Fig. 13.2 ). As early as 30 minutes after an acute insult, there is increased synthesis of interleukin 8 (IL-8), a potent neutrophil chemotactic and activating agent, by pulmonary macrophages. Release of IL-8 and other factors, such as IL-1 and tumor necrosis factor (TNF), leads to endothelial activation and sequestration and activation of neutrophils in pulmonary capillaries. Neutrophils are thought to have an important role in the pathogenesis of ARDS. Histologic examination of lungs early in the disease process shows increased numbers of neutrophils within the vascular space, the interstitium, and the alveoli. Activated neutrophils release a variety of products (e.g., reactive oxygen species, proteases) that damage the alveolar epithelium and endothelium. The assault on the endothelium and epithelium causes vascular leakiness and loss of surfactant that render the alveolar unit unable to expand. Of note, the destructive forces unleashed by neutrophils can be counteracted by an array of endogenous anti-proteases and anti-oxidants that are upregulated by proinflammatory cytokines. In the end, it is the balance between the destructive and protective factors that determines the degree of tissue injury and clinical severity of the ARDS.
MORPHOLOGYIntheacute phase of ARDS, thelungsaredarkred,firm,airless,andheavy.Microscopicexaminationrevealscapillarycongestion,necrosisofalveolarepithelialcells,interstitialandintra-alveolaredemaandhemorrhage,and(particularlywithsepsis)collectionsofneutrophilsincapillaries.Themostcharacteristicfindingisthepresenceofhyaline membranes, particularly http://ebooksmedicine.net
NORMAL ALVEOLUS Type I cell Surfactant layer Type II cell Interstitium Alveolar macrophage Bronchial epithelium Basement membrane Sloughed bronchial epithelium Necrotic type I cell Edema fluid Hyaline membrane Fibroblast Procollagen Fibrin Neutrophil sequestration and migration into alveolus Alveolus Leukotrienes Inactivated surfactant PAF Proteases TNF IL-1 TNF Chemokines ACUTE LUNG INJURY Capillary Endothelial cell Injured, swollen endothelial cells Cellular debris Edema
Fig. 13.2 Thenormalalveolus(left) andtheinjuredalveolusintheearlyphaseofacutelunginjuryandtheacuterespiratorydistresssyndrome.UndertheinfluenceofproinflammatorycytokinessuchasinterleukinsIL-8andIL-1andtumornecrosisfactor(TNF)(releasedbymacrophages),neutrophilsaresequesteredinthepulmonarymicrovasculatureandthenegressintothealveolarspace,wheretheyundergoactivation.Activatedneutrophilsreleaseleukotrienes,oxidants,proteases,andplatelet-activatingfactor(PAF),whichcontributetolocaltissuedamage,accumulationofedemafluid,surfactantinactivation,andhyalinemembraneformation.Subsequently,thereleaseofmacrophage-derivedfibrogeniccytokinessuchastransforminggrowthfactor-β (TGF-β)andplatelet-derivedgrowthfactor(PGDF)stimulatefibroblastgrowthandcollagendepositionassociatedwiththehealingphaseofinjury.(Modified from Ware LB: Pathophysiology of acute lung injury and the acute respiratory distress syndrome, SeminRespirCritCareMed27:337, 2006.)