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Shock
definition
State in which organ damage is caused by decreased perfusion, or the tissue responds as if there is decreased perfusion
- -Most types of shock cause low BP
- -V= I*R
- -ΔP (MAP-CVP) = CO*SVR
- -low BP from low CO, or low SVR
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Causes of low cardiac output (CO)
- Low venous filling:
- -"dehydration" = ↓ ECV
- -blood loss
- -Loss of fluid from vasculature: "3rd spacing" (capillary leak)
- Cardiac dysfunction:
- -heart failure
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Low CO Symptoms
low venous fillinng vs cardiac dysfunction
- Low venous filling:
- -Low skin turgor
- -Flat neck veins
- -Lungs clear
- Cardiac dysfunction:
- -Skin edema
- -Distended neck veins
- -Lungs edematous
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Low Systemic Vascular Resistance (SVR)
Cause
- Vasodilation:
- -unusual to happen alone (e.g. nitroglycerine, nifedipine overdose)
- -Large part of sepsis
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Shock signs and sx
Low CO vs Low SVR
- Low CO:
- -Cold extremities
- -Pale skin
- -Slow nail bed refill
- -Compensation:
- 1. Increased SVR - preferential flow to vital organs
- 2. Attempt to increase CO - tachycardia, increase stroke volume (?)
- Low SVR:
- -Warm extremities
- -Normal or pink skin
- -Brisk nail bed refill
- -Compensation:
- 1. Attempt to increase SVR - preferential flow to vital organs
- 2. Increased CO - tachycardia, stroke volume
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Complications of shock
- Hemodynamic compromise: hypoperfusion
- Systemic inflammatory response
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Hypoperfusion
What's the problem?
- Oxygen is required for electron tranport chain to function: generation of 36 ATP vs 2 ATP
- -Recycles NADH → NAD+
- -Recycles FADH2 → FADH
*Krebs cycle does NOT require oxygen
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Signs of decreased perfusion
- Brain → confusion
- Heart → Tachycardia, low stroke volume
- Kidney → Low urine output
- Intestine → Low peristalsis
- Skin → Pallor, diaphoresis
- Respiratory → Tachypnea
- Cellular metabolism → Lactic acid cycle supplements aerobic metabolism
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Lactic acidosis
- Lactate itself can lower blood pH
- -Acidosis → cardiac dysfunction
- -some drugs (vasopressors) won't work as well
- Strong evidence that cells are starving
- -cellular death
- -organ damage
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Systemic inflammatory response
- Elevated levels of circulating proinflammatory mediators:
- -TNF α
- -Interleukins
- -Prostaglandins
- -Other
- Activation of endothelial cells and leukocytes:
- -Activated endothelial cells produce nitric oxide (vasodilator)
- -Intracellular adhesion molecules; leukocytes express corresponding ligands
- -Leukocytes collect in the capillaries and postcapillary venules; invade lung and systemic tissues
- -Endothelial and parenchymal cells make chemotactic cytokines
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Endothelial-Leukocyte interactions
- -Activated leukocytes release oxygen free radicals
- -Complement and coagulation pathways activated → Damaged RBCs, WBCs, fibrin, platelets accumulate in capillaries, impairing O2 delivery
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Disseminated intravascular coagulation (DIC)
definition and sx
- -Extreme, widespread coagulation in capillaries
- -Body attempts to remove clots via fibrinolysis
- -Coagulation factors get used faster than they are made
- -Risk of bleeding and of capillary thrombosis
- Effects on tissue:
- -Direct damage via leukocyte action
- -Perfusion problems due to microvascular clot and debris
- -Capillary leak → tissue edema; lowers intravascular volume and cardiac output
- -Organs become very unhappy
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Vasodilation
- Activated vascular endothelial cells produce nitric oxide (a vasodilator)
- Prostaglandin I2 (PGI2) causes vasodilation of the systemic vasculature (low SVR)
- Thromboxane A2 causes vasoconstriction of pulmonary arteries and pulmonary hypertension
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Sepsis → shock
- Endotoxins and other mediators cause:
- 1. Cellular poisoning that mimics hypoperfusion:
- -similar effect of cyanide poisoning: uncoupling of the H+-ATPase
- -Anaerobic metabolism → lactic acidosis
2. Low venous filling → decreased CO
3. Systemic vasodilation
4. Cardiac dysfunction
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Sepsis
what to look for
- Signs of shock
- Signs of infection
- Warm extremities
- Unexplained organ dysfunction
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Multiple organ dysfunction syndrome (MODS)
- Complication of shock manifested by damage to and dysfunction of several organ systems
- Type and severity of damage is related to severity and duration of the shock
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MODS
Brain injury
- Mild confusion is very common
- Coma can even occur
- Brain is locked in skull
- Brain has difficulty autoregulating flow when mean arterial pressure is low
- High pCO2 or low pO2 can dilate cerebral vessels, further disrupting autoregulation
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MODS
Heart
- Poor contractility due to impaired O2 extraction weakens force of systole
- Incomplete relaxation due to injury reduces ventricular filling during diastole
- Circulating catecholamines can cause vasoconstriction of the coronary arteries and their branches
- Increased demand combined with impaired blood supply and O2 utilization can cause ischemia
- Lactica acidosis in the myocardium is common
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MODS
Lungs
- The most commonly damaged organ in MODS
- Acute Respiratory Distress Syndrome "ARDS"
- The lung has massive surface area and exposure to endothelium
- Survival depends on gas-blood interactions
- Inflammatory edema with extravasation of blood proteins into the alveoli → surfactant function is markedly compromised
- Pulmonary capillary bed gets obstructed with active debris
- Inflammatory mediators and activated cells from everywhere all end up passing through the lung, where they get trapped
- Deadly gas exchange abnormalities → ventilation perfusion mismatching
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MODS
Liver
- Centrilobar hepatic necrosis
- Leakage of transaminases (ALT, AST)
- Liver synthetic function declines
- -Bilirubin increases
- -Coagulation factors and albumin can decrease
- Decrease phagocytosis
- Hypoglycemia (severe dysfunction)
- Decreased clearance of toxic substances (drugs, metabolites can damage other organs)
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MODS
GI system
- Intestinal dysfunction is very common
- Edema of the mucosa
- Necrosis of the intestinal villa
- Submucosal hemorrhage
- End stage: hemorrhagic necrosis of the gut
- **Gut ischemia/damage might be involved in the escalation of MODS
- →Breakdown of mucosal barrier between gut
- →translocation of bacteria and/or toxins into the blood and lymphatics
- →Ineffective clearance by the compromised liver
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MODS
Kidney
- Renal function is a good indicator of a person's tolerance of MODS (urine continuously)
- Glomerular filtration rate can dramatically decrease
- →decreased renal blood flow
- →vasoconstriction of the arteries
- Ischemia can cause renal tubules to necrose
- Cellular debris can clog tubule lumen
- The medulla can't stay hypertonic, which impairs countercurrent function
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MODS
Blood and endocrine
- Blood
- -Decreased hematopoiesis
- -Impaired immune cell function
- -Thrombocytopenia
- -Coagulopathy, including disseminated intravascular coagulation
- Endocrine-Insulin derangements
- -Adrenal dysfunction
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MODS
probability of death
- Infection (no SIRS): ~20%
- Sepsis: ~20%
- Severe sepsis: ~35%
- Sepsis with MODS: ~50%
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Sepsis
Treatment
- Cellular poisoning → Treat infection rapidly
- Low venous filling/decreased cardiac output → Administer large volumes of fluidSystemic vasodilation → Administer vasopressors
- Cardiac dysfunction → possibly administer inotropic agents
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MODS
Treatment
- Prevent organ ischemia early
- Support organ function: mechanical ventilation, dialysis
- Find/remove source of MODS: abx, surgery
- Await development of future therapies
- For now...
- -Early goal directed therapy: fluid management
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