AN INTRODUCTION TO LABORATORY TESTS

1. AN INTRODUCTION TO LABORATORY TESTS

2. 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 testswithin 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

3. REFERENCE VALUES

4. 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

5. 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

6. 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

7. 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)

8. 1. RENAL FUNCTION TESTS HIGH SERUM CREATININE signifies • GFR • Renal impairment

9. RENAL IMPAIRMENT • 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

10. 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

11. 2. ELECTROLYTESTOTAL BODY WATER

12. 2. ELECTROLYTESINTRA and EXTRA CELLULAR FLUID

13. 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

14. 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

15. 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.

16. 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)

17. 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

18. 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

19. 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]

20. 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]).

21. 3. LIVER FUNCTION TESTSBILIRUBIN and UROBILINOGEN