Disorders of vascular flow: edema, congestion, hemorrhage, thrombosis, embolism. Shock. Infarction.

1. Disorders of vascular flow: edema, congestion, hemorrhage, thrombosis, embolism. Shock. Infarction. 2011

2. EDEMA • abnormal accumulation of fluid in the intercellular space or in the body cavities • Edema may occur • Localized • generalised • Severe and generalised oedema, with marked swelling of the subcutaneous tissue-anasarca • edematous collection in body cavities: • hydrothorax - chest cavity • hydropericardium - pericardial cavity • hydroperitoneum (ascites) - abdominal cavity

3. pathogenesis of edema • increased hydrostatic pressure • may results of the impaired venous outflow, caused by thrombosis- most common in legs- thus localized oedema • generalised increase in venous pressure- occurs in right-sided congestive heart failure • reduced osmotic pressure • results from the excessive loss or reduced synthesis of serum albumin. • the most important cause of plasma protein loss- nephrotic syndrome (increased permeability of glomerular membranes) • causes of decreased synthesis of plasma proteins- in liver cirrhosis, in severe malnutrition

4. lymphatic obstruction • impaired lymphatic drainage results in lymphedema (due to obstruction-inflammatory, neoplastic) • filariasis-parasitic infection- often causes massive fibrosis of the lymph nodes and lymphatic channels- excessive lymphedema of legs and external genitalia - elephantiasis • cancer of the breast- sometimes treated by removal also axillary lymph nodes- may cause severe postoperative oedema of the arm • sodium retention -water retention • in acute reduction of renal function- in acute renal failure

5. Edema

6. MORPHOLOGY OF THE EDEMA • changes are evident grossly • edema is encountered most often at three sites = lower extremities, lungs, brain • subcutaneous oedema of the lower extremities- manifestation of heart failure (of right ventricle)- legs are subject to the highest hydrostatic pressures. • Distribution of oedema fluid in heart failure is influenced by gravity, it is termed „dependent„. • in contrast, oedema in acute renal failure-results of proteinuria and sodium retention, tends to be generalised, more severe than cardiac oedema, affects all parts of the body equally, manifests mostly in loose connective tissue matrices-periorbital oedema • pulmonary oedema-is a prominent feature of left ventricle heart failure, alveolar spaces are filled with eosinophilic fluid • oedema of the brain- is encountered in a variety of clinical circumstances, such as brain trauma, meningitis, hypertensive crisis

7. In case of pulmonary edema the alveoli are filled with eosinophilic edematous fluid

8. HYPERAEMIA OR CONGESTION • local increase of volume of the blood - caused by dilatation of the small vessels • active hyperemia:results from an augmented arterial inflow • in muscles during exercise • in inflammation • passive hyperemia:results from diminished venous outflow, is always accompanied by oedema • in cardiac failure • in obstructive venous disease • chronic passive congestion and edema of the lung • indicator of left ventricular cardiac failure • chronic passive congestion of the liver, kidney, spleen • represents an indicator of right ventricular failure

9. Chronic congestion In case of passive chronic congestion the lung is heavier, stiffer and dark red to brown in color (so-called brown induration)

10. Chronic congestion The brown color results from accumulation of siderophages, i. e. macrophages containing iron that stains blue with Perls stain

11. Chronic congestion • Causes of impaired hepatic venous outflow Chronic passive congestion: very common, results from chronic right-sided heart failure Budd-Chiari syndrome(thrombosis of the major hepatic veins): hematologic disorders, use of contraceptive, tumors, intrahepatic infections, idiopathic Venoocclusive disease (wall thickening, sclerosis and even occlusion of multiple small and central veins ):consequence of drug administration, including some anti-cancer agents, or may be caused by radiation

12. Chronic congestion Nutmeg liver

13. Histology may show various regressive changes (e. g. steatosis, atrophy or necrosis) mainly in the centrilobular region and in severe long-standing congestion even fibrosis

14. HEMORRHAGE • hemorrhage results from rupture of a blood vessel • rupture of large artery or vein- caused by some type of injury, such as trauma, atherosclerosis, inflammatory or neoplastic erosion of a blood vessel wall • rupture of small arteries-in systemic diseases • Haemorrhages may be • external-may cause exsanguinating • internal- is referred to if blood is trapped in tissues • hematoma – haemorrhage • Petechiae- minor multiple hematomas in the skin, mucosal and serosal surfaces • Purpura- multiple slightly larger hematomas • Ecchymoses- large subcutaneous or subserous hematomas (more than 1-2 cm in diameter)

15. blood collection in body cavities: • hemothorax= the blood accumulates in pleural cavities • hemopericardium= in pericardial cavity • hemoperitoneum • hemarthros

16. A: Punctate petechial hemorrhages of the colonic mucosa- thrombocytopenia. B: Fatal intracerebral hemorrhage.

17. CLINICAL SIGNIFICANCE: • depends on the volume of blood lost by hemorrhage and on the site of hemorrhage • larger and acute blood loss - may cause posthemorrhagic shock • site- when located in brain- even smaller hemorrhage may cause death • repeated external hemorrhages- may result in severe lack of iron- iron deficiency anemia

18. THROMBOSIS • thrombosis= the formation of clotted mass of blood, the clotted mass itself= thrombus • thrombus may flow downstream in blood vessel system= embolism • the process of clotting and embolism- closely related= thromboembolism • potential consequence of embolism and thrombosis= ischemic necrosis= infarction • thromboembolic infarctions of heart, brain, lungs, are dominating causes of death • pathogenesis of thrombosis =inappropriate activation of normal hemostasis • Normal hemostasis :there are three major contributing aspects of normal hemostasis- platelets, endothelial cells and coagulation system

19. Thrombosis Virchow triad in thrombosis

20. 1 intact endothelial cells serve to protect blood platelets and coagulation protein from highly thrombogenic subendothelial substance (collagen) • injury - loss of anticoagulative mechanism • thrombi appear often on ulcerated plaques in atherosclerotic arteris (mostly the aorta), at sites of inflammatory or traumatic injury to arteries (the walls have been infiltrated by cancer) • thrombi appear regularly in heart chambers when there has been injury to endocardium (due to hypoxia) adjacent to myocardial infarct or in any form of myocarditis

21. 2 stasis and turbulence of blood • constitutes the second major thrombogenic influence • in normal lamelar flow- blood cells are separated from the endothelial surface • Stasis, turbulance, and decrease of rate of blood flow- permits erythrocytes and platelets to come to contact with endothelial cells • prevents dilution of clooting factors in plasma • decreases inflow of clotting factor inhibitors • promotes endothelial cell hypoxia and injury • Stasis play dominant role in thrombosis in veins- low speed of blood flow in veins - origin of venous thrombi in sinuses behind venous valves in deep vein in low extremities • similar phenomen- in auricular appendices of heart chambers - in atrial fibrillation • stasis and turbulence contribute to thrombosis in arterial aneurysmal dilatations

22. 3 hypercoaguability of the blood • thrombotic diathesis • nephrotic syndrome • late pregnancy • disseminated cancer • use of oral contraceptives- increase in plasma level of prothrombin, fibrinogen and other coagulative factors can be demonstrated • trauma, surgery, burns • cardiac failure • advanced age, immobilization and reduced physical activiy increase the risk of venous thrombosis

23. Thrombosis Coronary thrombosis occurs mainly in the setting of atherosclerosis Thrombosis of coronary artery

24. MORHOLOGY OF THROMBI • arterial and cardiac thrombi: arise at sites of endothelial injury, atherosclerosis- often at the site of branching of the artery- white or mixed thrombi- composed of fibrin white blood cells and erythrocytes • mural thrombus- thrombus attached to one wall of the artery- mural thrombi also develop in abnormally dilated arteries-aneurysms • occlusive thrombi - thrombus completely obstructs the lumen- in smaller arteries • most commonly affected arteries: coronary, cerebral, femoral, iliac, mesenteric, popliteal • venous thrombi: also known as „phlebothrombosis„- mural or occlusive • in slower-moving blood in veins- red coagulative or stasis thrombi -composed mostly of fibrin and erythrocytes • most commonly affected veins: veins of lower extremity (deep calf, femoral, popliteal, iliac), periprostatic plexus, portal vein etc

25. Mural thrombi A: Thrombus in the left and right ventricular apices, overlying white fibrous scar. B: Laminated thrombus in a dilated abdominal aortic aneurysm

26. DEVELOPMENT OF THROMBUS: • thrombus may continue to grow into adjacent vessels • thrombus may embolize • thrombus may be removed by fibrinolytic activities • it may undergo organization- when thrombus persists in situ for several days- it may be organized= ingrowth of granulation tissue and mesenchymal cells into the fibrinous thrombus • thrombus is populated with spindle mesenchymal cells and capillary channels are formed within thrombus • the surface of thrombus becomes to be covered by endothelial cells • capillary channels anastomose- recanalization = reestablishing the continuity of original vessel

27. CLINICAL SIGNIFICANCE of thrombosis • cause obstruction- lead to infarction • may provide the source of embolism • superficial veins-varicosities, such thrombi may cause local edema and congestion and pain, rarely give rise to emboli, local edema predispose to infection-varicous ulcers difficult to heal • deep veins of the leg (popliteal, femoral, iliac)- the most important source of emboli, they also may cause edema, pain, tenderness but approximately half of the patients with deep vein thrombosis are asymptomatic

28. EMBOLISM • Embolism refers to occlusion of some part of the cardiovascular system by the impaction of embolus transported to the site of occlusion by the blood stream. • most emboli represent parts of thrombi, thus the term thromboembolism, • much less commonly-other material such as fat droplets, gas bubbles, atherosclerotic debris, tumor fragments • TYPES OF EMBOLISM: • 1. pulmonary embolism • 2. systemic embolism • 3. paradoxical embolism

29. TYPES OF EMBOLISM • 1. pulmonary embolism • 2. systemic embolism • 3. paradoxical embolism

30. Embolism

31. Recent pulmonary embolia

32. Postembolic fibrous bridge

33. PULMONARY EMBOLISM • thrombus originates in deep venous system of legs • occasionally from right side of heart • embolus or emboli are transported into right heart ventricle and to pulmonary arteries

34. Consequencies of PE • multiple small emboli in peripheric branches of pulmonary artery • smaller emboli impact in medium-sized arteries- if cardiovascular circulation is normal, the vitality of lung tissue is maintained, but alveolar spaces are usually filled with erythrocytes= pulmonary hemorrhage • with compromised cardiovascular status (in congestive heart failure)- hemorrhagic infarction • Pulmonary infarction is sharply circumscribed necrosis of triangular shape with apex pointing towards the hilus of the lung • pleural surface is covered with fibrinous exudate • large snake-like emboli-large emboli impact in main pulmonary arteries-death • saddle embolus-massive embolism in main pulmonary artery, death suddenly from hypoxia or right ventricle heart failure (acute cor pulmonale) - no time to develop morphologic changes in lung tissue

35. Pulmonary embolism

36. Pulmonary hemorrhagic infarct

37. Pulmonary hemorrhagic infarct Infarct Normal lung parenchyma

38. SYSTEMIC EMBOLISM • to systemic arteries -brain, kidney, spleen, etc • Severe consequencies-necrosis • Sources of the emboli • intracardiac mural thrombi (in myocardial infarction) • atherothrombotic fragments from the aorta and the large arteries • heart valves • left heart atrium - in atrial fibrillation • left ventricle aneurysm

39. PARADOXICAL EMBOLISM • most common source- clots in deep leg veins, and most common target organs- arteries of the brain, kidney, spleen • abnormal opening between right and left atrium ( foramen ovale ), higher blood pressure on right side than on left allows embolization from systemic veins to systemic arteries

40. FAT EMBOLISM • fatty droplets and minute globules of fat in blood capillaries • complication of bone fractures • about 90% patients with severe skeletal injuries fat embolism, but very few have clinical course known as • fat embolism syndrom acute respiratory insufficiency, neurological symptoms, anemia and thrombocytopenia - typically syndrom appears about 2 - 3 days after injury • fat embolism syndrome has mortality of about 10% • pathogenesis of fat embolism syndrom • not absolutely clear, both mechanical obstruction and chemical injury are involved • microaggregates of fat cause occlusions in microcirculation of lungs and brain and free fatty acids cause endotheial cell damage - microglobules of fat are found in capillaries in many organs- most important- brain

41. AIR EMBOLISM • = is defined as entry of air into venous or arterial blood vessels • -in venous air embolism- small quantities are innoculous, but 100 ml and more may be fatal • -in arterial air embolism- even small quantity may be fatal, most commonly - complication of abortion, chest surgery • caisson disease is a particular form of gas embolism =decompression sickness • may appear in deep-sea divers who ascend rapidly to high altitudes, the gases within pressurized air are dissolved in the blood, tissues and fat • if the diver then ascends up rapidly to the surface- the dissolved oxygen, nitrogen and carbon dioxide come out of solution in the form of small bubbles • -most dangerous in this respect seems to be nitrogen, because of its low solubility- nitrogen persists as gas bubbles • - mainly in the brain - brain necroses • -the same process may affect other highly vascularized tissues and organs, such as heart and kidney, skeletal muscles, etc. • -in the lungs- sudden respiratory distress syndrom • TREATMENT: rapid placing of the affected person into the compression chamber- and slow decompression

42. AMNIOTIC FLUID EMBOLISM • is characterized by sudden onset, rapid dyspnea, cyanosis, collapse and coma with convulsions • occurs rarely, is totally unpredictable, may be fatal - is one of major causes of maternal death after delivery • typical findings: • in pulmonary arteries and capillaries- epithelial squames from fetal skin, lanugo hairs, • fibrin thrombi indicative of DIC - in small vessels of uterus, lungs, kidney, thyroid, myocardium pathogenesis of amniotic fluid embolism is unclear • the main cause of syndrom is infusion of amniotic fluid into the blood, such entry may occur through cervical uterine veins, from the uteroplacental site , etc • it is suspected that vasoactive substances from the amniotic fluid are responsible for pulmonary vasoconstriction • -thrombogenic substances from amniotic fliud- may cause intravascular coagulation leading to DIC • hemorrhages and acute renal failure

43. DISSEMINATED INTRAVASCULAR COAGULATION (DIC) is characterized by activation of coagulation sequence that leads to formation of multiple minute fibrin thrombi in capillaries and small venules • the thrombi are mostly composed of fibrin and aggregations of platelets • leads to widespread thromboses with consumption of platelets and of coagulation factors and with subsequent fibrinolysis (secodary effect)- DIC is also called microvasculary thrombosis • thromboses cause focal ischemia - multiple foci of necrosis mostly in the lungs, kidneys, brain, heart • increased bleeding tendency causes multiple hemorrhages

44. main clinical disorders associated with DIC: • DIC is not primary disease, it is a complication of some underlying diseases , such as • amniotic fluid embolism • EPH gestosis • septic abortion • retained dead fetus or abruption placentae • severe infections (gram-negative sepsis for example) • neoplasms, such as carcinoma of pancreas, prostate, lungs • massive tissue injury, burns • extensive surgery, etc

45. morphology of DIC • widespread occurrence of fibrin thrombi in capillaries of kidney, adrenal glands, brain, and other organs • -ischemia and multiple microinfarcts • -necrosis in adrenals may cause Waterhouse-Fridrichsen syndrom • -necrosis in brain- severe neurologic complications • -DIC leads to hemorrhagic diathesis, because of consumption of clotting factors in multiple microthrombi • increased bleeding tendency causes multiple hemorrhages

46. INFARCTION • infarct is a localized ischemic necrosis in an organ or tissue resulting from sudden occlusion of arterial supply • CAUSES OF INFARCTIONS: • thrombotic or embolic occlusions • 1. thrombosis = in situ formation of the blood clot that occluds the lumen of the blood vessel • 2. embolism = a portion of the thrombus in one area breaks off and lodges into the blood vessel of the other area usually of narrower lumen • less common causes of infarcts include: • 3. atherosclerosis = narrowing of lumen or the total obstruction of the lumen by atherosclerotic plaque alone- due to ulceration, hemorrhage, or edema of the plaque

47. 4. spasm of artery = due to active pathologic vasocontriction • 5. hypotension - causes severe temporary impairments of blood supply in an area of compromised circulation • 6. twisting of the blood vessel with occlusion of both arteries and veins • in a hernial sac or under peritoneal adhesion • in cases of torsion of organs or tissues that have the blood supply through a pedicle, such as ovaries, testes • 7. pressure of blood vessel - caused by expanding tumor or due to mechanical pressure in decubital ulcer

48. MORPHOLOGY OF INFARCTS: • Infarcts can be divided into two types: • white (anemic) • red (hemorrhagic) • the distinction is given only by amount of hemorrhage that occurs in necrotic area, the difference is not principal • 1. WHITE, PALE INFARCTS • in solid organs (heart, spleen, kidney)- firm consistency of the organ does not permit blood inflow into the necrotic area • 2. RED, HEMORRHAGIC INFARCTS • in loose, spongy tissues (lungs, intestine) permits blood to collect in necrosis from the anastomosing capillary circulation - • hemorrhagic infarcts are also encountered if the venous outflow from the necrotic area is limited -for example hemorrhagic venous infarction of intestine • in some intstances, spasm of vessels about clot subsequently relaxes causing partial hemorrhagic infarction

49. A, Hemorrhagic, roughly wedge-shaped pulmonary infarct (red infarct). B, Sharply demarcated pale infarct in the spleen (white infarct).

50. MORPHOLOGY OF DEVELOPING INFARCT • 1- at the onset- all infarcts tend to be poorly defined and slightly hemorrhagic due to anoxic leakage of residual blood from capillaries in affected area - early infarcts are grossly red • 2- at later stage- white infarcts in solid organs- (spleen, kidney) become well circumscribed, progressively pale, sharply delimited with hyperemic border - • hemorrhagic infarcts in spongy organs - (lung, intestine), first the infarct is cyanotic, later is firmer and brown (hemosiderin deposits), the delimitation of infarcts- inflammatory reaction and hyperemia at the margins of necrosis • in organs with excellent collaterals- the infarction remains red because blood continues to be poured to the affected area • in venous occlusion- infarction is usually hemorrhagic • in heart- appearance may be mixed red and white, yellow color is due to accumulation of leukocytes • in brain- cerebral infarction usually undergoes liquefaction