1. 2nd Year Pathology 2010 Vascular Disturbances I Oedema, Hyperaemia and Haemorrhage

2. 2nd Year Pathology 2010 Haemodynamic Disorders Cell and tissue survival dependent on intact circulation and normal fluid homeostasis Haemodynamic disturbances –Affect all ages –Major causes of morbidity and mortality (myocardial infarction, stroke, pulmonary embolism) –Include the following: 1.Oedema, hyperaemia, congestion, haemorrhage 2.Thrombosis, embolism 3.Infarction, shock

3. 2nd Year Pathology 2010 Haemodynamic Disorders Oedema –Increased volume of fluid in the interstitial (extravascular, extracellular) space in a tissue Hyperaemia & congestion –Increased volume of blood (within blood vessels) in a particular tissue/organ Haemorrhage –Extravasation of blood because of vessel rupture

4. 2nd Year Pathology 2010 Oedema

5. 2nd Year Pathology 2010 Oedema Extravascular fluid collections can be classified as follows: –Exudate: rich in protein and/or cells (grossly cloudy) –Transudate: an ultrafiltrate of plasma with little protein and few or no cells (grossly clear) Oedema = increased volume of fluid in interstitial space Effusion = increased fluid in a body cavity –pleural / pericardial / peritoneal cavity Oedema and effusions have similar pathogenesis

6. 2nd Year Pathology 2010 Normal homeostasis Movement of fluid between microcirculation (arterioles, capillaries, veins) and interstitium dependent on –intravascular hydrostatic pressure –intravascular colloid osmotic pressure Normally –net outflow at arteriolar end (hydrostatic > osmotic) –no net flow across capillaries (hydrostatic = osmotic) –net inflow at venular end (hydrostatic < osmotic) –any excess interstitial fluid removed by lymphatics –no net increase in interstitial fluid volume

7. 2nd Year Pathology 2010 Normal homeostasis ARTERIOLEVENULECAPILLARY BED Net flow inNo net flowNet flow out LYMPHATICS Excess fluid hydrostatic P oncotic P

8. 2nd Year Pathology 2010 Increased hydrostatic pressure ARTERIOLEVENULECAPILLARY BED No net flow Net flow out hydrostatic P oncotic P Net flow out Overall excess flow out

9. 2nd Year Pathology 2010 Decreased oncotic pressure ARTERIOLEVENULECAPILLARY BED No net flow Net flow out hydrostatic P oncotic P Net flow out Overall excess flow out

10. 2nd Year Pathology 2010 Lymphatic obstruction ARTERIOLEVENULECAPILLARY BED Net flow inNo net flowNet flow out Excess fluid hydrostatic P oncotic P Excess fluid collects LYMPHATIC

11. 2nd Year Pathology 2010 Pathogenesis of Oedema Increased hydrostatic pressure Reduced plasma oncotic pressure Lymphatic obstruction Sodium and water retention Inflammation Protein- poor transudate Protein-rich exudate

12. 2nd Year Pathology 2010 Increased hydrostatic pressure Results in increased outflow of fluid Causes: –Impaired venous return local –venous thrombosis –venous compression / prolonged dependency –cirrhosis (giving rise to ascites) generalised –congestive heart failure / constrictive pericarditis –Arteriolar dilatation heat / neurohumoral dysregulation

13. 2nd Year Pathology 2010 Reduced oncotic pressure Results in decreased resorption of fluid Causes: –nephrotic syndrome –cirrhosis –protein losing enteropathies –malnutrition

14. 2nd Year Pathology 2010 Lymphatic obstruction Results in decreased resorption of fluid Usually localised Causes: –Surgical removal of lymph nodes and lymphatics –Tumour metastases to lymph nodes –Irradiation –Filariasis (parasitic infection)

15. 2nd Year Pathology 2010 Sodium and water retention Results in: –Expansion of intravascular fluid volume –Increased hydrostatic pressure –Dilutional decrease in vascular osmotic pressure Causes: –Excessive salt intake –Renal diseases Acute renal failure Renal hypoperfusion Chronic renal disease –Often complicates / exacerbates oedema due to other causes

16. 2nd Year Pathology 2010 Sodium and water retention Mechanisms –Cardiac failure  Decreased cardiac output  renal hypoperfusion –Hypoproteinaemia  Contraction of blood volume  renal hypoperfusion Compensatory mechanisms –Renal hypoperfusion Decreased GFR  increased tubular resorption of Na and H2O Activation of renin-angiotensin-aldosterone axis  renal retention of Na –Contraction of blood volume ADH secretion  renal retention of H2O

17. 2nd Year Pathology 2010 Inflammation Due to vasodilation and hyperpermeable vessels –vasoactive mediators e.g. histamine –cytokines e.g. IL-1, TNF –endothelial injury Characterised by: –protein-rich and inflammatory cell-rich exudate –Usually localized to sites of acute inflammation –Can be generalised and life-threatening e.g. anaphylaxis

18. 2nd Year Pathology 2010 Localised oedema - blister Generalised oedema – laryngeal oedema in anaphylaxis

19. 2nd Year Pathology 2010 Morphology Grossly –organomegaly or tissue swelling –subcutaneous tissues (CCF/nephrotic syndrome) dependent body parts: sacrum / legs, pitting oedema tissues with loose extracellular matrix (ECM): eyelids –lungs (CCF/renal failure/ARDS/hypersensitivity) heavy, contain frothy blood-tinged fluid –brain (neoplasm/infection/hypertension/venous obstruction) swollen with narrowed sulci and flattened gyri +/- evidence of herniation

20. 2nd Year Pathology 2010 Pitting Subcutaneous Oedema

21. 2nd Year Pathology 2010 Morphology Microscopically –subtle cell swelling –subtle separation of extracellular connective tissue elements –lungs - pink amorphous fluid in alveolar spaces

22. 2nd Year Pathology 2010 Acute pulmonary oedema

23. 2nd Year Pathology 2010 Consequences Subcutaneous oedema –Sign of underlying disease –Impair wound healing Pulmonary oedema –Impair gas exchange –Encourage infection Brain oedema –Herniation +/- brain stem compression & death –Compression of brain stem vascular supply

24. 2nd Year Pathology 2010 Cerebral Oedema & Herniation Flattened sulci and uncal herniation

25. 2nd Year Pathology 2010 Cerebral Oedema & Herniation Tonsillar herniation and pontine haemorrhage

26. 2nd Year Pathology 2010 Effusions Similar pathogenesis and aetiology as oedema –Increased hydrostatic pressure Left heart failure: –backpressure into pulmonary system - pleural effusions –Hypoproteinaemia Cirrhosis - ascites –Fluid overload (salt and water retention) Renal failure –Inflammation Pleural effusion associated with pneumonia / TB

27. 2nd Year Pathology 2010 Effusions Transudates: –Serous: mainly edema fluid, very few cells pleural effusion = hydrothorax pericardial effusion = hydropericardium peritoneal effusion = hydroperitoneum / ascites –Serosanguinous: serous fluid + red blood cells –Causes:  hydrostatic pressure,  oncotic pressure, salt and water retention

28. 2nd Year Pathology 2010 Effusions Exudates: –Fibrinous (serofibrinous): protein-rich exudate containing fibrin strands –Purulent: numerous inflammatory cells, mainly neutrophils (also called "empyema" in the pleural space) –Causes: Inflammation / infection e.g. Pleural effusion due to pulmonary infarct (fibrinous)/ pneumonia (purulent)

29. 2nd Year Pathology 2010 Effusions Other: –Haemorrhagic (blood): hemo-thorax/pericardium/peritoneum Cause: trauma, ruptured MI / aortic aneurysm –Chylous (lymphatic fluid): chylo-thorax/pericardium/peritoneum Cause: trauma (often surgical) to major lymphatic vessels

30. 2nd Year Pathology 2010 Serous pleural effusion

31. 2nd Year Pathology 2010

32. Serosanginous pleural effusion

33. 2nd Year Pathology 2010 Fibrinous pericarditis

34. 2nd Year Pathology 2010 Haemothorax

35. 2nd Year Pathology 2010 Chylous Ascites

36. 2nd Year Pathology 2010 Hyperaemia vs Congestion

37. 2nd Year Pathology 2010 Hyperaemia vs Congestion Hyperaemia active process arteriolar dilation e.g. skeletal muscle during exercise (physiologic), inflammation (pathologic) Congestion passive process impaired venous outflow e.g. cardiac failure (systemic), venous obstruction (local) Both = Increased volume of blood in tissue

38. 2nd Year Pathology 2010 ARTERIOLEVENULECAPILLARY BED Arteriolar dilation  engorgement with oxygenated blood Hyperaemia Normal

39. 2nd Year Pathology 2010 Impaired outflow  accumulation of deoxygenated blood (cyanosis) ARTERIOLEVENULECAPILLARY BED Congestion Normal IMPAIRED VENOUS OUTFLOW

40. 2nd Year Pathology 2010 Consequences of Impaired Venous Outflow Increased intravascular pressure Stasis HAEMORRHAGE NECROSIS CONGESTION OEDEMA HYPOXIA FIBROSIS Capillary rupture AcuteChronic

41. 2nd Year Pathology 2010 Consequences of Impaired Venous Outflow Congestion –stasis of deoxygenated blood Haemorrhage –increase in capillary pressure, capillary rupture Oedema –increased intravascular pressure Chronic hypoxia –+/- tissue necrosis followed by scarring

42. 2nd Year Pathology 2010 Congestion & Cardiac Failure Left Ventricular Failure Pulmonary congestion Acute: –engorged capillaries –alveolar haemorrhage –alveolar oedema Chronic –engorged capillaries –fibrosis 2 o hypoxia –haemosiderin-laden macs (heart failure cells) 2 o haemorrhage Right Ventricular Failure Hepatic congestion Acute: –centrilobular (central vein) congestion –centrilobular haemorrhage Chronic: –centrilobular necrosis –centrilobular fibrosis –centrilobular with haemosiderin-laden macs 2 o haemorrhage

43. 2nd Year Pathology 2010 Acute pulmonary congestion Pulmonary congestion, haemorrhage and oedema

44. 2nd Year Pathology 2010 Chronic pulmonary congestion Pulmonary congestion and old haemorrhage (heart failure cells)

45. 2nd Year Pathology 2010 Chronic hepatic congestion Centrilobular congestion and necrosis - nutmeg liver

46. 2nd Year Pathology 2010 Chronic hepatic congestion Centrilobular congestion and necrosis - nutmeg liver

47. 2nd Year Pathology 2010 Chronic hepatic congestion Centrilobular congestion and fibrosis – cardiac cirrhosis

48. 2nd Year Pathology 2010 Haemorrhage

49. 2nd Year Pathology 2010 Haemorrhage Extravasation of blood due to vessel rupture Trivial or life threatening Aetiology: –Large artery/vein Trauma Atherosclerosis Vasculitis Degeneration e.g. Marfan’s Erosion by tumour

50. 2nd Year Pathology 2010 Aetiology Capillary –Congestion –Vasculitis –Haemorrhagic diathesis Predisposition to haemorrhage Inherited / Acquired Increased vascular fragility Platelet disorders Coagulation defects Combination

51. 2nd Year Pathology 2010 Haemorrhage Grouped according to size Petechiae: 1-2mm, skin, mucous membranes, serosal surfaces –  intravasc pressure, low platelets, diatheses Purpura: >3mm –Above causes + vasculitis, trauma Ecchymoses: >1–2cm, subcutaneous tissue –Trauma + above causes Haematomas: larger, confined within tissue Haemorrhagic effusions: confined within body cavity – e.g. haemoarthrosis (joint cavity) External haemorrhage

52. 2nd Year Pathology 2010 Natural history Depends on volume and rate of blood loss –Depends on size of injured vessel Hypovolaemic shock –Rapid loss of > 20% of blood volume Compensatory mechanisms –Rapid loss of < 20% blood / Slow loss of larger volume –Renal hypoperfusion and contraction of blood volume Decreased GFR + activation of renin-angiotensin-aldosterone axis Renal retention of sodium and water ADH secretion  renal retention of water Small losses resorbed over time (phagocytosis of RBC’s): –Haemoglobin (red-blue)  bilirubin (dark green)  biliverdin (blue-green)  haemosiderin (golden brown) Larger losses can give rise to jaundice

53. 2nd Year Pathology 2010 Natural history Depends on location –Subcutaneous tissues – often trivial –Body cavities – little resistance to flow –Abdomen – can result in major losses prone to injury no bony surround vascular organs (kidney, spleen, liver) –Enclosed cavities – compression of contained viscera Haemopericardium - Cardiac tamponade Intracranial haemorrhage

54. 2nd Year Pathology 2010 Causes of acute fatal haemorrhage 1.Aortic aneurysm 2.Aortic dissection 3.Aortic transection 1 2 3

55. 2nd Year Pathology 2010 Traumatic Liver Lacerations

56. 2nd Year Pathology 2010 Haemopericardium

57. 2nd Year Pathology 2010 Summary Oedema –Normal homeostasis –Pathogenesis, morphology & consequences –Types of effusions Hyperaemia vs Congestion –Consequences of Impaired Venous Outflow –Congestion & Cardiac Failure Haemorrhage –Aetiology –Types of haemorrhage –Natural history