Reverse suction. Tubular reabsorption
Tubular reabsorption - This is the process of absorption by the cells of the tubules and transport into the cells of the fluid and capillaries of the kidneys of substances necessary for the body from primary urine.
In the proximal tubules, 80% of substances are reabsorbed: all glucose, all vitamins, hormones, microelements; about 85% NaCl and H2O, as well as about 50% urea, which enter the capillaries of the tubules and return to the general circulatory system.
For the reabsorption process, the concept of the withdrawal threshold is essential. The withdrawal threshold is the concentration of a substance in the blood at which it cannot be completely reabsorbed. Almost all biologically important substances for the body have an excretion threshold. For example, the excretion of glucose in the urine (glucosuria) occurs when its concentration in the blood exceeds 10 mmol/l. With glucosuria, the osmotic pressure of urine increases, which leads to an increase in the amount of urine (polyuria). There are also non-threshold substances that are released at any concentration in the plasma and ultrafiltrate.
The mechanism of reabsorption including pathways: first, substances enter the tubule cells from the filtrate, then they are transported by membrane transport systems into the intercellular space; from the intercellular spaces diffuse into highly permeable biliary tubules and capillaries.
Transportation can be active or passive. Active reabsorption occurs with the participation of special enzymatic systems with energy consumption against an electrochemical gradient. Phophates and Na + are actively reabsorbed. Due to active reabsorption, substances can be reabsorbed from urine into the blood, even when their concentration in the blood is equal to the concentration in the tubular fluid or higher.
Associated transportation glucose and amino acids. From the cavity of the tubules into the cells, substances are transported using a carrier, which necessarily additionally attaches Na +. Inside the cell, the complex disintegrates. The concentration of glucose increases, and along the concentration gradient it leaves the cell.
Passive reabsorption occurs without energy consumption due to diffusion and osmosis. A major role in this process belongs to the difference in hydrostatic pressure in the capillaries of the tubules. Due to passive reabsorption, H2O, chlorides, and urea are reabsorbed.
Another reabsorption mechanism is pinocytosis. This is how proteins are absorbed.
As a result of the active transport of Na + and the accompanying anions, the osmotic pressure of the filtrate decreases and an equivalent amount of water passes into the capillaries by osmosis. As a result, a filtrate is formed in the tubules, isotonic with the blood of the capillary. This filtrate enters the loop of Henle. Further reabsorption and concentration of urine takes place here due to rotary counterflow systems. Urine concentration occurs as follows. In the ascending part of the nephron loop, which passes through the medulla, Na, K, Ca, Mg, Cl, and urea are actively reabsorbed, entering the intercellular fluid, they increase the osmotic pressure there. The descending part of the loop of Henle passes in an area of high osmotic pressure, so water exits from this part of the loop into the intercellular space according to the laws of osmosis. The release of H2O from the descending part of the loop causes the urine to become more concentrated relative to the blood plasma. This promotes the reabsorption of Na + in the ascending part of the loop, which in turn causes the release of H2O in the descending part. These two processes are coupled, as a result, urine loses a large amount of H2O and Na + in the loop of Henle, and at the exit from the loop, the urine again becomes isotonic.
Thus, the role of the loop of Henle as counterflow The concentrating mechanism is determined by the following factors:
1) close rotation of the ascending and descending knees;
2) permeability of the descending limb for H2O;
3) impermeability of the descending limb to dissolved substances;
4) permeability of the ascending segment for Na +, K +, Ca2 +, Mg2 +, SG;
5) the presence of active transport mechanisms in the ascending limb.
IN distal part of the tubule further reabsorption of Na +, K +, Ca2 +, Mg2 +, H2O occurs, which depends on the concentration of these substances in the blood - facultative reabsorption. If there are a lot of them, then they are not reabsorbed; if there are few, then they return to the blood. The distal section regulates and maintains the constant concentration of Na + and K + ions in the body. The permeability of the walls of the distal part of the tubule for H2O is regulated ADH(ADH) of the pituitary gland (the secretion of which depends on the osmotic pressure of the blood). With an increase in osmotic pressure (that is, a decrease in the amount of H2O), the osmoreceptors of the hypothalamus are excited, the secretion of ADH increases, the permeability of the tubule walls for H20 increases and it is reabsorbed into the blood, that is, retained in the body, and the osmotic pressure decreases.
The reabsorption of water in the harvesting tube is similarly regulated, which is also involved in the formation of hypertonic or hypotonic urine, depending on the body's need for water.
The amount of tubular reabsorption substances are determined by the difference between their amounts in the primary and final urine. The amount of tubular reabsorption of water (RH2O) is determined by the difference between the glomerular filtration rate (GFR) and the amount of final urine and is expressed as a percentage of GFR. RH 2 O = Sip - V / Sip × 100%
Under normal conditions, the reabsorption rate is 98-99%. To assess the function of the proximal tubules, the maximum reabsorption of glucose (Tmg) is determined by increasing its concentration in the blood plasma to a limit that significantly exceeds the threshold. Tmg = Sip × Pg - Ug × V , where Sip is GFR; Pg - blood glucose concentration Ug - urine glucose concentration; V is the amount of urine excreted in 1 minute. The average Tmg value in men is 34.7 mmol/l. After the age of 40, Tmg decreases by 7% for every 10 years of life.
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 the volume of primary urine(approximately 120 l/day. It was 170 l, 1.5 was released): water, mineral salts, all 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 “excretion threshold”). For glucose, the elimination threshold is 10 mmol/l (with a normal blood glucose concentration of 4.4-6.6 mmol/l).
Non-threshold substances are always excreted regardless of their concentration in the blood plasma. They are not reabsorbed or are partially reabsorbed, for example, urea and other metabolites.
The mechanism of operation of various parts of the renal filter.
1. In the proximal tubule The process of concentrating the glomerular filtrate begins, and the most important point here is the active absorption of salts. With the help of active transport, about 67% of Na+ is reabsorbed from this part of the tubule. An almost proportionate 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 from it will be reabsorbed. 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 this arrangement of the absorbent surface, the area of the cell membrane increases enormously 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 active transport of solutes through the wall of the tubule. In this area of the nephron, NaCl penetrates very poorly through the wall of the tubule, urea - somewhat better, and water passes through without difficulty.
3. Wall of the thin portion of the ascending limb of the loop of Henle also inactive regarding salt transport. However, it is highly permeable to Na+ and Cl-, but low 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 said loop. It actively transports 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 limb, 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 nephron lumen and the transport of Na+, Cl- and H2O from the nephron lumen into the tissue fluid. Since 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 of the formation of hyperosmotic urine. Reabsorption of NaCl also occurs in the duct, but due to the active transfer of Na+ through the wall. The collecting duct is impermeable to salts, but its permeability varies with respect to water. 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 using special transporters of the brush border of the apical membrane of epithelial cells. These transporters transport glucose only if they simultaneously bind and transport sodium. Passive movement of sodium along the concentration gradient into cells leads to transport across the membrane and transporter with glucose.
To implement this process, a low concentration of sodium in the epithelial cell is required, creating 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 simport, i.e., joint passive transport of one substance (glucose) due to the active transport of another (sodium) using one carrier. If there is an excess of glucose in the primary urine, all transport molecules may be completely loaded and glucose will no longer be able to be absorbed into the blood.
This situation is characterized by the concept “ maximum tubular transport of substance"(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 maximum tubular transport corresponds to the concept of “renal excretion threshold”.
Renal excretion threshold they call that one concentration of a substance in the blood and, accordingly, in primary urine, in which it can no longer be completely reabsorbed in the tubules and appears in the final urine. Such substances for which an excretion threshold can be found, i.e., completely reabsorbed at low concentrations in the blood, but not completely at elevated concentrations, are called threshold substances. An example is glucose, which is completely absorbed from the 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 the blood plasma is above 10 mmol/L. Hence, for glucose, the elimination threshold is 10 mmol/l.
Secretion mechanisms 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 drugs: penicillin, etc.). Secretion of organic acids and bases occurs via a secondary active sodium-dependent mechanism.
Secretion of potassium ions.
Most of the potassium ions easily filtered in the glomeruli 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 greatly in response to the body's excess consumption of this ion.
However, the distal tubules and collecting ducts are capable of not only reabsorbing, but also secreting potassium ions. By secreting potassium, these structures strive to achieve ionic homeostasis in the event of an unusually large amount of this metal entering the body. Transport of K+ appears to depend on its entry into tubular cells from the tissue fluid, due to the activity of the usual Nar+ - Ka+ pump, with leakage of K+ from the cytoplasm into the tubular fluid. Potassium can simply diffuse along an electrochemical gradient from the renal tubular cells into the lumen because the tubular fluid is electronegative with respect to the cytoplasm. K+ secretion through these mechanisms is stimulated by the adrenocortical hormone aldosterone, which is released in response to an increase in K+ levels in the blood plasma.
Reabsorption of various substances in the tubules is ensured by active and passive transport. If a substance is reabsorbed against electrochemical and concentration gradients, the process is called active transport. There are two types of active transport: primary active and secondary active. Primary active transport is called when a substance is transferred against an electrochemical gradient due to the energy of cellular metabolism. An example is the transport of Na + ions, which occurs with the participation of the enzyme Na + ,K + -ATPase, which uses the energy of ATP. Secondary active is the transfer of a substance against a concentration gradient, but without the expenditure of cell energy directly on this process; This is how glucose and amino acids are reabsorbed. From the lumen of the tubule, these organic substances enter the cells of the proximal tubule with the help of a special transporter, which must attach the Na + ion. This complex (carrier + organic matter + Na +) promotes the movement of the substance through the brush border membrane and its entry into the cell. The driving force for the transfer of these substances through the apical plasma membrane is the sodium concentration in the cell cytoplasm, which is lower than in the lumen of the tubule. The sodium concentration gradient is caused by the continuous active removal of sodium from the cell into the extracellular fluid with the help of Na + ,K + -ATPase, localized in the lateral and basement membranes of the cell.
Reabsorption of water, chlorine and some other ions, urea is carried out using passive transport - along an electrochemical, concentration or osmotic gradient. An example of passive transport is the reabsorption of chlorine in the distal convoluted tubule along the electrochemical gradient created by active sodium transport. Water is transported along an osmotic gradient, and the rate of its absorption depends on the osmotic permeability of the tubule wall and the difference in the concentration of osmotically active substances on both sides of its wall. In the contents of the proximal tubule, due to the absorption of water and substances dissolved in it, the concentration of urea increases, a small amount of which is reabsorbed into the blood along the concentration gradient. Advances in the field of molecular biology have made it possible to establish the structure of the molecules of ion and water channels (aquaporins) of receptors, autacoids and hormones and thereby gain insight into the essence of some cellular mechanisms that ensure the transport of substances through the wall of the tubule. The properties of cells in different parts of the nephron are different, and the properties of the cytoplasmic membrane in the same cell are different.
Let's consider the cellular mechanism of ion reabsorption using Na + as an example. In the proximal tubule of the nephron, the absorption of Na + into the blood occurs as a result of a number of processes, one of which is the active transport of Na + from the lumen of the tubule, the other is the passive reabsorption of Na + following both bicarbonate and Cl - ions actively transported into the blood. When one microelectrode was introduced into the lumen of the tubules, and the second into the peritubular fluid, it was revealed that the potential difference between the outer and inner surfaces of the proximal tubule wall turned out to be very small - about 1.3 mV; in the area of the distal tubule it can reach 60 mV. The lumen of both tubules is electronegative, and in the blood (and therefore in the extracellular fluid), the concentration of Na + is higher than in the fluid located in the lumen of these tubules, so Na + is reabsorbed actively against the electrochemical potential gradient. In this case, Na + enters the cell from the lumen of the tubule through the sodium channel or with the participation of a transporter. The interior of the cell is negatively charged, and positively charged Na + enters the cell along a potential gradient, moves towards the basal plasma membrane, through which it is released into the intercellular fluid by the sodium pump; the potential gradient across this membrane reaches 70-90 mV. There are substances that can affect individual elements of the Na + reabsorption system. Thus, the sodium channel in the cell membrane of the distal tubule and collecting duct is blocked by amiloride and triamterene, as a result of which Na + cannot enter the channel. There are several types of ion pumps in cells. One of them is Na + ,K + -ATPase. This enzyme is located in the basal and lateral membranes of the cell and ensures the transport of Na + from the cell into the blood and the entry of K + from the blood into the cell. The enzyme is inhibited by cardiac glycosides, for example strophanthin, ouabain. In the reabsorption of bicarbonate, an important role is played by the enzyme carbonic anhydrase, the inhibitor of which is acetazolamide - it stops the reabsorption of bicarbonate, which is excreted in the urine.
Filtered glucose is almost completely reabsorbed by the cells of the proximal tubule, and normally a small amount of it is excreted in the urine per day (no more than 130 mg). The process of glucose reabsorption occurs against a high concentration gradient and is secondary active. In the apical (luminal) membrane of the cell, glucose combines with a transporter, which must also attach Na +, after which the complex is transported through the apical membrane, i.e. Glucose and Na + enter the cytoplasm. The apical membrane is highly selective and one-way permeable and does not allow either glucose or Na + to pass back from the cell into the lumen of the tubule. These substances move towards the base of the cell along a concentration gradient. The transfer of glucose from the cell to the blood through the basal plasma membrane is of the nature of facilitated diffusion, and Na +, as noted above, is removed by the sodium pump located in this membrane.
Amino acids are almost completely reabsorbed by proximal tubule cells. There are at least 4 systems for transporting amino acids from the lumen of the tubule into the blood that carry out reabsorption: neutral, dibasic, dicarboxyl amino acids and imino acids. Weak acids and bases can exist, depending on the pH of the environment, in two forms - non-ionized and ionized. Cell membranes are more permeable to non-ionized substances. If the pH value of the tubular fluid is shifted to the acidic side, then the bases are ionized, poorly absorbed and excreted in the urine. The process of “nonionic diffusion” affects the kidneys’ excretion of weak bases and acids, barbiturates and other drugs.
A small amount of protein filtered in the glomeruli is reabsorbed by the cells of the proximal tubules. The excretion of proteins in the urine is normally no more than 20-75 mg per day, and in case of kidney disease it can increase to 50 g per day. An increase in the excretion of proteins in the urine (proteinuria) may be due to a violation of their reabsorption or an increase in filtration.
Unlike the reabsorption of electrolytes, glucose and amino acids, which, having penetrated the apical membrane, reach the basal plasma membrane unchanged and are transported into the blood, protein reabsorption is ensured by a fundamentally different mechanism. The protein enters the cell via pinocytosis. Molecules of the filtered protein are adsorbed on the surface of the apical membrane of the cell, while the membrane participates in the formation of a pinocytotic vacuole. This vacuole moves towards the basal part of the cell. In the perinuclear region, where the lamellar complex (Golgi apparatus) is localized, vacuoles can merge with lysosomes, which have high activity of a number of enzymes. In lysosomes, captured proteins are broken down and the resulting amino acids and dipeptides are removed into the blood through the basal plasma membrane.
The amount of reabsorption in the kidney tubules is determined by the difference between the amount of the substance filtered in the glomeruli and the amount of the substance excreted in the urine. When calculating relative reabsorption (% R), the proportion of the substance that has been reabsorbed relative to the amount of the substance filtered in the glomeruli is determined.
To assess the reabsorption capacity of proximal tubular cells, it is important to determine the maximum value of glucose transport. This value is measured when the tubular transport system is completely saturated with glucose. To do this, a glucose solution is introduced into the blood and thereby increases its concentration in the glomerular filtrate until a significant amount of glucose begins to be excreted in the urine.
In the human kidneys, up to 170 liters of filtrate are formed in one day, and 1-1.5 liters of final urine are released, the rest of the liquid is absorbed in the tubules. Primary urine is isotonic with blood plasma (i.e. it is blood plasma without proteins). Reabsorption of substances in the tubules is to return all vital substances in the required quantities from primary urine.
Volume of reabsorption = volume of ultrafiltrate – volume of final urine.
The molecular mechanisms involved in the implementation of reabsorption processes are the same as the mechanisms that operate during the transfer of molecules across plasma membranes in other parts of the body: diffusion, active and passive transport, endocytosis, etc.
There are two pathways for the movement of reabsorbed material from the lumen to the interstitial space.
The first is movement between cells, i.e. through a tight junction of two neighboring cells - this is the paracellular pathway . Paracellular reabsorption can be carried out through diffusion or due to the transfer of a substance along with a solvent. Second route of reabsorption - transcellular ("through" the cell). In this case, the reabsorbed substance must cross two plasma membranes on its way from the lumen of the tubule to the interstitial fluid - the luminal (or apical) membrane, separating the fluid in the lumen of the tubule from the cytoplasm of the cells, and the basolateral (or counterluminal) membrane, separating the cytoplasm from the interstitial fluid. Transcellular transport defined by the term active , for brevity, although the crossing of at least one of the two membranes is carried out through a primary or secondary active process. If a substance is reabsorbed against electrochemical and concentration gradients, the process is called active transport. There are two types of transport - primary active and secondary active . Primary active transport is called when a substance is transferred against an electrochemical gradient due to the energy of cellular metabolism. This transport is provided by the energy obtained directly from the breakdown of ATP molecules. An example is the transport of Na ions, which occurs with the participation of Na + ,K + ATPase, which uses the energy of ATP. Currently, the following primary active transport systems are known: Na + , K + - ATPase; H+-ATPase; H + ,K + -ATPase and Ca + ATPase.
Secondary active is called the transfer of a substance against a concentration gradient, but without the cell expending energy directly on this process, this is how glucose and amino acids are reabsorbed. From the lumen of the tubule, these organic substances enter the cells of the proximal tubule with the help of a special transporter, which must attach the Na + ion. This complex (carrier + organic matter + Na +) promotes the movement of the substance through the brush border membrane and its entry into the cell. The driving force for the transfer of these substances through the apical plasma membrane is the sodium concentration in the cell cytoplasm, which is lower than in the lumen of the tubule. The sodium concentration gradient is caused by the direct active removal of sodium from the cell into the extracellular fluid using Na + , K + -ATPase, localized in the lateral and basal membranes of the cell. Reabsorption of Na + Cl - is the most significant process in terms of volume and energy costs.
Different parts of the renal tubules differ in their ability to absorb substances. By analyzing fluids from various parts of the nephron, the composition of the fluid and the characteristics of the functioning of all parts of the nephron were established.
Proximal tubule. Reabsorption in the proximal segment is obligate (obligatory). In the proximal convoluted tubules, most of the components of primary urine are reabsorbed with an equivalent amount of water (the volume of primary urine decreases by approximately 2/3). In the proximal nephron, amino acids, glucose, vitamins, the required amount of protein, trace elements, and a significant amount of Na +, K +, Ca +, Mg +, Cl _, HCO 2 are completely reabsorbed. The proximal tubule plays a major role in returning all these filtered substances to the blood through efficient reabsorption. Filtered glucose is almost completely reabsorbed by the cells of the proximal tubule, and normally a small amount (no more than 130 mg) can be excreted in the urine per day. Glucose moves against the gradient from the tubular lumen through the luminal membrane into the cytoplasm via a sodium cotransport system. This movement of glucose is mediated by a transporter and is a secondary active transport, since the energy required to carry out the movement of glucose across the luminal membrane is generated by the movement of sodium along its electrochemical gradient, i.e. via cotransport. This cotransport mechanism is so powerful that it allows complete absorption of all glucose from the lumen of the tubule. After entering the cell, glucose must cross the basolateral membrane, which occurs through sodium-independent facilitated diffusion; this movement along the gradient is supported by the high concentration of glucose accumulating in the cell due to the activity of the luminal cotransport process. To ensure active transcellular reabsorption, the system operates: with the presence of 2 membranes that are asymmetric with respect to the presence of glucose transporters; energy is released only when it overcomes one membrane, in this case the luminal one. The decisive factor is that the entire process of glucose reabsorption ultimately depends on the primary active transport of sodium. Secondary active reabsorption when cotransported with sodium across the luminal membrane, in the same way as glucose amino acids are reabsorbed,inorganic phosphate, sulfate and some organic nutrients. Low molecular weight proteins are reabsorbed by pinocytosis in the proximal segment. Protein reabsorption begins with endocytosis (pinocytosis) at the luminal membrane. This energy-dependent process is initiated by the binding of filtered protein molecules to specific receptors on the luminal membrane. Isolated intracellular vesicles that appear during endocytosis merge inside the cell with lysosomes, whose enzymes break down proteins into low molecular weight fragments - dipeptides and amino acids, which are removed into the blood through the basolateral membrane. The excretion of proteins in urine is normally no more than 20 - 75 mg per day, and with kidney disease it can increase to 50 g per day (proteinuria ).
An increase in the excretion of proteins in the urine (proteinuria) may be due to a violation of their reabsorption or filtration.
Nonionic diffusion- weak organic acids and bases dissociate poorly. They dissolve in the lipid matrix of membranes and are reabsorbed along a concentration gradient. The degree of their dissociation depends on the pH in the tubules: when it decreases, acids dissociatedecreases,grounds rises.Acid reabsorption increases,bases – decreases. As pH increases, the opposite is true. This is used clinically to speed up the elimination of toxic substances - in case of barbiturate poisoning, the blood is alkalized. This increases their content in the urine.
Loop of Henle. In general, the loop of Henle always reabsorbs more sodium and chlorine (about 25% of the amount filtered) than water (10% of the volume of filtered water). This is an important difference between the loop of Henle and the proximal tubule, where water and sodium are reabsorbed in almost equal proportions. The descending portion of the loop does not reabsorb sodium or chloride, but it is very permeable to water and will reabsorb it. The ascending part (both its thin and thick sections) reabsorbs sodium and chlorine and practically does not reabsorb water, since it is completely impermeable to it. The reabsorption of sodium chloride by the ascending part of the loop is responsible for the reabsorption of water in its descending part, i.e. the passage of sodium chloride from the ascending limb into the interstitial fluid increases the osmolarity of this fluid, and this entails greater reabsorption of water through diffusion from the water-permeable descending limb. Therefore, this section of the tubule is called the distributing segment. As a result, the fluid, already hypoosmotic in the ascending thick part of the loop of Henle (due to the release of sodium), enters the distal convoluted tubule, where the dilution process continues and it becomes even more hypoosmotic, since in subsequent parts of the nephron organic substances are not absorbed into them, only ions are reabsorbed and H 2 O. Thus, it can be argued that the distal convoluted tubule and the ascending part of the loop of Henle function as segments where urine dilution occurs. As it moves along the medullary collecting duct, the tubular fluid becomes more and more hyperosmotic, because reabsorption of sodium and water continues in the collecting ducts, where the final urine is formed (concentrated, due to the regulated reabsorption of water and urea. H 2 O passes into the interstitial substance according to the laws of osmosis, since there is a higher concentration of substances. Percentage of reabsorption water can vary widely depending on the water balance of a given organism.
Distal reabsorption. Optional, adjustable.
Peculiarities:
1. The walls of the distal segment are poorly permeable to water.
2. Sodium is actively reabsorbed here.
3. Wall permeability regulated :for water- antidiuretic hormone, for sodium- aldosterone.
4. The process of secretion of inorganic substances occurs.
Threshold and non-threshold substances.
Reabsorption of substances depends on their concentration in the blood. The excretion threshold is the concentration of a substance in the blood at which it cannot be completely reabsorbed in the tubules and ends up in the final urine. The elimination threshold for different substances is different.
Threshold substances are substances that are completely reabsorbed in the renal tubules and appear in the final urine only if their concentration in the blood exceeds a certain value. Threshold - glucose is reabsorbed depending on its concentration in the blood. Glucose, when it increases in the blood from 5 to 10 mmol/l, appears in the urine, amino acids, plasma proteins, vitamins, Na + Cl _ K + Ca + ions.
Non-threshold substances - which are excreted in the urine at any concentration in the blood plasma. These are the end products of metabolism that must be removed from the body (eg inulin, creatinine, diodrast, urea, sulfates).
Factors influencing reabsorption
Kidney factors:
Reabsorption capacity of the renal epithelium
Extrarenal factors:
Endocrine regulation of the activity of the renal epithelium by the endocrine glands
ROTARY-COUNTERFLOW SYSTEM
Only the kidneys of warm-blooded animals have the ability to form urine with a higher osmotic concentration than blood. Many researchers tried to unravel the physiological mechanism of this process, but only in the early 50s of the twentieth century was the hypothesis substantiated according to which the formation of osmotically concentrated urine is associated with mechanism of a rotary-countercurrent multiplying system some areas of the nephron. The components of the countercurrent multiplying system are all the structural elements of the internal zone of the renal medulla: thin segments of the ascending and descending parts of the loops of Henle belonging to the juxtamedullary nephrons, the medullary sections of the collecting ducts, the ascending and descending straight vessels of the pyramids with capillaries connecting them, the interstitium of the renal papilla with those located in it interstitial cells. Structures located outside the papilla also take part in the work of the countercurrent multiplier - thick segments of the loops of Henle, afferent and efferent arterioles of the juxtamedullary glomeruli, etc.
Key points: the concentration of osmotically active substances in the contents of the collecting ducts increases as the fluid moves from the cortex to the papilla. This occurs due to the fact that the hypertonic tissue fluid of the interstitium of the inner zone of the medulla osmotically extracts water from the initially isosmotic urine.
The transition of water equalizes the osmotic pressure of urine in the convoluted tubules of the first order to the level of the osmotic pressure of tissue fluid and blood. In the loop of Henle, the isotonicity of urine is disrupted due to the functioning of a special mechanism - the rotary-countercurrent system.
The essence of the rotary-countercurrent system is that the two legs of the loop, descending and ascending, are in close contact with each other and function conjugately as a single mechanism. The epithelium of the descending (proximal) loop allows water to pass through, but does not allow Na + to pass through. The epithelium of the ascending (distal) loop actively reabsorbs Na, i.e. from tubular urine transfers it into the tissue fluid of the kidney, but does not allow water to pass through.
As urine passes through the descending limb of the loop of Henle, the urine gradually thickens due to the transition of water into the tissue fluid, since Na + passes from the ascending limb and attracts water molecules from the descending limb. This increases the osmotic pressure of the tubular fluid and it becomes hypertonic at the apex of the loop of Henle.
Due to the release of sodium from the urine into the tissue fluid, the urine, which is hypertonic at the apex of the loop of Henle, becomes hypotonic in relation to the blood plasma at the end of the ascending tubule of the loop of Henle. Between two adjacent sections of the descending and ascending tubules, the difference in osmotic pressure is not great. The loop of Henle works as a concentration mechanism. In it, a multiplication of the “single” effect occurs - leading to the concentration of liquid in one knee, due to dilution in the other. This multiplication is due to the opposite direction of fluid flow in both legs of the loop of Henle.
As a result, a longitudinal concentration gradient is created in the first section of the loop, and the liquid concentration becomes several times greater than with a single effect. This is the so called multiplying the concentrating effect. As the loop progresses, these small pressure differences in each section of the tubules add up, resulting in a very large difference (gradient) in osmotic pressure between the beginning or end of the loop and its top. The loop functions as a concentrating mechanism, resulting in the reabsorption of large amounts of water and Na+.
Depending on the state of the body’s water balance, the kidneys secrete hypotonic (osmotic dilution) or, on the contrary, hypertonic (osmotically concentrated) urine.
In the process of osmotic concentration of urine in the kidney, all sections of the tubules, vessels of the medulla, and interstitial tissue take part, which function as a rotary-countercurrent multiplying system.
The direct vessels of the medulla of the kidney, like the tubules of the nephron loop, form a countercurrent system. When blood moves towards the top of the medulla, the concentration of osmotically active substances in it increases, and during the return movement of blood to the cortex, salts and other substances diffuse through the vascular wall and pass into the interstitial tissue. Thus, the concentration gradient of osmotically active substances inside the kidney is maintained and the vasa recta function as a countercurrent system. The speed of blood movement through the straight vessels determines the amount of salts and urea removed from the medulla and the outflow of reabsorbed water.
Substance to be reabsorbed, must (1) move through the epithelial lining of the tubule into the intercellular fluid, and then (2) through the membranes of the peritubular capillaries - back into the blood. Therefore, the reabsorption of water and solutes is a multi-stage process. The transfer of substances through the tubular epithelium into the intercellular fluid is carried out using active and passive transport mechanisms. For example, water and substances dissolved in it are able to penetrate cells either directly through the membrane (transcellular) or using the spaces between cells (paracellular).
Then after entering the intercellular fluid The solutions complete the remainder of their journey by ultrafiltration (mass movement) mediated by hydrostatic and colloid-osmotic forces. Under the action of a net force aimed at reabsorbing water and substances dissolved in it from the interstitial fluid into the blood, the peritubular capillaries perform a function similar to the venous ends of most capillaries.
Using energy, produced during the metabolic process, active transport is capable of moving solutes against an electrochemical gradient. The type of transport that depends on the expenditure of energy obtained, for example, from the hydrolysis of adenosine triphosphate, is called primary active transport. As an example of such transport, let us consider sodium-potassium ATPase, whose activity is carried out in many parts of the tubular system.
View transport, which does not directly depend on the energy source, for example due to a concentration gradient, is called secondary active transport. An example of this type of transport is the reabsorption of glucose in the proximal tubule. Water is always reabsorbed passively through a mechanism called osmosis. This term refers to the diffusion of water from an area of low concentration of a substance (high water content) to an area of high concentration of a substance (low water content).
Solutes can move through the membrane of epithelial cells or through intercellular spaces.
Renal tubule cells, like other epithelial cells, are held together by tight junctions. On the sides of the cells in contact with each other, behind these connections, there are intercellular spaces. Solutes can be reabsorbed through the cell using the transcellular pathway or penetrate through the tight junction and intercellular spaces via the paracellular pathway. This mode of transport is also used in some segments of the nephron, especially in the proximal tubules, where water and substances such as potassium, magnesium, and chloride ions are reabsorbed.
Primary active transport through the membrane is associated with ATP hydrolysis. The special significance of primary active transport is that it allows solutes to move against an electrochemical gradient. The energy required for this type of transport is provided by ATP, the hydrolysis of the molecule of which is provided by membrane-bound ATPase. The ATPase enzyme is also an integral part of the transport system that attaches and moves solutes across the membrane. Known primary active substance transport systems include the following ATPases: sodium-potassium, hydrogen ion transport, hydrogen-potassium and calcium.
A striking example of how the system works primary active transport is the process of sodium reabsorption through the membrane of the proximal convoluted tubule. It is located on the lateral surfaces of epithelial cells closer to the basement membrane and is a powerful Na+/K+ pump. Its ATPase supplies the system with energy, released with ATP hydrolysis and used to transport Na+ ions from the cell to the intercellular space. At the same time, potassium is transferred from the intercellular fluid into the cell. The activity of this ion pump is aimed at maintaining a high concentration of potassium and a low concentration of sodium in the cell.
In addition, it creates relative potential difference with a charge inside the cell of about -70 mV. The excretion of sodium by a pump located on the membrane of the basolateral region of the cell promotes its diffusion back into the cell through the region facing the lumen of the tubule for the following reasons: (1) the presence of a concentration gradient for sodium directed from the lumen of the tubule into the cell, because . its concentration in the cell is low (12 meq/l), in the lumen it is high (140 meq/l); (2) the negative charge inside the cell (-70 mV) attracts positively charged Na ions.
Active sodium reabsorption with the help of sodium-potassium ATPase occurs in many parts of the nephron tubular system. In certain parts of it, there are additional mechanisms that ensure the reabsorption of large amounts of sodium into the cell. In the proximal tubule, the side of the cell facing the lumen of the tubule is represented by a brush border, increasing the surface area by approximately 20 times. This membrane also contains carrier proteins that bind and transport sodium from the lumen of the tubules into the cell, providing them with facilitated diffusion. These carrier proteins also play an important role in the secondary active transport of other substances such as glucose and amino acids. This process is described in detail below.
Thus, process of reabsorption of Na+ ions from the lumen of the tubules back into the blood consists of at least three stages.
1. Diffusion of Na+ ions through the membrane of the tubular epithelial cells (also called the apical membrane) into the cells along an electrochemical gradient maintained by the Na+/K+ pump, which is located on the basolateral side of the membrane.
2. Transfer of sodium across the basolateral membrane into the interstitial fluid. It is carried out against an electrochemical gradient using a Na+/K+ pump with ATPase activity.
3. Sodium reabsorption, water and other substances from the intercellular fluid into the peritubular capillaries by ultrafiltration - a passive process provided by gradients of hydrostatic and colloid-osmotic pressure.