Active And Passive Solute Transport

Up until this point, solute reabsorption in the proximal tubule has been discussed in general terms as

FIGURE 8 Effect of reduced plasma colloid osmotic pressure and increased interstitial fluid pressure on the permeability properties of the junctional complexes. It has been proposed that an increase in interstitial fluid pressure may be associated with an increased permeability of the junctional complexes between proximal tubule cells that would enable backflux diffusion of Na+, Cl-, HCO—, and water from the interstitium to the lumen, thus reducing the net reabsorption of solutes and water.

FIGURE 8 Effect of reduced plasma colloid osmotic pressure and increased interstitial fluid pressure on the permeability properties of the junctional complexes. It has been proposed that an increase in interstitial fluid pressure may be associated with an increased permeability of the junctional complexes between proximal tubule cells that would enable backflux diffusion of Na+, Cl-, HCO—, and water from the interstitium to the lumen, thus reducing the net reabsorption of solutes and water.

if all filtered solutes were being reabsorbed equally. In fact, some solutes, such as amino acids and glucose, are reabsorbed much more rapidly due to their direct coupling to Na+ reabsorption by specialized transport proteins in the luminal membrane. This preferential reabsorption causes the concentration of these substances in the proximal tubule fluid to fall below that in the plasma and the original ultrafiltrate. The movement of other substances down a concentration gradient from the lumen to the peritubular fluid results in passive reabsorption. This gradient develops as water is reabsorbed, producing a higher concentration of the passively reabsorbed solute in the lumen. The concentration of the passively reabsorbed solute increases in the tubular fluid until its rate of passive diffusion out of the tubular lumen is sufficient to match the rate of volume reabsorption. Therefore, the steady-state concentration of the passively reabsorbed solute will depend on its ability to pass through the tubular epithelium. The lower the permeability of the proximal tubule to the solute, the more its concentration must rise in the tubular fluid before it is reabsorbed at a sufficient rate to maintain a constant concentration in the lumen. Other substances are

FIGURE 9 Changes in the ratio of tubular fluid concentration to plasma concentration for various solutes along the length of the proximal tubule. The concentration ratio (TF/P) is plotted as a function of the percent of the total proximal tubule length. The tubular concentrations of the preferentially absorbed solutes such as HCO", glucose, and amino acids fall rapidly as they are actively reabsorbed. The tubular concentrations of passively reabsorbed or nonreabsorbed substances such as Cl" and inulin rise as water is reabsorbed. The tubular concentration of an actively secreted substance such as PAH rises even more rapidly.

FIGURE 9 Changes in the ratio of tubular fluid concentration to plasma concentration for various solutes along the length of the proximal tubule. The concentration ratio (TF/P) is plotted as a function of the percent of the total proximal tubule length. The tubular concentrations of the preferentially absorbed solutes such as HCO", glucose, and amino acids fall rapidly as they are actively reabsorbed. The tubular concentrations of passively reabsorbed or nonreabsorbed substances such as Cl" and inulin rise as water is reabsorbed. The tubular concentration of an actively secreted substance such as PAH rises even more rapidly.

actively secreted into the proximal tubular fluid and, consequently, have higher concentrations in the tubular fluid.

Because of these specialized transport processes, the composition of the proximal tubule fluid is markedly altered along the length of the proximal tubule. As shown schematically in Fig. 9, at the beginning of the proximal convoluted tubule, the fluid is simply an ultrafiltrate of plasma, but by the end of the proximal tubule virtually all filtered amino acids, glucose, and other metabolic substrates have been reabsorbed. Consequently, the concentration of Na+ salts is higher because they replace the solute deficit left by the preferentially reabsorbed solutes. Secreted solutes such as para-aminohippurate (PAH, discussed later; see also Chapter 24) develop TF/P ratios exceeding that of inulin (3.0) by the end of the proximal tubule; however, their actual concentrations are quite small, so they contribute little to the osmolality of the tubular fluid. The next sections describe the transport processes responsible for the preferential reabsorption of some solutes and secretion of others.

ACTIVE H+ SECRETION AND HCO" _REABSORPTION_

As mentioned earlier, one of the primary changes in the composition of the proximal tubular fluid is a rise in its Cl3 concentration, which is a consequence of the preferential reabsorption of HCO". This preferential reabsorption process causes the HCO" concentration of the proximal tubular fluid to fall, but, because electro-neutrality must be maintained, there must be a corresponding rise in the concentration of the most abundant anion, Cl".

Active secretion of protons (H+) into the lumen of the proximal tubule drives the preferential reabsorption of HCO". Protons entering the lumen are buffered by HCO", resulting in a loss of HCO" consumed in the formation of carbonic acid and its subsequent diffusion from the lumen as CO2. This complex process needs to be considered in more detail because it is essential not only to reabsorptive processes in the proximal tubule but also to the regulation of body acid-base balance.

As shown in Fig. 10, both proximal tubule cells and intercalated cells, which are found in the connecting tubule and collecting duct, are capable of actively

FIGURE 10 General mechanism of H+ and HCO" transport by the nephron. In this model, which applies to both the proximal tubule cells and intercalated cells, which are found in the connecting tubule and collecting duct, the details of the active H+ secretory mechanism and basolateral HCO3" exit are left unspecified in order to focus on the intracellular reactions producing H+ and HCO". Because of mass balance considerations, the active extrusion of H+ from the cell into the lumen causes the flow of the reactions increasing the HCO3" concentration in the cell. Because of this rise in the cell HCO" concentration, there is a favorable electrochemical potential gradient for the passive movement of HCO3" from the cell, and this process occurs only across the basolateral membrane because of specialized HCO3" transporters in that membrane.

FIGURE 10 General mechanism of H+ and HCO" transport by the nephron. In this model, which applies to both the proximal tubule cells and intercalated cells, which are found in the connecting tubule and collecting duct, the details of the active H+ secretory mechanism and basolateral HCO3" exit are left unspecified in order to focus on the intracellular reactions producing H+ and HCO". Because of mass balance considerations, the active extrusion of H+ from the cell into the lumen causes the flow of the reactions increasing the HCO3" concentration in the cell. Because of this rise in the cell HCO" concentration, there is a favorable electrochemical potential gradient for the passive movement of HCO3" from the cell, and this process occurs only across the basolateral membrane because of specialized HCO3" transporters in that membrane.

secreting H+ into the lumen. This H+ is derived from CO2 that is produced by metabolism or that enters the cells by diffusion from the extracellular fluid. As a gas, CO2 permeates cell membranes and rapidly attains diffusion equilibrium. CO2 in the cell is hydrated to form carbonic acid (H2CO3), a weak acid that partially dissociates to H+ and HCO^ (see also Chapter 20). The reaction of CO2 with water to form carbonic acid is normally at equilibrium because of the presence of the enzyme carbonic anhydrase in all cells. Proximal cells differ from intercalated cells in the mechanism used for active transport of H+ from the cytosol into the lumen, but this secretory process lowers the H+ concentration in the cell. As shown in Fig. 9, when intracellular pH rises (i.e., H+ concentration falls) the CO2/carbonic acid system in the cell favors the flow of equilibrium reactions to produce more product, that is, more H+ and HCO^. Thus, the active transport of H+ from the cell decreases the intracellular H+ concentration and increases the intracellular HCO^ concentration.

The HCO^ concentration in the cell would normally be low. If it were in electrochemical equilibrium with the extracellular fluid, its concentration would be only about 2 mmol/L. Because of the active H+ secretion from the cell, the HCO^ concentration can be much higher, leading to an electrochemical potential difference favoring HCO^ movement out of the cell. In both proximal tubule cells and intercalated cells, HCO^ leaves the cells across the basolateral membrane because this membrane has facilitated exit transporters, whereas the luminal membrane does not. The net effect is that H+ is actively transported into the lumen and HCO^ diffuses passively from the cell into the peritubular fluid.

The details of this process in the proximal tubule are shown in Fig. 11. The active H+ transport across the luminal membrane in the proximal tubule is driven primarily by an exchange mechanism for Na+, which is called an Na+/H+ antiporter. The active transport of H+ out of the cell against its electrochemical potential difference is driven by the energy made available by Na+ movement into the cell down its electrochemical potential difference. Just as the kinetic energy of moving water can be converted into useful work by a turbine, the kinetic energy of Na+ moving into the cell can be converted into work to move H+ into the lumen and acidify the tubular fluid. As H+ enters the lumen, the pH of the tubular fluid drops. This fall in pH is buffered by the filtered HCO^ in the lumen. The HCO^ buffers H+ as the pH falls, exactly the reverse of the process occurring in the cell. The resulting carbonic acid can dissociate to CO2 and water. Carbonic anhydrase is bound to the luminal brush border membrane in the proximal tubule. It catalyzes the dissociation of carbonic acid to CO2 and water, thereby allowing a rapid

FIGURE 11 Mechanism of HCO^" reabsorption in the proximal tubule. Active H+ secretion into the lumen is driven by exchange diffusion (antiport) for Na+ entering the cell. Movement of HCO^" out of the cell across the basolateral membrane occurs by a specialized transporter involving cotransport of three HCO^" ions with one Na+ ion. The high concentration of H+ in the tubular fluid titrates filtered HCO^" to produce CO2. This reaction is catalyzed by carbonic anhydrase enzyme bound to the luminal brush border membrane. HCO3" disappearing from the lumen is replaced by an equimolar amount of HCO^" leaving the cell across the basolateral membrane.

FIGURE 11 Mechanism of HCO^" reabsorption in the proximal tubule. Active H+ secretion into the lumen is driven by exchange diffusion (antiport) for Na+ entering the cell. Movement of HCO^" out of the cell across the basolateral membrane occurs by a specialized transporter involving cotransport of three HCO^" ions with one Na+ ion. The high concentration of H+ in the tubular fluid titrates filtered HCO^" to produce CO2. This reaction is catalyzed by carbonic anhydrase enzyme bound to the luminal brush border membrane. HCO3" disappearing from the lumen is replaced by an equimolar amount of HCO^" leaving the cell across the basolateral membrane.

conversion of the secreted H+ and the HCO^ buffer to CO2. As this reaction proceeds, the CO2 produced in the lumen rapidly diffuses down its concentration gradient back to the blood. The result is that HCO^ disappears from the lumen as the tubular fluid is acidified.

Given these reactions, why is the process referred to as bicarbonate reabsorption rather than HCO^ titration or some other term? Close inspection of the reaction scheme shown in Fig. 11 shows that the net result is the same as if the HCO^ were reabsorbed directly. For each H+ that is secreted and titrated by one HCO^ in the lumen, one HCO^ is also formed in the cell and diffuses across the basolateral membrane to the blood. Thus, each bicarbonate that disappears from the lumen is matched by one that appears in the peritubular capillaries and is returned to the systemic circulation. In producing the H+ and HCO^ within the cell, one CO2 produced by metabolism within the proximal tubular cell or elsewhere in the body is consumed; however, one

CO2 is produced in the lumen by the titration of HCO-and returns to the blood. The net effect of this circuitous process is that the luminal pH falls, and there is a loss of bicarbonate from the lumen and the addition of bicarbonate to the blood. There is no net gain or loss of CO2. Therefore, the process is equivalent to bicarbonate reabsorption with a corresponding luminal acidification.

As discussed in more detail in Chapter 31, this reabsorption of bicarbonate is essential to the maintenance of normal acid-base balance. Filtered HCO- is reclaimed from the glomerular filtrate and returned to the blood, where it can serve as a buffer for the H+ ions produced by metabolism.

The active H+ secretory process in the proximal tubule is limited in the extent to which it can acidify the lumen and, thus, reabsorb bicarbonate by the energy available from the Na+ electrochemical potential difference across the luminal membrane. It is also limited because the proximal tubule is a leaky epithelium and allows H+ to diffuse back toward the blood. Both factors set a lower limit of 6.6-6.8 on the pH that can be achieved in the lumen of the proximal tubule under normal systemic acid-base conditions.

At a pH of 6.6, the equilibrium concentration for HCO- in the lumen is about 3.8 mmol/L. Thus, the bicarbonate concentration falls from a normal filtered concentration of about 25 mmol/L to 3.8 mmol/L. However, about 95% of the filtered HCO- is reabsorbed. How is this possible? Consider bicarbonate mass balance along the proximal tubule. If 130 mL/min of fluid is filtered at the glomerulus containing 25 mmol/L of bicarbonate, the rate of HCO- filtration is (0.13 • 25) = 3.25 mmol/min. Because 66% of the filtered fluid is reabsorbed along the proximal tubule, the flow entering the loop of Henle is 44.2 mL/min. If the HCO-concentration of this fluid is 3.8 mmol/L, 0.168 mmol/ min of HCO- (0.0442 • 3.8) leaves the proximal tubule. Thus, (3.25 - 0.168) = 3.082 mmol/L, is reabsorbed along the proximal tubule, which is equivalent to a fractional reabsorption of 95% of the filtered load of HCO-.

As discussed in Chapter 31, HCO- reabsorption is regulated according to the requirements for acid-base balance. Merely by reducing the fractional reabsorption of bicarbonate in the proximal tubule, its excretion can be increased markedly, thus, causing the loss of base from the body.

Get Rid of Gallstones Naturally

Get Rid of Gallstones Naturally

One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.

Get My Free Ebook


Post a comment