Pathophysiology
Clinical meaning
Microcirculation failure refers to the breakdown of perfusion and oxygen delivery at the capillary level โ the terminal vascular bed where gas exchange, nutrient delivery, and waste removal actually occur. Even when macrocirculatory parameters (blood pressure, cardiac output, central venous pressure) appear adequate, microcirculatory dysfunction can produce tissue hypoxia, cellular injury, and organ failure. The microcirculation consists of arterioles (resistance vessels controlling flow distribution), capillaries (exchange vessels), and venules (capacitance vessels). Under normal conditions, arteriolar smooth muscle tone is regulated by local metabolic autoregulation (adenosine, CO2, pH, O2 tension), endothelial nitric oxide (NO) production, myogenic response to transmural pressure, and autonomic innervation. In sepsis โ the most common cause of microcirculatory failure โ endotoxin and inflammatory mediators (TNF-alpha, IL-1, IL-6) activate endothelial cells, causing several pathological changes simultaneously: endothelial glycocalyx degradation (loss of the protective carbohydrate layer that maintains vascular permeability barrier and mechanotransduction), upregulation of adhesion molecules (ICAM-1, VCAM-1, selectins) that promote neutrophil rolling, adhesion, and transmigration, increased endothelial permeability from VE-cadherin disruption allowing capillary leak (third-spacing of fluid, interstitial edema that increases oxygen diffusion distance), microvascular thrombosis from...