4.oedema,thrombosis,embolism

for basic knowledge

1. OEDEMA,THROMBOSIS AND EMBOLISM

2. CONTENTS: INTRODUCTION OEDEMA DEFINITION TYPES PATHOGENESIS THROMBOSIS DEFINITION TYPES PATHOGENESIS MORPHOLOGY

3. MICROSCOPIC PICTURE FATE EMBOLISM TYPES , CAUSES CONCLUSION REFERENCES PREVIOUS YEAR QUESTIONS

4. C C i i rcu rcu l l a a t t o o ry ry D D i i s s t t u u rb rb a a n n ce ce s s ( ( Dis Dis t t u u r r b b a a n n ce ce s s o o f f B B lo lo od od a a nd nd B B o o dy dy F F l l u u id id s) s) The health of cells and tissues depends not only on an intact circulation to deliver oxygen and remove wastes but also on normal fluid balance. Normal fluid homeostasis includes maintenance of vessel wall integrity (intact circulation) as well as intravascular pressure , blood volume , and protein content (osmolarity) within certain physiologic ranges . Therefore any change in one of these factors will affect the tissue homeostasis and may result in oedema or congestion . Normal fluid homeostasis also means maintaining blood as a liquid until such time as injury necessitates clot formation. Clotting at inappropriate sites (thrombosis) or migration of clots (embolism) obstructs blood flow to tissues & leads to cell death (infarction). Conversely inability to clot after injury results in haemorrhage . Extensive haemorrhage can result in shock. INTRODUCTION

5. HOMEOSTASIS • The mechanism by which the constancy of the internal environment is maintained and ensured is called the homeostasis. • Claude Bernarde (1949) – internal environment or milieu interieur

6. NORMAL FLUID EXCHANGE;

7. OEDEMA- DEFINITION The greek word ‘ oidema ’ means swelling. Oedema is defined as abnormal and excessive accumulation of “free fluid ‘’ in the interstititial tissue spaces and serous cavities - Occurs when there is free fluid i.e in body cavities or in interstitial spaces - -

8. BASED ON DISTRIBUTION LOCALIZED GENERALIZED BASED ON FLUID COMPOSITION TRANSUDATE EXUDATE TYPES

9. PATHOGENESIS Decreased plasma oncotic pressure Increased capillary hydrostatic pressure Lymphatic obstruction Tissue factors Increased capillary permeability Sodium and water retention.

10.  PATHOPHYSIOLOGICAL CATEGORIES OF EDEMA A) ↑ ed hydrostatic pressure : • OF CARDIAC DISEASES - CHF,constructive pericarditis ASCITIS OF LIVER PASSIVE CONGESTION POSTURAL B) ↓ ed plasma oncotic pressure: Oedema of renal diseases Ascitis hypoproteinemia •

11. c.Lymphatic obstruction: Post surgical eg:following radical mastectomy Pressure due to tumors Inflammatory –elephantiasis Occlusion of lymphatic channels via malignant cells MILROY’S DISEASE OR HERIDITARY LYMPHOEDEMA D.TISSUE FACTORS: quite small and insignificant May occur via elevation of oncotic pressure of IF or lowering tissue Tension eg : in eye lids and external genitalia

12. E.Increased capillary permeability: An intact endothelium acts as a semi permable membrane . When it is injured via ‘capillary poisons ‘ such as toxins , histamines etc leads to development of gaps and leakage of plasma fluids leading to edema Eg : Generalized edema Localized – inflammatory,angioneurotic

13. F.Mechanisms involved in oedema by sodium and water retention

14. PATHOGENESIS

15. Depending on the composition of fluid: transudate & exudate oedema TRANSUDATE Definition Filtrate of blood plasma without changes in endothelial permeability Character Non-inflammatory oedema Protein Low (less than 1 gm/dl); content mainly albumin, low fibrinogen; hence no tendency to coagulate Glucose Same as in plasma content EXUDATE Oedema of inflamed tissue associated with increased vascular permeability Inflammatory oedema High ( 2.5-3.5 gm/dl), readily coagulates due to high content of fibrinogen and other Coagulation factors Low (less than 60 mg/dl)

16. TRANSUDATE EXUDATE Specific gravity Low (less than 1.015) High (more than 1.018) pH > 7.3 < 7.3 LDH Low High Effusion LDH/ Serum < 0.6 > 0.6 LDH ratio Cells Few cells, mainly Many cells, inflammatory mesothelial cells as well as parenchymal and cellular debris Examples Oedema in congestive Purulent exudate such cardiac failure as pus

17. SPECIAL FORMS

18. RENAL OEDEMA • Generalised oedema occurs in certain diseases of renal origin- such as in nephrotic syndrome, some types of glomerulonephritis, and in renal failure due to acute tubular injury. • Initially manifests in tissues with loose connective tissue matrix - eyelids • Periorbital edema - characteristic

19. TYPES In nephrotic syndrome In nephritic syndrome Acute tubular injury

20. Differences between Nephrotic and Nephritic Oedema Feature Nephrotic Nephritic Cause Proteinuria Mechanism Degree of oedema Distribution Nephrotic syndrome Heavy ↓Plasma oncotic Pressure and Na+ and water retention Severe, generalised Subcutaneous tissues as well as visceral organs Glomerulonephritis (acute, rapidly progressive) Mild to Moderate Na+ and water retention Mild Loose tissues mainly (face, eyes, ankles, genitalia)

21. • OEDEMA IN ACUTE TUBULAR INJURY- damaged tubules lose their capacity for selective reabsorption and concentration of glomerular filtrate resulting in increased reabsorption.

22. PULMONARY OEDEMA • CAUSES - left ventricular failure, renal failure, acute respiratory distress syndrome and pulmonary inflammation or infection • CONSEQUENCES - impede oxygen diffusion- hypoxia - hypercapnia - favorable environment – bacterial infection

23. Mechanisms involved in the pathogenesis of pulmonary oedema. A, Normal fluid exchange at the alveolocapillary membrane (capillary endothelium and alveolar epithelium). B, Pulmonary oedema via elevated pulmonary hydrostatic pressure. C, Pulmonary oedema via increased vascular permeability.

24. CHF EDEMA • INCREASED VENOUS PRESSURE DUE TO FAILURE • DECREASED RENAL PERFUSION, triggering of RENIN- ANGIOTENSION-ALDOSTERONE complex, resulting ultimately in SODIUM RETENTION

25. HEPATIC OEDEMA • i) Hypoproteinaemia - impaired synthesis of proteins • ii) Portal hypertension - increased venous pressure in the abdomen - raised hydrostatic pressure. • iii) Failure of inactivation of aldosterone - hyperaldosteronism. • iv) Secondary stimulation of RAAS- sodium and water retention.

26. CEREBRAL OEDEMA • Brain edema -localized or generalized - nature extent -pathologic process or injury. 3 types- • VASOGENIC OEDEMA : increased filtration pressure or increased capillary permeability • CYTOTOXIC OEDEMA : disturbance in the cellular osmoregulation - response to cell injury • INTERSTITIAL OEDEMA : hydrocephalus

27. MISCELLANEOUS • Nutritional Oedema- • Due to nutritional deficiency of Proteins (Kwashiorkor, prolonged starvation, famine, fasting), Vitamins (beri-beri due to vitamin B1 deficiency) and Chronic alcoholism • Main contributing factors- Hypoproteinaemia & Sodium-water retention • Myxoedema- • Hypothyroidism -non pitting oedema occuring on skin of face and internal organs due to excessive deposition of glycosaminoglycans in the interstitium • Microscopically -basophilic mucopolysaccharides.

28. Thrombosis Definition Thrombosis is the formation of blood clot (thrombus) in an uninjuried vessels or thrombotic occlusion of a vessel after minor injury. The thrombus is formed of blood elements essentially platelets that develops inside the cardiovascular system during life. Types of Thrombi 1.Pale Thrombus In a flowing blood as in cardiac chambers or in arteries Formed mainly of platelets Firm pale reddish grey 2. Red Thrombus In a stagnant blood adjacent to complete vascular occlusion Formed of fibrin entrapping RBCs, leucocytes& platelets Soft dark red and gelatinous 3.Mixed Thrombus In a slowly flowing blood usually in veins & arteries Formed of alternating layers of platelets and fibrin entrapping RBCs and leucocytes. Alternating red &pale layers

29. Thrombosis Pathogenesis (Causes= Predisposing Factors) Three primary influences predispose to thrombus formation called Virchow’s triad Thrombosis Endothelial Injury Abnormal Blood Flow Hypercoagulability Myocardial infarction or valvulitis (cardiac chambers), atherosclerosis, vasculitis, hypertension, smoking, radiation, chemical irritation (arteries), prolonged recumbency & inflammation (veins) c h a m b e r s) Turbulence (arteries) Stasis (veins) &(cardiac Atherosclerosis, aneurysm, dilated atria, atrial fibrillation, venous stasis, varicose veins Primary causes (Genetic) Secondary Causes (Acquired): High Risk Causes & Low Risk Causes

30. 1.Endothelial Injury Exposure of subendothelial collagen and other platelet activators Release of tissue factor Increased Procoagulant Factors Decreased A n t i c o a g u l a n t Effectors Platelet Aggregation and Activation of Extrinsic Clotting Pathway Thrombus Formation Pathogenesis of Thrombosis

31. Pathogenesis of Thrombosis 1.Endothelial Injury

32. 2.Abnormal Blood Flow (Turbulence & Stasis) Pathogenesis : Normal blood flow is laminar such that the platelets flow centrally in the lumen , separated from the endothelium by a slower moving clear zone of plasma. Disrupt the laminar flow bringing the platelets into contact with the endothelium Prevent the dilution of the activated clotting factors by fresh flowing blood Retard the inflow clotting factors inhibitors Promote e n do t he li a l cell activation Thrombus Formation

33. Pathogenesis of Thrombosis 2.Abnormal Blood Flow (Turbulence & Stasis) Left atrial mural thrombus in a case of rheumatic mitral stenosis Iliac artery aneurysm with laminated thrombus

34. Pathogenesis of Thrombosis 3.Hypercoagulability: It is any alteration of the coagulation pathways that predispose to thrombosis. Primary (Genetic): Factor5 Mutations Prothrombin Mutation Antithrombin3 Deficiency Protein C or S Deficiency Secondary (Acquired): Prolonged bed rest or immobilization Myocardial Infarction Tissue Damage (surgery, fracture, burns) Cancer Prosthetic Cardiac Valves Disseminated Intravascular Coagulation Atrial Fibrillation Cardiomyopathy Hyperoestrogenic States & Contraceptive Pills Sickle Cell Anemia Smoking Systemic Lupus Erythematosis

35. Thrombosis Morphology Thrombi may develop anywhere inside the cardiovascular system i.e. heart, arteries, veins and capillaries. They are variable in size and shape depending on the site of origin and the causes of their development. An area of attachment to the underlying vessel or heart wall frequently firmest at the site of origin is characteristic of all thrombi . Arterial or Cardiac Thrombi They usually begin at a site of endothelial injury or turbulence (atherosclerotic plaques or other forms of injury as vasculitis or trauma). They tend to grow in a retrograde direction from the point of attachment. They are firmly attached to the injured endothelium. They are pale and composed of platelets, fibrin, RBCs, & leucocytes. Venous Thrombi They characteristically occur in sites of stasis. They extend in the direction of blood flow , that is toward the heart. The propagating tail may not be well attached and is prone to fragment, creating an embolus (to the lung). They are either of mixed or red type more RBCs due to sluggish blood flow.

36. Venous Thrombosis It commonly occurs in veins of lower limbs following operations , congestive heart failure , delivery , and severe injury due to: Slowing of circulation as a result of lack of muscular activity (stasis). Damage to the intima by pressure on calf muscles in recumbency (endothelial injury& change in blood flow). Increased number and adhesiveness of the platelets (hypercoagulability ). Phlebothrombosis Thrombophlebitis It results from damage of endothelium due to inflammation of the vein , either bacterial or nonbacterial: Septic or bacterial thrombophlebitis The thrombus is invaded by microorganisms from the vessel wall, then become fragmented and circulate in blood steam as septic emboli to form pyaemic abscesses wherever they settle. Nonseptic (nonbacterial) thrombophlebitis which is induced by ionizing radiation or chemicals.

37. Venous Thrombosis 3.Hypercoagulability: It is any alteration of the coagulation pathways that predispose to thrombosis. A case of deep venous thrombosis (DVT) in a patient suffering from systemic lupus erythematosus Swollen, painful, dusky red left lower limb

38. Venous Thrombosis Due to stasis, hypercoagulability &endothelial injury

39. Migratory Thrombophlebitis (Trousseau’s Syndrome) Disseminated cancers or certain types of malignancy as pancreatic carcinoma are sometimes associated with repeated attacks of multiple venous thrombosis at different and changing sites due to the procoagulant factors formed by cancer cells. This is referred to as migratory thrombophlebitis or Trousseau’s syndrome.

40. Capillary Thrombosis It is formed mainly of fused RBCs and are seen in some types of vasculitis and in disseminated intravascular coagulopathy (DIC). Disseminated Intravascular Coagulopathy A variety of disorders ranging from obstetric complications to advanced malignancy may be complicated by DIC, the sudden onset of widespread fibrin thrombi in the microcirculation. With the development of the multiple thrombi, there is rapid concurrent consumption of platelets & coagulation proteins (consumption coagulopathy); at the same time the fibrinolytic mechanisms are activated , and as a result an initially thrombotic disorder can evolve into a serious bleeding disorder.

41. in heart (atria , ventricles & on valves); in arteries ; in veins ; and in capillaries. Thrombosis Large mural thrombus on top of myocardial infarction Left atrial mural thrombus in a case of rheumatic mitral stenosis Sites of Thrombosis

42. The Microscopic Picture of a Thrombus Apparent laminations called lines of Zahn are seen formed of pale layers of platelets and fibrin that alternate with darker layers containing more red cells . RBCs Platelets & fibrin Platelets & fibrin RBCs

43. Fate of the Thrombus If the patient survives the immediate effects of a thrombotic vascular obstruction, thrombi undergo some combination of the following four events Propagation: the thrombus may accumulate more platelets and fibrin eventually obstructing other critical vessel. Dissolution: Thrombi may be removed by the fibrinolytic activity. 3.Embolization: Thrombi may dislodge as thrombotic emboli.

44. Fate of the Thrombus 4.Organization and Recanalization: Thrombi may induce inflammation and fibrosis (organization) and may eventually recanalize. Organization &Recanalization (multiple capillary channels)

45. To conclude

46. REFERENCES: Essential pathology for dental students –Harsh mohan Robbin’s basic pathology Web references and images

47. PREVIOUS YEAR QUESTIONS: SHORT ESSAY HEMOTHROMBOSIS(RGUHS 2010)