Prepared by Kasymkanov N.U.

Astana 2015

The main function of the kidneys is to remove water and water-soluble substances (end products of metabolism) from the body (1). The function of regulating the ionic and acid-base balance of the internal environment of the body (homeostatic function) is closely related to the excretory function. 2). Both functions are controlled by hormones. In addition, the kidneys perform an endocrine function, being directly involved in the synthesis of many hormones (3). Finally, the kidneys are involved in intermediary metabolism (4), especially gluconeogenesis and the breakdown of peptides and amino acids (Fig. 1).

A very large volume of blood passes through the kidneys: 1500 liters per day. From this volume, 180 liters of primary urine are filtered. Then the volume of primary urine decreases significantly due to the reabsorption of water, resulting in a daily urine output of 0.5-2.0 liters.

Excretory function of the kidneys. The process of urine formation

The process of urine formation in nephrons consists of three stages.

Ultrafiltration (glomerular or glomerular filtration). In the glomeruli of renal corpuscles, primary urine is formed from blood plasma in the process of ultrafiltration, isoosmotic with blood plasma. The pores through which the plasma is filtered have an effective average diameter of 2.9 nm. With this pore size, all blood plasma components with a molecular weight (M) of up to 5 kDa freely pass through the membrane. Substances with M< 65 кДа частично проходят через поры, и только крупные молекулы (М >65 kDa) are retained by the pores and do not enter the primary urine. Since most blood plasma proteins have a fairly high molecular weight (M > 54 kDa) and are negatively charged, they are retained by the glomerular basement membrane and the protein content in the ultrafiltrate is insignificant.

Reabsorption. Primary urine is concentrated (approximately 100 times its original volume) by reverse filtration of the water. At the same time, almost all low molecular weight substances, especially glucose, amino acids, as well as most electrolytes - inorganic and organic ions, are reabsorbed in the tubules by the mechanism of active transport (Figure 2).

Reabsorption of amino acids is carried out using group-specific transport systems (carriers).

Calcium and phosphate ions. Calcium ions (Ca 2+) and phosphate ions are almost completely reabsorbed in the renal tubules, and the process occurs with the expenditure of energy (in the form of ATP). The yield for Ca 2+ is more than 99%, for phosphate ions - 80-90%. The extent of reabsorption of these electrolytes is regulated by parathyroid hormone (parathyrin), calcitonin and calcitriol.

The peptide hormone parathyrin (PTH), secreted by the parathyroid gland, stimulates the reabsorption of calcium ions and simultaneously inhibits the reabsorption of phosphate ions. In combination with the action of other bone and intestinal hormones, this leads to an increase in the level of calcium ions in the blood and a decrease in the level of phosphate ions.

Calcitonin, a peptide hormone from the C cells of the thyroid gland, inhibits the reabsorption of calcium and phosphate ions. This leads to a decrease in the level of both ions in the blood. Accordingly, with regard to the regulation of calcium ion levels, calcitonin is an antagonist of parathyrin.

The steroid hormone calcitriol, produced in the kidneys, stimulates the absorption of calcium and phosphate ions in the intestine, promotes bone mineralization, and is involved in the regulation of the reabsorption of calcium and phosphate ions in the renal tubules.

Sodium ions. Reabsorption of Na + ions from primary urine is a very important function of the kidneys. This is a highly efficient process: about 97% Na + is absorbed. The steroid hormone aldosterone stimulates, and atrial natriuretic peptide [ANP], synthesized in the atrium, on the contrary, inhibits this process. Both hormones regulate the work of Na + /K + -ATPase, localized on that side of the plasma membrane of tubule cells (distal section and collecting ducts of the nephron), which is washed by blood plasma. This sodium pump pumps Na+ ions from primary urine into the blood in exchange for K+ ions.

Water. Water reabsorption is a passive process in which water is absorbed in an osmotically equivalent volume along with Na + ions. In the distal nephron, water can only be absorbed in the presence of the peptide hormone vasopressin (antidiuretic hormone, ADH), secreted by the hypothalamus. ANP inhibits water reabsorption. i.e., it enhances the removal of water from the body.

Due to passive transport, chlorine ions (2/3) and urea are absorbed. The degree of reabsorption determines the absolute amount of substances remaining in the urine and excreted from the body.

Reabsorption of glucose from primary urine is an energy-dependent process associated with ATP hydrolysis. At the same time, it is accompanied by concomitant transport of Na + ions (along a gradient, since the concentration of Na + in primary urine is higher than in cells). Amino acids and ketone bodies are also absorbed by a similar mechanism.

The processes of reabsorption and secretion of electrolytes and non-electrolytes are localized in various parts of the renal tubules.

Secretion. Most substances to be excreted from the body enter the urine through active transport in the renal tubules. These substances include H + and K + ions, uric acid and creatinine, and drugs such as penicillin.

Organic constituents of urine:

The main part of the organic fraction of urine consists of nitrogen-containing substances, the end products of nitrogen metabolism. Urea produced in the liver. is a carrier of nitrogen contained in amino acids and pyrimidine bases. The amount of urea is directly related to protein metabolism: 70 g of protein leads to the formation of ~30 g of urea. Uric acid serves as the end product of purine metabolism. Creatinine, which is formed due to the spontaneous cyclization of creatine, is the end product of metabolism in muscle tissue. Since daily creatinine excretion is an individual characteristic (it is directly proportional to muscle mass), creatinine can be used as an endogenous substance to determine glomerular filtration rate. The content of amino acids in urine depends on the nature of the diet and the efficiency of the liver. Amino acid derivatives (for example, hippuric acid) are also present in the urine. The content in the urine of derivatives of amino acids that are part of special proteins, for example, hydroxyproline, present in collagen, or 3-methylhistidine, part of actin and myosin, can serve as an indicator of the intensity of the breakdown of these proteins.

The constituent components of urine are conjugates formed in the liver with sulfuric and glucuronic acids, glycine and other polar substances.

Products of metabolic transformation of many hormones (catecholamines, steroids, serotonin) may be present in the urine. Based on the content of the final products, one can judge the biosynthesis of these hormones in the body. The protein hormone choriogonadotropin (CG, M 36 kDa), formed during pregnancy, enters the blood and is detected in the urine by immunological methods. The presence of the hormone serves as an indicator of pregnancy.

Urochromes, derivatives of bile pigments formed during the degradation of hemoglobin, give the yellow color to urine. Urine darkens during storage due to oxidation of urochromes.

Inorganic constituents of urine (Figure 3)

The urine contains Na +, K +, Ca 2+, Mg 2+ and NH 4 + cations, Cl - anions, SO 4 2- and HPO 4 2- and other ions in trace amounts. The content of calcium and magnesium in feces is significantly higher than in urine. The amount of inorganic substances largely depends on the nature of the diet. With acidosis, ammonia excretion may greatly increase. The excretion of many ions is regulated by hormones.

Changes in the concentration of physiological components and the appearance of pathological components of urine are used to diagnose diseases. For example, in diabetes, glucose and ketone bodies are present in the urine (Appendix).

4. Hormonal regulation of urine formation

The volume of urine and the content of ions in it are regulated due to the combined action of hormones and the structural features of the kidney. The volume of daily urine is influenced by hormones:

ALDOSTERONE and VASOPRESSIN (their mechanism of action was discussed earlier).

PARATHORMONE - a parathyroid hormone of a protein-peptide nature (membrane mechanism of action, through cAMP) also affects the removal of salts from the body. In the kidneys, it enhances the tubular reabsorption of Ca +2 and Mg +2, increases the excretion of K +, phosphate, HCO 3 - and reduces the excretion of H + and NH 4 +. This is mainly due to a decrease in tubular reabsorption of phosphate. At the same time, the concentration of calcium in the blood plasma increases. Hyposecretion of parathyroid hormone leads to the opposite phenomena - an increase in the phosphate content in the blood plasma and a decrease in the Ca + 2 content in the plasma.

ESTRADIOL is a female sex hormone. Stimulates the synthesis of 1,25-dioxyvitamin D 3, enhances the reabsorption of calcium and phosphorus in the renal tubules.

Homeostatic kidney function

1) water-salt homeostasis

The kidneys are involved in maintaining a constant amount of water by influencing the ionic composition of intra- and extracellular fluids. About 75% of sodium, chlorine and water ions are reabsorbed from the glomerular filtrate in the proximal tubule due to the mentioned ATPase mechanism. In this case, only sodium ions are actively reabsorbed, anions move due to the electrochemical gradient, and water is reabsorbed passively and isosmotically.

2) participation of the kidneys in the regulation of acid-base balance

The concentration of H + ions in plasma and in the intercellular space is about 40 nM. This corresponds to a pH value of 7.40. The pH of the internal environment of the body must be maintained constant, since significant changes in the concentration of runs are not compatible with life.

The constancy of the pH value is maintained by plasma buffer systems, which can compensate for short-term disturbances in the acid-base balance. Long-term pH equilibrium is maintained through the production and removal of protons. If there are disturbances in the buffer systems and if the acid-base balance is not maintained, for example as a result of kidney disease or disruptions in the frequency of breathing due to hypo- or hyperventilation, the plasma pH value goes beyond acceptable limits. A decrease in pH value of 7.40 by more than 0.03 units is called acidosis, and an increase is called alkalosis.

Origin of protons. There are two sources of protons - free acids in food and sulfur-containing amino acids in proteins obtained from food. Acids, such as citric, ascorbic and phosphoric, release protons in the intestinal tract (at an alkaline pH). The amino acids methionine and cysteine ​​formed during the breakdown of proteins make the greatest contribution to ensuring the balance of protons. In the liver, the sulfur atoms of these amino acids are oxidized to sulfuric acid, which dissociates into sulfate ions and protons.

During anaerobic glycolysis in muscles and red blood cells, glucose is converted into lactic acid, the dissociation of which leads to the formation of lactate and protons. The formation of ketone bodies - acetoacetic and 3-hydroxybutyric acids - in the liver also leads to the release of protons; an excess of ketone bodies leads to an overload of the plasma buffer system and a decrease in pH (metabolic acidosis; lactic acid → lactic acidosis, ketone bodies → ketoacidosis). Under normal conditions, these acids are usually metabolized to CO 2 and H 2 O and do not affect proton balance.

Since acidosis poses a particular danger to the body, the kidneys have special mechanisms to combat it:

a) secretion of H +

This mechanism includes the process of formation of CO 2 in metabolic reactions occurring in the cells of the distal tubule; then the formation of H 2 CO 3 under the action of carbonic anhydrase; its further dissociation into H + and HCO 3 - and the exchange of H + ions for Na + ions. Sodium and bicarbonate ions then diffuse into the blood, causing it to become alkaline. This mechanism has been tested experimentally - the introduction of carbonic anhydrase inhibitors leads to increased sodium loss in secondary urine and acidification of urine stops.

b) ammoniogenesis

The activity of ammoniogenesis enzymes in the kidneys is especially high under conditions of acidosis.

Ammoniogenesis enzymes include glutaminase and glutamate dehydrogenase:

c) gluconeogenesis

It occurs in the liver and kidneys. The key enzyme of the process is renal pyruvate carboxylase. The enzyme is most active in an acidic environment - this is how it differs from the same liver enzyme. Therefore, during acidosis in the kidneys, carboxylase is activated and acid-reacting substances (lactate, pyruvate) more intensively begin to convert into glucose, which does not have acidic properties.

This mechanism is important in acidosis associated with fasting (from a lack of carbohydrates or from a general lack of nutrition). The accumulation of ketone bodies, which are acidic in properties, stimulates gluconeogenesis. And this helps improve the acid-base state and at the same time supplies the body with glucose. During complete fasting, up to 50% of blood glucose is formed in the kidneys.

With alkalosis, gluconeogenesis is inhibited (as a result of changes in pH, PVK carboxylase is inhibited), proton secretion is inhibited, but at the same time glycolysis is enhanced and the formation of pyruvate and lactate increases.

Metabolic kidney function

1) Formation of the active form of vitamin D 3. In the kidneys, as a result of the microsomal oxidation reaction, the final stage of maturation of the active form of vitamin D 3 - 1,25-dioxycholecalciferol - occurs. The precursor of this vitamin, vitamin D 3, is synthesized in the skin, under the influence of ultraviolet rays from cholesterol, and then hydroxylated: first in the liver (at position 25), and then in the kidneys (at position 1). Thus, by participating in the formation of the active form of vitamin D 3, the kidneys influence phosphorus-calcium metabolism in the body. Therefore, in case of kidney diseases, when the processes of hydroxylation of vitamin D 3 are disrupted, OSTEODISTROPHY may develop.

2) Regulation of erythropoiesis. The kidneys produce a glycoprotein called renal erythropoietic factor (REF or ERYTHROPOETIN). It is a hormone that is capable of influencing red bone marrow stem cells, which are the target cells for PEF. PEF directs the development of these cells along the path of sritropoiesis, i.e. stimulates the formation of red blood cells. The rate of PEF release depends on the supply of oxygen to the kidneys. If the amount of incoming oxygen decreases, the production of PEF increases - this leads to an increase in the number of red blood cells in the blood and an improvement in oxygen supply. Therefore, in kidney diseases, renal anemia is sometimes observed.

3) Biosynthesis of proteins. In the kidneys, the processes of biosynthesis of proteins that are necessary for other tissues are actively taking place. Some components are synthesized here:

Blood coagulation systems;

Complement systems;

Fibrinolysis systems.

In the kidneys, RENIN is synthesized in the cells of the juxtaglomerular apparatus (JA).

The renin-angiotensin-aldosterone system works in close contact with another system for regulating vascular tone: the KALLIKREIN-KININ SYSTEM, the action of which leads to a decrease in blood pressure.

The protein kininogen is synthesized in the kidneys. Once in the blood, kininogen, under the action of serine proteinases - kallikreins, is converted into vasoactive peptides - kinins: bradykinin and kallidin. Bradykinin and kallidin have a vasodilating effect - they lower blood pressure. Inactivation of kinins occurs with the participation of carboxycathepsin - this enzyme simultaneously affects both systems of regulation of vascular tone, which leads to an increase in blood pressure. Carboxycathepsin inhibitors are used for medicinal purposes in the treatment of certain forms of arterial hypertension (for example, the drug clofelline).

The participation of the kidneys in the regulation of blood pressure is also associated with the production of prostaglandins, which have a hypotensive effect and are formed in the kidneys from arachidonic acid as a result of lipid peroxidation reactions (LPO).

4) Protein catabolism. The kidneys are involved in the catabolism of some low molecular weight proteins (5-6 kDa) and peptides that are filtered into primary urine. Among them are hormones and some other biologically active substances. In tubule cells, under the action of lysosomal proteolytic enzymes, these proteins and peptides are hydrolyzed to amino acids, which enter the blood and are reutilized by cells of other tissues.

Endocrine function of the kidneys

The kidneys produce several biologically active substances, which make it possible to consider it as an endocrine organ. Granular cells of the juxtaglomerular apparatus release renin into the blood when blood pressure in the kidney decreases, sodium content in the body decreases, and when a person moves from a horizontal to a vertical position. The level of renin release from cells into the blood also varies depending on the concentration of Na+ and C1- in the area of ​​the macula densa of the distal tubule, providing regulation of electrolyte and glomerular-tubular balance. Renin is synthesized in granular cells of the juxtaglomerular apparatus and is a proteolytic enzyme. In the blood plasma, it splits off from angiotensinogen, located mainly in the α2-globulin fraction, a physiologically inactive peptide consisting of 10 amino acids, angiotensin I. In the blood plasma, under the influence of the angiotensin-converting enzyme, 2 amino acids are split off from angiotensin I, and it turns into an active vasoconstrictor substance angiotensin II. It increases blood pressure due to the constriction of arterial vessels, enhances the secretion of aldosterone, increases the feeling of thirst, and regulates sodium reabsorption in the distal tubules and collecting ducts. All of these effects help normalize blood volume and blood pressure.

The kidney synthesizes plasminogen activator - urokinase. Prostaglandins are produced in the renal medulla. They participate, in particular, in the regulation of renal and general blood flow, increase the excretion of sodium in the urine, and reduce the sensitivity of tubular cells to ADH. Kidney cells extract the prohormone vitamin D3 produced in the liver from the blood plasma and convert it into a physiologically active hormone - active forms of vitamin D3. This steroid stimulates the formation of calcium-binding protein in the intestines, promotes the release of calcium from bones, and regulates its reabsorption in the renal tubules. The kidney is the site of production of erythropoietin, which stimulates erythropoiesis in the bone marrow. The kidney produces bradykinin, which is a strong vasodilator.

Metabolic kidney function

The kidneys are involved in the metabolism of proteins, lipids and carbohydrates. The concepts of “kidney metabolism,” i.e., the metabolic process in their parenchyma, through which all forms of kidney activity are carried out, and “metabolic function of the kidneys,” should not be confused. This function is due to the participation of the kidneys in ensuring the constant concentration in the blood of a number of physiologically significant organic substances. Low molecular weight proteins and peptides are filtered in the renal glomeruli. Cells in the proximal nephron break them down into amino acids or dipeptides and transport them across the basal plasma membrane into the blood. This helps restore the amino acid pool in the body, which is important when there is a deficiency of proteins in the diet. With kidney disease, this function may be impaired. The kidneys are capable of synthesizing glucose (gluconeogenesis). During prolonged fasting, the kidneys can synthesize up to 50% of the total amount of glucose produced in the body and entering the blood. The kidneys are the site of synthesis of phosphatidylinositol, an essential component of plasma membranes. The kidneys can use glucose or free fatty acids for energy expenditure. When the level of glucose in the blood is low, kidney cells consume fatty acids to a greater extent; with hyperglycemia, glucose is predominantly broken down. The importance of the kidneys in lipid metabolism is that free fatty acids can be included in the composition of triacylglycerol and phospholipids in the kidney cells and enter the blood in the form of these compounds.

Principles of regulation of reabsorption and secretion of substances in renal tubular cells

One of the features of the kidneys is their ability to change the intensity of transport of various substances over a wide range: water, electrolytes and non-electrolytes. This is an indispensable condition for the kidney to fulfill its main purpose - to stabilize the basic physical and chemical indicators of internal fluids. The wide range of changes in the rate of reabsorption of each substance necessary for the body filtered into the lumen of the tubule requires the existence of appropriate mechanisms for regulating cell functions. The action of hormones and mediators that affect the transport of ions and water is determined by changes in the functions of ion or water channels, carriers, and ion pumps. There are several known variants of the biochemical mechanisms by which hormones and mediators regulate the transport of substances by the nephron cell. In one case, the genome is activated and the synthesis of specific proteins responsible for the implementation of the hormonal effect is enhanced; in the other case, changes in permeability and pump operation occur without the direct participation of the genome.

Comparison of the features of the action of aldosterone and vasopressin allows us to reveal the essence of both variants of regulatory influences. Aldosterone increases Na+ reabsorption in renal tubular cells. From the extracellular fluid, aldosterone penetrates through the basal plasma membrane into the cell cytoplasm, connects with the receptor, and the resulting complex enters the nucleus (Fig. 12.11). In the nucleus, DNA-dependent tRNA synthesis is stimulated and the formation of proteins necessary to increase Na+ transport is activated. Aldosterone stimulates the synthesis of components of the sodium pump (Na+, K+-ATPase), enzymes of the tricarboxylic acid cycle (Krebs) and sodium channels through which Na+ enters the cell through the apical membrane from the lumen of the tubule. Under normal physiological conditions, one of the factors limiting Na+ reabsorption is the permeability of the apical plasma membrane to Na+. An increase in the number of sodium channels or the time of their open state increases the entry of Na into the cell, increases the Na+ content in its cytoplasm and stimulates active Na+ transport and cellular respiration.

The increase in K+ secretion under the influence of aldosterone is due to an increase in potassium permeability of the apical membrane and the entry of K from the cell into the lumen of the tubule. Increased synthesis of Na+, K+-ATPase under the action of aldosterone ensures increased entry of K+ into the cell from the extracellular fluid and favors the secretion of K+.

Let us consider another version of the mechanism of cellular action of hormones using the example of ADH (vasopressin). It interacts from the side of the extracellular fluid with the V2 receptor, localized in the basal plasma membrane of the cells of the terminal parts of the distal segment and collecting ducts. With the participation of G-proteins, the enzyme adenylate cyclase is activated and 3,5"-AMP (cAMP) is formed from ATP, which stimulates protein kinase A and the insertion of water channels (aquaporins) into the apical membrane. This leads to increased water permeability. Subsequently, cAMP is destroyed by phosphodiesterase and converted into 3"5"-AMP.

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Nephropathy is a pathological condition of both kidneys in which they cannot fully perform their functions. The processes of blood filtration and urine excretion are disrupted for various reasons: endocrine diseases, tumors, congenital anomalies, metabolic changes. Metabolic nephropathy is diagnosed more often in children than in adults, although the disorder may go unnoticed. The danger of developing metabolic nephropathy lies in the negative impact of the disease on the entire body.

Metabolic nephropathy: what is it?

A key factor in the development of pathology is a violation of metabolic processes in the body. There is also dysmetabolic nephropathy, which refers to a number of metabolic disorders accompanied by crystalluria (the formation of salt crystals detected during a urine test).

Depending on the cause of development, there are 2 forms of kidney disease:

1. Primary - occurs against the background of progression of hereditary diseases. It promotes the formation of kidney stones and the development of chronic renal failure.
2. Secondary - manifests itself with the development of diseases of other body systems, and may occur during the use of drug therapy.

Important! Most often, metabolic nephropathy is a consequence of calcium metabolism disorders, oversaturation of the body with phosphate, calcium oxalate and oxalic acid.

Development factors

The following pathologies are predisposing factors to the development of metabolic nephropathy:

Among metabolic nephropathies, there are subtypes that are characterized by the presence of salt crystals in the urine. Children more often have calcium oxalate nephropathy, where a hereditary factor influences the development of the disease in 70-75% of cases. In the presence of chronic infections in the urinary system, phosphate nephropathy is observed, and in the case of impaired uric acid metabolism, urate nephropathy is diagnosed.

Congenital metabolic disorders occur in children experiencing hypoxia during intrauterine development. In adulthood, the pathology is acquired. The disease can be recognized in time by its characteristic signs.

Symptoms and types of disease

Impaired kidney function due to metabolic failure leads to the following manifestations:

• development of inflammatory processes in the kidneys and bladder;
• polyuria - an increase in the volume of urine output by 300-1500 ml above normal;
• the occurrence of kidney stones (urolithiasis);
• the appearance of edema;
• disturbance of urination (delay or frequency);
• the appearance of pain in the abdomen, lower back;
• redness and swelling of the genitals, accompanied by itching;
• deviations from the norm in urine analysis parameters: detection of phosphates, urates, oxalates, leukocytes, protein and blood in it;
• decreased vitality, increased fatigue.

As the disease develops, a child may experience signs of vegetative-vascular dystonia - vagotonia (apathy, depression, sleep disturbances, poor appetite, feeling of lack of air, lump in the throat, dizziness, swelling, constipation, tendency to allergies) or sympathicotonia (hot temper, absent-mindedness, increased appetite, numbness of the limbs in the morning and heat intolerance, tendency to tachycardia and increased blood pressure).

Diagnostics

One of the main tests indicating the development of metabolic nephropathy is a biochemical urine test. It allows you to determine whether there are abnormalities in the functioning of the kidneys, thanks to the ability to detect and determine the amount of potassium, chlorine, calcium, sodium, protein, glucose, uric acid, cholinesterase.

Important! To carry out a biochemical analysis, you will need 24-hour urine, and to ensure the reliability of the result, you need to refrain from drinking alcohol, spicy, fatty, sweet foods, and foods that color the urine. A day before the test, you should stop taking uroseptics and antibiotics and warn your doctor about this.

The degree of change in the kidneys, the presence of an inflammatory process or sand in them will help to identify diagnostic methods: ultrasound, radiography.

The condition of the body as a whole can be judged by a blood test. Depending on the results of diagnosis of kidney disease, treatment is prescribed. Therapy will also be aimed at the organs that are the root cause of the metabolic failure.

Treatment and prevention

Since nephropathy can occur in various diseases, each specific case requires separate consideration and treatment.

The selection of medications is carried out only by a doctor. If, for example, nephropathy is caused by inflammation, the need to take antibiotics cannot be ruled out, and if there is an increased radioactive background, eliminating the negative factor or, if radiation therapy is necessary, introducing radioprotectors will help.

Drugs

Vitamin B6 is prescribed as a drug that corrects metabolism. With its deficiency, the production of the transaminase enzyme is blocked, and oxalic acid ceases to be converted into soluble compounds, forming kidney stones.

Calcium metabolism is normalized by the drug Xidifon. It prevents the formation of insoluble calcium compounds with phosphates, oxalates, and promotes the removal of heavy metals.

Cyston is a drug based on herbal components that improves blood supply to the kidneys, promotes urine secretion, relieves inflammation, and promotes the destruction of kidney stones.

Dimephosphone normalizes the acid-base balance in cases of kidney dysfunction due to the development of acute respiratory infections, lung diseases, diabetes mellitus, and rickets.

Diet

The generalizing factor of therapy is:

• the need to follow a diet and drinking regime;
• giving up bad habits.

The basis of dietary nutrition for metabolic nephropathy is a sharp limitation of sodium chloride, foods containing oxalic acid, and cholesterol. As a result, swelling is reduced, proteinuria and other manifestations of impaired metabolism are eliminated. Portions should be small and meals should be regular, at least 5-6 times a day.

Allowed for use:

• cereal, vegetarian, dairy soups;
• bran bread without adding salt and raising agents;
• boiled meat with the possibility of further frying: veal, lamb, rabbit, chicken;
• low-fat fish: cod, pollock, perch, bream, pike, flounder;
• dairy products (except salted cheeses);
• eggs (no more than 1 per day);
• cereals;
• vegetable salads without the addition of radish, spinach, sorrel, garlic;
• berries, fruit desserts;
• tea, coffee (weak and no more than 2 cups per day), juices, rosehip decoction.

It is necessary to eliminate from the diet:

• soups based on fatty meats, mushrooms;
• baked goods; regular bread; puff pastry, shortbread;
• pork, offal, sausages, smoked meat products, canned food;
• fatty fish (sturgeon, halibut, saury, mackerel, eel, herring);
• cocoa-containing foods and drinks;
• hot sauces;
• water rich in sodium.

You can prepare many dishes from the permitted foods, so sticking to the diet is not difficult.

An important condition for treatment is compliance with the drinking regime. A large amount of fluid helps eliminate stagnation of urine and removes salts from the body. Constantly exercising moderation in food and giving up bad habits will help normalize kidney function and prevent the onset of disease for people with metabolic disorders.

If symptoms of pathology occur, you should visit a specialist. The doctor will examine the patient and select the optimal method of therapy. Any attempts at self-medication can lead to negative consequences.

The kidneys are among the most well-supplied organs of the human body. They consume 8% of all blood oxygen, although their mass barely reaches 0.8% of body weight.

The cortex is characterized by an aerobic type of metabolism, the medulla is anaerobic.

The kidneys have a wide range of enzymes inherent in all actively functioning tissues. At the same time, they are distinguished by their “organ-specific” enzymes, the determination of the content of which in the blood in case of kidney disease has diagnostic value. These enzymes primarily include glycine amido-transferase (it is also active in the pancreas), which transfers the amidine group from arginine to glycine. This reaction is the initial step in creatine synthesis:

Glycine amido transferase

L-arginine + glycine L-ornithine + glycocyamine

From isoenzyme spectrum for the renal cortex, LDH 1 and LDH 2 are characteristic, and for the medulla, LDH 5 and LDH 4 are characteristic. In acute renal diseases, increased activity of the aerobic isoenzymes lactate dehydrogenase (LDH 1 and LDH 2) and the alanine aminopeptidase isoenzyme – AAP 3 is detected in the blood.

Along with the liver, the kidneys are an organ capable of carrying out gluconeogenesis. This process occurs in the cells of the proximal tubules. Main glutamine serves as a substrate for gluconeogenesis, which simultaneously performs a buffer function to maintain the required pH. Activation of the key enzyme of gluconeogenesis – phosphoenolpyruvate carboxykinase – caused by the appearance of acidic equivalents in the inflowing blood . Therefore, the state acidosis leads, on the one hand, to stimulation of gluconeogenesis, on the other, to an increase in the formation of NH 3, i.e. neutralization of acidic foods. However redundant ammonia production - hyperammoniemia - will already determine the development of metabolic alkalosis. An increase in the concentration of ammonia in the blood is the most important symptom of a violation of the processes of urea synthesis in the liver.

Mechanism of urine formation.

There are 1.2 million nephrons in the human kidney. The nephron consists of several parts that differ morphologically and functionally: the glomerulus (glomerulus), proximal tubule, loop of Henle, distal tubule and collecting duct. Every day, the glomeruli filter 180 liters of supplied blood plasma. Ultrafiltration of blood plasma occurs in the glomeruli, resulting in the formation of primary urine.

Molecules with a molecular weight of up to 60,000 Da enter primary urine, i.e. There is practically no protein in it. The filtration capacity of the kidneys is judged on the basis of the clearance (purification) of a particular compound - the number of ml of plasma that can be completely freed from a given substance when it passes through the kidney (more details in the physiology course).

The renal tubules carry out the resorption and secretion of substances. This function is different for different connections and depends on each segment of the tubule.

In the proximal tubules as a result of the absorption of water and Na +, K +, Cl -, HCO 3 - ions dissolved in it. concentration of primary urine begins. Water absorption occurs passively following the actively transported sodium. The cells of the proximal tubules also reabsorb glucose, amino acids, and vitamins from primary urine.

Additional Na + reabsorption occurs in the distal tubules. Water absorption here occurs independently of sodium ions. K +, NH 4 +, H + ions are secreted into the lumen of the tubules (note that K +, unlike Na +, can not only be reabsorbed, but also secreted). During the process of secretion, potassium from the intercellular fluid enters through the basal plasma membrane into the tubule cell due to the work of the “K + -Na + -pump”, and then passively, by diffusion, is released into the lumen of the nephron tubule through the apical cell membrane. In Fig. the structure of the “K + -Na+-pump”, or K + -Na + -ATPase is presented (Fig. 1)

Fig. 1 Functioning of K + -Na + -ATPase

The final concentration of urine occurs in the medullary segment of the collecting ducts. Only 1% of the fluid filtered by the kidneys turns into urine. In the collecting ducts, water is reabsorbed through embedded aquaporins II (water transport channels) under the influence of vasopressin. The daily amount of final (or secondary) urine, which has many times higher osmotic activity than primary urine, averages 1.5 liters.

The reabsorption and secretion of various compounds in the kidneys is regulated by the central nervous system and hormones. Thus, with emotional and pain stress, anuria (cessation of urination) can develop. Water absorption is increased by the action of vasopressin. Its deficiency leads to water diuresis. Aldosterone increases the reabsorption of sodium, and along with the latter, water. Parathyrine affects the absorption of calcium and phosphates. This hormone increases phosphate excretion, while vitamin D delays it.

The role of the kidneys in maintaining acid-base balance. The constancy of blood pH is maintained by its buffer systems, lungs and kidneys. The constancy of the pH of the extracellular fluid (and indirectly - intracellular) is ensured by the lungs by removing CO 2, the kidneys by removing ammonia and protons and reabsorption of bicarbonates.

The main mechanisms in the regulation of acid-base balance are the process of sodium reabsorption and the secretion of hydrogen ions formed with the participation carbanhydrase.

Carbanhydrase (Zn cofactor) accelerates the restoration of equilibrium in the formation of carbonic acid from water and carbon dioxide:

N 2 O + CO 2 ⇄ N 2 CO 3 ⇄ N + + VAT 3 –

At acidic values, the pH increases R CO2 and at the same time the concentration of CO2 in the blood plasma. CO 2 already diffuses in greater quantities from the blood into the cells of the renal tubules (). In the renal tubules, under the action of carbonic acid, carbon dioxide () is formed, dissociating into a proton and a bicarbonate ion. H + -ions are transported () into the lumen of the tubule using an ATP-dependent proton pump or by replacing them with Na +. Here they bind to HPO 4 2- to form H 2 PO 4 - . On the opposite side of the tubule (bordering the capillary), with the help of the carbonic acid reaction (), bicarbonate is formed, which, together with the sodium cation (Na + cotransport), enters the blood plasma (Fig. 2).

If carbanhydrase activity is inhibited, the kidneys lose their ability to secrete acid.

Rice. 2. The mechanism of reabsorption and secretion of ions in the kidney tubule cell

The most important mechanism contributing to the retention of sodium in the body is the formation of ammonia in the kidneys. NH3 is used in place of other cations to neutralize the acidic equivalents of urine. The source of ammonia in the kidneys is the processes of glutamine deamination and oxidative deamination of amino acids, primarily glutamine.

Glutamine is the amide of glutamic acid, formed when NH 3 is added to it by the enzyme glutamine synthase, or synthesized in transamination reactions. In the kidneys, the amide group of glutamine is hydrolytically cleaved from glutamine by the enzyme glutaminase I. This produces free ammonia:

glutaminase I

Glutamine Glutamic acid + NH 3

Glutamate dehydrogenase

α-ketoglutaric

acid + NH 3

Ammonia can easily diffuse into the renal tubules and there it is easy to attach protons to form ammonium ion: NH 3 + H + ↔NH 4 +

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An important aspect of kidney function, which has previously been underestimated, is its participation in the homeostasis of proteins, carbohydrates and lipids. The participation of the kidney in the metabolism of organic substances is by no means limited by the ability to reabsorb these compounds or excrete their excess. In the kidney, new and destroyed various peptide hormones that circulate in the blood occur, the consumption of low molecular weight organic substances (glucose, amino acids, free fatty acids, etc.) and the formation of glucose (gluconeogenesis), the processes of conversion of amino acids, for example glycine into serine, necessary for the synthesis phosphatidylserine, involved in the formation and exchange of plasma membranes in various organs.

It is necessary to distinguish between the concepts of “kidney metabolism” and “metabolic function of the kidney”. Metabolism, metabolism in the kidney, ensures the performance of all its functions. This section will not discuss issues related to the characteristics of the biochemical processes of kidney cells. We will talk only about some aspects of the kidney’s activity, which provide one of its most important homeostatic functions associated with maintaining a stable level of a number of components of carbohydrate, protein and lipid metabolism in the internal fluids.

Participation in protein metabolism

It was previously noted that the glomerular filtering membrane is practically impermeable to albumins and globulins, but low molecular weight peptides are freely filtered through it. Thus, hormones constantly enter the tubules - insulin, vasopressin, PG, ACTH, angiotensin, gastrin, etc. The breakdown of these physiologically active peptides into amino acids has a dual functional significance - amino acids enter the blood, used for synthetic processes in various organs and tissues, and the body is continuously freed from biologically active compounds entering the bloodstream, which improves the accuracy of regulatory influences.

A decrease in the functional ability of the kidney to remove these substances leads to the fact that in case of renal failure, hypergasprinemia may occur, and an excess of PG appears in the blood (in addition to an increase in its secretion). Due to the slower inactivation of insulin in the kidney in diabetic patients, the need for insulin may decrease when renal failure develops. Violation of the process of reabsorption and breakdown of low molecular weight proteins leads to the appearance of tubular proteinuria. In NS, on the contrary, proteinuria is caused by an increase in protein filtration; low molecular weight proteins are still reabsorbed, and albumin and large molecular weight proteins enter the urine.

Tubular reabsorption of individual amino acids, cleavage and reabsorption of polypeptides, absorption of proteins by endocytosis - each of these processes is saturated, i.e., has its own Tm value. This confirms the idea that the mechanisms of absorption of individual categories of proteins differ. Of significant importance is the higher filtration rate of denatured albumin in the glomeruli compared to native ones. It is very likely that this serves as one of the mechanisms for the elimination from the blood, the breakdown by tubular cells and the use of amino acids of those proteins that have changed and become functionally defective. There is information about the possibility of extracting some proteins and polypeptides by nephron cells from the peritubular fluid and their subsequent catabolism. These include, in particular, insulin and β2-μ-globulin.

Thus, the kidney plays an important role in the breakdown of low molecular weight and altered (including denatured) proteins. This explains the importance of the kidney in restoring the pool of amino acids for cells of organs and tissues, in quickly eliminating physiologically active substances from the blood and preserving their components for the body.

Participation in carbohydrate metabolism

Along with filtration and reabsorption of filtered glucose, the kidney not only consumes it in the metabolic process, but is also capable of significant glucose production. Under normal conditions, the rates of these processes are equal. The utilization of glucose for energy production in the kidney accounts for about 13% of the total oxygen consumption by the kidney. Gluconeogenesis occurs in the renal cortex, and the greatest activity of glycolysis is characteristic of its medulla. During metabolism in the kidney, glucose can be oxidized to CO2 or converted into lactic acid. The homeostatic significance of the leading biochemical pathways for the conversion of glucose in the kidney can be illustrated by the example of glucose metabolism during shifts in acid base.

In chronic metabolic alkalosis, glucose consumption by the kidney increases several times compared to chronic metabolic acidosis. It is important that the oxidation of glucose does not depend on acid base, and an increase in pH promotes a shift in reactions towards the formation of lactic acid.

The kidney has a very active glucose production system; the intensity of gluconeogenesis per 1 g of bale weight is significantly greater than in the liver. The metabolic function of the kidney, associated with its participation in carbohydrate metabolism, is manifested in the fact that during prolonged fasting the kidneys form half of the total amount of glucose entering the blood. The conversion of acidic precursors, substrates, into glucose, which is a neutral substance, simultaneously contributes to the regulation of blood pH. In alkalosis, on the contrary, gluconeogenesis from acidic substrates is reduced. The dependence of the rate and nature of gluconeogenesis on the pH value distinguishes the carbohydrate metabolism of the kidney from that of the liver.

In the kidney, changes in the rate of glucose formation are associated with changes in the activity of a number of enzymes that play a key role in gluconeogenesis. Among them, first of all, phosphoenolpyruvate carboxykinase, pyruvate carboxylase, glucose-6-phosphatase, etc. should be mentioned.

It is especially important that the body is capable of local changes in enzyme activity during generalized reactions. Thus, during acidosis, the activity of phosphonolpyruvate carboxykinase increases only in the renal cortex; in the liver, the activity of the same enzyme does not change. Under conditions of acidosis, gluconeogenesis increases in the kidney, mainly from those precursors that participate in the formation of oxaloacetic acid (oxal acetate). With the help of phosphoenolpyruvate carboxykinase, it is converted into phosphoenolpyruvate (hereinafter referred to as d-glyceraldehyde-3 PO4, fructose-1,6-diphosphate, fructose-6 PO4); finally, glucose-6 PO4, from which glucose is released using glucose-6-phosphatase.

The essence of activation of the key enzyme that ensures increased glucose formation during acidosis, phosphoenolpyruvate carboxykinase, apparently lies in the fact that during acidosis, the monomeric forms of this enzyme are converted into an active dimeric form, and the process of destruction of the enzyme slows down.

An important role in regulating the rate of gluconeogenesis in the kidney is played by hormones (PG, glucagon) and mediators that increase the formation of cAMP in tubular cells. This mediator helps to enhance the processes of conversion of a number of substrates (glutamine, succinate, lactate, etc.) into glucose in mitochondria. The content of ionized calcium, which is involved in increasing the mitochondrial transport of a number of substrates that ensure the formation of glucose, is important in regulation.

The conversion of various substrates into glucose, which enters the general bloodstream and is available for utilization in various organs and tissues, indicates that the kidney has an important function associated with participation in the energy balance of the body.

The intense synthetic activity of some kidney cells depends, in particular, on the state of carbohydrate metabolism. In the kidney, high glucose-6-phosphate dehydrogenase activity is characteristic of the cells of the macula densa, proximal tubule and part of the loop of Henle. This enzyme plays a critical role in the oxidation of glucose through the hexose monophosphate shunt. It is activated when the sodium content in the body decreases, which leads, in particular, to an intensification of the synthesis and secretion of renin.

The kidney turned out to be the main organ of oxidative catabolism of inositol. In it, myoinositol is oxidized into xylulose and then, through a series of stages, into glucose. Phosphatidylinositol is synthesized in kidney tissue - a necessary component of plasma membranes, which largely determines their permeability. Glucuronic acid synthesis is important for the formation of acidic mucopolysaccharides; there are many of them in the interstitium of the inner medulla of the kidney, which is essential for the process of osmotic dilution and concentration of urine.

Participation in lipid metabolism

Free fatty acids are extracted from the blood by the kidney and their oxidation contributes significantly to kidney function. Since free fatty acids are bound in plasma with albumin, they are not filtered, but enter the nephron cells from the intercellular fluid; transport across the membrane (cells is associated with a special transport mechanism. The oxidation of these compounds occurs more in the renal cortex than in its medulla.

In addition to the participation of free fatty acids in the energy metabolism of the kidney, the formation of triacylglycerols occurs in it. Free fatty acids are quickly incorporated into kidney phospholipids, which play an important role in various transport processes. The role of the kidney in lipid metabolism is that in its tissue free fatty acids are included in the composition of triacylglycerols and phospholipids and, in the form of these compounds, participate in the circulation.

Clinical Nephrology

edited by E.M. Tareeva