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

Transcription

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

2 Hemodynamic Disorders Thromboembolic Disease Shock

3 Overview Edema Hyperemia Congestion Hemorrhage Hemostasis Thrombosis Embolism Infarction Shock

4 EDEMA 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 HYDRO- -THORAX, -PERICARDIUM, -PERICARDIUM EFFUSIONS, ASCITES, ANASARCA

6 INCREASED HYDROSTATIC PRESSURE 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 ONCOTIC PRESSURE (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 Chronic inflammation Angiogenesis

11 Jv = ([Pc Pi] σ[πc πi])

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

13 HEPATIC ASCITES PORTAL HYPERTENSION HYPOALBUMINEMIA

14 ASCITES

15 RENAL EDEMA SODIUM RETENTION PROTEIN LOSING GLOMERULOPATHIES (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 < protein content < 3 g/dl Exudate results from damage to the capillary wall specific gravity > protein content > 3 g/dl

19 HYPEREMIA/(CONGESTION)

20 HYPEREMIA Active Process CONGESTION Passive Process Acute or Chronic

21 LUNG CONGESTION ACUTE CHRONIC LIVER ACUTE CHRONIC CEREBRAL

22 ACUTE PASSIVE HYPEREMIA/CONGESTION, LUNG

23 Kerley B Air Bronchogram

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26 CHRONIC PASSIVE HYPEREMIA/CONGESTION, LUNG

27 Acute Passive Congestion, Liver

28 Acute Passive Congestion, Liver

29 CHRONIC PASSIVE HYPEREMIA/CONGESTION, LIVER

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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

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39 HEMATOMA vs. CLOT

40 HEMOSTASIS OPPOSITE of THROMBOSIS PRESERVE LIQUIDITY OF BLOOD PLUG sites of vascular injury THREE COMPONENTS VASCULAR WALL, i.e., endoth/ecm PLATELETS COAGULATION CASCADE

41 SEQUENCE of EVENTS following 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 cascade thrombin fibrin (2 HEMOSTASIS) FIBRIN polymerizes, TPA limits plug

42 PLAYERS ENDOTHELIUM PLATELETS COAGULATION CASCADE

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

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45 ENDOTHELIUM 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 PROTHROMBOTIC PROPERTIES Makes vwf, which binds Plats Coll Makes TISSUE FACTOR (with plats) Makes Plasminogen inhibitors

47 ENDOTHELIUM ACTIVATED by INFECTIOUS AGENTS ACTIVATED by HEMODYNAMICS ACTIVATED by PLASMA

48 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

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

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52 PLATELET PHASES ADHESION SECRETION (i.e., release or activation or degranulation ) AGGREGATION

53 PLATELET ADHESION Primarily to the subendothelial ECM Regulated by vwf, which bridges platelet surface receptors to ECM collagen

54 PLATELET SECRETION BOTH granules, α and δ Binding of agonists to platelet surface receptors AND intracellular protein PHOSPHORYLATION

55 PLATELET AGGREGATION ADP TxA2 (Thromboxane A2) THROMBIN from coagulation cascade also FIBRIN further strengthens and hardens and contracts the platelet plug

56 PLATELET EVENTS ADHERENCE to ECM SECRETION of ADP and TxA2 EXPOSE phospholipid complexes Express TISSUE FACTOR PRIMARY SECONDARY PLUG STRENGTHENED by FIBRIN

57 COAGULATION CASCADE INTRINSIC(contact)/EXTRINSIC(TissFac) Proenzymes Enzymes 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

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59 COAGULATION TESTS (a)ptt INTRINSIC (HEP Rx) PT (INR) EXTRINSIC (COUM Rx) BLEEDING TIME (PLATS) (2-9min) Platelet count (150, ,000/mm3) Fibrinogen Factor assays

60 THROMBOSIS Pathogenesis Endothelial Injury Alterations in Flow Hypercoagulability Morphology Fate Clinical Correlations Venous Arterial (Mural)

61 THROMBOSIS Virchow s TRIANGLE ENDOTHELIAL INJURY ABNORMAL FLOW (NON-LAMINAR) HYPER- COAGULATION

62 ENDOTHELIAL INJURY Jekyll/Hyde disruption any perturbation in the dynamic balance of the pro- and antithrombotic effects of endothelium, not only physical damage

63 ENDOTHELIUM 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)

64 ENDOTHELIUM PROTHROMBOTIC PROPERTIES Makes vwf, which binds Plats Coll Makes TISSUE FACTOR (with plats) Makes Plasminogen inhibitors

65 ABNORMAL FLOW NON-LAMINAR FLOW TURBULENCE EDDIES STASIS DISRUPTED ENDOTHELIUM ALL of these factors may bring platelets into contact with endothelium and/or ECF

66 1 HYPERCOAGULABILITY (INHERITED) COMMONEST: Factor V and Prothrombin defects Common: Mutation in prothrombin gene, Mutation in methyltetrahydrofolate gene Rare: Antithrombin III deficiency, Protein C deficiency, Protein S deficiency Very rare: Fibrinolysis defects

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68 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

69 MORPHOLOGY ADHERENCE TO VESSEL WALL HEART (MURAL) ARTERY (OCCLUSIVE/INFARCT) VEIN OBSTRUCTIVE vs. NON-OBSTRUCTIVE RED, YELLOW, GREY/WHITE ACUTE, ORGANIZING, OLD

70 MURAL THROMBI, HEART

71 FATE of THROMBI PROPAGATION (Downstream) EMBOLIZATION DISSOLUTION ORGANIZATION RECANALIZATION

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73 OCCLUSIVE ARTERIAL THROMBUS

74 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

75 ARTERIAL/CARDIAC THROMBI ACUTE MYOCARDIAL INFARCTION = OLD ATHEROSCLEROSIS + FRESH THROMBOSIS ARTERIAL THROMBI also may send fragments DOWNSTREAM, but these fragments may contain flecks of PLAQUE also LODGING is PROPORTIONAL to the % of cardiac output the organ receives, i.e., brain, kidneys, spleen, legs, or the diameter of the downstream vessel

76 ATHEROEMBOLI CHOLESTEROL clefts are components of atherosclerotic plaques, NOT thrombi!!!

77 Disseminated Intravascular Coagulation D.I.C. OBSTETRIC COMPLICATIONS ADVANCED MALIGNANCY NOT a primary disease CONSUMPTIVE coagulopathy, e.g., reduced platelets, fibrinogen, F-VIII and other consumable clotting factors, brain, heart, lungs, kidneys, MICROSCOPIC ONLY

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79 EMBOLISM Pulmonary Systemic (Mural Thrombi and Aneurysms) Fat Air Amniotic Fluid

80 PULMONARY EMBOLISM USUALLY SILENT CHEST PAIN, LOW PO2, S.O.B. Sudden OCCLUSION of >60% of pulmonary vasculature, presents a HIGH risk for sudden death, i.e., acute cor pulmonale, 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

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83 SYSTEMIC EMBOLI PARADOXICAL EMBOLI 80% cardiac/20% aortic Embolization lodging site is proportional to the degree of flow (cardiac output) that area or organ gets, i.e., brain, kidneys, legs

84 OTHER EMBOLI FAT (long bone fx s ) AIR (SCUBA bends) AMNIOTIC FLUID, very prolonged or difficult delivery, high mortality

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87 INFARCTION Defined as an area of necrosis* secondary to decreased blood flow HEMORRHAGIC vs. ANEMIC RED vs. WHITE END ARTERIES vs. NO END ARTERIES ACUTE ORGANIZATION FIBROSIS

88 INFARCTION FACTORS NATURE of VASCULAR SUPPLY RATE of DEVELOPMENT SLOW (BETTER) FAST (WORSE) VULNERABILITY to HYPOXIA MYOCYTE vs. FIBROBLAST CHF vs. NO CHF

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92 SHOCK Pathogenesis Cardiac Septic Hypovolemic Morphology Clinical Course

93 SHOCK Definition: CARDIOVASCULAR COLLAPSE Common pathophysiologic features: INADEQUATE CARDIAC OUTPUT and/or INADEQUATE BLOOD VOLUME

94 GENERAL RESULTS INADEQUATE TISSUE PERFUSION CELLULAR HYPOXIA UN-corrected, a FATAL outcome

95 TYPES of SHOCK CARDIOGENIC: (Acute, Chronic Heart Failure) HYPOVOLEMIC: (Hemorrhage or Leakage) SEPTIC: ( ENDOTOXIC shock, #1 killer in ICU) NEUROGENIC: (loss of vascular tone) ANAPHYLACTIC: (IgE mediated systemic vasodilation and increased vascular permeability)

96 CARDIOGENIC shock MI VENTRICULAR RUPTURE ARRHYTHMIA CARDIAC TAMPONADE PULMONARY EMBOLISM (acute RIGHT heart failure or cor pulmonale )

97 HYPOVOLEMIC shock HEMORRHAGE, Vasc. compartment H2O VOMITING, Vasc. compartment H2O DIARRHEA, Vasc. compartment H2O BURNS, Vasc. compartment H2O

98 SEPTIC shock OVERWHELMING INFECTION ENDOTOXINS, i.e., LPS (Usually Gm-) Gm+ FUNGAL SUPERANTIGENS, (Superantigens are polyclonal T-lymphocyte activators that induce systemic inflammatory cytokine cascades similar to those occurring downstream in septic shock, toxic shock antigens by staph are the prime example.)

99 SEPTIC shock events* (overwhelming infection) Peripheral vasodilation Pooling Endothelial Activation DIC * Think of this as a TOTAL BODY inflammatory response

100 ENDOTOXINS Usually Gm- Degraded bacterial cell wall products Also called LPS, because they are Lipo- Poly-Saccharides Attach to a cell surface antigen known as CD-14

101 ENDOTOXINS

102 SEPTIC shock events (linear sequence) SYSTEMIC VASODILATION (hypotension) MYOCARDIAL CONTRACTILITY DIFFUSE ENDOTHELIAL ACTIVATION LEUKOCYTE ADHESION ALVEOLAR DAMAGE (ARDS) DIC VITAL ORGAN FAILURE CNS

103 CLINICAL STAGES of shock NON-PROGRESSIVE PROGRESSIVE IRREVERSIBLE

104 NON-PROGRESSIVE COMPENSATORY MECHANISMS CATECHOLAMINES VITAL ORGANS PERFUSED

105 PROGRESSIVE HYPOPERFUSION EARLY VITAL ORGAN FAILURE OLIGURIA ACIDOSIS

106 IRREVERSIBLE HEMODYNAMIC CORRECTIONS of no use

107 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?)

108 ARDS/DAD

109 MYOCARDIAL NECROSIS

110 ATN

111 DIC

112 CLINICAL PROGRESSION of SYMPTOMS Hypotension Tachycardia Tachypnea Warm skin Cool skin Cyanosis Renal insufficiency Obtundance Death