Myocardial Infarction• Presenter : Dr Gopal G Hargi» PG in dept of FM & T
• Acute Myocardial infarction is one ofthe pathological condition caused byprolonged ischemia where there isirreversible necrosis of the myocardialtissue
• IHD refers to a group of closely related syndromescaused by imbalance between myocardial oxygen demand &blood supply.• Ischemia is the most common type of cell injury, (incontrast to hypoxia ,the injury is faster)• IHD - 90% due to atherosclerosis affecting coronaryarteries• 10% other causes• Most common cause of ischemiaNarrowing of coronaries by atherosclerosis
Depending on rate & severity of myocardial injury one of 4syndromes may develop1)Angina pectoris2)MI3)Sudden cardiac death4)Chr IHD& CCFOther less common sequele (non cardiac) due to atherosclerosis• Perepheral vascular disease• aneurysms• Ischemic encephalopathy• mesentric artery occlusion
Pathology of atherosclerosis: affects primarilythe intima of large & medium sized musculararteries and is characterized by endothelialthickenings, fibro fatty plaques or atheromas.(atheros-porridge –ref to soft lipid rich material inthe centre of atheroma.sclerosis- CT in plaque.Common sites – Aorta/Coronaries/Cerebral vessels
• Clinical manifestation may develop at any age butmore common in older adults with peak incidenceafter age of 60 yrs in men & 70 yrs in women• Risk factors• Major : constitutional: age/sex/genetics/familial &raceacquired : ^ lipid/HT/DM/smoking• Minor : Environmental/obesity/hormones/physicalinactivity / stress/alcohol/infections(cmv ,herpes)
• Atherosclerosis formation – no of theories• 1) insudation theory ( virchows ) :also calledresponse to injury theory.cellular proliferation of intimal cells from imbibingof lipids from blood.2) Encrustation theory ( Rokitansky) : Atheromacauses a form of encrustation on the arterial wallfrom the components of blood to form thrombi (platelets ,fibrin, leucocytes)(currently reaction to injury& monoclonal theorybased on proliferation of SMC is accepted )
• The 4 key significant factors responsible are• Arterial SMC• Endothelial cells• Blood Monocytes• HyperlipidemiaReaction to injury is taken as the endothelialinjury followed by SMC proliferation so that earlylesion consists of SMC mainly .The lipoproteins enterinto the intima ,followed by lipid accumulation inmacrophages( foam cells)
• Earliest pathological lesions in atherosclerosis are• 1)Intimal thickening-• 2)Fatty streaks fore-runners in the evolution• of atherosclerosis.Fatty streaks : these lie under the endothelium& composed of closely packed foam cells ,lipidcontaining SMC & few lymphoid cells.3) Atheromatous plaques: also called fibrous plaque ,fibro fatty plaque & atheromas
• Complication:(fate of atheroma)• covering endothelium remains intact but dangerto life is caused by luminal reduction from bulgeof enlarging plaque• Fibroendothelial cap begins to breakdown underpressure by central necrosing process & erosionscaused by blood flow• May rupture into lumen leading to acuteobstruction causing death• Contents of the plaque may get washed downcausing embolism
Changes• Calcification• Ulceration• Thrombosis: plaque - internal necrosis - surfaceeroded –fibrofatty content exposed- nidus for thrombosis• Hemorrhages : rupture of blood vessels in theperiphery• aneurysm
• IHD - 90% due to atherosclerosis affecting coronaryarteries• 10% other causesOther causes ( non atherosclerotic )• Vasospasm• Stenosis of coronary ostia: syphilitic aortitis• Arteritis: kawasaki disease/TB/polyarteritis• Embolism: infective endocarditis• Thrombotic disease: polycythemia vera , SSA , TTP• Aneurysms: DAA into coronary artery• Compression: tumour of heart• Trauma: contusion to muocardium
• MI is the most feared consequence of CAD .Many die withinfew hrs ,remaining suffer from effects of impaired cardiacfunctions.• According to WHO statistics ,globally ,MI is responsible fornearly 32% & 27% of all the mortalities in males & femalesrespectively• 13.5 million alive today with history of MI• 5% of MI in people under 40 years , particularly with HTN• In 48% of men and 33% of women who died suddenly of MI,there were no previous symptoms
Acute MI is one of the pathological condition causedby prolonged ischemia where there is irreversiblenecrosis of the myocardial tissue due tocoronary blood flow myocardial demand,hypertrophyRisk factors• HTN• DM• Cigarettes• Dislipidemia with familial hypercholesteremia
• MI caused by ischemic injury .• Types are• 1)Full thickness or transmural(regional/focal) : chratherosclerosis• 2)Subendocardial or laminar: thrombi absent (diffusestenosing coronary atherosclerosis & therefore noplaque disruption or thrombosis.- hypoperfusion.MI typically begins in subendocardial region1) last area to be perfused2) intra mural pressure- inflow of blood
• Age of infarct is difficult to establish because onsetof symptoms are often much later ( 1- 1.5hrs)than theonset of the pathological lesions precipitated by theocclusion• Various methods of detection• Histochemical method• Flouroscent method• Enzyme chemistry• Immunohistochemical method
• 10%formol soln- non infarcted area-stain ,infarcted• Haematoxylin –eosin stain – eosinophilia & oedema• PAS- peripheral pink stain ,infarcted. Grey blue –healthy• Phosphotungstic acid haematoxylin- change instriation pattern of MI fibres• Histochemical –LDH activity of succindehydrogenase,malic dehydrogenase• Floroscene test-normal-brown.infarcted-green
• 1cc thick slices ,across ventricles ,washed .The slicesdipped into 1% soln of 2:3:5 triphenyl tetrazoliumchloride .After this the slices are treated with 10%formalin which fixes the stain .The brown stainedarea indicates increased activity of dehydrogenaseenzyme and viable tissue .The necrosed tissueappears pale. These detected tissues can be collectedfor histological examination
Myocardial infarctionA heart attack or acute myocardial infarction (MI) occurs when one of thearteries that supplies the heart muscle becomes blocked. Blockage may becaused by spasm of the artery or by atherosclerosis with acute clot formation.The blockage results in damaged tissue and a permanent loss of contraction ofthis portion of the heart muscle.
Time from Onset Gross Morphologic Finding18 - 24 Hours Pallor of myocardium24 - 72 HoursPallor with somehyperemia3 - 7 DaysHyperemic border withcentral yellowing10 - 21 DaysMaximally yellow and softwith vascular margins7 weeks White fibrosisGross morphologic changes evolve over time as follows:
Microscopic features:• Within 1 hour of ischemic injury, there isintercellular edema and “wavy fibers” may bepresent at the periphery of the infarct. Theseare noncontrctile dead fibers, stretched by theadjacent viable contracting myocytes• Electron microscopy shows reversible changes(swelling of mitochondria & endoplasmicreticulum and relaxation of myofibrils).• Histochemically, there is loss of oxidativeenzyme & fall of glycogen.• In 12 to 72 hours, there is infiltration ofneutrophils with progressive coagulativenecrosis of myocytes. Dead myocytes becomehypereosinophilic with loss of nuclei.•
This is normal myocardium. There are cross striations and central nuclei
This is an early acute myocardial infarction. (<iday) Note theprominent pink contraction bands.
1-2 daysThis is an early acute myocardial infarction. There is increasing loss ofcross striations, and some contraction bands are also seen, and the nuclei areundergoing karyolysis. Some neutrophils are beginning to infiltrate themyocardium.
3-4 days This is an acute myocardial infarction of several daysduration. There is a more extensive neutrophilic infiltrate alongwith the prominent necrosis and hemorrhage.
• Between 3 and 7 days after onset, dead myocytes begin todisintegrate and are removed by macrophages and enzymeproteolysis. There is proliferation of fibroblasts with formation ofgranulation tissue, which progressively replaces necrotic tissue.• After 6 weeks, healing is complete by fibrosis.Contraction band necrosis: Contraction band necrosis, contractedmyofibrils characterized by hypereosinophilic transverse bands ofprecipitated myofibrils in dead myocytes is usually seen at theedge of an infarct or with reperfusion (e.g. with thrombolytictherapy).• Reperfusion of an infarct: Reperfusion of an infarct is alsoassociated with more hemorrhage, acute inflammation, lesslimitation of the acute inflammation to the periphery in the firstfew days, reactive stromal cells, more macrophage infiltrationearlier and a more patchy distribution of necrosis, especiallyaround the periphery.
2-3 wks Toward the end of the first week, healing of the infarction becomesmore prominent, with capillaries, fibroblasts, and macrophages filled withhemosiderin. The granulation tissue seen here is most prominent from 2 to3 weeks following onset of infarction.
• Examination procedure for MI victims at autopsy• Examination of Coronaries: angiography,inj of barium-gelatin mix into coronary ostia.fix 24hrs. Wash –xray• Perfusion –fixation . Intra aortic perfusion of 10%formalin at a pressure of 100 mm of Hg• Dissection• Section tranversely at 3-5mm interval ,the RCA,LAD,CCX.Diagonal,obtuse,marginal & PD arteries .Grade thereduction of cross section area by atheroma as grade1=25%, grade 2=26-50%,grade3=50-75%, grade4=76-100%.• Look for thrombus ,plaque & dissection.• Section from sites of maximal narrowing
Cardiac dissection methods:1. Inflow-outflow method2. Short-axis method3. Four chamber method4. Long axis method5.Base of heart method6.Window method7.Unrolling method8.Partition method.Useful fordemonstratingcardiac pathologyAnatomicteaching andmuseumspecimendemonstrations/preparations.ConsiderableMutilationof theheart
• Examination of myocardium• Location/extent/distribution• Inflow-outflow method
• Complications: It depends on the size , locationduration of the lesion.With in minutes to 3 days of onset:1. Arrythmias :75-95% i) ventricular fibrillation ; ii)block of A-V bundles and its branches causing acuteheart failure.2. Cardiogenic shock 10-15%(usually in large infarct)causing acute heart failure.3. Thrombotic complication- 15-40% mural thrombusover infarct area or Atrial thrombus, causingembolism to brain, kidney etc.4. Rupture of heart.
• 3-14 days:Large infarct: There is softening of dead muscle(myomalacia cordis) leading to rupture & death.Site of rupture is ventricular wall, papillary muscle &interventricular septum.5. Acute fibrinous or hemorrhagic pericarditis - overinfarct area.After weeks or months:6. Chronic heart failure7. Cardiac aneurysm, which may rupture producinghemopericardium and death.
Complications• Arrythmias• CCF• Mural thrombi & thromboemnbolism• Rupture• Cardiac aneurysms• Pericarditis• Cardiac Tamponade• Post MI syndrome
Rupture (at the arrow) into the pericardial sac can produce a life-threatening cardiac tamponade, as seen here. The septum may alsorupture.
This is an acute myocardial infarction in the septum. After several days,there is a yellowish center with necrosis and inflammation surroundedby a hyperemic border.
This is an acute myocardial infarction of the anterior left ventricular free wall andseptum in cross section. Note that the infarction is nearly transmural. There is ayellowish center with necrosis and inflammation surrounded by a hyperemic borde
When the infarction is 3 to 5 days old, the necrosis and inflammation are mostextensive, and the myocardium is the softest, so that transmural infarctions may becomplicated by rupture. A papillary muscle may rupture as well to produce suddenvalvular insufficiency. Rupture through the septum results in a left-to-right shuntand right heart failure.