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BI11.1-2 | Organ Function tests and Hormones — Part 1
CLINICAL SCENARIO
A 38-year-old man from a village near Puducherry arrives at the MGMCRI outpatient with yellowish discolouration of the eyes for 5 days, fatigue, and mild upper abdominal discomfort. His urine is dark. He has no history of alcohol use. The RMO orders a "Liver Profile." The results come back:
Total Bilirubin: 8.2 mg/dL (N: <1.2)
Direct Bilirubin: 6.1 mg/dL
ALT (SGPT): 820 U/L (N: 7–56)
AST (SGOT): 680 U/L (N: 10–40)
ALP: 190 U/L (N: 44–147)
Albumin: 3.6 g/dL (N: 3.5–5.0)
Total Protein: 6.8 g/dL
Prothrombin Time: 14.2 sec (N: 11–13.5)
What is happening in his liver — and can you explain each abnormal value biochemically?
WHY THIS MATTERS
Organ function tests are the most ordered biochemistry panels in any hospital — from PHC to tertiary care. As a first-year student, you will be expected to:
- Order the right panel for the right clinical question
- Understand why each test is included (not just the normal range)
- Distinguish between patterns of disease (hepatocellular vs cholestatic, pre-renal vs renal vs post-renal, primary vs secondary endocrine dysfunction)
These tests also underpin BI11 competencies, which assess your ability to correlate biochemistry with clinical medicine — a core CBME skill.
RECALL
Before proceeding, quickly recall:
- The basic structure of the liver lobule (from Anatomy) — hepatocytes, portal triad, central vein
- The role of the kidneys in filtration and reabsorption (from Physiology)
- The thyroid gland anatomy and the HPT axis overview (from Physiology)
- General enzyme kinetics: what does enzyme elevation in plasma tell you about cellular damage?
These foundations make this module much easier to understand.
Liver Function Tests — The Panel and Its Logic
LFT Panel Components — What Each Test Measures
| Component | What It Measures | Rises In | Clinical Significance |
|---|---|---|---|
| Total Bilirubin | Bilirubin load (conjugated + unconjugated) | All liver disease, haemolysis | Jaundice visible when >2-3 mg/dL |
| Direct (Conjugated) Bilirubin | Conjugated by hepatocytes, excreted in bile | Hepatocellular injury, cholestasis | Indicates hepatocyte or biliary pathology |
| ALT (SGPT) | Cytoplasmic enzyme — hepatocyte-specific | Hepatocellular necrosis | Most specific marker of liver cell injury |
| AST (SGOT) | Cytoplasmic + mitochondrial — liver, muscle, heart | Hepatocellular, MI, myopathy | AST:ALT >2:1 suggests alcoholic hepatitis |
| ALP | Bound to bile canalicular membrane | Cholestasis, bone disease | Markedly elevated in biliary obstruction |
| GGT | Canalicular enzyme, alcohol-sensitive | Cholestasis, alcohol use | Confirms hepatic origin of elevated ALP |
| Albumin | Synthesised by hepatocytes (synthetic function) | Falls in chronic liver disease | Half-life 21 days — chronic marker |
| PT/INR | Clotting factor synthesis (all except VIII) | Impaired hepatic synthesis | Early marker of acute liver failure |
Liver Function Tests (LFT) is a panel of biochemical markers that assess different aspects of hepatic function. No single test tells the whole story — interpretation requires looking at the pattern.
Figure: Liver Function Tests — The Panel and Its Logic
What the LFT panel measures:
| Component | What It Measures | Rises in |
|---|---|---|
| Total Bilirubin | Bilirubin load (conjugated + unconjugated) | All liver disease, haemolysis |
| Direct (Conjugated) Bilirubin | Conjugated by hepatocytes, excreted in bile | Hepatocellular injury, cholestasis |
| ALT (Alanine Aminotransferase) | Cytoplasmic enzyme — hepatocyte-specific | Hepatocellular necrosis |
| AST (Aspartate Aminotransferase) | Cytoplasmic + mitochondrial — liver + muscle + heart | Hepatocellular, MI, myopathy |
| ALP (Alkaline Phosphatase) | Bound to bile canalicular membrane | Cholestasis, bone disease |
| GGT (Gamma-GT) | Canalicular enzyme, alcohol-sensitive | Cholestasis, alcohol use |
| Albumin | Synthesised by hepatocytes (reflects synthetic function) | Falls in chronic liver disease |
| Total Protein | Albumin + globulins | Complex interpretation |
| PT/INR | Clotting factor synthesis (all factors except VIII) | Impaired hepatic synthesis |
Key concept — ALT vs AST: ALT is cytoplasmic only and almost entirely hepatocyte-specific. AST is in both cytoplasm and mitochondria, and is present in heart, skeletal muscle, and kidney too. ALT elevation is a more specific indicator of liver cell injury. The AST:ALT ratio >2:1 suggests alcoholic hepatitis (alcohol depletes pyridoxal phosphate, needed more by ALT than AST).
Figure: What the LFT panel measures:
LFT Patterns — Hepatocellular vs Cholestatic
Hepatocellular vs Cholestatic Liver Injury Patterns
| Feature | Hepatocellular Pattern | Cholestatic Pattern |
|---|---|---|
| Predominant enzyme rise | ALT and AST (10-100x normal) | ALP and GGT (3-10x normal) |
| ALP level | Mildly elevated | Markedly elevated |
| ALT/AST level | Markedly elevated | Mildly elevated |
| Bilirubin type | Mixed or conjugated | Conjugated (direct) |
| Common causes (India) | Viral hepatitis (A, B, E), drug injury | Gallstones, pancreatic carcinoma, PBC |
| AST:ALT ratio clue | <1 in viral; >2 in alcoholic | Not diagnostically useful |
| Albumin/PT | PT prolonged early; albumin drops in chronic | Usually preserved initially |
Hepatocellular pattern: Severe rise in ALT and AST (often 10–100× normal) with modest rise in ALP. Seen in viral hepatitis (hepatitis A, B, E — the latter very common in India during monsoon), drug-induced liver injury, and ischaemic hepatitis.
Figure: LFT Patterns — Hepatocellular vs Cholestatic
Cholestatic pattern: Marked rise in ALP and GGT with modest rise in aminotransferases. Seen in bile duct obstruction (stones, stricture, carcinoma of the head of pancreas), primary biliary cholangitis, or intrahepatic cholestasis of pregnancy.
Direct vs indirect bilirubin:
- Unconjugated (indirect) hyperbilirubinaemia = problem before hepatocytes: haemolysis (malaria — highly prevalent in India), Gilbert's syndrome, crigler-Najjar syndrome
- Conjugated (direct) hyperbilirubinaemia = problem at or after hepatocytes: liver cell damage, bile duct obstruction, Dubin-Johnson syndrome
Interpreting the clinical scenario: ALT 820 + AST 680 = severe hepatocellular injury. ALP only mildly elevated → not primary cholestasis. Direct bili > indirect → conjugated hyperbilirubinaemia (hepatocyte unable to excrete conjugated bilirubin). Albumin normal + PT mildly prolonged → acute injury, synthetic function partly preserved. Diagnosis: acute viral hepatitis (likely hepatitis E in rural Tamil Nadu/Puducherry context).
CLINICAL PEARL
Hepatitis E is the commonest cause of epidemic jaundice in India — especially in rural areas and pregnant women. It is spread by contaminated water (faeco-oral route), peaks during and after monsoon flooding, and is usually self-limiting. However, in pregnant women (especially third trimester), it can cause fulminant hepatic failure with mortality up to 20%. This is why hepatitis E serology (IgM anti-HEV) should always be included in workup of jaundice in rural India and in any pregnant patient with liver disease.
SELF-CHECK — : LFT Interpretation
A 52-year-old man has LFT: ALT 45 U/L (normal), AST 48 U/L (mildly elevated), ALP 420 U/L (markedly elevated), Total Bilirubin 3.2 mg/dL, Albumin 3.8 g/dL. Which pattern does this represent?
A. Hepatocellular pattern — severe viral hepatitis
B. Cholestatic pattern — likely bile duct obstruction
C. Gilbert's syndrome — unconjugated hyperbilirubinaemia
D. Alcoholic hepatitis — AST:ALT ratio >2
Reveal Answer
Answer: B. Cholestatic pattern — likely bile duct obstruction
Which LFT parameter best reflects the liver's synthetic function (i.e., how well hepatocytes are working metabolically)?
A. ALT
B. ALP
C. Serum albumin
D. Total bilirubin
Reveal Answer
Answer: C. Serum albumin
Renal Function Tests — Assessing the Kidney
Standard Renal Function Test Panel
| Test | Normal Range | Interpretation | Limitations |
|---|---|---|---|
| Serum Creatinine | 0.7-1.3 mg/dL (males), 0.6-1.1 (females) | Rises when GFR falls below 50% | Affected by muscle mass, age, diet |
| Blood Urea Nitrogen (BUN) | 7-20 mg/dL | Rises in renal failure, dehydration, high-protein diet | Non-specific — affected by diet, GI bleeding, steroids |
| eGFR (CKD-EPI) | >90 mL/min/1.73m² | Best overall estimate of kidney function | Less accurate at extremes of body size |
| Serum Electrolytes (Na, K) | Na: 135-145, K: 3.5-5.0 mmol/L | Hyperkalemia in renal failure | Haemolysed sample causes pseudohyperkalaemia |
| Urine Routine/Microscopy | No protein, no RBCs, no casts | Proteinuria = glomerular damage, RBC casts = GN | Dipstick misses microalbuminuria |
Renal Function Tests (RFT) assess glomerular filtration, tubular function, and electrolyte homeostasis.
Figure: Renal Function Tests — Assessing the Kidney
The standard RFT panel:
| Test | Normal Range | Interpretation |
|---|---|---|
| Serum Creatinine | 0.6–1.2 mg/dL (M); 0.5–1.0 (F) | GFR surrogate — rises when GFR falls >50% |
| Blood Urea Nitrogen (BUN) | 7–20 mg/dL | Rises in renal failure, high protein catabolism, GI bleed |
| BUN:Creatinine Ratio | 10–20:1 | >20 suggests pre-renal cause; <10 suggests renal/tubular |
| eGFR (CKD-EPI equation) | >60 mL/min/1.73m² | Calculated from creatinine, age, sex — stages CKD 1–5 |
| Uric Acid | 3.5–7.2 mg/dL | Rises in gout, CKD, tumour lysis |
| Electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻) | See normal ranges | Electrolyte and acid-base balance |
Creatinine as a GFR marker: Creatinine is the waste product of creatine phosphate breakdown in muscle. It is freely filtered at the glomerulus and minimally secreted by tubules. Unlike urea, it is not significantly reabsorbed — making it a better GFR surrogate. However, it is a late marker: creatinine rises noticeably only when GFR has fallen by ~50%. Cystatin C is a newer, more sensitive marker available in tertiary centres.
Figure: The standard RFT panel:
BUN:Creatinine ratio:
- Pre-renal (reduced blood flow — dehydration, heart failure, haemorrhage): both BUN and creatinine rise, but urea rises proportionally more → ratio >20:1
- Renal (intrinsic kidney disease — glomerulonephritis, ATN): both rise but ratio stays 10–20:1
- Post-renal (obstruction — BPH, stones, ureteric obstruction): ratio usually normal initially, then rises