Chemical Pathology and Immunopathology/Serology
Interpret every result against a reference interval generated in a comparable population with the same method, and remember that preanalytical error, analytical interference (hemolysis, icterus, lipemia), and immunoassay artifacts explain more abnormal results than rare disease.
Core concepts: anion and osmolal gaps; the distinction between measured (freezing-point) and calculated osmolality; the albumin-corrected anion gap (add 2.5 mmol/L per 1 g/dL albumin below 4.0); eGFR with cystatin C confirmation when muscle mass is atypical; cardiac troponin kinetics and serial delta values; and HbA1c caveats (hemolysis, hemoglobin variants, iron deficiency, recent transfusion, renal failure). In immunopathology, know that ANA is a sensitive but poorly specific screen requiring confirmation with dsDNA or anti-Smith, that ANCA testing should be antigen-specific (PR3 versus MPO), and that HIV and syphilis algorithms are sequential rather than single-step.
Traps
- Pseudohyponatremia from indirect ion-selective electrode measurements in severe hyperlipidemia or hyperproteinemia.
- Pseudohyperkalemia from hemolysis, delayed processing, EDTA contamination, or marked thrombocytosis.
- Biotin interference: falsely low results in sandwich assays, falsely high in competitive assays; macro-TSH and heterophile antibodies cause spurious values.
- The hook effect at extreme antigen excess producing inappropriately low results.
Worked example. Sodium 128 mmol/L, glucose 90 mg/dL, BUN 14 mg/dL, measured osmolality 285 mOsm/kg. Calculated osmolality = 2(128) + 90/18 + 14/2.8 = 256 + 5 + 5 = 266 mOsm/kg; the osmolal gap is 19, above the ~10 threshold, prompting evaluation for an unmeasured osmole such as ethanol, methanol, or ethylene glycol. Note that ethanol itself raises measured osmolality.