6132 0
During CF, more than 100 mg of glucose enters the nephron lumen every minute, but it is completely absorbed by the cells of the proximal tubule, so glucose is usually not detected in the urine, and its daily excretion does not exceed 130 mg. Reabsorption of glucose into the blood occurs against a high concentration gradient, as no glucose is ultimately left in the tubular fluid.
The process of glucose transport is categorized as secondary active. This is due to the fact that the transfer of glucose from the lumen of the tubule through the brush border membrane occurs with the help of a carrier that requires the mandatory presence of a sodium ion. The brush border membrane does not actively transport either glucose or sodium, which is necessary for glucose reabsorption. Cellular energy for this process is created during the operation of the sodium pump, which removes sodium from the cell and is localized in the plasma membranes of the lateral and basal parts of the cell, that is, facing the intercellular fluid and blood capillaries.
As a result of the active transport of sodium from the cell, the sodium concentration in its cytoplasm decreases. This serves as a prerequisite for the passive, gradient entry of sodium into the cell through the brush border membrane. The carrier can transport glucose from the tubular fluid into the cell only when combined with glucose and sodium, which allows it to cross the membrane, and from the inside of the cell, glucose and sodium are released into the cytoplasm.
Thus, the sodium pump of the basolateral membranes serves as an energy source. It is the transport of sodium that consumes the energy of TF, which is used for the simultaneous conjugated transfer of glucose into the cell. Thus, the primary-active transfer of sodium provides the secondary-active coupled transport of glucose into the cell. This glucose reabsorption system is localized only in the brush border membrane, that is, in that part of the plasma membrane of the cell that faces the tubule lumen. There is no such mechanism of glucose transfer in the basal and lateral plasma membranes. The glucose entering the cell accumulates in the transport fund, where its concentration becomes higher than in the extracellular fluid. The cell membrane in the basal part has a low permeability to glucose; to ensure the reabsorption of sugar, its transfer from the cell is determined by special carriers that transport glucose into the extracellular fluid along a concentration gradient and without expending the energy of cellular respiration.
In the clinic, the ability of the kidney to reabsorb glucose is one of the important indicators of the functional state of the cells of the proximal tubule and the number of effectively functioning tubules. Features of glucose reabsorption are closely related to the mechanisms of glucosuria. From the above data on the essence of the process of glucose reabsorption, it follows that the maximum number of glucose molecules reabsorbed from the tubular fluid into the blood depends on the number of glucose carriers and the rate of their turnover in the membrane. Obviously, all the filtered glucose is reabsorbed until the number of carriers and the speed of their movement in the membrane ensure the transfer of all glucose molecules that have entered the lumen of the tubule.
Excretion of glucose in the urine begins only when its concentration in plasma increases so significantly that the amount of filtered glucose exceeds the reabsorption capacity of the tubules (Fig. 1). The amount of glucose reabsorbed at the maximum load of all membrane carriers involved in its transport serves under standard research conditions as an important functional indicator of the activity of the proximal tubule. The maximum glucose transport (TmG) in men is 375 ± 79.7, and in women - 303 ± 55.3 mg / min per 1.73 m² of body surface.
Rice. 1. The relationship between the concentration of glucose in blood plasma, its filtration, reabsorption and excretion [Valint R., 1969]. On the y-axis on the left - the amount of filtered, reabsorbed and extractable glucose, on the right - the clearance of glucose; on the abscissa axis - the concentration of glucose in blood plasma.
Studies with the introduction of glucose into the blood and the measurement of TmG in the clinic give an idea of the balance between CF and reabsorption in the proximal tubule of each of the nephrons. When a hypertonic glucose solution is infused into the blood, hyperglycemia does not cause glucosuria until the limit of its ability to reabsorb glucose is reached in any of the tubules. If in all nephrons there is a correspondence between the volume of filtered fluid (and thus glucose) and the ability to reabsorb it, then TmG will be reached simultaneously in all nephrons, and with a further increase in the concentration of glucose in the blood, glucosuria occurs.
If in two nephrons the filtration is the same, but the state of the tubules and the ability to reabsorb glucose are different, then TmG will not be reached simultaneously. The greater the differences between individual nephrons, the more heterogeneous the populations of nephrons, the less correspondence between the level of glucose CF and its reabsorption, the greater the discrepancy between nephrons in the time of onset of TmG with a gradual increase in plasma glucose concentration. In some nephrons, TmG is achieved at a plasma glucose concentration of 11.1 mmol/l, in others - 22.2 mmol/l. This phenomenon is called splitting of the nephron titration curve with glucose; it depends on the morphological and functional heterogeneity of nephron populations in the kidney.
TmG increases with acromegaly, after the administration of thyroxin, and its decrease is characteristic of Addison's disease, serum sensitization, and an increase in the concentration of 1-lysine and 1-alanine in the filtrate. In the course of the disease, the ratio between the volume of CP and tubular reabsorption of glucose may change. In patients with diabetes mellitus, glucosuria may decrease in the course of the disease, despite the constant high level glucose and plasma, which is due to the deposition of protein-mucopolysaccharide complexes in the glomerular capillaries with the formation of iptercapillary glomerulosclerosis in elderly people with a long course of diabetes. This causes a decrease in CF in individual nephrons, reduces the loading of the tubules with glucose, and they have time to reabsorb the filtered glucose, which leads to a decrease in glucosuria.
Clinical Nephrology
ed. EAT. Tareeva
Details
Reabsorption is the transport of substances from the lumen of the renal tubules into the blood flowing through the peritubular capillaries. Reabsorbed 65% of primary urine volume(about 120 l / day. It was 170 l, 1.5 was allocated): water, mineral salts, all the necessary organic components (glucose, amino acids). Transport passive(osmosis, diffusion along an electrochemical gradient) and active(primary active and secondary active with the participation of protein carrier molecules). Transport systems are the same as in the small intestine.
Threshold substances - usually completely reabsorbed(glucose, amino acids) and are excreted in the urine only if their concentration in the blood plasma exceeds a threshold value (the so-called "elimination threshold"). For glucose, the elimination threshold is 10 mmol/l (at a normal blood glucose concentration of 4.4-6.6 mmol/l).
Non-threshold substances - always excreted regardless of their concentration in the blood plasma. They are not reabsorbed or only partially reabsorbed, such as urea and other metabolites.
The mechanism of operation of various sections of the renal filter.
1. in the proximal tubule the process of concentrating the glomerular filtrate originates, and the most important point here is the active absorption of salts. With the help of active transport, about 67% Na + is reabsorbed from this part of the tubule. An almost proportional amount of water and some other solutes, such as chloride ions, follow the sodium ions passively. Thus, before the filtrate reaches the loop of Henle, about 75% of the substances are reabsorbed from it. As a result, the tubular fluid becomes isosmotic with respect to blood plasma and tissue fluids.
The proximal tubule is ideally suited for intensive reabsorption of salt and water. Numerous microvilli of the epithelium form the so-called brush border covering the inner surface of the lumen of the renal tubule. With such an arrangement of the absorbent surface, the area of the cell membrane is extremely increased and, as a result, the diffusion of salt and water from the lumen of the tubule into the epithelial cells is facilitated.
2. Descending limb of the loop of Henle and part of the ascending limb located in the inner layer medulla, consist of very thin cells that do not have a brush border, and the number of mitochondria is small. The morphology of thin sections of the nephron indicates the absence of an active transfer of dissolved substances through the tubule wall. In this area of the nephron, NaCl penetrates very poorly through the wall of the tubule, urea is somewhat better, and water passes without difficulty.
3. Wall of the thin portion of the ascending limb of the loop of Henle also inactive with respect to salt transport. Nevertheless, it has a high permeability to Na+ and Cl-, but it is slightly permeable to urea and almost impermeable to water.
4. Thick portion of the ascending limb of the loop of Henle, located in the renal medulla, differs from the rest of the specified loop. It carries out an active transfer of Na + and Cl - from the lumen of the loop into the interstitial space. This section of the nephron, together with the rest of the ascending knee, is extremely little permeable to water. Due to NaCl reabsorption, fluid enters the distal tubule somewhat hypoosmotic compared to tissue fluid.
5. Movement of water through the wall of the distal tubule- the process is complex. The distal tubule is of particular importance for the transport of K+, H+ and NH3 from the tissue fluid into the lumen of the nephron and the transport of Na+, Cl- and H2O from the lumen of the nephron into the tissue fluid. Since the salts are actively "pumped out" from the lumen of the tubule, water follows them passively.
6. collecting duct permeable to water, allowing it to pass from dilute urine into the more concentrated tissue fluid of the renal medulla. This is the final stage in the formation of hyperosmotic urine. Reabsorption of NaCl also occurs in the duct, but due to the active transfer of Na+ through the wall. For salts, the collecting duct is impermeable; for water, its permeability varies. An important feature of the distal portion of the collecting duct, located in the inner medulla of the kidneys, is its high permeability to urea.
Mechanism of glucose reabsorption.
Proximal(1/3) glucose reabsorption is carried out with the help of special carriers of the brush border of the apical membrane of epithelial cells. These carriers transport glucose only if they both bind and transport sodium. Passive movement of sodium along the concentration gradient into cells leads to transport across the membrane and a carrier with glucose.
To implement this process, a low sodium concentration in the epithelial cell is required, which creates a concentration gradient between the external and intracellular environment, which is ensured by energy-dependent work. basement membrane sodium-potassium pump.
This type of transport is called secondary active, or symport, i.e., joint passive transport of one substance (glucose) due to the active transport of another (sodium) using one carrier. With an excess of glucose in the primary urine, a complete loading of all carrier molecules can occur and glucose can no longer be absorbed into the blood.
This situation is characterized by maximum tubular transport of matter» (Tm glucose), which reflects the maximum load of tubular transporters at a certain concentration of the substance in the primary urine and, accordingly, in the blood. This value ranges from 303 mg / min in women to 375 mg / min in men. The value of the maximum tubular transport corresponds to the concept of "renal excretion threshold".
Renal elimination threshold call that the concentration of a substance in the blood and, accordingly, in the primary urine, at which it can no longer be completely reabsorbed in the tubules and appears in the final urine. Such substances for which the elimination threshold can be found, i.e., reabsorbed completely at low concentrations in the blood, and not completely at elevated concentrations, are called threshold. An example is glucose, which is completely absorbed from primary urine at plasma concentrations below 10 mmol/l, but appears in the final urine, i.e., is not completely reabsorbed, when its content in blood plasma is above 10 mmol/l. Consequently, for glucose, the elimination threshold is 10 mmol/l.
Mechanisms of secretion in the renal filter.
Secretion is the transport of substances from the blood flowing through the peritubular capillaries into the lumen of the renal tubules. Transport is passive and active. H+, K+ ions, ammonia, organic acids and bases are secreted (for example, foreign substances, in particular, medications: penicillin, etc.). The secretion of organic acids and bases occurs through a secondary active sodium-dependent mechanism.
secretion of potassium ions.
Most of the easily filtered potassium ions in the glomerulus are usually reabsorbed from the filtrate in the proximal tubules and loops of Henle. The rate of active reabsorption in the tubule and loop does not decrease even when the concentration of K+ in the blood and filtrate increases strongly in response to excess consumption of this ion by the body.
However, the distal tubules and collecting ducts are capable of not only reabsorbing but also secreting potassium ions. By secreting potassium, these structures tend to achieve ion homeostasis in the event of an unusually large amount of this metal entering the body. K+ transport seems to depend on its entry into the tubular cells from the tissue fluid, due to the activity of the usual Nar+ - Ka+ pump, with the leakage of K+ from the cytoplasm into the tubular fluid. Potassium can simply diffuse along the electrochemical gradient from the cells of the renal tubules into the lumen, because the tubular fluid is electronegative with respect to the cytoplasm. The secretion of K+ through these mechanisms is stimulated by the adrenocortical hormone aldosterone, which is released in response to an increase in the content of K+ in the blood plasma.
2 stage urine formation is reabsorption - reabsorption of water and substances dissolved in it. This has been accurately proven in direct experiments with the analysis of urine obtained by micropuncture from various parts of the nephron.
Unlike the formation of primary urine, which is the result of physicochemical filtration processes, reabsorption is largely carried out due to the biochemical processes of the cells of the nephron tubules, the energy for which is drawn from the breakdown of macroergs. This is confirmed by the fact that after poisoning with substances that block tissue respiration (cyanides), sodium reabsorption sharply worsens, and blockade of phosphorylation by monoiodoacetone sharply inhibits glucose reabsorption. Reabsorption also deteriorates with a decrease in metabolism in the body. For example, when the body is cooled in the cold, diuresis also increases.
As well as passive transport processes (diffusion, osmotic forces) in reabsorption, pinocytosis, electrostatic interactions between differently charged ions, etc. play an important role. There are also 2 types active transport:
primary active transport is carried out against the electrochemical gradient and at the same time transport occurs due to the energy of ATP,
secondary active transport is carried out against the concentration gradient and the energy of the cell is not wasted. With the help of this mechanism, glucose, amino acids are reabsorbed. With this type of transport, organic matter enters the cell of the proximal tubule with the help of a carrier, which must necessarily attach a sodium ion. This complex (carrier + organic matter + sodium ion) moves in the brush border membrane; this complex enters the cell due to the difference in Na + concentrations between the tubule lumen and the cytoplasm; there are more sodium ions in the tubule than in the cytoplasm. Inside the cell, the complex dissociates and Na + ions are removed from the cell due to the Na-K pump.
Reabsorption is carried out in all parts of the nephron, with the exception of the Shumlyansky-Bowman capsule. However, the nature of reabsorption and the intensity in various departments nephron is not the same. In the proximal departments of the nephron, reabsorption is very intensive and depends little on the water-salt metabolism in the body (mandatory, obligate). In the distal departments of the nephron reabsorption is very variable. It is called facultative reabsorption. It is reabsorption in the distal tubules and collecting ducts, to a greater extent than in the proximal section, that determines the function of the kidney as a homeostatic organ that regulates the constancy of osmotic pressure, pH, isotonicity, and blood volume.
Reabsorption in various parts of the nephron
Reabsorption of the ultrafiltrate occurs in the cuboidal epithelium of the proximal tubule. Microvilli are of great importance here. In this section, glucose, amino acids, proteins, vitamins, microelements, a significant amount of Na +, Ca +, bicarbonates, phosphates, Cl -, K + and H 2 O are completely reabsorbed. In the subsequent sections of the nephrons, only ions and H 2 O are absorbed.
The mechanism of absorption of these substances is not the same. The most significant in terms of volume and energy costs is the reabsorption of Na +. It is provided by both passive and active mechanisms and occurs in all parts of the tubules.
Active reabsorption of Na causes a passive release of Cl - ions from the tubules - which follow Na + due to electrostatic interaction: positive ions carry along negatively charged Cl - and other anions.
About 65-70% of water is reabsorbed in the proximal tubules. This process is carried out due to the difference in osmotic pressure - passively. The transition of water from the primary urine equalizes the osmotic pressure in the proximal tubules to its level in the tissue fluid. 60-70% of calcium and magnesium are also reabsorbed from the filtrate. Their further reabsorption continues in the loop of Henley and the distal tubules, and only about 1% of the filtered calcium and 5-10% of magnesium are excreted in the urine. Reabsorption of calcium and, to a lesser extent, magnesium is regulated by parathyroid hormone. Parathyroid hormone increases the reabsorption of calcium and magnesium and reduces the reabsorption of phosphorus. Calcitonin has the opposite effect.
Thus, all proteins, all glucose, 100% amino acids, 70-80% water, α, Cl, Mg, Ca are reabsorbed in the proximal convoluted tubule. In the loop of Henley, due to the selective permeability of its departments for sodium and water, an additional 5% of the ultrafiltrate is reabsorbed, and 15% of the primary urine volume enters the distal part of the nephron, which is actively processed in the convoluted tubules and collecting ducts. The volume of the final urine is always determined by the water and salt balance of the body and can range from 25 liters per day (17 ml/min) to 300 ml (0.2 ml/min).
Reabsorption in the distal parts of the nephron and collecting ducts ensures the return to the blood of an ideal osmotic and saline fluid, maintaining a constant osmotic pressure, pH, water balance and stability of ion concentration.
The content of many substances in the final urine is many times higher than in plasma and primary urine; passing through the tubules of the nephron, the primary urine is concentrated. The ratio of the concentration of a substance in the final urine to the concentration in plasma is called concentration index. This index characterizes the processes that occur in the system of nephron tubules.
Reabsorption of glucose
The concentration of glucose in the ultrafiltrate is the same as in plasma, but in the proximal nephron it is almost completely reabsorbed. Under normal conditions, no more than 130 mg is excreted in the urine per day. The reabsorption of glucose occurs against a high concentration gradient, i.e. Glucose reabsorption occurs actively, and it is transferred using the mechanism of secondary active transport. The apical membrane of the cell, i.e. the membrane facing the lumen of the tubule allows glucose to pass in only one direction - into the cell, and does not pass back into the lumen of the tubule.
The apical membrane of the proximal tubule cell has a dedicated glucose transporter, but glucose must be converted to glu-6 phosphate before it can interact with the transporter. The membrane contains the enzyme glucokinase, which provides phosphorylation of glucose. Glu-6-phosphate binds to the apical membrane transporter along with sodium.
This complex due to the difference in sodium concentration ( more sodium in the lumen of the tubule than in the cytoplasm) moves in the brush border membrane and enters the cell. In the cell, this complex dissociates. The carrier returns for new portions of glucose, and glu-6-phosphate and sodium remain in the cytoplasm. Glu-6-phosphate is broken down by the enzyme glu-6-phosphatase into glucose and a phosphate group. The phosphate group is used to convert ADP to ATP. Glucose travels to the basement membrane, where it combines with another carrier that transports it across the membrane into the blood. Transport across the cell basement membrane is facilitated by diffusion and does not require the presence of sodium.
The reabsorption of glucose is dependent on its concentration in the blood. Glucose is completely absorbed if its concentration in the blood does not exceed 7-9 mmol / l, normally it is from 4.4 to 6.6 mmol / l. If the glucose content is higher, then part of it is not reabsorbed and is excreted in the final urine - glucosuria is observed.
On this basis, we introduce the concept about the threshold excretion. Elimination threshold(reabsorption threshold) is the concentration of a substance in the blood at which it cannot be completely reabsorbed and enters the final urine . For glucose, this is more than 9 mmol / l, because. at the same time, the power of the carrier systems is insufficient and sugar enters the urine. In healthy people, this can be observed after the intake of large amounts of it (alimentary (food) glucosuria).
Reabsorption of amino acids
Amino acids are also completely reabsorbed by the cells of the proximal tubule. There are several specific reabsorption systems for neutral, dibasic, dicarboxylic amino acids and imino acids.
Each of these systems provides for the reabsorption of several amino acids of the same group:
1 group - glycine, proline, hydroxyproline, alanine, glutamic acid, creatine;
group 2 - dibasic - lysine, arginine, ornithine, histidine, cystine;
Group 3 - leucine, isoleucine.
Group 4 - Organic imino acids containing a divalent imino group (= NH) in the molecule, heterocyclic imino acids proline and hydroxyproline are part of proteins and are usually considered as amino acids.
Within each system there is a competitive relationship between the transfer of individual amino acids included in this group. Therefore, when there is a lot of one amino acid in the blood, the carrier does not have time to transport all the amino acids of this series - they are excreted in the urine. The transport of amino acids occurs in the same way as glucose, i.e. by the mechanism of secondary active transport.
Protein reabsorption
During the day, 30-50 g of protein enters the filtrate. Almost all of the protein is completely reabsorbed in the tubules of the proximal nephron, and in a healthy person only traces of it are in the urine. Proteins, unlike other substances, are reabsorbed into cells by pinocytosis. (Molecules of the filtered protein are adsorbed on the surface membrane of the cell, eventually forming a pinocytic vacuole. These vacuoles fuse with the lysosome, where, under the influence of proteolytic enzymes, proteins are cleaved and their fragments are transferred into the blood through the basal cytoplasmic membrane). With kidney disease, the amount of protein in the urine increases - proteinuria. It can be associated either with a violation of reabsorption, or with an increase in protein filtration. May occur after exercise.
Metabolic products excreted from the body, harmful to the body, are not actively reabsorbed. Those compounds that are not able to penetrate the cell by diffusion do not return to the blood at all and are excreted in the urine in the most concentrated form. These are sulfates and creatinine, their concentration in the final urine is 90-100 times higher than in plasma - this is non-threshold substances. end products of nitrogen metabolism (urea and uric acid) can diffuse into the tubular epithelium, so they are partially reabsorbed, and their concentration index is lower than sulfate and creatinine.
From the proximal convoluted tubule, isotonic urine enters the loop of Henle. Approximately 20-30% of the filtrate enters here. It is known that the loop of Henle, distal convoluted tubules and collecting ducts are based on the mechanism countercurrent-multiplier tubular system.
Urine moves in these tubules in opposite directions (why the system was called countercurrent), and the processes of transport of substances in one knee of the system are enhanced (“multiplied”) due to the activity of the other knee.
The principle of the countercurrent system is widespread in nature and technology. This is a technical term that defines the movement of two flows of liquid or gases in opposite directions, creating favorable conditions for the exchange between them. For example, in the limbs of arctic animals, arterial and venous vessels are close, blood flows in parallel arteries and veins. Therefore, arterial blood warms the cooled venous blood moving towards the heart. Contact between them is biologically beneficial.
This is how the loop of Henle and other parts of the nephron are arranged and work, and the mechanism of the countercurrent-multiplier system exists between the knees of the loop of Henle and the collecting ducts.
Consider how the loop of Henle works. The descending section is located in the medulla and stretches to the top of the renal papilla, where it bends 180° and passes into the ascending section, located parallel to the descending one. The functional significance of the various departments of the loop is not the same. The descending part of the loop is well permeable to water, and the ascending part is waterproof, but actively reabsorbs sodium, which increases the tissue osmolarity. This leads to even more water outflow from the descending part of the loop of Henle along the osmotic gradient (passive).
Isotonic urine enters the descending knee, and at the top of the loop, the concentration of urine increases 6-7 times due to the release of water, so concentrated urine enters the ascending knee. Here, in the ascending knee, active reabsorption of sodium and absorption of chlorine occurs, water remains in the lumen of the tubule, and hypotonic fluid (200 osmol / l) enters the distal tubule. An osmotic gradient of 200 milliosmoles constantly exists between the knee segments of the loop of Henle (1 osmol \u003d 1000 milliosmoles - the amount of a substance that develops an osmotic pressure of 22.4 atm in 1 liter of water). Over the entire length of the loop, the total difference in osmotic pressure (osmotic gradient or drop) is 200 milliosmoles.
Urea also circulates in the renal countercurrent system and is involved in maintaining high osmolarity in the renal medulla. Urea leaves the collecting duct (when the final urine moves into the pelvis). Enters the interstitium. It is then secreted into the ascending limb of the nephron loop. Then it enters the distal convoluted tubule (with urine flow), and again ends up in the collecting duct. Thus, circulation in the medulla is a mechanism for maintaining the high osmotic pressure that the nephron loop creates.
In the loop of Henle, an additional 5% of the initial volume of the filtrate is reabsorbed, and about 15% of the volume of primary urine enters the convoluted distal tubules from the ascending loop of Henle.
An important role in maintaining a high osmotic pressure in the kidney is played by direct renal vessels, which, like the loop of Henle, form a reverse-countercurrent system. The descending and ascending vessels run parallel to the nephron loop. Blood moving through the vessels, passing through layers with gradually decreasing osmolarity, gives salt and urea to the intercellular fluid and captures water. That. the countercurrent system of vessels represents a shunt for water, due to which conditions are created for the diffusion of dissolved substances.
Processing of the primary urine in the loop of Henle completes the proximal reabsorption of urine, due to which 100-105 ml/min of primary urine returns to the blood from 120 ml/min, and 17 ml goes further.
Tubular reabsorption is the process of reabsorption of water and substances from the urine contained in the lumen of the tubules into the lymph and blood.
The bulk of the molecules are reabsorbed in the proximal nephron. Here, amino acids, glucose, vitamins, proteins, microelements, a significant amount of Na +, C1-, HCO3- ions and many other substances are almost completely absorbed.
Electrolytes and water are absorbed in the loop of Henle, distal tubule, and collecting ducts.
Aldosterone stimulates Na+ reabsorption and K+ and H+ excretion into the renal tubules in the distal nephron, in the distal tubule and cortical collecting ducts.
Vasopressin promotes water reabsorption from the distal convoluted tubules and collecting ducts.
With the help of passive transport, water, chlorine, and urea are reabsorbed.
Active transport is the transfer of substances against electrochemical and concentration gradients. Moreover, primary-active and secondary-active transport are distinguished. Primary active transport occurs with the expenditure of cell energy. An example is the transfer of Na+ ions by the enzyme Na+/K+-ATPase, which uses the energy of ATP. In secondary active transport, the transfer of a substance is carried out at the expense of the transport energy of another substance. Glucose and amino acids are reabsorbed by the mechanism of secondary active transport.
The value of maximum tubular transport corresponds to the old concept of "renal excretion threshold". For glucose, this value is 10 mmol/l.
Substances, the reabsorption of which does not depend on their concentration in the blood plasma, are called non-threshold. These include substances that are either not reabsorbed at all (inulin, mannitol) or reabsorbed little and are excreted in the urine in proportion to their accumulation in the blood (sulfates).
Normally, a small amount of protein enters the filtrate and is reabsorbed. The process of protein reabsorption is carried out with the help of pinocytosis. Upon entering the cell, the protein is hydrolyzed by lysosome enzymes and converted into amino acids. Not all proteins undergo hydrolysis, some of them pass into the blood unchanged. This process is active and requires energy. The appearance of protein in the urine is called proteinuria. Proteinuria can also occur under physiological conditions, for example, after heavy muscular work. Basically, proteinuria occurs in the pathology of nephritis, nephropathies, and multiple myeloma.
Urea plays an important role in the mechanisms of urine concentration, being freely filtered in the glomeruli. In the proximal tubule, part of the urea is passively reabsorbed by the concentration gradient that occurs due to the concentration of urine. The rest of the urea reaches the collecting ducts. In the collecting ducts, under the influence of ADH, water is reabsorbed and the concentration of urea increases. ADH increases the permeability of the wall for urea, and it passes into the medulla of the kidney, creating here approximately 50% of the osmotic pressure. From the interstitium, urea diffuses along a concentration gradient into the loop of Henle and again enters the distal tubules and collecting ducts. Thus, intrarenal circulation of urea takes place. In the case of water diuresis, the absorption of water in the distal nephron stops, and more urea is excreted. Thus, its excretion depends on diuresis.
Reabsorption of weak acids and bases depends on whether they are in ionized or non-ionized form. Weak bases and acids in the ionized state are not reabsorbed and are excreted in the urine. The degree of ionization of bases increases in an acidic environment, so they are excreted more rapidly with acidic urine, weak acids, on the contrary, are more rapidly excreted with alkaline urine. This is of great importance, since many medicinal substances are weak bases or weak acids. Therefore, in case of poisoning with acetylsalicylic acid or phenobarbital (weak acids), it is necessary to administer alkaline solutions (NaHCO3) in order to transfer these acids to an ionized state, thereby facilitating their rapid elimination from the body. For the rapid excretion of weak bases, it is necessary to introduce acidic products into the blood to acidify the urine.
Water is reabsorbed in all parts of the nephron passively due to osmotically transported active substances: glucose, amino acids, proteins, sodium, potassium, calcium, chlorine ions. With a decrease in the reabsorption of osmotically active substances, the reabsorption of water also decreases. The presence of glucose in the final urine leads to an increase in diuresis (polyuria).
Sodium is the main ion responsible for passive absorption of water. Sodium, as mentioned above, is also necessary for the transport of glucose and amino acids. In addition, it plays an important role in creating an osmotically active environment in the interstitium of the renal medulla, thereby concentrating urine.
The flow of sodium from the primary urine through the apical membrane into the tubular epithelium cell occurs passively along the electrochemical and concentration gradients. The excretion of sodium from the cell through the basolateral membranes is carried out actively with the help of Na+/K+-ATPase. Since the energy of cellular metabolism is spent on the transfer of sodium, its transport is primary active. Sodium transport into the cell can occur through different mechanisms. One of them is the exchange of Na + for H + (countercurrent transport, or antiport). In this case, the sodium ion is transferred inside the cell, and the hydrogen ion is transferred outside. Another way of transferring sodium into the cell is carried out with the participation of amino acids, glucose. This is the so-called cotransport, or symport. In part, sodium reabsorption is associated with potassium secretion.
Cardiac glycosides (strophanthin K, oubain) are able to inhibit the enzyme Na + / K + -ATPase, which ensures the transfer of sodium from the cell to the blood and the transport of potassium from the blood to the cell.
Of great importance in the mechanisms of reabsorption of water and sodium ions, as well as the concentration of urine, is the work of the so-called rotary-countercurrent multiplying system. After passing through the proximal segment of the tubule, the isotonic filtrate in a reduced volume enters the loop of Henle. In this section, intense sodium reabsorption is not accompanied by water reabsorption, since the walls of this segment are poorly permeable to water even under the influence of ADH. In this regard, dilution of urine in the lumen of the nephron and the concentration of sodium in the interstitium occur. Diluted urine in the distal tubule loses excess fluid, becoming isotonic with plasma. A reduced volume of isotonic urine enters the collecting system running in the medulla, the high osmotic pressure in the interstitium of which is due to an increased concentration of sodium. In the collecting ducts, under the influence of ADH, the reabsorption of water continues in accordance with the concentration gradient. The vasa recta in the medulla function as countercurrent exchange vessels, taking sodium along the way to the papillae and releasing it before returning to the cortical layer. In the depth of the medulla, a high sodium content is maintained in this way, which ensures the resorption of water from the collecting system and the concentration of urine.
The formation of the composition of the final urine is carried out in the course of three processes - reabsorption and secretion in the tubules, tubules and ducts. It is represented by the following formula:
Excretion = (Filtration - Reabsorption) + Secretion.
The intensity of release of many substances from the body is determined to a greater extent by reabsorption, and some substances - by secretion.
Reabsorption (reverse absorption) - this is the return of substances necessary for the body from the lumen of the tubules, tubules and ducts to the interstitium and blood (Fig. 1).
Reabsorption is characterized by two features.
First, tubular reabsorption of fluid (water), like , is a quantitatively significant process. This means that the potential effect of a small change in reabsorption can be very significant for urine output. For example, a decrease in reabsorption by only 5% (from 178.5 to 169.5 l / day) will increase the volume of final urine from 1.5 l to 10.5 l / day (7 times, or 600%) at the same level filtration in the glomerulus.
Secondly, tubular reabsorption is highly selective (selectivity). Some substances (amino acids, glucose) are almost completely (more than 99%) reabsorbed, and water and electrolytes (sodium, potassium, chlorine, bicarbonates) are reabsorbed in very significant quantities, but their reabsorption can vary significantly depending on the needs of the body, which affects the content of these substances in the final urine. Other substances (for example, urea) are reabsorbed much worse and excreted in large quantities in the urine. Many substances after filtration are not reabsorbed and are completely excreted at any concentration in the blood (for example, creatinine, inulin). Due to the selective reabsorption of substances in the kidneys, precise control of the composition is carried out liquid media organism.
Rice. 1. Localization of transport processes (secretion and reabsorption in the nephron)
Substances, depending on the mechanisms and degree of their reabsorption, are divided into threshold and non-threshold.
threshold substances under normal conditions, they are almost completely reabsorbed from the primary urine with the participation of facilitated transport mechanisms. These substances appear in significant quantities in the final urine when their concentration in the blood plasma (and thus in the primary urine) increases and exceeds the "excretion threshold", or "renal threshold". The value of this threshold is determined by the ability of carrier proteins in the membrane of epithelial cells to ensure the transfer of filtered substances through the wall of the tubules. When the possibilities of transport are exhausted (supersaturated), when all carrier proteins are involved in the transfer, part of the substance cannot be reabsorbed into the blood, and it appears in the final urine. So, for example, the excretion threshold for glucose is 10 mmol / l (1.8 g / l) and is almost 2 times higher than its normal content in the blood (3.33-5.55 mmol / l). This means that if the concentration of glucose in the blood plasma exceeds 10 mmol / l, then there is glycosuria- Excretion of glucose in the urine (in quantities of more than 100 mg / day). The intensity of glucosuria increases in proportion to the increase in plasma glucose, which is important diagnostic sign gravity diabetes. Normally, the level of glucose in blood plasma (and primary urine), even after a meal, almost never exceeds the value (10 mmol / l) necessary for its appearance in the final urine.
Non-threshold substances do not have an excretion threshold and are removed from the body at any concentration in the blood plasma. These substances are usually metabolic products to be removed from the body (creatinine) and other organic substances (eg inulin). These substances are used to study kidney function.
Some of the removed substances can be partially reabsorbed (urea, uric acid) and not completely removed (Table 1), others are practically not reabsorbed (creatinine, sulfates, inulin).
Table 1. Filtration, reabsorption and excretion by the kidneys of various substances
Reabsorption - multi-step process, including the transition of water and substances dissolved in it, first from the primary urine into the intercellular fluid, and then through the walls of the peritubular capillaries into the blood. Carried substances can penetrate into the interstitial fluid from the primary urine in two ways: transcellularly (through tubular epithelial cells) or paracellularly (through intercellular spaces). Reabsorption of macromolecules in this case is carried out due to endocytosis, and mineral and low molecular weight organic substances - due to active and passive transport, water - through aquaporins passively, by osmosis. Dissolved substances are reabsorbed from the intercellular spaces into the peritubular capillaries under the influence of the force difference between the blood pressure in the capillaries (8-15 mm Hg) and its colloid osmotic (oncotic) pressure (28-32 mm Hg).
The process of reabsorption of Na + ions from the lumen of the tubules into the blood consists of at least three stages. At the 1st stage, Na+ ions enter from the primary urine into the tubular epithelium cell through the apical membrane passively by facilitated diffusion with the help of carrier proteins along the concentration and electrical gradients created by the operation of the Na+/K+ pump on the basolateral surface of the epithelial cell. The entry of Na + ions into the cell is often associated with the joint transport of glucose (carrier protein (SGLUT-1) or amino acids (in the proximal tubule), K + and CI + ions (in the loop of Henle) into the cell (cotransport, symport) or with countertransport (antiport ) H+, NH3+ ions from the cell into the primary urine.At the 2nd stage, the transport of Na+ ions through the basal geral membrane into the intercellular fluid is carried out by primary active transport against electrical and concentration gradients using the Na+/K+ pump (ATPase).Reabsorption of Na+ ions promotes the reabsorption of water (by osmosis), followed by the passive absorption of ions CI-, HCO 3 -, partially urea.At the 3rd stage, the reabsorption of Na + ions, water and other substances from the interstitial fluid into the capillaries occurs under the action of the forces of gradients of hydrostatic and .
Glucose, amino acids, vitamins are reabsorbed from primary urine by secondary active transport (symport together with Na + ion). The transporter protein of the apical membrane of the tubular epithelial cell binds the Na+ ion and an organic molecule (glucose SGLUT-1 or an amino acid) and moves them inside the cell, with Na+ diffusion into the cell along the electrochemical gradient being the driving force. Glucose (with the participation of the GLUT-2 carrier protein) and amino acids pass passively out of the cell through the basolagermal membrane by facilitated diffusion along a concentration gradient.
Proteins with a molecular weight of less than 70 kD, filtered from the blood into the primary urine, are reabsorbed in the proximal tubules by pinocytosis, partially cleaved in the epithelium by lysosomal enzymes, and low molecular weight components and amino acids are returned to the blood. The appearance of protein in the urine is denoted by the term "proteinuria" (usually albuminuria). Short-term proteinuria up to 1 g / l can develop in healthy individuals after intense prolonged physical work. The presence of constant and higher proteinuria is a sign of a violation of the mechanisms of glomerular filtration and (or) tubular reabsorption in the kidneys. Glomerular (glomerular) proteinuria usually develops with an increase in the permeability of the glomerular filter. As a result, the protein enters the cavity of the Shumlyansky-Bowman capsule and the proximal tubules in quantities exceeding the possibilities of its resorption by the mechanisms of the tubules - moderate proteinuria develops. Tubular (tubular) proteinuria is associated with a violation of protein reabsorption due to damage to the epithelium of the tubules or impaired lymph flow. With simultaneous damage to the glomerular and tubular mechanisms, high proteinuria develops.
Reabsorption of substances in the kidneys is closely related to the process of secretion. The term "secretion" to describe the work of the kidneys is used in two senses. First, secretion in the kidneys is considered as a process (mechanism) of transport of substances to be removed into the lumen of the tubules not through the glomeruli, but from the interstitium of the kidney or directly from the cells of the renal epithelium. In this case, the excretory function of the kidney is performed. The secretion of substances into the urine is carried out actively and (or) passively and is often associated with the formation of these substances in the epithelial cells of the tubules of the kidneys. Secretion makes it possible to quickly remove from the body ions K +, H +, NH3 +, as well as some other organic and medicinal substances. Secondly, the term "secretion" is used to describe the synthesis in the kidneys and their release into the blood of the hormones erythropoietin and calcitriol, the enzyme renin and other substances. The processes of gluconeogenesis are actively going on in the kidneys, and the resulting glucose is also transported (secreted) into the blood.
Reabsorption and secretion of substances in various parts of the nephron
Osmotic dilution and concentration of urine
Proximal tubules provide reabsorption of most of the water from the primary urine (approximately 2/3 of the volume of the glomerular filtrate), a significant amount of Na +, K +, Ca 2+, CI-, HCO 3 - ions. Almost all organic substances (amino acids, proteins, glucose, vitamins), trace elements and other substances necessary for the body are reabsorbed in the proximal tubules (Fig. 6.2). In other departments of the nephron, only the reabsorption of water, ions and urea is carried out. Such a high reabsorption capacity of the proximal tubule is due to a number of structural and functional features its epithelial cells. They are equipped with a well-developed brush border on the apical membrane, as well as a wide labyrinth of intercellular spaces and channels on the basal side of the cells, which significantly increases the absorption area (60 times) and accelerates the transport of substances through them. In the epithelial cells of the proximal tubules, there are a lot of mitochondria, and the intensity of metabolism in them is 2 times higher than that in neurons. This makes it possible to obtain a sufficient amount of ATP for the implementation of active transport of substances. An important feature of reabsorption in the proximal tubules is that water and substances dissolved in it are reabsorbed here in equivalent amounts, which ensures the isoosmolarity of the urine of the proximal tubules and its isosmoticity with blood plasma (280-300 mosmol / l).
In the proximal tubules of the nephron, primary active and secondary active secretion of substances into the lumen of the tubules occurs with the help of various carrier proteins. The secretion of excreted substances is carried out both from the blood of the peritubular capillaries and from chemical compounds formed directly in the cells of the tubular epithelium. Many organic acids and bases are secreted from the blood plasma into the urine (for example, para-aminohippuric acid (PAG), choline, thiamine, serotonin, guanidine, etc.), ions (H +, NH3 +, K +), medicinal substances (penicillin, etc. ). For a number of xenobiotics of organic origin that have entered the body (antibiotics, dyes, X-ray contrast agents), the rate of their excretion from the blood by tubular secretion significantly exceeds their excretion by glomerular filtration. The secretion of PAH in the proximal tubules is so intense that the blood is cleared of it already in one passage through the peritubular capillaries of the cortical substance (hence, by determining the clearance of PAH, it is possible to calculate the volume of the effective renal plasma flow involved in urine formation). In the cells of the tubular epithelium, when the amino acid glutamine is deaminated, ammonia (NH 3) is formed, which is secreted into the lumen of the tubule and enters the urine. In it, ammonia binds with H + ions to form the ammonium ion NH 4 + (NH 3 + H + -> NH4 +). By secreting NH 3 and H + ions, the kidneys take part in the regulation of the acid-base state of the blood (body).
AT loop of Henle reabsorption of water and ions are spatially separated, which is due to the peculiarities of the structure and functions of its epithelium, as well as hyperosmoticity of the renal medulla. The descending part of the loop of Henle is highly permeable to water and only moderately permeable to substances dissolved in it (including sodium, urea, etc.). In the descending part of the loop of Henle, 20% of water is reabsorbed (under the action of high osmotic pressure in the medium surrounding the tubule), and osmotically active substances remain in the tubular urine. This is due high content sodium chloride and urea in the hyperosmotic intercellular fluid of the renal medulla. The osmoticity of urine as it moves to the top of the loop of Henle (deep into the medulla of the kidney) increases (due to the reabsorption of water and the flow of sodium chloride and urea along the concentration gradient), and the volume decreases (due to the reabsorption of water). This process is called osmotic concentration of urine. The maximum osmoticity of tubular urine (1200-1500 mosmol/l) is reached at the top of the loop of Henle of the juxtamedullary nephrons.
Next, urine enters the ascending knee of the loop of Henle, the epithelium of which is not permeable to water, but permeable to ions dissolved in it. This department provides reabsorption of 25% of ions (Na +, K +, CI-) of their total amount that entered the primary urine. The epithelium of the thick ascending part of the loop of Henle has a powerful enzymatic system of active transport of Na + and K + ions in the form of Na + / K + pumps built into the basement membranes of epithelial cells.
In the apical membranes of the epithelium, there is a cotransport protein that simultaneously transports one Na+ ion, two CI- ions, and one K+ ion from the urine into the cytoplasm. The source of the driving force for this cotransporter is the energy with which Na + ions rush into the cell along the concentration gradient; it is also sufficient to move K ions against the concentration gradient. Na+ ions can also enter the cell in exchange for H ions using the Na+/H+ cotransporter. The release (secretion) of K+ and H+ into the lumen of the tubule creates an excess positive charge in it (up to +8 mV), which promotes the diffusion of cations (Na+, K+, Ca 2+ , Mg 2+) paracellularly, through intercellular contacts.
Secondary active and primary active transport of ions from the ascending limb of the loop of Henle to the space surrounding the tubule is the most important mechanism for creating high osmotic pressure in the interstitium of the renal medulla. In the ascending loop of Henle, water is not reabsorbed, and the concentration of osmotically active substances (primarily Na + and CI + ions) in the tubular fluid decreases due to their reabsorption. Therefore, at the outlet of the loop of Henle in the tubules, there is always hypotonic urine with a concentration of osmotically active substances below 200 mosmol / l. Such a phenomenon is called osmotic dilution of urine, and the ascending part of the loop of Henle - the distributing segment of the nephron.
The creation of hyperosmoticity in the renal medulla is considered as the main function of the nephron loop. There are several mechanisms for its creation:
- active work of the rotary-countercurrent system of tubules (ascending and descending) of the nephron loop and cerebral collecting ducts. The movement of fluid in the nephron loop in opposite directions towards each other causes the summation of small transverse gradients and forms a large longitudinal cortical-medullary osmolality gradient (from 300 mosmol/L in the cortex to 1500 mosmol/L near the top of the pyramids in the medulla). The mechanism of the loop of Henle is called rotary-countercurrent multiplying system of the nephron. The loop of Henle of the juxtamedullary nephrons, penetrating through the entire medulla of the kidney, plays a major role in this mechanism;
- circulation of two main osmotically active compounds - sodium chloride and urea. These substances make the main contribution to the creation of hyperosmoticity of the interstitium of the renal medulla. Their circulation depends on the selective permeability of the membrane of the ascending limb of the nsphron loop for electrolytes (but not for water), as well as the ADH-controlled permeability of the walls of the cerebral collecting ducts for water and urea. Sodium chloride circulates in the nephron loop (in the ascending knee, ions are actively reabsorbed into the interstitium of the medulla, and from it, according to the laws of diffusion, enter the descending knee and again rise to the ascending knee, etc.). Urea circulates in the system of the collecting duct of the medulla - the interstitium of the medulla - the thin part of the loop of Henle - the collecting duct of the medulla;
- passive rotary-countercurrent straight line system blood vessels The medulla of the kidneys has its origin from the efferent vessels of the juxtamedullary nephrons and runs parallel to the loop of Henle. Blood moves along the descending straight leg of the capillary to the area with increasing osmolarity, and then, after turning by 180°, in the opposite direction. At the same time, ions and urea, as well as water (in the opposite direction to ions and urea) shuttle between the descending and ascending parts of the straight capillaries, which maintains a high osmolality of the renal medulla. This is also facilitated by the low volumetric velocity of blood flow through straight capillaries.
From the loop of Henle, urine enters the distal convoluted tubule, then into the connecting tubule, then into the collecting duct and collecting duct of the renal cortex. All of these structures are located in the renal cortex.
In the distal and connecting tubules of the nephron and collecting ducts, the reabsorption of Na + ions and water depends on the state of the body's water and electrolyte balance and is under control. antidiuretic hormone, aldosterone, natriuretic peptide.
The first half of the distal tubule is a continuation of the thick segment of the ascending part of the loop of Henle and retains its properties - the permeability for water and urea is almost zero, but Na + and CI- ions are actively reabsorbed here (5% of their filtration volume in the glomeruli) by symport with Na + /CI- cotransporter. Urine in it becomes even more dilute (hypoosmotic).
For this reason, the first half of the distal tubule, as well as the ascending part of the nephron loop, is referred to as the segment diluting urine.
The second half of the distal tubule, the connecting tubule, collecting ducts and cortical ducts have a similar structure and similar functional characteristics. Among the cells of their walls, two main types are distinguished - the main and intercalary cells. Chief cells reabsorb Na+ ions and water and secrete K+ ions into the lumen of the tubule. The permeability of chief cells to water is (almost completely) regulated by ADH. This mechanism provides the body with the ability to control the amount of urine excreted and its osmolarity. Here begins the concentration of secondary urine - from hypotonic to isotonic (). Intercalated cells reabsorb K+ ions, carbonates and secrete H+ ions into the lumen. Proton secretion is primarily active due to the work of H+ transporting ATPases against a significant concentration gradient exceeding 1000:1. Intercalary cells play a key role in the regulation of acid-base balance in the body. Both types of cells are practically impermeable to urea. Therefore, urea remains in the urine at the same concentration from the beginning of the thick portion of the ascending limb of the loop of Henle to the collecting ducts of the renal medulla.
Collecting ducts of the renal medulla represent the department in which the composition of urine is finally formed. The cells of this department play an extremely important role in determining the content of water and dissolved substances in the excreted (final) urine. Here, up to 8% of all filtered water and only 1% of Na + and CI- ions are reabsorbed, and water reabsorption plays a major role in the concentration of the final urine. Unlike the overlying sections of the nephron, the walls of the collecting ducts, located in the medulla of the kidney, are permeable to urea. Urea reabsorption contributes to maintaining a high osmolarity of the interstitium of the deep layers of the renal medulla and the formation of concentrated urine. The permeability of the collecting ducts for urea and water is regulated by ADH, for Na+ and CI- ions by aldosterone. Collecting duct cells are able to reabsorb bicarbonates and secrete protons across a high concentration gradient.
Methods for studying the excretory function of the nights
Determination of renal clearance for various substances allows us to investigate the intensity of all three processes (filtration, reabsorption and secretion) that determine the excretory function of the kidneys. The renal clearance of a substance is the volume of blood plasma (ml) that is released from the substance with the help of the kidneys per unit of time (min). The clearance is described by the formula
K in * PC in \u003d M in * O m,
where K in - the clearance of the substance; PC B is the concentration of the substance in the blood plasma; M in — concentration of substance in urine; Om is the volume of excreted urine.
If the substance is freely filtered, but not reabsorbed or secreted, then the rate of its excretion in the urine (M in. O m) will be equal to the filtration rate of the substance in the glomeruli (GFR. PC in). From here it can be calculated by determining the clearance of the substance:
GFR \u003d M in. About m /pc in
Such a substance that meets the above criteria is inulin, the clearance of which is on average 125 ml / min in men and 110 ml / min in women. This means that the amount of blood plasma passing through the vessels of the kidneys and filtered in the glomeruli to deliver such an amount of inulin to the final urine should be 125 ml in men and 110 ml in women. Thus, the volume of primary urine formation in men is 180 l / day (125 ml / min. 60 min. 24 h), in women 150 l / day (110 ml / min. 60 min. 24 h).
Given that the polysaccharide inulin is absent in the human body and must be administered intravenously, another substance, creatinine, is more often used in the clinic to determine GFR.
By determining the clearance of other substances and comparing it with the clearance of inulin, it is possible to evaluate the processes of reabsorption and secretion of these substances in the renal tubules. If the clearances of the substance and inulin are the same, then this substance is isolated only by filtration; if the clearance of the substance is greater than that of inulin, then the substance is additionally secreted into the lumen of the tubules; if the clearance of the substance is less than that of inulin, then it, apparently, is partially reabsorbed. Knowing the intensity of excretion of a substance in the urine (M in. O m), it is possible to calculate the intensity of the processes of reabsorption (reabsorption \u003d Filtration - Isolation \u003d GFR. PC in - M in. O m) and secretion (Secretion \u003d Isolation - Filtration \u003d M in. O m - GFR. PC).
With the help of the clearance of some substances, it is possible to assess the magnitude of the renal plasma flow and blood flow. For this, substances are used that are released into the urine by filtration and secretion and are not reabsorbed. The clearance of such substances will theoretically be equal to the total plasma flow in the kidney. There are practically no such substances, however, the blood is cleared of some substances by almost 90% during one passage through the night. One of these natural substances is para-aminohyppuric acid, the clearance of which is 585 ml / min, which allows us to estimate the value of the renal plasma flow at 650 ml / min (585: 0.9), taking into account the coefficient of its extraction from the blood of 90%. With a hematocrit of 45% and a renal plasma flow of 650 ml/min, the blood flow in both kidneys will be 1182 ml/min, i.e. 650 / (1-0.45).
Regulation of tubular reabsorption and secretion
The regulation of tubular reabsorption and secretion is carried out mainly in the distal parts of the nephron with the help of humoral mechanisms, i.e. is under the control of various hormones.
Proximal reabsorption, unlike the transport of substances in the distal tubules and collecting ducts, is not subject to such careful control by the body, so it is often called obligatory reabsorption. It has now been established that the intensity of obligate reabsorption can change under the influence of certain nervous and humoral influences. So, the excitement of the sympathetic nervous system leads to an increase in the reabsorption of Na + ions, phosphates, glucose, water by the cells of the epithelium of the proximal tubules of the nephron. Angiotensin-N is also capable of causing an increase in the rate of proximal reabsorption of Na + ions.
The intensity of proximal reabsorption depends on the amount of glomerular filtration and increases with an increase in the glomerular filtration rate, which is called glomerular tubular balance. The mechanisms for maintaining this balance are not fully understood, but it is known that they are intrarenal regulatory mechanisms and their implementation does not require additional nervous and humoral influences from the body.
In the distal tubules and collecting ducts of the kidney, mainly water and ion reabsorption is carried out, the severity of which depends on the water and electrolyte balance of the body. Distal reabsorption of water and ions is called facultative and is controlled by antidiuretic hormone, aldosterone, atrial natriuretic hormone.
The formation of antidiuretic hormone (vasopressin) in the hypothalamus and its release into the blood from the pituitary gland increases with a decrease in the water content in the body (dehydration), a decrease in blood pressure blood (hypotension), as well as with an increase in the osmotic pressure of the blood (hyperosmia). This hormone acts on the epithelium of the distal tubules and collecting ducts of the kidney and causes an increase in its permeability to water due to the formation of special proteins (aquaporins) in the cytoplasm of epithelial cells, which are embedded in the membranes and form channels for the flow of water. Under the influence of antidiuretic hormone, there is an increase in water reabsorption, a decrease in diuresis and an increase in the concentration of urine formed. Thus, antidiuretic hormone contributes to the conservation of water in the body.
With a decrease in the production of antidiuretic hormone (trauma, tumor of the hypothalamus), a large amount of hypotonic urine is formed (diabetes insipidus); loss of fluid in the urine can lead to dehydration.
Aldosterone is produced in the glomerular zone of the adrenal cortex, acts on the epithelial cells of the distal nephron and collecting ducts, causes an increase in the reabsorption of Na + ions, water and an increase in the secretion of K + ions (or H + ions if they are in excess in the body). Aldosterone is part of the renin-angiotension-aldosterone system (the functions of which were discussed earlier).
Atrial natriuretic hormone is produced by atrial myocytes when they are stretched by excess blood volume, that is, with hypervolemia. Under the influence of this hormone, there is an increase in glomerular filtration and a decrease in the reabsorption of Na + ions and water in the distal nephron, resulting in an increase in the process of urination and the removal of excess water from the body. In addition, this hormone reduces the production of renin and aldosterone, which additionally inhibits the distal reabsorption of Na + ions and water.