4. hemodyn disorders,thrombosis, shock

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HEMODYNAMIC DISORDERS J v = ([Pc Pi] − σ[πc − πi])

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Transcript of 4. hemodyn disorders,thrombosis, shock

  • 1. HEMODYNAMICDISORDERSJv = ([Pc Pi] [c i])

2. HemodynamicDisordersThromboembolicDiseaseShock 3. Overview Edema Hyperemia Congestion Hemorrhage Hemostasis Thrombosis Embolism Infarction Shock 4. EDEMA ONLY 4 POSSIBILITIES!!!Increased Hydrostatic PressureReduced Oncotic PressureLymphatic ObstructionSodium/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 INTERSTITIALSPACE HYDRO- -THORAX, -PERICARDIUM, -PERICARDIUM EFFUSIONS, ASCITES, ANASARCA 6. INCREASED HYDROSTATICPRESSURE 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 renalinsufficiency Increased tubular reabsorption ofsodium Renal hypoperfusionIncreasedrenin-angiotensin-aldosteronesecretion 10. INFLAMMATION Acute inflammation Chronic inflammation Angiogenesis 11. Jv = ([Pc Pi] [c i]) 12. CHF EDEMA INCREASED VENOUS PRESSUREDUE TO FAILURE DECREASED RENAL PERFUSION,triggering of RENIN-ANGIOTENSION-ALDOSTERONEcomplex, resulting ultimately inSODIUM RETENTION 13. HEPATIC ASCITES PORTAL HYPERTENSION HYPOALBUMINEMIA 14. ASCITES 15. RENAL EDEMA SODIUM RETENTION PROTEIN LOSINGGLOMERULOPATHIES(NEPHROTIC SYNDROME) 16. EDEMA SUBCUTANEOUS (PITTING) DEPENDENT ANASARCA LEFT vs. RIGHT HEART PERIORBITAL (RENAL) 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 results from disturbance of Starling forces specific gravity < 1.012 protein content < 3 g/dl Exudate results from damage to the capillary wall specific gravity > 1.012 protein content > 3 g/dl 19. HYPEREMIA/(CONGESTION) 20. HYPEREMIAActive ProcessCONGESTIONPassive ProcessAcute or Chronic 21. CONGESTION LUNGACUTECHRONIC LIVERACUTECHRONIC CEREBRAL 22. ACUTE PASSIVEHYPEREMIA/CONGESTION,LUNG 23. Kerley BAirBronch-ogram 24. CHRONIC PASSIVEHYPEREMIA/CONGESTION,LUNG 25. Acute Passive Congestion,Liver 26. Acute Passive Congestion,Liver 27. CHRONIC PASSIVEHYPEREMIA/CONGESTION, LIVER 28. HEMORRHAGE EXTRAVASATION beyond vessel HEMORRHAGIC DIATHESIS HEMATOMA (implies MASS effect) DISSECTION PETECHIAE (1-2mm) (PLATELETS) PURPURA 1cm (BRUISE) HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS ACUTE, CHRONIC 29. EVOLUTION of HEMORRHAGE ACUTE CHRONIC PURPLE GREEN BROWN HGB BILIRUBIN HEMOSIDERIN 30. HEMATOMAvs.CLOT 31. HEMOSTASIS OPPOSITE of THROMBOSISPRESERVE LIQUIDITY OF BLOODPLUG sites of vascular injury THREE COMPONENTSVASCULAR WALL, i.e., endoth/ECMPLATELETSCOAGULATION CASCADE 32. 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 Activates coagulation cascadethrombinfibrin (2HEMOSTASIS) FIBRIN polymerizes, TPA limits plug 33. PLAYERSENDOTHELIUMPLATELETSCOAGULATIONCASCADE 34. ENDOTHELIUM NORMALLYANTIPLATELET PROPERTIESANTICOAGULANT PROPERTIESFIBRINOLYTIC PROPERTIES IN INJURYPRO-COAGULANT PROPERTIES 35. ENDOTHELIUM ANTI-Platelet PROPERTIES Protection from the subendothelial ECM Degrades ADP (inhib. Aggregation) ANTI-Coagulant PROPERTIESMembrane HEPARIN-like moleculesMakes THROMBOMODULIN Protein-C TISSUE FACTOR PATHWAY INHIBITOR FIBRINOLYTIC PROPERTIES (TPA) 36. ENDOTHELIUM PROTHROMBOTIC PROPERTIESMakes vWF, which binds PlatsCollMakes TISSUE FACTOR (with plats)Makes Plasminogen inhibitors 37. ENDOTHELIUM ACTIVATED by INFECTIOUS AGENTS ACTIVATED by HEMODYNAMICS ACTIVATED by PLASMA 38. PLATELETS ALPHA GRANULES Fibrinogen Fibronectin Factor-V, Factor-VIII Platelet factor 4, TGF-beta DELTA GRANULES (DENSE BODIES) ADP/ATP, Ca+, Histamine, Serotonin, Epineph. With endothelium, form TISSUE FACTOR 39. NORMAL platelet on LEFT, DEGRANULATING ALPHAGRANULE ON RIGHT AT OPEN WHITE ARROW 40. PLATELET PHASES ADHESION SECRETION (i.e.,release or activationor degranulation) AGGREGATION 41. PLATELET ADHESION Primarily to thesubendothelial ECM Regulated by vWF, whichbridges platelet surfacereceptors to ECM collagen 42. PLATELET SECRETION BOTH granules, and Binding of agonists toplatelet surface receptorsAND intracellular proteinPHOSPHORYLATION 43. PLATELET AGGREGATION ADP TxA2 (Thromboxane A2) THROMBIN from coagulationcascade also FIBRIN further strengthensand hardens and contracts theplatelet plug 44. PLATELET EVENTS ADHERENCE to ECM SECRETION of ADP and TxA2 EXPOSE phospholipidcomplexes Express TISSUE FACTOR PRIMARYSECONDARY PLUG STRENGTHENED by FIBRIN 45. COAGULATION CASCADE INTRINSIC(contact)/EXTRINSIC(TissFac) ProenzymesEnzymes Prothrombin(II)Thrombin(IIa) Fibrinogen(I)Fibrin(Ia) Cofactors Ca++ Phospholipid (from platelet membranes) Vit-K dep. factors: II, VII, IX, X, Prot. S, C, Z 46. COAGULATION TESTS (a)PTT INTRINSIC (HEP Rx) PT (INR) EXTRINSIC (COUM Rx) BLEEDING TIME (PLATS) (2-9min) Platelet count (150,000-400,000/mm3) Fibrinogen Factor assays 47. THROMBOSIS Pathogenesis Endothelial Injury Alterations in Flow Hypercoagulability Morphology Fate Clinical Correlations Venous Arterial (Mural) 48. THROMBOSIS Virchows TRIANGLEENDOTHELIALINJURYABNORMAL FLOW(NON-LAMINAR)HYPER-COAGULATION 49. ENDOTHELIAL INJURY Jekyll/Hyde disruptionany perturbation in the dynamicbalance of the pro- andantithrombotic effects ofendothelium, not only physicaldamage 50. ENDOTHELIUM ANTI-Platelet PROPERTIES Protection from the subendothelial ECM Degrades ADP (inhib. Aggregation) ANTI-Coagulant PROPERTIESMembrane HEPARIN-like moleculesMakes THROMBOMODULIN Protein-C TISSUE FACTOR PATHWAY INHIBITOR FIBRINOLYTIC PROPERTIES (TPA) 51. ENDOTHELIUM PROTHROMBOTIC PROPERTIESMakes vWF, which binds PlatsCollMakes TISSUE FACTOR (with plats)Makes Plasminogen inhibitors 52. ABNORMAL FLOWNON-LAMINAR FLOW TURBULENCE EDDIES STASIS DISRUPTED ENDOTHELIUMALL of these factors may bringplatelets into contact withendothelium and/or ECF 53. 1 HYPERCOAGULABILITY(INHERITED) COMMONEST: Factor V andProthrombin defects Common: Mutation in prothrombin gene,Mutation in methyltetrahydrofolate gene Rare: Antithrombin III deficiency, Protein Cdeficiency, Protein S deficiency Very rare: Fibrinolysis defects 54. 2 HYPERCOAGULABILITY(ACQUIRED) Prolonged bed rest or immobilization Myocardial infarction Atrial fibrillation Tissue damage (surgery, fracture, burns) Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis) Prosthetic cardiac valves Disseminated intravascular coagulation Heparin-induced thrombocytopenia Antiphospholipid antibody syndrome (lupus anticoagulant syndrome) Lower risk for thrombosis: Cardiomyopathy Nephrotic syndrome Hyperestrogenic states (pregnancy) Oral contraceptive use Sickle cell anemia Smoking, Obesity 55. MORPHOLOGY ADHERENCE TO VESSEL WALLHEART (MURAL)ARTERY (OCCLUSIVE/INFARCT) VEIN OBSTRUCTIVE vs. NON-OBSTRUCTIVE RED, YELLOW, GREY/WHITE ACUTE, ORGANIZING, OLD 56. MURAL THROMBI, HEART 57. FATE of THROMBI PROPAGATION (Downstream) EMBOLIZATION DISSOLUTION ORGANIZATION RECANALIZATION 58. OCCLUSIVE ARTERIAL THROMBUS 59. D.V.T. D. (CALF, THIGH, PELVIC) V.T. CHF a huge factor INACTIVITY!!! Trauma Surgery Burns Injury to vessels, Procoagulant substances from tissues Reduced t-PA activity 60. ARTERIAL/CARDIAC THROMBI ACUTE MYOCARDIAL INFARCTION =OLD ATHEROSCLEROSIS + FRESHTHROMBOSIS ARTERIAL THROMBI also may sendfragments DOWNSTREAM, but thesefragments may contain flecks ofPLAQUE also LODGING is PROPORTIONAL to the %of cardiac output the organ receives,i.e., brain, kidneys, spleen, legs, or thediameter of the downstream vessel 61. ATHEROEMBOLI CHOLESTEROL clefts arecomponents of atheroscleroticplaques, NOT thrombi!!! 62. Disseminated Intravascular CoagulationD.I.C. OBSTETRIC COMPLICATIONS ADVANCED MALIGNANCYNOT a primary diseaseCONSUMPTIVE coagulopathy, e.g.,reduced platelets, fibrinogen, F-VIII andother consumable clotting factors,brain, heart, lungs, kidneys,MICROSCOPIC ONLY 63. EMBOLISMPulmonary Systemic (Mural Thrombi andAneurysms) Fat Air Amniotic Fluid 64. PULMONARY EMBOLISM USUALLY SILENT CHEST PAIN, LOW PO2, S.O.B. Sudden OCCLUSION of >60% ofpulmonary vasculature, presents a HIGHrisk for sudden death, i.e., acute corpulmonale, ACUTE right heart failure SADDLE embolism often/usually fatal PRE vs. POST mortem blood clot: PRE: Friable, adherent, lines of ZAHN POST: Current jelly or chicken fat 65. SYSTEMIC EMBOLI PARADOXICAL EMBOLI 80% cardiac/20% aortic Embolization lodging site isproportional to the degree of flow(cardiac output) that area or organgets, i.e., brain, kidneys, legs 66. OTHER EMBOLIFAT (long bone fxs )AIR (SCUBA bends)AMNIOTIC FLUID,very prolonged or difficultdelivery, high mortality 67. INFARCTION Defined as an area of necrosis*secondary to decreased bloodflow HEMORRHAGIC vs. ANEMIC RED vs. WHITEEND ARTERIES vs. NO END ARTERIES ACUTEORGANIZATIONFIBROSIS 68. INFARCTION FACTORS NATURE of VASCULAR SUPPLY RATE of DEVELOPMENTSLOW (BETTER)FAST (WORSE) VULNERABILITY to HYPOXIAMYOCYTE vs. FIBROBLAST CHF vs. NO CHF 69. HEART 70. SHOCK PathogenesisCardiacSepticHypovolemic Morphology Clinical Course 71. SHOCK Definition: CARDIOVASCULAR COLLAPSE Common pathophysiologic features: INADEQUATE CARDIAC OUTPUT and/or INADEQUATE BLOOD VOLUME 72. GENERAL RESULTS INADEQUATE TISSUE PERFUSION CELLULAR HYPOXIA UN-corrected, a FATAL outcome 73. TYPES of SHOCK CARDIOGENIC: (Acute, Chronic HeartFailure) HYPOVOLEMIC: (Hemorrhage orLeakage) SEPTIC: (ENDOTOXIC shock, #1 killer inICU) NEUROGENIC: (loss of vascular tone) ANAPHYLACTIC: (IgE mediated systemic vasodilation and increasedvascular permeability) 74. CARDIOGENIC shock MI VENTRICULAR RUPTURE ARRHYTHMIA CARDIAC TAMPONADE PULMONARY EMBOLISM (acute RIGHTheart failure or cor pulmonale) 75. HYPOVOLEMIC shock HEMORRHAGE, Vasc. compartmentH2O VOMITING, Vasc. compartmentH2O DIARRHEA, Vasc. compartmentH2O BURNS, Vasc. compartmentH2O 76. SEPTIC shock OVERWHELMING INFECTION ENDOTOXINS, i.e., LPS (Usually Gm-) Gm+ FUNGAL SUPERANTIGENS, (Superantigens are polyclonalT-lymphocyte activators that induce systemic inflammatorycytokine cascades similar to those occurring downstreamin septic shock, toxic shock antigents by staph are theprime example.) 77. SEPTIC shock events*(overwhelming infection) Peripheral vasodilation Pooling Endothelial Activation DIC* Think of this as a TOTAL BODYinflammatory response 78. ENDOTOXINS Usually Gm- Degraded bacterial cell wall products Also called LPS, because they are Lipo-Poly-Saccharides Attach to a cell surface antigen known asCD-14 79. ENDOTOXINS 80. SEPTIC shock events(linear sequence) SYSTEMIC VASODILATION (hypotension) MYOCARDIAL CONTRACTILITY DIFFUSE ENDOTHELIAL ACTIVATION LEUKOCYTE ADHESION ALVEOLAR DAMAGE (ARDS) DIC VITAL ORGAN FAILURE CNS 81. CLINICAL STAGES of shockNON-PROGRESSIVEPROGRESSIVEIRREVERSIBLE 82. NON-PROGRESSIVE COMPENSATORY MECHANISMSCATECHOLAMINES VITAL ORGANS PERFUSED 83. PROGRESSIVE HYPOPERFUSION EARLY VITAL ORGAN FAILURE OLIGURIAACIDOSIS 84. IRREVERSIBLEHEMODYNAMICCORRECTIONSof no use 85. PATHOLOGY MULTIPLE ORGAN FAILURE SUBENDOCARDIAL HEMORRHAGE (why?) ACUTE TUBULAR NECROSIS (why?) DAD (Diffuse Alveolar Damage, lung) (why?) GI MUCOSAL HEMORRHAGES (why?) LIVER NECROSIS (why?) DIC (why?) 86. ARDS/DAD 87. MYOCARDIAL NECROSIS 88. ATN 89. DIC 90. CLINICAL PROGRESSIONof SYMPTOMS Hypotension Tachycardia Tachypnea Warm skin Cool skin Cyanosis Renal insufficiency Obtundance Death