CLINICAL LABORATORY TESTS

Most illnesses either have biochemical origin or result in a secondary disturbance to the intricate biochemical equilibrium that characterize the healthy human organism. It follows that careful measurement of selected analytes in blood or other body fluids can provide information useful in diagnosis, and such measurements also are useful in monitoring disease progression and the .response to therapy

THE BLOOD
.The blood is a tissue which circulates in a closed system of blood vessels :Functions - oxygen and carbon dioxide between the lung and the tissues. Carries -.Carries food materials from alimentary canal to the tissues -.Takes the waste products of metabolism from the tissues to be excreted by the kidneys -.Carries hormones from glands to sites of action .Immunity: it carries many immune bodies which are gamma globulins .The blood distributes the temperature equally all over the body.The blood has buffer systems that help in keeping the pH of tissues constant.Water balance-Hemostasis: it has the ability to clot so as to prevent bleeding from injured blood vessels:Composition :The blood consists of Cells :The cells .Blood cells constitute about 45% of blood volume Red blood cells: non nucleated cells :Count In men: 4.6-6.2 million cells/ml In women: 4.2-5.4 million cells/ ml 2- Plasma -1

.Decreased in cases of anemia Increased in cases of polycythemia . .Anemia: it means deficiency of red blood cells :Anemia may be due to -.(Loss of RBC's ( hemorrhage, bilharziasis -.(Destruction of RBC's ( drug poisoning, sickle cell anemia -Defective formation of RBC's ( deficiency of Fe, protein, pernicious anemia, destruction of bone .(marrow by toxins, x-ray :Polycythemia .When the tissue become hypoxic ( little oxygen), large quantities of RBC's are formed .It occurs in fetus before birth, but after birth, excess RBC's are destructed :White blood cells .Count: 4,000- 10,000 cells/ ml .Granular WBC's: neutrophils- eosinophils- basophils .Non- granular WBC's: lymphocytes- monocytes .Increased in: leukemia- active infection (Decreased in: leukopenia due to bone marrow depression ( as a result of drug poisoning or irradiation .When decreased, the body will be unprotected against bacteria (Platelets: ( thrombocytes Count:250,000- 500,000 cells/ ml .Platelets are responsible for releasing vasoconstricting substances when blood vessels are injured .And producing factors that are needed for blood coagulation .The PLasma .The plasma is the liquid medium in which blood cells are suspended :Composition water 2 8% solids 92%

.The solid material may be classified as organic and inorganic -Organic: plasma proteins- urea- amino acids creatine- creatinine- carbohydrates- lipids .vitamins- pigments- hormones .Inorganic: sodium- potassium- calcium- chloride- iron-magnesium :Hemoglobin content .Normal: 14-18 g/dl blood .g/dl blood .Decreased in cases of anemia :Some blood tests :The bleeding time .It is the time between the formation of a small cut and stop of bleeding from the cut .Normal= 2-5 minutes .Bleeding is stopped by vasoconstriction by serotonin released from platelets :The coagulation time .It is the time between the start of bleeding and formation of a clot .Normal= 5-8 minutes :The hematocrit value .It is the volume of RBC's present in 100 ml blood Normal: 477 in males .in females 455 -.Low values indicate anemia -High values indicate polycythemia in men in women 12-16

:The erythrocytes sedimentation rate .This parameter reflects the plasma protein content- It is measured by the height of clear plasma formed at the top of blood which is kept liquid with .an anticoagulant Normal male female After 1 hour 3-5mm 4-7mm After 2 hours 7-15mm 12-17mm

.Physiological increase occurs in normal pregnancy- menses:Pathological increase occurs in all conditions of tissue breakdown as in.infections- vaccination- toxemia- trauma- fractures- T.B- cancer- post-operative ,N.B. if the sedimentation rate is increased, this is not indicative of any particular disease, however it is important for when it is increased it indicates the presence of a disease and when it is decreased .to normal, it indicates improvement :Prothrombin time .It is used to check the activity of oral anticoagulants.Normal: 12-14 seconds .It is prolonged in liver diseases and in deficiency of vitamin K-

Plasma Proteins
Plasma proteins are a diverse group of molecules that perform a variety of functions. - More than 500 plasma proteins have been identified. - Most of plasma proteins are synthesized in the liver, the liver is also the major site of plasma proteins catabolism. - The balance between the synthesis and degradation maintains the level of plasma proteins within a relatively narrow range. - Most proteins are regulated independently of the others. Plasma proteins could be classified according to function or according to electrophoretic mobility. Abnormalities of plasma proteins arise from: - Congenital abnormalities. - Acquired abnormalities. - Variation in the physiologic state e.g age- gender- pregnancy. - Alterations secondary to a disease e.g cirrhosis- protein-losing syndrome. The total proteins may be measured on either serum or plasma. Serum samples are preferred because they are more convenient to use on automated equipments, if plasma is used, the total protein is 3-5% higher owing to the contribution of fibrinogen. The total serum protein includes both albumin (60%) and globulin (40%). -Dehydration causes a proportional increase in all the serum proteins, this occurs with decreased water intake or with increased water losses ( sweating- diarrhea- vomiting- salt-losing syndromediuresis). - Volume expansion causes a proportional decrease in serum proteins ( administration of intravenous fluids)- pregnancy- salt retention syndrome. Correction of fluid imbalance will correct the total concentration of proteins. - Infection, tissue injury, steroids( e.g oral contraceptives) will increase protein synthesis. - Malnutrition and chronic liver disease caused decreased protein synthesis and hypoproteinemia. - increased protein catabolism is seen in inflammation and neoplastic disease. - In nephrotic syndrome, extensive burns, excessive protein losses can occur. Changes in the total serum protein may result from changes in albumin, globulins or both, a change in one protein may be offset by a change in the opposite direction of another, so it may be useful to determine the ratio of albumin concentration to globulin concentration (A:G ratio) Increasing globulin concentration may be associated with a decrease in albumin concentration. i.e ratio is abnormal despite the total protein is normal.

ALBUMIN
Albumin is the most abundant protein in plasma ( 60% of total protein concentration) Albumin serves as an amino acids source to a variety of cells, functions as a major transport protein, it binds to bilirubin, free fatty acids, hormones ( T3, T4 ), many drugs bind to albumin ( reservoir ) e.g warfarin, salicylates, penicillin. Hyperalbuminemia results from dehydration. Hypoalbuminemia results from: - impaired synthesis ( chronic liver disease ). -increased catabolism. -excessive loss ( nephrotic syndrome, hemorrhage, burns ) -Increases in immunoglobulin levels lead to lower albumin level e.g tuberculosis, malignancy. - Malnutrition results in decreased synthesis. - Malabsorption syndromes.

GLOBULINS
Serum globulins are designated as -, - or globulins. globulin fraction of plasma is the source of almost all the immunologically active proteins of blood. Globulin is elevated in: - hepatic disease, infectious hepatitis, cirrhosis of liver. - biliary cirrhosis - plasma cell myeloma. - infectious disease ( malaria, schistosomiasis) Globulin is decreased in: -malnutrition - Agammaglobulinemia. - Hypogammaglobulinemia. -Leukemia. Fibrinogen It is present in plasma only. Fibrinogen is elevated in: - nephritis - infectious disease. Fibrinogen is decreased in: - Hepatic insufficiency. -Intravascular coagulation - Carcinoma of prostate. Normal values: Serum total protein 6-8 g/ dl. Albumin 3.5-5.5g/dl Globulin 2-3.6g/ dl Fibrinogen 0.2-0.6g/ d

BILIRUBIN Bilirubin is obtained from destruction of hemoglobin, conjugated in the liver to glucuronide and then excretred in the bile. It accumulates in plasma when: - liver insufficiency exists ( indirect = unconjugated ) - biliary obstructionis present ( direct = conjugated). - Rate of hemolysis increases ( indirect ) - deficiency of enzyme system involved in bilirubin metabolism in liver (glucuronyl transferase) ( indirect ). Jaundice It is a condition that is characterized by yellow coloration of the skin seen in some liver disease due to accumulation of bilirubin ( conjugated or unconjugated )in blood, and deposition in the skin. . Normal level: Total: 1.1-1.2 mg/dl Direct: 0.1-0.4 mg/ dl Indirect: 0.2-0.7 mg/ dl.

AMMONIA Ammonia in blood is derived from: - Large intestine, putrefactive action of bacteria on nitrogenous compounds. - Protein metabolism, ammonia is liberated, entering the portal vein, converted to urea in the liver ( urea cycle ). Liver disease results in increased blood ammonia concentration especially if protein consumption is high. Normal value: 10-60 g N/ dl. Elevated in : -Cases of congenital deficiency of any of the enzymes of the urea cycle. -Severe liver disease. - Severe hepatic failure. - Hepatic encephalopathy and coma

SODIUM

It is the major cation of extracellular fluid, it affects the distribution of body water. A shift of sodium into cells or a loss of sodium from the body results in a decrease of extracellular fluid volume, affecting circulation, renal function, and nervous system function. Normal value: 136-145 mmol/ l Increased in cases of: - dehydration - trauma of CNS. - Hyperadrenocorticism - Hyperaldosteronism. - Associated with hypertension and edema. Decreased in: - Renal insufficiency. -acute- chronic diarrhea - unusual sweating with inadequate sodium replacement. - Adrenal insufficiency. POTASSIUM It is the major intracellular cation. Potassium concentration in plasma determines neuromuscular and muscular irritability. It is important for normal muscle activity and contraction of the heart. Normal value: 3.5-5 mmol/ l The sample must be free from hemolysis ( as K may be released from RBC's and increases serum level). Increased in: - Renal insufficiency - Adrenal insufficiency ( hypoaldosteronism) Decreased in: - Starvation - Inadequate absorption - Vomiting. - Diarrhea. -Unusual renal loss. CHLORIDE It is the principle anion of the extracellular fluid. When chloride as HCl or NH4Cl is lost, alkalosis is obtained. When chloride is retained or ingested, acidosis is obtained. Cl- with Na+ has an important role in control of osmolarity of body fluids. Normal value: 96-106 mmol/ l

Increased in: - Renal insufficiency. - Dehydration. - Overtreatment with saline. Decreased in: - Vomiting - Diarrhea.. - Excessive sweating. - Adrenal insufficiency ( NaCl loss) CALCIUM - It is essential for: - Calcification of bones and teeth - Blood clotting - Contractility of heart and muscles. Normal level: 8.5-10.3 mg/ dl Increased in: - Hyperparathyroidism. - Vitamin D in excess. -Multiple myeloma ( osteolytic disease) - Metastatic cancer in bones. Decreased in: - Hypoparathyroidism. - Vitamin D deficiency. - Renal insufficiency. - Malabsorption. - Osteoporosis. - Ricketes. MAGNESIUM Magnesium is an activator for many enzymes. Magnesium is important for muscular excitability. Magnesium is important for normal cardiac function. Normal value: 2-4 mg/ dl. Increased in: renal failure Decreased in: - Hyperparathyroidism. - with some diuretics

RENAL FUNCTION TESTS

UREA Urea is the major nitrogen- containing metabolite from the degradation of protein arising from the ammonia produced from the deamination of amino acids. Urea is synthesized mainly in the liver, excreted by the kidney. The urea concentration in the glomerular filtrate is the same as in the plasma, the tubular reabsorption of urea varies inversely with the rate of urine flow. Normal value: 7-22 mg/ dl ( blood urea nitrogen BUN ) 21-53 mg/ dl urea Elevated in: Prerenal: -Increased urea production - High protein diet. - Malignancy. - Antianabolic drugs/ tetracycline - Sepsis. - Decreased renal perfusion. - Congestive heart failure. - Hypotension. - Renal vein thrombosis. - Dehydration. - Cirrhosis- ascites. Renal: - Glomerular disease. - Tubular disease. Postrenal: - Urinary trct obstruction - Decreased urine flow. - Carcinoma of bladder. - Calculi. Decreased in: - Low rate of urea production ( low protein intake, androgen or growth hormone administration , severe liver dysfunction) - Hemodilution ( overhydration, diabetes insipidus ) - Increased rate of urea excretion ( pregnancy, post-dialysis state )

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CREATINE AND CREATININE Creatine is synthesized in the liver, transported to muscle, it serves as a source of high energy phosphate. The creatine pool is related to muscle mass, 1.5% of creatine is degraded to creatinine each day by non enzymatic dehydration. Creatinine is excreted by glomerular filtration with no reabsorption. Creatine in plasma is increased with muscle necrosis, and most muscle disease. Serum creatinine level is determined by creatinine production, state of hydration and creatinine excretion. Normal value of creatinine in serum: 0.7-1.5 mg/ dl Values below 0.7 mg/dl are of no known significance. Elevated in: Prerenal: - Increased synthesis of creatinine. - Muscle hypertrophy - Muscle necrosis. - High meat diet. - Severe exercise. Decreased renal perfusion. - Hypotension. - Congestive heart failure. - Cirrhosis. Renal: - Decreased tubular secretion - Some drugs ( cimitidine, trimethoprim, probenecid ) Postrenal: - Urinary tract obstruction - Benign prostate hyperplasia - Calculi Clearance tests: Renal clearance of a substance: is the volume of plasma that can be completely cleared of that substance each minute by the kidney. Clearance(ml/min) = Urine concentration x urine volume (ml/min) -----------------------Plasma concentration The clearance of a substance that is freely filtered through the glomeruli and not subsequently reabsorbed or secreted by the tubule is a measure of the Glomerular filtration Rate ( GFR) Creatinine clearance is commonly used for the estimation of GFR.

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The amount of creatinine excreted in a 24h urine depends on the muscle mass. The amount is consistent for a given individual. Normal values of creatinine clearance: 125 ml/ min in adult male 115 ml/ min in adult female Decreased value ( decreased GFR ) in: - Decreased renal perfusion ( Congestive heart failure, cirrhosis, hemorrhage ) - Decreased tubular fluid flow ( postrenal obstruction e.g benign prostatic hyperplasia, carcinoma of prostate or urinary bladder, calculi) Increased value ( increased GFR ) in: - High renal perfusion ( pregnancy ). URIC ACID Uric acid is the major end product of nucleoprotein metabolism. It is produced in the liver and intestinal mucosa, excreted through the kidney. Plasma uric acid levels show day- to- day and seasonal variation in the same patient.It is higher in the summer than in the winter. It is low in child, reach adult level by age 18. Normal value: 4-7.5 mg/ dl in adult male 2.7-6 mg/dl in adult female Elevated ( Hyperuricemia ) in: - Increased uric acid synthesis.( Gout- purine-rich diet.- Increased tissue catabolism) - Radiation- chemotherapy of malignancy. - Decreased renal excretion ( renal failure- drugs e.g diuretics- small dose of aspirin (< 2g/ day) - Toxemia - Pregnancy. - Hypertension -Hyperparathyroidisim. Decreased levels in: -Acute hepatitis - Genetic deficiency of xanthine oxidase. - Treatment with allopurinol ( xanthine oxidase inhibitor ), probenecid. - Defect in renal tubular reabsorption of uric acid. N.B gout is a disorder characterized by increased level of the total body uric acid, precipitation of monosodium urate as deposits in and around joints, cartilage, bone, subcutaneous tissue.

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LIPIDS AND LIPOPROTEINS

Lipids = Fats Lipids include: Fatty acids- triglycerides- phospholipids- cholesterol- lipoproteins. Serum cholesterol is influenced by dietary fatty acids, the ingestion of saturated fatty acids produces elevation in serum cholesterol ( up to 16 C ), saturated fatty acids with 18 C had no effect on cholesterol level. The ingestion of polyunsaturated fatty acids has a beneficial effect on the total cholesterol ( corn oil, cottonseed oil, peanut oil, soybean oil, -3 fatty acids ) Lipoproteins are compounds that are formed of lipids and proteins to transport lipids through the blood, the different fractions of lipoproteins are: - chylomicrons : mainly consist of triglycerides, TG: Cholesterol= 20:1 - VLDL ( TG: Cholesterol= 5:1 ) - LDL ( Cholesterol> TG ) - HDL ( Cholesterol esters ) The different fractions of lipoproteins are characterized by electrophoresis. Hyperlipoproteinemia: Type I: severe chylomicronemia due to deficiency of lipoprotein lipase ( exogenous hyperlipidemia ), after a fatty meal. Type II: increased serum LDL due to: - defect in lipoprotein metabolism - secondary to hypothyroidism - nephrotic syndrome - diabetes mellitus. Type III: abnormal accumulation of VLDL ( genetic ) Type IV: increase in VLDL ( endogenous hyperlipidemia ) Type V: increase in VLDL and chylomicrons ( mixed hyperlipidemia ), due to low lipoprotein lipase and defective lipolysis. Type II ( familial hypercholesterolemia ) , in which the LDL receptors are defective or deficient due to genetic defects in the synthesis and expression of LDL receptors ( the patients are susceptible to heart disease and myocardial infarction ). The ingestion of too much saturated fats and cholesterol may be responsible for the elevation of serum LDL concentration. In addition, there are different risk factors for the development of atherosclerotic vascular diseases, these include: - age: men 45 years Women 55 years - A positive family history of premature coronary heart disease - Cigarette smoking - Hypertension - Low HDL cholesterol > 35 mg/ dl - diabetes mellitus 13

The total cholesterol value is a quantitation of all the cholesterol and cholesterol esters in all the lipoproteins taken together. Levels of serum cholesterol > 200 mg/ dl 200- 239 mg/ dl > 240 mg/ dl HDL cholesterol< 35 mg/ dl considered desirable border line- high blood cholesterol high blood cholesterol level low HDL cholesterol

If a person has never had a heart attack, a stroke, angina, a transient ischemic attack, peripheral arterial vascular disease, The total cholesterol will be normally < 200mg/ dl HDL cholesterol > 35mg/ dl If the total cholesterol is at the borderline HDL cholesterol > 35mg/ dl The patient must have dietary modification with physical activity If the patient with existing coronary heart disease, LDL cholesterol measurement must be obtained ( LDL cholesterol= total cholesterol HDL cholesterol triglycerides/ 5 ) LDL cholesterol level must be below 100mg/ dl, If LDL cholesterol > 100mg/ dl, lipid lowering therapy must be initiated. If the patient has no coronary heart disease but with one risk factor, LDL cholesterol must be less than 160mg/ dl If the patient has no coronary heart disease, but with 2 or more risk factors, LDL cholesterol must be less than 130mg/ dl N.B Regular exercise may elevate the HDL cholesterol level to be above 60mg/ dl, this eliminates a positive risk factor. Hypolipoproteinemia: it may be due to: -Deficiency in - lipoprotein ( HDL ) - absence of - lipoprotein ( LDL ) - secondary to malnutrition, malabsorption, liver disease. Triglycerides Normal value: < 165mg/ dl The triglycerides may be ingested as food ( exogenous ) and transported by chylomicrons, or synthesized in the liver from fatty acids and transported by VLDL ( endogenous)

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Glucose and glucose tolerance tests

The determination of blood glucose concentration is the procedure performed in the diagnosis and monitoring of Diabetes mellitus. Diabetes mellitus is a metabolic disease, that is characterized by an elevation of fasting blood glucose, caused by a relative or absolute deficiency in insulin. Fasting blood glucose level is taken as a measure for hyperglycemia and hypoglycemia. Hyperglycemia is a condition in which, the fasting blood glucose level is above 120 mg/dl Causes of hyperglycemia: - Diabetes mellitus - Emotional stress. - Pancreatitis and pancreatic carcinoma. - Hyperactivity of thyroid gland and pituitary gland. - Hyperactivity of adrenal gland ( Cushing syndrome ). - Infectious disease. Hypoglycemia is a condition that is characterized by a fasting blood glucose level below 80 mg/ dl Causes of hypoglycemia: - Overdose of insulin. - Hypothyroidisim and hypopituitarism. - Hypoactivity of adrenal gland ( Addison's disease ) - Insulin secreting tumor of the pancreas. - Glycogen storage disease type I, due to deficiency of G-6-phosphatase. Types of diabetes mellitus: Type I: Insulin-dependent: in which progressive loss of pancreatic -cell function, development of hyperglycemia, ketoacidosis. It accounts for about 10% of diabetic patients. It is recognized by the appearance of polyuria, polydipsia, polyphagia, fatigue, weight loss, fasting blood glucose level > 140mg/ dl. Type II: Non-insulin-dependent: About 90% of the diabetic patients have type II, its occurrence is almost completely determined by genetic factors. It is characterized by decreased insulin secretion or insulin resistance ( body cells become insensitive to insulin produced by the pancreas ) It is developed gradually. Glucose tolerance test: It describes the ability of the body to deal with a carbohydrate load. It measures the concentration of glucose at time intervals after a standard glucose load. It is useful in the diagnosis of diabetes mellitus. - In diabetic patients, the fasting blood glucose level is greater than 140 mg/ dl and rises to above 200 mg/ dl following oral glucose administration.

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- In normal individuals, the fasting glucose level = 70-90 mg/ dl, rises to about 140 mg/ dl following glucose administration and returns to normal after 2 hours. Impaired glucose tolerance: patients with abnormalities of glucose tolerance test without hyperglycemia, it may present during pregnancy as a result of the secretion of placental hormones that antagonize insulin action, and in hyperactivity of thyroid, pituitary and adrenal glands. Measurement of glycolated proteins; The measurement of the concentration of glycolated proteins ( glycosylated Hb, glycosylated albumin and fucosamine) is taken as a function of the degree of hyperglycemia according to the half life of the protein. Glycosylated Hb, gives an integrated estimate of blood sugar over the approximately 3-month life span of the erythrocytes. Glycosylated Hb should be monitored every 3-6 months in stable patients, and every 6-12 weeks at the onset of therapy ( for unstable diabetics requiring changes in therapy and in cases of pregnancy complicated with diabetes ) until the patient is stabilized.

ORAL GLUCOSE TOLERANCE CURVE

Enzymes of diagnostic importance

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Enzymes play a vital role in catalyzing the biochemical reactions necessary for normal human growth, maturation and reproduction. Diagnostic enzymology involves the measurement of enzymes in body fluids for the diagnosis of disease. In most cases, serum or blood levels are the most useful, although urine, cerebrospinal and extracellular fluid levels are sometimes important. Certain tissue cells contain characteristic enzymes which enter the blood only when the cells to which they are confined are damaged or destroyed. Most of these enzymes are used for diagnostic purposes, and they have no direct physiologic role in the blood. Normally: the rate of the release of these enzymes in plasma = the rate of removal from plasma ( metabolism or excretion) High levels of these characteristic enzymes in the blood can indicate increased cellular turnover and tissue necrosis caused by disease. Determination of enzyme levels assists in differentiating e.g liver disease, heart attack from other conditions that may cause the same symptoms.

Liver diseases
Liver has a variety of enzymes that are used in diagnosis, transaminases, alkaline phosphatase (ALP), lactate dehydrogenase (LDH). - No enzyme markers are specific for any single liver disease. - Transaminases are important in the synthesis and breakdown of amino acids. - The transaminases are useful enzyme markers in acute hepatocellular injury, however, LDH is elevated secondary to hepatocellular necrosis. - Alkaline phosphatase is distributed in placenta, bone, kidney and liver, but most of ALP originates from bones and liver, so isoenzymes measurements is useful for differentiation between bone and liver disease.. - The most important transaminases are alanine aminotransferase ( ALT ), aspartate aminotransferase (AST). Normal values: ALT 3-26 IU/L at 37C AST 6-25 IU/L at 37C The level of transaminases elevated in cases of: - Acute liver failure ( hepatitis B, toxic hepatitis caused by solvents, metals, drugs ) - Chronic hepatitis ( liver fibrosis, cirrhosis ) - Liver cancer ( long standing hepatitis B, liver cirrhosis ) N.B in acute liver disorders ALT levels are higher relative to the levels of AST, as AST is located in mitochonria, so it needs more time to pass through mitochondrial membrane to reach the circulation, but in chronic cases, AST/ALT is > 1. - AST is also useful in skeletal muscle disorders and in acute myocardial infarction (AMI).

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- At the end stage of the disease, the levels of the enzymes return to normal or even subnormal as hepatocytes become depleted of enzyme content. The level of transaminases is decreased in: - Renal insufficiency. - Pregnancy. In cases of liver transplantation, new markers are used, e.g glutathione- S- transferase, which is used as an enzyme marker for early liver transplantation rejection.

Myocardial Diseases
Unstable Angina and Acute Myocardial infarction (AMI) - Formation of lipid-filled plaques will cause narrowing of coronary arteries. - Rupture of these plaques results in unstable angina and myocardial infarction - Prolonged deprivation of blood flow results in irreversible myocardial damage. - The damage results in release of enzymes and proteins into the circulation. - The presence of cardiac-specific enzymes provides the basis for the biochemical diagnosis of AMI. Enzymes useful in myocardial diseases: - Creatine kinase (CK) - Creatine kinase is useful in different disorders: skeletal muscle disorders, myocardial diseases, brain, colon and ileum disorders. - Creatine kinase exists in different isoenzymes, CK- MM, CK- MB, CK- BB Normal value: 10-50 IU/L at 30C. Creatine kinase is useful in early diagnosis of AMI. CK- MB is more specific than total CK. The early diagnosis is important in the management of AMI particularly if thrombolytic therapy is to be used. Levels of CK begin to rise 6-10 hours after onset of myocardial attack, peak appears at 18-24 hours, return to normal within 3 days. Lowered levels appear in cases of alcoholic liver disease and rheumatoid arthritis. - Lactate dehydrogenase (LDH) - Lactate dehydrogenase is useful for different several diseases involving blood, liver, kidney, skeletal muscles, in addition to myocardial infarction. Normal value: 55-140 IU/ L at 30C - Lactate dehydrogenase is useful in cases of patients with a 3-4 day history of chest pain as CK might have already returned to normal. - Lactate dehydrogenase clearance and appearance are delayed because LDH is larger than CK. - Lactate dehydrogenase rises 24-48 hours after heart attack, peak appears after 2-3 days and returns normal after 5-10 days. In addition to these enzymes, some proteins are useful as markers in AMI such as: myoglobin and troponin. - Myoglobin appears early in circulation and useful in early diagnosis of AMI because of its small size.

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- Troponins are the most efficient markers for the diagnosis of AMI because troponin has a higher tissue distribution in myocytes than CK-MB or myoglobin. - the early release of troponin is more specific as no false +ve results are observed in patients with skeletal muscle disease or injury. - Troponin level may remains increased for 7-10 days, in addition, troponin is highly sensitive that can detects minor myocardial injury.

Skeletal Muscles Disorders - Enzymes that are important in diagnosis of skeletal muscles disorders are:
Creatine kinase-MM and AST. - Acute release of muscle enzymes occurs in: - Surgery - Trauma - Excessive muscular contraction ( uncontrolled convulsion) - Muscular dystrophy e.g Duchenne disease. - The measurement of enzymes is useful in the diagnosis of muscle disorders and in case of Duchenne muscular dystrophy, for the detection of the carrier state in women.

Bone disorders
-Alkaline phosphatase is present in high concentration in growing bone, in bile and in placenta. - The range of alkaline phosphatase is dependent on age, and relates to different stages of bone growth. - Children have higher reference ranges than adults. - Older populations have increasing ALP reference ranges reflecting increases in the incidence of osteoporosis. - Normal value: 2.8-6.7 units in children 0.8-2.3 units in adults - It is elevated in: - Children ( normal growth of bone ) - Osteoblastic bone disease - Hyperparathyroidisim - neoplastic bone disease - Ricketes and osteomalacia - Hepatic disease resulting from drugs such as chlorpromazine and methyltestosterone. - Hepatic duct obstruction due to stone or neoplasm. - It is decreased in: - Hypothyroidism - Growth retardation in children.

Pancreatic Diseases
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The enzymes that are useful in pancreatic diseases are: Amylase & Lipase Amylase: this enzyme originates from the pancreas and the salivary gland. Normal value: 80-180 units/ dl Lipase: Originates only from the pancreas. Normal value: 0.2-1.5 units - In acute pancreatitis both amylase and lipase levels rise, however, the level of lipase persists for a longer period than amylase. - The extent of elevation is not strongly correlated to the severity of the disease. - The specificity for the diagnosis of acute pancreatitis is only 40% for amylase and 60% for lipase. - The specificity of amylase is low because of the existence of non-pancreatic source of the enzyme ( salivary amylase ). - So pancreatic amylase isoenzymes determination is helpful in differentiating pancreatic from salivary enzyme. - chronic pancreatitis is present in patients with acute pancreatitis together with other disease like diabetes mellitus. - In chronic pancreatitis, there is gradual degradation of the exocrine function, and so amylase and lipase levels are very often within the normal limits and may be actually be low during the end stages of the disease because of the small amount of functional pancreatic tissue. - Injury or obstruction of surrounding tissue such as perforate ulcer or peritonitis may cause compression of the pancreas resulting in enzyme release. - The level of amylase is also seen in patients with renal failure as it is cleared by glomerular filtration. Tissue Liver Myocardium Brain Skeletal muscle Colon Bone Pancreas Prostate Enzymes used in diagnosis ALT- AST- ALP- LDH LDH- CK-MB CK-BB AST- CK-MM CK-BB ALPCK Amylase- lipase Acid phosphatase

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