Shock, Hemorrhage and Thrombosis

Shock Systemic hypoperfusion due to: –Reduction in cardiac output –Reduction in effective circulating blood volume

Spinal cord injury Vascular tone Hypotension Impaired tissue perfusion 5. Anaphylactic Pooling of blood Cellular hypoxia -IgE mediated hypersensitivity * high mortality

1 Stages of Shock: Basic Pathology 7/e

Non-Progressive Stage Progressive Stage Irreversible Stage

-compensatory reflex mechanisms activated (baroreceptors/ -tissue hypoperfusion & catechol. release) worsened circulatory -perfusion maintained metabolic imbalance -severe cell & tissue injury with no chance of recovery

Significance of Hemorrhage Congestion (Hyperemia)

NO CLINICAL HYPOVOLEMIC FINDINGS: SHOCK: Increased volume of blood in affected tissue 10-20% of bld. vol. lost larger blood losses •Mechanism: OR OR slow blood loss more rapid bld. loss bld. arterial and flow into capillaries arteriolar dilatation

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

Edema fluids: nomenclature

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

Extravascular/Edema Fluids:Terminology Transudate: -low protein content Mechanisms of edema formation -non-inflammatory -ultrafiltrate of plasma (mostly albumin) • plasma colloid oncotic pressure -due to osmotic/hydrostatic imbalance -no increase in vasc. permeab.) • hydrostatic pressure -S.G. < 1.012 • endothelial permeability Exudate: -high protein concentration • lymphatic blockage -inflammatory -due to altered permeab. of small bld. vessels -S.G. >1.020

3 Thrombosis: the Virchow triad

Endothelial injury

Thrombosis

Abnormal blood flow hypercoagulability

4 Types & Fate of Thrombi Types •Arterial: coronary, cerebral, aorta + branches •Venous: 90% in deep leg veins -also peri-uterine, peri-prostatic •Mural: heart Venous thrombi (“right-sided) Arterial thrombi (“left-sided”) Fate Lungs Brain Spleen •Propagation kidneys •Embolization •Dissolution •Organization and recanalization

brain

Paradoxical embolus: through patent foramen ovale to left side

saddle embolus Atrial appendage thrombi (often in mitral stenosis + atrial fibrillation)

mitral valve Mural thrombus endocarditis In left ventricle RV (e.g., after myocardial Infarction & hypokinesis) spleen

Pulmonary infarct (wedge- shaped region of necrotic kidneys lung). Seen in only approx. 10% of pulmonary emboli because of dual lung perfusion from bronchial arteries

Right-sided thromboemboli: Left-sided thromboemboli: Classic example is pulmonary emboli Classic examples are mural thrombi in Left atrium/ventricle or endocarditis

5 Acute myocardial infarction

6 Disseminated Intravascular Coagulation (DIC) (Consumption Coagulopathy) • Widespread thrombosis in microcirculation Pulmonary • Platelets & fibrin in capillaries Infarct • 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”)

Sepsis & Septic shock: definitions

systemic inflammatory response suspected or 1. SEPSIS: + syndrome: fever, tachycardia, proven infection tachypnea, leukocytosis

2. SEVERE ORGAN DYSFUNCTION: hypotension, hypoxemia, oliguria, SEPSIS: sepsis + metabolic acidosis, thrombocytope- nia, obtundation

ORGAN DYSFUNCTION, 3. SEPTIC severe + SHOCK: sepsis HYPOTENSION, despite adequate fluid resuscitation

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

sepsis Immune cell “cross-talk” in sepsis Sources:

bacteria pneumonia meningitis

NEJM 2003; inflam. bowel dis. GU tract 348: 138-150 (urosepsis)

7 systemic acute- Toll-like receptors •edema phase response (TLR) • vasc. permeab. •Family of PPR’s PG’s TNF (pattern recognition TLR’s IL-1 receptors) •TLR2: peptidoglycan Gram+ org’s PMN mac

•TLR 4: LPS upregulate adhesion molecules (endotoxin) Role of iNOS leukocyte Gram- org’s innate immune NO response in sepsis: vasodilation proinflam. cytokines

B damage LPS anti-inflam. tissue factor Role of adaptive levels of: shift in sepsis Roles of (thromboplastin) immune response T procoagulant- •Protein C in sepsis anti-coagulant •Protein S coagulation •Antithrombin III balance •Tissue factor- Th1 Th2 fibrin pathway inhibitor anti PRO thrombus PROINFLAM. cytokines: ANTI-INFLAM. cytokines: TNF, IL-1 IL-4, IL-10

Organ Dysfunction in Septic Shock

PMN Circulatory shock NO myocardial TNF contractility IL-6 acute lung injury

vascular resistance + vasodilation fluid renal failure NEJM 2006; 355: 1699-1713 (“pre-renal”)

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