Mechanisms of Recovery

Mechanisms by which substances move across membranes for reabsorption or secretion include active transport, diffusion, facilitated diffusion, secondary active transport, and osmosis. These were discussed in an earlier chapter, and you may wish to review them.

Active transport utilizes energy, usually the energy found in a phosphate bond of ATP, to move a substance across a membrane from a low to a high concentration. It is very specific and must have an appropriately shaped receptor for the substance to be transported. An example would be the active transport of Na⁺ out of a cell and K⁺ into a cell by the Na⁺/K⁺ pump. Both ions are moved in opposite directions from a lower to a higher concentration.

Simple diffusion moves a substance from a higher to a lower concentration down its concentration gradient. It requires no energy and only needs to be soluble.

Facilitated diffusion is similar to diffusion in that it moves a substance down its concentration gradient. The difference is that it requires specific membrane receptors or channel proteins for movement. The movement of glucose and, in certain situations, Na⁺ ions, is an example of facilitated diffusion. In some cases of facilitated diffusion, two different substances share the same channel protein port; these mechanisms are described by the terms symport and antiport.

Symport mechanisms move two or more substances in the same direction at the same time, whereas antiport mechanisms move two or more substances in opposite directions across the cell membrane. Both mechanisms may utilize concentration gradients maintained by ATP pumps. This is a mechanism described by the term “secondary active transport.” For example, a Na⁺ ATPase pump on the basilar membrane of a cell may constantly pump Na⁺ out of a cell, maintaining a strong electrochemical gradient. On the opposite (apical) surface, a Na⁺/glucose symport protein channel assists both Na⁺ and glucose into the cell as Na⁺ moves down the concentration gradient created by the basilar Na⁺ ATPase pumps. The glucose molecule then diffuses across the basal membrane by facilitated diffusion into the interstitial space and from there into peritubular capillaries.

Most of the Ca⁺⁺, Na⁺, glucose, and amino acids must be reabsorbed by the nephron to maintain homeostatic plasma concentrations. Other substances, such as urea, K⁺, ammonia (NH₃₎, creatinine, and some drugs are secreted into the filtrate as waste products. Acid–base balance is maintained through actions of the lungs and kidneys: The lungs rid the body of H⁺, whereas the kidneys secrete or reabsorb H⁺ and HCO₃^– (Table 25.6). In the case of urea, about 50 percent is passively reabsorbed by the PCT. More is recovered by in the collecting ducts as needed. ADH induces the insertion of urea transporters and aquaporin channel proteins.

Reabsorption in the Proximal Convoluted Tubule

The renal corpuscle filters the blood to create a filtrate that still contains many important molecules that the body needs to reclaim. The PCT reclaims more of these than any other portion of the nephron. The cells of the PCT have two surfaces: apical faces the lumen of the tubule and is in contact with the filtrate. The basal surface of the PCT cell faces the interstitial space near the peritubular capillary. Sodium is actively pumped by the PCT cells into the interstitial space and diffuses down its concentration gradient into the peritubular capillary. As it does so, water follows passively by osmosis. This is called obligatory water reabsorption, because water is “obliged” to follow the Na⁺ (Figure 25.5.2). Filtered amino acids and glucose move with sodium using specific membrane transport proteins (symports), accounting for 100% of reabsorption of these molecules in healthy individuals. Both glucose and Na+ bind simultaneously to the same symport proteins on the apical surface of the cell to be transported in the same direction, toward the interstitial space. Sodium moves down its electrochemical and concentration gradient into the cell and takes glucose with it. Na⁺ is then actively pumped out of the cell at the basal surface of the cell into the interstitial space. Glucose leaves the cell to enter the interstitial space by facilitated diffusion. The energy to move glucose comes from the Na⁺/K⁺ ATPase that pumps Na⁺ out of the cell on the basal surface. The numbers and particular types of pumps and channels vary between the apical and basilar surfaces (Table 25.7) as well as the directionality of movement. Some molecules do not require cellular transport proteins but instead move between adjacent cell membranes (paracellular) across the tubule and back into the blood.

About 67 percent of the water, Na⁺, and K⁺ entering the nephron is reabsorbed in the PCT and returned to the circulation. Almost 100 percent of glucose, amino acids, and other organic substances such as vitamins are normally recovered here. Some glucose may appear in the urine if circulating glucose levels are high enough that all the glucose transporters in the PCT are saturated, so that their capacity to move glucose is exceeded (transport maximum, or Tm) like that seen with diabetes mellitus. Fifty percent of Cl^– and variable quantities of HCO₃^–, Ca⁺⁺, Mg⁺⁺, and HPO₄²⁻ are also recovered in the PCT. The significant recovery of solutes from the PCT lumen to the interstitial space creates an osmotic gradient that promotes water recovery.

About 67 percent of the water, Na⁺, and K⁺ entering the nephron is reabsorbed in the PCT and returned to the circulation. Almost 100 percent of glucose, amino acids, and other organic substances such as vitamins are normally recovered here. Some glucose may appear in the urine if circulating glucose levels are high enough that all the glucose transporters in the PCT are saturated, so that their capacity to move glucose is exceeded (transport maximum, or T_m). In men, the maximum amount of glucose that can be recovered is about 375 mg/min, whereas in women, it is about 300 mg/min. This recovery rate translates to an arterial concentration of about 200 mg/dL. Though an exceptionally high sugar intake might cause sugar to appear briefly in the urine, the appearance of glycosuria usually points to type I or II diabetes mellitus. The transport of glucose from the lumen of the PCT to the interstitial space is similar to the way it is absorbed by the small intestine. Both glucose and Na⁺ bind simultaneously to the same symport proteins on the apical surface of the cell to be transported in the same direction, toward the interstitial space. Sodium moves down its electrochemical and concentration gradient into the cell and takes glucose with it. Na⁺ is then actively pumped out of the cell at the basal surface of the cell into the interstitial space. Glucose leaves the cell to enter the interstitial space by facilitated diffusion. The energy to move glucose comes from the Na⁺/K⁺ ATPase that pumps Na⁺ out of the cell on the basal surface. Fifty percent of Cl^– and variable quantities of Ca⁺⁺, Mg⁺⁺, and HPO₄²⁻ are also recovered in the PCT.

Recovery of bicarbonate (HCO₃^–) is vital to the maintenance of acid–base balance, since it is a very powerful and fast-acting buffer. An important enzyme is used to catalyze this mechanism: carbonic anhydrase (CA). This same enzyme and reaction is used in red blood cells in the transportation of CO₂, in the stomach to produce hydrochloric acid, and in the pancreas to produce HCO₃^– to buffer acidic chyme from the stomach. In the kidney, most of the CA is located within the cell, but a small amount is bound to the brush border of the membrane on the apical surface of the cell. In the lumen of the PCT, HCO₃^– combines with hydrogen ions to form carbonic acid (H₂CO₃). This is enzymatically catalyzed into CO₂ and water, which diffuse across the apical membrane into the cell. Water can move osmotically across the lipid bilayer membrane due to the presence of aquaporin water channels. Inside the cell, the reverse reaction occurs to produce bicarbonate ions (HCO₃^–). These bicarbonate ions are cotransported with Na⁺ across the basal membrane to the interstitial space around the PCT (Figure 25.5.3). At the same time this is occurring, a Na⁺/H⁺ antiporter excretes H⁺ into the lumen, while it recovers Na⁺. Note how the hydrogen ion is recycled so that bicarbonate can be recovered. Also, note that a Na⁺ gradient is created by the Na⁺/K⁺ pump.

HCO₃⁻+ H⁺ ↔ H₂CO₃ ↔ CO₂ + H₂O

Reabsorption in the Loop of Henle

The loop of Henle consists of two sections: thick and thin descending and thin and thick ascending sections. The loops of cortical nephrons do not extend into the renal medulla very far, if at all. Juxtamedullary nephrons have loops that extend variable distances, some very deep into the medulla. The descending and ascending portions of the loop are highly specialized to enable recovery of the remaining Na+ and water that were filtered by the glomerulus but not yet reabsorbed. As the filtrate moves through the loop, its osmolarity will change from iso-osmotic with blood (about 278–300 mOsmol/kg) to first a very hypertonic solution of about 1200 mOsmol/kg and then a very hypotonic solution of about 100 mOsmol/kg. These changes are accomplished by osmosis in the descending limb and active transport of salt in the ascending limb. Solutes and water recovered from these loops are returned to the circulation by way of the peritubular capillaries (cortical nephron) or vasa recta (juxtamedullary nephron).

Reabsorption in the Distal Convoluted Tubule and Collecting Ducts

Approximately 80 percent of filtered water has been recovered by the time the dilute filtrate enters the DCT. The DCT will recover another 10–15 percent before the filtrate enters the collecting ducts. Under hormonal action, additional water and solutes can be reabsorbed into the peritubular capillaries and returned to the circulation.

Cells of the DCT also recover Ca⁺⁺ from the filtrate. Receptors for parathyroid hormone (PTH) are found in DCT cells and when bound to PTH, induce the insertion of calcium channels on their luminal surface. The channels enhance Ca⁺⁺ recovery from the forming urine. In addition, as Na⁺ is pumped out of the cell, the resulting electrochemical gradient attracts Ca⁺⁺ into the cell. Finally, calcitriol (1,25 dihydroxyvitamin D, the active form of vitamin D) is very important for calcium recovery. It induces the production of calcium-binding proteins that transport Ca⁺⁺ into the cell. These binding proteins are also important for the movement of calcium inside the cell and aid in exocytosis of calcium across the basolateral membrane. Any Ca⁺⁺ not reabsorbed at this point is lost in the urine.

Tubular Secretion

Tubular secretion occurs mostly in the PCT and DCT where unfiltered substances are moved from the peritubular capillary into the lumen of the tubule. Secretion usually removes substances that are too large to be filtered (ex: antibiotics, toxins) or those that are in excess in the blood (ex: H⁺, K⁺).

Tubular Reabsorption and Secretion to Control pH

Recovery of bicarbonate (HCO₃^–) is vital to the maintenance of acid–base balance, since it is a very powerful and fast-acting buffer. An important enzyme is used to catalyze this mechanism: carbonic anhydrase (CA). This same enzyme and reaction is used in red blood cells in the transportation of CO₂, in the stomach to produce hydrochloric acid, and in the pancreas to produce HCO₃^– to buffer acidic chyme from the stomach. In the kidney, most of the CA is located within the cell, but a small amount is bound to the brush border of the membrane on the apical surface of the cell. In the lumen of the PCT, HCO₃^– combines with hydrogen ions to form carbonic acid (H₂CO₃). This is enzymatically catalyzed into CO₂ and water, which diffuse across the apical membrane into the cell. Water can move osmotically across the lipid bilayer membrane due to the presence of aquaporin water channels. Inside the cell, the reverse reaction occurs to produce bicarbonate ions (HCO₃^–). These bicarbonate ions are cotransported with Na⁺ across the basal membrane to the interstitial space around the PCT (Figure 25.5.4). At the same time this is occurring, a Na⁺/H⁺ antiporter excretes H⁺ into the lumen, while it recovers Na⁺. Note how the hydrogen ion is recycled so that bicarbonate can be recovered. Also, note that a Na⁺ gradient is created by the Na⁺/K⁺ pump.

HCO₃⁻+ H⁺ ↔ H₂CO₃ ↔ CO₂ + H₂O