Circulatory Pathology II PDF

CIRCULATORY PATHOLOGY II HELEN OWUSU-ASANTE (MRS)  THROMBOSIS ▪ Normal Hemostasis is the physiologic coagulation of blood with the purpose of preventing bleeding. ▪ It is a tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels...

CIRCULATORY PATHOLOGY II HELEN OWUSU-ASANTE (MRS)  THROMBOSIS ▪ Normal Hemostasis is the physiologic coagulation of blood with the purpose of preventing bleeding. ▪ It is a tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels and induces the rapid formation of a localized hemostatic plug at the site of vascular injury. ▪ Clotting can also occur after death or in a test tube ▪ Thrombosis is the pathologic formation of an intravascular fibrin-platelet thrombus during life. ▪ A thrombus is a mass formed from blood constituents within a vessel or the heart during life. ▪ Thrombosis represents the inappropriate activation of blood clotting in intact vasculature or after minor injury. ▪ Blood clotting is a physiological protective mechanism but thrombosis is a pathological process with serious consequences. ▪ Thrombosis can only occur during life ▪ Both hemostasis and thrombosis involve three structural and molecular components: – the vascular wall – platelets – the coagulation cascade ▪Intact endothelial cells maintain liquid blood flow by actively: inhibiting platelet adherence preventing coagulation factor activation lysing blood clots that may form ▪Dysfunctional endothelial cells can produce more pro-coagulant factors (e.g., platelet adhesion molecules, tissue factor) or may synthesize less anticoagulant effectors ▪Endothelial dysfunction can be induced by a wide variety of insults as: Hypertension Turbulent blood flow Bacterial endotoxins Radiation injury Metabolic abnormalities such as homocystinemia or hypercholesterolemia Toxins absorbed from cigarette smoke ▪Platelets functions to maintain the integrity of the vascular endothelium. ▪They also participate in endothelial repair through the contribution of PDGF (Platelet- derived growth factor) ▪They form platelet plugs and promote the coagulation cascade. ▪ Coagulation occurs via the sequential enzymatic conversion of a cascade of circulating and locally synthesized proteins ▪ Tissue factor elaborated at sites of injury is the most important initiator of the coagulation cascade ▪ At the final stage of coagulation, thrombin converts fibrinogen into insoluble fibrin, which helps to form the definitive hemostatic plug. FACTORS PREDISPOSING TO THROMBUS FORMATION ▪ There are three main factors, which contribute to thrombus formation. ▪ These factors together are called VIRCHOW’S TRIAD ▪ They are: ALTERATIONS OF BLOOD FLOW ▪ The main effect is to bring platelets into contact with the vessel wall. This results from ▪ (i) Slowing of blood flow, e.g. in cardiac failure or during bed rest. ▪ Turbulence, e.g. by deformation of vessel wall or around venous valves. ENDOTHELIAL INJURY ▪ This leads to platelet adhesion and aggregation. ▪ Common causes are: (a) Disease in vessel wall, e.g. atheroma. (b) Toxins from nearby inflammatory processes. (c) Local compression of vessels (e.g. during operations). ▪ Endothelial damage plays a major role in many arterial thrombi. HYPERCOAGULABILITY ▪ Any alteration of the coagulation pathways that predisposes to thrombosis. ▪ Hypercoagulability of blood can be caused by: ▪ (a) INCREASE in platelets, fibrinogen and prothrombin after operations and childbirth: usually after 5–10 days. ▪ (b) INCREASE in platelet adhesiveness – again after surgery. ▪ (c) Rare inherited abnormalities of thrombosis inhibitors – e.g. antithrombin III deficiency, protein C deficiency, factor V Leiden ▪ (d) Miscellaneous factors – e.g. oral contraceptives (estrogen increases synthetic activity of the liver, including clotting factors), smoking, advanced age, some cancers, nephrotic syndrome, Prolonged bed rest SITES OF THROMBOSIS ▪ Thrombi are common in arteries as a complication of atheroma. ▪ Forming in a rapid circulation, the thrombus consists mainly of PLATELETS (WHITE thrombus). ▪ Common sites include brain and heart ▪ Systemic venous thrombosis is common because of the slow blood flow and lower pressure. It consists of red cells, platelets and fibrin (RED thrombus). ▪ It is most common in the deep veins of the calf and frequently propagates in the femoral and iliac veins – from where it may embolise to the lungs. ▪ Bed rest, operations and cardiac disease are predisposing conditions. MORPHOLOGY OF RECENT THROMBI ▪ Gross morphology: Solid red to red-tan mass occluding or partially occluding the lumen of the blood vessel or lining the wall of a cardiac chamber. ▪ Microscopic morphology: Have Lines of Zahn, which are alternating layers of red blood cells, platelets, and fibrin within the thrombus. ▪ Lines of Zahn are produced by alternating pale layers of platelets and fibrin with darker layers of erythrocytes. FATE OF THROMBOSIS ▪ Propagate: Accumulate further fibrin/platelets. Arterial thrombi usually propagate against blood flow. Venous thrombi usually propagate with blood flow. ▪ Embolization: Thrombus detaches from vessel wall and travels to other sites ▪ Dissolution: Fibrinolytic mechanisms dissolve clot ▪ Organization and Re-canalization: involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. ▪ If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus ▪ However, this may not restore sufficient blood flow for the metabolic needs of the downstream tissue DISSEMINATED INTRAVASCULAR COAGULATION (DIC) ▪ Sudden or insidious onset of widespread fibrin thrombi in the microcirculation (microthrombi spread throughout the circulation "everywhere" ) ▪ Although these thrombi are not grossly visible, they are readily apparent microscopically ▪ Can cause diffuse circulatory insufficiency, particularly in the brain, lungs, heart, and kidneys. ▪ It can evolve into a bleeding catastrophe due to platelet and coagulation protein consumption (consumption coagulopathy) ▪ Since platelets and coagulation factors are consumed because of DIC there is not enough platelets for clotting in case of an injury ▪ At the same time, fibrinolytic mechanisms are activated. ▪ DIC is not a primary disease but rather a potential complication of any condition associated with widespread activation of thrombin. ▪ Ex. If someone has septicaemia, as a result of bacterial infection there will be widespread activation of thrombin which causes fibrin formation and hence thrombus. ▪ DIC is usually seen in ICU patients. ▪ Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. ▪ DIC may also be seen in pregnant females. ▪ Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, as well as platelets and heparin to prevent further thrombi formation  EMBOLISM ▪ DEFINITION: A detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin resulting in the occlusion of a vessel. ▪ Embolism can be caused by any obstruction of a blood vessel such as: ▪ Thromboemboli: most common (98%) Atheromatous emboli (severe atherosclerosis) ▪Fat emboli (bone fractures and soft tissue trauma) Bone marrow emboli (bone fractures and cardiopulmonary resuscitation [CPR]) ▪Gas emboli cause decompression sickness (“the bends” or caisson disease) when rapid ascent results in nitrogen gas bubbles in the blood vessels.  Amniotic fluid emboli are a complication of labor that may result in DIC; fetal squamous cells are seen in the maternal pulmonary vessels. Tumor emboli (metastasis) Talc emboli (IV drug abuse) Bacterial/septic emboli (infectious endocarditis) PULMONARY EMBOLISM ▪ In more than 95% of cases, venous emboli originate from deep leg vein thrombi above the level of the knee, through the progressively larger channels and pass through the right side of the heart entering the pulmonary vasculature. ▪ If a pulmonary thromboembolus obstructs more than 60% of the pulmonary vasculature, sudden death of the patient can result. ▪ Symptoms and signs of pulmonary embolism ▪ Sudden onset of chest pain and dyspnea; ▪ tachypnea; ▪ cough with or without hemoptysis is present in 50% of cases; ▪ and hypoxia (arterial pO2 is < 80%), respiratory alkalosis  INFARCTION ▪ Infarction is a localized area of tissue death or necrosis due to inadequate blood supply to the affected area. ▪ An infarct is the pathologic finding; an infarction is the process. ▪ Hypoxia and ischemia are the two main mechanisms that result in infarction of organs. ▪ Hypoxia is lack of oxygen to an organ, and ischemia is lack of blood flow to an organ. ▪ The heart, the lungs and the brain are the most common sites. Less common are the small intestines and the kidney and spleen. ▪ Nearly all cases of infarction are due to complete or near- complete occlusion of arterial blood flow due to embolism, most typically thromboembolism. ▪ Under rare circumstances arterial flow can also be completely disrupted anatomically due to twisting closed of the arterial supply as may occur during testicular torsion or bowel volvulus. TYPES ▪ Anemic infarcts (pale or white color) represent a lack of erythrocytes entering the ischemically injured tissue. This results when the occluded artery is the sole supply of the organ and the organ is relatively solid such as the spleen, kidney, and heart. ▪ Hemorrhagic infarcts (red color) occur in organs with a dual blood supply or collateral circulation, such as the lung and intestines, and can also occur with venous occlusion (e.g., testicular torsion). ▪ Microscopic pathology of infarction can show either coagulative necrosis (most organs) or liquifactive necrosis (brain). CAUSES: OBSTRUCTION OF VESSEL: Due to atherosclerosis, thrombi, emboli, damage to vasculature (e.g., trauma, neoplasms and cytomegalovirus infection), or external compression of an artery or vein (e.g., torsion of organ). ▪ GENERALIZED HYPOTENSION: As occurs in forms of shock. COMPLICATIONS OF AN INFARCT: ▪ Variable, depending on location and size. ▪ As with hemorrhage, think of location of infarct. ▪ ▪ A 2.0-cm infarct of the liver might not be noticed, but a 2.0-cm infarct of the brainstem would most likely cause death.