These hormones are produced in the hypothalamus. They accumulate in the neurohypophysis. In the cells of the supraoptic and paraventricular nuclei of the hypothalamus, oxytocin and antidiuretic hormone are synthesized. The synthesized hormones are transported to the posterior pituitary gland by axonal transport with the help of a neurophysin carrier protein along the hypothalamic-pituitary tract. Here, hormones are deposited and subsequently released into the blood.

Antidiuretic. hormone (ADH), or vasopressin, performs an antidiuretic effect in the body, which is expressed in the stimulation of water reabsorption in the distal nephron.

This action is carried out due to the interaction of the hormone with type V-2 vasopressin receptors, which leads to an increase in the permeability of the walls of the tubules and collecting ducts for water, its reabsorption and concentration of urine. In the cells of the tubules, hyaluronidase is also activated, which leads to increased depolymerization. hyaluronic acid, resulting in increased reabsorption of water and an increase in the volume of circulating fluid.

Insufficient formation of ADH develops diabetes insipidus, or diabetes insipidus, which is manifested by the release of large amounts of urine (up to 25 liters per day) of low density, increased thirst. Reasons not diabetes may be sharp and chronic infections in which the hypothalamus is affected (influenza, measles, malaria), craniocerebral trauma, tumor of the hypothalamus.

Excess secretion of ADH leads, on the contrary, to water retention in the body.

Oxytocin selectively acts on the smooth muscles of the uterus, causing it to contract during childbirth. There are special oxytocin receptors on the surface membrane of cells. Oxytocin does not increase during pregnancy contractile activity uterus, but before childbirth under the influence high concentrations estrogen dramatically increases the sensitivity of the uterus to oxytocin. Oxytocin is involved in the process of lactation. By increasing the contraction of myoepithelial cells in the mammary glands, it promotes the release of milk. An increase in the secretion of oxytocin occurs under the influence of impulses from the receptors of the cervix, as well as the mechanoreceptors of the nipples of the breast during breastfeeding. Estrogens increase the secretion of oxytocin. Functions of oxytocin in male body not studied enough.

The lack of production of oxytocin causes weakness of labor activity.

Thyroid

The thyroid gland consists of two lobes connected by an isthmus and located on the neck on both sides of the trachea below the thyroid cartilage. It has a lobed structure. The gland tissue consists of follicles filled with colloid, which contains the iodine-containing hormones thyroxine (tetraiodothyronine) and triiodothyronine in bound state with the protein thyroglobulin. In the interfollicular space are located parafollicular cells that produce the hormone thyrocalcitonin. The content of thyroxine in the blood is greater than that of triiodothyronine. However, the activity of triiodothyronine is higher than that of thyroxine. These hormones are formed from the amino acid tyrosine by iodination. Inactivation occurs in the liver through the formation of paired compounds with glucuronic acid.

Iodine-containing hormones perform the following functions in the body: 1) enhancing all types of metabolism (protein, lipid, carbohydrate), increasing basal metabolism and enhancing energy production in the body; 2) influence on growth processes, physical and mental development; 3) increase in heart rate; 4) stimulation of activity digestive tract: increased appetite, increased intestinal motility, increased secretion of digestive juices; 5) increase in body temperature due to increased heat production; 6) increased excitability of the sympathetic nervous system.

secretion of hormones thyroid gland regulated by thyroid-stimulating hormone of the adenohypophysis, thyroliberin of the hypothalamus, iodine content in the blood. With a lack of iodine in the blood, as well as iodine-containing hormones, the production of thyreoliberin increases according to the positive feedback mechanism, which stimulates the synthesis thyroid-stimulating hormone which in turn leads to an increase in thyroid hormone production. With an excess amount of iodine in the blood and thyroid hormones, a negative feedback mechanism works.

Thyroid function disorders are manifested by its hypofunction and hyperfunction. If the failure of function develops in childhood, then this leads to growth retardation, violation of the proportions of the body, sexual and mental development. This pathological condition is called cretinism.

In adults, hypofunction of the thyroid gland leads to the development pathological condition- myxedema. In this disease, inhibition of neuropsychic activity is observed, which manifests itself in lethargy, drowsiness, apathy, decreased intelligence, impaired sexual function, inhibition of all types of metabolism and a decrease in basal metabolism. In such patients, body weight is increased due to an increase in the amount of tissue fluid and puffiness of the face is noted. Hence the name of this disease: myxedema - mucous edema

Hypothyroidism can develop in people living in areas where there is a lack of iodine in water and soil. This is the so-called endemic goiter. In this disease, the thyroid gland is enlarged (goiter), the number of follicles increases, however, due to a lack of iodine, little o6 hormones are formed, which leads to corresponding disorders in the body, manifested as hypothyroidism.

With hyperfunction of the thyroid gland, the disease develops thyrotoxicosis (diffuse toxic goiter, Basedow's disease, Graves' disease). The characteristic signs of this disease are an increase in the thyroid gland (goiter), exophthalmos, tachycardia, an increase in metabolism, especially the main one, weight loss, an increase in appetite, a violation of the body's heat balance, increased excitability and irritability.

Calcitonin or thyrocalcitonin along with parathyroid hormone parathyroid glands participates in the regulation of calcium metabolism. Under its influence, the level of calcium in the blood decreases (hypocalcemia). It occurs as a result of the action of the hormone on bone tissue, where it activates the function of osteoblasts and enhances mineralization processes. The function of osteoclasts, which destroy bone tissue, on the contrary, is inhibited. In the kidneys and intestines, calcitonin inhibits calcium reabsorption and enhances phosphate reabsorption. The production of thyrocalcitonin is regulated by the level of calcium in the blood plasma by the feedback type. With a decrease in the calcium content, the production of thyrocalcitonin is inhibited, and vice versa.

There are five types of action of hormones on target tissues: metabolic, morphogenetic, kinetic, corrective and reactogenic.

1. Metabolic action of hormones

Metabolic action of hormones - causes a change in metabolism in tissues. It occurs due to three main hormonal influences.
First of all, hormones change the permeability of cell membranes and organelles, which changes the conditions of membrane transport of substrates, enzymes, ions and metabolites and, accordingly, all types of metabolism.
Secondly, hormones change the activity of enzymes in the cell, leading to a change in their structure and configuration, facilitating connections with cofactors, reducing or increasing the intensity of the breakdown of enzyme molecules, stimulating or suppressing the activation of proenzymes.
Thirdly, hormones change the synthesis of enzymes, inducing or suppressing their formation by influencing the genetic apparatus of the cell nucleus, both directly interfering in the processes of nucleic acid and protein synthesis, and indirectly through the energy and substrate-enzyme provision of these processes. Changes in metabolism caused by hormones underlie changes in the function of cells, tissues or organs.

2. Morphogenetic action hormones

Morphogenetic action - the influence of hormones on the processes of shaping, differentiation and growth of structural elements. These processes are carried out due to changes in the genetic apparatus of the cell and metabolism. Examples are the effect of somatotropin on body growth and internal organs, sex hormones - on the development of secondary sexual characteristics.

3. Kinetic action of hormones

Kinetic action - the ability of hormones to trigger the activity of the effector, to include the implementation of a specific function. For example, oxytocin causes contraction of the muscles of the uterus, adrenaline triggers the breakdown of glycogen in the liver and the release of glucose into the blood, vasopressin turns on the reabsorption of water in the collecting ducts of the nephron, which does not occur without it.

4. Corrective action hormones

Corrective action - a change in the activity of organs or processes that occur in the absence of a hormone. An example of the corrective action of hormones is the effect of adrenaline on the heart rate, the activation of oxidative processes by thyroxin, and the decrease in the reabsorption of potassium ions in the kidneys under the influence of aldosterone. A kind of corrective action is the normalizing effect of hormones, when their influence is aimed at restoring an altered or even disturbed process. For example, with the initial prevalence of anabolic processes of protein metabolism, glucocorticoids cause a catabolic effect, but if the breakdown of proteins predominates initially, glucocorticoids stimulate their synthesis.

In a broader sense, the dependence of the magnitude and direction of the effect of the hormone on the features of metabolism or function that are present before its action is determined by initial state ruleyaniya, described at the beginning of the chapter. The initial state rule shows that the hormonal effect depends not only on the number and properties of hormone molecules, but also on the reactivity of the effector, which is determined by the number and properties of membrane receptors for the hormone. Reactivity in this context is the ability of an effector to respond with a certain magnitude and direction of response to the action of a particular chemical regulator.

5. Reactogenic action of hormones

The reactogenic effect of hormones is the ability of a hormone to change the reactivity of a tissue to the action of the same hormone, other hormones, or mediators of nerve impulses. For example, calcium-regulating hormones reduce the sensitivity of the distal nephron to the action of vasopressin, folliculin enhances the effect of progesterone on the uterine mucosa, thyroid hormones enhance the effects of catecholamines. A type of reactogenic action of hormones is permissive action, meaning the ability of one hormone to allow the effect of another hormone to be realized. For example, glucocorticoids have a permissive effect on catecholamines, i.e. to realize the effects of adrenaline, the presence of small amounts of cortisol is necessary, insulin has a permissive effect on somatotropin (growth hormone), etc. hormonal regulation is that the reactogenic effect of hormones can be realized not only in target tissues, where the concentration of receptors for them is high, but also in other tissues and organs that have single receptors for the hormone.

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. It means that potential effect from a small change in reabsorption can be very significant for the amount of urine excreted. 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 are excreted into large quantities with 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, the composition of body fluids is precisely controlled.

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 in normal conditions reabsorbed from the primary urine almost completely 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 an important diagnostic sign of the severity of diabetes mellitus. 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 others. organic matter(for example, inulin). These substances are used to study kidney function.

Some of the removed substances can be partially reabsorbed (urea, uric acid) and are not completely excreted (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). The 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 may develop in healthy individuals after intense long physical work. The presence of persistent and higher proteinuria is a sign of a violation of the mechanisms 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 others necessary for the body substances 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 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 organic origin that entered the body (antibiotics, dyes, X-ray contrast agents), the rate of their release 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 (therefore, 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 the hyperosmosis 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 to the high content of sodium chloride and urea in the hyperosmotic intercellular fluid of the medulla of the kidney. 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 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-) from their total entering 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. source 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(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 limb of the loop of Henle, water is not reabsorbed, and the concentration is 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 main function nephron loops. 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 + and water ions depends on the state of the body's water and electrolyte balance and is controlled by antidiuretic hormone, aldosterone, and 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 ducts of the cortical substance 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 extremely important role in determining the content of water and dissolved substances in 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 role leading 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 intensity 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 averages 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, nevertheless, the blood is cleared of some substances by almost 90% during one passage through the night. One of these natural substances is paraaminohippuric 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. Thus, the excitation 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.

If cut kidney transplanted to the neck of the animal, connecting the renal artery with carotid artery, and the renal vein jugular vein, then such a kidney, devoid of nerve connections with the body, can work for many weeks and even months, excreting more or less normal urine. When the body is loaded with water or table salt the amount of water or salt secreted by the kidney increases. Therefore, even with complete denervation, almost normal kidney function. Moreover, despite the denervation, the activity of the transplanted kidney changes under the influence of stimuli acting on nervous system. So, with painful stimuli, the denervated kidney ceases to excrete urine in the same way as the normally innervated kidney.

Insufficiency of the function of the posterior lobe of the pituitary gland, which secretes antidiuretic hormone, turns off the action of the regulatory mechanism described above. The wall of the distal nephron becomes completely impermeable to water, and the kidney excretes a large amount of it in the urine. In these cases, up to 20-25 liters of urine can be excreted per day (diabetes insipidus). The secretion of antidiuretic hormone by the pituitary gland is regulated by the nuclei of the hypothalamus.

Diuresis is also influenced by the hormone of the adrenal medulla - adrenaline. With the introduction of small doses of adrenaline into the vessels of the kidney, the volume of the kidney increases. This is due to the fact that adrenaline narrows the efferent arterial vessels (vas efferens) and thereby leads to an increase in filtration pressure in the glomeruli.

AT large doses adrenaline also constricts the adductor vessels, which reduces blood flow to the glomeruli and leads to the cessation of diuresis.

Some of the hormones of the adrenal cortex, the so-called mineralocorticoids - aldosterone, deoxycorticosterone, act on the epithelium of the tubules, increase the absorption of sodium into the blood. Disease or removal of the adrenal glands turns off this mechanism and leads to a sharp loss of sodium in the urine and to severe disorders of the body.

The activity of the kidneys is also influenced by thyroid hormones and parathyroid glands.

Thyroid hormone reduces the binding of water and salt to tissues, causing them to pass into the blood, and in this way increases diuresis. In addition, it enhances all types of exchange, in particular protein metabolism, as a result of which the formation of end products of this metabolism increases, which also leads to increased diuresis. The parathyroid hormone promotes the transfer of calcium and phosphorus from the bones to the bloodstream and sharp increase the content of these substances in the blood, as a result, their excretion with urine increases.

PHYSIOLOGY OF THE KIDNEYS

Urine formation is carried out through three sequential processes:

glomerular filtration water and low molecular weight components from blood plasma into the capsule of the renal glomerulus with the formation of primary urine;

tubular reabsorption- reabsorption process of filtered substances and water from primary urine to blood;

tubular secretion- the process of transferring ions and organic substances from the blood into the lumen of the tubules.

Glomerular filtration

Carried out in the renal corpuscles. They filter blood plasma from the capillaries of the glomeruli into the cavity of the nephron capsule. Filtration is the process of passing water and substances dissolved in it under the influence of a pressure difference in the capillaries of the vascular glomerulus and pressure in the cavity of the nephron capsule. The filtering membrane through which fluid passes from the lumen of the capillaries into the cavity of the glomerular capsule consists of three layers: capillary endothelial cells, basement membrane and epithelium visceral layer capsules, or podocytes.

capillary endothelium strongly thinned and has round or oval holes with a diameter of 50-100 nm, occupying up to 30% of the cell surface. They cannot pass through these holes. shaped elements blood. The remaining components of blood plasma and water can freely reach the basement membrane.

basement membrane is the most important part of the kidney filter. The pores in the basement membrane are 3-7 nm.

Podocytes. These epithelial cells face the lumen of the renal corpuscle capsule. They have processes - legs that are attached to the basement membrane. Between the legs there are spaces - slit diaphragms, which, like the pores of the basement membrane, limit the filtration of substances with a diameter of more than 7 nm.

The resulting glomerular filtrate, similar in chemical composition with blood plasma, but not containing proteins, is called primary urine. During the day, 150-180 liters of primary urine are formed in the kidneys.

The main factor contributing to the filtration process is the high hydrostaticpressure in the capillaries of the glomeruli, equal to 70-90 mm Hg. Art. He is opposed oncotic pressure blood plasma proteins, equal to 25-30 mm Hg. Art. and fluid pressure in the cavity of the nephron capsule, those. primary urine, equal to 10-15 mm Hg. Hence, effective filtration

pressure is the difference between the hydrostatic pressure of the blood in the capillaries and the sum of the oncotic pressure of the blood plasma and the intrarenal pressure.

R filter. = P hydr. - (P onc. + P urine)

70 mmHg Art. – (30 mm Hg + 10 mm Hg) = 30 mm Hg Art.

Thus, the filtration pressure is 30 mm Hg. Art., and if the arterial pressure in the capillaries of the glomeruli is below 30 mm Hg. Art., then the filtration of urine stops.

tubular reabsorption (reverse suction)

Primary urine, formed in the renal corpuscles, turns into the final one due to the processes that occur in the renal tubules and collecting ducts. In the human kidney, 150-180 liters of primary urine is formed per day, and 1-1.5 liters of final urine is excreted. The rest of the liquid is absorbed in the tubules and collecting ducts. Tubular reabsorption is the process of reabsorption of water and substances from the urine contained in the lumen of the tubules into the blood, as a result of which the final urine differs sharply in composition from the primary. It does not contain glucose, amino acids, some salts, and the concentration of urea and a number of other substances is sharply increased. The main purpose of reabsorption is to keep the body alive important substances in the required quantities.

The bulk of the molecules are absorbed back into the blood in the proximal nephron. The nephron loop, distal convoluted tubule, and collecting ducts absorb electrolytes and water.

Reabsorption can occur actively and passively.

active reabsorption carried out due to the activity of the epithelium of the renal tubules with the participation of special enzyme systems with the expenditure of energy. Glucose, amino acids, phosphates, sodium salts are actively reabsorbed. Due to active reabsorption, it is possible to reabsorb substances from the urine into the blood even when their concentration in the blood is equal to the concentration of fluid in the tubules or higher.

passive reabsorption occurs without energy expenditure due to diffusion and osmosis. Due to passive reabsorption, water and chlorides are reabsorbed.

In the proximal nephron, the so-called threshold substances: amino acids, glucose, vitamins, trace elements, a significant amount of Na +, Cl - ions, etc. They are excreted in the urine only if their concentration in the blood is higher than the body's constant values. In this regard, there is the concept of the withdrawal threshold. Removal threshold - this is the concentration of substances in the blood at which it cannot be completely reabsorbed in the tubules and enters the final urine. An example of threshold substances is glucose, which, at its normal concentration in the blood (normal 4.45-6.65 mmol / l), is completely reabsorbed. Traces of glucose begin to be excreted in the urine at a blood sugar level of 8.34-10 mmol / l. This will be the threshold for glucose excretion.

In addition to the threshold, in the urine there are also non-threshold substances. They are excreted in the urine at any concentration in the blood. Getting from the blood into the primary urine, they are not reabsorbed (urea, creatinine, sulfates, ammonia, etc.). Due to reabsorption in the tubules of water, the content of non-threshold substances (i.e., metabolic products) in the final urine reaches large values. For example, there is 65 times more urea in the final urine than in the blood, 75 times more creatinine, and 90 times more sulfates.

The reverse absorption of substances from the primary urine into the blood in different parts of the nephron is not the same. So, for example, in the proximal convoluted tubules, the reabsorption of sodium and potassium ions is constant, little dependent on their concentration in the blood ( mandatory reabsorption). In the distal convoluted tubules, the reabsorption of these ions is variable and depends on their level in the blood. (facultative reabsorption) Therefore, the distal convoluted tubules regulate and maintain a constant concentration of sodium and potassium ions in the body.

In the mechanism of reabsorption of water and sodium ions, a special place is occupied by rotary-countercurrent system, which is formed by the descending and ascending limbs of the nephron loop. In close contact with each other, the descending and ascending knees function as a single mechanism. The essence of such joint work is as follows. The nephron loop has two knees: descending and ascending. The epithelium of the descending knee is permeable to water, and the epithelium of the ascending knee is impervious to water, but is able to actively conduct sodium ions and transfer them into the tissue fluid, and through it back into the blood.

Passing through the descending part of the nephron loop, urine gives off water, thickens, becomes more concentrated. This release of water occurs passively due to the fact that simultaneously in the ascending department is carried out active reabsorption of sodium ions. Entering the tissue fluid, sodium ions increase its osmotic pressure and thereby contribute to the attraction of water from the descending knee into the tissue fluid. In turn, an increase in the concentration of urine in the nephron loop due to the reabsorption of water in the descending knee facilitates the transition of sodium ions from urine to tissue fluid in the ascending knee. Thus, the nephron loop acts as a urine-concentrating mechanism. The thickening of urine continues further in the collecting ducts.

tubular secretion

In addition to reabsorption, the process of secretion is carried out in the tubules of the nephron. tubular secretion - it is the transport of substances from the blood to the lumen of the tubules (urine). Thanks to the secretory function of the tubules, substances are removed from the blood that do not pass through the renal filter in the glomeruli or are contained in the blood in in large numbers. Tubular secretion is a predominantly active process that occurs with energy expenditure. Tubular secretion allows you to quickly remove some ions, for example, potassium, organic acids (uric acid) and bases (choline, guanidine), including a number of substances foreign to the body, such as antibiotics (penicillin), radiopaque substances (diodrast), dyes (phenol red) , para-aminohippuric acid.

The cells of the renal tubules are able not only to secrete, but also synthesized b some substances from various organic and inorganic products. For example, they synthesize hippuric acid from benzoic acid and the amino acid glycocol, ammonia by deamination of certain amino acids, and so on.

Quantity, composition and properties of urine.

A person excretes an average of 1.5 liters of urine per day. After heavy drinking, consumption of protein foods, diuresis increases. With the consumption of a small amount of water, with increased sweating, diuresis decreases. The intensity of urination fluctuates throughout the day. Night. Urination is less than during the day.

Urine is a clear liquid of light yellow color, with a relative density of 1010-1025, which depends on the amount of fluid taken.

Urine reaction healthy person usually slightly acidic. However, pHee ranges from 5.0 to 7.0 depending on the nature of the diet. When eating predominantly protein food, the urine reaction becomes acidic, vegetable - neutral or even alkaline.

In the urine of a healthy person, protein is absent or its traces are determined.

During the day, an average of 60 g is excreted in the urine. dense substances (4%). Of these, organic substances are excreted in the range of 35-45 g / day, inorganic - 15-25 g / day.

Urine contains urea, uric acid, ammonia, purine bases, creatinine. Among the organic compounds of non-protein origin in the urine there are salts of oxalic acid, lactic acid.

Electrolytes are excreted in the urine (Na +, K +, Cl -, Ca 2+, Ma 2+, sulfates, etc.)

Regulation of urination

The activity of the kidneys is regulated by the nervous and humoral pathways. Direct nervous regulation of the kidneys is less pronounced than humoral. Usually, both types of regulationcarried outparallel hypothalamus or cerebral cortex. The nervous regulation of urination most of all affects the processes of filtration, and the humoral regulation affects the processes of reabsorption.

Nervous regulation of urination

The nervous system can influence the work of the kidneys in both conditioned reflex and unconditioned reflex ways. The unconditioned reflex subcortical mechanism for controlling urination is carried out by the centers of sympathetic and vagus nerves, conditioned reflex - bark hemispheres. Higher subcortical center of regulationurination is the hypothalamus.

When stimulated by sympathetic nerves filtration of urine, as a rule, decreases due to narrowing of the renal vessels that bring blood to the glomeruli. With painful irritations, a reflex decrease in urination is observed, up to a complete cessation (painful anuria). The narrowing of the renal vessels in this case occurs not only as a result of excitation of the sympathetic nerves, but also due to an increase in the secretion of the hormones vasopressin and adrenaline, which have a vasoconstrictive effect.

With irritation of the vagus nerves urinary excretion of chlorides increases by reducing their reabsorption in the tubules of the kidneys.

A decrease and increase in urine formation can be caused by a conditioned reflex, which indicates a pronounced effect of the higher parts of the central nervous system on the functioning of the kidneys. cerebral cortex affects the functioning of the kidneys both directly through the autonomic nerves and humorally through the hypothalamus, the neurosecretory nuclei of which are endocrine and produce antidiuretic hormone (ADH). This hormone is transported along the axons of neurons of the hypothalamus to the posterior pituitary gland, where it accumulates and, depending on the internal environment of the body, enters the blood in greater or lesser quantities, regulating the formation of urine. This shows the unity of nervous and humoral regulation.

Humoral regulation of urination

The leading role in the regulation of kidney activity belongs to the humoral system. Many hormones affect kidney function, the main ones being antidiuretic hormone (ADH), or vasopressin, and aldosterone.

Antidiuretic hormone (ADH), or vasopressin, promotes water reabsorption in the distal nephron by increasing the water permeability of the walls of the distal convoluted tubules and collecting ducts. With an excess of the hormone, the permeability of the walls of the tubules for water increases, and the amount of urine produced decreases. With a lack of ADH, the permeability of the walls of the tubules for water decreases and a serious disease develops - diabetes insipidus, or diabetes insipidus. With it, water ceases to be reabsorbed, as a result of which a large amount of light urine with an insignificant relative density (up to 25 liters per day) is released, in which there is no sugar.

Aldosterone – hormone of the adrenal cortex. Under the influence of this hormone, the process of reverse absorption of sodium ions increases and at the same time the reabsorption of potassium ions decreases. As a result, sodium excretion in the urine decreases and potassium excretion increases, which leads to an increase in the concentration of sodium ions in the blood and tissue fluid and an increase in osmotic pressure.

Natriuretic hormone (atrial peptide) is formed in the atria and enhances the excretion of sodium ions in the urine.

Adrenalin - a hormone of the adrenal medulla. In small doses, it narrows the lumen of the efferent arterioles, resulting in increased hydrostatic pressure, increased filtration and diuresis. In large doses, it causes constriction of both the efferent and afferent arterioles, which leads to a decrease in urine production up to a complete cessation.

Urination and urination

The final urine formed in the kidneys flows from the tubules to the collecting ducts, then to renal pelvis and from there to the ureter and bladder.

The bladder is innervated by:

sympathetic(hypogastric) nerve. When it is excited, the peristalsis of the ureters increases, the muscular wall Bladder relaxes, the contraction of the sphincters that prevent the outflow of urine increases, i.e. urine accumulates.

parasympathetic(pelvic) nerve. Excitation of the parasympathetic nerve causes the opposite effect: the muscular wall of the bladder contracts, the sphincters that prevent urine from flowing out relax, and urine is expelled from the bladder.

Urine entering the bladder gradually leads to stretching of its walls. When filling up to 250 ml, the mechanoreceptors of the bladder are irritated and impulses are transmitted along the afferent fibers of the pelvic nerve to the sacral region. spinal cord where the center of involuntary urination is located. Impulses from the center along the parasympathetic fibers reach the bladder and urethra and cause contraction of the muscle layer of the bladder and relaxation of the sphincter of the bladder and sphincter of the urethra, which leads to the emptying of the bladder. At the same time, excitation is transmitted from the spinal center of urination to the cerebral cortex, resulting in a sensation of the urge to urinate. The leading mechanism of irritation of the receptors of the bladder is its stretching, and not the increase in pressure.

The spinal center of urination is under the regulatory influence of the overlying parts of the central nervous system, in particular the cerebral cortex. Under its influence, urination can be delayed, increased and even voluntarily called.

Arbitrary urinary retention is absent in newborns. She appears only towards the end of the first year. Lasting conditioned reflex urinary retention is developed in children by the end of the second year. As a result of upbringing, the child develops a conditioned reflex delay in urge and a conditioned situational reflex: urination when certain conditions for its implementation appear.