Pathophysiology

Sepsis is a complex clinical syndrome caused by the host’s response to an invading pathogen. The pathophysiology of sepsis involves immunology, vascular, neuroendocrine, and metabolic responses which are both adaptive and maladaptive and contribute to the wide array of clinical phenotypes of septic patients. The increasing knowledge about the molecular mechanisms underlying sepsis has expanded our understanding of the disease. Sepsis is characterized by simultaneous hyperinflammation and immune suppression, and sepsis endotypes can be used to divide patients into different groups with distinct immune profiles and outcomes . The pathophysiology of sepsis includes an inflammatory response that stimulates a complex interaction between endothelial and complements with associated coagulation abnormalities. Early immunothrombotic changes could result in the early switch from infection to sepsis . Understanding the underlying disease pathology is crucial for effective treatment and prevention of long-term complications 

Sepsis is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. It begins when pattern recognition receptors on innate immune cells recognize pathogen-associated molecular patterns, triggering an inflammatory response. This leads to activation of immune cells and release of proinflammatory cytokines like IL-1, IL-6, and TNF-alpha. These cytokines activate neutrophils and vascular endothelial cells, increasing expression of inducible nitric oxide synthase and subsequent vasodilation.

Vascular endothelial injury leads to capillary fluid leak and decreased preload. Venodilation further reduces cardiac preload. Tissue oxygen delivery is impaired by decreased cardiac output, inadequate oxygen content from low hemoglobin, and impaired oxygen unloading from hemoglobin. Hemodynamic abnormalities lead to decreased perfusion, so oxygen consumption exceeds delivery and cellular injury results. This compounds the proinflammatory and procoagulant state, causing multi-organ dysfunction and possibly death.

Hypotension develops from inappropriate vasodilation and failure of vasoconstrictive pathways. Blood flow prioritizes heart and brain, diverting flow from other organs. When the endogenous response is insufficient, overt shock and hypotension occur. Septic shock involves particularly profound circulatory, cellular and metabolic abnormalities that substantially increase mortality. Clinical manifestations include fever, tachycardia, tachypnea, confusion, cold extremities, mottled skin, oliguria, and metabolic acidosis.