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shock definition
Cardiovascular collapse, resulting in systemic hypoperfusion caused by reduction either in cardiac output or effective circulating blood volume
* Results in hypotension, followed by impaired tissue perfusion and cellular hypoxia
* Persistence of shock eventually causes irreversible tissue injury> death
Hypovolemic Shock
Results from loss of blood or plasma volume
* Hemorrhage
* Fluid loss from severe burns or trauma
* Dehydration
Compensatory: increase HR, vasoconstriction > BP and BV rises
Cardiogenic Shock
Results from myocardial pump failure
* Intrinsic myocardial damage: infarction
* Ventricular arrhythmias
* Extrinsic compression: cardiac tamponade (fluid in pericardium)
* Outflow obstruction: pulmonary embolism
In all cases, diminution of systolic volume and cardiac output
Causes: DIC, metabolic acidosis
neurogenic shock
Loss of sympathetic tone and thus unopposed parasympathetic response driven by the vagus nerve.
Consequently, patients suffer from instability in blood pressure, heart rate, and temperature regulation
Results from vasomotor paralysis (autonomic nervous system)> loss of vascular tone + peripheral pooling of blood
* Spinal cord injury
* Anesthetic accident
* Encephalitis
* Excruciating pain (colic in horses, Gastric Dilation and Volvulus in dogs)
Anaphylactic (allergic) Shock
- Results from generalized IgE-mediated type 1 hypersensitivity response
- systemic vasodilation + ^ vascular permeability
- sudden ^ in vascular bed capacitance
- hypotension + tissue hypoperfusion + cellular anoxia
Septic shock
Results from spread and expansion of an initially localized infection (e.g., abscess, peritonitis, pneumonia) into bloodstream
^ incidence: improved life support for high-risk patients, ^ use of invasive procedures, ^ numbers of immunocompromised hosts
Causes:
* Endotoxin-producing Gram-negative bacilli: endotoxic shock
* Endotoxins: bacterial wall lipopolysaccharides (LPS) that are released when cell walls are degraded in an inflammatory response
* Analogous molecules in walls of Gram-positive bacteria and fungi can also elicit septic shock
Septic shock pathogenesis
- Free LPS attaches to a circulating LPS-binding protein
- complex binds to CD14
- complex binds to TLR-4
- TLR-4 signal transduction
- activates vascular wall cells and leukocytes + initiates a cascade of cytokine mediators
TLR-4 on endothelial cells
Down-regulation of natural anticoagulation mechanisms: decrease synthesis of tissue factor pathway inhibitor (TFPI) and thrombomodulin
TLR-4 on monocytes and macrophages
Profound mononuclear cell activation > primarily production of IL-1 and TNF > ultimate effect depends on LPS doses
Low dose LPS effecr
Produce TNF and IL-1 at levels with local effects
Act on endothelial cells to stimulate expression of adhesion molecules > enhance acute inflammatory response > eliminate bacteria
Activate complement > local bacterial eradication
LPS effect moderate dose
Produce TNF and IL-1 at levels with local and systemic effects
Systemic effects: fever, ^ synthesis of acute phase reactants
Produce secondary cytokines: NO
diminished endothelial cell production of thrombomodulin and TFPI > pro-thrombotic effect
High dose LPS effect
septic shock occurs
Due to massive systemic effect of TNF, IL-1, and secondary cytokines
* Systemic vasodilation (hypotension)
* Diminished myocardial contractility
* Widespread endothelial injury and activation > systemic leukocyte adhesion + pulmonary alveolar capillary damage (ARDS/DAD)
* Activation of coagulation system > DIC
Multiorgan failure and death: due to combined effects of widespread vasodilation, myocardial pump failure, and DIC
High dose LPS effect
septic shock occurs
Due to massive systemic effect of TNF, IL-1, and secondary cytokines
* Systemic vasodilation (hypotension)
* Diminished myocardial contractility
* Widespread endothelial injury and activation > systemic leukocyte adhesion + pulmonary alveolar capillary damage (ARDS/DAD)
* Activation of coagulation system > DIC
Multiorgan failure and death: due to combined effects of widespread vasodilation, myocardial pump failure, and DIC
Initial Non-Progressive Phase of shock
Involves activation of reflex compensatory mechanisms that maintain perfusion of organs
Compensatory mechanism are neurohormonal
* Baroreceptor reflexes
* Release of catecholamines
* Activation of renin-angiotensin axis
* Antidiuretic hormone release
* Generalized sympathetic stimulation
Effects
* Tachycardia
* Peripheral vasoconstriction
* Renal conservation of fluid
Progressive stage of shock
Involves onset of tissue hypoperfusion and worsening circulatory and metabolic imbalances (including acidosis) > organs begin to fail
However, damage is reversible if initiating insult corrected
Effects
1. Widespread tissue **hypoxia **
2. ^ anaerobic glycolysis
3. production of **lactic acidosis **
5. decrease tissue pH
6. blunts vasomotor response
7. Arteriolar dilation > **blood pools in microcirculation **
* decrease cardiac output
* Anoxic injury to endothelial cells > DIC
Irreversible stage of shock
Involves onset of irreversible organ failure due to tissue hypoperfusion
Effects: widespread irreversible cell injury
* Lysosomal enzyme leakage > further cell death
* NO synthesis > decrease myocardial contractile function
* Acute tubular necrosis > renal failure
Stages of shock
- Initial non progressive
- progressive
- irreversible
KNOW THIS GRAPH!!!
Fibrosis
The repair of damaged tissue by replacement with connective tissue (collagen)
5 components
* Inflammation
* Angiogenesis
* Fibroblast migration and proliferation
* Scar formation
* Connective tissue remodeling
Fibrosis
The repair of damaged tissue by replacement with connective tissue (collagen)
5 components
* Inflammation
* Angiogenesis
* Fibroblast migration and proliferation
* Scar formation
* Connective tissue remodeling
angiogenesis
Formation of new blood vessels
2 mechanisms:
* Angiogenesis from pre-existing vessels (Primary mechanism)
* Angiogenesis from endothelial precursor cells (EPC migrate from bone marrow to site of injury and differentiated into mature blood vessels)
New vessels (capillary buds) are leaky and the tissue around them is edematous
Angiogenesis = important in fibrosis AND tumor growth