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AN INTRODUCTION TO LABORATORY TESTS AN INTRODUCTION TO LABORATORY TESTS Aim - introduction to laboratory tests of clinical and diagnostic importance - biochemistry and haematology Use? Assist doctor in making a diagnosis and monitoring treatment Assist pharmacist in assessing and monitoring drug treatment Individual tests may provide insufficient information consider pattern of tests within a group Single tests are of less value than a series - show trends Expressed as a reference range - based on the assumption that 95% of the population are normal REFERENCE VALUES 1. RENAL FUNCTION TESTS Serum Creatinine, Creatinine Clearance, Urea – Used to give an estimate of glomerular filtration rate (GFR) – GFR gives an indication of the efficiency of the kidney and is decreased in renal impairment – In practice, this is crucial information to determine drug handling. Renally cleared drugs and metabolites will accumulate in renal impairment – Some drugs may reduce GFR e.g. NSAIDs and aminoglycosides 1. RENAL FUNCTION TESTS Serum Creatinine (Cr) – Reference range 80 -150 micromoles/L – Creatinine is a major metabolite of creatine phosphate, a major constituent of muscle. – Excreted almost exclusively by glomerular filtration – freely filtered. – GFR results in creatinine Creatinine Clearance (CrCl) – Renal impairment if< 50ml/min – Serum creatinine can be used in the Cockroft-Gault equation to estimate creatinine clearance. GFR approximates to CrCl COCKROFT and GAULT EQUATION Cr Cl = (140 - age) x Wt (kg) x F Cr Units are mls/minute Cr = serum creatinine in micromoles/litre F = 1.23 for males, 1.04 for females 1. RENAL FUNCTION TESTS Urea (4.2-6.4mmol/L) – Also known as blood urea nitrogen, BUN. – Used to estimate renal function, but poor measure of minor degrees of renal impairment as it is influenced by other factors. – End product of protein metabolism. (High protein diet increases urea) – Usually measured as urea and electrolytes (U&Es) 1. RENAL FUNCTION TESTS HIGH SERUM CREATININE signifies GFR Renal impairment RENAL IMPAIRMENT Grade GFR (Creatinine Clearance) ml/min Mild 20-50 Moderate 10-20 Severe <10 Serum Creatinine micromoles/L 150-300 300-700 >700 Renal impairment is arbitrarily divided into 3 grades ( see BNF) Glomerular Filtration rate, measured by creatinine clearance Note - definitions vary. Consult product literature for specific drugs 2. ELECTROLYTES Sodium, potassium, calcium, phosphate, glucose Sodium – Main extracellular cation. Osmolality of ECF is largely determined by sodium and associated anions – Intimately linked with distribution of water between intra and extracellular compartments (ICF and ECF). Reflects fluid status of patient – Changes in body sodium content result in changes in ECF volume – Reference value 133-144mmol/L 2. ELECTROLYTES TOTAL BODY WATER 2. ELECTROLYTES INTRA and EXTRA CELLULAR FLUID 2. ELECTROLYTES Hyponatraemia Indicates an increase in free water in ECF Caused by – Sodium (and water) loss e.g.diuretics – Water retention in excess of sodium e.g. carbamazepine, tricylclics – Symptoms if Na<120mmol/L – headache, nausea, cramps, confusion 2. ELECTROLYTES Hypernatraemia Indicates a loss of free water and an increase in sodium Caused by – Excessive water loss, or combined loss of water and sodium with predominant water loss e.g. diarrhoea in infants – Unlikely to be caused by sodium excess - thirst compensates Symptoms at Na>160mmol/L - thirst, mental confusion coma 2. ELECTROLYTES Potassium – Principal intracellular cation (<2-3% in ECF) – Involved in muscle excitation and cardiac function. Body sensitive to changes in serum potassium. – Reference values 3.5 - 5 mmol/L – Hypo - reduced muscle activity, arrhythmias, mental slowing. – Hyper - ventricular fibrillation and cardiac arrest. 2. ELECTROLYTES Hypokalaemia Decreased potassium Serious at <2.5mmol/L (reference range 3.5-5) Caused by – Diuretics (loop and thiazide) – Loss from GI tract (diarrhoea, vomiting) – Shift into cells (insulin, salbutamol) 2. ELECTROLYTES Hyperkalaemia Increased potassium Serious at >6.5 mmol/L (reference range 3.5-5) Caused by – – – – Potassium sparing diuretics Acute renal failure Catabolic states e.g. diabetic ketoacidosis Vast intracellular damage – cell lysis, release of K 3. LIVER FUNCTION TESTS No specific test to determine degree of liver impairment Important to look for a pattern using the following tests – ALP – AST and ALT – GGT – Bilirubin 3. LIVER FUNCTION TESTS Alkaline Phosphatase (ALP) – Found in cells lining the bile duct – rise usually signifies cholestasis [c] (obstruction to flow in bile duct) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) – Found in hepatocytes – rise usually signifies hepatocellular damage [h] Gamma-glutamyl transferase (GGT) – Synthesis of the enzyme induced by alcohol and drugs. Rise usually signifies hepatobiliary disease [hb] 3. LIVER FUNCTION TESTS Bilirubin Breakdown product of haemoglobin Rise in UNCONJUGATED form usually signifies » haemolysis (increased RBC destruction), or » direct hepatocellualr damage. Rise in CONGUGATED form usually signifies » cholestasis - obstruction to bile flow A rise in both CONJUGATED & UNCONJUGATED bilirubin suggests » mixed hepatocellular damage and cholestasis. Changes in LFTs may be due to disease process (e.g. gallstones, hepatitis) or due to drugs (e.g. chlorpromazine [h,c], flucloxacillin [c]). 3. LIVER FUNCTION TESTS BILIRUBIN and UROBILINOGEN