Renal Transport Mechanisms PDF

Renal Transport Mechanisms Dr. Mohammed Hamza Tubular Reabsorption • Tubular reabsorption is the transfer of materials from kidney tubule lumen to peritubular capillaries. • There are three important conclusions as to the glomerular filtration and tubular reabsorption processes: 1. The filtered lo...

Renal Transport Mechanisms Dr. Mohammed Hamza Tubular Reabsorption • Tubular reabsorption is the transfer of materials from kidney tubule lumen to peritubular capillaries. • There are three important conclusions as to the glomerular filtration and tubular reabsorption processes: 1. The filtered loads are enormous, generally larger than the total amounts of the substances in the body. • For example, the body contains about 40 L of water, but the volume of water filtered each day is 180 L. Tubular Reabsorption • There are three important conclusions as to the glomerular filtration and tubular reabsorption processes (continued): 2. Reabsorption of waste products is relatively incomplete (as in the case of urea), so that large fractions of their filtered loads are excreted in the urine. Tubular Reabsorption • There are three important conclusions as to the glomerular filtration and tubular reabsorption processes (continued): 3. Reabsorption of most useful plasma components, such as water, inorganic ions, and organic nutrients, is relatively complete so that the amounts excreted in the urine are very small fractions of their filtered loads. Average Values for Several Components That Undergo Filtration and Reabsorption Tubular Reabsorption • An important distinction should be made between reabsorptive processes that can be controlled physiologically and those that cannot. • The reabsorption rates of most organic nutrients, such as glucose, are always very high and are not physiologically regulated. • Therefore, the filtered loads of these substances are completely reabsorbed in a healthy kidney, with none appearing in the urine. Tubular Reabsorption • Therefore, the kidneys do not regulate the plasma concentrations of these organic nutrients. • Rather, the kidneys merely maintain whatever plasma concentrations already exist. Tubular Reabsorption • Recall that a major function of the kidneys is to eliminate soluble waste products. • To do this, the blood is filtered in the glomeruli. • One consequence of this is that substances necessary for normal body functions are filtered from the plasma into the tubular fluid. Tubular Reabsorption • To prevent the loss of these important nonwaste products, the kidneys have powerful mechanisms to reclaim useful substances from tubular fluid while simultaneously allowing waste products to be excreted. • The reabsorptive rates for water and many ions, although also very high, are under physiological control. • For example, if water intake is decreased, the kidneys can increase water reabsorption to minimize water loss. Tubular Reabsorption • In contrast to glomerular filtration, the crucial steps in tubular reabsorption do not occur by bulk flow. • Instead, two other processes are involved 1. Reabsorption of some substances from the tubular lumen by diffusion 2. Reabsorption of all other substances by mediated transport Tubular Reabsorption Tubular reabsorption begins as soon as filtrate enters the tubule cells. Paracellular transport occurs between cells (even though they have tight junctions) and is seen mainly with ions. Transport can be active (requires ATP) or passive (no ATP). Reabsorption by Diffusion • The reabsorption of urea by the proximal tubule provides an example of passive reabsorption by diffusion. • Some urea, although it is a waste product, is reabsorbed from the proximal tubule. • Because the corpuscular membranes are freely filterable to urea, the urea concentration in the fluid within Bowman’s space is the same as that in the peritubular capillary plasma and the interstitial fluid surrounding the tubule. Reabsorption by Diffusion • As the filtered fluid flows through the proximal tubule, water reabsorption occurs. • This removal of water increases the concentration of urea in the tubular fluid so it is higher than in the interstitial fluid and peritubular capillaries. • Therefore, urea diffuses down this concentration gradient from tubular lumen to peritubular capillary. • Urea reabsorption is thus dependent upon the reabsorption of water. Reabsorption by Mediated Transport • Many solutes are reabsorbed by primary or secondary active transport. • These substances must first cross the apical membrane (also called the luminal membrane). • Then, the substance diffuses through the cytosol of the cell and, finally, crosses the basolateral membrane. • The movement by this route is termed transcellular epithelial transport. Reabsorption by Mediated Transport • A substance does not need to be actively transported across both the apical and basolateral membranes. • For example, Na+ moves “downhill” (passively) into the cell across the apical membrane through specific channels or transporters. • Then, it is actively transported “uphill” out of the cell across the basolateral membrane via Na+/K+-ATPases in this membrane. Reabsorption by Mediated Transport • The reabsorption of many substances is coupled to the reabsorption of Na+. • The cotransported substance moves uphill into the cell via a secondary active cotransporter as Na+ moves downhill into the cell via this same cotransporter. • This is precisely how glucose, many amino acids, and other organic substances undergo tubular reabsorption. • The reabsorption of several inorganic ions is also coupled in a variety of ways to the reabsorption of Na+. Reabsorption by Mediated Transport • Many of the mediated-transport-reabsorptive systems in the renal tubule have a limit to the amounts of material they can transport per unit time known as the transport maximum (Tm). • This is due to the saturation of the binding sites on the membrane transport proteins. • An important example is the secondary active-transport proteins for glucose, located in the proximal tubule. Reabsorption by Mediated Transport • As noted earlier, glucose does not usually appear in the urine because all of the filtered glucose is reabsorbed. • Plasma glucose concentration in a healthy person normally does not exceed 150 mg/100 mL. • This concentration of plasma glucose is below the threshold value of 200 mg/100 mL at which glucose starts to appear in urine (glucosuria). Tubular Reabsorption of Glucose This transport maximum is why untreated diabetic patients have glucose in their urine. Reabsorption by Mediated Transport • Like glucose, most amino acids and water-soluble vitamins are filtered in large amounts each day. • But almost all of these filtered molecules are reabsorbed by the proximal tubule. • If the plasma concentration increases, the filtered load may exceed the tubular reabsorptive Tm and the substance will appear in the urine. Tubular Secretion • Tubular secretion is the transfer of materials from peritubular capillaries to kidney tubule lumen. • Like glomerular filtration, it constitutes a pathway from the blood into the tubule. • Like reabsorption, secretion can occur by diffusion or by transcellular mediated transport. Tubular Secretion • The most important substances secreted by the tubules are H+ and K+. • However, a large number of normally occurring organic anions, such as choline and creatinine, are also secreted; so are many foreign chemicals such as penicillin. Tubular Secretion • Active secretion of a substance requires active transport  either from the blood side (the interstitial fluid) into the tubule cell (across the basolateral membrane)  or out of the cell into the lumen (across the apical membrane). • As in reabsorption, tubular secretion is usually coupled to the reabsorption of Na+. Tubular Secretion • Tubular secretion is a mechanism to increase the ability of the kidneys to dispose of substances at a higher rate rather than depending only on the filtered load. Metabolism by the Tubules • The cells of the renal tubules synthesize glucose during fasting and add it to the blood. • They can also catabolize certain organic substances, such as peptides, taken up from either the tubular lumen or peritubular capillaries. • Catabolism eliminates these substances from the body just as if they had been excreted into the urine. Regulation of Membrane Channels and Transporters • Tubular reabsorption or secretion of many substances is under physiological control. • For most of these substances, control is achieved by regulating the activity or concentrations of the membrane channel and transporter proteins involved in their transport. • This regulation is achieved by hormones and paracrine or autocrine factors. Summary—Division of Labor • The majority of the reabsorption is accomplished by the proximal tubule and the loop of Henle. • Extensive reabsorption by the proximal tubule and loop of Henle ensures that the masses of solutes and the volume of water entering the tubular segments beyond the loop of Henle are relatively small. • These distal segments then do the fine-tuning for most substances, determining the final amounts excreted in the urine by adjusting their rates of reabsorption and, in a few cases, secretion.