Chem Path 01: Proteins and Enzymes

Plasma proteins serve diverse physiological functions: maintaining oncotic pressure, transporting molecules, participating in coagulation and immune defence, and acting as enzymes. Their measurement provides diagnostic and prognostic information across a wide range of diseases.

Albumin is the most abundant plasma protein (reference interval approximately 35–50 g/L), accounting for approximately 80% of plasma colloid osmotic pressure. It is synthesised exclusively by hepatocytes and has a half-life of approximately 21 days. Albumin transports fatty acids, bilirubin, drugs (warfarin, phenytoin), calcium, and hormones. Hypoalbuminaemia causes oedema (reduced oncotic pressure → fluid shifts to interstitium), activates the renin-angiotensin-aldosterone (RAA) system (perceived underfilling), and increases the free fraction of protein-bound drugs (risk of toxicity). In neonates, low albumin increases the risk of kernicterus (unconjugated bilirubin competes with bilirubin for limited albumin binding, and free bilirubin crosses the blood-brain barrier). Causes of hypoalbuminaemia: decreased synthesis (liver disease, malnutrition), increased losses (nephrotic syndrome, protein-losing enteropathy), increased catabolism (sepsis), and dilutional (excess IV fluids).

Immunoglobulins (antibodies) are plasma glycoproteins composed of two heavy and two light chains linked by disulfide bonds. In multiple myeloma, a clonal plasma cell proliferation secretes a single immunoglobulin (monoclonal protein, M-protein, or paraprotein) detectable as a sharp discrete band on serum protein electrophoresis (SPE). Bence Jones proteins are free immunoglobulin light chains (kappa or lambda) excreted in urine; their detection suggests multiple myeloma or light-chain amyloidosis. In nephrotic syndrome, massive proteinuria (>3.5 g/day) leads to loss of smaller proteins (albumin, antithrombin) while larger immunoglobulins are retained.

Plasma enzymes are measured because their release from damaged or proliferating cells provides organ-specific diagnostic information. Alanine aminotransferase (ALT): present primarily in hepatocytes; markedly elevated in acute hepatocellular damage (viral hepatitis, drug toxicity, ischaemic hepatitis); the most liver-specific enzyme. Aspartate aminotransferase (AST): present in hepatocytes, cardiac muscle, skeletal muscle, and red cells; elevated in liver disease, MI, haemolysis, and rhabdomyolysis. An AST:ALT ratio >2 suggests alcoholic liver disease (AST disproportionately elevated because alcohol depletes pyridoxal phosphate, reducing ALT synthesis). Alkaline phosphatase (ALP): found in liver (canalicular membrane), bone (osteoblasts), placenta, and intestine; elevated in cholestasis (obstructed bile flow) and bone disease (Paget's disease, bone metastases, hyperparathyroidism). Gamma-glutamyl transferase (γGT): hepatobiliary marker; elevated in cholestasis and induced by alcohol (γGT is an inducible enzyme — useful marker of alcohol intake); more sensitive than ALP for hepatobiliary disease. Lactate dehydrogenase (LDH): non-specific marker of tissue damage; elevated in haemolysis, MI, liver disease, lymphoma, and many other conditions. Creatine kinase (CK): isoforms — CK-MM (skeletal muscle), CK-MB (cardiac muscle, approximately 25% of cardiac CK), CK-BB (brain); CK-MB and troponin are cardiac markers. Lipase: pancreatic enzyme; elevated >3× ULN is specific for acute pancreatitis; more specific and longer-lasting than amylase. Troponin I and T: cardiac-specific structural proteins; the standard biomarker for MI diagnosis.