Renal tubular development

The nephron is faced with the enormous task of maintaining a constant composition and volume of the extracellular fluid. The amount of electrolytes and water ingested and absorbed must be eliminated, and the waste products from metabolism must also be excreted. This challenge is all the more complex as our dietary intake is quite variable from day to day. Despite this variable intake, there is virtually no change in the volume or composition of the extracellular fluid volume from day to day. There are two possible ways that our kidney could balance ingestion and excretion. The kidney could be a secretory organ where all the excess solutes and water ingested would be excreted by tubular secretion. This would be very inefficient and require an enormous amount of energy. In addition, in times of a disturbance in the extracellular fluid volume such as a high salt intake or volume loss from diarrhea, the regulatory systems necessary to maintain a constant extracellular fluid volume and composition while excreting waste products would be very complex. On the other hand, the kidney could filter an enormous quantity of extracellular fluid, which would be very efficient in removing waste products, and reclaim the desired salt, organic solutes, and water. With volume depletion, a greater fraction of salt and water could be reabsorbed, and when one has a dietary indiscretion such as the salt intake from a pepperoni pizza, there could be a reduction in sodium reabsorption leading to an increase in excretion to bring us back into balance. The mammalian kidney actually uses both mechanisms to perform its job which is necessary for our survival on land. The adult kidney filters ~150 l of isotonic fluid a day and reclaims most of it, leaving the waste produces to be excreted in about 1.5 l of urine. In addition, there are secretory processes for solutes such as organic anions and cations in the proximal tubule and secretory mechanisms to excrete the excess acid generated from metabolism in the distal nephron which aid in maintaining homeostasis. To accomplish the remarkable task of reclamation of the necessary solutes and water to maintain a constant composition of the extracellular fluid volume, the mammalian kidney has evolved into a highly specialized organ with thousands of units called nephrons. Each human kidney has approximately one million nephrons. Each nephron is a tube consisting of epithelial cells and is divided into 12 specialized segments as shown in Fig. 1. The epithelial cells allow for the vectorial transport of solutes. The proximal tubule is responsible for the bulk reclamation of solutes and water and for the secretion of organic cations and anions. Approximately two-thirds of the glomerular filtrate is reabsorbed by the proximal tubule in an isotonic fashion. Virtually all of the organic solutes, as well as the majority of bicarbonate, phosphate, and chloride, are reabsorbed in this segment. The proximal tubule is divided into S1, S2, and S3 segments based on the rates of transport of some solutes and morphological changes that occur down the proximal tubule. The proximal tubule transitions into the thin descending limb which can be of variable length and then makes a hairpin