Diagnostic importance of enzymes.pptx

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1. ENZYMES OF DIAGNOSTIC IMPORTANCE IN Liver Disease Myocardial infarction Bone disease Muscle disease Prostate Cancer

2. Specific Learning Objectives At the end of the lecture, student should be able to: Define enzymes Explain enzymes of diagnostic importance in liver disease

3. Introduction Enzymes are biocatalysts – the catalysts of life. A catalyst is defined as a substance that increases the velocity or rate of a chemical reaction without itself undergoing any change in the overall process .

4. Liver Diseases It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases:  Diseases caused by viruses, such as hepatitis A, hepatitis B, hepatitis C. Diseases caused by drugs, poisons, or too much alcohol .

5. ALT(alanine aminotransferase ) The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. This test to find out if a disease, drug, or injury has damaged liver. Liver does a lot of important things for human It makes a fluid called bile that helps the body digest food.

6. According to the American College of Gastroenterology, the normal value for ALT in blood for people without risk factors for liver disease ranges from  29 to 33 international units per liter (IU/L) for males and 19 to 25 IU/L for females .

7. Aspartate aminotransferase (AST ) An AST test measures the level of aspartate aminotransferase in your blood. AST is an enzyme that is normally present in the liver, heart, brain, pancreas, kidneys, and many other muscles and tissues in the body. Enzymes like AST help facilitate fundamental biological processes in these organs

8. Alkaline phosphatase  (ALP) Alkaline phosphatase is a protein found in all body tissues. Tissues with higher amounts of ALP include the liver, bile ducts, and bone. A blood test can be done to measure the level of ALP. A related test is the ALP isoenzyme test

9. A gamma- glutamyl transferase (GGT) A gamma- glutamyl transferase (GGT) test measures the amount of GGT in the blood. GGT is an enzyme found throughout the body, but it is mostly found in the liver. When the liver is damaged, GGT may leak into the bloodstream.

10. Cont.. High levels of GGT in the blood may be a sign of liver disease or damage to the bile ducts. Bile ducts are tubes that carry bile in and out of the liver. Bile is a fluid made by the liver. It is important for digestion .

11. Conti.. It is used for A GGT test is most often used to: Help diagnose liver disease Figure out if liver damage is due to liver disease or a bone disorder Check for blockages in the bile ducts Screen for or monitor alcohol use disorder

12. Conti.. GGT test may need if Patient have symptoms of liver disease. Symptoms include:

13. Conti.. If results show higher than normal levels of GGT, it may be a sign of liver damage. The damage may be due to one of the following conditions:

14. Enzyme literally commits suicide Also called mechanism base inactivation Normal enzyme reaction mechanism is used to inactivate the enzyme They inhibitors act as drugs – e.g. aspirin, penicillin, disulfiram Conti..

15. Introduction Creatine kinase (CK) is an enzyme that's found in your skeletal muscle, heart muscle and brain. When any of these tissues are damaged, they leak creatine kinase into your bloodstream. Elevated CK levels may indicate muscle injury or disease.  Creatine kinase (CK)

16. Conti.. Creatine kinase (CK) and its isoenzyme CK-MB are important tools for the diagnosis of acute myocardial infarction. The content of CK-MB relative to total CK in myocardial cells is variable; it is low in normal myocardium and increased several-fold in hypoxic myocardium.

17. DEFINITION Creatine kinase is an important enzyme in such tissues. Clinically, creatine kinase is assayed in blood tests as a marker of damage of CK-rich tissue such as in myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy, autoimmune myositides , and acute kidney injury.

18. Conti.. CK is present in large amounts in both skeletal muscle as well as heart muscle and also found in brain It lacks specificity as cardiac marker due to increased level in trauma or post-surgery patients CK enzyme is formed from 2 dimers M & B (each weighs 40kDa) and forms 3 isoforms 1. CK-MM 2. CK-MB 3. CK-BB CK-MB is of major concern in MI 

19. Conti.. Rises at about 3-4 hrs after MI, peaks in 10-24 hrs and returns to normal within 72 hrs. CK-MB isoenzyme is quickly and easily measured and is widely available it was the gold standard cardiac biomarker until the discovery of the more specific and sensitive cardiac troponin

20. Conti.. coexisting skeletal muscle injury (including exercise and rhabdomyolysis ) can reduce the specificity of CK-MB. CK-MB is outperformed in specificity by contemporary cTn assays, and the newer more sensitive cTn assays are likely to take over any remaining clinical utility or CK-MB.

21. Heart-type fatty acid binding protein (H-FABP) H-FABP is a low molecular weight (15kDa) protein involved in myocardial fatty-acid metabolism Under aerobic conditions, long chain free fatty acid metabolism represents the major source of ATP generated in the myocardium FFA are poorly soluble in the aqueous phase and circulate in plasma mainly bound to albumin

22. Conti.. Low conc. present in skeletal muscle, distant tubules of the kidneys, brain, lactating mammary glands and placenta 9 distinct types It is rapidly released early in myocardial infarction and necrosis into the cytosol However, studies attempting to use H-FABP alone for early diagnosis of AMI have produced disappointing results. 

23. Conti.. H-FABP released from injured Myocardium (recognized in 1988) Detectable in plasma within 1.5 h of MI, peaks in 4-6 h and returns to baseline within 20 h more recent studies demonstrated that H-FABP levels were clearly associated with the composite end point of death, myocardial infarction and heart failure at 10 months

24. Conti.. when added to Troponin for risk stratification, 1 . a negative troponin and H-FABP level < 5.8 mcg/L was associated with zero mortality at six months; 2 . a negative Troponin but H-FABP level > 5.8 mcg/L was associated with a 4.93-fold increase in risk of death and 3 . 7.93-fold increase in risk if Troponin was positive and H-FABP > 5.8 mcg/L. 29

25. Copeptin A peptide of 39 a . a with effects on osmoregulation and cardiovascular homeostasis C-terminal part of pro-arginine vasopressin (AVP ) that released together with AVP Involve in the regulation of the endogenous stress response and is present at elevated conc. in MI, heart failure and different states of shock Elevated 0-4 h after the onset of symptoms of AMI Copeptin can rule out MI earlier in addition to a negative Troponin T test

26. Myoglobin Myoglobin is an oxygen-binding protein of cardiac and skeletal muscle with a molecular mass of 17,800 Da. The low molecular weight and cytoplasmic location of the protein probably account for its early appearance in the circulation following muscle (heart or skeletal) injury. Appearance in circulation within 1-3 hr of MI, peaking at 6-9 hrs and returning normal by 24-36 hrs No difference in myoglobin protein localization has been noted in the heart versus skeletal muscle .

27. Myoglobin Increases in serum myoglobin occur after trauma to skeletal or cardiac muscle, as is seen in crush injury or MI. Serum myoglobin methods are unable to distinguish the tissue of origin Because myoglobin is cleared really, changes in the glomerular filtration rate (GFR) will cause increases. It has a very short half-life of 10 minutes in blood.

28. Lactate Dehydrogenase Isoenzymes Lactate dehydrogenase (LD) (MW 180,000 Da) is localized in the cytoplasm of tissue The highest activities of LD are found in skeletal muscle, liver, heart, kidney, and red blood cells. five isoenzymes, composed of four subunit peptides of two distinct types, designated M (for muscle) and H (for heart).

29. Conti.. LD-1 is found in highest concentrations in the heart, kidney (cortex), and red blood cells. LD-5 is found in highest concentrations in liver and skeletal muscle. The hybrid LD isoenzymes LD-2 (H3M), LD-3 (H2M2), and LD-4 (HM3) are also found in these and several other tissues

30. Cardiactroponins T he most important cardiac proteins involved in the diagnosis of AMI are TnC , TnI and TnT .   TnT and TnI are known as cardiac troponins because they are present in heart and skeletal muscle. Cardiac proteins are synthesized and released from cardiac muscle. These proteins interact with tropomyosin to form the main structure of the striated heart muscle

31. Conti.. Cardiac troponin ( cTn ) acts on myocardial contraction by regulating the calcium-dependent interaction of actin and myosin. cTn has many isoforms specific to tissue.   TnC has no cardiac specificity, because it is the same as the troponin isoform found in smooth muscle. On the other hand, cTnT and I are completely different from troponins in the skeletal muscle, because they are coded by different genes. 

32. Conti.. These proteins are present in myocytes, the cytosolic pool, and the contractile apparatus. The amount of TnC present in the cytosolic pool is similar to the amount of CK-MB , but there is also a significant amount of cTn in the contractile apparatus. Therefore , the amount of TnC per gram of myocardium is 13–15 times greater than the amount of CK-MB.

33. Conti.. This can thus explain the higher sensitivity of cTn compared with CK-MB in the early period and the elevated level of cTn in peripheral blood despite the normal level of CK-MB after myocardial tissue damage <1 g (due to ischemia, infarct, trauma, toxic damage, or inflammation).

34. Conti..   As cardiac and noncardiac causes. Therefore , elevation of troponins should not always be interpreted in favor of coronary ischemia. A healthy person has low levels of TnC in serum, but it reaches a level to be measured in the case of myocyte damage due to release from the cytosolic pool in the early period and from the contractile apparatus in the late period to the peripheral blood.

35. Conti.. Therefore, blood levels increase within 2–4 hours after acute myocardial damage and reach peak levels in 24 hours. Blood cTn levels are high for 2–3 weeks. Unlike the CK-MB level, the reason for the long-lasting elevation is the continuation of the release of cTn from the contractile apparatus in the late period. New troponin tests today can in fact detect even very low levels of troponin

36. Aspartate aminotransferase in diagnosis of AMI Ladue et al suggested in 1954 that AST (formerly called glutamate oxaloacetate transaminase) released from the necrotic cardiac myocytes to the circulation could be helpful in diagnosing AMI. This was the first biomarker used in the diagnosis of AMI, but is no longer used today because it is not specific to the heart. However, the age of the enzyme in the diagnosis of AMI in cardiology had been initiated. Just 1 year after the assertion that AST could help to diagnose AMI, LDH was seen to be a useful marker in the diagnosis of AMI.

37. Lactate dehydrogenase in diagnosis of AMI LDH is expressed in many organs, including skeletal muscle (maximal), kidney, liver, heart, lung, and erythrocytes. LDH has five isoenzymes. The heart has LDH1, but it is not highly specific to the heart. Because it is released from erythrocytes, kidney, brain, skeletal muscle, stomach, and pancreas, it can be elevated in some tumors (seminoma/ dysgerminoma ).

38. Conti.. It increases within 6–12 hours from the onset of chest pain, peaks over 1–3 days, and returns to normal values within 8–14 days. An LDH1:LDH2 ratio >1 is reported to be specific for AMI, but currently it is not used in the diagnosis of AMI . Today , the only use of LDH is in distinguishing acute from subacute MI in patients who reach hospital in the late stage of the disorder, with positive troponins whose CK and CK-MB values have returned to normal levels

39. Creatine kinase  (CK) muscle Creatine kinase  (CK) muscle is an enzyme that's found in skeletal muscle, heart muscle and brain. When any of these tissues are damaged, they leak creatine kinase into your bloodstream. Elevated CK levels may indicate muscle injury or disease. In this case, when CK is elevated, a CK-MB test may be used as a follow-up test to determine whether the increase is due to heart damage or skeletal muscle damage. Chest pain and increased CK levels plus elevated CK-MB indicate that it is likely that a person has recently had a heart attack

40. Serum enzymes in bone diseases

41. Conti..

42. Conti.. pancreatic CPK BB –prostate, lung, breast, colon, ovarian GGT – liver LDH – liver , lymphoma, leukemia Neuron specific enolase – tumors of neuroendocrine origin Prostate specific antigen (PSA or semenogelase ) From secretory epithelium of prostate gland kDa glycoprotein Mild Serine protease activity 1- 5 μ g/L Levels between 4 -10 μ g/L –increased risk of prostate cancer >10 μ g/L - suggestive of Ca prostate >20 μ g/L - Ca prostate with metastases 54

43. Prostate cancer Prostate cancer is cancer that occurs in the prostate. The prostate is a small walnut-shaped gland in males that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of cancer. Many prostate cancers grow slowly and are confined to the prostate gland, where they may not cause serious harm. However, while some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly .

44. Prostat specific antigen(PSA) The PSA test is used primarily to screen for prostate cancer. A PSA test measures the amount of prostate-specific antigen (PSA) in your blood. PSA is a protein produced in the prostate, a small gland that sits below a man's bladder. Prostate cancer is the most common nonskin cancer in men, and it's the second leading cause of cancer-related death in men after lung cancer. Early detection may be an important tool in getting appropriate and timely treatment. The PSA test can detect high levels of PSA that may indicate the presence of prostate cancer. However, many other conditions, such as an enlarged or inflamed prostate, can also increase PSA levels.

45. Conti.. There is a lot of conflicting advice about PSA testing. Ultimately, whether you have a PSA test is something you should decide after discussing it with your doctor, considering your risk factors and weighing your personal preferences. The PSA test is only one tool used to screen for early signs of prostate cancer. Another common screening test, usually done in addition to a PSA test, is a digital rectal exam. In this test, your doctor inserts a lubricated, gloved finger into your rectum to reach the prostate. By feeling or pressing on the prostate, the doctor may be able to judge whether it has abnormal lumps or hard areas

46. ACIDIC PHOSPHATASE ENZYME (ACP ) Acid phosphatase include all the phosphatases catalyzing the following reaction at an optimal pH below ; Orthophosphoric monoester + H2O alcohol + H3PO4 Acid phosphatase is an enzyme found throughout the body, but primarily in the prostate gland; The male prostate gland has 100 times more acid phosphatase than any other body tissue. Tissues other than prostate have small amounts of acid phosphatase, including bone, spleen, kidney, and red blood cells and platelets.

47.   TYPES OF ACID PHOSPHATASE 1 . Based on pH it works a. Type one works at pH of 6 -found in erythrocytes. b. Type two works at pH of 5 - found in Prostate epithelium, spleen, kidney, plasma, liver, pancreas. 2. Based on source a. Prostate ACP. Found in prostate gland ; The prostatic enzyme is strongly inhibited by dextrorotatory tartrate ions. b. Non prostate ACP. found in other tissues; These can not be inhibited by L. tartrate and therefore they can be inhibited by others like Formaldehyde and cupric ions .

48. synonyms are PAP, ACP-3 and ACP3 This gene codes for production of this enzyme thus on its mutation there will be impaired production of ACP enzyme. Their main function is energy preserving effect on spermatozoa and protective effect against phagocytic cell in the female genital tract. CLINICAL IMPORTANCE Damage to containing tissues causes increase in acid phosphatase level in the plasma, prostate gland being the most where 1/3 to ½ of plasma acid phosphatase is from prostate glands. Normal serum contains 0.6 to 3.1 K.A. units/100 ml . of acid phosphatase. Thus an increase or decrease in plasma level it dictate an abnormality in the prostate gland .

49. Conti.. The decrease of plasma acidic phosphatase below normal value indicates that the is malfunction in the production of the enzyme which may be due to mutation. The increase in the plasma level of ACP above normal indicate that there is enzyme leakage in the prostate gland which actually is due to cancer(prostate carcinoma ).

50. Expected Question Essay/Situational Question myocardial infarction CK, cardiac troponins, AST, LDH Short Question muscle CK, Aldolase and bone disease ALP prostate cancer PSA, ACP

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