Embolism, Infarction, and Shock PDF

Embolism, Infarct and Shock Debra Hazen-Martin, PhD Office: 792-2906 Email: [email protected] Inflammation 1: Embolism, Infarction, and Introduction to Shock Outline: I. II. III. Embolism A. Definition B. Origin and Outcomes C. Types 1) Pulmonary Thromboembolism 2) Systemic Thromboembolism 3) Par...

Embolism, Infarct and Shock Debra Hazen-Martin, PhD Office: 792-2906 Email: [email protected] Inflammation 1: Embolism, Infarction, and Introduction to Shock Outline: I. II. III. Embolism A. Definition B. Origin and Outcomes C. Types 1) Pulmonary Thromboembolism 2) Systemic Thromboembolism 3) Paradoxical Embolism 4) Fat Embolism 5) Air/Gas Embolism 6) Amniotic Fluid Embolism Infarct A. Definition and Significance B. Morphologic Types 1) Red Infarct 2) White Infarct Introduction to Shock A. Definition and overview of mechanism B. Categories and nomenclature C. Stages of shock D. Histopathology of shock Suggested Reading: Robbins Basic Pathology, Chapter 4 (112-119) Objectives: 1. 2. Define embolus, infarct, and shock. Describe possible origins of emboli and where they are likely to lodge, based on origin. 3. Differentiate between pulmonary and systemic emboli. 4. Discuss the possible causes and pathogenesis of fat emboli syndrome. 5. Describe the terminology of red and white infarcts and detail the factors that determine the classification of each type. 6. Review coagulative and liquefactive necrosis. 7. Describe the major categories of shock and mechanisms that lead to hypoperfusion in each. 8. List and describe the stages of shock with emphasis on compensatory mechanisms. 9. Discuss the role of inflammatory mediators in the pathogenesis of septic shock due to gram- negative organisms. 10. Describe the morphology of shock in various organs. 1 Embolism, Infarct and Shock I. Embolism A. Definition of Embolism: A detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin (Basic Pathology, 9th Ed.) B. Origin of Emboli: 99% of emboli arise from an existing thrombus. Dislodged pieces of arterial or venous thrombi may form thromboemboli. The remaining 1% originate from air, fat, bone marrow, atherosclerotic debris, amniotic fluid, tumor fragments, or exogenous foreign bodies (like a bullet). Emobli -venous arterial The main outcome and danger of emboli, especially thromboemboli, is that they will lodge within the first vessel that has a smaller diameter than the embolus itself. The embolus obstructs the blood flow within the vessel and result is ischemic infarct and necrosis of downstream tissues. Emboli arising from venous thrombi will lodge in the pulmonary artery or its branches. Emboli arising from arterial thrombi will lodge in the systemic arterial vasculature. 2 Embolism, Infarct and Shock C. Types of Emboli: 1. Pulmonary Thromboembolism Pulmonary embolism is estimated to occur in 20-25 of every 100,000 (24/1000) hospitalized patients. It is fatal in 2% of cases and accounts for 200,000 deaths/ year in US. About 95% of the time, the origin of the embolism is a deep vein thrombus (DVT) of lower limb above level of knee. There are multiply risk factors for development of DVT as described in the adjacent slide and previous lectures. Large emboli from DVT may lodge and block the entire pulmonary trunk and the main right and left pulmonary arteries. They become “stuck” at the bifurcation and are called a saddle embolus. This results in a sudden increase in the pulmonary artery pressure proximal to the embolus, a drop in cardiac output (easily exceeding 60%) and sudden death (cor pulmonale). Obstruction of 60% or more of the pulmonary vasculature will result in a fatal outcome. This may be accomplished by a single large thromboembolus (saddle embolus, previous slide) or multiple smaller emboli impacting multiple medium to small sized arteries. You may also see a shower of smaller emboli passing into the distal vasculature. 3 Embolism, Infarct and Shock 60-80% of all incidents of pulmonary thromboembolism are clinically silent. Small emboli are resolved by rapid fibrinolytic cleavage. Others will undergo a process of organization and incorporation into the vascular wall. In individuals with intact cardiovascular systems, the embolus may not cause infarct due to the dual blood supply to lung parenchyma. The bronchiolar arteries (branches of the aorta) will provide adequate arterial supply to affected areas. The same sized embolus in a patient with compromised cardiac function (left sided heart failure and inadequate blood flow from the bronchial arteries) will likely have greater impact and is more likely to cause an infarct. Recurrent pulmonary thromboemboli are common. Most individuals who have one episode will be at higher risk for recurrent embolic events. Repeated pulmonary emboli may lead to pulmonary hypertension and/or right ventricular failure (cor pulmonale) due to progressive vascular sclerosis. 4 Embolism, Infarct and Shock 2. Systemic Thromboembolism Emboli that originate in the arterial system will lodge in tissues supplied by the systemic arteries. This will result in infarct downstream of occluded vessels and the consequence of infarct will be determined by the size of the embolus, the type of tissue affected, and whether the tissue has a dual blood supply. 80% of systemic thromboemboli originate from cardiac mural thrombi predominantly in the left ventricle (75%) following infarct in that area of the heart. They may also originate from mural thrombi in the left atrium secondary to mitral valve disease and subsequent dilation of the atrium. The remaining 20% may arise from sites of aortic aneurysm, ulcerated atherosclerotic plaque, or fragments of vegetative lesions on heart valves. Systemic emboli will lodge in the lower extremities (75%), brain (10%) and intestines, kidneys, or spleen. 5 Embolism, Infarct and Shock 3. Paradoxical Embolism occurs when venous thrombi give rise to emboli that travel to the right ventricle and then move into the left ventricle for system distribution via a defect in the inter-ventricular wall. 4. Fat Embolism: Fat from the marrow of fractured long bones or soft tissues involved in trauma may form emboli. 90% of individuals with severe skeletal trauma will develop emboli but only 10% will have clinical consequence. Of those 10% with clinical consequences, 1% will show symptoms of the Fat Embolism Syndrome (FES) with a sudden onset of the following symptoms 1-3 days post trauma: rapid breathing (tachypnea), difficulty breathing (dyspnea), rapid heart rate (tachycardia), irritability that proceeds to delirium and coma. 10% of those with FES will die. What are the mechanisms for the respiratory distress, neurologic symptoms, anemia and thrombocytopenia observed? 6 Embolism, Infarct and Shock The pathogenesis of FES involves mechanical obstruction with hypoxia and infarct in multiple tissues. The release of free fatty acids and endothelial cell injury also initiates an inflammatory response with release of chemical mediators leading to platelet aggregation and activation. FES is fatal in 10% of patients who develop the syndrome. 5. Air Embolism: >100 ml of air must be introduces into the vasculature to produce any clinical effect. This may occur due to chest wall injury, obstetric procedures of sudden changes in atmospheric pressure as in rapid decompression from a high pressure environment (ex: under water). Gases are as obstructive as the solid emboli previously described and may cause distal ischemic injury. When divers go deep, gases are dissolved into the blood and tissues. With rapid ascent, the gases expand and bubble out of solution resulting in the “bends” (skeletal/muscular pain) and the “chokes” (respiratory pain). 6. Amniotic Fluid Embolism is a rare complication of labor and the immediate postpartum period which occurs in 1 of 40,000-50,000 deliveries. It leads to a maternal mortality rates of 40 - 80%. The amniotic fluid enters the maternal circulation via a tear in the placental membranes and rupture of the uterine veins. Amniotic fluid embolism accounts for 10% of all maternal deaths in the US and 85% of the survivors will suffer permanent neurologic defects. 7 Embolism, Infarct and Shock Amniotic fluid embolic events result in the sudden onset of maternal dyspnea, cyanosis, hypotensive shock, seizure and coma. In the adjacent slide of the maternal lung you can see emboli lodged in the small arteries of the lung. The emboli contain fetal elements including squamous cells, lanugo hair, vernix caseosa, and respiratory or GI mucins. These substances are thrombogenic and initiate systemic microemboli leading to disseminated intravascular coagulation (DIC). II. Infarction A. Definition: An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue. 99% are due to thrombosis or thromboembolic events. Of these most are arterial (systemic). Venous events are more likely to cause obstruction and congestion. The remaining 1% is due to occlusions resulting from any of the events listed on the adjacent slide. 8 Embolism, Infarct and Shock B. Classification of infarcts by color: Red infarcts are hemorrhagic and usually occur in loose tissues with sluggish venous outflow or venous occlusion. The primary reason that the infarct is red is that there is good collateral blood flow or access to a second source of blood allowing repression of the damaged area. In this slide, a segment of gut supplied by the superior mesenteric artery is infarcted by blockage of the entire large artery. Because there are anastomotic connections along the length of the gut, the infarcted segment has been reperfused following the initial occlusive event. In this slide, a red infarct is seen in the lung due to the dual blood supply (pulmonary and bronchiolar arteries) and the loose nature of the tissue. White infarcts are seen in cases of arterial occlusion and in dense solid organs where there is a single end artery supply as in the spleen and kidney observed here. 9 Embolism, Infarct and Shock Most white infarcts are wedge-shaped with the occluded vessel at the apex and the base at the serosal surface of the organ. Ischemic coagulative necrosis is the dominant histologic picture and in a large infarct this will lead to a scar. III. Shoc k A. Definition and Overview of Mechanisms Shock is the final common pathway for a variety of lethal events. In previous lectures we have alluded to shock as outcome for hemorrhage, extreme trauma or burn, large myocardial infarct, massive pulmonary embolism, microbial sepsis, and other conditions. The common factor in the outcome of shock is systemic hypoperfusion. The hypoperfusion results from either 1) reduced cardiac output (failure of the pump) or 2) loss of effective circulating blood volume and pressure(failure to keep or contain fluid). Systemic hypoperfusion leads to hypotension, impaired tissue perfusion, cellular hypoxia, reversible cellular injury and with time irreversible tissue injury and death. 10 Embolism, Infarct and Shock B. Classification of Types of Shock 3 Major Categories of Shock: Your textbook refers to 3 major categories of shock: Cardiogenic, Hypovolemic, and Septic Shock. It indicates that 2 other categories are far less common and include Anaphalactic Shock and Neurogenic Shock. (listed on the left side of the table). Be aware: Other textbooks and individuals will classify shock in a slightly different way (see right side of table). These are not contradictory. The classification system on the right focuses more discretely on the point of system failure. Cardiogenic shock is due to a failure of the pump and has a 70% mortality rate resulting in 2/3 of all in-hospital deaths. The causes of cardiogenic shock include: Myocardial infarct Ventricular arrhythmia Extrinsic compression (cardiac tamponade) Outflow obstruction (pulmonary embolism >60%) 11 Embolism, Infarct and Shock Hypovolemic shock is due to loss of blood or plasma volume secondary to hemorrhage, severe burns, trauma, vomiting or diarrhea. Septic Shock is due to microbial infection by the following types of organisms or agents and subsequent systemic reaction to microbial products: Gram negative - endotoxins Gram-positive – exotoxins, currently most common with advent of MSRA Fungal sepsis - becoming more prevalent Superantigens – toxic shock syndrome Septic shock has a mortality rate of 25-50% and results in 750,000 deaths annually in the US. Why is this classified by some as a Distributive Shock?? Until the advent of MRSA, the most common form of septic shock was that resulting from gram - endotoxins. Reaction to bacterial wall lipopolysaccharides (LPS) is responsible. Free LPS binds to LPSbinding proteins in the circulation and the complex binds CD14 receptors on monocytes, macrophages, and neutrophils. This binding occurs through a toll-like receptor (TLR-4) and activates elaboration of inflammatory cytokines. The acute inflammation is followed by acute phase reaction driven by IL-1, TNF, and IL-6. 12 Embolism, Infarct and Shock Recall the components of the acute phase reaction in this slide from your previous lecture. One of the outcomes of the increased synthesis of coagulation proteins will be to promote clot formation. In addition secondary chemical mediators including NO and platelet activating factor (PAF) are produced. Both are potent vasodilators. At high quantities the products of the acute phase response and secondary chemical mediators (NO, PAF) will lead to systemic vasodilation causing hypotension, tissue and endothelial damage with widespread activation of the coagulation cascade culminating in DIC. Another less common category of shock includes Neurogenic Shock which may occur due to an anesthetic accident or spinal cord injury where a total loss of vascular tone (explaining its inclusion in Distributive Shock) that leads to peripheral pooling of blood and, indirectly, loss of cardiac output. 13 Embolism, Infarct and Shock Anaphylactic shock is a result of immunoglobulin E hypersensitivity reactions resulting in systemic vasodilation and dramatic increased in permeability leading to the edema seen in the larynx pictured in this slide. C. 3 Stages of shock - There is a progression through the following stages (generalized largely from the events of hypovolemic shock): 1. Nonprogressive stage - The body is trying to maintain cardiac output and blood pressure so this phase includes responses that attempt to compensate by increasing fluid volume (reninangiotensin axis activation, antidiuretic hormone) and reflex neurohumoral mechanisms (sympathetic stimulation) to produce tachycardia and peripheral vasoconstriction both in an effort to elevate blood pressure. 2. Progressive stage – in this phase widespread hypoxia results from failure of the compensatory measures above and results in imbalances due to anaerobic glycolysis, production of lactic acid, lower tissue pH leading to loss of vasomotor response so blood pools peripherally. The widespread endothelial cell injury promotes responses that lead to development of DIC 3. Irreversible stage – further damage proceeds due to necrosis and leads to total organ failure. Cell damage will occur in many tissues of the body due to continued hypoxia necrotic cell death with lysosomal enzyme leakage. Renal failure (acute tubular necrosis) and loss of cardiac function (elaboration of NO) ensue. Note that in septic (distributive shock) there will likely be initial peripheral vasodilation and the skin will be warm and flushed in contrast to the early compensatory vasoconstriction mentioned above. 14 Embolism, Infarct and Shock D. Histopathologic changes of shock – Kidney cortex is illustrated in the adjacent slide. But evidence of damage will be evident throughout other tissues: • • • • • • Brain – ischemic encephalopathy Heart- coagulative necrosis and/or contraction band necrosis Adrenal gland – cortical lipid depletion GI- hemorrhage and mucosal necrosis leading to hemorrhagic enteropathy Liver- fatty change and central hemorrhagic necrosis Fibrin microemboli in the vasculature of many organs due to DIC 15