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Report Outline
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Etymology
Myocardium heart muscle
Infarction tissue death dueto Oxygen starvation(ischemia)
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Incidence Rate
WHO (2010):
Leading cause of NCDdeaths in 2008 were CVD
Approximately 17 milliondeaths or 48% of all NCDdeaths
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Incidence Rate
DOH (2010):
Diseases of the heart ranked1st in the list of diseases
that cause death (NCD and CD)
Approximately 63,000 death or
24% of all NCD and CD death
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Precipitating Factors
Age
Family History Sex : Male
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Predisposing Factors
Hypertension
High levels of LDL and lowlevels of HDL
Smoking
High in saturated fat diet
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S/Sx
Sweating
Varying degree of chest pain radiates to the jaw, neck, leftarm, back and epigastrum;
lasts 20 minutes Anxiety
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S/Sx
Fainting
Light-headedness
Shortness of breath (Dyspnea)
*Approx. of all MI patients
experience warning symptoms likeAngina Pectoris prior to infarction
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Summary of Mechanisms Involved in the Causation
of Myocardial InfarctionDevelopment of atherosclerosis
(usually polygenic)
Plaque rupture
Formation of large thrombus in a coronary
artery
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Diagram :
1. occlussion of a branch of the left coronary artery
2. myocardial infarction resulting from #1 at the anterior wall of the heart
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Summary of Mechanisms Involved in the Causation
of Myocardial InfarctionDeprivation of blood supply (ischemia) to an
area of the myocardium
Shift to anaerobic glycolysis decreased
synthesis of ATP, depletion of adenine
nucleotide pool
Increase of NADH due to inactive terminal
electron transport chain: due to lack of oxygen
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Summary of Mechanisms Involved in the Causation
of Myocardial InfarctionAccumulation of lactic acid and other
metabolites in myocardial muscle, causing
increased cellular osmolarity and altered
membrane permeability
Decrease in Ph in heart muscle cells
Increasingly inefficient contraction of heart
muscle
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Summary of Mechanisms Involved in the Causation
of Myocardial InfarctionCessation of contraction
Activation of membrane phospholipases,degradation of proteins by proteases, influx of
Ca nucleotide pool
Death of affected area of heart muscle
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Management:
Treatment with Drugs
Vasodilator gives immediate
relief from pain
Beta-blockers decreases the
need of heart for extra metabolicOxygen during stressful condition
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Surgical Treatment
Aortic-Coronary Bypass divert
or shunt the flow of blood
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Coronary Angioplastyreconstruction of damaged
blood vessels
Surgical Treatment
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Lecture Objectives
Discuss significant enzymes inMyocardial Infarction.
Enumerate and differentiatesignificant Isoenzymes.
Discuss other protein cardiacmarkers.
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What are the significant
enzymes in diagnosis of MI?
Lactate dehydrogenase (LDH)
Creatine Kinase (CK)
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Cytoplasmic enzyme
Tetramer of 2 subunitsH (for heart) and M (for muscle)
Produce 5 isoenzyme
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Isoenzyme
HHHH (LDH-1) heart and RBC
17-27% of the normal serum total.
HHHM (LDH-2) heart, RBC, renal cortex
27-37% of the normal serum total.
HHMM (LDH-3) variety of organs18-25% of the normal serum total.
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HMMM (LDH-4)variety of organs
3-8% of the normal serum total.
MMMM (LDH-5)liver and skeletalmuscle
0-5% of the normal serum total.
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Lactate dehydrogenase
Flipped LD ratio
LDH 1 > LDH 2
rise within 12-24 hours
peaks within 48-72 hours
remains elevated for 10-14 days.
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Creatine Kinase
transfer of energy in musclemetabolism
comprised of two subunits
the B (brain) and the M (muscle)
resulting the 3 CK isoenzyme.
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CK-BB (CK-1) brain , smooth muscles
CK-MB (CK-2)35% in cardiac muscle
CK-MM (CK-3) muscles, normalserum.
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Creatine kinase
rise within 4-6 hours
peak at 24 hours return to baseline by 48-72
hours
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Enzyme Rise Peak Decline
LDH 12-24 hours 48-72 hours 10 -14 days
CK 4-6 hours 24 hours 48-72 hours
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Other significant protein in diagnosingMyocardial Infarction
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Troponin
marker of all heart muscle damage
Not present in normal serum
Regulatory complex of 3 protein
TnT (tropomyosin binding complex)
TnI (Inhibitory subunit binds to actin)
TnC (Calcium binding subunit)
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Troponin T
Early and late diagnosis of AMI
Rise within a few hours
Peak by day 2
Elevated beyond 7 days
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Troponin I
Only found in the myocardium
Specific for cardiac disease
Rise within 4-6 hours
Peaks at 12-18 hours
Elevated until 7 days
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Myoglobin
Heme-containing protein
Related to muscle mass and activity
Lack specificity to myocardium
Cleared by renal filtration
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Myoglobin
2-3 hours following onset of MI,
peaks about 6 hours
returns to baseline after 24 hours
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Therapeutic Enzymes
Outline:Enzymes that have therapeutic
value to MI.
What other drugs can be used for MI?
Reperfusion Injury and its relevance tothrombolytic therapy
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Therapeutic Enzymes
Thrombolytics: also known asplasminogen activators or fibrinolytic
drugs
Streptokinase
UrokinaseTissue PlasminogenAcivator
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Thrombolytics:
Streptokinase
- Protein secreted by several species ofstreptococci-onset is immediate; long-acting(duration is about 12 hours, but canbe as long as 24 hours)
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Thrombolytics:
Urokinase
-Produced in renal parenchymal cells- almost same function as
streptokinase- onset is same with streptokinase
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Thrombolytics:
Tissue Plasminogen Activator (TPA)
- Synthesized in the endothelial cells- most commonly used thrombolytic
- tPA (Alteplase): onset is immediate;effects may linger up to 4 hoursafter infusion
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Thrombolytics:
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Thrombolytics:
Important To Note:
- efficiency depends on the ageof the clot
- administration of any anticoagulant or
antiplatelet drugs is contraindicatedwithin 24-48 hours
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- thrombolytics administration iscontraindicated to known surgerywithin 10 days, or any known case
of internal bleeding
Other anti thrombotic
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Other anti-thromboticdrugs:
Anti-platelet drugs
Anticoagulant drugs
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Anti-platelet drugs:
Aspirin
-Inhibits platelet cyclooxygenase
- Side Effects: GI side effect (ulceration),
risk for bleeding
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A i l l d
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Anti-platelet drugs:
ADP-receptor antagonist:-Prevents ADP from attaching to receptor;platelet clumping
-Ticlopidine, Clopidogrel- may cause thrombocytopenia & neutropenia(Ticlopidine)
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Anti-platelet drugs:
ADP-receptorantagonist
A i l l d
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Anti-platelet drugs:
Glycoprotein IIb/IIIa receptor inhibitor:
-Prevent cross-linking of platelets- used by specialists; not used in anoutpatient setting
- may cause major bleeding, thrombocytopenia-Abciximap
A i l l dGlycoprotein IIb/IIIa receptor inhibitor:
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Anti-platelet drugs:y p / p
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- Sites of platelet
inhibitors
TXA2 Inhibitors X
A ti l t D
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Anticoagulant Drugs:
- Used as blood thinner
Intravenous Heparin Oral Anticoagulant (Warfarin)
R f i I j
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Reperfusion Injury
Refers to myocardial, vascular or
electrophysiological dysfunction
factors that contribute to reperfusion injury:- damage to cellular and organelle
membranes, including mitocondria- myocyte hypercontracture
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- free radical formation
- leukocyte aggregation andinflammatory mediators
- endothelium damage
R f i I j
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Reperfusion Injury:
Clinical manifestations:
- Arrhythmias
- microvascular dysfunction(No reflow phenomenon)
- myocyte death
R f i I j
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Reperfusion Injury:
Potential Therapies:
- No clear solutions yet; management- combination of techniques for rapid
reperfusion, use of antioxidants,neutrophil inhibitors