HEMODYNAMIC DISORDERS

1. HEMODYNAMIC DISORDERS Jv = ([Pc − Pi] − σ[πc − πi])

2. Hemodynamic Disorders • Thromboembolic Disease • Shock

3. Overview • Edema (increased fluid in the ECF) • Hyperemia (INCREASED flow) • Congestion (INCREASED backup) • Hemorrhage (extravasation) • Hemo-stasis* (opposite of thrombosis) • Thrombosis (clotting blood) • Embolism (downstream travel of a clot) • Infarction (death of tissues w/o blood) • Shock (circulatory failure/collapse)

4. EDEMA= ↑ECF • ONLY 4 POSSIBILITIES!!! • Increased Hydrostatic Pressure • Reduced Oncotic Pressure • Lymphatic Obstruction • Sodium/Water Retention

5. WATER • 60% of body • 2/3 of body water is INTRA-cellular • The rest is INTERSTITIAL • Only 5% is INTRA-vascular • EDEMA is SHIFT to the INTERSTITIAL SPACE FROM EITHER DIRECTION • HYDRO- • -THORAX, -PERICARDIUM, -PERITONEAL • EFFUSIONS, ASCITES, ANASARCA

6. INCREASED HYDROSTATIC PRESSURE (i.e.,VENOUS) • Impaired venous return • Congestive heart failure   • Constrictive pericarditis   • Ascites (liver cirrhosis)   • Venous obstruction or compression • Thrombosis     • External pressure (e.g., mass) • Lower extremity inactivity with prolonged dependency • Arteriolar dilation • Heat   • Neurohumoral dysregulation

7. REDUCED PLASMA ONCOTICPRESSURE (HYPOPROTEINEMIA) • Protein-losing glomerulopathies (nephrotic syndrome) • Liver cirrhosis (ascites) • Malnutrition • Protein-losing gastroenteropathy

8. LYMPHATIC OBSTRUCTION(LYMPHEDEMA) • Inflammatory • Neoplastic • Postsurgical • Postirradiation

9. Na+ RETENTION • Excessive salt intake with renal insufficiency • Increased tubular reabsorption of sodium • Renal hypoperfusion Increased renin-angiotensin-aldosterone secretion

10. INFLAMMATION • Acute inflammation (r,c,d,T) • Chronic inflammation • Angiogenesis

11. Jv = ([Pc − Pi] − σ[πc − πi])

12. CHF EDEMA-2 REASONS • INCREASED VENOUS PRESSURE DUE TO FAILURE • DECREASED RENAL PERFUSION, triggering of RENIN-ANGIOTENSION-ALDOSTERONE complex, resulting ultimately in SODIUM RETENTION

13. HEPATIC ASCITES- 2 REASONS • PORTAL HYPERTENSION • HYPOALBUMINEMIA

14. ASCITES

15. RENAL EDEMA- 2 REASONS • SODIUM RETENTION • PROTEIN LOSING GLOMERULOPATHIES (NEPHROTIC SYNDROME)

16. EDEMA • SUBCUTANEOUS (“PITTING”) • “DEPENDENT” • ANASARCA • LEFT vs RIGHT HEART • PERIORBITAL • PULMONARY • CEREBRAL (closed cavity, no expansion) • HERNIATION of cerebellar tonsils • HERNIATION of hippocampal uncus over tentorium • HERNIATION, subfalcine

17. “Pitting” Edema

18. Transudate vs. Exudate • Transudate (water) • results from disturbance of Starling forces • specific gravity < 1.012 • protein content < 3 g/dl, LDH LOW, ↓ Cells • Exudate (goo) • results from damage to the capillary wall • specific gravity > 1.012 • protein content > 3 g/dl, LDH HIGH, ↑ Cells

19. HYPEREMIA/(CONGESTION)

20. HYPEREMIA Active Process CONGESTION Passive Process Acute or Chronic

21. CONGESTION • LUNG, best example R. CHF • ACUTE • CHRONIC, hemosiderin • LIVER, best example L. CHF • ACUTE • CHRONIC, necrosis • CEREBRAL

22. ACUTE PASSIVE HYPEREMIA/CONGESTION, LUNG  septae alveoli

23. Kerley B Air Bronch-ogram

26. CHRONIC PASSIVE HYPEREMIA/CONGESTION, LUNG

27. Acute Passive Congestion, Liver

28. Acute Passive Congestion, Liver

29. CHRONIC PASSIVE HYPEREMIA/CONGESTION, LIVER

32. HEMORRHAGE • EXTRAVASATION beyond vessel • “HEMORRHAGIC DIATHESIS” • HEMATOMA (implies MASS effect) • “DISSECTION” • PETECHIAE (1-2mm) (PLATELETS) • PURPURA <1cm • ECCHYMOSES >1cm (BRUISE) • HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS • ACUTE, CHRONIC

33. EVOLUTION of HEMORRHAGE • ACUTE CHRONIC • PURPLE GREEN BROWN • HGB BILIRUBIN HEMOSIDERIN

39. HEMATOMAvs.“CLOT”(Pre-mortem vs. Post-mortem)

40. HEMO”STASIS” • OPPOSITE of THROMBOSIS • PRESERVE LIQUIDITY OF BLOOD • “PLUG” sites of vascular injury • THREE COMPONENTS • 1 VASCULAR WALL, i.e., endoth/ECM • 2 PLATELETS, “PRIMARY” COAG. • 3 COAGULATION CASCADE, or “SECONDARY” COAGULATION

41. SEQUENCE of EVENTSfollowing VASCULAR INJURY • ARTERIOLAR VASOCONSTRICTION • Reflex Neurogenic • Endothelin, from endothelial cells • THROMBOGENIC ECM at injury site • Adhere and activate platelets • Platelet aggregation (1˚ HEMOSTASIS) • TISSUE FACTOR released by endothelium, plats. • Activates coagulation cascadethrombinfibrin (2˚ HEMOSTASIS) • FIBRIN polymerizes, TPA limits plug

42. PLAYERS • 1) ENDOTHELIUM • 2) PLATELETS • 3) COAGULATION “CASCADE”, or SEQ.

43. ENDOTHELIUM • NORMALLY • ANTIPLATELET PROPERTIES • ANTICOAGULANT PROPERTIES • FIBRINOLYTIC PROPERTIES • IN INJURY • PRO-COAGULANT PROPERTIES

45. ENDOTHELIUM-JEKYLL • ANTI-Platelet PROPERTIES • Protection from the subendothelial ECM • Degrades ADP (inhib. Aggregation) • ANTI-Coagulant PROPERTIES • Membrane HEPARIN-like molecules • Makes THROMBOMODULIN Protein-C • TISSUE FACTOR PATHWAY INHIBITOR • FIBRINOLYTIC PROPERTIES (TPA)

46. ENDOTHELIUM-HYDE • PROTHROMBOTIC PROPERTIES • Makes vWF, which binds PlatsColl • Makes TISSUE FACTOR (with plats) • Makes Plasminogen inhibitors

47. ENDOTHELIUM • ACTIVATED by INFECTIOUSAGENTS • ACTIVATED by HEMODYNAMICS • ACTIVATED by PLASMA • ACTIVATED by ANYTHING which disrupts it, including physical trauma “DISRUPTION”

48. PLATELETS • ALPHA GRANULES • Fibrinogen • Fibronectin, a big CAM • Factor-V, Factor-VIII • Platelet factor 4, TGF-beta • DELTA GRANULES (DENSE BODIES) • ADP/ATP, Ca+, Histamine, Serotonin, Epineph. • With endothelium, form TISSUE FACTOR

50. NORMAL platelet on LEFT, “DEGRANULATING” ALPHA GRANULE ON RIGHT AT OPEN WHITE ARROW