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2. Pathology 301 • Awatif Jamal, MD, MSc, FRCPC, FIAC • Consultant & Associate Professor • Department of Pathology • King Abdulaziz University Hospital

5. Hemodynamic Disorders Thrombosis & Shock • Edema Edema Hyperemia and Congestion Hemorrhage Hemostasis & Thrombosis Embolism Infarction Shock

6. INTRODUCTION • The health of cells and tissues depend on; • 1-Intact circulation ; to deliver oxygen and remove wastes. • 2-Normal fluid homeostasis; which encompasses the following; • A- maintenance of BV wall integrity . • B- maintenance of intravascular pressure. • C- maintenance of protein content or osmolarity within BV. • D- maintenance of blood as a liquid until such time as injury necessitates clot formation.

7. EDEMA • Fluid extravasations and accumulation in the interstitial spaces 60% of body weight is water, distributed as follow: Two thirds intracellular 5% intravascular The rest is interstitial

8. EDEMA Increased fluid in theinterstitial tissue spaces • Fluid may also accumulate in body cavities: • Hydrothorax • Hydropericardium • Hydroperitoneum is also called Ascites • Massive generalized edema is called Anasarca

9. Pathogenesis • The opposing effects of vascular hydrostatic pressure and plasma colloid osmotic pressure are the major factors that control the movement of fluid between vascular and interstitial tissues. • Normally, the exit of fluid into the interstitium from the arteriolar end of microcirculation is nearly balanced by inflow of fluid at the venular end; a small residual amount of excess interstitial fluid is drained by the lymphatics

10. Fluid Homeostasis Lymphatics

11. Fluid Homeostasis • Homeostasis is maintained by the opposing effects of: • Vascular Hydrostatic Pressure • and • Plasma Colloid Osmotic Pressure

12. Edema Fluid = TRANSUDATE • transudate is protein-poor (specific gravity <1.012) • An exudate is protein-rich (specific gravity >1.020) = (inflammatory edema)

14. Pathophysiologic Categories of Edema II. Reduced Plasma Oncotic Pressure • III. Inflammation • IV. Others I. Increased Hydrostatic Pressure

15. Patho-physiologic Categories of Edema Increased Hydrostatic Pressure Increased intravascular pressure may be due to 1- Impaired venous return; • Localized:Venous Thrombosis in lower extremities (local edema). • Generalized:Congestive Heart Failure (generalized edema). 2- Increasedarteriolar dilatation; • Heat • Neurohumoral dysregulation

16. Increased Hydrostatic Pressure Congestive Heart Failure: Congestive Heart Failure is the most common cause of EDEMA due to Increased Hydrostatic Pressure “Generalized increased venous pressure, resulting in systemic edema, occur most commonly in CONGESTIVE HEART FAILURE”

17. Increased Hydrostatic Pressure Congestive Heart Failure Mechanism: • The Pump is FAILING!!!  Cardiac output • Blood backs up, first into the lungs  then into the venous circulation  increasing Central Venous Pressure (CVP)  increased capillary pressure (Hydrostatic Pressure) • Leading to Generalized Edema

18. Congestive Heart Failure & Decreased Renal Perfusion • Congestive heart failure  Decreased Cardiac Output Decreased ARTERIAL blood volume  “Less arterial blood…Less renal perfusion... The Kidney doesn’t see enough bloodcoming through …….

19. Congestive Heart Failure & Decreased Renal Perfusion Decreased Renal Perfusion activates the Renal Defense Mechanisms: • Renin-Angiotensin-Aldosterone axis  Na & H2O retention • Renal Vasoconstriction • Increased Renal Anti-diuretic Hormone (ADH)

20. Congestive Heart Failure & Decreased Renal Perfusion • The net result will be increased intravascular volume to increase the COP. • The failing heart can’t increase the COP so the extra fluid load will lead to additional increase in the venous pressure and MoreEDEMA .

21. Renin ADH Central Venous Pressure Renal Perfusion Renal Vasoconstriction Congestive Heart Failure

23. Pathophysiologic Categories ofEdema • I. Increased Hydrostatic Pressure II. Reduced Plasma Oncotic Pressure • III. Inflammation • IV. Others

24. II. Reduced Plasma Oncotic Pressure • “…Albumin: the serum protein MOST responsible for the maintenance of colloid osmotic pressure.” • A decrease in osmotic pressure can result from: •  Protein Loss or •  Protein Synthesis

25. II. Reduced Plasma Oncotic Pressure • Increased albumin Loss: • Nephrotic Syndrome • Increased permeability of the glomerular basement membrane  loss of protein • Reduced albumin synthesis: • Cirrhosis • Protein malnutrition • EFFECT: • is movement of fluid into the interstitial tissue with resultant plasma volume contraction.

27. Pathophysiologic Categories ofEdema IV. Others I. Increased Hydrostatic Pressure II. Reduced Plasma Oncotic Pressure III. Inflammation Localized Edema Increased Vascular Permeability

29. Pathophysiologic Categories ofEdema I. Increased Hydrostatic Pressure II. Reduced Plasma Oncotic Pressure III. Inflammation • IV. Others • Lymphatic Obstruction • Water and Sodium Retention

30. Lymphatic Obstruction • Impaired lymphatic drainage with resultant lymphedema • LOCALIZED EDEMA • caused by : • INFLAMMATION or • NEOPLASTIC OBSTRUCTION

31. Inflammatory Lymphatic Obstruction • Filariasis – • A parasitic infection which leads to lymphatic and lymph node fibrosis in the inguinal region resulting in edema of the external genitalia and lower extremity called ELEPHANTIASIS

32. Neoplastic Lymphatic Obstruction • In cases of CA breast the resection and/or radiation of axillary lymphatic channels and lymph nodes can lead to -- arm edema • Carcinoma of breast with obstruction of superficial lymphatics can lead to edema of the skin with an unusual appearance of the breast skin - “peau d’orange” (orange peel)

33. EDEMA - Summary • HEART • LIVER • KIDNEY INCREASED HYDROSTATIC PRESSURE Congestive Heart Failure Ascites Venous Obstruction DECREASED ONCOTIC PRESSURE Nephrotic Syndrome Cirrhosis Protein Malnutrition LYMPHATIC OBSTRUCTION Inflammatory Neoplastic INCREASED PERMEABILITY Inflammation

34. Edema Fluid

35. GENERALIZED EDEMA • HEART • LIVER • KIDNEY

36. Edema of the subcutaneous tissue is most easily detected Grossly (not microscopically) Push your finger into it and a depression remains Annoying but Points to Underlying Disease It can impair wound healing or clearance of Infection Subcutaneous Edema

37. Dependent Edemais a prominent feature of Congestive Heart Failure; in legs if standing or sacrum in sleeping patient Periorbital edemais often the initial manifestation of Nephrotic Syndrome, while late cases will lead to generalized edema. Edema

38. Pulmonary Edema is most frequently seen in Congestive Heart Failure May also be present in renal failure, adult respiratory distress syndrome (ARDS), pulmonary infections and hypersensitivity reactions

39. Pulmonary Edema • The Lungs are typically 2-3 times normal weight • Cross sectioning causes an outpouring of frothy, sometimes blood-tinged fluid • It may interfere with pulmonary function

40. Normal lung

41. Pulmonary Edema

42. Pulmonary Edema Clinical Correlation May cause death by interfering with Oxygen and Carbon Dioxide exchange • Creates a favorable environment for infection • THINK it resembles “Culture Media”!!!

43. Brain Edema • Trauma, Abscess, Neoplasm, Infection (Encephalitis due to say… West Nile Virus), etc

44. Brain Edema Clinical CorrelationThe big problem is: There is no place for the fluid to go! • Herniation into the foramen magnum will kill

45. Clinical Correlation of Edema • The effect of edema may be just annoying to fatal condition. • It usually points to an underlying disease. • However, it can impair wound healing or clearance of Infection. • Creates a favorable environment for infection. • THINK “Culture Media” • May cause death by interfering with Oxygen and Carbon Dioxide exchange.

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