Physiological and clinical implications of medullary hypoxia.

Abstract

Because of countercurrent capillary flow, the renal medulla of mammalian kidneys is perpetually hypoxic, the ambient oxygen tension hovering close to the critical Po2 that limits respiration. Within this environment, the mitochondria-rich cells of the medullary thick ascending limb (mTAL) require large amounts of energy to accomplish the work of ion transport. These cells are therefore uniquely vulnerable to anoxic damage, as is demonstrated by morphological changes in isolated perfused rat kidneys. The lesions of hypoxia in mTAL cells of perfused kidneys can be greatly exaggerated by maneuvers that increase the work of transport and practically eliminated by inhibitors of active transport, like ouabain or furosemide, or by interrupting glomerular filtration. The close dependence of experimental ischemic injury on active transport suggests that endogenous inhibitors of transport may play an important physiological role in modulating the susceptibility of the medulla to anoxic injury in health and disease. Candidates for this role include adenosine and locally formed derivatives of arachidonic acid that have been shown to influence metabolism and transport.