Clinical Chemistry
The clinical chemistry domain tests your command of analytical principles (spectrophotometry, ion-selective electrodes, enzymatic reactions), the interpretation of abnormal results across organ systems, and the interferences that distort them.
Measurement principles
Beer-Lambert law: A = εbc, so absorbance is proportional to concentration only within the linear range. Above that range, stray light and detector saturation flatten the curve - dilute and re-run. Endpoint assays measure the total absorbance change after the reaction completes; kinetic assays measure rate over a fixed interval and are less vulnerable to blank absorbance. Ion-selective electrodes measure activity, not concentration. Indirect ISE dilutes the sample and assumes normal protein and lipid, producing pseudohyponatremia in severe hyperproteinemia or hyperlipidemia; direct ISE on a blood gas analyzer avoids this.
Methods to recognize
Glucose: hexokinase (reference) or glucose oxidase. BUN: urease coupled to glutamate dehydrogenase. Creatinine: alkaline picrate Jaffe (nonspecific, affected by ketones and protein - use a compensated or enzymatic method). Uric acid: uricase. ALT and AST: IFCC coupled enzyme reactions. Bilirubin: diazo; direct (conjugated) measured and indirect calculated. Calcium: arsenazo or o-cresolphthalein complexone. HbA1c: HPLC, immunoassay, or enzymatic, reported NGSP/DCCT-aligned.
Interference
Hemolysis releases potassium, LDH, and AST and interferes with bilirubin and some immunoassays. Lipemia scatters light and dilutes aqueous phase, distorting indirect ISE results. Icterus interferes at short wavelengths. Serum indices (H, I, L) flag these automatically.
Worked example
Sodium 138 mmol/L, glucose 90 mg/dL, BUN 14 mg/dL, measured osmolality 302 mOsm/kg. Calculated osmolality = 2(138) + 90/18 + 14/2.8 = 276 + 5 + 5 = 286. The osmolal gap of 16 suggests an unmeasured osmole such as ethanol, methanol, or ethylene glycol. Then check the anion gap: Na minus (Cl + HCO3).
Traps that cost marks
- Reporting a potassium from a hemolyzed specimen.
- Using the Friedewald calculation when triglycerides exceed 400 mg/dL (4.5 mmol/L); use direct LDL.
- Delayed separation allowing cellular glucose consumption even in a fluoride tube after several hours.
- Ignoring that bicarbonate decreases with delayed separation as cells metabolize.
- Failing to call a critical value promptly and document the read-back.