increased base deficit or blood lactate level, may also signal diminished organ perfusion early in shock As shock continues, early compensatory mechanisms fail to maintain cardiac output and SVR and blood pressure falls Shock with hypotension is referred to as uncompensated shock In addition to hypotension, clinical signs include worsening tachycardia (or bradycardia in infants) and tachypnea, mottled skin, cold extremities, and markedly delayed capillary refill (>4 seconds) Tachypnea and respiratory distress may herald underlying pulmonary disease, but may also reflect an increase in minute ventilation (to decrease PaCO2 ) to compensate for an increasing metabolic acidosis Signs of organ dysfunction are typically evident, including further alterations in mental status (agitation, confusion, lethargy, stupor), gastrointestinal ileus, azotemia, coagulopathy, thrombocytopenia, and hyperbilirubinemia All types of shock encompass some degree of absolute or functional hypovolemia Absolute hypovolemia exists in cases of dehydration from fluid losses (e.g., diarrhea, severe emesis, hyperthermia), hemorrhage, and “third spacing” of fluid due to increased vascular permeability, as in sepsis or burn injuries Functional hypovolemia exists when vascular capacity increases, as in septic shock, spinal cord injury, anaphylaxis, or certain medication effects In addition to volume loss, microcirculatory dysfunction is characterized by a maldistribution of capillary blood flow and is common to all types of shock Even with reestablishment of global circulation, the activation of inflammatory cytokines in response to pathogen-associated molecular patterns (PAMPs) from invading microorganisms in sepsis and danger-associated molecular patterns (DAMPs) from cell injury in trauma, as well as endothelial cell activation and microthrombi formation, leads to regional changes in blood flow within and across organ systems This contributes to local tissue ischemia that fuels a vicious cycle of tissue injury and inflammation that can result in the multiorgan dysfunction syndrome (MODS) Furthermore, a second wave of reperfusion injury may occur due to an increase in oxidant and nitrogenous stress even after the primary insult of decreased tissue perfusion in shock is corrected