4. hemodyn disorders,thrombosis, shock

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

Transcript of 4. hemodyn disorders,thrombosis, shock

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HEMODYNAMIC DISORDERS

Jv = ([Pc − Pi] − σ[πc − πi])

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•Hemodynamic Disorders

•Thromboembolic Disease

•Shock

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Overview• Edema

• Hyperemia

• Congestion

• Hemorrhage

• Hemostasis

• Thrombosis

• Embolism

• Infarction

• Shock

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EDEMA• ONLY 4 POSSIBILITIES!!!

–Increased Hydrostatic Pressure–Reduced Oncotic Pressure–Lymphatic Obstruction–Sodium/Water Retention

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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

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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

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REDUCED PLASMA ONCOTICPRESSURE (HYPOPROTEINEMIA)• Protein-losing glomerulopathies

(nephrotic syndrome)

• Liver cirrhosis (ascites)

• Malnutrition

• Protein-losing gastroenteropathy

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LYMPHATIC OBSTRUCTION(LYMPHEDEMA)

• Inflammatory

• Neoplastic

• Postsurgical

• Postirradiation

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Na+ RETENTION• Excessive salt intake with renal

insufficiency

• Increased tubular reabsorption of sodium

• Renal hypoperfusionIncreased renin-angiotensin-aldosterone secretion

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INFLAMMATION• Acute inflammation

• Chronic inflammation

• Angiogenesis

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Jv = ([Pc − Pi] − σ[πc − πi])

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CHF EDEMA• INCREASED VENOUS PRESSURE

DUE TO FAILURE

• DECREASED RENAL PERFUSION, triggering of RENIN-ANGIOTENSION-ALDOSTERONE complex, resulting ultimately in SODIUM RETENTION

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HEPATIC ASCITES

• PORTAL HYPERTENSION

• HYPOALBUMINEMIA

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ASCITES

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RENAL EDEMA• SODIUM RETENTION

• PROTEIN LOSING GLOMERULOPATHIES (NEPHROTIC SYNDROME)

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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

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“Pitting” Edema

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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

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HYPEREMIA/(CONGESTION)

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HYPEREMIAActive Process

CONGESTIONPassive ProcessAcute or Chronic

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CONGESTION• LUNG

–ACUTE

–CHRONIC

• LIVER–ACUTE

–CHRONIC

• CEREBRAL

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ACUTE PASSIVE HYPEREMIA/CONGESTION,

LUNG

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Kerley B

Air Bronch-ogram

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CHRONIC PASSIVE HYPEREMIA/CONGESTION,

LUNG

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Acute Passive Congestion, Liver

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Acute Passive Congestion, Liver

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CHRONIC PASSIVE HYPEREMIA/CONGESTION, LIVER

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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

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EVOLUTION of HEMORRHAGE

• ACUTE CHRONIC

• PURPLE GREEN BROWN

• HGB BILIRUBIN HEMOSIDERIN

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HEMATOMAvs.

“CLOT”

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HEMOSTASIS• OPPOSITE of THROMBOSIS

–PRESERVE LIQUIDITY OF BLOOD

–“PLUG” sites of vascular injury

• THREE COMPONENTS–VASCULAR WALL, i.e., endoth/ECM

–PLATELETS

–COAGULATION CASCADE

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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 (2˚ HEMOSTASIS)

• FIBRIN polymerizes, TPA limits plug

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PLAYERS•ENDOTHELIUM

•PLATELETS

•COAGULATION “CASCADE”

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ENDOTHELIUM• NORMALLY

–ANTIPLATELET PROPERTIES

–ANTICOAGULANT PROPERTIES

–FIBRINOLYTIC PROPERTIES

• IN INJURY–PRO-COAGULANT PROPERTIES

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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)

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ENDOTHELIUM• PROTHROMBOTIC PROPERTIES

–Makes vWF, which binds PlatsColl

–Makes TISSUE FACTOR (with plats)

–Makes Plasminogen inhibitors

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ENDOTHELIUM• ACTIVATED by INFECTIOUS AGENTS

• ACTIVATED by HEMODYNAMICS

• ACTIVATED by PLASMA

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

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PLATELET PHASES

• ADHESION

• SECRETION (i.e., “release” or “activation” or “degranulation”)

• AGGREGATION

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PLATELET ADHESION

• Primarily to the subendothelial ECM

• Regulated by vWF, which bridges platelet surface receptors to ECM collagen

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PLATELET SECRETION

• BOTH granules, α and δ• Binding of agonists to

platelet surface receptors AND intracellular protein PHOSPHORYLATION

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PLATELET AGGREGATION

• ADP

• TxA2 (Thromboxane A2)

• THROMBIN from coagulation cascade also

• FIBRIN further strengthens and hardens and contracts the platelet plug

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PLATELET EVENTS

• ADHERENCE to ECM

• SECRETION of ADP and TxA2

• EXPOSE phospholipid complexes

• Express TISSUE FACTOR

• PRIMARYSECONDARY PLUG

• STRENGTHENED by FIBRIN

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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

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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

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THROMBOSIS• Pathogenesis

• Endothelial Injury

• Alterations in Flow

• Hypercoagulability

• Morphology

• Fate

• Clinical Correlations

• Venous

• Arterial (Mural)

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THROMBOSIS• Virchow’s TRIANGLE

ENDOTHELIAL INJURY

ABNORMAL FLOW(NON-LAMINAR)

HYPER-COAGULATION

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ENDOTHELIAL “INJURY”

• Jekyll/Hyde disruption–any perturbation in the dynamic

balance of the pro- and antithrombotic effects of endothelium, not only physical “damage”

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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)

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ENDOTHELIUM• PROTHROMBOTIC PROPERTIES

–Makes vWF, which binds PlatsColl

–Makes TISSUE FACTOR (with plats)

–Makes Plasminogen inhibitors

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ABNORMAL FLOW• NON-LAMINAR FLOW

• TURBULENCE

• EDDIES

• STASIS

• “DISRUPTED” ENDOTHELIUM

ALL of these factors may bring platelets into contact with endothelium and/or ECF

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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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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

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MORPHOLOGY• ADHERENCE TO VESSEL WALL

– HEART (MURAL)

– ARTERY (OCCLUSIVE/INFARCT)

– VEIN

• OBSTRUCTIVE vs. NON-OBSTRUCTIVE

• RED, YELLOW, GREY/WHITE

• ACUTE, ORGANIZING, OLD

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MURAL THROMBI, HEART

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FATE of THROMBI• PROPAGATION (Downstream)

• EMBOLIZATION

• DISSOLUTION

• ORGANIZATION

• RECANALIZATION

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OCCLUSIVE ARTERIAL THROMBUS

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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

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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

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ATHEROEMBOLI• “CHOLESTEROL” clefts are

components of atherosclerotic plaques, NOT thrombi!!!

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Disseminated Intravascular Coagulation

D.I.C.• OBSTETRIC COMPLICATIONS

• ADVANCED MALIGNANCYNOT 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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EMBOLISM•Pulmonary• Systemic (Mural Thrombi and

Aneurysms)

• Fat

• Air

• Amniotic Fluid

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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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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

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OTHER EMBOLI•FAT (long bone fx’s )

•AIR (SCUBA bends)

•AMNIOTIC FLUID, very prolonged or difficult delivery, high mortality

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INFARCTION• Defined as an area of necrosis*

secondary to decreased blood flow

• HEMORRHAGIC vs. ANEMIC

• RED vs. WHITE– END ARTERIES vs. NO END ARTERIES

• ACUTEORGANIZATIONFIBROSIS

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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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HEART

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SHOCK• Pathogenesis

–Cardiac

–Septic

–Hypovolemic

• Morphology

• Clinical Course

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SHOCK• Definition: CARDIOVASCULAR COLLAPSE

• Common pathophysiologic features:– INADEQUATE CARDIAC OUTPUT and/or– INADEQUATE BLOOD VOLUME

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GENERAL RESULTS• INADEQUATE TISSUE PERFUSION

• CELLULAR HYPOXIA

• UN-corrected, a FATAL outcome

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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)

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CARDIOGENIC shock• MI

• VENTRICULAR RUPTURE

• ARRHYTHMIA

• CARDIAC TAMPONADE

• PULMONARY EMBOLISM (acute RIGHT heart failure or “cor pulmonale”)

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HYPOVOLEMIC shock

• HEMORRHAGE, Vasc. compartmentH2O

• VOMITING, Vasc. compartmentH2O

• DIARRHEA, Vasc. compartmentH2O

• BURNS, Vasc. compartmentH2O

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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” antigents by staph are the prime example.)

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SEPTIC shock events*(overwhelming infection)

• Peripheral vasodilation• Pooling• Endothelial Activation• DIC

* Think of this as a TOTAL BODY inflammatory response

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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

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ENDOTOXINS

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SEPTIC shock events(linear sequence)

• SYSTEMIC VASODILATION (hypotension)

• ↓ MYOCARDIAL CONTRACTILITY• DIFFUSE ENDOTHELIAL ACTIVATION• LEUKOCYTE ADHESION• ALVEOLAR DAMAGE (ARDS)

• DIC

• VITAL ORGAN FAILURE CNS

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CLINICAL STAGES of shock

•NON-PROGRESSIVE

•PROGRESSIVE

• IRREVERSIBLE

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NON-PROGRESSIVE• COMPENSATORY MECHANISMS

•CATECHOLAMINES• VITAL ORGANS PERFUSED

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PROGRESSIVE• HYPOPERFUSION

• EARLY “VITAL” ORGAN FAILURE

• OLIGURIA

•ACIDOSIS

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IRREVERSIBLE

•HEMODYNAMIC CORRECTIONS of no use

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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?)

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ARDS/DAD

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MYOCARDIAL NECROSIS

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ATN

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DIC

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CLINICAL PROGRESSIONof SYMPTOMS

• Hypotension • Tachycardia • Tachypnea • Warm skin Cool skin Cyanosis

• Renal insufficiency• Obtundance

• Death