Liver Function Test Final
Liver Function Test Final
Liver Function Test Final
Bio data
Name: Sumera w/o Farooq Age: 20years Occupation: house wife Residance: Larkana Marital status: married Date of admission: 17/07/11 Mode of admission: emergency
Presenting complaints
Jaundice------ since childhood Generalized weakness--------10 days Vomitting-------10 days Fever-----------2 days
HX of presenting illness
The patient has hx of jaundice since 3 months of her life when at that time she gradually developed yellow discoluration of her eyes along with discolouration of urine and some rash but no hx of fever , vomitting, abdominal pain at that time and since than intensity of jaundice varies but never completely resolved. For this complaints pt underwent liver biopsy at the age of 5 years but no record avialable
The patient also diagnosed as epileptic for 2 years but fit free for 6 months and currently 27 weeks pregnant and was in her usual state of health 15 days back when she developed vomittings. Vomitting usually occur after taking food, yellow in colour, non projectile , not blood stained. No hx of abdominal pain, melena, itching associated but pt initially experienced few episodes of diarrhea
The pt also has generalized weakness for 15 days and feels difficult to perform daily activities The pt also has hx of fever for last 2 days. Fever is low grade, intermittent not associated with chills or rigors.
Past history
Medical: hx of generalized tonic clonic fits for 2 years associated with uprolling of eyes and urinary and fecal incontinance.Fits occur1-2/month but now fit free for last 6 months although took antiepileptic for just 1.5 months surgical: not significant Blood transfusion:nil
Personal hx
Sleep: decreased Apetite: decreased Bowel habits: constipation Micturition: normal Addiction: nil
Gynea/ obs hx
Married for 2 years Primary gravida No previous abortions/IUD/ still births Menstrual hx: normal
Family history
parents alive and healthy 1 of her younger sister(7 years old) also suffering from jaundice since childhood 1 sister had some abdominal mass for which she underwent laparotomy
Drug history
She has been taking syp hepamrez for many years
socioeconomic
Belong to low socioeconomic status
Aneamia: ++ Jaundice: +++ Edema: +(dorsum of feet, pitting) dehydration: -ve Cynosis: -ve Clubbing: -ve JVP: not raised Lymph node: not enlarged Palmer erythema: -ve
Abdominal examination
Distended, no visible veins, striae, pulsations, moving equally with respiration HOF :26 weeks Liver: edge just palpable Spleen: palpable 2-3 cm below costal margin No signs of free fluid Gut sounds: audible
CNS examination
GCS: 15/15 Moving all 4 limbs Plantars: bilaterally down going SOMI: -ve Horizontal nystagmus in both eyes Cranial nerves: intact
chest
Equal air entery on both sides NVB with no added sounds
CVS
S1 and s2 audible in all 4 areas
Differential daignosis
Acute hepatitis? Hepatitis E Heamoglobinopathy Congenital hyperbillirubinemia e.g Gilberts/ crigler najjar Chronic liver disease Epilepsy
investigations
CBC Hb: 6.7 gm/dl MCV: 67.8fl PCV: 26.5% MCH: 17.0pg MCHC: 25.2gm/dl TLC: 8.6 X10e9/l Neutrophil: 84% Platelets:370x10E9/L
UCE
BUN: 11 mg/dl Cr: 0.4mg/dl Na: 136meq/l K: 3.7meq/l Cl: 100meq/l
LFTs
Billi T: 27.64mg/dl Billi Direct: 3.26 mg/dl Billi indirect: 24.38mg/dl SGPT: 146U/L ALP: 200 U/L
RBS: 103 mg/dl LDH: 359 U/L Uric acid: 4.07 mg/dl Retic count: 4.9% ( corrected retic = 2.88%)
Coagulation profile
PT: 26.5/26 APTT: 10.3/10.5
Protein total: 5.0g/dl Albumin: 2.3 g/dl Globulin: 2.7 gm/dl A/G ratio: 0.9
Urine DR
pH: 6.0 RBCs: 1-2/hpf Pus cells: numerous/hpf Protein: ++ Glucose: -ve
Viral profile
HBsAg: -ve Anti HCV: -ve Anti HAV IgM: -ve Anti HEV IgM: -ve
MPx3: all ve ICT malaria: -ve (for both vivax and falciparum)
U/S abdomen
Liver:enlarged, 17.1 cm with decreased echogenecity. PV: normal, intrahepatic ducts not dilated Gall bladder: sludge and multiple calculi largest measuring 1.0 cm CBD: normal Spleen:enlrged measuring15.3 cm
Hospital course
2nd DOA(18/07/11) Pt had episode of GTCs at 12 am for about 20 sec during blood transfusion and she was given inj diazepam and 25% dextrose water No spike of fever recorded
3rd day of admission(19/07/11) Pt had another episode of GTCs at 11 am and was given inj phenytoin as loading dose and serum Ca sent that came out 7.2 mg/dl so inj ca gluconate was also given Pt now developed ALOC and GCS droped to 10/15 At 5 pm she suddenly delievered alive fetus and remained semiconsious Her chest had bilateral crepts and she was
Course in MICU
Consious level remain same GCS 9/15 Further episodes of GTCs despite maintainance dosing of phenytoin LP was done and inj ceftriaxone 2gm bid started in place of fortum and flagyl Blood transfusions given LFTs starts improving
CSF DR
Colourless, Clear, Web not seen Protein: 70 mg% Glucose: 93 mg% Leucocytes: <05/cumm Erythrocytes: 1-2/ hpf Gram stain: no organism seen
19/07/11 21/07/11 23/07/11 25/07/11 20.68 3.63 18.04 2.24 11.28 1.61 9.76 1.22
17.05
77 158
15.08
63 169
9.67
36 172
8.54
32 165
ABGs
Fio2: 21% pH: 7.50 PCO2: 26 mm Hg PO2: 113 mmHg SO2: 99% HCO3 :20 meq/l ABE: -2
Hb electrophoresis -----awaited ANA and serum ceruloplasmin-----awaited Neuro opinion seeked: plan for MRI brain Phenytoin levels sent
Final diagnosis
Moderate (times)
2-3 to 20 2-3 to 20 1.5-2 to 5 2-3 to 10
Marked (times)
>20 >20 >5 >10
Initial Approach
history and physical examination algorithm approach useful mainly when no clinical clues
history patients symptoms risk factors for liver disease concomitant conditions medications occupational exposure to hepatotoxins physical examination body habitus splenomegaly ascites cutaneous stigmata of chronic liver disease
AST
Bilirubin ALP PT
Hepatocellular damage
Cholestasis, impair conjugation, or biliary obstruction Cholestasis, infiltrative disease, or biliary obstruction Synthetic function
Albumin
GGT
Synthetic function
Cholestasis or biliary obstruction
Bile acids
5`-nucleotidase LDH
Albumin
depend on nutrition, volume status, vascular integrity, catabolism, hormone, loss in stool and urine not specific for liver disease T1/2 19-21 D
not reliable indicator of acute liver disease
Hypoalbuminemia
globulin 1.decrease synthesis -protein malnutrition -chronic liver disease -chronic inflammation 2.increase loss chol/TG Hb
-NS
3.increase Vd (ascites, overhydration) 4.increase turnover (catabolic state, steroid)
Globulin
produced by stimulated B lymphocyte elevation in chronic liver disease chronic inflammation and malignant disease
Prothrombin time
liver synthesize coagulation factor except FVIII most present in excess, clotting abnormality occur only when substantial impairment in ability of liver to synthesis PT : FI, II, V, VII, IX and X T1/2 FVII 6 hrs. (shortest)
Prothrombin time
prolonged : vitamin K deficiency (malnutrition, malabsorption, antibiotics) massive transfusion congenital disease liver disease (acute as well as chronic) warfarin DIC
AST, ALT
level of transminase elevation predominant AST / ALT elevation
rate of transaminase declination
AST/ALT ratio
< 1 : majority of liver disease >2
extrahepatic source alcoholic hepatitis ischemic and toxin acute Wilsons disease : hemolysis cirrhosis
AST/ALT ratio
90 80 70
60
50
40
30
20
10
alcoholic
chronic hepatitis
obstructive jaundice
viral hepatitis
slow acute viral hepatitis long half life drug AIH metabolic disease
Alcoholic hepatitis
appropriate history of alcoholic consumption, serologic exclusion of other liver disease 40-80 g/D, 20-40 g/D 10-12 yrs. characteristic pattern
AST rarely exceeds 300 IU/dl AST/ALT >1 in 92%, >2 in 70%
pyridoxine deficiency alcohol induces release of mitochondrial AST
GGT/ALP >2.5
AST predominate : medication/toxin, ischemic >75 times : ischemic, toxic, viral (less common)
Ischemic hepatitis
Ischemic hepatitis
sudden and massive (>2000) elevation of liver enzyme, tend to decrease rapidly and return normal within 1 wk. mild and transient elevation of bilirubin (80% < 2 mg/dl) and ALP extreme elevation LDH (>5000), ALT/LDH < 1.5 rare acute liver failure Rx and prognosis underlying disease
Ischemic hepatitis
LDH
non specific rhabdomyolysis, MI, hemolysis, stroke, renal infarction, acute or chronic liver disease use in
ischemic hepatitis : transient, massive elevation malignant infiltration of liver : sustained elevation with ALP
Bilirubin
UDP-glucoronyltransferase
hepatocyte UCB+ligandin
bile
urobilinogen
stercobilinogen
Bilirubin
Direct bilirubin : reacted directly with reagent Indirect bilirubin : require addition of alcohol for color development Unconjugated bilirubin = indirect form Conjugated bilirubin = bilirubin mono and di-glucoronides
elevated bilirubin
History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin
ineffective erythropoiesis : folate, drug : rifampicin, ribavirin, probenecid resolution of hematoma Gilberts syndrome Crigler-Najjar syndrome
Gilberts syndrome
benign, unconjugated hyperbilirubinemia with otherwise normal liver chemistries up to 5% of normal population polymorphism in gene encoding bilirubin UDP-GT impair ability to conjugate bilirubin prominent in fasting state, systemic illnesses, hemolysis, some medications
Gilberts syndrome
Dx :
asymptomatic, healthy mild unconjugated hyperbilirubinemia (<4 mg/dl) with otherwise normal liver chemistries test exclusion medications and hemolysis
Indirect Hyperbilirubinemia
Bilirubin hemolysis Gilberts syndrome 5 mg/dl 5 mg/dl AST, ALT increase AST normal Alb N N Glob N N PT N N
elevated bilirubin
History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin
Conjugated hyperbilirubinemia
DB > 50% of total bilirubin cant differentiate obstruction and parenchymal disease Delta fraction
CB tightly bound to albumin tendency of hyperbilirubinemia to resolve more slowly than other biochemical tests
Conjugated hyperbilirubinemia
Bile duct obstruction Hepatitis Cirrhosis Medications/Toxins Primary biliary cirrhosis Primary sclerosing cholangitis Sepsis Total parenteral nutrition Intrahepatic cholestasis of pregnancy Benign recurrent cholestasis Vanishing bile duct syndromes Dubin-Johnson syndrome Rotor syndrome
elevated bilirubin
History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin normal ALP, ALT, AST abnormal ALP, ALT, AST
Rotors syndrome Dubin-Johnson syndrome
elevated bilirubin
History and PE
conjugated bilirubin normal ALP, ALT, AST abnormal ALP, ALT, AST
AST, ALT ALP Dubin-Johnson syndrome predominate predominate / /
as elevated ALT evaluation U/S Rotors syndrome
present
absent
ERCP
Alkaline phosphatase
family of isoenzyme catalyze hydrolysis of No. of P esters at alkaline pH require Zn for activity present in nearly all tissues (liver, bone, intestinal, placenta, kidney) liver ALP
isoenzyme, 5-nucleotidase, GGT
Alkaline phosphatase
Physiologic >60 yr. child and adolescent pregnancy blood group O post meal (fatty meal) Pathologic intrahepatic extrahepatic
Alkaline phosphatase
Intrahepatic
viral alcohol drug pregnancy PBC PSC TPN sepsis vanishing bile duct syndrome benign recurrent cholestasis benign post-op. cholestasis paraneoplastic syndrome venoocclusive disease GVHD
Extrahepatic
intraluminal obstruction : gall stones, ascariasis, hemobilia disease of BD : PSC, choledochal cyst, cholangioCA, AIDS cholangiopathy external compression : LN, GB CA, Mirizzis syndrome, CA pancreas, ampullar adenoma
Alkaline phosphatase
in biliary obstruction
induction of ALP synthesis 2 to enhanced translation of mRNA ALP levels, may not rise until 1-2 days T1/2 1 wk, take several days for levels to normalise after resolution
in malignancy ..
no identifiable liver/bone involvement biochemical distinct from liver ALP associated variety of different CA ex lung CA
Alkaline phosphatase
initial evaluation : determine hepatic or nonhepatic origin, concomitant elevation of other serum LFT level not a reliable indicator of severity of underlying liver disease degree not help to distinguish intrahepatic and extrahepatic
Infiltrative diseases
modest (up to 3x) rise in aminotransferase, and up to 20x rise in ALP, bilirubin N-5x
TB Fungal infection HCC Lymphoma Metastatic malignancy Amyloidosis Sarcoidosis Other granulomatous diseases
Alkaline phosphatase
ALP > 1000 : malignant biliary obstruction, sepsis, AIDS with systemic infection decrease : hypothyroidism, pernicious anemia, Zn deficiency, congenital, Wilsons disease, severe hepatic insufficiency
Gold salts Imipramine Indinavir Iprindole Nevirapine Methytestosterone Methylenedioxymethamphetam ine Oxaprozin Pizotyline Quinidine Tolbutamide TPN Trimethoprimsulfamethoxazole
elevated ALP
History and PE normal bilirubin, ALT, AST abnormal liver chemistries
GGT or 5nucleotidase
negative positive
yes
U/S
no
not hepatobiliary
no duct dilatation
ERCP
AMA
negative
observation
> 6 months
-glutamyltransferase (GGT)
catalyzed transfer of -glutamyl groups of peptides to other amino acid abundant in liver, kidney, pancreas, intestine, and prostate, spleen, heart, brain but not in bone T1/2
7-10 days 28 days in alcohol-associated liver injury
-glutamyltransferase (GGT)
increase
alcohol drug anticonvulsant (CBZ, phenytoin, and barbiturate), warfarin, OC almost all type of liver diseases COPD, renal failure, DM, hyperthyroidism, RA, AMI, pancreatic disease
Summary
Hepatocellular necrosis toxin/ ischemia AST/ALT ALP Bilirubin PT albumin 50-100X 1-3X 1-5X viral 5-50X 1-3X 1-30X alcohol 2-5X 1-10X 1-30X Biliary obstruction complete 1-5X 2-20X 1-30X partial 1-5X 2-10X 1-5X 1-3X 1-20X 1-5X normal normal Infiltration
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