Makindo Medical Notes

💡 Chemical Pathology (Clinical Biochemistry) is the branch of laboratory medicine that deals with the measurement and interpretation of biochemical changes in health and disease. It provides crucial information for diagnosis, monitoring, prognosis, and screening of medical conditions.

📖 Introduction

Chemical pathology underpins everyday clinical practice: from checking electrolytes in the acutely unwell, to monitoring HbA1c in diabetes, or troponins in chest pain. It focuses on the quantitative and qualitative analysis of blood, urine, and other body fluids. Interpretation must consider clinical context, as abnormal results may reflect pre-analytical, analytical, or post-analytical issues.

🔬 Core Areas of Chemical Pathology

• Electrolytes & Acid-Base: Sodium, potassium, chloride, bicarbonate — crucial in fluid balance, renal disease, acidosis/alkalosis.
• Renal function tests: Urea, creatinine, eGFR, urine electrolytes.
• Liver function tests (LFTs): ALT, AST, ALP, GGT, bilirubin, albumin, INR.
• Bone profile: Calcium, phosphate, ALP, vitamin D, PTH.
• Endocrinology: Hormone assays (TSH, cortisol, oestradiol, testosterone, etc.).
• Lipidology: Cholesterol, triglycerides, HDL, LDL.
• Diabetes & metabolism: Glucose, HbA1c, ketones.
• Tumour markers: PSA, CA-125, CEA, AFP (interpret cautiously).
• Toxicology & drug monitoring: Paracetamol levels, digoxin, lithium, anticonvulsants.

⚡ Pre-analytical Factors

• Patient preparation (fasting vs non-fasting glucose/lipids).
• Timing (cortisol has diurnal variation).
• Specimen handling (e.g. haemolysis can falsely elevate K⁺).
• Contamination (IV fluids → sodium/glucose errors).

🧪 Common Investigations Explained

1. Electrolytes & Acid-Base

• Hyponatraemia: Causes include SIADH, fluid overload (CHF, cirrhosis), adrenal insufficiency, diuretics. Symptoms: confusion, seizures.
• Hyperkalaemia: Causes include renal failure, ACEi/ARB, haemolysis, Addison’s. ECG: peaked T-waves, risk of cardiac arrest.
• Acid-Base: Metabolic acidosis (DKA, renal failure), respiratory acidosis (COPD), metabolic alkalosis (vomiting, diuretics).

2. Renal Profile

• Urea & Creatinine: Reflect GFR. Creatinine depends on muscle mass; eGFR is adjusted for age/sex.
• AKI diagnosis: Rise in creatinine ≥26 µmol/L in 48 h, or ≥1.5 × baseline, or urine output <0.5 mL/kg/h.

3. Liver Function Tests

• ALT/AST: Hepatocellular damage.
• ALP/GGT: Cholestasis, biliary obstruction.
• Bilirubin: Pre-hepatic (haemolysis), hepatic (hepatitis), post-hepatic (obstruction).
• Albumin & INR: Synthetic liver function (chronicity).

4. Bone Profile

• Hypercalcaemia: Primary hyperparathyroidism, malignancy.
• Hypocalcaemia: Hypoparathyroidism, vitamin D deficiency, CKD.
• ALP: Raised in bone disease (Paget’s, metastases) and cholestasis.

5. Endocrine Biochemistry

• Thyroid: TSH and free T4 are first-line; interpret together.
• Adrenal: Cortisol, ACTH — consider diurnal variation, synacthen test for Addison’s.
• Reproductive hormones: LH, FSH, oestradiol, testosterone, prolactin — guide infertility/menstrual disorders.

6. Diabetes & Lipids

• Glucose: Fasting glucose ≥7.0 mmol/L = diabetes; random ≥11.1 mmol/L if symptomatic.
• HbA1c: ≥48 mmol/mol (6.5%) diagnostic of diabetes (not valid in haemoglobinopathies, anaemia).
• Lipids: TC, LDL, HDL, TG — cardiovascular risk stratification.

7. Tumour Markers

• Useful for monitoring, not screening.
• PSA: Prostate cancer, but also rises with prostatitis, BPH.
• CA-125: Ovarian cancer, but raised in endometriosis, benign ovarian cysts.
• AFP: Hepatocellular carcinoma, germ cell tumours.
• CEA: Colorectal, gastric cancers, but non-specific.

8. Toxicology & Drug Monitoring

• Paracetamol: Levels plotted on nomogram to guide NAC therapy.
• Digoxin: Narrow therapeutic index; toxicity causes arrhythmias, GI upset.
• Lithium: Monitored for toxicity (tremor, nephropathy, hypothyroidism).
• Antiepileptics: Carbamazepine, phenytoin, valproate levels may be checked in toxicity or poor control.

⚠️ Clinical Red Flags in Biochemistry

• Severe hyperkalaemia (≥6.5 mmol/L or ECG changes).
• Severe hyponatraemia (confusion, seizures).
• Markedly deranged LFTs (AST/ALT >1000: viral hepatitis, ischaemia, paracetamol toxicity).
• Very high corrected calcium (>3.5 mmol/L: risk of arrhythmia, coma).
• Raised troponin in chest pain — acute coronary syndrome until proven otherwise.

👩‍⚕️ Case Example

Mrs B, 72, presents with confusion and constipation. Bloods show calcium 3.3 mmol/L, suppressed PTH, low phosphate. Interpretation: Hypercalcaemia of malignancy. She is treated with IV fluids and bisphosphonates. This illustrates how chemical pathology can rapidly guide emergency care.

📌 Teaching Pearls

• Always interpret results in clinical context — labs are not diagnostic in isolation.
• Trends > single results: one abnormal lab may be artefact; repeat if uncertain.
• Be aware of pre-analytical errors (haemolysis, incorrect sampling).
• Chemical pathology is key in both acute medicine (electrolytes, troponin, paracetamol) and chronic disease (diabetes, thyroid, CKD).

📚 References

• NICE guidelines: CKD (NG203), Diabetes (NG17/NG136), Hyperparathyroidism (NG132).
• Orell & Sterrett’s Clinical Biochemistry for Medical Students (UK edition).
• Cochrane Reviews on biochemical test utility in chronic disease.