For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
🧪 Clinical biochemistry - interpreting laboratory tests. About 70% of clinical decisions involve a laboratory result. Interpreting them well means knowing what each test measures, what changes it physiologically and artefactually, and which patterns point to which diagnoses. This chapter covers sample handling and pre-analytical error, renal and liver function, bone profile, lipids, endocrine tests, tumour markers, cardiac markers and therapeutic drug monitoring - the core of data interpretation stations and MRCP questions. Your four questions for any result: Is the sample valid (haemolysis, delay, wrong tube, drip arm)? Is the result outside the reference range, and by how much? What pattern do the results make together? Has it changed from previous results (trend and reference change value)?
Pre-analytical Errors and Sample Handling
Most laboratory errors are pre-analytical (before the sample reaches the analyser).
Haemolysis (difficult draw, small needle, shaking, delayed separation) → falsely high K⁺, phosphate, LDH, AST, magnesium.
Delayed separation or refrigerated samples - potassium leaks out of cells (high K⁺); glucose falls (glycolysis) unless a fluoride oxalate tube is used.
Drip arm contamination - glucose or saline infusion → bizarre results (high glucose, low other analytes, high Na⁺/Cl⁻).
EDTA contamination (wrong order of draw - purple-top EDTA before serum tubes) → very high K⁺ and very low calcium (EDTA is potassium salt and chelates calcium).
Pseudohyperkalaemia - also in very high platelet or white cell counts (e.g. CLL) - check a lithium heparin sample transported quickly.
Pseudohyponatraemia - extreme hyperlipidaemia or hyperproteinaemia (myeloma) with indirect ion-selective electrode methods - measured osmolality is normal.
Order of draw (UK): blood cultures → citrate (coagulation) → serum (with/without gel) → heparin → EDTA → fluoride oxalate.
Timing: lithium 12 hours post-dose; digoxin ≥6 hours post-dose; gentamicin per regimen; cortisol at 9 am; testosterone in the morning; day 21 progesterone (7 days before the next period).
Reference change value - the change between two results needed to be significant given analytical and biological variation (e.g. a creatinine rise of about 15–20% is meaningful).
Assay interference:biotin supplements (falsely abnormal thyroid tests and troponin in streptavidin-based assays), heterophile antibodies, macroprolactin and macro-CK/amylase (large complexes - spuriously high), hook effect (very high prolactin or hCG falsely low).
Units: check SI units (e.g. glucose mmol/L, HbA1c mmol/mol, creatinine µmol/L).
Renal Function - Creatinine, eGFR, Urea and Urine Tests
Creatinine - from muscle creatine; depends on muscle mass (low in older, frail, amputee or cachectic patients; high in muscular people and after cooked meat); about 50% of nephron function can be lost before creatinine rises above the reference range.
eGFR (CKD-EPI) - estimates GFR from creatinine, age and sex (UK laboratories now use CKD-EPI without an ethnicity coefficient). Not valid in AKI (non-steady state), extremes of muscle mass, pregnancy, or children. Cystatin C is less affected by muscle mass.
Creatinine clearance (Cockcroft–Gault) - used for dosing some drugs (DOACs, some antibiotics, chemotherapy).
Drugs raising creatinine without reducing GFR - trimethoprim, cimetidine (block tubular secretion); fenofibrate.
AKI (KDIGO): creatinine rise ≥26.5 µmol/L in 48 hours, or ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/h for 6 hours. Stages 1–3 by severity.
Urine tests:
Albumin:creatinine ratio (ACR) - CKD and diabetes screening (≥3 mg/mmol abnormal).
Protein:creatinine ratio (PCR) - quantifies non-albumin proteinuria (e.g. myeloma, tubular disease); PCR >30 mg/mmol significant in pregnancy.
Urine sodium - <20 mmol/L suggests pre-renal sodium avidity (unreliable on diuretics); fractional excretion of sodium <1% pre-renal.
"LFTs" are mostly markers of liver injury (ALT, AST, ALP, GGT), not function. True synthetic function tests: albumin, prothrombin time (INR), bilirubin, and glucose.
Liver screen for persistently abnormal LFTs (BSG): hepatitis B and C serology, autoantibodies (anti-smooth muscle, anti-mitochondrial, ANA), immunoglobulins, ferritin and transferrin saturation, caeliac serology, ceruloplasmin (under 40), α-1 antitrypsin, ultrasound; assess fibrosis in NAFLD with FIB-4 then ELF test or transient elastography.
Calcium (adjusted), phosphate, ALP, albumin ± PTH, vitamin D and magnesium. See the Physiology chapter for the patterns of hyperparathyroidism, malignancy, vitamin D deficiency and CKD.
Paget's disease - very high ALP, normal calcium and phosphate.
Osteoporosis - normal bone biochemistry (the profile is used to exclude secondary causes such as osteomalacia, hyperparathyroidism and myeloma).
Osteomalacia - low/normal calcium, low phosphate, high ALP, high PTH, low vitamin D.
Bone metastases - raised calcium and ALP (lytic and sclerotic deposits); myeloma usually has a normal ALP (purely lytic, osteoblasts suppressed).
Hypophosphataemia - refeeding, alcohol, DKA treatment, hyperparathyroidism, IV iron (ferric carboxymaltose), vitamin D deficiency.
Non-fasting samples are acceptable for most assessments (NICE); fast if triglycerides are high (>4.5 mmol/L) on a non-fasting sample.
Non-HDL cholesterol (total − HDL) is the preferred NICE treatment target (≥40% reduction in primary prevention); LDL is calculated (Friedewald) or measured directly.
Check TSH, LFTs, HbA1c and renal function before starting lipid-lowering drugs (secondary causes, baseline for statins). CK only if symptomatic or at high risk.
High-sensitivity troponin (T or I) - released from damaged myocytes; rises within about 3 hours of MI and stays raised for 7–14 days. Use serial testing (0 and 1–3 hours per local protocol) - a rising or falling pattern above the 99th centile (sex-specific) with clinical evidence defines acute MI (Fourth Universal Definition).
Type 2 MI - supply–demand mismatch (anaemia, tachycardia, hypotension, hypoxia).
NT-proBNP / BNP - released in response to ventricular stretch; rule-out test for heart failure (NICE: NT-proBNP <400 ng/L makes heart failure unlikely in untreated patients; >2,000 ng/L - urgent echo and specialist assessment within 2 weeks). Raised by age, AF, renal failure, PE, sepsis; lowered by obesity and diuretics/ACEi/ARB/ARNI treatment.
TSH is the first-line thyroid test; add free T4 (and free T3 if TSH is suppressed). Interpret with care in non-thyroidal illness, pregnancy (trimester-specific ranges), amiodarone, biotin use and pituitary disease (TSH unreliable in secondary hypothyroidism).
HbA1c - average glucose over about 2–3 months; unreliable with altered red cell lifespan (haemolysis, haemoglobinopathies, recent transfusion, iron deficiency - falsely high; pregnancy, CKD/erythropoietin).
Cortisol - 9 am sample; <100 nmol/L strongly suggests adrenal insufficiency; >450 makes it unlikely (assay-dependent). Oral oestrogen raises total cortisol. Exogenous steroids (prednisolone cross-reacts in many assays; dexamethasone does not) affect interpretation.
Prolactin - stress raises it; check for macroprolactin if no symptoms.
Testosterone - 9–11 am, repeat if low; check SHBG, LH and FSH.
hCG - urine tests detect about 25 IU/L; serum hCG doubles every 48 hours in a viable intrauterine pregnancy (a <63% rise in 48 hours raises concern for ectopic or failing pregnancy).
Paracetamol overdose - measure the level at least 4 hours after ingestion; treat with acetylcysteine if above the single treatment line (100 mg/L at 4 hours) or if staggered/uncertain timing, or presenting late with abnormal LFTs. The SNAP regimen (12-hour) is now widely used in the UK.
Salicylate - mixed respiratory alkalosis and metabolic acidosis, tinnitus; urinary alkalinisation or haemodialysis.
Albumin - made by the liver; low in inflammation (negative acute phase reactant), liver disease, nephrotic syndrome, protein-losing enteropathy, malnutrition (late), haemodilution. Not a reliable marker of nutrition in acute illness.
Globulins - raised in chronic inflammation, chronic liver disease, myeloma (paraprotein), HIV; low in immunodeficiency (hypogammaglobulinaemia - CLL, myeloma, primary).
CRP - rises within 6 hours and halves in about 19 hours; high in bacterial infection and inflammation; often modest in SLE (unless serositis or infection), ulcerative colitis and viral infections.
ESR - slower; raised by anaemia, age, female sex, pregnancy and immunoglobulins (very high in myeloma, GCA, TB).
Serum protein electrophoresis - identifies a paraprotein (M band); with serum free light chains and urine Bence Jones protein in suspected myeloma (bone pain, hypercalcaemia, renal impairment, anaemia - "CRAB").
α-1 antitrypsin - deficiency causes emphysema (basal, young, non-smoker or light smoker) and liver disease.
Scenario. A 75-year-old has potassium 6.4 mmol/L on a sample taken in GP surgery yesterday afternoon and delivered this morning. ECG is normal. What next?
Answer: Likely pseudohyperkalaemia from delayed separation (potassium leaks from cells overnight). Repeat urgently with prompt delivery to the laboratory; act on the repeat (and on any ECG changes or clinical risk).
Scenario. A woman with raised ALP and GGT, itching and positive anti-mitochondrial antibodies.
Answer: Primary biliary cholangitis - cholestatic pattern; treat with ursodeoxycholic acid; check for associated autoimmune disease and assess fibrosis.
Scenario. A patient on lithium becomes confused with coarse tremor and diarrhoea after starting ibuprofen and ramipril. What is the mechanism?
Answer: NSAIDs and ACE inhibitors reduce renal lithium clearance → toxicity. Stop lithium and the interacting drugs, check the level and U&E, give IV fluids; haemodialysis if severe.