Lung, acute pulmonary congestion and edema – Gross, cut surface Lung, acute pulmonary congestion and edema – Gross, cut surface The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. Lung, acute pulmonary congestion and edema – Gross, cut surface Lung, acute pulmonary congestion and edema – Gross, cut surface The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. Lung, acute pulmonary congestion and edema – Gross, cut surface Lung, acute pulmonary congestion and edema – Gross, cut surface The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. The lung has a red, hyperemic cut surface, reflecting passive congestion, due to increased hydrostatic pressure, as seen in cases of left heart failure. The transudate, mixed with air in the alveoli, gives the cut surface a frothy appearance. Gross cut surface Lung acute pulmonary congestion and edema
Low power Lung, acute passive congestion and edema
Gross, cross section Veins, iliac, with thrombi (death caused by massive pulmonary embolus) –
High power Vein with organizing and recanalizin g thrombus
Gross, cross section Coronary artery, right, with thrombus
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.
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? Questions
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.
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.
Gross, cross section Coronary artery, right, with thrombus
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.
Medium power Lung, acute pulmonary congestion and edema
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.
High power Lung, chronic passive venous congestion
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
What might the symptoms be? Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and cough
Did this patient have clinical features suggestive of pulmonary thromboembolism? Yes. He had deep vein thrombosis in his left leg, which most likely was the source of an embolus. His chest pain that was exaggerated by breathing suggests pleural inflammation overlying an infarct in the right lower lobe. Massive pulmonary thromboembolism was the probable cause of his death.
Why are some infarcts red and others pale? Red infarcts result from hemorrhage into the necrotic area. This is likely to occur in tissues that have a loose texture and dual blood supply (eg, lung); by contrast, pale infarcts occur in compact tissues and those in which the collaterals do not readily refill the necrotic area (eg, heart).
What conditions predispose to venous thrombosis? Venous stasis caused by prolonged immobilization (eg, in hospitalized patients after surgery) or by congestive heart failure.
What is the most common source of clinically significant pulmonary emboli (ie, thrombi from which vessels in the leg)? The vessels are the large, deep veins of the leg above the knee joint. These include popliteal veins, femoral veins, and iliac veins. Thrombi in these vessels often do not produce local symptoms. In contrast, thrombi in superficial veins often produce pain, edema, and varicose ulcers, but usually do not embolize.
What is the most common symptom associated with such venous thrombi? There are no symptoms in about 50% of cases. Local pain and edema occur in the remaining cases.
What is the most common symptom of pulmonary embolism? There are usually no symptoms. Most pulmonary emboli (60-80%) are clinically silent because of their small size and because of the dual blood flow through the bronchial circulation. With time, these emboli organize and are incorporated into the vessel wall.
How and when does pulmonary thromboembolism cause sudden death? If more than 60% of the pulmonary circulation is obstructed by emboli, the patient is at a high risk of sudden death due to acute right heart failure (cor pulmonale) or shock (cardiovascular collapse).
When does pulmonary thromboembolism result in infarction? The possibility of developing pulmonary infarction is higher in a previously diseased lung, especially in the setting of sluggish bronchial arterial flow or prior pulmonary congestion due to left heart failure.
What is the risk of recurrence of pulmonary thromboembolism? In general, the patient who has had one pulmonary embolus is at a higher risk of having more.
In what respects does fat embolism significantly differ from a typical venous pulmonary thromboembolism? Fat embolism occurs after fractures of long bones, major soft tissue trauma, or severe burns. Most patients with fat embolism are asymptomatic, just like venous thromboembolism. But in those cases (less than 10%) that are symptomatic, besides pulmonary insufficiency, patients also develop neurologic symptoms, skin rashes, and, sometimes, anemia and thrombocytopenia. Microscopically, the emboli consist of fat or marrow particles.
In what respects does amniotic fluid embolism significantly differ from a typical venous pulmonary thromboembolism? Amniotic fluid embolism, in contrast, is a grave condition, with mortality in excess of 80% due to respiratory insufficiency, shock, DIC, seizures, and coma. This condition is a rare complication of labor (1 in 50,000 deliveries). Microscopically, pulmonary vessels contain squamous cells and mucin (contents of amniotic fluid) derived from fetal skin and intestinal tract.