Shock, Hemorrhage and Thrombosis - Columbia University€¦ · 2 Shock Systemic hypoperfusion due to: –Reduction in cardiac output –Reduction in effective circulating blood volume

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Shock, Hemorrhage Shock, Hemorrhage andand

ThrombosisThrombosis

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ShockSystemic hypoperfusion due to:

–Reduction in cardiac output–Reduction in effective circulating

blood volume

Hypotension Impaired tissue perfusionCellular hypoxia

Spinal cord injuryVascular tonePooling of blood5. Anaphylactic

-IgE mediated hypersensitivity

* high mortality

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Stages of Shock: Basic Pathology 7/e

Non-Progressive Stage Progressive Stage Irreversible Stage

-compensatory reflexmechanisms activated(baroreceptors/catechol. release)-perfusion maintained

-tissue hypoperfusion & worsened circulatorymetabolic imbalance

-severe cell & tissueinjury with no chance of recovery

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Significance of Hemorrhage

NO CLINICAL FINDINGS:

10-20% of bld. vol. lostOR

slow blood loss

HYPOVOLEMICSHOCK:

larger blood lossesOR

more rapid bld. loss

Congestion (Hyperemia)Congestion (Hyperemia)

Increased volume of blood in affected tissue•Mechanism:

arterial and arteriolar dilatation

bld.flow intocapillaries

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Edema

*The abnormal accumulation of fluid in the intercellular tissue spaces or body cavities

-localized-systemic

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Edema fluids: nomenclature

-abdomen: ascites-pleural cavities: effusions / hydrothorax-pericardium: effusion-total body: anasarca

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Extravascular/Edema Fluids:TerminologyExtravascular/Edema Fluids:TerminologyTransudate:

-low protein content-non-inflammatory

-ultrafiltrate of plasma (mostly albumin) -due to osmotic/hydrostatic imbalance-no increase in vasc. permeab.)

-S.G. < 1.012

Exudate:-high protein concentration-inflammatory

-due to altered permeab. of small bld. vessels

-S.G. >1.020

Transudate:-low protein content-non-inflammatory

-ultrafiltrate of plasma (mostly albumin) -due to osmotic/hydrostatic imbalance-no increase in vasc. permeab.)

-S.G. < 1.012

Exudate:-high protein concentration-inflammatory

-due to altered permeab. of small bld. vessels

-S.G. >1.020

Mechanisms of edema formation

• plasma colloid oncotic pressure• hydrostatic pressure• endothelial permeability• lymphatic blockage

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Thrombosis: the Virchow triad

Thrombosis

Endothelial injury

Abnormal blood flow hypercoagulability

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Types & Fate of Thrombi

•Arterial: coronary, cerebral, aorta + branches •Venous: 90% in deep leg veins

-also peri-uterine, peri-prostatic•Mural: heart

•Propagation•Embolization•Dissolution•Organization and recanalization

Types

FateBrainSpleenkidneys

Arterial thrombi(“left-sided”)Lungs

Venous thrombi(“right-sided)

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Right-sided thromboemboli:Classic example is pulmonary emboli

Paradoxical embolus: throughpatent foramen ovale to left side

saddleembolus

RV

Left-sided thromboemboli:Classic examples are mural thrombi inLeft atrium/ventricle or endocarditis

Pulmonary infarct (wedge-shaped region of necroticlung). Seen in only approx.10% of pulmonary emboli becauseof dual lung perfusion from bronchialarteries

brain

spleen

kidneys

Atrial appendagethrombi (often inmitral stenosis +atrial fibrillation)

mitral valveendocarditisMural thrombus

In left ventricle(e.g., after myocardialInfarction & hypokinesis)

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Acute myocardial infarctionAcute myocardial infarction

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PulmonaryInfarct

Disseminated Intravascular Coagulation (DIC)(Consumption Coagulopathy)

• Widespread thrombosis in microcirculation• Platelets & fibrin in capillaries• Mechanism: Activate intrinsic pathway• Clinical: sepsis—obstetrical catastrophe--

cancer—extensive tissue damage• Hematologic: rapid consumption of fibrinogen,

platelets, prothrombin, V, VIII, X– Generation of d-dimers (“fibrin split products”)

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Sepsis & Septic shock: definitions

1. SEPSIS: suspected or proven infection

+ systemic inflammatory responsesyndrome: fever, tachycardia,tachypnea, leukocytosis

2. SEVERESEPSIS: sepsis +

ORGAN DYSFUNCTION:hypotension, hypoxemia, oliguria,metabolic acidosis, thrombocytope-nia, obtundation

3. SEPTIC SHOCK:

severesepsis

+ORGAN DYSFUNCTION,HYPOTENSION, despiteadequate fluid resuscitation

750,000 cases of sepsis / yr. in U.S.

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bacteriapneumonia

meningitis

inflam. bowel dis. GU tract(urosepsis)

Sources:

sepsis

Immune cell “cross-talk”

in sepsis

NEJM 2003;348: 138-150

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Toll-like receptors(TLR)

•Family of PPR’s(pattern recognition

receptors)•TLR2: peptidoglycan

Gram+ org’s

•TLR 4: LPS (endotoxin)

Gram- org’sleukocyte

macPMN

TLR’sTNFIL-1

PG’s

upregulateadhesion molecules

iNOS

NO

vasodilation

Role ofinnate immuneresponse insepsis:proinflam. cytokines

•edema• vasc. permeab.

systemic acute-phase response

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B

T

Th1 Th2

PROINFLAM. cytokines:TNF, IL-1

ANTI-INFLAM. cytokines:IL-4, IL-10

Role of adaptiveimmune responsein sepsis

anti-inflam.shift in sepsis

Roles ofprocoagulant-anti-coagulantbalance

LPSdamage

tissue factor(thromboplastin)

coagulation

fibrinthrombus

levels of:•Protein C•Protein S•Antithrombin III•Tissue factor-

pathway inhibitorPRO

anti

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NEJM 2006; 355: 1699-1713

Organ Dysfunction in Septic Shock

vasodilation

fluid

vascularresistance

hypovolemia

myocardialcontractility

+

NOTNFIL-6

Circulatory shock

renalfailure(“pre-renal”)

PMN

acute lung injury