FIGURE.

Pathophysiology of acute chest syndrome. Infection or other inflammatory stimuli cause pulmonary hypoxia and increased expression of endothelial adhesion molecules, including integrin α4β1 and vascular cell adhesion molecule (VCAM)-1; this precipitates sickle-cell haemoglobin (HbS) polymerisation and vaso-occlusion, causing further hypoxia and inflammation, and creating a constant cycle. Vaso-occlusion causes the release of free plasma haemoglobin, which reduces nitric oxide (NO) availability, altering VCAM-1 expression. Vaso-occlusion and bone marrow infarction can cause fat embolism, further damaging the pulmonary circulation. The micrograph shows oil-red O staining of pulmonary alveolar macrophages, showing the characteristic red lipid inclusions that are diagnostic of fat embolism. Secretory phospholipase A2 concentrations, which increase in response to inflammation and are known to be very high in acute chest syndrome, further increase expression of adhesion molecules in the pulmonary vasculature, causing more vaso-occlusion. Adapted from Rees et al. (2010), with permission from the publisher.