Download
1 / 65
660 likes | 1.14k Views
Hemodynamic Disorders . Tutorial Activities Dr: Awatif Jamal . Gross cut surface Lung acute pulmonary congestion and edema. Low power Lung, acute passive congestion and edema. Gross, cut surface Lung, chronic passive congestion –. Medium power Lung, chronic passive congestion.
E N D
Hemodynamic Disorders Tutorial Activities Dr: Awatif Jamal
Gross, cut surface Liver, chronic passive congestion with centrilobular necrosis –
Gross, cut surface Spleen, chronic passive congestion (case of heart failure)
Breast, lymphedema secondary to breast carcinoma – Clinical presentation
Gross, cross sectionVeins, iliac, with thrombi (death caused by massive pulmonary embolus) –
Clinical Case A 65-year-old man presented to the emergency room with a recent (4-hour) history of severe chest pain radiating to his left arm. He was suspected to have had a "heart attack." Coronary angiography revealed a complete occlusion of the left anterior descending branch about 2 cm from its origin. He was given a therapeutic dose of recombinant human tissue plasminogen activator (t-PA). This treatment restored coronary artery blood flow, and his chest pain improved. Simultaneously, he was started on one tablet of aspirin per day.
Clinical Case • Seven days later, he noted swelling of both legs and feet and was found to have pitting edema of the legs; his liver was somewhat enlarged; and his neck veins (jugular) appeared full. • He was given diuretics and asked to consume a salt-restricted diet. Because of considerable weakness, he remained in bed most of the time.
Clinical Case • A few days later, he developed sudden pain in the lower right part of his chest, which was aggravated by taking a deep breath. • Physical examination revealed that his left leg had developed more swelling than the right. • X-ray of his chest showed a faint shadow in the peripheral part of the lower lobe of the right lung. Intravenous heparin was started. • Two days later, he became very breathless and died suddenly.
Questions 1-What is the basis of thrombosis in the coronary artery? 2- What are the factors that predispose to arterial versus venous thrombosis? 3-Why was t-PA given? What is the mechanism of action of t-PA? 4-What are the other naturally occurring anticoagulants? 5- Why is aspirin given in such cases? What stage of hemostasis is affected by aspirin? 4- Why did the patient develop edema initially? 5- What are the factors that predispose to generalized edema? 6- Why did he later develop more edema in one leg? Why are patients with edema given a salt-free diet? 7- What are the clinical settings in which venous thrombosis of leg veins occurs? What is the most feared consequence?
What therapeutic agent can be used to lyse the clots in coronary vessels? How do the various natural anticoagulants act? • Thrombolysis can be accomplished by tissue plasminogen activator (t-PA) or streptokinase; both cause fibrinolysis by generating plasmin.
Why was aspirin given? What stage of hemostasis is affected by aspirin? Aspirin prevents thrombogenesis by inhibiting platelet aggregation. This is achieved by inhibition of cyclooxygenase, thereby preventing the generation of thromboxane A2.
How do the various natural anticoagulants act? There are three natural anticoagulants: (1) The protein C system generates active protein C that inactivates cofactors V and VIII. Protein C itself is activated by thrombin after the latter binds to thrombomodulin on the endothelium. (2) Antithrombin is activated by binding to heparin-like molecules on the endothelium; activated antithrombin causes proteolysis of active factors IX, X, and XI, and thrombin. (3) Plasmin cleaves fibrin. It is derived from its circulating precursor, plasminogen, by the action of tissue plasminogen activator, which is synthesized by endothelial cells.
low-power micrograph Heart, coronary artery - Angiography & radiograph
What is the difference between a postmortem clot and a thrombus? • Postmortem clots are not attached to endothelium; they are gelatinous, rubbery, dark red at the ends and yellowish elsewhere. • Thrombi are attached to endothelium and are traversed by pale grey fibrin strands that can be seen on cut section; they are more firm but fragile.
What stage in the formation of a thrombus is targeted by the currently used antithrombotic medications? The most important stage in thrombogenesis that is inhibited by the current antithrombotic medications is platelet aggregation. This crucial step requires binding of platelets by fibrinogen molecules, which attach to platelets at the GPIIb/IIIa receptor. Different antithrombotic drugs inhibit platelet aggregation in different ways. For example, aspirin inhibits synthesis of thromboxane A2. Newer drugs inhibit ADP-mediated structural alterations in the GPIIb/IIIa receptor, thus preventing binding of fibrinogen to this receptor. Drugs that directly bind and inhibit the GPIIb/IIIa receptor are also available for experimental trials.
What are other causes of arterial thrombosis? Arterial thrombosis is caused by injury to the endothelium. In addition to atherosclerosis, other causes are vasculitis and trauma.
What is the thrombus made of? Fibrin, platelets, and red cells.
What causes arterial thrombosis? ..venous thrombosis? Arterial thrombosis is caused by endothelial damage (eg, atherosclerosis or vasculitis); venous thrombosis is caused by stasis (sluggishness) of blood flow. Both types of vessels are affected in hypercoagulable states such as antithrombin or protein C deficiency.
What are the various fates of thrombi? Propagation, embolism, dissolution, and organization with recanalization.
Which of these fates is clinically most significant in the arterial circulation vs. the venous circulation? • The most significant problem with arterial thrombi is propagation leading to luminal obstruction, resulting in infarction of the tissue supplied. Important examples include myocardial and cerebral infarction. In contrast, the most significant problem with venous thrombi is the possibility of potentially fatal embolization into the pulmonary circulation.
Heart, myocardial infarct: acute vs healed - Gross, cross section • Healed infarct fibrosis • Acute infarct coagulative necrosis and surrounded by hyperemia
What are the major similarities between a myocardial and a cerebral infarct? • The major similarity is in the etiology. • Both types of infarcts are commonly caused by thrombotic occlusion of the arteries supplying them. • Thrombi usually form on the same underlying disease process (ie, atherosclerotic arterial disease). • Also, the early histologic reactions, such as neutrophilic infiltration and granulation tissue formation, are common to both.
What are the major differences between a myocardial and a cerebral infarct? • A myocardial infarct typically features coagulative necrosis, which heals by fibrosis and leaves behind a fibrous scar. In contrast, a cerebral infarct is typically liquefactive necrosis, in which dead tissue is digested without being replaced by fibrosis, leaving behind a cystic, cavitary lesion.
What is the mechanism of formation of hemorrhagic infarcts in brain? • Brain infarcts can be pale or hemorrhagic. Hemorrhagic infarcts are due to arterial occlusion followed by reperfusion. • Examples are embolic occlusion followed by fragmentation of emboli or occlusive vasospasm that later is relieved.
What caused enlargement of the liver, edema, and fullness of the neck veins in this patient? This patient had ischemic heart disease due to coronary thrombosis. This led to failure of the left ventricle and, eventually, of the right ventricle, giving rise to congestive heart failure. Because of impaired venous return to the heart, the neck veins become distended, the liver becomes enlarged, and fluid collects in interstitial spaces (edema).
What is the brown pigment that is derived from hemoglobin? • Hemosiderin.
What is the pathogenesis of pulmonary edema? • Left ventricular failure (eg, caused by a myocardial infarct) causes pump failure, and secondarily there is impaired flow of blood from the lung to the left atrium. This causes increased hydrostatic pressure in pulmonary alveolar capillaries and subsequent transudation of fluid into alveoli. • Pulmonary edema in other cases may also result from damage to alveolar capillaries (eg, in adult respiratory distress syndrome).
How does this type of edema differ from that seen in acute inflammation? The fluid in pulmonary edema is a transudate (ie, it is protein poor, has low specific gravity, and does not contain inflammatory cells). Edema in inflammation is an exudate.
Are the alveolar septa normal in thickness? • They are thickened, due to edema and reactive fibrosis.
What effect would such a histologic picture have on gaseous exchange in the lung? • It would be markedly impaired
