Chemistry2009 Laboratory


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Chemistry2009 Laboratory

  1. 1. Chemistry Laboratory
  2. 2. <ul><li>It is often necessary to measure several blood chemicals to establish a pattern of abnormalities. </li></ul><ul><li>A wide range of tests can be grouped under the headings of enzymes, electrolytes, blood sugars, lipids, hormones, proteins, vitamins, minerals, and drug investigation. </li></ul>
  3. 3. General Biochemical Profiles <ul><li>Profiles are a group of select tests that screen for certain conditions </li></ul><ul><ul><li>Chemistry panels </li></ul></ul><ul><ul><li>Cardiac markers (MI) </li></ul></ul><ul><ul><li>Electrolyte panel </li></ul></ul>
  4. 4. <ul><li>Kidney functions, disease </li></ul><ul><ul><li>BUN, Phosphorus, LDH, Creatinine, creatinine clearance, total protein, A/G ratio, albumin, calcium, glucose, CO 2 </li></ul></ul><ul><li>Lipids (coronary risk) </li></ul><ul><ul><li>Cholesterol, triglycerides, HDL, lipoprotein electrophoresis (LDL, VLDL, HDL) </li></ul></ul>
  5. 5. <ul><li>Liver function, disease </li></ul><ul><ul><li>Total bilirubin, alkaline phosphatase, GGT, total protein, A/G ratio, albumin, AST, LDH, viral hepatitis panel, PT </li></ul></ul><ul><li>Thyroid function </li></ul><ul><ul><li>T 3 uptake, free T 4 , total T 4 , T 7 , FTI, TSH </li></ul></ul><ul><li>Basic metabolic screen </li></ul><ul><ul><li>Chloride, sodium, potassium, carbon dioxide, glucose, BUN, creatinine </li></ul></ul>
  6. 6. <ul><li>Syndrome X (metabolic syndrome) </li></ul><ul><ul><li>Blood lipid; glucose; cholesterol </li></ul></ul><ul><ul><li>Definition of metabolic syndrome includes three or more of the following: </li></ul></ul><ul><ul><ul><li>abdominal obesity (>40 inches in men and >35 inches in women); </li></ul></ul></ul><ul><ul><ul><li>HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women); </li></ul></ul></ul><ul><ul><ul><li>blood pressure >130/85 mmHg; </li></ul></ul></ul><ul><ul><ul><li>fasting glucose > 110 mg/dL </li></ul></ul></ul>
  7. 7. <ul><li>Acute Hepatitis Panel (ACUTE HEP) Hepatitis A, AB, IgM, hepatitis B core antibody, IgM, hepatitis B surface antigen, IgM, hepatitis C, AB 7-mL red-topped tube </li></ul><ul><li>Lipid Panel (LIPID PN) Cholesterol, HDL, triglycerides (LDL and CHO/HDL ratio included, as calculated values) </li></ul>
  8. 8. <ul><li>Sophisticated automated instrumentation </li></ul><ul><ul><li>makes it possible to conduct a wide variety of chemical tests </li></ul></ul><ul><ul><li>on a single sample of blood </li></ul></ul><ul><ul><li>and to report results in a timely manner. Numerical results may be reported with low, high, panic, toxic, or D (ie, fails Delta check) comments along with normal reference range. </li></ul></ul><ul><ul><li>Computerized interfaces allow direct transmission of results between laboratory and clinical settings. </li></ul></ul><ul><ul><li>Hard-copy” printouts can then become a permanent part of the health care record. </li></ul></ul>
  9. 9. Enzymes <ul><li>All known enzymes are proteins </li></ul><ul><li>Enzymes are simply biological catalysts , made (mostly) of protein </li></ul><ul><li>Many enzymes require the presence of other compounds - cofactors - before their catalytic activity can be exerted </li></ul><ul><li>This entire active complex is referred to as the holoenzyme; </li></ul><ul><li>i.e., apoenzyme (protein portion) </li></ul><ul><li>plus the cofactor (coenzyme, prosthetic group or metal-ion-activator) is called the holoenzyme. </li></ul><ul><li>Apoenzyme + Cofactor = Holoenzyme </li></ul>
  10. 10. Specificity of Enzymes <ul><li>One of the properties of enzymes that makes them so important as diagnostic and research tools is the specificity they exhibit relative to the reactions they catalyze. </li></ul><ul><li>A few enzymes exhibit absolute specificity; that is, they will catalyze only one particular reaction. </li></ul><ul><li>Other enzymes will be specific for a particular type of chemical bond or functional group. </li></ul>
  11. 11. <ul><li>In general, there are four distinct types of specificity: </li></ul><ul><ul><li>1. Absolute specificity - the enzyme will catalyze only one reaction. </li></ul></ul><ul><ul><li>2. Group specificity - the enzyme will act only on molecules that have specific functional groups, such as amino, phosphate and methyl groups. </li></ul></ul><ul><ul><li>3. Linkage specificity - the enzyme will act on a particular type of chemical bond regardless of the rest of the molecular structure. </li></ul></ul><ul><ul><li>4. Stereochemical specificity - the enzyme will act on a particular steric or optical isomer. </li></ul></ul>
  12. 12. <ul><li>Enzymes are classified based on what they do to their substrates, according to the Enzyme Commission (EC) classification </li></ul><ul><li>Oxidoreductases transfer electrons (often as hydride ions H−). </li></ul><ul><li>Transferases transfer chemical groups between molecules. </li></ul><ul><li>Hydrolases add or remove H2O from molecules. </li></ul><ul><li>Lyases manipulate double bonds by elimination reactions. </li></ul><ul><li>Isomerases transfer chemical groups within molecules. </li></ul><ul><li>Ligases condense C-{S/N/C/O} bonds using energy from ATP. </li></ul>
  13. 13. Enzyme Classification <ul><li>Addition or removal of water </li></ul><ul><ul><li>Hydrolases - these include esterases, carbohydrases, nucleases, deaminases, amidases, and proteases </li></ul></ul><ul><ul><li>Hydrases such as fumarase, enolase, aconitase and carbonic anhydrase </li></ul></ul><ul><li>Transfer of electrons </li></ul><ul><ul><li>Oxidases </li></ul></ul><ul><ul><li>Dehydrogenases </li></ul></ul><ul><li>Transfer of a radical </li></ul><ul><ul><li>Transglycosidases - of monosaccharides </li></ul></ul><ul><ul><li>Transphosphorylases and phosphomutases - of a phosphate group </li></ul></ul><ul><ul><li>Transaminases - of amino group </li></ul></ul><ul><ul><li>Transmethylases - of a methyl group </li></ul></ul><ul><ul><li>Transacetylases - of an acetyl group </li></ul></ul><ul><li>Splitting or forming a C-C bond </li></ul><ul><ul><li>Desmolases </li></ul></ul><ul><li>Changing geometry or structure of a molecule </li></ul><ul><ul><li>Isomerases </li></ul></ul><ul><li>Joining two molecules through hydrolysis of pyrophosphate bond in ATP or other tri-phosphate </li></ul><ul><ul><li>Ligases </li></ul></ul>
  14. 14. Enzyme Kinetics <ul><li>Enzymes are catalysts and increase the speed of a chemical reaction without themselves undergoing any permanent chemical change. </li></ul><ul><li>They are neither used up in the reaction nor do they appear as reaction products. </li></ul><ul><li>The basic enzymatic reaction can be represented as follows: </li></ul><ul><li>E + S ⇌ ES -> E + P </li></ul><ul><li>where E represents the enzyme catalyzing the reaction, S the substrate, the substance being changed, and P the product of the reaction </li></ul>
  15. 15. Aspartate Transaminase (Aminotransferase, AST); Serum Glutamic-Oxaloacetic Transaminase (SGOT) <ul><li>decreasing concentrations of AST found in the heart, liver, skeletal muscle, kidney, brain, pancreas, spleen, and lungs. </li></ul><ul><li>is released into the circulation following injury or death of cells. Any disease that causes change in these highly metabolic tissues will result in a rise in AST levels. </li></ul><ul><li>amount of AST in the blood is directly related to the number of damaged cells and the amount of time that passes between injury to the tissue and the test. </li></ul><ul><li>Following severe cell damage , the blood AST level will rise in 12 hours and remain elevated for about 5 days . </li></ul><ul><li>evaluate liver and heart disease. </li></ul>
  16. 16. <ul><li>AST Normal Values </li></ul><ul><li>Men: 14–20 U/L </li></ul><ul><li>Women: 10–36 U/L </li></ul><ul><li>Newborns: 47–150 U/L </li></ul><ul><li>Children: 9–80 U/L </li></ul>
  17. 17. Sample <ul><li>Obtain a 5-mL venous sample (red-topped tube). Serum is used. </li></ul><ul><li>Observe standard precautions. </li></ul><ul><li>Place specimen in a biohazard bag </li></ul><ul><li>Avoid hemolysis. </li></ul>
  18. 18. Clinical Implications AST <ul><li>  Increased AST levels occur in </li></ul><ul><ul><li>MI. </li></ul></ul><ul><ul><ul><li>In MI, may be increased to 4 to 10 times the normal </li></ul></ul></ul><ul><ul><ul><li>peak in 24 hours and returns to normal by post-MI day 3 to 7. </li></ul></ul></ul><ul><ul><ul><li>Secondary rises in AST levels suggest recurrence of MI. </li></ul></ul></ul><ul><ul><ul><li>liver diseases (10–100 times normal). </li></ul></ul></ul><ul><li> a.   Acute/chronic hepatitis (ALT > AST) </li></ul><ul><li>b.   Active cirrhosis (drug induced; alcohol induced: AST > ALT) </li></ul><ul><li> c.   Infectious mononucleosis </li></ul><ul><li> d.   Hepatic necrosis and metastasis </li></ul><ul><li> e.   Primary or metastatic carcinoma </li></ul><ul><li> f. Alcoholic hepatitis </li></ul>
  19. 19. <ul><li>Decreased AST levels occur in the following conditions: </li></ul><ul><li>a.   Azotemia </li></ul><ul><li>b.   Chronic renal dialysis </li></ul><ul><li>c.   Vitamin B 6 deficiency </li></ul>
  20. 20. Alanine Aminotransferase (Aminotransferase, ALT); Serum Glutamic-Pyruvic Transaminase (SGPT) <ul><li>High concentration in liver, and low in heart, muscle, and kidney. </li></ul><ul><li>primarily used to diagnose liver disease </li></ul><ul><li>monitor treatment for hepatitis </li></ul><ul><li>more sensitive in the detection of liver disease than in biliary obstruction. </li></ul><ul><li>ALT also differentiates between hemolytic jaundice and jaundice due to liver disease. </li></ul>
  21. 21. <ul><li>Normal </li></ul><ul><li>Adults: </li></ul><ul><ul><li>Males: 10–40 U/L </li></ul></ul><ul><ul><li>Females: 7–35 U/L   </li></ul></ul><ul><ul><li>Newborns: 13–45 U/L </li></ul></ul><ul><li>ALT values slightly higher in males and black persons. </li></ul>
  22. 22. <ul><li>Increased ALT levels </li></ul><ul><li>Hepatocellular disease (moderate to high increase) </li></ul><ul><li>Alcoholic cirrhosis (mild increase) </li></ul><ul><li>Metastatic liver tumor (mild increase) </li></ul><ul><li>Obstructive jaundice or biliary obstruction (mild increase) </li></ul><ul><li>Viral, infectious, or toxic hepatitis (30–50 times normal) </li></ul><ul><li>Infectious mononucleosis </li></ul><ul><li>Pancreatitis (mild increase) </li></ul><ul><li>Myocardial infarction, heart failure </li></ul><ul><li>Polymyositis </li></ul><ul><li>Severe burns </li></ul><ul><li>Trauma to striated muscle </li></ul><ul><li>Severe shock </li></ul>
  23. 23. <ul><li>AST/ALT comparison: </li></ul><ul><ul><li>AST level is always increased in acute MI, </li></ul></ul><ul><ul><li>ALT level does not always increase unless there is also liver damage. </li></ul></ul><ul><ul><li>ALT is increased more than AST in acute extrahepatic biliary obstruction. </li></ul></ul><ul><ul><li>ALT more specific than AST for liver disease </li></ul></ul><ul><ul><li>AST is more sensitive to alcoholic liver disease. </li></ul></ul>
  24. 24. Alkaline Phosphatase (ALP) <ul><li>enzyme originating mainly in bone, liver, and placenta, </li></ul><ul><li>functions best at a pH of 9. </li></ul><ul><li>levels are age and gender dependent. </li></ul><ul><ul><li>Postpuberty ALP is mainly of liver origin. </li></ul></ul><ul><li>used as an index of liver and bone disease </li></ul><ul><ul><li>when correlated with other clinical findings. </li></ul></ul><ul><li>In bone disease, </li></ul><ul><ul><li>level rises in proportion to osteoblastic activity and the deposit of calcium in the bones. </li></ul></ul><ul><li>In liver disease, </li></ul><ul><ul><li>level rises when excretion is impaired as a result of obstruction in the biliary tract. </li></ul></ul><ul><ul><li>Used alone, alkaline phosphatase may be misleading </li></ul></ul>
  25. 25. <ul><li>Elevated levels of ALP in liver disease (correlated with abnormal liver function tests) occur in the following conditions: </li></ul><ul><ul><li>Obstructive jaundice (gallstones obstructing major biliary ducts; accompanying elevated bilirubin) </li></ul></ul><ul><ul><li>Space-occupying lesions of the liver such as cancer (hepatic carcinoma) and malignancy with liver metastasis </li></ul></ul><ul><ul><li>Hepatocellular cirrhosis </li></ul></ul><ul><ul><li>Biliary cirrhosis </li></ul></ul><ul><ul><li>Intrahepatic and extrahepatic cholestasis </li></ul></ul><ul><ul><li>  Hepatitis, infectious mononucleosis, cytomegalovirus </li></ul></ul><ul><ul><li>Diabetes mellitus (causes increased synthesis), diabetic hepatic lipidosis </li></ul></ul><ul><ul><li>Chronic alcohol ingestion </li></ul></ul>
  26. 26. <ul><li>  Bone disease and elevated ALP levels occur in the following conditions: </li></ul><ul><ul><li>Paget’s disease (osteitis deformans; levels 10 to 25 times normal) </li></ul></ul><ul><ul><li>Metastatic bone tumor </li></ul></ul><ul><ul><li>Osteogenic sarcoma </li></ul></ul><ul><ul><li>Osteomalacia (elevated levels help differentiate between osteomalacia and osteoporosis, in which there is no elevation) </li></ul></ul>
  27. 27. <ul><li>  Other diseases involving elevated ALP levels include the following: </li></ul><ul><li>Hyperparathyroidism (accompanied by hypercalcemia), hyperthyroidism </li></ul><ul><li>Pulmonary and myocardial infarctions </li></ul><ul><li>Hodgkin’s disease </li></ul><ul><li>Cancer of lung or pancreas </li></ul><ul><li>Ulcerative colitis, peptic ulcer </li></ul><ul><li>Sarcoidosis </li></ul><ul><li>Perforation of bowel (acute infarction) </li></ul>
  28. 28. Interfering Factors <ul><li>Physiologically high levels of ALP </li></ul><ul><ul><li>Young children, pregnant women, and postmenopausal women have; slightly increased in older persons. </li></ul></ul><ul><ul><li>After IV administration of albumin, there is sometimes a marked increase in ALP for several days. </li></ul></ul><ul><ul><li>  ALP levels increase at room temperature and in refrigerated storage. Testing should be done the same day. </li></ul></ul><ul><ul><li>ALP levels decrease if blood is anticoagulated </li></ul></ul><ul><ul><li>ALP levels increase after fatty meals.(fasting specimen) </li></ul></ul>
  29. 29. Gamma Glutamyltransferase (gamma-Glutamyl Transpeptidase, GGT, GT) <ul><li>present mainly in the liver, kidney, and pancreas. </li></ul><ul><li>kidney has the highest level of this enzyme,but the liver is considered the source of normal serum activity. </li></ul><ul><li>GT has no origin in bone or placenta. </li></ul>
  30. 30. GGT, GT <ul><li>used to determine liver cell dysfunction and to detect alcohol-induced liver disease. </li></ul><ul><li>very sensitive to the amount of alcohol consumed </li></ul><ul><ul><li>monitor cessation or reduction of alcohol consumption </li></ul></ul><ul><li>activity is elevated in all forms of liver disease. </li></ul><ul><li>much more sensitive than either the AP, SGOT, SGPT in detecting obstructive jaundice, cholangitis, and cholecystitis. </li></ul>
  31. 31. <ul><li>Normal </li></ul><ul><li>Men: 7–47 U/L </li></ul><ul><li>Women: 5–25 U/L </li></ul><ul><li>Values are higher in newborns and in the first 3–6 months. </li></ul><ul><li>Values in adult males are 25% higher than in females. </li></ul><ul><li>Serum is used. </li></ul>
  32. 32. <ul><li>Increased GT levels associated with Liver diseases </li></ul><ul><ul><ul><li>  Hepatitis (acute and chronic) </li></ul></ul></ul><ul><ul><ul><li>Cirrhosis (obstructive and familial) </li></ul></ul></ul><ul><ul><ul><li>Liver metastasis and carcinoma </li></ul></ul></ul><ul><ul><ul><li>Cholestasis (especially during or following pregnancy) </li></ul></ul></ul><ul><ul><ul><li>Chronic alcoholic liver disease </li></ul></ul></ul><ul><ul><ul><li>Infectious mononucleosis </li></ul></ul></ul>
  33. 33. <ul><li>GT levels are also increased in the following conditions: </li></ul><ul><ul><li>Pancreatitis </li></ul></ul><ul><ul><li>Carcinoma of prostate </li></ul></ul><ul><ul><li>Carcinoma of breast and lung </li></ul></ul><ul><ul><li>Systemic lupus erythematosu </li></ul></ul><ul><ul><li>Glycogen storage disease </li></ul></ul>
  34. 34. <ul><li>In MI, GT is usually normal. </li></ul><ul><ul><ul><li>if increased, it occurs about 4 days after MI and probably implies liver damage secondary to cardiac insufficiency. </li></ul></ul></ul><ul><li>Increased in Hyperthyroidism,d ecreased in hypothyroidism. </li></ul><ul><li>GT values are normal in: </li></ul><ul><ul><ul><li>bone disorders, </li></ul></ul></ul><ul><ul><ul><li>bone growth, </li></ul></ul></ul><ul><ul><ul><li>pregnancy, </li></ul></ul></ul><ul><ul><ul><li>skeletal muscle disease, </li></ul></ul></ul><ul><ul><ul><li>strenuous exercise, </li></ul></ul></ul><ul><ul><ul><li>renal failure. </li></ul></ul></ul><ul><ul><ul><li>Children and adolescents </li></ul></ul></ul>
  35. 35. GGT <ul><li>Interpret test results and monitor as appropriate for liver, pancreatic, or thyroid disease and cancer recurrence. </li></ul>
  36. 36. Lactate Dehydrogenase (LD, LDH) <ul><li>intracellular enzyme, widely distributed in the tissues of the body: </li></ul><ul><ul><li>kidney, heart, skeletal muscle, brain, liver, and lungs. </li></ul></ul><ul><li>Increases indicate cellular death and leakage of the enzyme from the cell. </li></ul>
  37. 37. Lactate Dehydrogenase (LD, LDH) <ul><li>elevated levels of LDH are nonspecific, </li></ul><ul><li>useful in confirming pulmonary infarction </li></ul><ul><li>also helpful in the differential diagnosis of muscular dystrophy and pernicious anemia </li></ul><ul><li>More specific findings by breaking down the LDH into its five isoenzymes. (When LD values are reported or quoted, total LDH is meant.) </li></ul>
  38. 38. Normal <ul><li>Newborn: 160–450 U/L </li></ul><ul><li>•   Children: 60–170 U/L </li></ul><ul><li>•   Adults: 140–280 U/L </li></ul><ul><li>Serum is used. </li></ul><ul><li>Avoid hemolysis in obtaining blood sample. </li></ul>
  39. 39. Increased LDH (LD) <ul><li>  High levels within 36 to 55 hours after MI and continue longer than elevations of SGOT or CPK (3–10 days). Differential diagnosis of acute MI may be accomplished without LDH isoenzymes. </li></ul><ul><li>In pulmonary infarction, within 24 hours of pain onset. The pattern of normal SGOT and elevated LDH that levels off 1 to 2 days after an episode of chest pain is indicative of pulmonary infarction. </li></ul>
  40. 40. <ul><li>Elevated levels of LDH are also observed: </li></ul><ul><li>Congestive heart failure </li></ul><ul><li>Liver diseases (eg, cirrhosis, alcoholism, acute viral hepatitis) </li></ul><ul><li>Malignant neoplasms, cancer, leukemias, lymphoma </li></ul><ul><li>Hypothyroidism </li></ul><ul><li>Lung diseases </li></ul><ul><li>Skeletal muscle diseases (muscular dystrophy), muscular damage </li></ul><ul><li>Megaloblastic and pernicious anemias, hemolytic anemia, sickle cell disease </li></ul><ul><li>Delirium tremens, seizures </li></ul><ul><li>Shock, hypoxia, hypotension </li></ul><ul><li>Hyperthermia </li></ul><ul><li>Renal infarct </li></ul><ul><li>CNS diseases </li></ul><ul><li>Acute pancreatitis </li></ul><ul><li>Fractures, other trauma including head injury </li></ul>
  41. 41. Interfering Factors <ul><li>Note: Decreased LDH levels are associated with a good response to cancer therapy. </li></ul><ul><li>Strenuous exercise and the muscular exertion involved in childbirth cause increased LDH levels. </li></ul><ul><li>Skin diseases can cause falsely increased LDH levels. </li></ul><ul><li>Hemolysis of red blood cells due to freezing, heating, or shaking the blood sample will cause falsely increased LDH levels </li></ul>
  42. 42. <ul><li>Clinical Alert LDH is found in nearly every tissue of the body; therefore, elevated levels are of limited diagnostic value by themselves. Differential diagnoses may be accomplished with LD isoenzyme determination. </li></ul>
  43. 43. (LDH, LD) Isoenzymes (Electrophoresis) <ul><li>The origins of the LDH isoenzymes are as follow: </li></ul><ul><li>LD 1 and LD 2 are present in cardiac tissue and erythrocytes; </li></ul><ul><li>LD 3 originates mainly from lung, spleen, pancreas, and placenta; </li></ul><ul><li>and LD 4 and LD 5 originate from skeletal muscle and liver. </li></ul>
  44. 44. <ul><li>The five isoenzyme fractions of LDH show different patterns in various disorders. </li></ul><ul><li>Abnormalities in the pattern suggest which tissues have been damaged. </li></ul><ul><li>This test is useful in the differential diagnosis of </li></ul><ul><ul><ul><li>acute MI, </li></ul></ul></ul><ul><ul><ul><li>megaloblastic anemia (eg, folate deficiency, pernicious anemia), </li></ul></ul></ul><ul><ul><ul><li>hemolytic anemia </li></ul></ul></ul><ul><ul><li>These entities are characterized by LD 1 increases, often with LD 1 :LD 2 inversion (flip). </li></ul></ul>
  45. 45. <ul><li>Normal </li></ul><ul><li>LD 1 : 17%–27% of total or 0.17–0.27 </li></ul><ul><li>LD 2 : 29%–39% of total or 0.29–0.39 </li></ul><ul><li>LD 3 : 19%–27% of total or 0.19–0.27 </li></ul><ul><li> LD 4 : 8%–16% of total or 0.08–0.16 </li></ul><ul><li> LD 5 : 6%–16% of total or 0.06–0.16 </li></ul>
  46. 46. <ul><li>Obtain a 5-mL venous blood sample (red-topped tube). Serum is needed. </li></ul><ul><li>2.   Avoid hemolysis. </li></ul><ul><li>3.   Observe standard precautions. Place specimen in a biohazard bag. </li></ul><ul><li>Be aware that serial determinations may be ordered (3 consecutive days). </li></ul>Clinical Alert LDH isoenzymes should be interpreted in light of clinical findings.
  47. 47. <ul><li>Disease LD 1 LD 2 LD 3 LD 4 LD 5 </li></ul><ul><li>Myocardial infarction X X       </li></ul><ul><li>Pulmonary infarction       X X </li></ul><ul><li>Congestive heart failure       X X </li></ul><ul><li>Viral hepatitis       X X </li></ul><ul><li>Toxic hepatitis       X X Leukemia,granulocytic   X X     </li></ul><ul><li>Pancreatitis   X X     </li></ul><ul><li>Carcinomatosis (extensive)   X X     </li></ul><ul><li>Megaloblastic anemia X X       </li></ul><ul><li>Hemolytic anemia X X       </li></ul><ul><li>Muscular dystrophy X X       </li></ul>
  48. 48. Cardiac Troponin T (cTnT); Troponin I (cTnI) <ul><li>unique to the heart muscle and is highly concentrated in cardiomyocytes. </li></ul><ul><li>high degree of cardiac specificity. </li></ul><ul><li>released with very small areas of myocardial damage </li></ul><ul><li>as early as 1 to 3 hours after injury, </li></ul><ul><li>levels return to normal within 5 to 7 days. </li></ul>
  49. 49. <ul><li>Troponin I remains increased longer than CK-MB and is more cardiac specific. </li></ul><ul><li>Troponin T is more sensitive but less specific, being positive with angina at rest. </li></ul><ul><li>the most important addition to the clinical assessment of cardiac injury. </li></ul><ul><li>Cardiac troponin is the preferred test to diagnose MI. </li></ul>
  50. 50. <ul><li>used in the early diagnosis of small myocardial infarcts that are undetectable by conventional diagnostic methods. </li></ul><ul><li>also used later in the course of MI because they remain elevated for 5 to 7 days after injury. </li></ul><ul><li>serial sampling 0, 4, 8, and 12 hours after chest pains may be ordered to rule out acute MI. </li></ul>
  51. 51. Cardiac Markers markers Initial Elevation Time of peak Back to Nl CK-MB 4-8 hr 12-24 hr 72-96 hr Myoglobin 2-4 hr 8-10 hr 24 hr Troponin I 4-6 hr 12 h 3-10 days
  52. 52. <ul><li>Normal </li></ul><ul><li>Negative (Qualitative) </li></ul><ul><li>Troponin I: <0.35 ng/mL </li></ul><ul><li>Total CK: 0–120 ng/mL </li></ul><ul><li>CK-MB: 0–3 ng/mL </li></ul><ul><li>Myoglobin: <55 ng/mL </li></ul><ul><li>Troponin: <0.4 ng/mL </li></ul>
  53. 53. <ul><li>Positive or elevated cardiac troponin I levels indicate: </li></ul><ul><li>Small infarcts; increases remain for 5 to 7 days. </li></ul><ul><li>Myocardial injury during surgery </li></ul>
  54. 54. Interfering Factors <ul><li>Cardiac troponin I levels may be increased in chronic muscle or renal disease and trauma. </li></ul><ul><li>Levels are not affected by orthopedic or lung surgery. </li></ul>
  55. 55. Creatine Phosphokinase (CPK); Creatine Kinase (CK); CPK and CK Isoenzymes <ul><li>higher concentrations in heart and skeletal muscles </li></ul><ul><li>smaller brain tissue. </li></ul><ul><li>used as a specific index of injury to myocardium and muscle. </li></ul><ul><li>three isoenzymes: MM, BB, and MB </li></ul><ul><li>Skeletal muscle contains primarily MM; </li></ul><ul><li>cardiac muscle contains primarily MM and MB; </li></ul><ul><li>and brain tissue, GI system, and genitourinary tract contain primarily BB. </li></ul><ul><li>Normal CK levels are virtually 100% MM isoenzyme. </li></ul><ul><li>A slight increase in total CPK is reflected from elevated BB from CNS injury. </li></ul><ul><li>CPK isoenzyme studies help distinguish whether the CPK originated from the heart (MB) or the skeletal muscle (MM). </li></ul>
  56. 56. The CK (CPK) test <ul><li>used in the diagnosis of MI </li></ul><ul><li>reliable measure of skeletal and inflammatory muscle diseases. </li></ul><ul><li>helpful in recognizing muscular dystrophy before clinical signs appear. </li></ul><ul><li>CK levels may rise significantly with CNS disorders such as Reye’s syndrome. </li></ul><ul><li>CK isoenzymes may be helpful in making a differential diagnosis. </li></ul><ul><li>Elevation of MB, the cardiac isoenzyme, provides a more definitive indication of myocardial cell damage than total CK alone. </li></ul><ul><li>MM isoenzyme is an indicator of skeletal muscle damage. </li></ul>
  57. 57. CPK <ul><li>Normal </li></ul><ul><li>Men: 38–174 U/L </li></ul><ul><li>Women: 26–140 U/L </li></ul><ul><li>Infants: 2–3 times adult values </li></ul>
  58. 58.   Increased CK/CPK levels occur in the following <ul><li>Acute MI </li></ul><ul><li>Severe myocarditis </li></ul><ul><li>After open heart surgery </li></ul><ul><li>Cardioversion (cardiac defibrillation) </li></ul><ul><li>Myocarditis </li></ul>
  59. 59. Other diseases and procedures that cause increased CK/CPK levels include the following: <ul><li>Acute cerebrovascular disease </li></ul><ul><li>  Progressive muscular dystrophy (levels may reach 20–200 times normal), Duchenne’s muscular dystrophy, female carriers of muscular dystrophy </li></ul><ul><li>Dermatomyositis and polymyositis </li></ul><ul><li>Delirium tremens and chronic alcoholism </li></ul><ul><li>Electric shock, electromyography </li></ul><ul><li>Malignant hyperthermia </li></ul><ul><li>Reye’s syndrome </li></ul><ul><li>Convulsions, ischemia, or subarachnoid hemorrhage </li></ul><ul><li>Last weeks of pregnancy and during childbirth </li></ul><ul><li>Hypothyroidism </li></ul><ul><li>Acute psychosis </li></ul><ul><li>CNS trauma, extensive brain infarction </li></ul><ul><li>Neoplasms of prostate, bladder, or GI tract </li></ul><ul><li>Rhabdomyolysis with cocaine intoxication </li></ul>
  60. 60. Elevated MB (CK 2 ) isoenzyme levels occur in the following conditions: <ul><li>Myocardial infarct </li></ul><ul><li>Myocardial ischemia, </li></ul><ul><li>angina pectoris </li></ul><ul><li>Duchenne’s muscular dystrophy </li></ul><ul><li>Subarachnoid hemorrhage </li></ul><ul><li>Reye’s syndrome </li></ul><ul><li>Muscle trauma, surgery (postoperative) </li></ul><ul><li>Circulatory failure and shock </li></ul><ul><li>Infections of heart—myocarditis </li></ul><ul><li>Chronic renal failure </li></ul><ul><li>Malignant hyperthermia, hypothermia </li></ul><ul><li>CO poisoning </li></ul><ul><li>Polymyositis </li></ul><ul><li>Myoglobulinemia </li></ul>
  61. 61. Interfering Factors <ul><li>Strenuous exercise, weight lifting, and surgical procedures that damage skeletal muscle may cause increased levels   </li></ul><ul><li>Alcohol and other drugs of abuse increase CK levels. </li></ul><ul><li>Athletes have a higher CK value because of greater muscle mass </li></ul><ul><li>Multiple IM injections may cause increased Many drugs may cause increased CK levels </li></ul><ul><li>Childbirth may cause increased CK levels. </li></ul><ul><li>  Hemolysis of blood sample causes increased CK levels. </li></ul>
  62. 62. Angiotensin-Converting Enzyme (ACE) <ul><li>catalyzes the conversion of angiotensin I to the vasoactive peptide angiotensin II. </li></ul><ul><li>Angiotensin I is concentrated in the proximal tubules. </li></ul><ul><li>This test is used primarily to evaluate the severity and activity of sarcoidosis. </li></ul><ul><li>Serial determinations may be helpful in following the clinical course of the disease with steroid treatment. </li></ul><ul><li>It is also used in the investigation of Gaucher’s disease. </li></ul>
  63. 63. <ul><li>ACE: 8–53 U/L </li></ul><ul><li>Obtain a 5-mL venous blood sample (red-topped tube). Serum or heparinized plasma is used. </li></ul><ul><li>  Freeze specimen if test is not performed immediately. </li></ul>
  64. 64. Increased ACE levels <ul><li>Sarcoidosis </li></ul><ul><li>Gaucher’s disease </li></ul><ul><li>Leprosy </li></ul><ul><li>Acute and chronic bronchitis </li></ul><ul><li>Connective tissue diseases </li></ul><ul><li>Amyloidosis </li></ul><ul><li>Pulmonary fibrosis </li></ul><ul><li>Fungal diseases and histoplasmosis </li></ul><ul><li>Untreated hyperthyroidism </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Psoriasis </li></ul>
  65. 65. Interfering Factors <ul><li>This test should not be done in persons <20 years of age because they normally have a very high level of ACE. </li></ul><ul><li>About 5% of the normal adult population has elevated ACE levels. </li></ul><ul><li>ACE is inhibited by EDTA anticoagulant. </li></ul><ul><li>Some antihypertensives may cause low ACE values. </li></ul>
  66. 66. Amylase <ul><li>enzyme that changes starch to sugar, </li></ul><ul><li>is produced in the salivary (parotid) glands and pancreas; </li></ul><ul><li>much lower activities are present in the ovaries, intestines, and skeletal muscle. </li></ul><ul><li>If there is an inflammation of the pancreas or salivary glands, much amylase enters the blood. </li></ul>
  67. 67. Lipase <ul><li>glycoprotein that changes fats to fatty acids and glycerol. </li></ul><ul><li>The pancreas is the major source of this enzyme. </li></ul><ul><li>Lipase appears in the blood following pancreatic damage at the same time amylase appears (or slightly later) </li></ul><ul><li>but remains elevated much longer than amylase (7 to 10 days). </li></ul>
  68. 68. <ul><li>Amylase and lipase </li></ul><ul><ul><li>tests are used to diagnose and monitor </li></ul></ul><ul><ul><ul><li>treatment of acute pancreatitis </li></ul></ul></ul><ul><ul><ul><li>and to differentiate pancreatitis from other acute abdominal disorders </li></ul></ul></ul><ul><ul><li>(80% of patients with acute pancreatitis will have elevated amylase and lipase levels; </li></ul></ul><ul><li>Lipase assay provides better sensitivity and specificity </li></ul>
  69. 69. <ul><li>Normal </li></ul><ul><ul><li>Amylase </li></ul></ul><ul><li>•   Newborns: 6–65 U/L </li></ul><ul><li>•   Adults: 25–125 U/L </li></ul><ul><li>•   Elderly persons (>60 years): 24–151 U/L </li></ul><ul><ul><li>Lipase </li></ul></ul><ul><li>•   Adults: 10–140 U/L </li></ul><ul><li>•   Elderly persons (>60 years): 18–180 U/L </li></ul>Children up to 2 years of age have virtually no pancreatic amylase .
  70. 70. <ul><li>Obtain a 5-mL venous blood sample (red-topped tube). Serum is used. (EDTA, citrate, and oxalate anticoagulant interfere with lipase testing.) </li></ul>
  71. 71. Clinical Implications <ul><li>Greatly increased amylase levels occur in acute pancreatitis early in the course of the disease. </li></ul><ul><ul><ul><li>The increase begins in 3 to 6 hours after the onset of pain. </li></ul></ul></ul><ul><li>Increased amylase levels also occur in the following conditions: </li></ul><ul><ul><li>Chronic pancreatitis, </li></ul></ul><ul><ul><li>pancreatic trauma, </li></ul></ul><ul><ul><li>pancreatic carcinoma, obstruction of pancreatic duct </li></ul></ul><ul><ul><li>Partial gastrectomy </li></ul></ul><ul><ul><li>Acute appendicitis, peritonitis </li></ul></ul><ul><ul><li>Perforated peptic ulcer </li></ul></ul><ul><ul><li>Cerebral trauma, shock </li></ul></ul><ul><ul><li>Obstruction or inflammation of salivary duct or gland and mumps </li></ul></ul><ul><ul><li>Intestinal obstruction with strangulation </li></ul></ul><ul><ul><li>Ruptured tubal pregnancy and ectopic pregnancy </li></ul></ul><ul><ul><li>Ruptured aortic aneurysm </li></ul></ul><ul><ul><li>Macroamylasemia </li></ul></ul>
  72. 72. Decreased amylase levels <ul><li>Pancreatic insufficiency </li></ul><ul><li>Hepatitis, severe liver disease </li></ul><ul><li>Advanced cystic fibrosis </li></ul><ul><li>Pancreatectomy </li></ul>
  73. 73. Elevated lipase levels <ul><li>occur in pancreatic disorders </li></ul><ul><ul><li>(eg, pancreatitis, alcoholic and nonalcoholic; pancreatic carcinoma). </li></ul></ul><ul><li>  Increased lipase values also are associated with the following conditions: </li></ul><ul><ul><ul><li>Cholecystitis </li></ul></ul></ul><ul><ul><ul><li>Hemodialysis </li></ul></ul></ul><ul><ul><ul><li>Strangulated or infarcted bowel </li></ul></ul></ul><ul><ul><ul><li>Peritonitis e.   </li></ul></ul></ul><ul><ul><ul><li>Primary biliary cirrhosis </li></ul></ul></ul><ul><ul><ul><li>Chronic renal failure </li></ul></ul></ul>
  74. 74. <ul><li>Serum lipase levels are normal in patients with elevated amylase who have : </li></ul><ul><ul><li>peptic ulcer, </li></ul></ul><ul><ul><li>salivary adenitis, </li></ul></ul><ul><ul><li>inflammatory bowel disease, </li></ul></ul><ul><ul><li>intestinal obstruction </li></ul></ul>
  75. 75. Interfering Factors <ul><li>Amylase  </li></ul><ul><li>Anticoagulated blood gives lower results. Do not use EDTA, citrate, or oxalate. </li></ul><ul><li>Lipemic serum interferes with test. </li></ul><ul><li>Increased levels are found in alcoholic patients and pregnant women and in diabetic ketoacidosis. </li></ul><ul><li>Many drugs can interfere with this test </li></ul>
  76. 76. Interfering Factors <ul><li>Lipase </li></ul><ul><li>  EDTA anticoagulant interferes with test. </li></ul><ul><li>  Lipase is increased in about 50% of patients with chronic renal failure </li></ul><ul><li>Lipase increases in patients undergoing hemodialysis. </li></ul><ul><li>Many drugs can affect outcomes. </li></ul>
  77. 77. Homocysteine (tHcy) <ul><li>Amino acid resulting from the synthesis of cysteine from methionine and enzyme reaction of cobalamin and folate. </li></ul>
  78. 78. homocystinemia associated with <ul><li>-Increased risk for vascular disease </li></ul><ul><li>-Increased risk for venous thrombosis </li></ul><ul><li>-has a direct toxic effect on endothelium </li></ul><ul><li>-Elevated in folic acid deficiency and B 12 deficiency </li></ul><ul><li>-Increased risk for pregnancy complications and neural tube defects </li></ul>
  79. 79. <ul><li>This test measures the blood plasma level of homocysteine. </li></ul><ul><li>It is useful </li></ul><ul><ul><li>diagnosing individuals with potential increased risk factors for coronary artery disease and thromboses, </li></ul></ul><ul><ul><li>providing a functional assay for folic acid deficiency, </li></ul></ul><ul><ul><li>diagnosing homocystinemia. Homocysteine is retained by persons with reduced renal function. </li></ul></ul>
  80. 80. Clinical Implications <ul><li>Increased or elevated homocysteine levels occur in the following conditions: </li></ul><ul><ul><li>Folic acid deficiency </li></ul></ul><ul><ul><li>Abnormal vitamin B 12 metabolism and deficiency </li></ul></ul><ul><ul><li>Homocystinuria </li></ul></ul>
  81. 81. <ul><li>The End </li></ul>