Acute Inflammation III: Local and Systemic Effects

Arteriolar vasodilation increases blood flow to the inflamed area, causing redness and warmth. This vascular change is one of the earliest local responses, driven by inflammatory mediators released during the acute inflammation inflammatory response. The increased blood flow also delivers immune cells to combat infection and clear debris.

Increased vascular permeability shifts Starling forces toward filtration, allowing protein-rich plasma to leave the circulation and accumulate in surrounding tissues. This exuded fluid, combined with immune cell infiltration, enlarges local tissue volume and causes edema. The protein-rich exudate also forms a provisional matrix that aids leukocyte migration and early repair.

Prostaglandins and bradykinin are released by damaged tissue and immune cells, then diffuse through surrounding tissue to sensitize nociceptors—pain receptors. This lowers the firing threshold of nerve endings, resulting in pain sensation. Pain and swelling together restrict movement and reduce function, a protective mechanism called functio laesa.

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, producing fever. These cytokines are released during severe infections or extensive injuries when inflammatory signaling becomes systemic. Fever is part of the coordinated systemic response to limit injury and eliminate pathogens.

Leukocytosis is an increase in white blood cell production and mobilization. During systemic inflammation, cytokines promote leukocytosis by accelerating bone marrow output and mobilizing marginated pools of neutrophils. This response increases circulating immune cells to fight infection and clear debris from damaged tissues.

Severe systemic inflammation produces tachycardia, tachypnea, malaise, and anorexia. In sepsis, diffuse endothelial activation, vasodilation, and capillary leak cause hypotension. Dysregulated coagulation can culminate in disseminated intravascular coagulation (DIC), a life-threatening condition where blood clots form throughout the body and tissues are damaged.

Acute-phase proteins such as C-reactive protein and fibrinogen are synthesized by the liver during systemic inflammation. These proteins enhance opsonization—marking pathogens for immune destruction—and modulate the coagulation process. Their production is part of the coordinated systemic response to contain infection and prepare for tissue repair.