CHAPTER 4 - PowerPoint PPT Presentation

Chapter 4
Download
1 / 124

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.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha

Download Presentationdownload

CHAPTER 4

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

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


Body fluid compartments

Body Fluid Compartments


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


Facultycjminarcikch4

Starling Forces Affecting Fluid Movement

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Starling forces

Starling Forces


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


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Volume repletion reaction

Volume Repletion Reaction

Goldman: Cecil Textbook of Medicine, 22nd ed.


Localization of edema

Localization of Edema

  • 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

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


Ascites

Ascites


Facultycjminarcikch4

Kerley B

Air Bronch-ogram


Transudate vs exudate

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


Facultycjminarcikch4

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


Facultycjminarcikch4

Sensitivity of Tests to Distinguish Exudative from Transudative Effusions

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


Facultycjminarcikch4

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


Facultycjminarcikch4

Normal

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Hyperemia

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Hemorrhage

Hemorrhage

  • Site

    • external

    • hematoma

  • Size

    • petechiae: 1-2 mm, non-palpable

    • purpura: ≥ 3mm

    • ecchymoses > 1 cm

  • Within body cavities

    • hemothroax

    • hemopericardium

    • hemoperitoneum


Petechiae

Petechiae


Purpura

Purpura


Ecchymosis

Ecchymosis


Phases of hemostasis

Phases of Hemostasis

  • 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

  • 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


Vasoconstriction

Vasoconstriction

  • Endothelin release

  • Reflex neurogenic

  • Thrombaxane A2 (released with 1° hemostasis)


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Primary hemostasis

Primary Hemostasis

  • Platelet Adhesion

  • Platelet Release

  • Platelet Aggregation

  • Formation of platelet plug


Platelet adhesion

Platelet Adhesion

  • exposed collagen

  • platelet surface receptors (GpIb)

  • von Willebrand factor


Facultycjminarcikch4

Platelet adhesion and aggregation

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Platelet granules

Platelet Granules

  • 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

  • Thrombaxane A2

  • ADP (adenosine diphosphate)

  • vWF and other clotting factors

  • Platelet derived growth factor


Platelet release1

Platelet Release


Platelet aggregation

Platelet Aggregation

  • Thrombaxane A2 and ADP set up autocatalytic reaction

  • Thrombin furthers aggregation and initiates fibrin clot

  • Viscous metamorphosis-irreversibly fused mass of platelets


Facultycjminarcikch4

Platelet adhesion and aggregation

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Coagulation cascade

Coagulation Cascade

  • Enzyme (activated coagulation factor)

  • Substrate (proenzyme form of factor)

  • cofactor (reaction accelerator)

  • Phospholipid complex (assembly site)


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Clinically important coagulation reactions

Clinically Important Coagulation Reactions

Harrison’s Internal Med, 16th Ed


Facultycjminarcikch4

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Central Roles Of Thrombin In Hemostasis And Cellular Activation

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Extrinsic and intrinsic interaction

Extrinsic and Intrinsic Interaction

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

  • 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


Natural anticoagulants

Natural Anticoagulants

  • 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

  • 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)


Facultycjminarcikch4

Pro- And Anticoagulant Activities Of Endothelial Cells

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

The Fibrinolytic System

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Clinically important coagulation reactions1

Clinically Important Coagulation Reactions


Facultycjminarcikch4

Virchow Triad In Thrombosis

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Abnormal blood flow

Abnormal Blood Flow

  • 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

  • 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

  • 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


Facultycjminarcikch4

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

  • 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

  • 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)Hypercoaguable 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

  • 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

  • Propagation

  • Embolization

  • Dissolution – Fibrinolysis

    • older thrombi with cross linked fibrin are resistant to lysis

  • Organization and recanalization.


Facultycjminarcikch4

Potential Outcomes Of Venous Thrombosis

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Heparin induced thrombocytopenia hit

Heparin Induced Thrombocytopenia (HIT)

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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


Facultycjminarcikch4

Pulmonary Embolus

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Helical ct of pulmonary emboli

Helical CT of Pulmonary Emboli

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


Ultrasound of femoral vein

Ultrasound of Femoral Vein

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


Infarction

Infarction

  • 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

  • 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


Facultycjminarcikch4

Examples of infarcts

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Histology of infarction

Histology of Infarction

  • 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

  • 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


Facultycjminarcikch4

Mural Thrombi

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Disseminated intravascular coagulation dic

Disseminated Intravascular Coagulation (DIC)

  • 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

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

  • 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

  • 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

  • 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

  • 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

  • Myocardial pump failure

    • myocardial infarction

    • myocardial rupture

    • cardiac arrhythmia

  • extrinsic compression

    • cardiac tamponade

  • Outflow obstruction

    • pulmonary embolus


Hypovolemic shock

Hypovolemic Shock

  • Hemorrhage

    • external

    • internal

      • GI tract

      • hemothorax

      • peritoneal or retroperitoneal space

  • Loss of fluid into third space

    • burns

    • pancreatitis


Septic shock

Septic Shock

  • 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

  • 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

  • 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

  • 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


Facultycjminarcikch4

Cytokine Cascade In Sepsis

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Facultycjminarcikch4

Effects OfLipopolysaccharide (LPS) And Secondarily Induced Effector Molecules

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier


Treatment of septic shock

Treatment of Septic Shock

  • 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

  • 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

  • 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

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

  • 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)


ad
  • Login