Organ Function Tests
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Organ Function Tests
A battery of organ-specific laboratory tests is used to assess the functional integrity of major organs. Below is a systematic overview covering the liver, kidneys, heart, lungs, thyroid, and adrenal glands.
1. Liver Function Tests (LFTs)
The liver performs three broad functional roles, each tested differently.
A. Hepatocyte Integrity (Chemical-Metabolic System)
| Test | Normal Range | Significance |
|---|---|---|
| ALT (alanine aminotransferase / SGPT) | 10-40 IU/L | Most specific for hepatocellular damage; very high in viral hepatitis & hepatocellular necrosis |
| AST (aspartate aminotransferase / SGOT) | 10-40 IU/L | Elevated in hepatocellular injury; also rises in cardiac/skeletal muscle damage |
| LDH (lactate dehydrogenase) | Varies | Elevated in hepatitis, mass lesions, infarction |
- AST:ALT disproportionately high (>10,000 IU/L) in acute fulminant hepatic failure - this is a medical emergency requiring liver transplantation.
- In viral hepatitis, ALT is typically higher than AST; an AST:ALT ratio >2 suggests alcoholic liver disease.
B. Synthetic Function
| Test | Significance |
|---|---|
| Serum albumin | Low in cirrhosis/fulminant failure (>80% liver destroyed); reflects long-term synthetic function |
| Total protein | Decreases only when >80% of liver tissue is destroyed |
| Serum ammonia | Elevated in severe hepatic failure (liver is the only organ that detoxifies ammonia via the urea cycle); causes hepatic encephalopathy |
| Prothrombin time (PT) | Prolonged because the liver synthesizes coagulation factors; sensitive marker of acute liver failure |
C. Biliary/Canalicular System
| Test | Significance |
|---|---|
| Serum bilirubin (total, direct/conjugated, indirect/unconjugated) | Normal mean ~6 mmol/L, upper limit ~20 mmol/L. Indirect (unconjugated) fraction predominates in prehepatic jaundice; conjugated bilirubin rises in hepatic and posthepatic obstruction |
| Alkaline phosphatase (ALP) | Rises in biliary obstruction, bone disease, pregnancy, Paget's disease |
| Gamma-glutamyl transferase (GGT) | Elevated in obstructive jaundice and liver disease; sensitive marker of alcohol use |
| 5'-Nucleotidase | Specific hepatic marker for obstruction (helps confirm ALP is of hepatic, not bony, origin) |
Patterns of LFTs in Disease
| Condition | AST/ALT | ALP/GGT | Bilirubin | Albumin | Ammonia |
|---|---|---|---|---|---|
| Acute hepatitis | ↑↑↑ | Mildly ↑ | Direct ↑ | Normal | Normal |
| Cirrhosis | Normal/↓ | Normal | ↑ (both) | ↓ | ↑ |
| Biliary obstruction | Normal | ↑↑ | Direct ↑↑ | Normal | Normal |
| Space-occupying lesion | Normal | ↑ (ALP+LDH isolated) | Normal | Normal | Normal |
| Fulminant hepatic failure | ↑↑↑↑ | ↑ | ↑ | ↓↓ | ↑↑ |
Note: The liver has a high functional reserve - patchy lesions may show no abnormality until 80% of the liver is destroyed. (Pye's Surgical Handicraft, 22nd Ed.)
2. Renal Function Tests
A. Serum Creatinine
- A waste product of muscle metabolism; filtered freely by the glomerulus.
- Rises inversely with GFR. However, a "normal" serum creatinine can mask significant renal impairment in elderly, frail, or low-muscle-mass patients.
B. Creatinine Clearance (CrCl) / GFR
The Cockcroft-Gault formula estimates CrCl from serum creatinine:
Men:
CrCl = [(140 - Age) × Lean Body Weight] ÷ [72 × Serum Creatinine (mg/dL)]
Women: Multiply male value by 0.85
| CrCl (mL/min) | Interpretation |
|---|---|
| 74-160 | Normal |
| 40-60 | Mild renal impairment |
| 15-40 | Moderate renal impairment |
| <15 | Severe impairment (dialysis indicated) |
Important clinical point: Two patients with an identical serum creatinine of 1.4 mg/dL - a 71-year-old woman (CrCl ~32 mL/min, moderate impairment) vs a 21-year-old man (CrCl ~118 mL/min, normal) - have vastly different actual renal function. (Roberts and Hedges' Clinical Procedures in Emergency Medicine)
C. Blood Urea Nitrogen (BUN)
- Urea is the end-product of protein catabolism; synthesized in the liver, excreted by kidneys.
- BUN:Creatinine ratio >20:1 suggests prerenal azotemia.
D. Fractional Excretion of Sodium (FENa)
Used to differentiate causes of acute kidney injury (AKI):
FENa (%) = (SCr × UNa) ÷ (SNa × UCr) × 100
| FENa | Interpretation |
|---|---|
| <1% | Prerenal AKI (kidneys retaining Na due to poor perfusion) |
| 1-2% | Indeterminate |
| >2% | Intrinsic renal disease (e.g., ATN) |
| >4% | Postrenal (obstructive) cause |
E. Urinalysis
- Proteinuria: marker of glomerular disease
- Casts: red cell casts suggest glomerulonephritis; granular casts suggest ATN
- Urine osmolality: concentrated urine (>500 mOsm/kg) in prerenal; isosthenuria (~300 mOsm/kg) in ATN
3. Cardiac Function Tests
A. Cardiac Biomarkers for Myocardial Infarction
| Marker | Rise | Peak | Duration | Notes |
|---|---|---|---|---|
| Cardiac Troponin I (cTnI) | 4-8 hrs | 12-16 hrs | 5-9 days | Most specific for cardiac muscle; values ≥1.5 ng/mL suggest AMI |
| Troponin T (cTnT) | 4-8 hrs | 12-16 hrs | 5-14 days | May be elevated in renal failure without MI |
| CK-MB | 3-6 hrs | 12-24 hrs | 24-48 hrs | Historically used; now secondary to troponins |
| Myoglobin | 1-3 hrs | 6-9 hrs | 12-24 hrs | Earliest marker; not cardiac-specific; high negative predictive value |
| AST | 8-12 hrs | 18-36 hrs | 3-4 days | Historical; non-specific |
| LDH (LD1:LD2 "flipped ratio") | 24-48 hrs | 48-72 hrs | 7-10 days | Now largely replaced by troponins |
The "flipped ratio" of LDH isoenzymes (LD1:LD2 >0.75) occurs 36-48 hours post-MI. Troponin assays have now largely replaced this. (Henry's Clinical Diagnosis and Management by Laboratory Methods)
B. Cardiac Risk Assessment
- Total cholesterol, LDL, HDL: The LDL:HDL ratio predicts atherosclerosis risk.
- BNP / NT-proBNP: Elevated in heart failure due to ventricular wall stress; used for diagnosis and monitoring.
- Homocysteine, hsCRP, Lp(a): Emerging cardiovascular risk markers.
4. Pulmonary Function Tests (PFTs)
PFTs do not diagnose specific diseases directly - they detect patterns of dysfunction that, combined with clinical context, characterize disease type and severity. (Murray & Nadel's Textbook of Respiratory Medicine)
A. Spirometry
| Parameter | Description | Significance |
|---|---|---|
| FEV1 (Forced Expiratory Volume in 1 sec) | Volume exhaled in the first second | Reduced in obstructive disease |
| FVC (Forced Vital Capacity) | Total volume forcibly exhaled | Reduced in restrictive disease |
| FEV1/FVC ratio | Key diagnostic ratio | <0.70 = obstructive pattern (COPD, asthma); normal or elevated in restrictive pattern |
| PEFR (Peak Expiratory Flow Rate) | Maximum flow rate | Used to monitor asthma |
B. Lung Volumes (Body Plethysmography / Helium Dilution)
| Volume | Description |
|---|---|
| TLC (Total Lung Capacity) | All lung volume; reduced in restrictive disease |
| RV (Residual Volume) | Volume after maximal expiration; increased in air-trapping (emphysema) |
| FRC (Functional Residual Capacity) | Volume after normal expiration |
| RV/TLC ratio | Elevated in hyperinflation |
C. Diffusing Capacity (DLCO)
- Measures carbon monoxide transfer across alveolar-capillary membrane.
- Reduced in: emphysema, interstitial lung disease, pulmonary vascular disease, anemia.
- Elevated in: pulmonary hemorrhage, polycythemia.
D. Pattern Recognition
| Pattern | FEV1 | FVC | FEV1/FVC | TLC | Example Diseases |
|---|---|---|---|---|---|
| Obstructive | ↓ | Normal/↓ | ↓ (<0.70) | Normal/↑ | COPD, asthma |
| Restrictive | ↓ | ↓ | Normal/↑ | ↓ | IPF, sarcoidosis, obesity |
| Mixed | ↓ | ↓ | ↓ | ↓ | Advanced COPD + fibrosis |
5. Thyroid Function Tests
| Test | Purpose |
|---|---|
| TSH (Thyroid-Stimulating Hormone) | Best screening test; raised in hypothyroidism, suppressed in hyperthyroidism |
| Free T4 (free thyroxine) | Confirms hypo/hyperthyroidism; preferred over total T4 (unaffected by TBG changes) |
| Free T3 (triiodothyronine) | Useful in T3 toxicosis; elevated when FT4 is normal but symptoms of hyperthyroidism persist |
| TRH stimulation test | Historically used to confirm subclinical thyrotoxicosis; largely replaced by sensitive TSH assays |
| Thyroid antibodies | Anti-TPO and anti-thyroglobulin antibodies confirm Hashimoto's thyroiditis; TSH receptor antibodies (TRAb) confirm Graves' disease |
| Thyroid scan (99mTc or 131I) | Measures uptake and distribution; "cold nodules" (minimal uptake) may be cysts, carcinoma (up to 10% of cold nodules), or thyroiditis |
Total T4 is seldom measured today because free T4 assays are widely available and unaffected by changes in thyroid-binding globulin concentration. (Harper's Illustrated Biochemistry, 32nd Ed.)
6. Adrenal Function Tests
| Test | Condition Detected | Details |
|---|---|---|
| Serum cortisol (AM/PM) | Cushing syndrome | Loss of diurnal variation (normally highest at 8 AM, lowest at midnight) is an early sign of hypercorticism |
| Dexamethasone suppression test (DST) | Cushing syndrome | 1 mg dexamethasone at midnight; failure of 8 AM cortisol suppression confirms adrenal hyperfunction |
| 24-hour urine free cortisol | Cushing syndrome | Elevated in hypercorticism |
| ACTH stimulation test (Synacthen test) | Addison's disease | Failure of cortisol to rise adequately after synthetic ACTH confirms adrenal insufficiency |
| Serum ACTH level | Differentiates adrenal causes | High ACTH = primary adrenal failure (Addison's); low ACTH = secondary (pituitary) |
| Serum aldosterone + renin | Conn's syndrome | High aldosterone with low renin = primary hyperaldosteronism |
Summary Table
| Organ | Key Tests | Primary Markers |
|---|---|---|
| Liver | LFTs | ALT, AST, ALP, GGT, bilirubin, albumin, PT, ammonia |
| Kidney | Renal panel | Creatinine, BUN, CrCl/GFR, FENa, urinalysis |
| Heart | Cardiac panel | Troponin I/T, CK-MB, BNP, lipid profile |
| Lungs | PFTs | FEV1, FVC, FEV1/FVC, TLC, DLCO |
| Thyroid | TFTs | TSH, Free T4, Free T3, thyroid antibodies |
| Adrenal | Adrenal panel | Cortisol (AM/PM), DST, ACTH, aldosterone/renin |
Sources:
- Henry's Clinical Diagnosis and Management by Laboratory Methods - Liver, Cardiac Function Test patterns
- Pye's Surgical Handicraft, 22nd Ed. - Liver and Thyroid function tests
- Roberts and Hedges' Clinical Procedures in Emergency Medicine - Renal function (CrCl, FENa)
- Murray & Nadel's Textbook of Respiratory Medicine - Pulmonary function tests
- Harper's Illustrated Biochemistry, 32nd Ed. - Thyroid and Adrenal function tests
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