You are on page 1of 25

HBC/BC 306 Clinical Biochemistry

• Basic biochemistry emphasizing human metabolic pathways & their relationship to health & disease. • Biochemical tests are used in the diagnosis, management, treatment and subsequent follow-up, of human disease Type of Samples
Concentration of different analytes determined in: •Blood •Serum or plasma •Urine •Cerebrospinal fluid (CSF)

Within-Individual Variation 1. Time of day- diurnal variation of: • Plasma iron • Adrenocorticotropic hormone (ACTH) • Cortisol 2. Diet • Plasma [triglyceride] • Response to glucose tolerance tests • Urinary calcium excretion 3. Muscular Exercise • Increase plasma creatine kinase activity • Increase blood [lactate] • Lower blood pyruvate

of pituitary gonadotrophins & ovarian steroids & their metabolites • Amts of hormones & their metabolites excreted in urine 5. Age • Plasma [phosphate] & alkaline phosphatase activity . Drugs • Oestrogen-containing oral contracetives affect plasma constituents Between-Individual Variation 1. Menstrual Cycle • Plasma [iron] • Plasma conc.4.

urea conc. • Plasma & urinary conc. of sex hormones 3.• Plasma & urinary conc. of gonadotrophins & sex hormones 2. Race • Plasma [cholesterol] & [protein] • Diet??? Reference Ranges • Set of results from a particular defined population • No clear-cut distinction between normal & abnormal conc. of any constituent . Sex • Plasma creatine. iron.

know: • Reference range for healthy individuals • Expected values for patients with disease • Prevalence of disease in population Sensitivity of test • Ability to show +ve results in patients with particular disease (true +ve rate) • The higher the sensitivity. the lower the false –ve rate Specificity of test • % of –ve results among people who do not have the disease • The higher the specificity.To interpret results. the greater the detection rate. the lower the false +ve rate .

Increased rate of cell turnover 3. Therapeutic agents Release of Enzymes from Cells 1. Transaminases 4. Creatine kinase (CK) 3.Use of Enzymes in Clinical Biochemistry 1. of enzymes within cells 4. Analytical reagents 3. Duct obstruction Enzymes Commonly Used in Diagnosis 1. Indicators of various diseases 2. Necrosis or severe damage to cells 2. Alkaline phosphate (ALP) . Lactate dehydrogenase (LD) 2. Increased conc.

lesion formed when cells of the myocardium die due to severe ischemia (territorial distribution of blood) Common cause.protects myocardium from permanent damage by restoring blood flow • Streptokinase • Recombinant tissue plasminogen activator .Artery obstruction caused by formation of thrombus (blood clot) Anti-thrombolytic therapy.Serum Markers in the Diagnosis of Tissue Damage Myocardial Infarction Myocardial infarct .

Myoglobin • earliest marker • not cardiac specific • raised by any form muscle damage .• Measurement of circulatory proteins (enzymes & non-enzyme proteins) released from necrotic myocardial tissue are useful in diagnosis • Rise rapidly to a peak between 18 & 36 hrs • Return to normal dependent on ½ life each protein in the plasma 1.

early marker • Higher cardiac specificity over total CK 4. CKMB • Rel. MB. early marker • Cardiac specific . MM • Rel. Total CK • 3 principal CK isoenzymes • Dimers BB. Cardiac Troponin T • Rel. early marker • Not cardiac specific 3.2.

Cardiac Troponin I • Rel.• But elevated in diseases of regeneration of skeletal muscle & chronic renal disease 5. LDH Isoenzymes • Late marker • Not cardiac specific • LD1/LD2 determination increases cardiac specificity . early marker • Highly cardiac specific 6.

Acute Pancreatitis Obstruction of pancreatic duct that delivers pancreatic juice to small intestine • Gall stones • Alcohol abuse Inappropriate release of pancreatic enzymes & their premature activation • Eg Trypsinogen is activated to trypsin .converts many other enzymes to their active forms .

Serum Lipase • Higher specificity than amylase . Serum Amylase • Elevated levels – sensitive diagnostic indicator • Low specificity • Many non-pancreatic causes of hyperamylasemia 2. Diagnosis involves measurement of pancreatic digestive enzymes. 1.Lab.

Production of urine • Elimination of metabolic end products.water & electrolyte balance . Endocrine Functions .Renal Function Tests • To identify renal dysfunction • To diagnose renal disease & monitor progress • To monitor response to treatment Functions of the Kidney 1. ie urea & creatinine • Elimination of foreign materials – drugs • Control of volume & composition of extracellular fluid .acid / base balance 2.

Urinalysis .Erythropoietin .Antidiuretic hormone Biochemical Tests .Vitamin D ..Appearance.Valid sample = fresh sample 2.Tubular function tests Tests rarely establish the cause BUT help in screening for damage & monitoring progression of disease Urinalysis 1.Unusual colour due to blood or infection? .Measurement of glomerular filtration rate .

Decreased tubular reabsorption of protein? 7. fat droplets? Measurement of Glomerular Filtration Rate (GFR) .Proteinuria.Raised plasma low MW proteins.Glomerular leak? .Urine sediments.Glucose – increased blood glucose?? 6.detected using urine sticks . myoglobin? .Specific gravity. Bence Jones.sticks measure ionic species only & NOT glucose 4.microscopic examination for cells.pH – normally acidic except after a meal 5.3.GFR is essential to renal function & is a frequently performed test .

Freely filtered by glomerulus .Measurement is based on concept of clearance “ The determination of the volume of plasma from which a substance is removed by glomerular filtration during its passage through the kidney” Clearance = (U x V) / P Where U = urinary conc. Creatinine Clearance (ml/min) =Urine[creatinine] x urine vol (ml) Plasma [creatinine] collection time (min) If clearance = GFR then substance .. ie no tubular secretion or reabsorption . of substance V = rate of urine formation in ml/min P = plasma conc.Easily measurable . .Glomerulus is sole route of excretion.Has constant plasma conc. of substance Units = vol / unit time (ml/min) Eg.

glucose Acute Renal Failure (ARF) Due to reduced glomerular filtration rate with resultant retention of • Urea & creatinine • Na & water • Acid with metabolic acidosis . amino acids.Tubular Function Tests Specific renal tubule disorders may affect ability to • Concentrate urine • Excrete appropriately acidic urine • Cause impaired reabsorption of phosphate.

urea conc. renal or postrenal Chronic Renal Failure (CRF) Progressive loss of nephrons resulting permanently impaired renal function • Retention of urea. toxins • Rate of urea excretion falls & cannot balance rate of production • Plasma urea rises.• Potassium with hyperkalaemia (potassium is released from cells & acidosis promotes the leakage) ARF may manifest as pre-renal. creatinine. in filtrate of functioning nephrons rises .

phospholipids.• May cause osmotic diuresis in these nephrons • Sodium & potassium excretion? Liver Function Tests Functions of the Liver 1. cholesterol . Carbohydrate metabolism • Glycogen synthesis. Lipid metabolism • Synthesis of almost all lipoproteins. storage & breakdown • Gluconeogenesis 2.

3. Protein Synthesis • Many plasma proteins. most coagulation factors are synthesized in hepatic cells 4. B12 & iron 5. Excretion & Detoxification • Bile pigments & cholesterol are excreted in bile • Many drugs are detoxicated by the liver • Ammonia derived from amino acid metabolism is converted to urea • Steroid hormones are inactivated by conjugation with glucuronate & sulphate in liver & excreted in urine . Storage functions • Vitamins A. D.

bilirubin is coupled to glucuronic acid & the conjugated bilirubin is excreted into bile . cytochromes) are freed of iron & converted to bilirubin • Bilirubin is a yellow pigment that is strongly lipophilic & cytotoxic • Transported to liver. bound to serum albumin • At the liver. Reticulo-endothelial function • Kupffer cells lining sinusoids of liver form part of reticulo-endothelial system Bilirubin Metabolism • Heme groups (from haemoglobin myoglobin.6.

causes acute release of intracellular constituents into bloodstream • Detected by measuring plasma enzymes.Jaundice • Clinically detectable increase in plasma bilirubin levels • Due to predominant rise in unconjugated bilirubin from excessive haemolysis or decreased excretion Biochemical Tests in Liver Disease Hepatocellular Damage • Damage to liver cells. alanine & aspartate aminotransferases (transaminases) . with or without necrosis.

alkaline phosphatase (ALP)& gamma. coagulation factors & bilirubin metabolism • Hypoalbuminaemia & a prolonged prothrombin time are detectable when damage is extensive & prolonged • Deficiency of Vit K may also cause prolonged prothrombin time .glutamyltransferase (GGT) • Obstruction of biliary tract with jaundice indicates cholestasis Impaired Hepatocellular Function • Affects synthesis of albumin.Biliary Tract Involvement • Characterized by increased production & raised plasma levels of hepatobiliary enzymes.

if cholestasis is present Specific Liver Diseases Acute Hepatitis • Caused by viruses or toxins . of all plasma lipid fractions.Disordered Metabolism Patients with severe liver disease may have: • Significant decreases in plasma [urea] due to failure of liver to convert amino acids & ammonia to urea • Hypoglycaemia due to impaired gluconeogenesis or glycogen breakdown • Raised conc.

• Cell damage detectable by plasma enzyme estimations Cirrhosis • During active cellular destruction. transaminase levels rise. sometimes with jaundice • In alcoholic cirrhosis. GGT levels are elevated .