Lecture 5. Infarction The process by which necrosis results from ischemia is called infarction...
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Transcript of Lecture 5. Infarction The process by which necrosis results from ischemia is called infarction...
![Page 1: Lecture 5. Infarction The process by which necrosis results from ischemia is called infarction Ischemic necrosis of myocardial cells is one of the commonest.](https://reader035.fdocuments.net/reader035/viewer/2022062314/56649db65503460f94aa7647/html5/thumbnails/1.jpg)
Myocardial infarctionLecture 5
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InfarctionThe process by which necrosis results from
ischemia is called infarctionIschemic necrosis of myocardial cells is one of
the commonest cause of death in industrialized countries.
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Pathology AtherosclerosisNarrowing of arterial lumenReduced coronary blood supplyClinical manifestations
Chest pain
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Diagnosis History ECGBiomarkers
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WHO classification of MI2/3 these criteria:Ischemic symptomsEKG changes.Increased serum markers.
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ECG
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CARDIAC PROFILE TESTENZYMES
Creatinine Kinase –MB(CK-MB)Lactate Dehydrogenase(LDH 1 and 2)Aspartate Aminotransferase(AST)/Serum Glutamate Oxaloacetate
Transaminase(SGOT)Alanine Aminotransferase(ALT)/ Serum Pyruvate
Transaminase(SGPT)
• PROTEINS MyoglobinTroponin
LIPID PROFILECHOLESTEROL TRIGLYCERIDEHDLLDL
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ASTfound in all tissue, especially the heart, liver, and skeletal muscles
It catalyzes the transfer of the amino group of aspartic acid to alpha-ketoglutaric acid to form oxaloacetic acid and glutamic acid
Reference range: < 35 U/L in male and < 31 in female
Considerations in AST assays -Serum is the best specimen-Hemolyzed samples must be avoided-Muscle trauma like intramuscular injections, exercise, or
surgical operation can significantly increase AST levels
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Clinical significance
Myocardial infarction In myocardial infarction, AST levels are
usually 4-10 times the upper limit of normal These develop within 4-6 hours after the onset
of pain Peak on the 24th – 36th hour Usually normalize on the 4th or 5th day
Muscular dystrophy Hepatocellular disordersSkeletal muscle disorders
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LACTATE DEHYDROGENASE (LDH)
Catalyzes the reversible oxidation of lactate to pyruvate
Used to indicate AMIIs a cytoplasmic enzyme found in most cells
of the body, including the heartNot specific for the diagnosis of cardiac
disease
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Distribution of LD isoenzymes
LD1 and LD2 (HHHH, HHHM)Fast moving fractions and are heat-stableFound mostly in the myocardium and erythrocytesAlso found in the renal cortex
LD3 (HHMM)Found in a number of tissues, predominantly in the
white blood cells and brain
LD4 and LD5 (HMMM, MMMM)Slow moving and are heat labileFound mostly in the liver and skeletal muscle
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Considerations in LD assaysRed cells contain 150 times more LDH than
serum, therefore hemolysis must be avoidedLDH has its poorest stability at 0°C
Clinical Significance In myocardial infarction, LD increases 3-12
hours after the onset of painPeaks at 48-60 hours and remain elevated for 10-
14 daysIn MI, LD1 is higher than LD2, thus called
“flipped” LD pattern
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flipped LDHAn inversion of the ratio of LD isoenzymes LD1 and LD2; LD1 is a tetramer of 4 H–heart subunits, and is the predominant cardiac LD isoenzyme;
Normally the LD1 peak is less than that of the LD2, a ratio that is inverted–flipped in 80% of MIs within the first 48 hrs DiffDx. LD flips also occur in renal infarcts, hemolysis, hypothyroidism, and gastric CA
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Increased levels of LDTrauma Megaloblastic anemiaPulmonary infarctionGranulocyte leukemiaHemolytic anemiaProgressive muscular dystrophy (PMD)
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CREATINE KINASE (CK)
Is a cytosolic enzyme involved in the transfer of energy in muscle metabolism
Catalyzes the reversible phosphorylation of creatine by ATP
-Is a dimer comprised of two subunits, resulting in three CK isoenzymes The B, or brain formThe M, or muscle form
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isoenzymesCK-BB (CK1) isoenzyme
Is of brain origin and only found in the blood if the blood-brain barrier has been breached
CK-MM (CK3) isoenzyme Accounts for most of the CK activity in skeletal muscle
CK-MB (CK2) isoenzyme Has the most specificity for cardiac muscle It accounts for only 3-20% of total CK activity in the heart Is a valuable tool for the diagnosis of AMI because of its relatively
high specificity for cardiac injury Established as the benchmark and gold standard for other cardiac
markers
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Clinical Significance -In myocardial infarction, CK will rise 1-3
hours after the onset of pain-Peaks at 18-30 hours and returns to normal
on the third day -CK is the most specific indicator for
myocardial infarction (MI)Ratio of CK-MB/ total CK activity (specificity)CK-MB mass instead of activity (sensitivity)
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Raised levels of CKProgressive muscular dystrophyPolymyositis Acute psychosisAlcoholic myopathy HypothyroidismMalignant hyperthermiaAcute cerebrovascular diseaseTrichinosis and dermatomyositisExercise and intramuscular injections causes CK
elevations
Normal Value:a. Male – 25-90 IU/mL b. Female – 10-70 IU/mL
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Myoglobin Non specific markerFrequently elevated in other conditions Most useful when not detectedCan not be used alone for the diagnosis of
MI.
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TroponinsProteins that regulate muscle contractionT & I are specific for cardiac muscles
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Cardiac troponins:1. Troponin C: binds with calcium.2. Troponin T: binds with
tropomyosin.3. Troponin I: inhibits contraction.
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Troponin T & I Require myocardial necrosis for release from
sarcomere. Early rise (4-12 hours after symptom). Peak 12-24 hours (sensitivity is 100%). Continuous release up to 10-14 days
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Myocardial infarction: elevation of serum troponin T/I >0.1. (AHA)
Negative troponin and normal EKG, mortality 1%.
Negative troponin and ischemic EKG: mortatity 4% at 1 month.
Troponin and EKG changes complementary. Problems with TnI: variability of assays. Complement clinical risk factors and EKG
changes.
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