Liver functions test simplify
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I now have excellent material. Here is a clear, simplified breakdown of Liver Function Tests (LFTs):
Liver Function Tests (LFTs) - Simplified
First, a quick note on the name: "Liver function tests" is actually a misnomer. Most of the tests measure liver cell damage, not true liver function. Only albumin and PT/INR truly measure what the liver does. - Schwartz's Principles of Surgery, p.1380
The Liver Has 3 Key Systems Being Tested
| System | What It Does | How We Test It |
|---|---|---|
| Hepatocyte (cell) system | Metabolism, protein synthesis | AST, ALT |
| Kupffer cell system | Breaks down old red blood cells / hemoglobin | Bilirubin (indirect) |
| Bile secretion system | Excretes bilirubin into bile ducts | ALP, GGT, Bilirubin (direct) |
The Individual Tests
1. AST & ALT (Transaminases) - "Cell Damage Markers"
- What they are: Enzymes that live inside liver cells
- Why they rise: When liver cells are damaged, they burst and release these enzymes into the blood
- ALT is more specific to the liver
- AST is found in liver, heart, muscle, kidney, brain - so less specific
Degree of elevation tells you a lot:
| Elevation Level | Likely Cause |
|---|---|
| Mild (1-3x) | Fatty liver (NAFLD), chronic viral hepatitis, medications |
| Moderate (3-10x) | Acute viral hepatitis |
| Massive (>1000 IU/L) | Ischemia, acetaminophen toxicity, fulminant hepatitis |
| AST:ALT ratio >2:1 | Alcoholic liver disease |
2. ALP (Alkaline Phosphatase) - "Bile Duct Marker"
- Made by: Bile duct epithelium (and also bone, placenta, intestine)
- Why it rises: Bile duct obstruction triggers increased synthesis and release
- Key point: ALP is NOT liver-specific - it also rises in bone disease, pregnancy, and normal childhood growth
- How to confirm liver origin: Check GGT - if GGT is also elevated, the ALP is hepatic; if GGT is normal, think bone
3. GGT (Gamma-Glutamyl Transferase) - "Bile Duct + Alcohol Marker"
- Made by: Biliary epithelium and hepatocytes
- Sensitive for: Any hepatobiliary injury, especially biliary tract
- Classic finding: Elevated in ~70% of chronic alcoholics
- Can be 2-3x upper limit of normal in heavy drinkers
- Levels correlate with alcohol consumption
- Used alongside ALP to confirm hepatic origin
4. Bilirubin - "Breakdown Product Marker"
- Where it comes from: Breakdown of hemoglobin in old red blood cells
- Two forms matter clinically:
| Type | Also Called | Meaning When Elevated |
|---|---|---|
| Unconjugated (Indirect) | Pre-hepatic | Hemolysis, Gilbert's syndrome, impaired uptake |
| Conjugated (Direct) | Post-hepatic | Bile duct obstruction, intrahepatic cholestasis |
- Normal: >90% of serum bilirubin is unconjugated
- Conjugated bilirubin is water-soluble, so it spills into urine → dark urine (bilirubinuria)
5. Albumin - "Synthetic Function Marker"
- Made only by the liver (~10g/day)
- Why it falls: When the liver is severely damaged (>80% destroyed), it can't make enough albumin
- Half-life is 15-20 days - so albumin is a chronic marker, not useful in acute injury
- Also falls in: malnutrition, nephrotic syndrome, protein-losing enteropathy
6. PT / INR - "Best Synthetic Function Test"
- The liver makes almost all clotting factors (except Factor VIII)
- PT/INR measures how quickly blood clots (using factors II, VII, IX, X)
- INR is the gold standard for assessing acute hepatic synthetic function
- Also prolonged in: Vitamin K deficiency, warfarin therapy
Pattern Recognition - What Pattern Points to What?
| Pattern | AST/ALT | ALP/GGT | Bilirubin | Albumin/PT | Likely Diagnosis |
|---|---|---|---|---|---|
| Hepatocellular | ↑↑↑ | Normal or mild ↑ | ↑ (mixed) | Normal (acute) / ↓ (chronic) | Hepatitis, toxins, ischemia |
| Cholestatic | Normal or mild ↑ | ↑↑↑ | ↑ (direct) | Normal | Biliary obstruction, PSC, PBC |
| Cirrhosis | Normal or mild ↑ | Mild ↑ | ↑ | ↓↓ | Chronic liver disease |
| Fulminant failure | ↑↑↑↑ (>10,000) | ↑ | ↑↑ | ↓↓ | Medical emergency - needs transplant |
| Alcoholic hepatitis | ↑ (AST:ALT >2:1) | GGT ↑↑ | ↑ | ↓ | Alcohol-related liver disease |
Quick Memory Framework
LFTs = 3 categories:
1. DAMAGE markers → AST, ALT (liver cells leaking)
2. CHOLESTASIS markers → ALP, GGT, Direct bilirubin (bile duct blocked)
3. FUNCTION markers → Albumin, PT/INR (liver failing to make things)
The higher the AST/ALT, the more acute and severe the cell injury.
The lower the albumin and higher the INR, the more the liver has lost its ability to work.
Sources: Henry's Clinical Diagnosis and Management by Laboratory Methods | Schwartz's Principles of Surgery, 11th Ed. | Quick Compendium of Clinical Pathology, 5th Ed.
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