Clinical Chemistry: Measurement, Interference and Interpretation
Clinical Chemistry on the CSMLS exam tests whether you can take a number off an analyser and decide if it is real, artefactual, or critically abnormal. Questions cluster around measurement principles, electrolyte and acid-base arithmetic, organ-panel interpretation, and pre-analytical interference.
Measurement principles
- Most assays are photometric and follow Beer-Lambert: absorbance is proportional to concentration and path length. Bichromatic readings subtract a secondary wavelength to cancel cuvette and turbidity effects.
- Kinetic (rate) enzyme methods require a lag phase before the linear monitoring window; results above the linearity limit must be diluted and re-run, not extrapolated.
- Ion-selective electrodes: direct ISE measures undiluted sample and is unaffected by protein or lipid; indirect ISE dilutes first and therefore causes pseudohyponatremia when protein or lipid is very high.
- Creatinine by Jaffe reaction is fast but non-specific (glucose, uric acid, ketones, cephalosporins interfere); enzymatic methods are more specific.
Interpretation rules
- Anion gap = Na - (Cl + HCO3), reference roughly 8-12 mmol/L without potassium. Add 2.5 mmol/L to the gap for every 1 g/dL albumin below 4.0 g/dL to unmask a hidden high-gap acidosis.
- Osmolal gap = measured osmolality - (2Na + glucose + urea), normally under 10 mmol/kg; a raised gap suggests an unmeasured osmole such as methanol, ethylene glycol, mannitol or isopropanol.
- Corrected sodium in hyperglycaemia: add about 0.3 mmol/L per 1 mmol/L glucose above normal.
Worked example
Na 140, Cl 104, HCO3 24, albumin 20 g/L (2.0 g/dL). The uncorrected gap is 140 - 128 = 12 mmol/L, which looks normal. Correcting for albumin: 12 + 2.5 x (4.0 - 2.0) = 17 mmol/L, a clearly elevated gap. Reasoning: each gram of albumin contributes roughly 2.5 mmol/L of unmeasured anion, so low albumin masks a high-anion-gap acidosis. Reporting 12 without comment would falsely reassure the clinician.
Traps that cost marks
- EDTA carry-over from a lavender tube raises potassium and lowers calcium, magnesium and alkaline phosphatase; repeat from a heparin or serum tube.
- Haemolysis falsely raises potassium, LDH, AST and phosphate and interferes with bilirubin photometry; lipaemia and icterus are flagged by HIL indices.
- Glucose falls by roughly 5-7% per hour in an unpreserved tube because of glycolysis, so fluoride tubes are required for accurate glucose.
- A tourniquet left on for more than one minute concentrates protein, potassium and cells.
- Never report a critical value without documented read-back and notification.