest X-ray
9 g/dl
10 109/l
180 109/l
82 fl
136 mmol/l
6 mmol/l
43 mmol/l
500 mol/l
2.0 mmol/l
1.7 mmol/l
305 iu/l
35 g/l
Slight increase in the
cardiothoracic ratio
Upper lobe venous
distension
Bilaterally shrunken kidneys
382
Answer 381
1. i. Arteriovenous nipping.
ii. Flame-shaped haemorrhages.
iii. Cotton wool spots or retinal infarcts.
iv. Blurred disc or papilloedema.
2. Chronic renal failure (Table A).
3. Failure of 1a-hydroxylation of vitamin D, causing
low levels of 1,25-dihydroxycholecalciferol, which
is an active vitamin D metabolite.
4. Subperiosteal bone resorption and severe
demineralization of the third metacarpals
bilaterally. There is also an expansion in the
proximal phalanx of the left third digit. Such a
cystic appearance is seen in severe
hyperparathyroid-related bone disease.
5. Deficiency of erythropoietin.
6. Uraemic acidosis. Pulmonary oedema is less likely,
given the relatively clear chest and absence of
interstitial shadowing on the chest X-ray (Table B).
7. Haemodialysis.
8. i. Regular haemodialysis.
ii. Control hypertension.
iii. Erythropoietin for anaemia.
iv. a-1-calcidol for hypocalcaemia.
v. Calcium carbonate to bind phosphate and prevent
osteodystrophy.
The patient presents with hypertension, grossly abnormal
renal function, grade IV hypertensive retinopathy (Table
C) and drowsiness. These features could be explained by
primary accelerated hypertension; however, the anaemia,
bone biochemistry and X-ray appearance of the hand
indicate that the most likely cause of the hypertension is
chronic renal failure. It is difficult to be certain about the
aetiology of the renal impairment because the past history
is vague and the kidneys are shrunken. Renal biopsy in
these instances reveals extensive glomerular scarring and is
rarely helpful in the management of the patient. The
history of intermittent abdominal pain and vomiting and
investigation for short stature suggest that the cause may
be chronic pyelonephritis. Other causes of chronic renal
failure and its complications are shown (Tables A and B).
The long- and short-term management of this patient is
outlined in 7 and 8 above. It is important to be aware that
erythropoietin itself may worsen hypertension; therefore,
extra care is required in managing hypertension in an
individual taking erythropoietin. Good hypertensive
control will reduce the rate of decline in renal function;
however, given his weight of just 45 kg, a serum creatinine
of 500 "mol/l almost certainly represents end-stage renal
failure requiring dialysis. In some patients with chronic
renal failure and hypertension, reducing intravascular
volume with dialysis is all that is required to control blood
pressure.
Chronic glomerulonephritis
Chronic pyelonephritis
APCKD
Diabetes mellitus
Chronic hypertension
Renal artery stenosis
Renal papillary necrosis secondary to chronic
analgesia
Hyperuricaemic nephropathy
Chronic nephrolithiasis
Clinical Cases
383
Question 382
A 42-year-old male was investigated for a three-year
history of intermittent abdominal pain. He had suffered
four episodes of pyelonephritis in the past four years
which were treated by his GP. There was a long history
of migraines, for which he took mefenamic acid and
paracetamol. Over the past few months he had
complained of increasing lethargy. There was no history
of diarrhoea, weight loss, urinary hesitancy, nocturia or
post-micturition dribble. Four months ago he was noted
to have a blood pressure of 180/110 mmHg, which was
under review. He was a florist by occupation. He was a
non-smoker and consumed very occasional alcohol. His
father died suddenly from a subarachnoid haemorrhage at
the age of 40 years, but his mother was still alive and
well. He had three brothers aged 44, 45 and 46 years
respectively; the eldest brother had hypertension.
On examination, he appeared well at rest. There was
no clubbing or peripheral oedema. The blood pressure
was 180/105 mmHg. Examination of the abdomen
revealed tenderness in both loins. Deep palpation of the
loins was difficult owing to tenderness. The percussion
note throughout the abdomen was resonant and
auscultation demonstrated normal bowel sounds.
Examination of the cardiovascular and respiratory system
was normal. Fundoscopy demonstrated silver wiring and
arteriovenous nipping.
Investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
Serum renin
Urinalysis
15 g/dl
5 109/l
240 109/l
15 mm/h
128 mmol/l
3.8 mmol/l
20 mmol/l
400 mol/l
2.1 mmol/l
1.9 mmol/l
39 g/l
Elevated
Protein ++
Blood ++
24-hour urinary sodium
89 mmol/l
Question 383
A 16-year-old East African female was admitted with a
two-week history of intermittent, sharp, right upper
quadrant pain which was worse on inspiration. The pain
radiated to the umbilicus and right loin and was most
severe on the night of admission. There were no other
symptoms. She had just finished menstruating. Her family
had very recently immigrated to Britain from Kenya.
On examination, she had shallow respiration. The
temperature was 37.5C (99.5F). There were tenderness
Hb
WCC
Platelets
ESR
U&E
Chest X-ray
Urinalysis
13 g/dl
16 109/l (neutrophil leucocytosis)
590 109/l
70 mm/h
Normal
Raised right hemidiaphragm
Clear lung fields
Normal
384
Answer 382
d. Genetic polycystic kidney disease.
This middle-aged patient presents with abdominal pain
and advanced renal failure. All of the options given may
cause abdominal pain and renal failure (Table). The
episodes of pyelonephritis in a middle-aged male should
raise suspicion of obstructive uropathy or an anatomical
abnormality in the renal tract. In the context of the
possibility of the latter, the family history of subarachnoid
haemorrhage and hypertension should arouse the
suspicion of APCKD. The normal Hb in the presence of
chronic renal failure should clinch the diagnosis because
APCKD is one of the few causes of chronic renal failure
where the Hb is preserved. This is due to inappropriate
erythropoietin secretion in some patients with the
condition. Hypernephroma may also cause polycythaemia
for the same reason but does not cause a salt-losing
nephropathy as seen in this case.
APCKD is inherited as an autosomal dominant trait. It
is characterized by multiple thin-walled cysts in the
kidney, which become progressively larger over the years
and cause renal failure by compression of the nephrons.
In 90% of patients, the abnormal gene is on the short arm
of chromosome 16 (PKD 1) which encodes a
transmembrane protein termed polycystin. The exact
function of it is unclear but it is thought to be involved in
mediating cell-matrix interactions. Of the other 10% of
patients, some have abnormalities linked to a locus on
HenochSchnlein purpura
Haemolytic uraemic syndrome
Polyarteritis nodosa
APCKD
Nephrolithiasis
Analgesic nephropathy
Retroperitoneal fibrosis
Dissecting aortic aneurysm
Legionnaires disease
Acute pancreatitis
Ethylene glycol poisoning
Answer 383
1. Hepatic abscess secondary to Entamoeba histolytica
(amoebic liver abscess).
2. i. Ultrasound of the liver.
ii. Microscopy from liver aspirates.
iii. Indirect haemagglutination tests (over 95% with
liver abscess are positive, but the test cannot
distinguish between past and current infection).
The patient presents with hepatomegaly, a raised right
hemidiaphragm, and localized tenderness in the 9th
intercostal space. These features are consistent with a
hepatic abscess. She has been in East Africa, which makes
an amoebic abscess the most probable cause of her signs
and symptoms. Some 50% of patients with amoebic
abscess have no history of dysentery. Symptoms include
right hypochondrial pain, fever, sweating, intermittent
fever and rigors. There may also be hepatic enlargement
Clinical Cases
385
Question 384
384a
384b
40
97 90 75 50 25 10 3
97
90 75 50 25 10 3
Weight (kg)
Height (cm)
140
130
120
30
20
110
Early (+2SD) maturers
Late (-2SD) maturers
100
6
50
50
9 10 11 12 13 14 15 16
Age, years
384c
A 14-year-old male was admitted to hospital with a 12hour history of colicky right-sided abdominal pain and
vomiting. He had a past history of recurrent chest
infections that had been treated by his GP. He was also
thought to be asthmatic, and took a regular
bronchodilating inhaler. He had intermittent loose, bulky
stool but had never experienced abdominal pain. He had a
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Total protein
Albumin
Calcium
Phosphate
Chest X-ray (384c)
Abdominal X-ray (384d)
10 g/dl
14 109/l
480 109/l
80 fl
135 mmol/l
3.2 mmol/l
9 mmol/l
70 g/l
34 g/l
2.2 mmol/l
0.7 mmol/l
10
6
10 11 12 13 14 15 16
Age, years
384d
younger brother and sister who were well. His father was
a shop assistant and his mother was a part time GPs
receptionist.
On examination, he did not appear acutely unwell. He
had mild clubbing. The abdomen was distended. There
was generalized tenderness on palpation, as well as a firm
mass in the right iliac fossa. Bowel sounds were tinkling.
The rectum was empty. Auscultation of the lung fields
revealed coarse crackles throughout the lung fields.
Growth charts for height and weight are shown
(384a, b). Investigations are shown.
386
Answer 384
1. This patient has fallen off the third centile for height
at the age of 10 years and for weight at the age of
14 years.
2. The chest X-ray is grossly abnormal. There is
widespread fibrotic change, patchy consolidation,
and bronchiectasis. In the context of this history the
findings are consistent with cystic fibrosis.
3. The erect abdominal X-ray reveals dilated loops of
small bowel and multiple fluid levels consistent with
small bowel obstruction.
4. Meconium ileus equivalent. This is bowel
obstruction resulting from a combination of
steatorrhoea and viscid intestinal secretions causing
faecal impaction in the ascending colon or the
ileocaecal junction.
5. The management steps are as follows:
Rest the bowel; the patient should be completely
restricted from oral solids and fluids and should
have intravenous fluid supplements. A nasogastric
tube should be placed in situ to prevent gastric
dilatation and vomiting.
Diagnostic and therapeutic manoeuvres: a
6.
7.
Recurrent pneumonia
Lung abscess/empyema
Haemoptysis
Aspergillus infection
Lung fibrosis
Pneumothorax
Cor pulmonale
Gastrointestinal
Meconium ileus (birth)
Rectal prolapse (neonate)
Steatorrhoea (pancreatic insufficiency)
Meconium ileus equivalent (infancy onwards)
Malabsorption (fat-soluble vitamins due to pancreatic insufficiency usually, or biliary obstruction)
Gall stones
Secondary biliary cirrhosis
Miscellaneous
Non-erosive arthropathy
Infertility in males
Clinical Cases
Hypothyroidism
Familial hypoparathyroidism
Mucopolysaccharidoses
-1 antitrypsin deficiency
Addisons disease
387
Question 385
A 6-year-old female was seen in the Accident and
Emergency Department with a two-year history of a
painful swollen right knee which developed after she fell
at school. Two years previously she had a similar episode
affecting the left knee, following which she had persistent
swelling and discomfort for several weeks. At that stage
she had an FBC which was normal and an X-ray of the
left knee which revealed soft tissue swelling. In the
interim she had recurrent episodes of painful swelling of
the left knee for no obvious reason, which would subside
after a few days. At the age of two years she sustained a
large haematoma on her forehead after a fall at home.
The only other past history of note was a recent review
by the ophthalmologist for a left convergent squint.
She had achieved her milestones normally, but had
problems with reading which were attributed to her
squint. She was one of three siblings. All three were
adopted and had come from different families. Her
parents appeared very caring. The father was a
businessman who spent many days away from home and
the mother was a housewife.
On examination, she was below the third centile for
height and was on the 50th centile for weight. There was
a painful swelling over the left knee consistent with a
synovial effusion. The right knee was not swollen, but
movement of the knee demonstrated crepitus. There was
an obvious convergent squint. The neck was short and
the hands, particularly the fourth and fifth digits,
appeared small.
Investigations are shown.
Hb
WCC
Platelets
Blood film
PT
APTT
BT
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Albumin
X-ray of left knee
X-ray of right knee
11 g/dl
6 109/l
112 109/l
Normal
12 s
94 s
8 min
136 mmol/l
3.8 mmol/l
6 mmol/l
80 mol/l
2.3 mmol/l
1.0 mmol/l
40 g/l
Soft-tissue swelling
No bony deformity
Chondrocalcinosis
388
Answer 385
1. i. Turners syndrome.
ii. Haemophilia A or haemophilia B.
2. Haemarthrosis; bleeding into the knee joint.
3. i. Haemophilia A.
ii. Haemophilia B.
4. i. Buccal smear for karyotyping to confirm Turners
syndrome.
ii. Factor VIII assay or Factor IX assay to confirm
haemophilia A or B respectively.
The patient has several morphological features of Turners
syndrome (Table C, Answer 397). All of these
morphological features, particularly short metacarpals, may
also occur in pseudohypoparathyroidism; however, the
normal bone biochemistry is against the diagnosis. Short
metacarpals may occur in other conditions (Table A).
The patient also has an important clotting abnormality,
suggested by the elevated APTT. The swollen knee is most
probably due to haemorrhage into the joint. The right knee
has features of chondrocalcinosis possibly due to recurrent
haemarthroses. The PT is normal, suggesting that the
defect is in the intrinsic pathway of the clotting cascade.
Causes of a raised APTT include deficiency in any one of
Turners syndrome
Noonans syndrome
Pseudohypoparathyroidism
Sickle cell dactylitis
Juvenile chronic arthritis
Recurrent hand trauma
HA
HB
Von Willebrands
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Question 386
A 48-year-old clerical worker in a large insurance
company was admitted with malaise, increasing shortness
of breath and confusion. One week before admission he
had a dry cough, chills, headaches and generalized aches
throughout his body. He saw his GP, who prescribed
amoxycillin 500 mg three times daily. Two days later, the
patient developed generalized abdominal pain and loose
motion. Over the next 24 hours, he had become
increasingly confused, and started to hallucinate. His wife
became concerned, and brought him to the Accident and
Emergency Department. He had been in Spain six weeks
before his illness. He smoked 20 cigarettes a day, and
consumed 4 units of alcohol a night.
Clinical Cases
Hb
WCC
13.5 g/dl
12.1 109/l (neutrophils
10.2 109/l; lymphocytes
1.5 109/l)
Platelets
140 109/l
Sodium
128 mmol/l
Potassium
4 mmol/l
Urea
10 mmol/l
Creatinine
160 mol/l
Bilirubin
22 mol/l
ALT
75 iu/l
Alkaline phosphatase 102 iu/l
Gamma GT
102 iu/l
Albumin
29 g/l
ECG
Urinalysis
389
7.37
7.3 kPa
4 kPa
18 mmol/l
83%
Right lower lobe
consolidation, and a small
associated pleural effusion
Sinus tachycardia
Trace of blood
Protein ++
Question 387
A 34-year-old West African female presented with a
three-month history of increasing ankle oedema and
abdominal distension. There was no history of cough,
exertional dyspnoea or orthopnoea. She was married with
a five-year-old daughter. She was a non-smoker, and
drank alcohol very occasionally. She had worked as a fishfarm administrator in Nigeria before moving to England
three years ago.
On examination, there was no evidence of pallor,
jaundice or lymphadenopathy. She had considerable,
pitting, lower-limb oedema. The heart rate was 100
beats/min, and irregularly irregular. The blood pressure
was 95/75 mmHg. The JVP was elevated to the level of
the ear lobes. On examination of the precordium the
apex beat was not palpable. The heart sounds were soft.
There were no cardiac murmurs. Auscultation of the lung
fields was normal. Abdominal examination revealed firm
hepatomegaly palpable 6 cm below the costal margin and
shifting dullness. The spleen was not palpable.
Neurological examination and examination of the skin
were normal.
Investigations are shown.
Hb
WCC
Platelets
Urinalysis
Chest X-ray
ECG
12 g/dl
7 109/l
(normal differential)
300 109/l
Protein +
Normal cardiac size and clear
lung fields
Low QRS voltage and nonspecific lateral T-wave
changes
390
Answer 386
1. Legionnaires disease.
2. i. Syndrome of inappropriate ADH secretion.
ii. Diarrhoea and vomiting.
iii. Salt-losing nephritis/acute tubulointerstitial
nephritis.
3. i. Urine for Legionella antigen.
ii. Direct immunofluorescent antibody test on
sputum, bronchial washings, pleural effusion or
blood.
iii. IgM RMAT for Legionella.
4. Intravenous cefotaxime and oral erythromycin.
5. i. Oxygen.
ii. Intravenous erythromycin or azithromycin and
oral rifampicin.
iii. Intravenous rehydration with CVP monitoring.
This previously fit middle-aged man presents with
respiratory problems, abdominal symptoms and confusion.
Biochemical tests reveal a low sodium and evidence of
renal dysfunction. The full blood count reveals a mildly
raised WCC with a relative lymphopenia. The most
probable diagnosis which ties all of this together is
Legionnaires disease. The condition is caused by the
organism Legionella pneumophilia. Epidemic outbreaks can
occur among previously fit individuals staying in hotels,
institutions or hospitals where the cooling systems have
been contaminated with the organism. It can also occur in
sporadic cases and in the immunocompromised where the
source of infection is unknown. It is spread via the aerosol
route. Incubation period is between 2 and 10 days. Males
are affected more than females.
Legionnaires disease is preceded by a prodromal illness
similar to a viral infection with headaches, myalgia,
anorexia and pyrexia. Approximately 50% have abdominal
symptoms (nausea, vomiting and diarrhoea). Neurological
symptoms such as confusion, hallucinations, peripheral
neuropathy, myelitis and, rarely, a cerebellar syndrome can
occur. Patients may develop renal failure, usually secondary
to an acute tubulointerstitial nephritis. Liver involvement is
usually mild and characterized by abnormal LFT.
Hyponatraemia is common and is usually due to
inappropriate ADH secretion; however, loss of sodium
from the kidneys (acute tubulointerstitial nephritis) and
gastrointestinal tract (diarrhoea and vomiting) may also
contribute. Other biochemical features include
hypocalcaemia, hypophosphataemia, and raised creatinine
kinase (myositis). On the blood film there is a normal or
mildly raised WCC with a moderate neutrophilia and
relative lymphopenia. A mild coagulopathy can occur.
Chest X-ray usually shows a unilateral lobar and then
multilobar shadowing, with or without an associated
pleural effusion.
Clinical Cases
391
Answer 387
1. i. Echocardiography.
ii. Cardiac MRI.
iii. Left and right cardiac catheter.
2. i. Pericardial constriction.
ii. Restrictive cardiomyopathy.
The patient has signs of severe right-heart failure, but the
chest X-ray reveals a normal-sized heart. The differential
diagnosis of severe heart failure in the absence of
significant cardiac enlargement is between pericardial
constriction and a restrictive cardiomyopathy.
If we consider the possibility of restrictive
cardiomyopathy (Table A), then there is little information
in the history to suggest systemic sclerosis,
haemochromatosis, carcinoid syndrome or anthracycline
therapy. We are left with the possibility of malignancy,
amyloidosis, EMF or idiopathic restrictive
cardiomyopathy; however, the latter is extremely rare and
some cardiologists are unsure if it even exists. There is no
real evidence of malignancy. Cardiac amyloidosis is
usually associated with myeloma, of which there is no real
Temperate
Acute
Common
Common
Uncommon
High
Bacterial pericarditis
Radiotherapy
Tropical
Insidious
Unusual
Unusual
Very common
Normal
392
Pericardial constriction
Enlarged/normal
Normal
Normal
Normal
Normal
Restrictive cardiomyopathy
Enlarged
Usually normal/enlarged
Bright
Normal/bright
Affected (mitral and tricuspid
regurgitation)
Large E*, small A**
Normal
387
LV
LV
RV
RV
Pericardial constriction
Restrictive cardiomyopathy
Question 388
Hb
WCC
Platelets
HIV serology
CD4 count
Viral RNA
Chest X-ray
13 g/dl
6 109/l
310 109/l
IgG HIV antibody-positive
510 106/l
(NR 5001,300 106/l)
20,000 copies/ml
Normal
Question 389
A 57-year-old male was admitted with a seven-month
history of increasing breathlessness and swollen ankles.
Just before admission he had developed paroxysmal
Clinical Cases
389a
393
389b
389c
389d
family history of cardiovascular disease. He was a nonsmoker and consumed about 7 units of alcohol per week.
He had been a patron for a large charity organization for
several years.
On examination, he appeared pale and was breathless
on very slight exertion. The heart rate was 100
beats/min, and regular; blood pressure was 90/60
mmHg. The JVP was raised 6 cm above the sternal angle
and revealed prominent a- and cv waves. The apex was
not palpable, but on auscultation of the precordium there
was a loud third heart sound. On examination of the
lungs there was reduced air entry bilaterally at both lung
bases. Abdominal examination revealed hepatomegaly
palpable 7 cm below the costal margin, and some ascites.
Investigations are shown.
1. Comment on the chest X-ray.
2. Comment on the ECG.
3. What is the renal diagnosis?
4. What is the cause of cardiac failure?
Hb
WCC
Platelets
MCV
ESR
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
ECG (389a)
Chest X-ray (389b)
Renal US
11 g/dl
6 109/l
100 109/l
88 fl
70 mm/h
135 mmol/l
3.9 mmol/l
15 mmol/l
110 mol/l
33 mol/l
64 iu/l
200 iu/l
18 g/l
Echocardiogram (389c)
Renal biopsy (389d)
394
Answer 388
1. The patient is HIV-positive. His CD4 count is
within normal limits, but he has a very heavy viral
load, which is generally a poor prognostic marker
of disease progression and an indicator for
treatment.
2. A combination of two nucleoside analogues and a
protease inhibitor.
Patients infected with HIV may present following the
seroconversion syndrome, with generalized
lymphadenopathy or with AIDS-defining opportunistic
illnesses (Table). The management of HIV infection is
dependent on the CD4 count and the viral RNA load.
Recommendations for initiating therapy in patients
infected with HIV include all patients with a CD4 count
of <500 ! 106/l, as well as asymptomatic patients who
have a CD4 count >500 ! 106/l but evidence of active
viral RNA (>10,000 viral copies per ml). Some experts
will initiate treatment in patients with a CD4 count >500
! 106/l in the presence of any detectable level of virus.
Patients with AIDS-defining illnesses usually have a CD4
<200 ! 106/l. Treatment is in the form of triple therapy,
comprising combinations of nucleoside analogues that
AIDS-defining conditions
Pneumocystis carinii pneumonia
TB (Mycobacterium avium intracellulare)
Cryptococcus neoformans
Cryptosporidium
Isospora belli
Oesophageal or disseminated Candida (but not
oral)
Herpes infection
CMV retinitis, colitis, oesophagitis and encephalitis
Oral leukoplakia
Toxoplasmosis
Kaposis sarcoma
Answer 389
1. i. Bilateral pleural effusions, the right effusion being
larger than the left.
ii. Prominent pulmonary arteries.
2. Small voltage complexes with T-wave inversion in
the lateral leads.
3. Nephrotic syndrome due to renal amyloidosis.
4. Restrictive cardiomyopathy secondary to cardiac
amyloid.
5. Primary amyloidosis.
6. i. Serum immunoglobulins/
immunoelectrophoresis.
ii. Urinalysis for Bence-Jones protein estimation.
The combination of nephrotic syndrome and cardiac
failure should always raise the suspicion of primary
amyloidosis or AL amyloid. Primary amyloid affects
approximately 1015% of all patients with myeloma. In
primary amyloidosis, the amyloid is made up of
immunoglobulin light chains and glycoprotein. Clinical
features include restrictive cardiomyopathy, macroglossia,
peripheral neuropathy, nephrotic syndrome, purpura, and
isolated clotting Factor X deficiency. Cardiac amyloid has a
poor prognosis as it results in a stiff ventricle with poor
systolic and diastolic function. It responds poorly to
Clinical Cases
395
Question 390
A 28-year-old female presented with a four-week history
of progressive difficulty with walking, clumsiness of her
hands, and slurring of the speech. Before this she had
been relatively well, with the exception of occasional
episodes of central chest pain and breathlessness when
she was stressed, or on rushing suddenly. In the past four
weeks she had fallen twice because she was not in
control of her lower limbs. Her hands were clumsy and
she was having difficulty washing dishes or holding cups.
There was no history of headaches or any family history
of neurological disease. She was a non-smoker and
consumed 12 glasses of wine per week.
On examination, she appeared well at rest. She
measured 1.81 m. She had a high-arched palate,
kyphoscoliosis and mild bilateral pes cavus. Her speech
was mildly dysarthric. On examination of her upper limbs
the power was normal. The tone was slightly increased in
both forearms. There was clinical evidence of an
intention tremor, past pointing, finger nose ataxia and
dysdiadochokinesia. The reflexes were brisk bilaterally.
On examination of the lower limbs the power was slightly
Question 391
A 44-year-old Nigerian male was investigated for right
upper quadrant pain, abdominal distension and ankle
swelling:
Chamber
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left ventricle
Aorta
Pressure
(mmHg)
19
48/20
40/20
18
90/20
85/65
Oxygen
saturation (%)
68
68
68
96
96
391a
396
Answer 390
1. Friedreichs ataxia.
2. Hypertrophic cardiomyopathy (hypertrophic
obstructive cardiomyopathy).
3. i. Diabetes mellitus.
ii. Optic atrophy.
The patient has pes cavus and signs of cerebellar and
pyramidal tract disease. In addition there is a history of
chest pains and breathlessness, suggesting cardiovascular
disease, and a cardiac murmur that is compatible with
dynamic left ventricular outflow tract obstruction
characteristic of hypertrophic obstructive cardiomyopathy.
The complete diagnosis is Friedreichs ataxia.
Friedreichs ataxia is an autosomal recessive condition
due to a mutation in a gene encoding the protein frataxin
on chromosome 9. The mutation comprises unstable
expansions of the GAA repeat of variable size
(1201,700) in the first intron. The exact function of
frataxin is unknown, but early reports suggest that it is a
mitochondrial iron transport protein. The prevalence is
1/50,000. It is the most common example of the
hereditary ataxias. There is degeneration of the dorsal
spinal column, the spinocerebellar tracts, the pyramidal
tracts, and the dorsal root ganglion cells. The syndrome is
dominated by progressive ataxia. The usual age of onset is
the second decade, but the disease may not appear until as
late as the fourth decade. The lower limbs are generally
Answer 391
1. i. Elevated and equal right and left atrial pressures.
ii. Elevated and equal left and right ventricular enddiastolic pressures.
2. Calcification of the pericardium (391b, arrowed).
3. The findings are consistent with the diagnosis of
pericardial constriction.
391b
Clinical Cases
397
Question 392
Hb
WCC
Platelets
MCV
Neutrophils
Myoblasts
Myelocytes
Metamyelocytes
Lymphocytes
Eosinophils
Basophils
Nucleated red cell
9 g/dl
52 109/l
680 109/l
88 fl
67%
8%
10%
8%
2%
1%
2%
2%
Question 393
A 59-year-old female presented to the Accident and
Emergency Department with sudden onset of retrosternal
pain on bending down to get into her car. On examination,
she was jaundiced. Her blood pressure was 140/80
mmHg. She was extremely tender over the mid-sternal area,
particularly when she attempted deep inspiration. The heart
sounds were normal and her chest was entirely clear.
Abdominal examination revealed hepatomegaly, which was
palpable 4 cm below the costal margin, and a palpable tip of
the spleen. Only three days earlier she had seen her GP with
a six-week history of malaise and was noted to have
jaundice, which was under preliminary investigation. There
was no history of abdominal pain or weight loss. She also
complained of increasing weakness, with particular difficulty
in rising from a sitting position. She had never had any
previous hospital admissions, but had seen the GP for
troublesome pruritus over the past four years for which she
took chlorpheniramine. She was noted to have a serum
cholesterol level of 10.5 mmol/l during a routine health
check one year ago, for which she had been taking
simvastatin. She was widowed two years ago and now lived
alone. There was no recent history of travel abroad.
Investigations are shown.
Hb
WCC
Platelets
MCV
Sodium
Potassium
Urea
Creatinine
Bilirubin
AST
Alkaline phosphatase
Albumin
Protein
Calcium
Phosphate
Cholesterol
Creatinine kinase
Chest X-ray
ECG
11 g/dl
10 109/l
108 109/l
90 fl
135 mmol/l
4.7 mmol/l
9 mmol/l
125 mol/l
90 mol/l
70 iu/l
400 iu/l
33 g/l
80 g/l
2.0 mmol/l
0.9 mmol/l
7 mmol/l
900 u/l
Normal-sized heart
(PA view)
Clear lung fields
Loosers zone right
clavicle
Sinus rhythm
Partial RBBB
398
Answer 392
1. i. Chronic myeloid leukaemia.
ii. Myelofibrosis.
2. i. Neutrophil leucocyte alkaline phosphatase.
ii. Karyotype for Philadelphia chromosome.
392
Features which may help distinguish chronic myeloid leukaemia from myelofibrosis
Parameter
Myelofibrosis
WCC
>50 109/l
>50 109/l
Large spleen
Present
Present
Blood film
Leucoerythroblastic
Tear drop cells
Neutrophil leucocyte
alkaline phosphatase
Low
Normal/high
Philadelphia chromosome
Present in 90%
Absent
Marrow
Numerous granulocytes at
varying stages of maturation
Answer 393
1. Fractured sternum due to osteomalacia.
2. Lateral chest X-ray.
3. Proximal myopathy due to osteomalacia.
4. Reduced excretion of cholesterol owing to biliary
stasis.
5. Simvastatin-induced myositis/rhabdomyolysis.
Clinical Cases
399
Question 394
A 35-year-old female with Crohns disease since the age
of 15 years presented with a six-month history of foulsmelling diarrhoea and weight loss.
Investigations are shown.
Hb
WCC
Platelets
MCV
Serum folate
Serum B12
Faecal fat
Schilling test
10 g/dl
7 109/l
199 109/l
106 fl
22 g/l
65 ng/l
50 mmol/l
(NR <20 mmol/l)
Pre-intrinsic factor 2% B12
isotope excreted
Post-intrinsic factor 2% B12
isotope excreted
400
Answer 394
1. i. Primary B12 malabsorption.
ii. Bacterial overgrowth.
2. Repeat Schilling test after a two-week course of antibiotics.
Bacterial overgrowth
Abnormal
Terminal ileal stricture
Normal bacteria
Positive
Normal
Fistulae, jejunal strictures
High concentration of
Escherichia coli/Bacteroides
Positive
Clinical Cases
394
Schilling
test
part 1
Normal
Abnormal
Pernicious anaemia
Gastrectomy
Chronic atrophic gastritis
Congenital intrinsic factor
deficiency
Bacterial
overgrowth
Jejunal diverticuli
Blind loop
syndrome
Terminal ileal disease
Fish tapeworm
Drugs:
colchicine
neomycin
para-amino-salicylic acid
401
Normal
Vegan
Transcobalamin II deficiency
Pregnancy
Thyrotoxicosis
Normal
Repeat part 1
after antibiotics*
Abnormal
Question 395
A 65-year-old male was seen in the out-patients clinic
with a one-year history of dizziness which was worse on
getting out of bed, and occasionally associated with
collapse. The patient also complained of weakness
affecting both legs. On further questioning, he admitted
to urinary incontinence and his wife noted that he was
generally slow and had an intermittent tremor affecting
his right hand.
On examination, he appeared slightly withdrawn. His
pulse was 84 beats/min, and blood pressure
155/85 mmHg. The heart sounds were normal.
Examination of the respiratory and gastrointestinal
systems was normal. On examination of the central
nervous system he had sluggish pupillary reflexes and
402
Answer 395
1. Multi-system atrophy or ShyDrager syndrome.
2. i. Lying and standing blood pressure.
ii. Autonomic nervous system testing (loss of sinus
arrhythmias on ECG, loss of reflex bradycardia on
carotid sinus massage, absence of a reflex
tachycardia after the Valsalva manoeuvre).
The patient has a pill-rolling tremor and increased
muscular tone, indicating an extrapyramidal syndrome
such as Parkinsons disease. The presence of additional
neurological findings suggests that he has a Parkinsonplus syndrome. There are several Parkinson-plus
syndromes in the literature, but the ones which are most
commonly tested include multi-system atrophy and the
SROS. Multi-system atrophy is the name given to a
sporadically occurring condition which begins in adult
life, usually in the sixth decade. It is characterized by
neuronal cell loss and gliosis changes in:
The substantia niagra pathways that cause
Parkinsonism.
The olivopontocerebellar tract causing ataxia,
dysarthria, nystagmus and pyramidal signs.
The intermediolateral cell column (pre-ganglionic
sympathetic neurones in the lateral horns of the spinal
cord) causing autonomic nervous system failure.
Other causes of autonomic failure are shown (Table).
These changes often overlap and may present as a
mixture of neurological abnormalities. When features of
Parkinsons disease predominate, the disorder is called
striatonigral degeneration. When features of the
autonomic failure predominate, the disorder is commonly
known as ShyDrager syndrome, and when cerebellar
features predominate it is called olivopontocerebellar
atrophy. When all three systems are involved the disorder
is known as multi-system atrophy. Unlike Parkinsons
disease, there is a shortened life expectancy, with a
median survival of 9.3 years.
In ShyDrager syndrome impotence is often the first
symptom. Incontinence is common in both sexes. Speech
differs from the hypophonic monotony of Parkinsons
disease, incorporating quivering, straining, slurring, and
dysarthric components. Patients may develop aphonia,
anarthria and dysphagia, which are the same as in
Parkinsons disease. Respiratory stridor can occur in
about 30% of patients. There is no specific treatment for
multi-system atrophy and the associated disorders. The
use of compression stockings, fludrocortisone, and
pressor agents such as ephedrine have been used for the
postural symptoms. The response to L-dopa is usually
absent or poor.
SteeleRichardsonOlszewski syndrome
This is another multisystem degeneration syndrome. It is
characterized by cell loss and neurofibrillary tangles in the
brainstem, globus pallidus, subthalamic and dentate
nuclei, and causes the syndrome of progressive
supranuclear palsy. It begins in the seventh decade.
Patients present with imbalance, particularly falling
backwards, a coarse dysarthria, involuntary groans and
dysphagia. Perseverance may be obvious in speech with
repetition of syllables and words (palilalia) or even of
whole phrases (palilogia). Involuntary eye closure is often
seen. The brow may be furrowed and the eyebrows raised
from frontalis hyperactivity in an attempt to keep the eyes
open, resulting in a surprised expression. The
characteristic feature in SROS is a supranuclear palsy of
voluntary gaze. Voluntary downgaze is slow and
incomplete, but when the patients neck is passively
extended while fixing his gaze on the examiners nose, a
downward gaze is obtained. Patients may therefore have
problems with reading and eating. Patients with SROS
can masquerade as having Parkinsons disease because of
axial rigidity and gait disturbances, but lack features of
distal Parkinsonism (distal limb akinesia or rigidity).
Resting tremor is almost never seen. There is no effective
treatment. Median survival is about 67 years.
Clinical Cases
403
Question 396
396a
A 31-year-old male was admitted to hospital with a twoweek history of progressive dyspnoea on exertion and
wheeze. He complained of aches and pains in his arms
and legs. He had suffered from ulcerative colitis for four
years, and required several courses of high-dose
prednisolone until the last two months, when his colitis
was relatively quiescent. He also had a past history of
hyperthyroidism which was medically treated with
carbimazole. He was currently maintained on
sulphasalazine 1 g twice daily for the ulcerative colitis.
On examination, he was dyspnoeic, had mild cervical
and axillary lymphadenopathy, and a generalized
maculopapular rash. He had a fever of 38.5C (101.3F).
The heart rate was 110 beats/min and regular. The
blood pressure was 140/80 mmHg. Heart sounds were
normal. Auscultation of the lung fields demonstrated
widespread wheeze. His abdomen was very muscular and
difficult to examine. All other examinations were
essentially normal.
Investigations are shown.
Hb
WCC
13 g/dl
15.3 109/l
(neutrophils 10.1 109/l,
lymphocytes 1.0 109/l,
eosinophils 4.2 109/l)
Platelets
308 109/l
Sodium
126 mmol/l
Potassium
4.3 mmol/l
Urea
7 mmol/l
Creatinine
100 mol/l
ESR
98 mm/h
Blood and sputum cultures: Negative
Arterial blood gases (on air):
pH
7.4
PaCO2
3.3 kPa
PaO2
8.7 kPa
Bicarbonate
21 mmol/l
O2 saturation
92%
Chest X-ray (396a)
404
Answer 396
b. Eosinophilic pneumonitis.
The patient has a generalized illness consisting of a
widespread macular rash, generalized lymphadenopathy,
and a very high eosinophil count. He has a wheeze, and
his chest X-ray reveals patchy consolidation, which is
worse in the right lung. He had been on prednisolone for
ulcerative colitis but has recently commenced
sulphasalazine. The symptoms and signs appeared after
the drug was commenced, and the most likely diagnosis
for his respiratory problem is an eosinophilic pneumonia.
This question tests the readers knowledge of causes of
eosinophilia (396b) of which there are many; however,
the most common cause is allergy. An allergic reaction to
drugs may precipitate a profound eosinophilia with multisystem involvement, including eosinophilic infiltration
into the lungs. Sulphonamides are a well-recognized
cause of eosinophilia and subsequent eosinophilic
consolidation. Other drugs implicated include
erythromycin, nitrofurantoin and imipramine. The most
obvious management of a drug-related eosinophilia is to
stop the culprit agent. Pulmonary involvement responds
well to high-dose steroids, which may be tailed off over a
few weeks. However, relapse is not uncommon and some
396b
Mild 0.52.0
Eosinophilia
>0.5 109
Severe >5
Chest X-ray
Allergies
Addisons disease
Lymphoma (Hodgkins)
Immunodeficiency
(WiskottAldrich)
Vasculitidies
(ChurgStrauss syndrome)
Radiation
Ulcerative colitis
Normal
Abnormal
Parasites*
or
Blistering
skin disease
Eosinophilic pneumonia
Tropical pulmonary
eosinophilia
Eosinophilic leukaemia
Hypereosinophilic syndrome
*May be associated with severe eosinophilia and abnormal X-ray.
Drugs:*
Sulphonamides
Chlorpropamide
Erythromycin
Nitrofurantoin
Asthma
Allergic rhinitis
Allergic bronchopulmonary
aspergillosis
Wucheria bancrofti
Strongyloides
Other worms
Pemphigus
Pemphigoid
Erythema multiforme
Clinical Cases
405
Question 397
A 16-year-old female is investigated for short stature. The
results of a dynamic pituitary function tests following
Time
(min)
Glucose
(mmol/l)
GH
mu/l
Cortisol
(nmol/l)
TSH
mu/l
LH
iu/l
FSH
iu/l
Oestradiol
pmol/l
0
20
30
40
60
4.0
2.8
1.6
1.5
2.2
1.4
12.0
28
32
20
400
860
1270
1450
1120
2.0
5.2
8
29
40
34
16
24
20
4
5
Question 398
398
406
Answer 397
1. e. There is evidence of primary hypogonadism.
2. a. Buccal smear for karyotyping.
3. b. Turners syndrome.
In order to answer this question correctly the reader
requires knowledge of the normal results of dynamic
pituitary function tests and gonadotrophin and sex
hormone levels (Tables A and B).
In this case, there is an adequate stimulus to GH and
cortisol secretion. The GH response is normal, and there
is no evidence of hypothyroidism. The basal oestradiol is
low and the basal LH and FSH are high, suggesting
primary hypogonadism. The LHRH test is normal (as is
the case) in primary hypogonadism. The most probable
diagnosis is Turners syndrome. Turners syndrome is
characterized by a single X chromosome (karyotype 45
XO). It has an incidence of approximately 1 in 2,500.
The main abnormality is gonadal dysgenesis, the
consequences of which are primary amenorrhoea and
infertility. Oestradiol levels are low, resulting in elevated
gonadotrophin levels via the positive feedback on the
pituitary. The patients are typically short and have a
number of other morphological abnormalities (Table C).
The diagnosis is confirmed by a buccal smear which
reveals an absent Barr body. There are several other
causes of hypogonadism in females (Table D).
Polycystic ovary syndrome may also cause partial
hypogonadism, but in contrast with the other causes of
hypogonadism given in Table D, the oestradiol levels are
only slightly reduced and the FSH level is low (Table E).
Although coeliac disease is a recognized cause of short
stature (and also delayed puberty), the gonadotrophin
response to LHRH is entirely normal. The commonly
Table B Normal gonadotrophin and sex hormone levels in males and females
Females
Follicular phase, FSH 110 iu/l and LH 220 iu/l
Oestradiol <110 pmol/l
Testosterone 0.53 nmol/l
Males
FSH 17 iu/l and LH 110 iu/l
Testosterone 1035 nmol/l
Clinical Cases
407
Renal anomalies
Horse-shoe kidneys
Miscellaneous abnormalities
Webbed neck (fused cervical vertebrae)
Lymphoedema
Low hair line
Multiple naevi
Increased incidence of auto-immune thyroiditis
and diabetes
Turners syndrome
Pure ovarian dysgenesis*
Swyers syndrome**
Auto-immune oophoritis
Ovariectomy
Chemotherapy
Steroid biosynthetic defect
(17--hydroxylase deficiency)
* The pathology is the same as Turners, but differs in that there is a normal complement of chromosomes and the
other morphological features of Turners syndrome are absent. Some patients may have sensorineuronal deafness.
** Swyers syndrome is characterized by the XY karyotype and gonadal dysgenesis. Affected individuals are
phenotypically female. It is associated with a high incidence of gonadoblastomas.
Irregular menstruation
Impaired fertility
Hirsutism
Acne
Obesity
Low oestradiol levels
Constitutional delay*
Familial
* Slow growth from the beginning, spontaneous puberty, slight delay in bone maturity, normal LHRH test.
Answer 398
a. Serum potassium.
408
Question 399
A 65-year-old female was referred to a neurologist with a
six-month history of progressive weakness and clumsiness
of her left hand. She mentioned having particular
difficulty in washing the dishes and using the gear stick
while driving her car. Her husband noticed that her gait
had been unsteady and she had suffered a few falls in the
past year. On systemic enquiry there was no history of
headaches, visual disturbance or weight loss, but she had
experienced dizziness on turning her head suddenly.
On examination she was thin and had marked
kyphoscoliosis. There was evidence of wasting of the
small muscles of the hands, which was more prominent
on the left side than the right. There was reduced power
on flexion and abduction of the arms. The supinator and
biceps reflexes on the left side were absent but present on
the right. The triceps reflexes were brisk bilaterally. The
power in both lower limbs was grade 4 out of 5 in all
muscle groups. The tone was increased. The ankle and
knee reflexes were brisk bilaterally. The left plantar
response was upgoing but the right one was equivocal.
Sensation was normal with the exception of vibration
sense at both ankle joints.
Question 400
A young alcoholic who is well known to the local Accident
and Emergency Department was admitted to hospital after
being found collapsed. On examination, he was unrousable.
His temperature was 36.5C (97.7F). His heart rate was
Hb
WCC
Platelets
MCV
INR
Sodium
Potassium
Urea
Creatinine
Bicarbonate
Calcium
Phosphate
Albumin
AST
Bilirubin
Alkaline phosphatase
Gamma GT
Glucose
Urinalysis
7 g/dl
23 109/l
50 109/l
102 fl
1.9
131 mmol/l
5.6 mmol/l
17 mmol/l
200 mol/l
16 mmol/l
1.9 mmol/l
1.0 mmol/l
30 g/l
64 iu/l
53 mol/l
204 iu/l
190 iu/l
21 mmol/l
Protein +1
Blood 0
Ketones +1
Clinical Cases
409
Question 401
401a
401b
FEV1(l)
FVC (l)
TLC (l)
KCO (mmol/min/kPa)
Sodium
Potassium
Urea
Creatinine
Calcium
Phosphate
Alkaline phosphatase
Blood glucose
X-ray of hands (401b)
Fluid deprivation test:
Time (min)
PmOsm/l
0
303
60
310
120
318
180
328
240
335
8 h after desmopressin
Actual
2.2
2.5
3.3
0.9
Predicted
4.1
5.4
6.3
1.40
143 mmol/l
4.5 mmol/l
6 mmol/l
90 mol
2.3 mmol/l
1.1 mmol/l
120 iu/l
4.2 mmol/l
UmOsm/l
120
120
120
120
120
800
410
Answer 399
1. d. Cervical myelopathy.
2. b. MRI scan cervical spine.
The patient presents with progressive weakness affecting
her arms and hands. She has a combination of upper and
lower motor neurone signs in the upper limbs and purely
upper motor neurone signs in the lower limbs. There is
loss of vibration sense at the level of the ankles. This may
be a normal finding in patients in their seventh decade
but may indicate pathology in the dorsal columns.
The differential diagnosis is between motor neurone
disease, cervical cord tumour and cervical myelopathy,
and subacute combined degeneration of the spinal cord.
Features against motor neurone disease include her
gender (more common in males), the mid-cervical reflex
pattern (absent supinator and biceps reflex but
exaggerated triceps reflex), which is more suggestive of
cervical myelopathy, the association of her symptoms
with rigidity in the neck and dizziness on turning
suddenly, which again suggests pathology in the cervical
cord, and the absence of weight loss, which is usually
marked in motor neurone disease.
Subacute combined degeneration of the spinal cord is
a remote possibility, but one would want more evidence
of a sensory neuropathy in this condition, for example,
absence of light touch and proprioception and absent
knee or ankle jerks.
Both cervical myelopathy and a cervical cord tumour
may present with predominantly upper limb signs, which
characteristically produce lower motor neurone
disturbances at the level of the lesion and upper motor
signs below it. The best investigation to differentiate
between the two is an MRI scan of the spinal cord, which
Answer 400
1. d. Acute pancreatitis.
2. i. Serum amylase.
ii. Arterial blood gases.
iii. Full clotting screen.
iv. Chest X-ray.
v. Ultrasound of the abdomen.
The clinical scenario is of an alcohol abuser who presents
with unconsciousness and a rigid abdomen. The
differential diagnosis is between a perforated duodenal
ulcer, acute pancreatitis, ethylene glycol poisoning and
methanol poisoning, as all four are recognized causes of
abdominal pain in alcoholism. The raised gamma GT
supports alcohol abuse. The low calcium favours either
acute pancreatitis or ethylene glycol poisoning (oxidation
of ethylene glycol to oxalic acid results in chelation of
Hepatic encephalopathy
Wernickes encephalopathy
Methanol poisoning
Ethylene glycol poisoning
Alcohol intoxication
Subdural haemorrhage
Haemorrhage from peptic ulcer or varices
Acute haemorrhagic pancreatitis
Tuberculous meningitis
Alcohol-induced hypoglycaemia
Clinical Cases
411
Answer 401
Other conditions
Behets syndrome
TB
Leprosy
Histoplasmosis
Yersinia
Neisseria meningitidis
and gonococcal
infections
Pasteurella pestis
412
Mumps
Sarcoidosis
Lymphoma
Leukaemia
Sjgrens syndrome
Alcohol abuse
Bulimia
Cystic fibrosis
Haemochromatosis
Amyloidosis
Acromegaly
Malabsorption syndromes
Drugs; propylthiouracil
Toxins; lead
Hyperlipidaemia
P mOsm/l
300
300
>300
>300
U mOsm/l
Over 720 or double the plasma osmolality
Incomplete response, i.e. the U mOsm/l is not
quite 720 and does not exceed twice the value
of the P mOsm/l. Typical value 600700 mOsm/l
<150; over 720 mOsm/l after desmopressin
<150; remains <150 mOsm/l after desmopressin
Clinical Cases
413
Question 402
A 26-year-old female presented with a six-month history
of light-headedness on hanging the washing. She was
seen by her GP at the onset of her illness and he noted a
blood pressure of 80/50 mmHg in both arms but no
other abnormality. Over six months she had one episode
of weakness and numbness of the right arm and face for
almost an hour and two near syncopal episodes. She
developed increasing lethargy, night sweats, and aches
and pains in her upper limbs. Her appetite had reduced
and she had lost almost 3 kg in weight. There was no
other past medical history of note. She had smoked 10
cigarettes per day for three years from the age of 17.
On examination she had flushed cheeks but there was
no skin rash. The heart rate was 90 beats/min and
regular. The systolic blood pressure was 80 mmHg in
both upper limbs, but the diastolic blood pressure could
not be ascertained. On examination of the precordium,
the apex was heaving in nature but not displaced. On
auscultation there was an audible fourth heart sound.
The radial pulses were absent bilaterally, the brachial
pulses were weak bilaterally, the right carotid pulse was
absent. The left carotid pulse was prominent. Both
femoral pulses were easily palpable. Neurological
examination was normal.
Investigations are shown.
Hb
WCC
Platelets
ESR
Sodium
Potassium
Urea
Creatinine
Glucose
Cholesterol
Autoantibody screen
Syphilis serology
Chest X-ray
ECG
CT scan brain
9.4 g/dl
8 109/l
430 109/l
112 mm/h
135 mmol/l
4.5 mmol/l
6 mmol/l
84 mol/l
4.5 mmol/l
5.3 mmol/l
Rheumatoid factor absent
Antinuclear antibodies
present in a titre of 1 in 16
VDRL and TPHA absent
Normal-sized heart
Clear lung fields
Voltage criteria for left
ventricular hypertrophy
Normal
414
Answer 402
1. d. Takayasus arteritis.
2. a. Aortography.
3. c. Hypertension secondary to renal artery stenosis.
g. Acquired co-arctation of the aorta.
h. Reduced distensibility of the ascending aorta.
The absence of pulses in the arms and neck and the
associated high ESR value in a young woman should raise
the diagnosis of Takayasus arteritis. Takayasus arteritis is
a rare disorder with a prevalence of 1.52 per million. It
has a strong female predisposition and is more common
in parts of Africa and Asia. The mean age of onset is 29
years, but it can occur from any age between infancy and
middle age. It is very uncommon after middle age. The
condition is caused by granulomatous vasculitis of large
vessels, particularly the aortic arch, which results in
obliterative changes in the lumina of the vessels affected.
Inflammation may be multi-segmental, interspersed with
normal segments. Symptoms comprise a systemic illness
(sweats, weight loss, anorexia and myalgia) as well as
vascular insufficiency in the limbs affected. Physical signs
402
415
Ca
PO4
Alkaline
phosphatase
1 and 3 hyperparathyroidism
Additional
2 hyperparathyroidism/CRF
/N
Hypoparathyroidism
PTH absent
Pseudohypoparathyroidism
PTH elevated
Magnesium deficiency
PTH normal
Pseudopseudohypoparathyroidism
Osteomalacia/rickets
Osteoporosis
Myeloma
N*
Pagets disease
N**
N/
Sarcoidosis
N/
Vitamin D intoxication
urinary hydroxyproline
Genetics
Patterns of inheritance
Autosomal dominant inheritance
Males and females are equally affected.
All individuals inheriting the abnormal gene are affected.
Offspring of affected parents (irrespective of the parental
sex) have a 50% chance of inheriting the disease.
This is in contrast to X-linked conditions where male-tomale transmission of disease does not occur.
Autosomal recessive inheritance
Males and females are equally affected, but are fewer in
number than in autosomal dominant conditions.
Not all generations will be affected.
If both parents are carriers for the recessive gene 25% of
the offspring will be affected, 50% will become carriers,
but will not have the disease and 25% will not have the
abnormal gene.
If an affected individual marries a carrier, then 50% offspring will be affected and 50% offspring will be carriers.
If an affected individual marries another affected, then all
offspring will be affected.
416
Audiograms
An audiogram of both ears may be presented on the same
graph, or there may be a separate audiogram for each ear.
A separate suffix will be given to differentiate between air
conduction (AC) and bone conduction (BC).
In sensorineuronal deafness, both air and bone conduction are diminished. The airbone gap is usually narrow,
i.e. there is not much difference between air and bone
conduction. In conduction deafness, bone conduction is
superior to air conduction on the affected side.
Normal hearing can detect sounds of a frequency
between 2508,000 Hz at a sound intensity of 010 dB
(1). The following audiograms are most commonly
tested in higher post-graduate examinations.
Sensorineuronal deafness at progressively higher frequencies. In degenerative sensorineuronal loss (presbycusis), deafness is usually bilateral most profound at sounds
-10
10
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
BC
100
60
70
80
90
100
Right
110
120
Left
120
140
130
Unmasked
125
250
500
1000
2000
Frequency HZ
4000
140
8000
10
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
BC
100
Right
110
250
500
1000
2000
Frequency HZ
4000
8000
125
250
500
1000
2000
Frequency HZ
4000
8000
50
60
70
80
90
100
110
120
Left
120
130
Unmasked
130
140
125
-10
-10
50
110
130
-10
125
250
500
1000
2000
Frequency HZ
4000
8000
140
0
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
0
10
BC
100
70
80
90
100
Right
110
Left
120
130
Unmasked
125
250
500
1000
2000
Frequency HZ
4000
140
8000
0
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
0
10
BC
100
250
500
1000
2000
Frequency HZ
4000
8000
50
60
70
80
90
100
110
Right
110
120
Left
120
130
130
Unmasked
125
250
500
1000
2000
Frequency HZ
4000
140
8000
125
250
500
1000
2000
Frequency HZ
4000
8000
-10
-10
0
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
BC
100
0
10
50
60
70
80
90
100
110
Right
110
120
Left
120
130
140
125
-10
-10
60
120
130
50
110
140
-10
-10
140
417
Unmasked
125
250
500
1000
2000
Frequency HZ
4000
8000
130
140
125
250
500
1000
2000
Frequency HZ
4000
8000
418
-10
10
10
20
20
30
30
40
40
50
AC
60
Right
70
Left
80
90
BC
100
-10
50
60
70
80
90
100
110
Right
110
120
Left
120
130
140
Unmasked
125
250
500
1000
2000
Frequency HZ
4000
8000
130
140
125
250
500
1000
2000
Frequency HZ
4000
8000
419
Examples:
Chronic bronchitis.
Emphysema.
Asthma.
Bronchiectasis.
Examples:
Interstitial lung disease:
sarcoidosis,
fibrotic lung disease
Pulmonary emboli.
Pulmonary oedema.
Neuromuscular disease affecting respiratory muscles.
Pulmonary haemorrhage.
Lymphangitis carcinomatosa.
Thoracic cage defects.
Spirometry
FEV1 (l)
FVC (l)
FEV1/FVC
TLC (l)
RV
TLCO (l)
KCO (mmol/min/kPa)
<70% (normal
7080%)
(gas trapping)
Spirometry
FEV1 (l)
FVC (l)
FEV1/FVC
TLC (l)
RV
TLCO (l)
KCO** (mmol/min/kPa)
>80%
KCO
Increased KCO:
Polycythaemia.
Left-to-right shunts.
Pulmonary haemorrhage.
Asthma (exceptionally rare).
Thoracic cage deformities (may be normal).
Reduced KCO:
Interstitial lung disease.
Primary pulmonary hypertension.
Multiple pulmonary emboli.
Pulmonary oedema.
Lymphangitis carcinomatosa.
Arteriovenous malformation.
Anaemia (spirometry normal).
Obstructive airways disease (rare exception is asthma).
420
Interpretation of Respiratory Flow Loop Curves
The normal flow loop curve has a triangular expiratory
flow limb and a semi-circular inspiratory flow limb (7).
The explanation for this is as follows: following a full inspiration, the lungs recoil is maximal, as is pleural pressure. The onset of expiratory flow is therefore explosive
and reaches its peak within 0.01 s. The expiratory curve
decreases its flow gradually as the lung volume drops
from TLC to RV. This reflects the gradual drop in the
lungs elastic recoil as the lung gets smaller. In contrast
to expiration, inspiration does not reach an instant
maximal flow. As the respiratory muscles contract, the
power increases progressively from the start of the
inspiration to achieve a maximal flow. This takes a
relatively long time, and the maximal inspiratory flow is
only achieved by the mid-point of the vital capacity. The
flow then slows again as the maximum inspired volume is
reached, giving the inspiratory limb a semi-circular
appearance.
Flow loops tested in the examination are those of
obstructive airways disease, extrathoracic airways obstruction, intrathoracic airways obstruction, and a restrictive
lung defect.
7
Flow (l/sec)
10
8
6
Expiration
4
2
0
2
Inspiration
6
8
10
0 1 2 3 4 5 6 7 8
Change in lung volume (l)
8
Flow (l/sec)
Flow (l/sec)
10
8
6
Expiration
Expiration
4
2
0
2
Inspiration
Inspiration
8
10
6
0
1
2
3
4
5
Change in lung volume (l)
0
2
4
6
Change in lung volume (l)
Flow (l/sec)
10
11
Flow (l/sec) 10
8
Expiration
421
6
4
Expiration
2
0
Inspiration
Inspiration
6
8
10
4
0
1
2
Change in lung volume (l)
0
2
4
6
8
Change in lung volume (l)
Echocardiography
Echocardiography has featured, and will continue to
feature, in postgraduate examinations because it is widely
requested, and pictures from still frames are relatively
easy to interpret. Both M-mode and two-dimensional
(2-D) echocardiography are tested, although the latter is
being shown with an increasing frequency because it
allows the reader to have a better appreciation of cardiac
chambers.
Normal values for cardiac dimensions are shown in the
table.
2-D echocardiography
The view which is shown most often is the parasternal
long-axis view (12). In this view it is not always easy to
study the right ventricle in detail, and therefore it is
unusual to be shown right-sided pathology in the
Measurement
Left atrium
Left ventricular diastolic size
Interventricular septum
Posterior wall
<4.5 cm
<5.5 cm
<1.2 cm
<1.2 cm
12
13
1
6
3
4
8
Key:
1 Interventricular septum
2 Left ventricle
3 Mitral valve
4 Left atrium
5 Left ventricular posterior wall
6 Aorta
7 Right ventricle
8 Right atrium
422
14
Interventricular
septum
15
Right ventricular
outflow tract
Right
ventricle
Aorta
Aortic valve
Left ventricle
Left
atrium
Mitral valve
Left
ventricle
Interventricular
septum
Mitral valve
Tricuspid
valve
Pericardium
Right
atrium
16
17
18
19
Left
atrium
Interatrial
septum
423
20
21
22
23
24
25
424
26
Hypertrophic
cardiomyopathy
Vegetation on
aortic valve
Calcific aortic
stenosis
Mitral stenosis
27
Hypertrophic
cardiomyopathy
(asymmetric
septal
hypertrophy)
Mitral stenosis
Vegetation
on mitral
valve
Atrial
myxoma
29
Left
ventricle
Left ventricular
posterior wall
Pericardium
30
31
Left ventricular
thrombus
Vegetation
on mitral
valve
Atrial
myxoma
Pericardial effusion
Left ventricular
thrombus
28 Chest wall
425
32
33
Mitral stenosis
Atrial myxoma
HCM
The mitral valve moves forward towards the septum in systole (a phenomenon
termed systolic anterior motion of the mitral valve (SAM). In addition, the left
ventricular cavity is small and there is septal hypertrophy
Aortic regurgitation
As the regurgitant jet flows back into the left ventricle it tickles the anterior
leaflet, causing a fluttering appearance
AMVL
PMVL
Normal systolic
appearance
Echo on AMVL
Mitral stenosis
Vegetation on
mitral valve
Loss of M-shape
Reduced excursion
Forward movement of PMVL
Vegetation
on PMVL
Normal
Mitral valve prolapse
diastolic
appearance Hammocking of the leaflets in mid systole
Myxoma
Echogenic mass in
mitral valve orifcie
Hypertrophic
cardiomyopathy
34
Systolic anterior
motion of MV
Fluttering
of AMVL
Aortic
regurgitation
426
Acidbase Disturbance
Acidosis
The main source of acid (H+ ions) in the body is tissue
respiration. Carbon dioxide produced by cellular respiration is converted to carbonic acid, which dissociates to
generate H+ (acid) and HCO3 ions (buffering base). The
retention of CO2, increase in H+ or reduction in HCO3
may result in an acidosis.
CO2 + H2O H2CO3 H+ + HCO3
Three types of acidosis are recognized:
Respiratory acidosis.
Metabolic acidosis with a high anion gap.
Metabolic acidosis with a normal anion gap.
Respiratory acidosis is characterized by a fall in arterial
pH (<7.35) due to CO2 retention. Metabolic acidosis
may result from the retention of fixed or organic acids
causing a reduction in the bicarbonate level (which is the
main buffering agent for H+ in the blood) without any
change in the chloride situation. In these situations, it is
termed metabolic acidosis with a high anion gap. Alternatively, metabolic acidosis may occur as a consequence of
bicarbonate loss from the gastrointestinal tract or the
kidneys. In these situations, chloride is retained, resulting
in a hyperchloraemic acidosis or a metabolic acidosis with
a normal anion gap. The anion gap is calculated by subtracting the sum of the sodium and potassium concentrations from the sum of the chloride and bicarbonate
concentrations. The normal anion gap is between
1018 mmol/l. The hallmark of metabolic acidosis of
either type is a low arterial pH and a low bicarbonate
level.
Regulation of arterial pH is controlled by the kidneys
and the lungs. Acidosis can be compensated for either by
removing CO2 from the body (lungs) or by retaining
bicarbonate ions (kidneys). Respiratory acidosis is
compensated for by the kidneys, which retain bicarbonate
ions. In compensated respiratory acidosis the pH is
normal, or almost normal, and the bicarbonate level is
high. In compensated metabolic acidosis the arterial pH
is normal, or almost normal, and the pCO 2 is low.
Respiratory acidosis is compensated by the respiratory
system through a centrally mediated mechanism which
results in hyperventilation and a consequent reduction in
the pCO2. Causes of respiratory and metabolic acidosis
are given (Table).
Alkalosis
Alkalosis may be respiratory or metabolic in origin. In
respiratory alkalosis, there is a high pH due to hyperventilation, causing a low pCO2. Metabolic alkalosis is
usually due to increased loss of H+ from the kidney or
gastrointestinal tract, or to increased ingestion of alkaline
Normal Ranges
Normal Ranges
Haematology
ESR
Hb
MCH
MCHC
MCV
PCV (haematocrit)
Platelet count
RBCs
Reticulocyte count
WCC
male
female
male
female
male
female
total
neutrophils
lymphocytes
monocytes
eosinophils
basophils
SI units
Traditional units
010 mm in 1st h
130180 g/l
115150 g/l
2732 pg
3236 g/dl
7695 fl
0.400.54 l/l
0.350.47 l/l
150400 x 109/l
4.56.5 x 1012/l
3.95.6 x 1012/l
0.22%
411 x 109/l
27.5 x 109/l
1.54.0 x 109/l
0.20.8 x 109/l
0.040.4 x 109/l
<0.1 x 109/l
010 mm in 1st h
1318 g/dl
11.515 g/dl
3236%
7695 x 106/mm3
4054%
3547%
150400 x 103/mm3
4.56.5 x 106/mm3
3.95.6 x 106/mm3
0.22%
411 x 103/mm3
27.5 x 103/mm3
1.54.0 x 103/mm3
0.20.8 x 103/mm3
0.040.4 x 103/mm3
<0.1 x 103/mm3
3046 s
28 min
24 g/l
1214 s
1519 s
3046 s
28 min
0.20.4 g/dl
1214 s
1519 s
170700 nmol/l
<140 nmol/l
<10 "g/l
5001,100 pmol/l
<360 mu/l
24 "g/l/h
514 "g/l/h
1035 nmol/l
0.93.1 nmol/l
68174 nmol/l
0.43.6 mu/l
6.125.2 "g/dl
5.0 "g/dl
<10 ng/ml
5001,100 pmol/l
<360 "u/ml
24 ng/ml/h
514 ng/ml/h
310 ng/ml
0.31.0 ng/ml
4.513.6 "g/dl
0.43.6 "u/ml
<10 ku/l
530 iu/l
3448 g/l
25100 iu/l
1040 iu/l
160900 ng/l
2230 mmol/l
217 "mol/l
<10 u/ml
530 mu/ml
3.44.8 g/dl
25100 mu/ml
1040 mu/ml
160900 pg/ml
2230 mEq/l
0.121.0 mg/dl
Clotting
APTT
BT
Fibrinogen
PT
TT
Endocrinology
Cortisol
09.00 h
24.00 h
GH
Oestradiol mid-cycle
Prolactin
Renin
lying
standing
Testosterone
male
female
Thyroxine
TSH
Biochemistry
-fetoprotein
ALT
Albumin
Alkaline phosphatase
AST
B12 (serum)
Bicarbonate
Bilirubin
427
428
Biochemistry (continued)
Calcium
Cholesterol
Chloride
C-reactive protein
Creatinine
Creatinine kinase
Ferritin
Folate
Gamma GT
Glucose (blood)
Iron (serum)
males
females
serum
red cell
males
females
Osmolality
Phosphate
Potassium
Protein
Sodium
TIBC
Urate
Urea
SI units
Traditional units
2.22.7 mmol/l
3.67.8 mmol/l
100106 mmol/l
010 mg/l
50120 "mol/l
17148 iu/l
1079 iu/l
15250 "g/l
320 "g/l
160460 "g/l
530 u/l
2.57.5 mmol/l
1432 "mol/l
1030 "mol/l
280296 mOsm/kg
0.81.5 mmol/l
3.55.0 mmol/l
6280 g/l
135146 mmol/l
4080 "mol/l
0.120.42
2.56.7 mmol/l
8.810.8 mg/dl
139302 mg/dl
100106 mEq/l
01.0 mg/dl
0.571.36 mg/dl
17148 mu/ml
1079 mu/ml
1.525.0 "g/dl
320 ng/ml
160460 ng/ml
530 u/l
45135 mg/dl
78180 "g/dl
56168 "g/dl
280296 mOsm/kg
2.54.65 mg/dl
3.55.0 mEq/l
6.28.0 g/dl
135146 mEq/l
224448 "g/dl
2.07.0 mg/dl
15.040.2 mg/dl (BUN)
0.84.0 g/l
7.018.0 g/l
0.42.5 g/l
80400 mg/dl
7001,800 mg/dl
40250 mg/dl
4.76.0 kPa
11.214.0 kPa
7.357.45
3545 mmHg
84105 mmHg
7.357.45
Immunology
IgA
IgG
IgM
Cardiology
Venae cavae
Right atrium
Right ventricle
Pulmonary artery
PCWP
Left atrium
Left ventricle
Aorta
mean
a-wave
v-wave
mean
systolic
end diastolic
systolic
diastolic
mean
a-wave
v-wave
mean
systolic
end diastolic
systolic
diastolic
mean
mmHg
28
36
14
15
2030
27
1630
413
918
4.512
414
616
611
90140
612
90140
7090
70110
Index
429
Index
References are to case numbers.
acanthosis nigricans 173
ACE inhibitors
contraindications/side-effects 10,
132
coronary artery disease 11, 237
diabetic nephropathy 92
heart failure 10, 296
hypertension 25, 103, 123, 198
myocardial infarction 121
achalasia 231
acidosis
combined respiratory/metabolic 34
lactic 283
metabolic 48, 82, 329
renal tubular 326
respiratory 333
acromegaly 261
acute tubular necrosis (ATN) 60, 289
Addisons disease 218, 273, 372, 373
adrenal hyperplasia, congenital 238,
334
adrenocorticotrophic hormone
(ACTH) ectopic 379
AIDS-defining conditions 262, 388
alcohol-related disease 81, 90, 206,
224, 312, 371, 400
alkalosis
hypokalaemic 220, 275
metabolic 181
respiratory 214, 329
alkaptonuria 71
-1 antitrypsin deficiency 72
Alports syndrome 85
alveolitis
cryptogenic fibrosing (CFA) 217,
343
extrinsic allergic 45, 61, 272
amaurosis fugax 211
amenorrhoea 238, 334
aminophylline 20
amiodarone 22, 68
toxicity 36, 54
amylase, serum 201, 400
amyloidosis 124, 346, 389
amyotrophy, neuralgic 274
anaemia
auto-immune haemolytic 204, 299
hypothyroidism 199
iron deficiency 126, 313, 338
leucoerythroblastic 336
microangiopathic haemolytic
(MAHA) 152
pernicious 102, 199, 376
renal failure 126
rheumatoid arthritis 320
sickle cell 69, 263, 308
sulphasalazine-induced 175
anaesthesia 186
430
Clinistix test 71
clotting disorders 265, 385
cocaine abuse 332
coeliac disease 3, 276, 293
Cogans syndrome 128
colitis, ulcerative 6, 104
common peroneal nerve palsy 108
commotio cordis 266, 353
complement deficiency 234
Conns syndrome 220, 275
copper metabolism 6
coproporphyria, hereditary 257, 310
corneal calcification 168
coronary angiography 121
coronary artery disease 1, 11, 121,
179, 197, 237
corticosteroid excess 379
Coxsackie virus 264
creatinine kinase, raised 199
Crohns disease 19, 31, 104,
24950, 394
cryoglobulinaemia 15, 109
CSF abnormalities 267, 268, 322
Cushings syndrome 173
cyclophosphamide 8
cystic fibrosis 47, 252, 356, 384
cytomegalovirus infection 294
dantrolene 186
dapsone 316
deafness, sensorineuronal 145
delirium tremens 224
dementia, Lewy body 365
dermatitis herpetiformis 316
dextrocardia 66
diabetes insipidus 230, 401
diabetes mellitus 261, 293
HONK 23, 84
ketoacidosis 82
management 125, 242
nephropathy 89, 92, 254, 328
digoxin 223, 296
toxicity 68, 226
diuretics 296
abuse 181
thiazide 25, 123, 125, 132, 181,
301
drug reactions, allergic 396
dural sinus thrombosis, septic 128
dystonia 57
ECG, in metabolic abnormalities 220
echocardiography, transoesophageal
(TOE) 62, 291, 324
E. coli 0157:H7 152
Ecstasy abuse 172
Eisenmengers phenomenon 167, 246
emphysema 222
empyema 56
encephalitis, herpes simplex 280
encephalomyelitis, viral 267
endocarditis
infective 32, 44
prosthetic valve 62, 63
Index
hyponatraemia 9, 172, 230, 386
hypopituitarism 372, 373
hypotension 323
postural 218
hypothermia 140
hypothyroidism 199, 281, 376
immotile ciliary syndrome 252
immunosuppression 44, 77, 251
intervertebral disc prolapse 330
intracranial hypertension, benign
23941
iron deficiency 126, 162, 211, 313
Kartageners syndrome 252
Kawasakis disease 324
ketoacidosis
diabetic 82
euglycaemic 90
Kleinfelters syndrome 146
lead poisoning 213, 257
Legionnaires disease 171, 225, 386
leptospirosis 221
leucoencephalopathy, progressive
multifocal (PMLE) 345
leukaemia
acute myeloid 216
chronic lymphatic 204, 299
chronic myeloid 120, 392
protomyelocytic 258
leukaemoid reaction 142
Liddles syndrome 275
Listeria meningoencephalitis 267
lithium toxicity 28, 116, 284
liver abscess, amoebic 383
liver disease
methotrexate-induced 77
simultaneous heart disease 74
liver function tests 6, 182
Lofgrens syndrome 401
long QT syndrome 266, 353, 368
lung defect
obstructive/restrictive 35
restrictive 111, 217
lung fibrosis
apical 177
causes 35, 36, 217, 343
cyclophosphamide-induced 8
lung lesions
calcified nodules 363
cavitating 355
lung lobe collapse 227, 302
lupus anticoagulant 49, 70
Lyme disease 149, 267
lymphocytosis 267
macrocytosis 165, 376
malabsorption syndromes 162, 276,
394
malaria 158
MalloryWeiss tear 133
Marfans syndrome 79
MCV, raised 102, 161, 163, 271, 375
meningitis
bacterial 83
viral 51, 267
meningococcal septicaemia 26, 234
mesenteric ischaemia 75
mesothelioma 61
metabolic syndrome 182
methaemoglobinaemia 316
methanol toxicity 48, 90
methotrexate 77
microalbuminuria 89, 92
Mikulicz syndrome 401
mitochondrial gene mutations 315
mitral valve prolapse 40
mitral valve stenosis 80, 178
monoclonal gammopathy of
undetermined significance
(MGUS) 219
mononucleosis, infectious 16
motor neurone disease 139, 200
MRI scans, interpretation 18
multiple endocrine neoplasia 1
(MEN 1) 76
multiple endocrine neoplasia 2
(MEN 2) 39
multiple sclerosis 105, 2556
myasthenia gravis 65, 200, 253
myelofibrosis 120, 392
myeloma, multiple 38, 117, 124,
346, 358
myocardial infarction
aortic dissection 160
atrial fibrillation 223
cardiogenic shock 287
coronary reperfusion 1
non-ST elevation 121, 199, 243
normal coronary arteries 332
posterior 323
ST-segment elevation 197, 323
thrombolysis 180, 197
myopathy
steroid-induced 379
thyrotoxic 330
myotonic dystrophy 192
narcolepsy 67
Neisseria meningitidis 26
nephritis
acute interstitial 118, 119, 317
IgA (Bergers nephritis) 171, 185,
278
nephropathy
diabetic 89, 92, 254, 328
hyperuricaemic 216
penicillamine-induced 17
nephrotic syndrome 59, 137, 389
neuralgia, migrainous 292
neurofibromatosis 145
neuroleptic agents 30, 57
neuroleptic malignant syndrome 209
neutropenia, severe septic 351
nifedipine 237
NSAIDs 118, 339
renal manifestations 317
431
432
polyuria 35, 230, 401
porphyria
acute intermittent 147
variegate 310
porphyria cutanea tarda (PCT) 81
pre-eclampsia 1302
pregnancy 248
anticoagulation 122
cardiomyopathy 193
cystic fibrosis 356
epilepsy 87, 190
HELLP syndrome 348
hypertension 1302
proteinuria 17, 59, 185
pseudohypoparathyroidism 46, 159
pseudopolycythaemia 73
pseuodotumour cerebri 23941
psittacosis 41
psoriasis 116
psychiatric ward, patient collapse
209
puberty onset 260
pulmonary emboli 113, 156, 196,
341, 380
multiple 327
pulmonary haemorrhage 171, 210
pulmonary oedema 53, 2445, 291
pulmonary stenosis 13
radiation enteritis 162
Raynauds phenomenon 15, 236
Reiters syndrome 31
renal artery stenosis 53, 1302,
2445
renal carcinoma 29
renal failure
with abdominal pain 382
acute 60, 289, 317
Alports syndrome 85
anaemia 126
chronic 126, 171, 344, 381
and eosinophilia 4
hyperuricaemic nephropathy 216
myeloma 38, 117
renal stones 24950
renal transplantation 44, 251, 354,
357
renal tubular acidosis (RTA) 326
retinitis pigmentosa 360
retinopathy, hypertensive 381
rhabdomyolysis 153
rheumatoid arthritis 17, 77, 96, 196,
222, 320
rickets 321