Active transport through the renal tubular membrane
Active transport can move the solute in the opposite direction of the electrochemical ladder and require the energy generated from the metabolism.
When the dialysis solution enters the tubule, it flows through the sections of the proximal tubule, the Henle loop, the distal tubule, the connecting tubule, and finally the collecting tubule, before urinary excretion. During this process, some substances are reabsorbed back into the bloodstream, while others are excreted from the bloodstream into the lumen.
In the end, urine is formed and all substances in the urine are the synthesis of three basic kidney processes by glomerular filtration, renal tubular secretion and reabsorption:
Urinary excretion = glomerular filtration - tubular reuptake + renal tubular secretion
For many substances, tubular reabsorption plays a much more important role than excretion in determining the rate of final excretion in the urine. However, excretion explains significant amounts of potassium ions, hydrogen ions, and a few other substances that appear in the urine.
Active transport can move the solute in the opposite direction of the electrochemical ladder and require the energy generated from the metabolism. Transport that is directly connected to an energy source, like the hydrolysis of ATP, is called primary active transport. An example of this mechanism is the sodium-potassium-ATPase channel that functions in most parts of the renal tubule. The transport is directly associated with an energy source, eg the ion concentration ladder is referred to as the secondary active transport. Glucose reabsorption by the renal tubules is an example of secondary active transport. Although the solute can be reabsorbed by either active or passive tubular mechanisms, water is always reabsorbed by a passive physical mechanism called osmosis,
The solute can be transported across cell membranes or between cells
Tubular epithelial cells, like other epithelial cells, are connected by a tight junction. The cytoplasm lies behind the ring and separates the tubular epithelial cells. Solutes can be reabsorbed or excreted through the cell through the cellular pathway or through the intercellular space as in the paracellular transport pathway. Sodium is a solute that travels both ways, but most sodium is transported by cell. In some segments of the nephron, especially the proximal tubule, the water is reabsorbed through cell transport, and the water-soluble substances, especially the potassium, magnesium, and chloride ions are dragged along with the absorbed fluid. between cells.
Primary active transport through the renal tubular membrane is bound to the ATP hydrolysis enzyme
A particularly important feature of primary active transport is that it can move the solute in the opposite direction of the electrochemical ladder. The energy for this active transport comes from the hydrolysis of ATP by the enzyme ATPase attached to the cell membrane, which is also part of the transmembrane transport mechanism. The primary active transport in the kidneys includes sodium-KaliATPase, Hydro ATPase, hydro-potassium ATPase, and calcium ATPase. A good example of primary active transport is the sodium ion reabsorption across the proximal tubular membrane, shown in the figure.
Figure. Basic mechanism for the active transport of sodium through tubular epithelial cells. The sodium-potassium pump transports sodium from inside the cell across the basal membrane, creating a low intracellular sodium concentration and a negative intracellular potential. The low intracellular sodium concentration and the negative potential cause sodium ions to diffuse from the lumen into the cell via the brush contour.
In the basal membrane of the tubular epithelium, the membrane has a large amount of sodium-potassium-ATPase pump, which hydrolyzes the ATP and uses energy to transport sodium ions out of the cell into the interstitial space. At the same time, potassium is transported from the interstitial space into the cell. This ion pump works to maintain concentration
The sodium is low and the potassium is high in the cell, and at the same time produces a negative charge of about -70 millivons in the cell.
The active pump pushes sodium through the basal membrane to allow sodium to passively diffuse through the parietal membrane, from the lumen of the renal tubule into the cell, for two reasons: (1) A concentration gadient exists between the sodium concentration in low cell (12 mEq / L) and high concentration of sodium in the tubule lumen (140 mEq / L) cause sodium diffuse into the cell and (2) potential of -70 million in the cell absorbs sodium ions from the tubular lumen enters the cell.
Sodium reabsorption of the sodium-potassium-ATPase channel is present in most components of the renal tubules. In some parts of the nephron, there are also other aids to move large amounts of sodium into cells. At the proximal tubule, the membrane tip surface has brush edges (towards the tube bed) to increase the surface area by about 20 times. There are also sodium ion binding proteins located on the top of the cell, then releasing sodium into the cell, which is a method of diffusion of sodium through the cell membrane. Sodium-carrying proteins are also important in the secondary active transport of other substances, such as glucose and amino acids.
Thus, the process of sodium reabsorption from the lumen into the bloodstream consists of at least 3 steps:
1. Sodium diffuses through the membrane of the tube (also known as the apical membrane) into the cell under the effect of the potential gradient created by the sodium-potassium-ATPase pump located in the cell basal membrane.
2. Sodium is transported through the basilar membrane in the opposite direction of the electrochemical ladder by pumping sodium-potassium-ATPase.
3. Sodium, water, and other solutes are reabsorbed from the interstitial fluid into the parietal capillaries through ultrafiltration, a passive process regulated by differential hydrostatic and colloidal pressure. plasma.
Secondary active reabsorption across the apical membrane
In secondary active transport, two or more solutes interact with a specific membrane protein (a carrier) and are transported together across the cell membrane. When a solute (eg sodium) diffuses in the direction of its potential gradient, the energy released is used to transport the other solute (eg glucose) in the opposite direction of the potential gradient.
Consequently, secondary active transport does not need to be energized directly from ATP or from other phosphate-rich sources. Instead, the energy is released directly from the electrochemical step diffusion of the same carrier.
The figure shows the secondary positive transport of glucose and amino acids at the proximal tubule. In both cases, the brush edge-specific protein combines both sodium ions with an amino acid molecule or 1 molecule of glucose. This transport mechanism eliminates most of the glucose and amino acids in the tubular lumen. Once inside the cell, glucose and amino acids escape through the basal membrane by diffusion, thanks to the high concentrations of glucose and amino acids in the cell that specific transport proteins produce.
Sodium-glucose co-transporters (SGLT2 and SGLT1) lie on the brush edge of the proximal tubule cell and transport glucose into the cytoplasm against the electrochemical ladder, as has been previously discussed.
About 90% of the glucose is reabsorbed by SGLT2 at the proximal tubule end (segment S1), and the remaining 10% is transported by SGLT1 at the proximal tubule. In the basal membrane of the cell, glucose diffuses from the cell into the interstitial space by transporting glucose-GLUT2 channels in the S1 and GLUT1 segments in the posterior portion (segment S3) of the proximal tubule.
Although the electrochemical ladder reverse transport of glucose does not use ATP directly, glucose reabsorption is dependent on the energy dissipated during the primary active transport of the sodium Kali ATPase channel in the basal membrane of the cell.
Figure. Secondary active transport mechanism. The upper cell shows the co-transport of glucose and amino acids along with sodium ions across the apex of the tubular epithelial cell, followed by favourable diffusion across the basal membrane. The lower cell shows counter-transport of hydrogen ions from the inside of the cell through the apical membrane and into the lumen; migration of sodium ions into the cell, following an electrochemical gradient established by the sodium-potassium pump on the basal membrane, providing the energy to transport hydrogen ions from the inside of the cell into the lumen. ATP, adenosine triphosphate; GLUT, glucose transporter; NHE, sodium hydrogen metabolite; SGLT, a sodium-glucose co-transporter.
Through the action of this pump, the electrochemical gradient for the diffusion which is facilitated across the apical membrane is maintained, and it is the diffusion of sodium into the cell that powers the simultaneous transport of glucose across the apical membrane. planing. This process of glucose reabsorption is therefore called "primary active transport" because the glucose is absorbed in the opposite direction of the electrochemical scale, but is secondary to the primary active transport of sodium.
Another important point is that a substance is actively transported when at least one step in the reabsorption process is involved in the primary or secondary active transport, even though the other step in the reabsorption is the absorption. moving. For glucose reabsorption, secondary active transport occurs in the apical membrane, but passively favourable diffusion occurs in the basal membrane, and passive uptake by ultrafiltration occurs in the cell basal membrane. capillaries around the renal tubules.
Secondary active excretion into the renal tubules
Some solutes are excreted into the renal tubules by secondary active transport, often involving a reverse transport of sodium. In reverse transport, the energy released from the forward movement of one substance (eg sodium ions) allows the second substance to move in the opposite direction.
An example of reverse transport, shown in the figure, is the active excretion of hydrogen ions along with sodium reabsorption in the apical membrane of the proximal tubule. In this case, sodium enters the cell with the hydrogen out of the cell by sodium-hydrogen reverse transport. The mediator of this transport is a specific protein (sodium-hydrogen exchange) at the brush edge of the apical membrane.
When sodium is transported into the cell, hydrogen ions exit the cell in the opposite direction into the lumen. Basic principles of primary and secondary active transport.
Hydrophilic - active transport, mechanism of protein reabsorption
Some parts of the renal tubule, especially the proximal tubule, reabsorb large molecules such as proteins by moist cells, an enterocyte. In this process, the protein attaches to the brush edge of the apical membrane, which is recessed into the cell until completely separated, forming a protein-containing bag. Once inside the cell, the protein breaks down into amino acids and is reabsorbed across the basal membrane into the interstitial space. Because the humidifier requires energy, it is considered a form of active transport.
The maximum transport level of the actively reabsorbed substances
The majority of the solutes that are actively reabsorbed and excreted are transported to the limit, called the maximum transport rate. This limit is due to the saturation of the transport system when the amount of substance entering the renal tubule (called the tubular load) exceeds the capacity of the carrier protein and the specific enzyme involved in the transport process.
The coherent tubular cell lucidity system is a prime example. Normally, almost no glucose in the urine because glucose filtered through the glomeruli is reabsorbed in the proximal tubule. However, when the filtration load exceeds the renal tubule's ability to reabsorb glucose, glucose is excreted in the urine.
In the adult population, the average glucose transport maximum is about 375 mg / min, when the glucose filtration load is about 125 mg / min (GFR x plasma glucose = 125 ml / min x 1 mg / ml).
With increased glomerular filtration flow and/or increased plasma glucose concentration, glucose filtration load above 375 mg/min, excess glucose is not reabsorbed and excreted in the urine.
The figure shows the relationship between plasma glucose concentration, glomerular filtration glucose, renal tubular glucose transport threshold, and urine glucose ratio. When the plasma glucose concentration is 100 mg / 100 ml and the filtration capacity is normal (125 mg/min) there is no glucose in the urine. However, when the plasma glucose concentration increases by about 200 mg / 100 ml, the glomerular filtration rate increases to about 200 mg/min, a small amount of glucose begin to appear in the urine. This is called the renal glucose threshold. Note that glucose appears in the urine (excess threshold) that occurs before maximum transport is reached. The reason for this difference between the threshold and maximum transport is that not all nephrons reach maximum glucose transport at once, some begin to excrete glucose before others reach a transport level. max.
Plasma glucose in healthy people is hardly so high that glucose is excreted in the urine, even after meals. However, in diabetes, plasma glucose increases to a high level, causing the filtration load of glucose to exceed the maximum transport level of glucose, leading to the excretion of glucose in the urine. The following are maximum transport rates of some of the important positively resorption important substances.
Solute and maximum transport rate
Glucose 375 mg/min.
Phosphate 0.10 mmol/phút.
Sulfate 0.06 mmol / min.
Amino acids 1.5 mmol/phút.
Urate 15 mg / min.
Lactate 75 mg / min.
Plasma protein 30 mg/min.
The maximum transport rate of actively excreted solutes also positively excreted solutes also exhibit the following maximum transport rates:
Solute and maximum transport rate
Creatinine 16 mg / min.
Para-aminohippuric acid 80 mg / min.
Substances are actively transported but do not represent a maximum transport rate
The reason that actively transported solutes often exhibit transport maximums is that the carrier system becomes saturated as the tube load increases. Some passively reabsorbed substances do not demonstrate maximum transport because their transport rates are determined by other factors, such as (1) the electrochemical gradient for the diffusion of the substance. through the membrane, (2) the membrane permeability to the substance, and (3) the length of time that the liquid containing the substance remains in the tube. This type of transport is known as gradient time transport because the transport rate depends on the electrochemical gradient and the time the substance stays in the tube, and therefore on the flow rate of the tube.
Figure. Relationship between the amount of filtered glucose, the rate of renal tubular glucose reabsorption, and the rate of glucose excretion in the urine. The maximum transport rate is the maximum rate at which glucose can be reabsorbed from the tube. The glucose threshold refers to the amount of filtered glucose at which glucose begins to be excreted in the urine.
Passively transported substances do not exhibit maximum transport and have gradient-time transport characteristics, meaning that the transport speed depends on (1) the electrochemical gradient, (2) permeability. of the membrane to the substance, and (3) the time the liquid containing the substance is in contact with the cell membrane of the tubule.
An example of time gradient transport is sodium reabsorption in the proximal tubule, where the maximum transport yield of the basal membrane sodium-potassium-ATPase pump is often much greater than the net diffusion rate of the basal membrane. Sodium when a significant amount sodium is transported across the intercellular space into the lumen of the renal tubule through the epithelial membrane. The degree of renal leakage of fluid into the interstitial space depends on (1) the permeability of the sealing membrane and (2) the physical forces at the interstitial space, which determine the degree of reabsorption of ultrafiltration from the interstitial fluid into the capillary. paranasal vessels. Therefore, sodium transport in the proximal tubule mainly follows the principle of time-gradient transport rather than the tubular maximum transport.
This means that the greater the sodium concentration in the proximal tubule, the greater the degree of its reabsorption. In addition, as the renal tubular fluid flow rate slows, the percentage of sodium reabsorbed from the proximal tubule increases.
In the distal segments of nephrons, epithelial cells have more sealing membranes and transport less sodium. In these segments, sodium reabsorption exhibits the same maximum transport as other actively transported solutes. Furthermore, maximum transport may be increased by hormones, such as aldosterone.