he pathophysiological response to this cascade is selective vasodilation with maldistribution of blood low. Leukocyte and platelet aggregation cause capillary plugging. Worsening endothelial injury causes profound permeability, capillary leakage, and interstitial fluid accumulation (Fig. 47-4). Depending on the degree of injury and inflammatory response, a pathophysiological and clinical continuum evolves as depicted in Figure 47-3. The clinical syndrome begins with subtle signs of
Cytokines and other inflammatory mediators lead to endothelial junction separation
FIGURE 47-4 Endothelial permeability. The normal interendothelial interface is shown in the left inset. Cytokines and other inflammatory mediators disassemble the cellular junctions, resulting in microvascular leaks (right).
sepsis from infection and terminates with septic shock, which is defined by hypotension unresponsive to intravenous hydration. In its early stages, clinical shock results primarily from decreased systemic vascular resistance that is not compensated fully by increased cardiac output. Hypoperfusion results in lactic acidosis, decreased tissue oxygen extraction, and end-organ dysfunction that includes acute lung and kidney injury.
he sepsis syndrome has myriad clinical manifestations that, at least in part, are dependent on the specific invading microorganism and its particular endo-or exotoxins. Some of the general efects of LPS are as follows: 1.
Central nervous system: confusion, delirium, somnolence, coma, combativeness, fever 2.
Cardiovascular: tachycardia, hypotension 3.
Pulmonary: tachypnea, arteriovenous shunting with dysoxia and hypoxemia, exudative iniltrates from endothelialalveolar damage, pulmonary hypertension 4.
Gastrointestinal: gastroenteritis-nausea, vomiting, and diarrhea; ileus; hepatocellular necrosis-jaundice, transaminitis 5.
Renal: prerenal oliguria, azotemia, acute kidney injury, proteinuria 6.
Hematological: leukocytosis or leukopenia, thrombocytopenia, activation of coagulation with disseminated intravascular coagulopathy 7.
Endocrine: hyperglycemia, adrenal insuiciency 8.
Cutaneous: acrocyanosis, erythroderma, bullae, digital gangrene.
Thus, although capillary leakage initially causes hypovolemia, if intravenous crystalloid is given at this point, then sepsis hemodynamically can be described as a high cardiac output, low systemic vascular resistance condition (Fig. 47-5). Concomitantly, pulmonary hypertension develops, and despite the high cardiac output, severe sepsis also causes myocardial depression (Munford, 2015; Ognibene, 1988). This is often referred to as the warm phase of septic shock. hese indings are the most common cardiovascular manifestations of early sepsis, but they can be accompanied by some of the other clinical or laboratory aberrations listed above.