1. AN INTRODUCTION TO LABORATORY TESTS

2. Aim - introduction to laboratory tests of clinical and diagnostic importance - biochemistry and haematology Aim - introduction to laboratory tests of clinical and diagnostic importance - biochemistry and haematology Use? 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 Individual tests may provide insufficient information - consider pattern of tests within a group Single tests are of less value than a series - show trends 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 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 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) 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) 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 Cl = (140 - age) x Wt (kg) x F Cr 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) 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 GFR Renal impairment Renal impairment

9. RENAL IMPAIRMENT Renal impairment is arbitrarily divided into 3 grades ( see BNF) Renal impairment is arbitrarily divided into 3 grades ( see BNF) Glomerular Filtration rate, measured by creatinine clearance Glomerular Filtration rate, measured by creatinine clearance Note - definitions vary. Consult product literature for specific drugs Note - definitions vary. Consult product literature for specific drugs GradeGFR (Creatinine Clearance) ml/min ml/minSerumCreatininemicromoles/L Mild20-50150-300 Moderate10-20300-700 Severe<10>700

10. 2. ELECTROLYTES Sodium, potassium, calcium, phosphate, glucose Sodium 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. ELECTROLYTES TOTAL BODY WATER

12. 2. ELECTROLYTES INTRA and EXTRA CELLULAR FLUID

13. 2. ELECTROLYTES Hyponatraemia Indicates an increase in free water in Indicates an increase in free water inECF Caused by 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 Indicates a loss of free water and an increase in sodium Caused by 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 Symptoms at Na>160mmol/L - thirst, mental confusion coma

15. 2. ELECTROLYTES Potassium 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 Decreased potassium Serious at <2.5mmol/L Serious at <2.5mmol/L (reference range 3.5-5) Caused by Caused by –Diuretics (loop and thiazide) –Loss from GI tract (diarrhoea, vomiting) –Shift into cells (insulin, salbutamol)

17. 2. ELECTROLYTES Hyperkalaemia Increased potassium Increased potassium Serious at >6.5 mmol/L Serious at >6.5 mmol/L (reference range 3.5-5) Caused by 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 No specific test to determine degree of liver impairment Important to look for a pattern using the following tests Important to look for a pattern using the following tests –ALP –AST and ALT –GGT –Bilirubin

19. 3. LIVER FUNCTION TESTS Alkaline Phosphatase (ALP) 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 Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) Alanine aminotransferase (ALT) –Found in hepatocytes – rise usually signifies hepatocellular damage [h] Gamma-glutamyl transferase (GGT) 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 Bilirubin Breakdown product of haemoglobin 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 TESTS BILIRUBIN and UROBILINOGEN