Clinical Chemistry

Clinical Chemistry

Clinical chemistry is the branch of laboratory medicine concerned with analysis of body fluids (blood, urine, CSF) to provide diagnostic, monitoring, and prognostic information. It encompasses biochemical marker testing, quality control, and reference interval establishment.

Specimen Types & Handling

  • Whole Blood: Collected in EDTA (prevents clotting by chelating Ca²+) for hematology; Li-heparin for chemistry
  • Serum: Blood clotted → centrifuge → liquid part. No fibrinogen, no clotting factors. Used for most biochemistry tests.
  • Plasma: Blood with anticoagulant → centrifuge → liquid. Contains fibrinogen. For coagulation tests (PT, PTT).
  • Urine: Spot (random) or 24-hour collection. Creatinine clearance, protein quantification, hormones, toxicology.
  • CSF: Lumbar puncture; glucose, protein, cells, cultures, oligoclonal bands.
  • Hemolysis, Lipemia, Icterus (HLI): Major interferents in clinical chemistry measurements — must be recognized and managed.

Key Clinical Chemistry Tests

  • Blood Glucose: Fasting 70–100 mg/dL; Post-load <140 mg/dL. Glucose oxidase or hexokinase methods. HbA1c for monitoring.
  • Creatinine & BUN: Markers of kidney function. Creatinine generated from creatine phosphate at constant rate. BUN (Blood Urea Nitrogen) reflects urea. BUN:Cr ratio: >20:1 = pre-renal azotemia; <15:1 = intrinsic renal disease; post-renal variable. eGFR calculated from creatinine, age, sex (CKD-EPI or MDRD formula).
  • Electrolytes: Na+, K+, Cl⁻, HCO₃⁻ — measured by ion-selective electrodes (ISE)
  • Liver Function Tests: ALT (hepatocellular damage), AST (less specific), ALP (cholestasis/bone), GGT (sensitive alcohol marker), Total/Direct/Indirect Bilirubin (hyperbilirubinemia type), Albumin (synthetic function), PT (coagulation, also synthetic function)
  • Lipid Panel: Total Cholesterol, LDL, HDL, Triglycerides. Friedewald equation: LDL = TC − HDL − TG/5 (valid only if TG <400 mg/dL).
  • Thyroid Function: TSH (best screening test), Free T4, Free T3.
  • Cardiac Markers: Troponin I/T (MI — most sensitive/specific; rises within 3h, peaks 12–24h, normalizes 7–14 days), CK-MB (earlier marker), BNP/NT-proBNP (heart failure), Myoglobin (earliest but not specific)

Point-of-Care Testing (POCT)

Rapid tests performed at or near the patient. Examples: Glucose meters, urine dipstick, ABG, coagulometers, bedside troponin, pregnancy test (β-hCG), COVID antigen test. Advantages: Rapid results, ease of use. Disadvantages: Less precision, quality control challenges, higher per-test cost.

Quality Control (QC) in Clinical Labs

  • Accuracy: Closeness to true value (reduced by calibration with standards)
  • Precision: Reproducibility of results (reduced by within-run and between-run variability)
  • Levey-Jennings Chart: QC values plotted over time; Westgard rules identify systematic errors (shift, trend) and random errors
  • Reference Intervals: Values from 95% of healthy reference population (mean ±2 SD for normal distribution)
  • Critical Values (Panic Values): Life-threatening results requiring immediate clinician notification (e.g., K+ <2.5 or >6.5 mEq/L, glucose <40 or >500 mg/dL)

Urinalysis

Physical (color, clarity, SG, pH), Chemical (dipstick: glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase), Microscopic (RBCs, WBCs, casts, crystals). Proteinuria >150 mg/day = pathological. Microalbuminuria (30–300 mg/day) = early diabetic nephropathy marker.