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Organ Function Tests - Biochemistry
Source: Harper's Illustrated Biochemistry, 32nd Ed; Henry's Clinical Diagnosis and Management by Laboratory Methods
Organ function tests are groups of biochemical tests that together assess the functioning of a specific organ. The major panels include tests of kidney, liver, thyroid, adrenal function, and cardiovascular markers.
1. Tests of Kidney Function
A. Urinalysis (Complete)
| Parameter | Significance |
|---|
| Volume (24-hr) | Oliguria (<400 mL/day) in renal failure |
| Specific gravity | Reflects concentrating ability |
| pH | Acid-base status |
| Colour/Appearance | Turbidity suggests infection/cells |
| Protein (qualitative) | Normally absent by routine tests |
| Glucose | Renal glycosuria |
| Ketone bodies | DKA, starvation |
| Blood | Haematuria |
| Bile salts/pigments | Obstructive jaundice |
B. Protein Excretion
- Normal: <150 mg/day total protein; <30 mg/day albumin
- Proteinuria: >150 mg/day - sign of renal disease
- The most common cause is loss of glomerular basement membrane integrity (nephrotic syndrome, diabetic nephropathy) - mainly albumin is lost
- Microalbuminuria: 30-300 mg albumin in 24-hr urine - earliest marker of renal damage in diabetes mellitus
C. Blood Urea & Serum Creatinine
| Marker | Normal | Comments |
|---|
| Blood urea nitrogen (BUN) | 7-20 mg/dL | Affected by many non-renal factors (diet, catabolism) - less specific |
| Serum creatinine | ~0.6-1.2 mg/dL | More specific - not significantly altered by non-renal factors |
- Creatinine is preferred over urea as a marker of renal function
- Serum creatinine only rises significantly after ~50% decline in GFR - poor sensitivity for early disease
D. Creatinine Clearance & GFR
Formula:
Clearance (mL/min) = (U × V) / P
Where:
-
U = urine concentration of analyte (timed sample, usually 24 hr)
-
P = plasma concentration of analyte
-
V = urine volume per minute (total volume ÷ 1440)
-
Creatinine clearance estimates GFR - detects early renal failure
-
Creatinine overestimates GFR slightly (tubular secretion adds some)
-
Inulin clearance is the gold standard - freely filtered, not reabsorbed or secreted - but requires IV infusion
2. Liver Function Tests (LFTs)
LFTs assess diagnosis, prognosis, and monitoring of liver disease. Each test targets a specific aspect of hepatic function.
The Three Systems of the Liver
- Chemical metabolic system - tested by aminotransferases
- Reticuloendothelial (Kupffer cell) system - haemoglobin/bilirubin metabolism
- Biliary secretion system - bilirubin conjugation and excretion
A. Aminotransferases (Transaminases)
| Enzyme | Significance |
|---|
| ALT (Alanine Aminotransferase) | More specific for liver disease; NOT elevated in cardiac/skeletal muscle injury |
| AST (Aspartate Aminotransferase) | Elevated in liver AND cardiac/skeletal muscle injury |
| LDH (Lactate dehydrogenase) | Rises in hepatocyte injury and mass lesions |
- In acute viral hepatitis: ALT and AST rise several days BEFORE jaundice onset
- Hepatocyte injury/necrosis causes the greatest rises
B. Bilirubin
| Condition | Conjugated (Direct) | Unconjugated (Indirect) |
|---|
| Obstructive jaundice | Markedly elevated | Normal/slightly elevated |
| Hepatocellular disease | Both elevated | Both elevated |
| Pre-hepatic (haemolysis) | Normal | Elevated |
C. Proteins & Coagulation
- Total protein and albumin: Low in chronic liver disease (cirrhosis) - falls only when >80% liver tissue is destroyed
- Prothrombin time (PT): Prolonged in acute liver disorders due to impaired synthesis of coagulation factors
- Ammonia: Rises to toxic levels when >80% liver is destroyed (liver is the only organ that metabolises ammonia via the urea/Krebs-Henseleit cycle)
D. Enzymes of the Biliary (Canalicular) System
| Enzyme | Location | Significance |
|---|
| Alkaline Phosphatase (ALP) | Canalicular surface | Elevated in obstructive jaundice AND bone disease |
| GGT (gamma-Glutamyltransferase) | Hepatic surface of canaliculus | Rises in biliary obstruction; also elevated in alcohol use |
| 5'-Nucleotidase (5'-N) | Biliary system | Helps differentiate liver vs. bone origin of high ALP |
E. Six Patterns of LFTs in Liver Disease (Henry's)
| Pattern | AST/ALT | ALP/GGT | Bilirubin | Albumin/PT |
|---|
| Acute hepatitis | Markedly ↑ | Mildly ↑ | ↑ (direct) | Normal early |
| Obstructive jaundice | Mildly ↑ | Markedly ↑ | ↑ (mainly conjugated) | Normal |
| Cirrhosis | ↑ | ↑ | ↑ | ↓↓, PT prolonged |
| Fatty liver | Mildly ↑ | Mildly ↑ | Normal | Normal |
| Fulminant failure | Very high | Variable | Very high | Very low, PT very prolonged |
| Infiltrative disease | Normal/mild ↑ | ↑ | Mild ↑ | Normal |
3. Thyroid Function Tests
The thyroid secretes T4 (thyroxine/tetraiodothyronine) and T3 (triiodothyronine).
| Test | Interpretation |
|---|
| TSH (Thyroid-Stimulating Hormone) | Best first-line test; ↓ in hyperthyroidism, ↑ in hypothyroidism |
| Free T4 (FT4) | More reliable than total T4 |
| Free T3 (FT3) | Useful in T3-toxicosis |
| Total T4/T3 | Rarely measured now - affected by changes in thyroid-binding globulin (TBG) independent of thyroid disease |
- Hyperthyroidism: Low TSH, High FT4/FT3
- Hypothyroidism: High TSH, Low FT4/FT3
- Total thyroxine is seldom measured today because free thyroxine assays are readily available
4. Adrenal Function Tests
Tests confirm Cushing syndrome (hyperfunction) or Addison disease (hypofunction).
- Cortisol shows diurnal variation: Highest in early morning, lowest at midnight
- Loss of diurnal variation = earliest sign of adrenal hyperfunction
- Dexamethasone Suppression Test: 1 mg dexamethasone at midnight; normally suppresses 8 AM cortisol. Failure of suppression confirms Cushing syndrome
- Addison disease: Low cortisol, high ACTH; confirmed by ACTH stimulation test (Synacthen test)
5. Cardiovascular Risk Markers & Myocardial Infarction
| Marker | Purpose |
|---|
| Total plasma cholesterol | Cardiovascular risk screening |
| LDL : HDL cholesterol ratio | Index of atherosclerosis risk |
| Cardiac Troponin I/T | Preferred marker for myocardial infarction - highly specific and sensitive |
| Creatine Kinase-MB (CK-MB) | Confirms MI when ECG is non-diagnostic |
- When ECG does not show typical changes after MI, elevation in cardiac troponin or CK-MB confirms the infarction
- Plasma lipoproteins originally separated by centrifugation (density-based names); now measured by precipitating ApoB-containing lipoproteins to calculate HDL
Quick Reference Summary
| Organ | Key Markers |
|---|
| Kidney | Serum creatinine, creatinine clearance, urine protein, microalbuminuria |
| Liver | ALT, AST, ALP, GGT, bilirubin (total, direct, indirect), albumin, PT, ammonia |
| Thyroid | TSH, Free T4, Free T3 |
| Adrenal | Serum cortisol (diurnal), dexamethasone suppression test |
| Heart | Troponin I/T, CK-MB, LDL:HDL ratio |
- Harper's Illustrated Biochemistry, 32nd Ed, pp. 585-586
- Henry's Clinical Diagnosis and Management by Laboratory Methods