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CHAPTER 4. Hemodynamic Disorders Thromboembolic Disease Shock. Overview. Edema Hyperemia and Congestion Hemorrhage Hemostasis and Thrombosis Embolism Infarction Shock. Fluid Compartments. Goldman: Cecil Textbook of Medicine, 22nd ed. Body Fluid Compartments. Walter B Cannon.

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Presentation Transcript
Chapter 4
CHAPTER4

  • Hemodynamic Disorders

  • Thromboembolic Disease

  • Shock


Overview
Overview

  • Edema

  • Hyperemia and Congestion

  • Hemorrhage

  • Hemostasis and Thrombosis

  • Embolism

  • Infarction

  • Shock


Fluid compartments
Fluid Compartments

Goldman: Cecil Textbook of Medicine, 22nd ed



Walter b cannon
Walter B Cannon

  • Fight or flight response

  • Concept of homeostasis

    • maintenance of internal environment or milieu

    • usually involves negative feedback loops

  • Mechanisms of homeostatis

    • physiologic circumstances

      • have evolved over thousands of years

      • adaptations usually beneficial-“Wisdom of the Body”

    • pathologic conditions

      • sick individuals do not survive in nature

      • adaptations may be harmful- “ folly of the body ”


Edema
Edema

  • Definition

    • abnormally increased interstitial fluid

  • Location

    • Peripheral

    • Cerebral

    • Pulmonary

  • Special Types

    • hydrothroax (pleural effusion)

    • hydroperitoneum (ascites)

    • Anasarca


Starling Forces Affecting Fluid Movement

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Starling law of capillary interstitial liquid exchange
Starling Law Of Capillary-interstitial Liquid Exchange

Liquid Accumulation =

K[(PC – PIF) - δ (πPL - πIF)] - Q lymph

K, hydraulic conductance (directly proportional to membrane surface area and inversely proportional to membrane thickness)

PC, mean intracapillary pressure

PIF, mean interstitial liquid pressure

δ , reflection coefficient of macromolecules

π IF, oncotic pressure of interstitial liquid

π PL, oncotic pressure of the plasma

Q lymph, lymphatic flow


Pathophysiologic categories of edema
Pathophysiologic Categories of Edema

  • Increased Hydrostatic Pressure

  • Reduced Plasma Osmotic Pressure (Hypoproteinemia)

  • Lymphatic Obstruction

  • Sodium Retention

  • Inflammation


Increased hydrostatic pressure
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


Reduced plasma osmotic pressure hypoproteinemia
Reduced Plasma Osmotic Pressure (Hypoproteinemia)

  • Protein-losing glomerulopathies (nephrotic syndrome)

  • Liver cirrhosis (ascites)

  • Malnutrition

  • Protein-losing gastroenteropathy


Lymphatic obstruction
Lymphatic Obstruction

  • Inflammatory

  • Neoplastic

  • Postsurgical

  • Postirradiation


Sodium retention
Sodium Retention

  • Excessive salt intake with renal insufficiency

  • Increased tubular reabsorption of sodium

  • Renal hypoperfusion

  • Increased renin-angiotensin-aldosterone secretion


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Volume repletion reaction
Volume Repletion Reaction Disease (on 27 June 2005 07:26 PM)

Goldman: Cecil Textbook of Medicine, 22nd ed.


Localization of edema
Localization of Edema Disease (on 27 June 2005 07:26 PM)

  • Generalized

    • hypoproteinemia: delicate tissues-periorbital, face

    • accentuated in dependent areas

  • Localized

    • Cerebral

      • abscess, neoplasm-localized

      • head trauma, anoxia, encephalitis-generalized

    • Pulmonary

      • left heart failure

      • infection and toxins

    • One leg

      • thrombophlebitis


Hyperemia and congestion
Hyperemia and Congestion Disease (on 27 June 2005 07:26 PM)

both involve increased blood volume

  • Hyperemia – active process

    • functional

    • Inflamatory

  • Congestion – passive process

    • acute

    • chronic – secondary changes

      • fibrosis

      • hemosiderin laden macrophages


Pitting edema
Pitting Edema Disease (on 27 June 2005 07:26 PM)


Ascites
Ascites Disease (on 27 June 2005 07:26 PM)


Kerley B Disease (on 27 June 2005 07:26 PM)

Air Bronch-ogram


Transudate vs exudate
Transudate vs Exudate Disease (on 27 June 2005 07:26 PM)

  • 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


Leading Causes of Pleural Effusion in the United States, According to Analysis of Patients Subjected to Thoracentesis

Light, R. W. N Engl J Med 2002;346:1971-1977


Sensitivity of Tests to Distinguish Exudative from Transudative Effusions

Light, R. W. N Engl J Med 2002;346:1971-1977


Transtentorial Herniation Of The Temporal Lobe With Compression Of The Brain Stem

Carter, B. S. et al. N Engl J Med 2004;350:707-716


Normal Compression Of The Brain Stem

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Hyperemia Compression Of The Brain Stem

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Hemorrhage
Hemorrhage Disease (on 27 June 2005 07:26 PM)

  • Site

    • external

    • hematoma

  • Size

    • petechiae: 1-2 mm, non-palpable

    • purpura: ≥ 3mm

    • ecchymoses > 1 cm

  • Within body cavities

    • hemothroax

    • hemopericardium

    • hemoperitoneum


Petechiae
Petechiae Disease (on 27 June 2005 07:26 PM)


Purpura
Purpura Disease (on 27 June 2005 07:26 PM)


Ecchymosis
Ecchymosis Disease (on 27 June 2005 07:26 PM)


Phases of hemostasis
Phases of Hemostasis Disease (on 27 June 2005 07:26 PM)

  • Vasoconstriction

  • Primary Hemostasis

    • formation of platelet plug

  • Secondary Hemostasis

    • clot formation

  • Thrombus and Antithrombotic Events

    • regulation of thrombus formation and dissolution


Effects of hemorrhage
Effects of Hemorrhage Disease (on 27 June 2005 07:26 PM)

  • Site of hemorrhage

    • brain, pericardium, pleural space

    • internal: iron can be reutilized

    • external: may lead to iron deficiency

  • Rate of blood loss

    • acute

      • loss of > 20% of blood volume may cause hypotension or hypovolemic shock

      • hemoglobin concentration not altered

    • non-acute

      • volume loss compensated by shift of fluid from extravascular to intravascular compartment

      • hemoglobin concentration decreased


Hematocrit
Hematocrit Disease (on 27 June 2005 07:26 PM)


Vasoconstriction
Vasoconstriction Disease (on 27 June 2005 07:26 PM)

  • Endothelin release

  • Reflex neurogenic

  • Thrombaxane A2 (released with 1° hemostasis)


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Primary hemostasis
Primary Hemostasis Disease (on 27 June 2005 07:26 PM)

  • Platelet Adhesion

  • Platelet Release

  • Platelet Aggregation

  • Formation of platelet plug


Platelet adhesion
Platelet Adhesion Disease (on 27 June 2005 07:26 PM)

  • exposed collagen

  • platelet surface receptors (GpIb)

  • von Willebrand factor


Platelet adhesion and aggregation Disease (on 27 June 2005 07:26 PM)

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Platelet granules
Platelet Granules Disease (on 27 June 2005 07:26 PM)

  • Alpha Granules

    • P-selectin

    • fibrinogen and other clotting factors

    • platelet derived growth factor

  • Dense Granules

    • ADP and ATP

    • histamine

    • serotonin

    • epinephrine


Platelet release
Platelet Release Disease (on 27 June 2005 07:26 PM)

  • Thrombaxane A2

  • ADP (adenosine diphosphate)

  • vWF and other clotting factors

  • Platelet derived growth factor


Platelet release1
Platelet Release Disease (on 27 June 2005 07:26 PM)


Platelet aggregation
Platelet Aggregation Disease (on 27 June 2005 07:26 PM)

  • Thrombaxane A2 and ADP set up autocatalytic reaction

  • Thrombin furthers aggregation and initiates fibrin clot

  • Viscous metamorphosis-irreversibly fused mass of platelets


Platelet adhesion and aggregation Disease (on 27 June 2005 07:26 PM)

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Coagulation cascade
Coagulation Cascade Disease (on 27 June 2005 07:26 PM)

  • Enzyme (activated coagulation factor)

  • Substrate (proenzyme form of factor)

  • cofactor (reaction accelerator)

  • Phospholipid complex (assembly site)


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Clinically important coagulation reactions
Clinically Important Coagulation Reactions Disease (on 27 June 2005 07:26 PM)

Harrison’s Internal Med, 16th Ed


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Central Roles Of Thrombin In Hemostasis And Cellular Activation

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Extrinsic and intrinsic interaction
Extrinsic and Intrinsic Interaction Activation

Harrison’s Internal Med, 16th Ed


Differences in the clinical manifestations of disorders of primary and secondary hemostasis
Differences in the Clinical Manifestations of Disorders of Primary and Secondary Hemostasis

Harrison’s Internal Med, 16th Ed


Evaluation of hemostasis
Evaluation of Hemostasis Primary and Secondary Hemostasis

  • Clinical History

    • family history

    • previous challenges to hemostasis

  • Partial Thromboplastin Time (PTT)

    • measures intrinsic coagulation system

  • Prothrombin Time (PT)

    • measures extrinsic coagulation system

  • Platelet Count

  • Bleeding Time (BT)


Relationship of platelet count to bt
Relationship of Platelet Count to BT Primary and Secondary Hemostasis


Natural anticoagulants
Natural Anticoagulants Primary and Secondary Hemostasis

  • Antithrombin III

    • interacts with heparin like molecules

    • inactives thrombin (IIa) and Xa

  • Thrombomodulin

    • binds to thrombin

    • activtes protein C – protein S system

  • Protein C - Protein S System

    • inhibits Va and VIIIa

  • Tissue factor pathway inhibitor

    • inactivates VIIa and Xa


The fibrinolytic system
The Fibrinolytic System Primary and Secondary Hemostasis

  • Tissue Plasminogen Activator (tPA)

    • produced by endothelial cells

    • binds to fibrin to localize action

    • converts plasminogen to plasmin

    • inactivated by plasminogen activator inhibitor (PAI)

    • analogs produced by recombinant DNA are in widespread clinical use for myocardial infarction and stroke

  • Urokinase

    • similar fibrinolytic system in kidney

  • Streptokinase

    • produced by streptococcal organisms

    • lyses both fibrinogen and fibrin (non-specific)


Pro- And Anticoagulant Activities Of Endothelial Cells Primary and Secondary Hemostasis

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The Fibrinolytic System Primary and Secondary Hemostasis

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Clinically important coagulation reactions1
Clinically Important Coagulation Reactions Primary and Secondary Hemostasis


Virchow Triad In Thrombosis Primary and Secondary Hemostasis

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Abnormal blood flow
Abnormal Blood Flow Primary and Secondary Hemostasis

  • Stasis - venous

  • Turbulence - arterial

  • Laminar flow

    • peripheral static layer

    • more central layers with increasingly faster flow

    • platelets and cells are in the central portion and do not touch vessel wall


Primary genetic hypercoaguable states
Primary (Genetic) Hypercoaguable States Primary and Secondary Hemostasis

  • Common

    • Mutation in factor V gene (factor V Leiden)

    • Mutation in prothrombin gene

    • Mutation in methyltetrahydrofolate gene

  • Rare

    • Antithrombin III deficiency

    • Protein C deficiency

    • Protein S deficiency

  • Very rare

    • Fibrinolysis defects


Hereditary thrombophilia
Hereditary Thrombophilia Primary and Secondary Hemostasis

  • Less than 50 years of age

  • Family history of venous thrombosis

  • History of recurrent events

  • Absence of acquired risk factors except for pregnancy and oral contraceptive use


Frequency of Inherited Thrombophilias among Healthy Subjects and Unselected and Selected Patients with Venous Thrombosis

Seligsohn, U. et al. N Engl J Med 2001;344:1222-1231


Factor v leiden
Factor V Leiden and Unselected and Selected Patients with Venous Thrombosis

  • Present in 2-15% of Caucasians

  • Substitution of glutamine for arginine at position 506

  • Renders the factor Va resistant to inactivation by protein C (APC resistance)

    • homozygous – 20 fold increased risk of thrombosis

    • heterozygous + BC Pills – 15 fold increase

  • In patients with deep vein thrombosis, carrier state is as high as 60%


Prothrombin gene mutation
Prothrombin Gene Mutation and Unselected and Selected Patients with Venous Thrombosis

  • Point mutation of Guanine to Adenine at position 20210 (G20210A) in prothrombin gene

  • Present in 1-2% of the population

  • Occurs in untranslated portion and results in a 30% increase in prothrombin levels

  • Prothrombin protein is structurally normal


Secondary acquired hypercoaguable states
Secondary (Acquired) and Unselected and Selected Patients with Venous ThrombosisHypercoaguable States

  • High risk for thrombosis

    • Prolonged bed rest or immobilization

    • Myocardial infarction

    • Atrial fibrillation

    • Tissue damage (surgery, fracture, burns)

    • Cancer

    • 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


Morphology of thrombi
Morphology of Thrombi and Unselected and Selected Patients with Venous Thrombosis

  • Arterial (usually occlusive)

    • site of endothelial injury

    • retrograde propagation

  • Cardiac (usual mural)

    • ventricles: site of endothelial injury

    • atria: occur in sites of stasis

  • Venous

    • occur in sites of stasis

    • propagate in direction of blood flow

  • Heart Valves (vegetations)

    • infective endocarditis

    • non-bacterial thrombotic endocarditis


Fate of the thrombus
Fate of the Thrombus and Unselected and Selected Patients with Venous Thrombosis

  • Propagation

  • Embolization

  • Dissolution – Fibrinolysis

    • older thrombi with cross linked fibrin are resistant to lysis

  • Organization and recanalization.


Potential Outcomes Of Venous Thrombosis and Unselected and Selected Patients with Venous Thrombosis

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Heparin induced thrombocytopenia hit
Heparin Induced Thrombocytopenia (HIT) and Unselected and Selected Patients with Venous Thrombosis

  • Caused by induction of antibodies to complex formed by heparin and platelet factor 4 (heparin neutralizing protein)

  • Antibodies induce platelet activation, aggregation, thrombocytopenia, DIC, and paradoxical thrombosis

  • Is life threatening

  • More common with unfractionated heparin

  • Less common with low molecular weight heparin, but antibodies cross react

  • Anticoagulation with direct thrombin inhibitors usually necessary to prevent further clotting (argatrobin, lepirudin)


Antiplatelet agents anticoagulants and thrombolytics
Antiplatelet Agents, Anticoagulants and Thrombolytics and Unselected and Selected Patients with Venous Thrombosis

  • Antiplatelet

    • Aspirin: inhibit cyclooxygenase

    • clopidogrel (Plavix): ADP blockade

    • Glycoprotein IIa/IIIb inhibitors-final common pathway

  • Anticoagulants

    • unfractionated heparin: Xa and IIa

    • low molecular weight heparin: Xa > IIa

    • warfarin (Coumadin): inhibits synthesis of vitamin K dependent factors-II, VII, IX, X, proteins C and S

  • Thrombolytics

    • tissue plasminogen activators

    • streptokinase


Antiphospholipid antibody syndrome general
Antiphospholipid Antibody Syndrome-General and Unselected and Selected Patients with Venous Thrombosis

  • Associated with high titers of antibodies to anionic phospholipids (e.g. Cardiolipins)

  • Result in false positive serologic tests for syphilis

  • Antibodies inhibit assembly of phospholipid complexes, inhibiting in vitro coagulation tests

  • In Vivo result in a hypercoaguable state


Antiphospholipid antibody syndrome classification
Antiphospholipid Antibody Syndrome-Classification and Unselected and Selected Patients with Venous Thrombosis

  • Secondary antiphospholipid syndrome

    • most frequent type

    • associated with autoimmune syndromes such as lupus erythematosis

  • Primary antiphospholipid syndrome

    • no underlying autoimmune disorder


Clinical findings in antiphospholipid antibody syndrome
Clinical Findings in Antiphospholipid Antibody Syndrome and Unselected and Selected Patients with Venous Thrombosis

  • recurrent venous or arterial thrombi

    • venous thrombi in leg veins most common

    • arterial thrombi in cerebral circulation

  • repeated miscarriages

    • fetal loss related to inhibition of t-PA activity necessary for trophoblastic invasion of uterus

  • cardiac valvular vegetations

  • thrombocytopenia


Embolism
Embolism and Unselected and Selected Patients with Venous Thrombosis

  • Definition

    • An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin.

  • Composition

    • thrombi – by far the most common. Embolus without qualification is understood to be a thromboembolus

    • air

    • amniotic fluid

    • tumor

    • cholesterol

  • Consequence

    • decreased perfusion of tissue distal to embolus with possible infarction


Pulmonary thromboembolism
Pulmonary Thromboembolism and Unselected and Selected Patients with Venous Thrombosis

  • Cause 200,000 deaths / year in the USA

  • Most arise from deep leg vein thrombi above the level of the knee

  • Most (60-80%) are clinically silent

  • Large emboli (>60% obstruction) can cause cardiovascular collapse

  • Medium sized emboli may not cause infarction

  • Small end-artery emboli may cause infarction


Pulmonary Embolus and Unselected and Selected Patients with Venous Thrombosis

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Helical ct of pulmonary emboli
Helical CT of Pulmonary Emboli and Unselected and Selected Patients with Venous Thrombosis

Emergency Medicine Clinics of North AmericaVolume 22 • Number 3 • August 2004


Ultrasound of femoral vein
Ultrasound of Femoral Vein and Unselected and Selected Patients with Venous Thrombosis

Emergency Medicine Clinics of North AmericaVolume 22 • Number 3 • August 2004


Infarction
Infarction and Unselected and Selected Patients with Venous Thrombosis

  • An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue.

  • Causes of occlusion

    • thrombosis or embolism—99%

    • local vasospasm

    • compression of vessel by hematoma or tumor

    • Torsion of vessels-testicular torsion, bowel vovulus


Morphology of infarcts
Morphology of Infarcts and Unselected and Selected Patients with Venous Thrombosis

  • Red (hemorrhagic) Infarct

    • venous occlusion- e.g. testicular torsion

    • loose tissues- e.g. lung

    • tissues with dual circulations: lung and gut

    • with reperfusion

  • White Infarct

    • solid organs with end-arterial circulation such as kidney, heart, spleen


Examples of infarcts and Unselected and Selected Patients with Venous Thrombosis

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Histology of infarction
Histology of Infarction and Unselected and Selected Patients with Venous Thrombosis

  • Coagulation necrosis

    • necrosis occurs in minutes to hours

    • light microscopic changes noted in 10-12 hours

    • inflamatory response in 1-2 days

    • reparative response

  • Liquefaction Necrosis

    • characteristic of brain infarcts


Clinical correlations
Clinical Correlations and Unselected and Selected Patients with Venous Thrombosis

  • Nature of blood supply

    • end-artery blood supply

    • dual blood supply

  • Rate of development of occlusion

    • role of collateral circulation

  • Vulnerability of tissue to ischemia

    • brain: 3-4 minutes

    • heart: 20-30 minutes

  • Oxygen content of blood

    • hemoglobin concentration and saturation


Mural Thrombi and Unselected and Selected Patients with Venous Thrombosis

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Disseminated intravascular coagulation dic
Disseminated Intravascular Coagulation (DIC) and Unselected and Selected Patients with Venous Thrombosis

  • Widespread fibrin thrombi in the micro-circulation (brain, heart, lungs, kidneys)

  • Consumption of platelets and coagulation proteins (consumption coagulopathy)

  • Production of fibrin split products with fibrinolysis

  • Is a syndrome, not a disease, and occurs in sepsis, malignancy and other conditions


Systemic thromboembolism
Systemic Thromboembolism and Unselected and Selected Patients with Venous Thrombosis

Emboli traveling in arterial circulation

Source

intracardiac mural thrombi (80%)

left atrium: dilation and fibrillation (25%)

heart valve vegetations

aortic mural thrombi

paradoxical

Sites of embolization

lower extremities (75%)

brain (10%)

intestine, kidney, spleen

Consequences of embolization

affected by collateral or dual blood supply

infarction of tissue


Fat embolism
Fat Embolism and Unselected and Selected Patients with Venous Thrombosis

  • severe trauma with multiple fractures

  • sites of embolization

    • lungs: pulmonary insufficiency

    • brain: restlessness, delirium, coma

  • pathogenesis

    • mechanical obstruction

    • chemical irritation from release of fatty acids, endothelial injury, platelet activation and aggregation, hemolysis, and intravascular coagulation

  • Prognosis

    • asymptomatic (up to 90% of cases)

    • fatal in severe cases


Air embolism
Air Embolism and Unselected and Selected Patients with Venous Thrombosis

  • Entry of air bubbles into circulation

    • chest trauma

    • obstetrical procedures

    • vascular surgery

    • decompression events

  • Usually more than 100 ml of air needed to produce symptoms


Amniotic fluid embolism
Amniotic Fluid Embolism and Unselected and Selected Patients with Venous Thrombosis

  • Obstetrical complication with entry of amniotic fluid into uterine venous circulation

  • Amniotic fluid contains

    • squamous cells from fetal skin

    • lanugo hair

    • fat from vernix caseosa

    • mucin from fetal respiratory and digestive tract

  • Consequences

    • pulmonary and cerebral dysfunction

    • disseminated intravascular coagulation


Shock
Shock and Unselected and Selected Patients with Venous Thrombosis

  • Shock is the clinical syndrome that results from inadequate tissue perfusion

  • Classification of shock

    • Cardiogenic shock

    • Hypovolemic shock

    • Septic shock

    • Other less common types of shock

      • neurogenic shock

      • Anaphylactic shock

      • Hypoadrenal shock


Cardiogenic shock
Cardiogenic Shock and Unselected and Selected Patients with Venous Thrombosis

  • Myocardial pump failure

    • myocardial infarction

    • myocardial rupture

    • cardiac arrhythmia

  • extrinsic compression

    • cardiac tamponade

  • Outflow obstruction

    • pulmonary embolus


Hypovolemic shock
Hypovolemic Shock and Unselected and Selected Patients with Venous Thrombosis

  • Hemorrhage

    • external

    • internal

      • GI tract

      • hemothorax

      • peritoneal or retroperitoneal space

  • Loss of fluid into third space

    • burns

    • pancreatitis


Septic shock
Septic Shock and Unselected and Selected Patients with Venous Thrombosis

  • Leading cause of death in intensive care units

  • Causes 200,000 deaths in USA / year

  • Most cases (70%) are caused by gram negative bacteria (LPS-lipopolysaccharide)

  • Also can occur with gram positive bacteria and fungal organisms


Low doses of lps
Low Doses of LPS and Unselected and Selected Patients with Venous Thrombosis

  • activation of monocytes and macrophages, with production of cytokines, mainly TNF, IL-1, IL-6, and chemokines

  • TNF and IL-1 both act on endothelial cells to stimulate the expression of adhesion molecules

  • direct activation of complement


Moderate doses of lps
Moderate Doses of LPS and Unselected and Selected Patients with Venous Thrombosis

  • cytokine-induced secondary effectors (e.g., nitric oxide) become significant.

  • systemic effects of the cytokines such as TNF and IL-1 may begin to be seen; these include fever and increased synthesis of acute phase reactants

  • LPS at higher doses also results in diminished endothelial cell production of thrombomodulin and TFPI, tipping the coagulation cascade toward thrombosis.


High levels of lps
High Levels of LPS and Unselected and Selected Patients with Venous Thrombosis

  • Highest levels of LPS result in the syndrome of septic shock

  • The same cytokines and secondary mediators, now at high levels, result in:

  • Systemic vasodilation (hypotension)

    • Diminished myocardial contractility

    • Widespread endothelial injury and activation, causing systemic leukocyte adhesion and pulmonary alveolar capillary damage (acute respiratory distress syndrome)

    • Activation of the coagulation system, culminating in DIC


Cytokine Cascade In Sepsis and Unselected and Selected Patients with Venous Thrombosis

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Effects Of and Unselected and Selected Patients with Venous ThrombosisLipopolysaccharide (LPS) And Secondarily Induced Effector Molecules

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Treatment of septic shock
Treatment of Septic Shock and Unselected and Selected Patients with Venous Thrombosis

  • Supportive care

  • Elimination of infection

  • Control of inflammatory cascade

    • modulators of TNF, IL-1, and secondary mediators have not been effective

    • recombinant activated protein C (aPC, which acts as an anticoagulant) has been approved by the FDA.


Homeostatic mechanisms in shock
Homeostatic Mechanisms in Shock and Unselected and Selected Patients with Venous Thrombosis

  • Baroreceptor reflexes and catecholamine release

    • maintain cerebral and cardiac perfusion

    • decrease perfusion to gut, skin and kidneys

  • Activation of renin-angiotensin system

    • angiotensin II constricts efferent arteriole of glomerulus to maintain GFR

    • aldosterone promotes sodium retention

  • Release of Arginine Vasopressin (ADH)

    • promotes renal conservation of water


Clinical findings
Clinical Findings and Unselected and Selected Patients with Venous Thrombosis

  • Hypotension

  • Signs of adrenergic activity

    • tachycardia

    • peripheral vasoconstriction (not w/septic shock)

    • sweating

  • decreased urine output

  • Lactic acidosis

  • Anoxic tissue damage (↑serum LDH)


Morphology of shock
Morphology of Shock and Unselected and Selected Patients with Venous Thrombosis

Hypoxic injury to multiple organs

  • kidneys

    • medulla and tubules most affected

    • acute tubular necrosis

  • gastrointestinal tract

    • mucosa most sensitive to hypoxia

  • brain

  • heart

    • subendocardial necrosis of myocardium

  • Lungs

    • resistant to hypoxia but involved with septic shock


Clinical course
Clinical Course and Unselected and Selected Patients with Venous Thrombosis

  • Hypovolemic shock

    • if patient is young and healthy, most survive if resuscitation restores perfusion

  • Cardiogenic shock and septic shock

    • up to 75% mortality even with best care

  • Patients succumb with multi-organ failure

    • tubular necrosis of kidneys

    • ischemic enteropathy (possibly w/sepsis)

    • disseminated intravascular coagulation

    • Acute respiratory distress syndrome (septic shock)


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