Acute Inflammation III: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.

Local Effects

At the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased vascular permeability shifts Starling forces toward filtration, permitting protein-rich plasma to leave the circulation and form edema. The accumulation of immune cells further enlarges local tissue volume. Prostaglandins—especially PGE₂—and bradykinin diffuse through the interstitium and sensitize nociceptors, lowering firing thresholds and producing pain. Together, pain and swelling restrict movement and reduce function (functio laesa). Exuded fibrin and plasma proteins create a provisional matrix that aids leukocyte migration and early repair.

Systemic Responses and Severe Inflammation

When inflammatory signaling becomes systemic, as in extensive injury or severe infection, cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) act on the hypothalamus to increase prostaglandin E2 and raise the thermoregulatory set point, thereby producing fever. The same mediators promote leukocytosis—often neutrophilia—by accelerating bone marrow output and mobilizing marginated pools to fight infection and clear debris. Additional findings include tachycardia, tachypnea, malaise, and anorexia. The liver increases the synthesis of acute-phase proteins (for example, C-reactive protein and fibrinogen), which enhance opsonization and modulate the coagulation process. In severe systemic inflammation, exemplified by sepsis, diffuse endothelial activation, vasodilation, and capillary leak contribute to hypotension, while dysregulated coagulation can culminate in disseminated intravascular coagulation (DIC).