Ischemia and Infarction

Ischemia is defined as a condition of inadequate blood supply to an area of tissue.
Infarction- Localized area of ischemic necrosis in an organ or tissue resulting most often from reduction of arterial blood supply or occasionally its venous drainage
Public Health Significance- Long-term exposure to other lung irritants also is a risk factor for COPD leading to IHD. Examples of other lung irritants include secondhand smoke, air pollution, and chemical fumes and dust from the environment or workplace.

1. ISCHAEMIA AND INFARCTION Presented By- Dr. Ankit Mohapatra DEPARTMENT OF PUBLIC HEALTH DENTISTRY 1

2. CONTENTS Ischaemia Harmful Effects Of Ischaemia Causes General Causes Local Causes Arterial Obstruction Venous Obstruction Capillary Obstruction Factors Determining Ischaemia Subsidiary Factors 2

3. Mechanism Changes occurring Symptoms Treatment Infarction Etiology Pathogenesis Types of Infarction Pathologic Changes Healing Of An Infarct 3

4. Infarct of different organs Pulmonary Infarct Renal Infarct Infarct of Spleen Infarct Of Liver Cerebral Infarct Myocardial Infacrt Public Health Significance References 4

5. ISCHAEMIA It is a state, when a tissue or organ has it’s arterial perfusion lowered relative to its metabolic needs. OR Ischemia is defined as a condition of inadequate blood supply to an area of tissue. Ischaemia [ ischaem = to check and haim = blood ] is inadequate blood supply to a part of the body, even to the point of complete deprivation . Is simply defined as a condition of inadequate blood supply. When ischemia is severe death of tissue results. ( necrosis of cells occur) 5

6. There are three harmful effects of ischemia: Hypoxia - Oxygen deprivation. By far the most important factor for ischemic tissue damage of very active cells. Eg . muscles Malnutrition - blood contains glucose and amino acids that could be metabolised by the amount of oxygen it contain, hence it is of less importance. Failure to remove waste products - ‘accumulation of metabolites is the most explanatory pain in muscle ischaemia ’. HARMFULL EFFECTS OF ISCHAEMIA 6

7. CAUSES OF ISCHAEMIA General Causes - May be caused by inadequate cardiac output but not all tissues are equally affected because of redistribution of avaliable blood. Symmterical gangrene of the extremities is an occasional manifestation. 7

8. Local causes- By far the most important cause of ischaemia is obstruction of arterial flow. Extensive venous and capillary damage also produces ischaemia . 8

9. ARTERIAL OBSTRUCTION 9

10. Complete obstruction by occlusive thrombosis. Most frequentely found in small and medium sized arteries eg : coronary or cerebral arteries. THROMBOSIS 10

11. Embolism The effects of the embolus are by the reflex spasm of the arterial wall and completed by the rapid development of thrombus over the embolus. 11

12. Spasm Generalized vaasoconstriction following haemorrhage and dehydration. 12

13. Atherosclerosis P roduction of partial obstruction in medium-sized vessels eg : cerebral, coronary and renal. 13

14. Occlusive pressure from outside- caused by tourniquets and tightly fitting plasters. 14

15. Effects of arterial obstruction Effects depend on degree of ischaemia ranging from sudden death to no damage: Ischaemia is obviated by collateral channels then there is no effect on tissues supplied by vessels. The collateral channels supply sufficient blood during inactivity of tissue but sustain normal exercise, there may be functional disturbances eg:angina pectoris. 15

16. 3. There may be cellular degeneration affecting the parenchyma eg : fatty changes leading to necrosis. This is a patchy affair, and leads to atropy accompanied by replacement fibrosis or in central nervous system gliosis . 4 . Both arterial and venous obstruction leads to circumscribed necrosis of tissue called infarction . 16

17. VENOUS OBSTRUCTION 17

18. Mesenteric venous thrombosis- leads to intestinal infarction 18

19. Strangulation of a hernia obstruction at the neck of the hernia leads to damage before the arterial blood flow is implicated 19

20. Torsion of the testis - leads to haemorrhagic infarction of the organ. 20

21. Cavernous sinus thrombosis- leads to retinal vein thrombosis and retinal changes resulting in blindness 21

22. Varicose veins of the legs -venous blood from the deep calf veins are pumped by contraction of calf muscles through communicating veins to the superficial veins. These dilate and become varicose so that their valves become incompetent. The high venous pressure causes distension of capillaries and venules of the skin changing its colour to dusky blue. 22

23. CAPILLARY OBSTRUCTION 23

24. Acute leucocytoclastic vasculitis - Affected vessels with necrosis having their lumens occlueded by fibrin and walls infiltered by neutrophils showing degeneration with karyorrhexis and clinically the skin appears as palpable purpura . 24

25. Frost bite- Harmful effect of excessive cold on the exposed body parts, damages small blood vessels resulting in, arteriolar spasm and aggravation of ischaemia . 25

26. Occlusion of fibrin -disseminated intravascular coagulation is characterized by occlusion of small vessels by deposition of fibrin mixed with platelets. Occlusion of precipitated cryoglobulins - exposure of the extremities to cold leads to vascular occlusion and hemorrhages. 26

27. Occluision of capillaries by red cells - Exposure of the limbs to to cold leads to haemolysis . Ischaemia precipitated by cold is a feature of sickle cell disease, in which chronic leg ulcers are seen. Raynaud’s syndrome may occur due to vascular obstruction. 27

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29. Occlusion by white cells- Due to abnormal clumping of white cells in chronic myeloid leukaemic condition infarcts may occur. Eg : spleen 29

30. Arteriolosclerosis - The benign and malignant types of arteriolosclerosis can affect small vessels in many organs; involvement of the retina and kidney is very serious. 30

31. FACTORS DETERMINING ISCHAEMIA Three crucial factors: Speed of onset - if obstruction is sudden effect is more serious because of less time for effective collateral circulation. Extent of obstruction - complete obstruction is more serious than partial eg : partial coronary occlusion due to atherosclerosis is tolerated while complete obstruction causes infarction and death. 31

32. 3. Anatomy of collateral circulation – end arteries can have serious effects as demonstrated by steal syndrome’s eg : obstruction of the first part of subclavian artery can cause blood to be diverted down the vertebral artery to the arm, leading to brain stem ischaemia . 32

33. SUBSIDIARY FACTORS State of collateral circulation- a collateral circulation is affected with spasm, atherosclerosis, failing to maintain a good alternative blood supply. State of oxygenation of blood- it is in respect of arterial partial oxygen and haemoglobin level. Efficiency of heart Nature of affected tissue- brain and heart are more vulnerable to ischaemia . 33

34. MECHANISM : Ischaemia causes damage to tissue through : 34

35. CHANGES There are basically two extreme effects of Ischaemia . Absence of any damage Sudden death But in between there are four changes that occur 35

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37. SYMPTOMS OF ISCHAEMIA Although pain is common, ischemia may occur without any symptoms. Generally, symptoms depend on the location of the ischemia. 37

38. ISCHEMIA OF THE HEART Symptoms of cardiac ischemia include: Chest pain or pressure, which may radiate to the back, arm, shoulder, neck, jaw or stomach Limitations of physical abilities Nausea with or without vomiting Palpitations or irregular heart rhythms Profuse sweating Shortness of breath 38

39. ISCHEMIA OF THE BRAIN Symptoms of ischemia of the brain include: Abnormal pupil size or non reactivity to light Balance problems, difficulty walking, and falls Confusion Difficulty with memory, thinking, talking, comprehension, writing or reading Dizziness Droopy eyelid 39

40. Headache Loss of muscle coordination Loss of vision or changes in vision Nausea with or without vomiting Numbness or weakness Paralysis Vision problems (double vision, blurriness, loss of visual field, sudden blindness) Weakness (loss of strength) 40

41. OTHER TYPES OF ISCHEMIA Symptoms from ischemia in other parts of the body can include: Abdominal discomfort when eating Bloody stool (the blood may be red, black, or tarry in texture) Diarrhea Leg pain with walking or climbing stairs Nausea with or without vomiting Non-healing sores Pain Skin changes 41

42. SYMPTOMS INDICATING A LIFE- THREATENING CONDITION Abnormal pupil size or nonreactivity to light Change in level of consciousness or alertness, such as passing out or unresponsiveness Chest pain, chest tightness, chest pressure, palpitations Droopy eyelid Garbled or slurred speech or inability to speak Hallucinations Paralysis or inability to move a body part 42

43. Respiratory or breathing problems such as shortness of breath Seizure Severe abdominal pain or headache Sudden change in vision, loss of vision Vomiting blood or bloody stool 43

44. TREATMENT Treatment of ischemia begins with seeking regular medical care throughout your life. Regular medical care allows a health care professional to provide early screening tests and to promptly evaluate symptoms and your risks for developing ischemia. The goal of treating ischemia is to restore blood flow and prevent further damage. Surgery may be needed to remove dead tissue or repair injured areas. Once the initial event is managed, treatment turns to prevention of future ischemia . 44

45. Common treatments to reduce ischemia and restore blood flow include: Medications to control pain and dilate blood vessels Medications to prevent ongoing clot formation Medications to reduce the heart’s workload. 45

46. Oxygen therapy Procedures to expand blood vessels Surgery or procedures to remove clots Surgery to bypass blocked blood vessels Thrombolytic drugs to dissolve clots 46

47. INFARCTION Localized area of ischemic necrosis in an organ or tissue resulting most often from reduction of arterial blood supply or occasionally its venous drainage 47

48. ETIOLOGY Most Commonly - Infarcts are caused by Interruption in arterial blood supply, called ischemic necrosis Less commonly - Venous obstruction can produce infarcts termed stagnant hypoxia 48

49. Generally - Sudden, complete and continuous occlusion by thrombosis or embolism Torsion of a vessel, e.g. in testicular torsion Traumatic rupture or vascular compromise by edema, e.g. anterior compartment syndrome. Non occlusive circulatory insufficiency. 49

50. PATHOGENESIS OF INFARCTION Infarction usually leads to circumscribed area of coagulative necrosis which is subsequently organized into scar tissue. Death of cells in an area deprived of blood supply but blood continues to seep into the devitalized area for a short time. 50

51. THREE POSSIBLE PROCESSESS OF BLOOD TO SEEP INTO THE DEVITALIZED AREA 51

52. NOTE: At all the events infarcts contain a great deal of blood and are swollen and red in colour . The red cells entering the effected area escape through damaged capillaries and lie free on the dead tissues. Also, a great deal of fibrin derived from blood lie on the dead tissue. 52

53. DEATH OF CELLS IN AN AREA DEPRIVED OF BLOOD SUPPLY 53

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55. After phase of demolition , there is slow progressive in-growth of granulation tissue from the periphery and eventually infarct organizes to a fibrous scar which later undergoes hyaline changes. 55

56. As the dead tissue undergoes necrosis in solid organs, associated swelling of cells squeeze the blood out of infarct in this way making it look paler. Until necrosis is visible the ischaemic area cannot be called infarct. Hence, human dead body is not possible to distinguish post-mortem changes from early infarcton Practically it takes 12-24 hours for a myocardial infarct to be visible macroscopically recognizable. But the first microscopic changes of necrosis can be seen only from 6-12 hours after ischaemic episode 56

57. Types COLOUR 57

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59. BLAND : when free of bacterial contamination (infarcts of streptococcus virdians endocarditis behave in a bland way because organisms in the emboli are rapidly destroyed at the site of infarction) SEPTIC : when infected (a rapid transition from the stage of necrosis to one of suppuration resulting in large ragged abscess) 59

60. PATHOLOGIC CHANGES Grossly, infarcts of solid organs - wedge-shaped apex -pointing towards occluded artery wide base - on the surface of the organ. Infarcts due to arterial occlusion - pale venous obstruction - hemorrhagic. Most infarcts become pale later as the red cell are lysed but pulmonary infarcts never become pale due to extensive amount of blood. 60

61. Cerebral infarcts : poorly defined with central softening ( encephalomalacia ). Recent infarcts : slightly elevated over the surface Old infarcts : shrunken , depressed under the surface of the organ. 61

62. MICROSCOPICALLY The pathognomic cytologic change in all infarcts is coagulative ( ischaemic ) necrosis of the affected area of tissue or organ. In cerebral infarcts- characteristic liquefactive necrosis. 62

63. At periphery of an infarct , inflammatory reaction is noted. Initially neutrophils predominate ,later macrophages and fibroblasts appear. Eventually, necrotic area is replaced by fibrous scar tissue, may show dystrophic calcification. In cerebral infarcts , the liquefactive necrosis is followed by gliosis i.e. replacement by microglial cells distended by fatty material ( gitter cells). 63

64. HEALING OF AN INFARCT 64

65. Necrosed tissue is autolysed and much of autolysed material and blood fluid part is absorbed through lymphatics . Undigestible red cells, necrotic tissue and insoluble fibrin are removed through phagocytosis by macrophages. In case of septic infarct both bacterial products and enzymes of leucocytes are concerned in liquefaction of dead tissue. In organs like brain and heart the former is not possible. so the end result is a scar which might show deposits of iron and calcium . 65

66. INFARCT OF DIFFERENT ORGANS 66

67. Infarcts of different organs Location Gross appearance Outcome 1 Myocardial infraction Pale Frequently lethal 2 Pulmonary infraction Hemorrhagic Less commonly fatal 3 Cerebral infraction Hemorrhagic & Pale Fatal if massive 4 Intestinal infraction Hemorrhagic Frequently lethal 5 Renal infraction Pale Not lethal unless massive & bilateral 6 Infract spleen Pale Not lethal 7 Infract liver Pale Not lethal 8 Infracts of lower extremity Pale Not lethal 67

68. PULMONARY INFARCTION Embolism of the pulmonary arteries May occur in patients who have inadequate circulation : Chronic lung diseases Congestive heart failure. 68

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70. GROSS: PULMONARY INFARCTS : W edge-shaped Base on the pleura, hemorrhagic, variable in size lower lobes. Cut surface : dark purple Shows blocked vessel near the apex of the infarcted area. Old organized and healed pulmonary infarcts appear as retracted fibrous scars. 70

71. MICROSCOPICALLY Characteristic histologic feature : coagulative necrosis of the alveolar walls. Initially: infiltration by neutrophils and intense alveolar capillary congestion hemosiderin , phagocytes and granulation tissue. 71

72. RENAL INFARCTION Renal infarcts are Common -caused by Thromboemboli -most commonly originating from heart such as mural thrombi in the left atrium , MI,Vegetative endocarditis Less commonly -renal artery atherosclerosis, - arteritis -sickle cell anemia. 72

73. Grossly : MULTIPLE AND BILATERAL Characteristically : Wedge shape Base - under capsule Apex-pointing towards medulla Narrow rim of preserved renal tissue is spared Cut surface in first 2 to 3 days : red and congested 4 th day: centre turns pale yellow. 1 week: typically anemic , depressed below the surface 73

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75. MICROSCOPICALLY Characteristic: affected area shows coagulative necrosis of renal parenchyma i.e. ghosts of renal tubules and glomeruli without intact nuclei and cytoplasmic content. The margin of the infarct shows inflammatory reaction – initially acute but later macrophages and fibrous tissue predominate. 75

76. INFARCT OF SPLEEN Common site for infarcts It results from Occlusion of one of the splenic arteries or its branches. Most common cause : thromboemboli arising in heart( eg.mural thrombi in the left atrium vegetative endocarditis myocarditis myocardial infarction) 76

77. Less frequently by obstruction of microcirculation (e.g. in myeloproliferative diseases, sickle cell anemia, arteritis , Hodgkin's disease, bacterial infections). Grossly, splenic infarcts are often multiple. Characteristically pale or anemic, wedge-shaped base - at the periphery apex -pointing towards hilum . 77

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79. Features are similar to those found in anemic infarcts in kidney. Coagulative necrosis and inflammatory reaction are seen. Later, the necrotic tissues is replaced by shrunken fibrous scar. MICROSCOPICALLY 79

80. INFARCT OF LIVER Uncommon Dual blood supply Obstruction of the portal vein is usually secondary to other diseases : Hepatic cirrhosis, IV invasion of primary CA of liver, CA of pancreas Generally does not produce ischemic infarction but instead reduced blood supply to hepatic parenchyma causes non-ischemic infarct called infarct of Zahn . 80

81. Obstruction of the hepatic artery or its branches: arteritis , arterio -sclerosis, bland or septic emboli. Grossly, anemic but sometimes hemorrhagic due to stuffing of the site by blood from the portal vein. Infarcts of Zahn (non-ischemic infarcts) produce sharply defined red - blue area in liver parenchyma. 81

82. MICROSCOPICALLY Infarcts of Zahn occurring due to reduced portal blood flow result in atrophy of hepatocytes and dilatation of sinusoids . 82

83. CEREBRAL INFARCTION Local vascular occlusion Occasionally, non-occlusive cause compression of the cerebral arteries from outside and from hypoxic encephalopathy. 83

84. Clinically, the signs and symptoms depend upon the region infarcted . In general, the focal neurologic deficit termed stroke, is present. However, significant atherosclerotic cerebrovascular disease may produce transient ischemic attacks (TIA ). 84

85. ARTERIAL OCCLUSION Occlusion of the cerebral arteries by thrombi- common Embolic arterial occlusion is commonly derived from the heart mural thrombosis complicating MI arterial fibrillation and endocarditis . 85

86. VENOUS OCCLUSION Infrequent phenomenon due to good communications of the cerebral venous drainage. However in cancer, due to increased predisposition to thrombosis, superior sagittal thrombosis may occur leading to bilateral, parasagittal , multiple hemorrhagic infarcts. 86

87. NON-OCCLUSIVE CAUSES Compression of the cerebral arteries from outside occurs during herniation 87

88. PATHOLOGIC CHANGES Anemic or hemorrhagic Affected area : soft and swollen blurring of junction between grey and white matter. 88

89. Within 2-3days, the infarct undergoes softening and degeneration. Central liquefaction with peripheral firm glial reaction thickened leptomeninges , forming a cystic infarct. Hemorrhagic infarct : red and superficially resembles a hematoma 89

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92. MYOCARDIAL INFARCTION Most Important consequence of coronary artery disease Patient may die within first few hours of the onset while remainder suffer from effects of cardiac function INCIDENCE : Occurs at all age but more common in elderly. 92

93. MI Classification ANATOMIC DIAGNOSTIC STEMI NSTEMI TRANSMURAL SUBENDOCARDIAL MI 93

94. Transmural infract & Subendocardial infarct Feature Transmural infract Subendocardial infarct 1 Definition Full-thickness, solid Inner third to half, patchy 2 Frequency Most frequent (95%) Less frequent 3 Distribution Specific area of coronary supply Circumferential 4 Pathogenesis > 75% coronary stenosis Hypoperfusion of myocardium 5 Coronary thrombosis Common Rare 6 Epicarditis Common None 94

95. Normal Sinus Rhythm Q wave representing septal depolarisation R wave representing ventricular depolarisation S wave representing depolarisation of the Purkinje fibres   P wave , which represents the depolarization of the atria T wave  represents the  repolarization  (or recovery) of the  ventricles 95

96. STEMI ST segment elevations T wave changes Q wave development Enzyme elevations 96

97. NSTEMI ST segment depressions T wave changes No Q wave development Mild enzyme elevations 97

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100. ETIOPATHOGENESIS Mechanism of myocardial ischemia Role of platelets Complicated plaques Non – atherosclerotic causes 100

101. MECHANISM OF MYOCARDIAL ISCHEMIA DIMINISHED CORONARY BLOOD FLOW Coronary artery disease,shock MYOCARDIAL OXYGEN DEMAND Exercise,emotion HYPERTROPHY OF HEART W/O SIMULTANEOUS INCREASE IN CORONARY BLOOD FLOW Hypertension,Valvular heart disease 101

102. ROLE OF PLATELETS Rupture of atherosclerotic plaque exposes : sub endothelial collagen to platelets which undergo aggregation, activation & release reaction . These events contribute to the build up of the platelet mass that gives rise to emboli or initiate thrombosis. 102

103. COMPLICATED PLAQUES Two complications occur Superimposed coronary thrombosis – seen in about half of the cases of acute MI. Infusion of fibrinolysins in the first few hours of development of acute MI in such cases restores blood flow in the blocked vessel in majority of cases. Intramural hemorrhage – is found in about one third of cases of acute MI. Hemorrhage and thrombosis may occur together in some cases. 103

104. NON-ATHEROSCLEROTIC CAUSES Coronary vasospasm Coronary ostial stenosis , Embolism, Thrombotic diseases, Trauma and outside compression. 104

105. LOCATION OF INFARCTS LV RV is less susceptible , due to its thin wall, having less metabolic requirements and is thus adequately nourished Atrial infarcts, whenever usually accompany infarct of LV LA is relatively protected because it is supplied by oxygenated blood in the left atrial chamber. 105

106. REGION OF INFARCTION Area of obstructed blood supply by one or more of three coronary arterial trunks in descending order: 1.Left anterior descending coronary artery :40 to 50% 2.Right coronary artery :30 to 40% 3.Left circumflex coronary artery:15 to 20% 106

107. 3 REGIONS OF MYOCARDIAL INFRACTION. Stenosis of the left anterior descending coronary is the most common (40-50%). Region of infarction in the anterior part of the left ventricle including the apex and the anterior two-thirds of the interventricular septum. 107

108. Stenosis of the right coronary artery is the next most frequent (30-40%) . It involves the posterior part of the left ventricle and the posterior one-third of the interventricular septum. 108

109. Stenosis of the left circumflex coronary artery is seen least frequently (15-20%). Its area of involvement is the lateral wall of the left ventricle. 109

110. The changes are similar in both transmural and subendocardial infracts. There is ischemic coagulative necrosis of the myocardium which eventually heals by fibrosis. However, sequential microscopic changes are observed. MICROSCOPICALLY 110

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112. Treatment Options The immediate goal for any acute MI is to restore normal coronary blood flow to vessels and salvage myocardium. There are a variety of medical and medicinal therapies to treat an MI. 112

113. GENERAL TREATMENT MONA Morphine Oxygen Nitroglycerin Aspirin 113

114. FIBRINOLYTIC THERAPY Indicated for patients with STEMI. Should be given within 12 hours of symptom onset. Fibrinolytics will break down clots found within the vessles Contraindications: post op surgical patients, history of hemorrhagic stroke, ulcer disease, pregnancy, etc. 114

115. CARDIAC CATHETERIZATION A diagnostic angiography which includes angioplasty and possible stenting . Performed by an interventional cardiologist with a cardiac surgeon on stand by. Percutaneous procedure through the femoral or brachial artery. 115

116. Upon arrival to the cath lab all actue MI patients will receive: A bolus dose of plavix IV Integrelin Heparin dose either subcu or IV drip Angiomax : a DTI may be substituted for heparin and integrelin . 116

117. CORONARY ARTERY BYPASS GRAFT Surgical treatment where saphenous vein is harvested from the lower leg and used to bypass the occluded vessels. 117

118. LONG TERM CARE Smoking Cessation and lifestyle modifications. Aspirin, Beta Blockers and Clopidogrel will be indefinite. Lipid lowering medication along with diet modifications. 118

119. PUBLIC HEALTH SIGNIFICANCE Occupational heavy lifting- It was found that people with high amount of physical activity and those who endorse in heavy weight lifting during their day to day physical activity were at a high risk of IHD. Petersen CB, Eriksen L, Tolstrup JS, Søgaard K, Grønbæk M, Holtermann A. Occupational heavy lifting and risk of ischemic heart disease and all-cause mortality. BMC public health. 2012 Dec 11;12(1):1070. 119

120. CORONARY OBSTRUCTIVE PULMONARY DISEASE COPD, or chronic obstructive pulmonary (PULL- mun - ary ) disease, is a progressive disease that makes it hard to breathe. Most people who have COPD smoke or used to smoke. Long-term exposure to other lung irritants also is a risk factor for COPD leading to IHD. Examples of other lung irritants include secondhand smoke, air pollution, and chemical fumes and dust from the environment or workplace. 120

121. There is a high risk of ischaemic heart disease caused by exposure to environmental tobacco smoke or second hand smoking. Breathing other people's smoke is an important and avoidable cause of ischaemic heart disease, increasing a person's risk by a quarter. Law M R, Morris J K, Wald N J. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence  BMJ  1997;315 :973 121

122. REFERENCES Robbins and Cotran - Pathologic basis of diseases. 8 th edition. Harsh Mohan – Text book of pathology. 3 rd edition. Mc Gee, Isaacson and Wright – Oxford text book of Pathology. Principles of Pathology volume 1. Anderson’s Pathology – 10 th edition Y.M. Bhende’s - General Pathology, 5 th edition Edward Sheffild - Pathology in Dentistry 1 st edition 122

123. http://www.virtualmedstudent.com http://www.emsa.ca.gov http://nstemi.org https://e n .wikipedia.org REFERENCES 123

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