critical care medicine
Shock
Pathophysiology of Shock
The fundamental defect in shock is reduced perfusion of vital tissues. Once perfusion declines and oxygen delivery to cells is inadequate for aerobic metabolism, cells shift to anaerobic metabolism with increased production of carbon dioxide and elevated blood lactate levels. Cellular function declines, and if shock persists, irreversible cell damage and death occur. B), which leads to production of additional cytokines and nitric oxide (NO), a potent vasodilator. Sepsis and Septic Shock may be more proinflammatory than other forms of shock because of the actions of bacterial toxins, especially endotoxin. In septic shock, vasodilation of capacitance vessels leads to pooling of blood and hypotension because of “relative” hypovolemia (ie, too much volume to be filled by the existing amount of blood). Localized vasodilation may shunt blood past the capillary exchange beds, causing focal hypoperfusion despite normal cardiac output and blood pressure. Additionally, excess nitric oxide is converted to peroxynitrite, a free radical that damages mitochondria and decreases ATP (adenosinetriphosphate) production. Blood flow to microvessels, including capillaries, is reduced even though large-vessel blood flow is preserved in settings of septic shock. Mechanical microvascular obstruction may, at least in part, account for such limiting of substrate delivery. Leukocytes and platelets adhere to the endothelium, and the clotting system is activated with fibrin deposition. Multiple mediators, along with endothelial cell dysfunction, markedly increase microvascular permeability, allowing fluid and sometimes plasma proteins to escape into the interstitial space ( Pathophysiology references ). In the gastrointestinal tract, increased permeability possibly allows translocation of the enteric bacteria from the lumen, potentially leading to sepsis or metastatic infection. Neutrophil apoptosis may be inhibited, enhancing the release of inflammatory mediators. In other cells, apoptosis may be augmented, increasing cell death and thus worsening organ function. Blood pressure is not always low in the early stages of shock (although hypotension eventually occurs if shock is not reversed). Similarly, not all patients with “low” blood pressure have shock. The degree and consequences of hypotension vary with the adequacy of physiologic compensation and the patient’s underlying diseases. Thus, a modest degree of hypotension that is well tolerated by a young, relatively healthy person might result in severe cerebral, cardiac, or renal dysfunction in an older person with significant arteriosclerosis. Initially, when oxygen delivery (DO2) is decreased, tissues compensate by extracting a greater percentage of delivered oxygen. Low arterial pressure triggers an adrenergic response with sympathetic-mediated vasoconstriction and often increased heart rate. Initially, vasoconstriction is selective, shunting blood to the heart and brain and away from the splanchnic circulation. Circulating beta-adrenergic amines (epinephrine,norepinephrine) also increase cardiac contractility and trigger release of Corticosteroids from the adrenal gland Renin from the kidneys Glucose from the liver Corticosteroids enhance the effects of catecholamines. Renin stimulates volume retention and vasoconstriction. Increased glucose increases pyruvate uptake in the mitochondria which increases lactate production when there is insufficient oxygen. Reperfusion of ischemic cells can cause further injury. As substrate is reintroduced, neutrophil activity may increase, increasing production of damaging superoxide and hydroxyl radicals. After blood flow is restored, locally concentrated inflammatory mediators may be circulated to other organs. The combination of direct and reperfusion injury may cause MODS—the progressive dysfunction of ≥ 2 organs consequent to life-threatening illness or injury. MODS can follow any type of shock but is most common when infection is involved; organ failure is one of the defining features of Sepsis and Septic Shock . MODS also occurs in Multiple organ dysfunction syndrome is the progressive dysfunction of ≥ 2 organs consequent to life-threatening illness or injury. Any organ system can be affected, but the most frequent target organs are the lungs, in which increased membrane permeability leads to flooding of alveoli and further inflammation. Progressive hypoxia may be increasingly resistant to supplemental oxygen therapy. This condition is termed acute lung injury or, if severe, Acute Hypoxemic Respiratory Failure (AHRF, ARDS) (ARDS). The kidneys are injured when renal perfusion is critically reduced, leading to Acute Tubular Necrosis (ATN) and renal insufficiency manifested by oliguria and a progressive rise in serum creatinine. In the heart, reduced coronary perfusion and increased inflammatory mediators (including tumor necrosis factor and interleukin-1) may depress contractility, worsen myocardial compliance, and down-regulate beta-receptors. These factors decrease cardiac output, further worsening both myocardial and systemic perfusion and causing a vicious circle that often culminates in death. Arrhythmias may occur. In the gastrointestinal tract, ileus and submucosal hemorrhage can develop. Liver hypoperfusion can cause focal or extensive hepatocellular necrosis, transaminase and bilirubin elevation, and decreased production of clotting factors. Coagulation can be impaired, including the most severe manifestation, Disseminated Intravascular Coagulation (DIC) . 1.Salmon AH, Satchell SC: Endothelial glycocalyx dysfunction in disease: Albuminuria and increased microvascular permeability.J Pathol226:562–74, 2012. doi: 10.1002/path.3964 2.Chelazzi C, Villa G, Mancinelli P, et al: Glycocalyx and sepsis-induced alterations in vascular permeability.Crit Care19(1):26, 2015. doi:10.1186/s13054-015-0741-z 3.Martin L, Koczera P, Zechendorf E, et al: The endothelial glycocalyx: New diagnostic and therapeutic approaches in sepsis.Biomed Res Int2016:3758278, 2016. doi:10.1155/2016/3758278 