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
2 Edema
*The abnormal accumulation of fluid in the intercellular tissue spaces or body cavities -localized -systemic
Edema fluids: nomenclature
-abdomen: ascites -pleural cavities: effusions / hydrothorax -pericardium: effusion -total body: anasarca
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 hypovolemia fluid renal failure NEJM 2006; 355: 1699-1713 (“pre-renal”)
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