Reabsorption and Secretion Along Different Parts of the Nephron

In the previous sections, we discussed the basic principles by which water and solutes are transported across the tubular membrane. With these generalizations in mind, we can now discuss the different characteristics of the individual tubular segments that enable them to perform their specific excretory functions. Only the tubular transport functions that are quantitatively most important are discussed, especially as they relate to the reabsorption of sodium, chloride, and water. In subsequent chapters, we discuss the reabsorption and secretion of other specific substances in different parts of the tubular system.

Proximal Tubular Reabsorption

Normally, about 65 per cent of the filtered load of sodium and water and a slightly lower percentage of filtered chloride are reabsorbed by the proximal tubule before the filtrate reaches the loops of Henle. These percentages can be increased or decreased in different physiologic conditions, as discussed later.

Proximal Tubules Have a High Capacity for Active and Passive

Reabsorption. The high capacity of the proximal tubule for reabsorption results from its special cellular characteristics, as shown in Figure 27-6. The proximal tubule epithelial cells are highly metabolic and have large numbers of mitochondria to support potent active transport processes. In addition, the proximal

Figure 27-6

Cellular ultrastructure and primary transport characteristics of the proximal tubule. The proximal tubules reabsorb about 65 per cent of the filtered sodium, chloride, bicarbonate, and potassium and essentially all the filtered glucose and amino acids. The proximal tubules also secrete organic acids, bases, and hydrogen ions into the tubular lumen.

tubular cells have an extensive brush border on the luminal (apical) side of the membrane as well as an extensive labyrinth of intercellular and basal channels, all of which together provide an extensive membrane surface area on the luminal and basolateral sides of the epithelium for rapid transport of sodium ions and other substances.

The extensive membrane surface of the epithelial brush border is also loaded with protein carrier molecules that transport a large fraction of the sodium ions across the luminal membrane linked by way of the co-transport mechanism with multiple organic nutrients such as amino acids and glucose. The remainder of the sodium is transported from the tubular lumen into the cell by counter-transport mechanisms, which reabsorb sodium while secreting other substances into the tubular lumen, especially hydrogen ions. As discussed in Chapter 30, the secretion of hydrogen ions into the tubular lumen is an important step in the removal of bicarbonate ions from the tubule (by combining H+ with the HCO3_ to form H2CO3, which then dissociates into H2O and CO2).

Although the sodium-potassium ATPase pump provides the major force for reabsorption of sodium, chloride, and water throughout the proximal tubule, there are some differences in the mechanisms by which sodium and chloride are transported through the luminal side of the early and late portions of the proximal tubular membrane.

In the first half of the proximal tubule, sodium is reabsorbed by co-transport along with glucose, amino acids, and other solutes. But in the second half of the proximal tubule, little glucose and amino acids remain to be reabsorbed. Instead, sodium is now reabsorbed mainly with chloride ions. The second half of the proximal tubule has a relatively high concentration of chloride (around 140 mEq/L) compared with the early

Proximal Tubule Length

% Total proximal tubule length

Figure 27-7

% Total proximal tubule length

Figure 27-7

Changes in concentrations of different substances in tubular fluid along the proximal convoluted tubule relative to the concentrations of these substances in the plasma and in the glomerular filtrate. A value of 1.0 indicates that the concentration of the substance in the tubular fluid is the same as the concentration in the plasma. Values below 1.0 indicate that the substance is reabsorbed more avidly than water, whereas values above 1.0 indicate that the substance is reabsorbed to a lesser extent than water or is secreted into the tubules.

proximal tubule (about 105 mEq/L) because when sodium is reabsorbed, it preferentially carries with it glucose, bicarbonate, and organic ions in the early proximal tubule, leaving behind a solution that has a higher concentration of chloride. In the second half of the proximal tubule, the higher chloride concentration favors the diffusion of this ion from the tubule lumen through the intercellular junctions into the renal interstitial fluid.

Concentrations of Solutes Along the Proximal Tubule. Figure 27-7 summarizes the changes in concentrations of various solutes along the proximal tubule. Although the amount of sodium in the tubular fluid decreases markedly along the proximal tubule, the concentration of sodium (and the total osmolarity) remains relatively constant because water permeability of the proximal tubules is so great that water reabsorption keeps pace with sodium reabsorption. Certain organic solutes, such as glucose, amino acids, and bicarbonate, are much more avidly reabsorbed than water, so that their concentrations decrease markedly along the length of the proximal tubule. Other organic solutes that are less permeant and not actively reabsorbed, such as creati-nine, increase their concentration along the proximal tubule. The total solute concentration, as reflected by osmolarity, remains essentially the same all along the proximal tubule because of the extremely high permeability of this part of the nephron to water.

Secretion of Organic Acids and Bases by the Proximal Tubule.

The proximal tubule is also an important site for secretion of organic acids and bases such as bile salts, oxalate, urate, and catecholamines. Many of these substances are the end products of metabolism and must be rapidly removed from the body. The secretion of these substances into the proximal tubule plus filtration into the proximal tubule by the glomerular capillaries and the almost total lack of reabsorption by the tubules, all combined, contribute to rapid excretion in the urine.

In addition to the waste products of metabolism, the kidneys secrete many potentially harmful drugs or toxins directly through the tubular cells into the tubules and rapidly clear these substances from the blood. In the case of certain drugs, such as penicillin and salicylates, the rapid clearance by the kidneys creates a problem in maintaining a therapeutically effective drug concentration.

Another compound that is rapidly secreted by the proximal tubule is para-aminohippuric acid (PAH). PAH is secreted so rapidly that the average person can clear about 90 per cent of the PAH from the plasma flowing through the kidneys and excrete it in the urine. For this reason, the rate of PAH clearance can be used to estimate the renal plasma flow, as discussed later.

Solute and Water Transport in the Loop of Henle

The loop of Henle consists of three functionally distinct segments: the thin descending segment, the thin ascending segment, and the thick ascending segment. The thin descending and thin ascending segments, as their names imply, have thin epithelial membranes with no brush borders, few mitochondria, and minimal levels of metabolic activity (Figure 27-8).

The descending part of the thin segment is highly permeable to water and moderately permeable to most solutes, including urea and sodium. The function of this nephron segment is mainly to allow simple diffusion of substances through its walls. About 20 per cent of the filtered water is reabsorbed in the loop of Henle, and almost all of this occurs in the thin descending limb. The ascending limb, including both the thin and the thick portions, is virtually impermeable to water, a characteristic that is important for concentrating the urine.

The thick segment of the loop of Henle, which begins about halfway up the ascending limb, has thick epithelial cells that have high metabolic activity and are capable of active reabsorption of sodium, chloride, and potassium (see Figure 27-8). About 25 per cent of the filtered loads of sodium, chloride, and potassium are reabsorbed in the loop of Henle, mostly in the thick ascending limb. Considerable amounts of other ions, such as calcium, bicarbonate, and magnesium, are also reabsorbed in the thick ascending loop of Henle. The thin segment of the ascending limb has a much lower reabsorptive capacity than the thick segment,

Thin descending loop of Henle

Thin descending loop of Henle

Loops Henle Thin Segment Cell

Renal interstitial fluid

Loop Henle Reabsorption And Secretion
Figure 27-8

Cellular ultrastructure and transport characteristics of the thin descending loop of Henle (top) and the thick ascending segment of the loop of Henle (bottom).The descending part of the thin segment of the loop of Henle is highly permeable to water and moderately permeable to most solutes but has few mitochondria and little or no active reabsorption. The thick ascending limb of the loop of Henle reabsorbs about 25 per cent of the filtered loads of sodium, chloride, and potassium, as well as large amounts of calcium, bicarbonate, and magnesium. This segment also secretes hydrogen ions into the tubular lumen.

and the thin descending limb does not reabsorb significant amounts of any of these solutes.

An important component of solute reabsorption in the thick ascending limb is the sodium-potassium ATPase pump in the epithelial cell basolateral membranes. As in the proximal tubule, the reabsorption of other solutes in the thick segment of the ascending loop of Henle is closely linked to the reabsorptive capability of the sodium-potassium ATPase pump, which maintains a low intracellular sodium concentration. The low intracellular sodium concentration in turn provides a favorable gradient for movement of sodium from the tubular fluid into the cell. In the thick ascending loop, movement of sodium across the luminal membrane is mediated primarily by a 1-sodium, 2-chloride, 1-potassium co-transporter (Figure 27-9). This co-transport protein carrier in the luminal membrane uses the potential energy released by downhill diffusion of sodium into the cell to drive the reabsorption of potassium into the cell against a concentration gradient.

Tubular cells

Paracellular diffusion

Tubular lumen (+8 mV)

Nephron Tubular Secretion

Mechanisms of sodium, chloride, and potassium transport in the thick ascending loop of Henle. The sodium-potassium ATPase pump in the basolateral cell membrane maintains a low intracellular sodium concentration and a negative electrical potential in the cell. The 1-sodium, 2-chloride, 1-potassium co-transporter in the luminal membrane transports these three ions from the tubular lumen into the cells, using the potential energy released by diffusion of sodium down an electrochemical gradient into the cells. Sodium is also transported into the tubular cell by sodium-hydrogen counter-transport. The positive charge (+8 mV) of the tubular lumen relative to the interstitial fluid forces cations such as Mg++ and Ca++ to diffuse from the lumen to the interstitial fluid via the paracellular pathway.

Figure 27-9

Mechanisms of sodium, chloride, and potassium transport in the thick ascending loop of Henle. The sodium-potassium ATPase pump in the basolateral cell membrane maintains a low intracellular sodium concentration and a negative electrical potential in the cell. The 1-sodium, 2-chloride, 1-potassium co-transporter in the luminal membrane transports these three ions from the tubular lumen into the cells, using the potential energy released by diffusion of sodium down an electrochemical gradient into the cells. Sodium is also transported into the tubular cell by sodium-hydrogen counter-transport. The positive charge (+8 mV) of the tubular lumen relative to the interstitial fluid forces cations such as Mg++ and Ca++ to diffuse from the lumen to the interstitial fluid via the paracellular pathway.

The thick ascending limb of the loop of Henle is the site of action of the powerful "loop" diuretics furosemide, ethacrynic acid, and bumetanide, all of which inhibit the action of the sodium 2-chloride, potassium co-transporter. These diuretics are discussed in Chapter 31.

There is also significant paracellular reabsorption of cations, such as Mg++, Ca++, Na+, and K+, in the thick ascending limb owing to the slight positive charge of the tubular lumen relative to the interstitial fluid. Although the 1-sodium, 2-chloride, 1-potassium co-transporter moves equal amounts of cations and anions into the cell, there is a slight backleak of potassium ions into the lumen, creating a positive charge of about +8 millivolts in the tubular lumen. This positive charge forces cations such as Mg++ and Ca++ to diffuse from the tubular lumen through the paracellular space and into the interstitial fluid.

The thick ascending limb also has a sodium-hydrogen counter-transport mechanism in its luminal cell membrane that mediates sodium reabsorption and hydrogen secretion in this segment.

The thick segment of the ascending loop of Henle is virtually impermeable to water. Therefore, most of the water delivered to this segment remains in the tubule, despite reabsorption of large amounts of solute. The tubular fluid in the ascending limb becomes very dilute as it flows toward the distal tubule, a feature that is important in allowing the kidneys to dilute or concentrate the urine under different conditions, as we discuss much more fully in Chapter 28.

Distal Tubule

The thick segment of the ascending limb of the loop of Henle empties into the distal tubule. The very first portion of the distal tubule forms part of the juxta-glomerular complex that provides feedback control of GFR and blood flow in this same nephron. The next part of the distal tubule is highly convoluted and has many of the same reabsorptive characteristics of the thick segment of the ascending limb of the loop of Henle. That is, it avidly reabsorbs most of the ions, including sodium, potassium, and chloride, but is virtually impermeable to water and urea. For this reason, it is referred to as the diluting segment because it also dilutes the tubular fluid.

Approximately 5 percent of the filtered load of sodium chloride is reabsorbed in the early distal tubule. The sodium-chloride co-transporter moves sodium chloride from the tubular lumen into the cell, and the sodium-potassium ATPase pump transports sodium out of the cell across the basolateral membrane (Figure 27-10). Chloride diffuses out of the cell into the renal interstitial fluid through chloride channels in the basolateral membrane. The thiazide diuretics, which are widely used to treat disorders such as hypertension and heart failure, inhibit the sodium-chloride co-transporter.

Mechanism of sodium chloride transport in the early distal tubule. Sodium and chloride are transported from the tubular lumen into the cell by a co-transporter that is inhibited by thiazide diuretics. Sodium is pumped out of the cell by sodium-potassium ATPase and chloride diffuses into the interstitial fluid via chloride channels.

Late Distal Tubule and Cortical Collecting Tubule

The second half of the distal tubule and the subsequent cortical collecting tubule have similar functional characteristics. Anatomically, they are composed of two distinct cell types, the principal cells and the intercalated cells (Figure 27-11). The principal cells reab-sorb sodium and water from the lumen and secrete potassium ions into the lumen. The intercalated cells reabsorb potassium ions and secrete hydrogen ions into the tubular lumen.

Principal Cells Reabsorb Sodium and Secrete Potassium.

Sodium reabsorption and potassium secretion by the principal cells depend on the activity of a sodium-potassium ATPase pump in each cell's basolateral membrane (Figure 27-12). This pump maintains a low sodium concentration inside the cell and, therefore, favors sodium diffusion into the cell through special

Collecting Tubule Potassium
Late distal tubule
Early Distal Tubule Concentrations
Figure 27-11

Cellular ultrastructure and transport characteristics of the early distal tubule and the late distal tubule and collecting tubule. The early distal tubule has many of the same characteristics as the thick ascending loop of Henle and reabsorbs sodium, chloride, calcium, and magnesium but is virtually impermeable to water and urea. The late distal tubules and cortical collecting tubules are composed of two distinct cell types, the principal cells and the intercalated cells. The principal cells reabsorb sodium from the lumen and secrete potassium ions into the lumen. The intercalated cells reabsorb potassium and bicarbonate ions from the lumen and secrete hydrogen ions into the lumen. The reabsorption of water from this tubular segment is controlled by the concentration of antidiuretic hormone.

Collecting Tubule Potassium

Mechanism of sodium chloride transport in the early distal tubule. Sodium and chloride are transported from the tubular lumen into the cell by a co-transporter that is inhibited by thiazide diuretics. Sodium is pumped out of the cell by sodium-potassium ATPase and chloride diffuses into the interstitial fluid via chloride channels.

Tubule Sodium Potassium Channel

Figure 27-12

Mechanism of sodium chloride reabsorption and potassium secretion in the late distal tubules and cortical collecting tubules. Sodium enters the cell through special channels and is transported out of the cell by the sodium-potassium ATPase pump. Aldosterone antagonists compete with aldosterone for binding sites in the cell and therefore inhibit the effects of aldosterone to stimulate sodium reabsorption and potassium secretion. Sodium channel blockers directly inhibit the entry of sodium into the sodium channels.

Figure 27-12

Mechanism of sodium chloride reabsorption and potassium secretion in the late distal tubules and cortical collecting tubules. Sodium enters the cell through special channels and is transported out of the cell by the sodium-potassium ATPase pump. Aldosterone antagonists compete with aldosterone for binding sites in the cell and therefore inhibit the effects of aldosterone to stimulate sodium reabsorption and potassium secretion. Sodium channel blockers directly inhibit the entry of sodium into the sodium channels.

channels. The secretion of potassium by these cells from the blood into the tubular lumen involves two steps: (1) Potassium enters the cell because of the sodium-potassium ATPase pump, which maintains a high intracellular potassium concentration, and then (2) once in the cell, potassium diffuses down its concentration gradient across the luminal membrane into the tubular fluid.

The principal cells are the primary sites of action of the potassium-sparing diuretics, including spirono-lactone, eplerenone, amiloride, and triamterene. Aldosterone antagonists compete with aldosterone for receptor sites in the principal cells and therefore inhibit the stimulatory effects of aldosterone on sodium reabsorption and potassium secretion. Sodium channel blockers directly inhibit the entry of sodium into the sodium channels of the luminal membranes and therefore reduce the amount of sodium that can be transported across the basolateral membranes by the sodium-potassium ATPase pump. This, in turn, decreases transport of potassium into the cells and ultimately reduces potassium secretion into the tubular fluid. For this reason the sodium channel blockers as well as the aldosterone antagonists decrease urinary excretion of potassium and act as potassium-sparing diuretics.

Intercalated Cells Avidly Secrete Hydrogen and Reabsorb Bicarbonate and Potassium Ions. Hydrogen ion secretion by the intercalated cells is mediated by a hydrogen-ATPase transport mechanism. Hydrogen is generated in this cell by the action of carbonic anhydrase on water and carbon dioxide to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions. The hydrogen ions are then secreted into the tubular lumen, and for each hydrogen ion secreted, a bicarbonate ion becomes available for reabsorption across the basolateral membrane. A more detailed discussion of this mechanism is presented in Chapter 30. The intercalated cells can also reabsorb potassium ions.

The functional characteristics of the late distal tubule and cortical collecting tubule can be summarized as follows:

1. The tubular membranes of both segments are almost completely impermeable to urea, similar to the diluting segment of the early distal tubule; thus, almost all the urea that enters these segments passes on through and into the collecting duct to be excreted in the urine, although some reabsorption of urea occurs in the medullary collecting ducts.

2. Both the late distal tubule and the cortical collecting tubule segments reabsorb sodium ions, and the rate of reabsorption is controlled by hormones, especially aldosterone. At the same time, these segments secrete potassium ions from the peritubular capillary blood into the tubular lumen, a process that is also controlled by aldosterone and by other factors such as the concentration of potassium ions in the body fluids.

3. The intercalated cells of these nephron segments avidly secrete hydrogen ions by an active hydrogen-ATPase mechanism. This process is different from the secondary active secretion of hydrogen ions by the proximal tubule because it is capable of secreting hydrogen ions against a large concentration gradient, as much as 1000 to 1. This is in contrast to the relatively small gradient (4- to 10-fold) for hydrogen ions that can be achieved by secondary active secretion in the proximal tubule. Thus, the intercalated cells play a key role in acid-base regulation of the body fluids.

4. The permeability of the late distal tubule and cortical collecting duct to water is controlled by the concentration of ADH, which is also called vasopressin. With high levels of ADH, these tubular segments are permeable to water, but in the absence of ADH, they are virtually impermeable to water. This special characteristic provides an important mechanism for controlling the degree of dilution or concentration of the urine.

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Responses

  • macario
    What solutes are transported in the different tubules of the nephron?
    5 years ago
  • Duenna
    How are different solutes reabsorbed in the different sites of the nephron?
    4 years ago
  • grant
    Does water rebsorbed along with sodium and chloride?
    4 years ago
  • Karolina
    Why is sodium and chloride ions almost reabsorbed immediately?
    4 years ago
  • Alyx Thompson
    Where are hydrogen ions reabsorbed?
    3 years ago
  • MAXIMA
    What is labyrinth of intercellular and basal channels?
    3 years ago
  • Duncan
    What percentage of sodium is reabsorbed in the descending loop of henle?
    3 years ago
  • ahti
    How the epithelium of nephron secretes substances into lumen?
    2 years ago
  • Archie
    Which part of the tubules is impermeable in water?
    1 year ago
  • ISENGAR
    Is sodium reclaimed along the nephron?
    10 months ago
  • ishbel graham
    What approximate percentage of reabsorption and secretion occurs in the proximal tubules?
    9 months ago
  • Kara
    Which portions of the nephron reabsorb water in response to ADH concentrations?
    6 months ago
  • amina
    What is secreted and reabsorbed in the parts of a nephron?
    6 months ago
  • yonas osman
    Can a substance be directly secreted into the tubule lumen?
    5 months ago
  • Fiyori
    How much sodium is absorbed at each segment of the nephron?
    4 days ago

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