The kidneys maintain homeostasis while functioning under a tremendous range of environmental water and salt availability.
For example, the kidneys have the capacity to excrete free water in freshwater fish, varying amounts of water and solute in humans, and an extremely concentrated urine in the kangaroo rat, which can live its entire life without access to water. The kidneys are a pair of encapsulated organs located in the retroperitoneal area. A renal artery enters and a renal vein exits from each kidney at the hilum. Approximately 20% of cardiac output goes to the kidneys. Blood is filtered in the kidneys, removing wastes—in particular urea and nitrogen-containing compounds—and regulating extracellular electrolytes and intravascular volume. Because renal blood flow is from cortex to medulla and because the medulla has a relatively low blood flow for a high rate of metabolic activity, the normal oxygen tension in the medulla is lower than in other parts of the kidney. This makes the medulla particularly susceptible to ischemic injury.
The anatomic unit of kidney function is the nephron, a structure consisting of a tuft of capillaries termed the glomerulus, the site at which blood is filtered, and a renal tubule from which water and salts in the filtrate are reclaimed. Each human kidney has approximately 1 million nephrons.
A glomerulus consists of an afferent and an efferent arteriole and an intervening tuft of capillaries lined by endothelial cells and covered by epithelial cells that form a continuous layer with those of the Bowman capsule and the renal tubule. The space between capillaries in the glomerulus is called the mesangium. Material comprising a basement membrane is located between the capillary endothelial cells and the epithelial cells .
Closer examination of glomerular histology and cell biology reveals unique features not found in most peripheral capillaries. First, the glomerular capillary endothelium is fenestrated. However, because the endothelial cells have a coat of negatively charged glycoproteins and glycosaminoglycans, they normally exclude plasma proteins such as albumin. On the other side of the glomerular basement membrane are the epithelial cells. Termed “podocytes” because of their numerous extensions or foot processes, these cells are connected to one another by modified desmosomes.
The mesangium is an extension of the glomerular basement membrane but is less dense and contains two distinct cell types: intrinsic glomerular cells and tissue macrophages. Both cell types contribute to the development of immune-mediated glomerular disease by their production of, and response to, cytokines such as transforming growth factor-β (TGF-β).
Understanding the complex organization of the glomerulus is crucial for understanding both normal renal function and also the characteristics of different glomerular diseases. Thus, in some conditions immune complexes may accumulate under the epithelial cells, whereas in others they accumulate under the endothelial cells. Likewise, because immune cells are not able to cross the glomerular basement membrane, immune complex deposition under the epithelial cells is generally not accompanied by a cellular inflammatory reaction.
The renal tubule itself has a number of different structural regions: the proximal convoluted tubule, from which most of the electrolytes and water are reclaimed; the loop of Henle; and a distal convoluted tubule and collecting duct, where the urine is concentrated and additional electrolyte and water changes are made in response to hormonal control.
