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Total testing process: pre-analytical (test request, patient preparation, sample collection, labelling, transport and storage), analytical (measurement with quality control) and post-analytical (validation, reporting, interpretation). Pre-analytical errors (haemolysis, wrong tube, contamination, delays, incorrect identification) are the commonest source of error. Biological variation depends on time of day, fasting, posture, exercise and medication.

Reference interval: usually the central 95 percent of values in a healthy reference population, so 5 percent of healthy people fall outside it. Results are also compared with previous results in the same person (delta check) and clinical decision limits. Diagnostic accuracy: sensitivity (proportion of diseased people with a positive result), specificity (proportion of healthy people with a negative result), positive and negative predictive values (which depend on prevalence). A highly sensitive test is good for ruling out disease (SnNout), a highly specific test for ruling in (SpPin). Precision (repeatability) and accuracy (closeness to the true value) describe analytical performance.

1. Which phase of the testing process causes most errors? 2. What proportion of healthy people fall outside a 95 percent reference interval? 3. Which test property is most useful to rule out a disease? 4. Distinguish accuracy and precision.

1. The pre-analytical phase. 2. About 5 percent. 3. High sensitivity. 4. Accuracy is closeness to the true value; precision is reproducibility of repeated measurements.

Cardiac troponin T and I are structural proteins released into blood when cardiomyocytes are damaged. High-sensitivity assays detect small rises, rising 3-4 hours after injury, peaking at about 24 hours and staying raised for 7-14 days. Diagnosis of myocardial infarction requires a rise and/or fall of troponin with at least one value above the 99th percentile plus evidence of ischaemia; serial measurements (0 and 1-3 hours) are used. Troponin can also be raised in myocarditis, pulmonary embolism, sepsis, renal failure and heart failure. BNP and NT-proBNP are released by ventricular wall stretch. High values support the diagnosis of heart failure and predict prognosis; a low value makes heart failure unlikely. They are affected by age, renal function, obesity and atrial fibrillation.

Normal arterial values: pH 7.35-7.45, PaCO2 35-45 mmHg, HCO3- 22-26 mmol/L. Approach: (1) acidaemia or alkalaemia from the pH; (2) whether the primary change is respiratory (PaCO2) or metabolic (HCO3-); (3) whether compensation is appropriate; (4) the anion gap Na minus (Cl + HCO3), normal 8-12. - Metabolic acidosis: high anion gap (lactate, ketones, uraemia, toxins) or normal anion gap (diarrhoea, renal tubular acidosis). - Metabolic alkalosis: vomiting, diuretics. - Respiratory acidosis: hypoventilation. - Respiratory alkalosis: hyperventilation.

1. What are the kinetics of cardiac troponin after infarction? 2. Name two causes of raised troponin without infarction. 3. Calculate the anion gap for Na 140, Cl 100, HCO3 15. 4. What acid-base disorder is caused by vomiting?

1. It rises after 3-4 hours, peaks at about 24 hours and remains raised for 7-14 days. 2. Pulmonary embolism, myocarditis, sepsis, renal failure. 3. 140 minus 115 = 25 (raised: high anion gap acidosis). 4. Metabolic alkalosis.

Parameters: haemoglobin, haematocrit, red cell count, MCV (size), MCH and MCHC (haemoglobin content), RDW (variation in size), reticulocytes (bone marrow response). Anaemia work-up: microcytic (iron deficiency, thalassaemia, chronic disease), normocytic (chronic disease, haemorrhage, haemolysis, renal disease), macrocytic (B12 or folate deficiency, alcohol, myelodysplasia). Iron studies: low ferritin is diagnostic of iron deficiency; ferritin is an acute-phase reactant and may be high in inflammation; transferrin saturation low. Haemolysis: high reticulocytes, LDH and indirect bilirubin, low haptoglobin.

Normal white cells 4-11 x 10^9/L. Neutrophilia: bacterial infection, inflammation, steroids, stress. Neutropenia (below 1.5 x 10^9/L): drugs, viral infection, marrow failure; severe neutropenia carries a high risk of infection. Lymphocytosis: viral infection, chronic lymphocytic leukaemia. Eosinophilia: allergy, parasites, drugs. Monocytosis: chronic infection. Blasts in the film suggest acute leukaemia.

- Prothrombin time (PT) and INR: extrinsic and common pathways; used to monitor warfarin and assess liver synthetic function. - Activated partial thromboplastin time (aPTT): intrinsic and common pathways; used to monitor unfractionated heparin; prolonged in haemophilia A and B. - Platelet count, fibrinogen, D-dimer (fibrin degradation; high negative predictive value for thrombosis, raised in DIC, infection and surgery), bleeding time. Interpretation: prolonged PT alone suggests factor VII deficiency, vitamin K deficiency or warfarin; prolonged aPTT alone suggests haemophilia or heparin; both prolonged suggests common pathway deficiency, liver disease or DIC.

Fractions: albumin (largest), alpha-1, alpha-2, beta and gamma globulins. Patterns: acute inflammation (raised alpha-1 and alpha-2, low albumin); nephrotic syndrome (low albumin, raised alpha-2); cirrhosis (low albumin, polyclonal gamma rise with beta-gamma bridging); monoclonal gammopathy such as multiple myeloma (a narrow M-spike in the gamma or beta region, confirmed by immunofixation); hypogammaglobulinaemia (low gamma).

1. How do you interpret a low MCV with low ferritin? 2. Which test monitors warfarin and which monitors unfractionated heparin? 3. What does an isolated prolonged aPTT suggest? 4. What electrophoresis finding suggests myeloma?

1. Iron deficiency anaemia. 2. INR (PT) for warfarin; aPTT for unfractionated heparin. 3. Haemophilia (factor VIII, IX or XI deficiency) or heparin effect. 4. A monoclonal M-spike, confirmed by immunofixation.