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Transcript of Clinical Laboratory Test-modified
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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:
1-Cells 2- Plasma
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
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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:
92%water 8% solids
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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 in men.
12-16g/dl blood in women.
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
455in females.Low values indicate anemia-.
High values indicate polycythemia-
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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.
After 2 hoursAfter 1 hourNormal
7-15mm3-5mmmale
12-17mm4-7mmfemale
-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.
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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 decreasedwater intake or with increased water losses ( sweating- diarrhea- vomiting- salt-losing syndrome-
diuresis).
- 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.
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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
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BILIRUBIN
Bilirubin is obtained from destruction of hemoglobin, conjugated in the liver to glucuronideand 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
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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 extracellularfluid 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
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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
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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 ureaElevated 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 ofGFR.
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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 male115 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 aresusceptible 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
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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 considered desirable
200- 239 mg/ dl border line- high blood cholesterol
> 240 mg/ dl high blood cholesterol level
HDL cholesterol< 35 mg/ dl 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 ofDiabetes 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 bygenetic 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 atthe 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 humangrowth, 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 ), aspartateaminotransferase (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, skeletalmuscles, 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 withskeletal 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 Enzymes used in diagnosis
Liver ALT- AST- ALP- LDH
Myocardium LDH- CK-MB
Brain CK-BB
Skeletal muscle AST- CK-MM
Colon CK-BBBone ALPCK
Pancreas Amylase- lipase
Prostate Acid phosphatase