Q1 LONG ANSWER 10M ★ High-yield

Classify the liver function tests. Describe the biochemical findings in the three types of jaundice.

Biochemistry · 1st Professional — Pre-Clinical

Functions of the Liver

Metabolic — the hub of carbohydrate, lipid and protein metabolism; glycogen storage, gluconeogenesis, ketogenesis, lipogenesis
Synthetic — albumin, clotting factors, most plasma proteins, urea, cholesterol, bile acids
Excretory — bilirubin, bile salts, cholesterol, drugs
Detoxification — ammonia to urea; cytochrome P450 biotransformation
Storage — glycogen, vitamins A, D, B12, iron, copper
Immunological — Kupffer cells

Classification of Liver Function Tests

Group	Tests	What they reflect
Excretory	Serum bilirubin (total, direct, indirect); urine bile pigments	Uptake, conjugation and excretion
Hepatocellular damage	ALT (SGPT), ast (SGOT)	Leakage from damaged hepatocytes
Cholestasis	Alkaline phosphatase, GGT, 5′-nucleotidase	Obstruction to bile flow
Synthetic function	Serum albumin, prothrombin time / INR	The true measure of liver function
Detoxification	Blood ammonia, blood urea	Urea cycle capacity

CLINICAL PEARL

The transaminases measure damage, not function. A patient with end-stage cirrhosis may have near-normal ALT because little viable liver remains. Albumin and prothrombin time are the tests that measure what the liver can still do, and prothrombin time is the more sensitive, since clotting factors have a half-life of hours against albumin's 20 days.

Individual Tests

Test	Normal	Interpretation
Total bilirubin	0.2–1.0 mg/dL	Jaundice becomes visible above 2–2.5 mg/dL
Direct (conjugated)	< 0.3 mg/dL	Raised in hepatocellular and obstructive jaundice
ALT	7–40 U/L	More liver-specific; > 10× suggests viral hepatitis
Ast	10–40 U/L	Also from heart and muscle; ast:ALT > 2 suggests alcohol
Alkaline phosphatase	40–130 U/L	> 3× suggests obstruction; also bone origin
GGT	10–50 U/L	Most sensitive marker of alcohol intake; confirms a raised ALP is hepatic
Albumin	3.5–5.0 g/dL	Falls in chronic disease; half-life 20 days
Prothrombin time / INR	11–14 s / 0.9–1.2	The most sensitive index of acute synthetic failure

Patterns in the Three Types of Jaundice

Feature	Pre-hepatic (haemolytic)	Hepatic	Post-hepatic (obstructive)
Total bilirubin	↑	↑↑	↑↑↑
Type predominating	Unconjugated	Both	Conjugated
Urine bilirubin	Absent (unconjugated is protein-bound, not filtered)	Present	Present (dark urine)
Urine urobilinogen	Increased	Variable	Absent
Stool	Dark	Normal or pale	Clay-coloured
ALT / ast	Normal	↑↑↑	Mildly ↑
Alkaline phosphatase	Normal	↑	↑↑↑
Prothrombin time	Normal	Prolonged, not corrected by vitamin K	Prolonged, corrected by vitamin K

The vitamin K response distinguishes hepatocellular from obstructive jaundice — in obstruction the liver is capable but the vitamin is not absorbed; in hepatocellular disease the liver cannot use it
Absent urine urobilinogen with dark urine is characteristic of complete biliary obstruction

Specific Patterns

Condition	Characteristic finding
Acute viral hepatitis	ALT and ast > 10×, ALT > ast
Alcoholic hepatitis	Ast : ALT > 2, both usually < 300; GGT high
Obstructive jaundice	ALP > 3× with GGT raised; modest transaminase rise
Cirrhosis	Low albumin, prolonged INR, reversed A:G ratio; transaminases may be normal
Paracetamol overdose	Very high transaminases with rapidly rising INR
Gilbert syndrome	Isolated unconjugated hyperbilirubinaemia with all else normal, worse on fasting

Other Tests

Serum protein electrophoresis — cirrhosis shows low albumin with a diffuse rise in γ and β–γ bridging
Blood ammonia — raised in hepatic encephalopathy; must be sent on ice
α-Fetoprotein — screening for hepatocellular carcinoma
Autoantibodies, viral serology, caeruloplasmin, ferritin, α1-antitrypsin to establish the cause

Applied Aspects

A "liver function test" panel mostly measures damage; the term is a misnomer that misleads students and clinicians alike
Blood urea is low in liver failure, not high — the urea cycle has failed. This surprises most students
Isolated raised ALP — check GGT: if normal, the source is bone, placenta or intestine, not liver
Prothrombin time is the single best prognostic marker in acute liver failure and forms part of the King's College transplant criteria
Normal liver tests do not exclude significant liver disease — up to a third of patients with cirrhosis have normal transaminases

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