1. Hemodynamic Disorders
Tutorial Activities
Dr: Awatif Jamal

2. Gross cut surface Lung acute pulmonary congestion and edema
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.
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.
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.
Gross cut surface Lung acute pulmonary congestion and edema
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.     

3. Low power Lung, acute passive congestion and edema
At low power, the tortuous, congested capillaries are evident in the alveolar septa. Compare with normal lung. The transudate in the alveoli is a thin fluid that escaped when the tissue was cut. Thus, it is usually not seen in sections. For a view of edema fluid, see the feature "Acute pulmonary congestion and edema" with the next image.  

4. Gross, cut surface Lung, chronic passive congestion –
The lung has a red-brown color due to accumulation of hemosiderin from extravasated erythrocytes. Fibrosis causes the cut edges to stand up rather than collapse.  

5. Medium power Lung, chronic passive congestion
The alveolar walls are thickened by the deposition of collagen. The alveoli contain numerous macrophages that contain hemosiderin pigment. These features are characteristic of chronic passive congestion.     

6. Gross, cut surface Liver, chronic passive congestion with centrilobular necrosis –
The red areas represent the congested and necrotic central zones of the lobules. The pale areas are the periportal areas.  

7. Medium power Liver, chronic passive congestion
The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.      The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.      The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.      The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.      The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.      The hepatocytes in the periportal area appear relatively normal, while around the central vein, the cords of cells become thin and atrophic. The smudgy, eosinophilic area represents congestion and hemorrhage. Compare with normal liver.     

8. Medium power Liver, chronic passive congestion
Recall that blood flow within hepatic lobules is from branches of the portal vein and hepatic artery in portal areas towards a central vein. The central portions of the lobules are the last areas to receive blood supply and are thus first to undergo atrophy and necrosis with circulatory compromise. Chronic passive congestion causes atrophy of central hepatic cells by an ischemic process (not due to direct pressure). As liver cords go from portal to central areas, note gradual narrowing (atrophy) of cords and distension of sinusoids. Centrilobular necrosis results from exaggeration of a previous congestive circulatory defect. Compare to normal liver.     

9. Gross, cut surface Spleen, chronic passive congestion (case of heart failure)
The spleen is enlarged secondary to passive congestion, reflecting portal hypertension. Fine white trabeculae reflect fibrous scarring.     

10. Lymphedema, filaria infection – Clinical presentation
This is a case of elephantiasis caused by filariasis, a parasitic infection that causes scarring of the lymph nodes, leading to lymphatic congestion and consequent edema and massive swelling of both legs.     

11. Breast, lymphedema secondary to breast carcinoma – Clinical presentation
Breast cancer cells have blocked the lymphatic channels draining fluid from the skin of the right breast, leading to passive congestion and resulting in a peau d'orange (orange skin) appearance. Compare with the normal left breast.     

12. Gross Heart and lungs, pulmonary thromboembolus -
This image illustrates a large pulmonary thromboembolus from an autopsy performed on an elderly woman who died suddenly while hospitalized for evaluation of an abdominal mass. The main pulmonary artery has been opened anteriorly to reveal a massive thromboembolus that straddles the bifurcation of the main pulmonary artery and completely occludes the right and left pulmonary arteries. Postmortem examination of the abdomen revealed a mucin-producing adenocarcinoma (cancer) of the sigmoid colon that had spread throughout much of the peritoneal cavity.     

13. Gross Pulmonary artery, pulmonary thromboembolus -
This is a closer view of the pulmonary thromboembolus illustrated in the previous image, demonstrating complete occlusion of both the right and left pulmonary arteries by the saddle embolus. Delicate fibrin-platelet lamellae, or lines of Zahn, are visible on the external surface of the thromboembolus.     

14. Deep vein thrombosis - Clinical presentation
Because of impaired venous return and locally increased venous pressure, a lower extremity with a deep vein thrombosis is often dusky red and edematous, as seen in this image.     

15. Gross, cross section Veins, iliac, with thrombi (death caused by massive pulmonary embolus) –
The thrombi are red, due to entrapped erythrocytes, and have a laminated appearance, reflecting varying composition of the thrombus, which relates to the rate of blood flow at the time the thrombus was forming.     

16. High power Vein with organizing and recanalizing thrombus
A higher power view of the area of attachment to the vessel wall shows granulation tissue formation, which may eventually lead to recanalization of the thrombus.     

17. Gross, cross section Coronary artery, right, with thrombus
This is a view of the external surface of the heart, where a coronary artery has been cross-sectioned, revealing a thrombus filling and completely occluding the lumen. Thrombi in coronary arteries are almost always due to endothelial damage resulting from atherosclerosis.     

18. 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.

19. 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.

20. 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.

21. 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?

22. Heart, coronary artery angiography Radiograph
Note the narrowing of the artery, due most likely to atherosclerosis. Damage to the intima due to atherosclerosis is a major cause of thrombosis in arteries. The resultant ischemia of the myocardium can lead to ischemic necrosis (ie, an infarct).  

23. 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.

24. 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.

25. 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.

26. low-power micrograph Heart, coronary artery - Angiography & radiograph
The left frame shows marked narrowing as seen by angiography. The right frame shows the histology of the narrowed area. There is marked thickening of the wall due to fibrosis of the intima. This results from coronary atherosclerosis, a process characterized by lipid deposition in the intimal layer followed by laying down of collagen and calcification. At this late stage, there is no lipid visible in the vessel wall. The red mass in the narrowed lumen is a postmortem clot.  

27. 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.

28. 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.

29. 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.

30. Gross, cross section Coronary artery, right, with thrombus
The lumen of the coronary artery is completely occluded by a dark red thrombus. Thrombosis in this case and in arteries in general results from damage to the endothelium. The most common and the most important cause of arterial thrombosis is atherosclerosis, a disease in which the intima is primarily involved.  

31. Low power Heart, coronary artery thrombosis
This cross section of the coronary artery in the previous image shows marked concentric thickening of the intima, due to intimal damage and subsequent deposition of fibrous tissue. On one side, a fresh thrombus is attached to the damaged endothelium. In some parts of the thrombus, there is formation of new capillary channels. This process, called recanalization, can restore blood flow. Note that the media is thinned, secondary to compression by the thickened intima.

32. What is the thrombus made of?
Fibrin, platelets, and red cells.

33. 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.

34. What are the various fates of thrombi?
Propagation, embolism, dissolution, and organization with recanalization.

35. 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.

36. Heart, myocardial infarct: acute vs healed - Gross, cross section
Healed infarct fibrosis
Acute infarct coagulative necrosis and surrounded by hyperemia
The well-defined pale area in the acute myocardial infarct represents coagulative necrosis. It is surrounded by a red area of reactive hyperemia. In contrast, the ill-defined pale area in the old myocardial infarct represents a fibrous scar.     

37. Gross, coronal section Brain, cerebral infarct: acute
The well-defined hemorrhagic area in the acute cerebral infarct represents hemorrhagic liquefactive necrosis. In contrast, the cystic cavitary area representing the remote infarct is the end result of liquefactive necrosis.  

38. The major similarity is in the etiology.
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.

39. 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.

40. 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.

41. Gross, cut surface Liver, chronic passive venous congestion
This condition is caused by resistance or obstruction to the outflow of venous blood from the liver, as may occur in chronic right heart failure (congestive heart failure). The area surrounding the central veins (centrizonal) becomes intensely congested, and the hepatocytes in the central zone may even become necrotic due to hypoxia. These centrilobular areas are seen as the dark red spots on the cut surface. The alternating pale areas represent the periportal hepatocytes, which have sustained a lesser degree of hypoxia. This gross appearance is also called nutmeg liver. Remember that in the hepatic lobules, blood flows from the periportal to the central zones, and hence the centrilobular areas are more vulnerable to hypoxia than are the peripheral hepatocytes.  

42. 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).

43. Gross Lung, chronic passive venous congestion
This is caused by any chronic condition that retards the outflow of pulmonary venous blood from the lungs to the left side of the heart (eg, chronic mitral valve stenosis). Pooling of blood in the lung capillaries and associated microhemorrhages produce a dark brown discoloration, noted here. In addition, septal fibrosis causes the lung to become stiff. The fibrosis causes the lung to feel firm to the touch; also, the fibrosis causes the cut edges to be raised or to stand up. This gross appearance is also called brown induration of the lung.     Questions:

44. What is the brown pigment that is derived from hemoglobin?
Hemosiderin.

45. Medium power Lung, acute pulmonary congestion and edema
The alveolar septa are prominent, due to marked congestion of the capillaries. The alveolar lumens contain pale-staining edema fluid. Compare this form of pulmonary congestion with chronic passive congestion in the next image.  

46. 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).

47. 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.

48. High power Lung, chronic passive venous congestion

49. Are the alveolar septa normal in thickness?
They are thickened, due to edema and reactive fibrosis.

50. It would be markedly impaired
What effect would such a histologic picture have on gaseous exchange in the lung?
It would be markedly impaired

51. What might the symptoms be?
Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and cough

52. Gross, cut surface Lung, pulmonary infarct
This image shows a triangular, peripheral, subpleural area that is solid and airless. This is the typical appearance of a pulmonary infarct. It represents an area of coagulative necrosis resulting from loss of oxygen. The anoxia (ischemia) is most commonly due to a detached venous thrombus that is carried from the leg veins to the right side of the heart and ultimately occludes a pulmonary arterial branch (pulmonary thromboembolism). The infarct appears red because of hemorrhage into the necrotic area. Hemorrhage is favored by the dual blood supply of the lung and the loose texture of the lung.

53. 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.

54. 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).

55. What conditions predispose to venous thrombosis?
Venous stasis caused by prolonged immobilization (eg, in hospitalized patients after surgery) or by congestive heart failure.

56. 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.

57. 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.

58. Medium power Lung, infarct
On the left side, air spaces and alveolar septa can be seen; however, the right half looks solid and eosinophilic. On careful examination, it is possible to see faint outlines of the alveoli, but otherwise the tissue looks structureless. These features are typical of coagulative necrosis, which in this case resulted from occlusion of a pulmonary vessel by a thrombus that originated from the veins of the leg. This is called pulmonary thromboembolism.     

59. 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.

60. 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).

61. 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.

62. High power Lung, infarct
Note that the outlines of the pulmonary alveoli can be seen, but the structural details have been obscured in this area of coagulative necrosis. There are no intact nuclei. The pulmonary airspaces seem filled with debris, derived in this case from remnants of red blood cells (ie, there was hemorrhage in this area of necrosis). This appearance is typical of pulmonary infarcts. They appear red on gross inspection, because there is hemorrhage into the area of necrosis (red infarcts).

63. 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.

64. 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.

65. 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.