MS5 Shock and MODS

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

• Low venous filling:
• -"dehydration" = ↓ ECV
• -blood loss
• -Loss of fluid from vasculature: "3rd spacing" (capillary leak)

• Cardiac dysfunction:
• -heart failure

• Low venous filling:
• -Low skin turgor
• -Flat neck veins
• -Lungs clear

• Cardiac dysfunction:
• -Skin edema
• -Distended neck veins
• -Lungs edematous

• Vasodilation:
• -unusual to happen alone (e.g. nitroglycerine, nifedipine overdose)
• -Large part of sepsis

• 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

• Hemodynamic compromise: hypoperfusion
• Systemic inflammatory response

• 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

• 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

• 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

• 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

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

• -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

• 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

• 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

• Signs of shock
• Signs of infection
• Warm extremities
• Unexplained organ dysfunction

• 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

• 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

• 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

• 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

• 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)

• 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

• 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

• Blood
• -Decreased hematopoiesis
• -Impaired immune cell function
• -Thrombocytopenia
• -Coagulopathy, including disseminated intravascular coagulation

• Endocrine
• -Insulin derangements
• -Adrenal dysfunction

• Infection (no SIRS): ~20%
• Sepsis: ~20%
• Severe sepsis: ~35%
• Sepsis with MODS: ~50%

• Cellular poisoning → Treat infection rapidly
• Low venous filling/decreased cardiac output → Administer large volumes of fluid
• Systemic vasodilation → Administer vasopressors
• Cardiac dysfunction → possibly administer inotropic agents

• 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