Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure?
It has been suggested that generalized endothelial damage and permeability changes, induced by prolonged activation of the complement system and ensuing release of lysosomal enzymes, prostaglandins and toxic oxygen products, underlie the genesis of the Adult Respiratory Distress Syndrome (ARDS) and Multiple Organ Failure (MOF). The effects in New Zealand white rabbits were investigated of a 4 h infusion of activated complement and its combination with a short hypoxic episode on respiratory function, leukocyte count, platelet count and morphology of the lungs, heart, liver, kidney and spleen. Prolonged activation of the complement system induced hyperventilation with respiratory alkalosis and hypocapnia, depletion of granulocytes (PMN), and a variable accumulation PMN in the capillaries of all organs examined, in combination with interstitial, and, in the liver, cellular oedema. Electron microscopy of the lungs revealed degranulation of PMN, endothelial swelling and widening of the alveolar septa. The combination of hypoxia and systemic complement activation appeared to aggravate this microvascular injury with the occurrence of protein rich alveolar oedema and haemorrhage in the lungs and accumulation of PMN debris containing macrophages in the spleen. The alterations in respiratory function and pulmonary morphology in these rabbits, imitate the clinical and morphological characteristics of the early phase of ARDS. The inflammatory reaction, found in all other organs examined, might represent the early phase of MOF. If so, ARDS and MOF -- clinically closely interconnected syndromes -- might be interpreted as manifestations of the same syndrome and as the clinical expression of an uncontrolled whole body inflammation.
D000818:Animals; D002196:Capillaries / Q000648:ultrastructure; D002245:Carbon Dioxide / Q000097:blood; D003167:Complement Activation; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D006098:Granulocytes; D006863:Hydrogen-Ion Concentration; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008168:Lung / Q000648:ultrastructure; D009102:Multiple Organ Failure / Q000209:etiology* / Q000473:pathology; D010100:Oxygen / Q000097:blood; D010976:Platelet Count; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology; D013154:Spleen / Q000473:pathology
D002245:Carbon Dioxide; D010100:Oxygen