13.5 Physiology of Urine Formation: Tubular Reabsorption and Secretion

Tubular Reabsorption and Secretion: Membrane Transport Mechanisms

Tubular reabsorption and secretion each involve transport of substances across plasma membranes. The membrane transport mechanisms utilized are simple diffusion, facilitated diffusion, osmosis, primary active transport, and cotransport (secondary active transport) (Table 13.2). Each of these is reviewed below. For a detailed explanation of each, visit Chapter 4.

In simple diffusion, a substance moves from a higher to a lower concentration down its concentration gradient, directly through the lipid bilayer of the plasma membrane. Simple diffusion is a type of passive transport: it requires no cellular energy. Osmosis is the diffusion of water across a semipermable membrane (in living systems, this is the plasma membrane); water moves from an area of lower solute concentration to an area of higher solute concentration, in other words from a more dilute solution to a less dilute solution.

Facilitated diffusion is similar to simple diffusion in that the substance moves down its concentration gradient. The difference is that facilitated diffusion requires specific membrane carrier proteins or protein channels for movement. For example, the Na+ and K+ leakage channels found in plasma membranes carry out facilitated diffusion: Na+ and K+ are moving down their gradients through the channels. Facilitated diffusion is passive; it requires no cellular energy.

Active transport mechanisms move substances across the plasma membrane against their gradients: from lower to higher concentration. Active transport requires energy. Primary active transport proteins (pumps) directly use the energy stored in the phosphate bonds in ATP: primary active transport proteins catalyze the hydrolysis of ATP to ADP and phosphate. The energy released in this reaction is used my primary active transport pumps to move substances against their gradients. An example of a primary active transport protein is the Na⁺/K⁺ pump (Na+/K+ ATPase). Secondary active transport, also called cotransport, uses energy stored in ion gradients to move substances against their gradients across the membrane. Cotransport always involves the movement of one substance (usually an ion) down its gradient and another substance against its gradient: the movement of the ion down its gradient releases energy that is used to move the other substance against its gradient. Recall from chapter 4 that a symport is a cotransporter that moves substances in the same direction across the membrane, while an antiport moves two substances in opposite directions across the membrane.

In addition to moving across the plasma membrane (the transcellular route), some substances move in between cells as they are reabsorbed. This route of movement is called the paracellular route (Figure 13.5.1). Figure 13.5.1 also reviews the polarity, or sidedness, found all in epithelial cells: epithelia possess an apical and a basolateral (basal) side. Regarding the nephron tubules, the apical side is the side facing the lumen of the tubule, and the basolateral (basal) side is the side facing the interstitial fluid and capillary bed.

Table 13.5.1 summarizes the mechanisms by which substances are reabsorbed and secreted in different portions of the nephron.

Tubular Reabsorption

As previously mentioned, up to 180 L of filtrate is formed per day by the nephrons, and approximately 99% of that filtrate is reabsorbed, resulting in about 1 to 2 L urine formed/day. Reabsorption is essential to reclaim substances from the filtrate that the body needs and to prevent their excretion.

Various portions of the nephron differ in their capacity to reabsorb water and specific solutes (Table 13.5.1 and Figure 13.5.2).

Reabsorption in the Proximal Convoluted Tubule

While reabsorption occurs throughout the nephron, the majority of reabsorption occurs in the PCT. Table 13.5.2 highlights the main substances reabsorbed here.

Table 13.5.2. Reabsorption of Major Solutes by the PCT 

Substance Reabsorbed (Amount Reabsorbed from Filtrate)	Mechanism
Na+ (65%)	primary active transport via Na+/K+ ATPases on basolateral side; cotransport on apical side
Nutrients (glucose, amino acids, vitamins) (100%)	Cotransport with Na+
Cl– (50%) K+ (65%) Ca++ (60% to 70%) Mg++ (variable)	passive; paracellular route
Water (65%)	osmosis; driven by solute reabsorption (obligatory water reabsorption)
lipid soluble solutes (variable)	diffusion driven by concentration gradient created by water reabsorption
HCO3– (80% to 90%)	cotransport with Na+; coupled with H+ secretion
Urea (50%)	passive; mainly paracellular route

About 65% of the Na⁺ entering the nephron is reabsorbed in the PCT and returned to the circulation. Na⁺ is reabsorbed by the PCT via a variety of transport mechanisms, including active transport via activity of Na⁺/K⁺ ATPases on the basolateral side (Figure 13.5.3). The activity of the Na+/K+ pumps drives the reabsorption of many other substances by the PCT. The Na+/K+ pumps create concentration gradients that drive:

1. reabsorption of 100% of amino acids and glucose in the filtrate via cotransport with Na⁺
2. reabsorption of more Na+ via a Na+/H+ antiport
3. reabsorption of 65% of water in the filtrate via osmosis through aquaporins; this is obligatory water reabsorption, water reabsorption that occurs due to solute reabsorption: water is “obliged” to follow the solutes regardless of the body’s hydration state. This water movement out of the filtrate increases the concentration of solutes still in the filtrate, which then leads to their passive reabsorption. This includes
4. reabsorption of ions such as Cl^–, K⁺, Mg⁺⁺, and Ca⁺⁺ mainly via paracellular route
5. reabsorption of 80% to 90% of HCO₃^– in the filtrate via cotransport with Na+*
6. reabsorption of lipid-soluble substances by the transcellular route
7. reabsorption of urea via the paracellular route**

* Bicarbonate reabsorption is coupled to H+ secretion and is extremely important in maintaining acid-base balance in the body. This is discussed in detail in Chapter 14.

** Although urea is a nitrogenous waste, 50% of filtrate urea is reabsorbed by the PCT. Urea will be discussed in a later section of this chapter.

Reabsorption in the Loop of Henle

The loops of Henle 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 limbs of the loop differ in their permeability to salt and to water, as discussed next. Solutes and water reabsorbed from the filtrate in the loop of Henle are returned to the circulation by way of the peritubular capillaries (cortical nephrons) or vasa recta (juxtamedullary nephrons.)

Descending Limb of the Loop of Henle

About 15% of the water in the filtrate is reabsorbed by the descending limb. Virtually no solutes are reabsorbed here. Plasma membranes in the descending limb have permanent aquaporins that allow obligatory water reabsorption out of the descending limb into the surrounding interstitial fluid. The interstitial fluid osmolarity in the kidney increases in concentration from the cortex to the medulla (Figure 13.5.5.) This vertical osmotic gradient in the interstitium is what causes water to move passively out of the descending limb. (It then enters the vasa recta).

As water is reabsorbed from the filtrate, filtrate osmolarity increases from about 300 mOsm to about 1200 mOsm at the hairpin turn of the longest loops of Henle.

About 80% of the solutes that were filtered in the glomerulus have now been recovered along with a majority of the water in the filtrate. As the filtrate enters the ascending loop, the permeability of the cells of the loop changes significantly.

Ascending Limb of the Loop of Henle

The ascending limb is not permeable to water; no water reabsorption occurs here. As seen in figure 13.5.6, NaCl is reabsorbed here. It is important to note that other solutes are reabsorbed by the ascending limb as well, but by convention many texts just show NaCl for clarity. Solute reabsorption occurs via active transport processes. The main transporter is a Na+-K+-2Cl cotransporter in the apical membrane, often abbreviated NKCC2. This symport is essential for reabsorption Na+, Cl-, and K+ from the filtrate. The reabsorption of of solutes, but not water, results in a filtrate that is relatively dilute (about 100 Osm) by the time is reaches the DCT.

Image Descriptions

Figure 13.5.1. This diagram illustrates the cellular anatomy and transport mechanisms of a nephron tubule. The image shows a cross-sectional view of tubular epithelial cells with distinct membrane regions. The yellow area on the left represents the lumen of the tubule containing the filtrate, while the red cylinder on the right represents the peritubular capillary. The epithelial cells feature an apical membrane facing the tubular lumen, characterized by a brush border with microvilli and light junction connections between cells. The basolateral membrane faces the interstitial space and capillary. Various transport proteins are depicted as curved structures embedded in both membranes, showing the movement of substances between the tubular lumen and blood. Blue arrows indicate the direction of transport from the tubule toward the peritubular capillary. The diagram also labels the transcellular route (transport through cells) and paracellular route (transport between cells through tight junctions). The interstitial space is shown in light blue between the basolateral membrane and the capillary. This illustration demonstrates how the nephron reabsorbs filtered substances from the tubular fluid back into the bloodstream. [Return to Figure 13.5.1]

Figure 13.5.2. This diagram illustrates the selective reabsorption and secretion processes occurring throughout the nephron tubule. The image shows the complete nephron structure, starting with the glomerulus and Bowman’s capsule at the top left (shown in darker brown/red), continuing through the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct. Black arrows indicate the direction of substance movement into or out of the tubule at different segments. At the proximal tubule, a large purple box shows reabsorbed substances including glucose, amino acids, protein, vitamins, lactate, urea, uric acid, along with ions Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, and H2O. A tan box shows secreted substances including urea, uric acid, creatinine, some drugs, H+, and NH4+. Throughout the tubule’s length, additional boxes indicate reabsorption and secretion of Na+, Cl-, HCO3-, H2O, K+, H+, NH4+, and urea at various segments. The final collecting duct shows H2O and urea reabsorption. This comprehensive diagram demonstrates how the nephron processes filtrate through selective reabsorption of needed substances and secretion of waste products to form urine. [Return to Figure 13.5.2]

Figure 13.5.3. This diagram illustrates the mechanism of water reabsorption across tubular epithelial cells in the nephron. The image shows a cross-sectional view with the tubular lumen on the left (yellow), tubular cells in the center (green), the interstitial space (cyan/light blue), and a capillary on the right (red). Water molecules (H2O) move from the tubular lumen through the apical membrane into the tubular cells, then across the basolateral membrane into the interstitial space, and finally into the capillary. Purple circles with arrows represent aquaporin water channels embedded in both the apical and basolateral membranes, facilitating the passive transport of water. White arrows indicate the direction of water movement through these channels. Additional transport mechanisms are shown with symbols: Na+ (sodium), K+ (potassium), and Cl- (chloride) ions are depicted moving across membranes via various transporters (shown as different colored circles), creating osmotic gradients that drive water reabsorption. The diagram demonstrates how water follows solute reabsorption through both transcellular pathways (via aquaporins through cells) and potentially paracellular pathways (between cells). [Return to Figure 13.5.3]

Figure 13.5.4. This three-panel diagram illustrates the concept of transport maximum (Tm) for renal tubular reabsorption of substances, specifically showing sodium (Na+) and potassium (K+) transport. Each panel shows a simplified nephron tubule segment with the tubular lumen on the left and blood capillary on the right. Red circles represent one substance (likely sodium) and blue star-shaped symbols represent another substance (likely potassium or a transport protein). The top panel labeled “below the Transport Maximum” shows all red circles being reabsorbed from the tubular lumen into the blood vessel, with none appearing in the final urine (indicated by the downward arrow on the right). The middle panel labeled “at the Transport Maximum” shows the carriers becoming saturated, with most but not all red circles being reabsorbed. The bottom panel labeled “above the Transport Maximum” demonstrates that when the filtered load exceeds the transport capacity, excess red circles remain in the tubular fluid and appear in the urine, as the limited number of blue transport proteins cannot reabsorb all the filtered substance. Black arrows on the right indicate the direction of urine flow. This diagram effectively demonstrates how tubular transport mechanisms have a finite capacity, beyond which substances will be excreted in urine. [Return to Figure 13.5.4]

Figure 13.5.5. This diagram illustrates the countercurrent multiplier mechanism in the loop of Henle, showing how the kidney generates and maintains a medullary osmotic gradient. The image depicts the descending and ascending limbs of the loop of Henle, with the cortex at the top (shown in red) and the pelvis at the bottom (shown in yellow). Osmolarity values are labeled along both limbs, starting at 300 mOsm at the cortex and progressively increasing to 1200 mOsm at the bottom of the loop near the pelvis, then decreasing back to 100 mOsm as fluid ascends. The descending limb (left side) is permeable to water (H2O) as indicated by outward arrows, causing the tubular fluid to become progressively more concentrated as it descends. The ascending limb (right side) shows active transport of sodium and chloride (Na+ and Cl-) out of the tubule, as indicated by arrows and symbols, while being impermeable to water. Blue arrows within the tubule indicate the direction of fluid flow down the descending limb and up the ascending limb. A vertical osmolarity scale on the right shows the gradient from cortex to medulla, with a large red arrow indicating increasing osmolarity toward the pelvis. The interstitial fluid osmolarity values (300, 400, 600, 800, 1000, 1200 mOsm) are shown in the space between the limbs, demonstrating the hyperosmotic medullary interstitium. This countercurrent multiplication system enables the kidney to produce concentrated urine by establishing and maintaining the osmotic gradient necessary for water reabsorption in the collecting duct. [Return to Figure 13.5.5]

Figure 13.5.6. This diagram illustrates the mechanism of water reabsorption regulation in the collecting tubule through aquaporin channels. The image shows a cross-sectional view of a collecting tubule cell with the lumen on the left (pale yellow), the cell interior in the middle (tan/beige), and the bloodstream/plasma on the right (red). Blue arrows labeled H2O indicate water movement from the tubular lumen toward the bloodstream. Pink/magenta circles represent aquaporin-containing storage vesicles within the cytoplasm of the collecting tubule cell. The apical membrane (facing the lumen) contains aquaporin pores that allow water to enter the cell. Text labels indicate “Aquaporin storage vesicle” at the top, “Lumen of collecting tubule” on the left, “Collecting tubule cell” in the center, “Aquaporin” marking the channel proteins, “Bloodstream” and “Plasma” on the right side, and “Interstitial fluid” at the bottom right. A key annotation at the bottom states “Aquaporin pores are inserted into cell membrane, increasing flow of H2O out of tubule.” This process is regulated by antidiuretic hormone (ADH), which triggers the insertion of aquaporin-2 channels from storage vesicles into the apical membrane, thereby increasing water permeability and allowing more water to be reabsorbed from the collecting tubule into the bloodstream, resulting in more concentrated urine. [Return to Figure 13.5.6]

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