Renal Pathology – Pathophysiology of The Urinary System

In nephrology, a science that studies the physiology and pathology of the kidneys, significant advances have now been made. The data obtained in the study of renal processes at the subcellular and molecular levels helped to clarify the mechanisms of homeostatic functions of the kidneys and their disorders.

A kind of revolution in nephrology was made by the introduction of the puncture biopsy method, the role of which is difficult to overestimate. The clinical and morphological approach to the study of kidney diseases has made it possible to revise the existing concepts in nephrology. The role of the structural “break” of the renal tissue has become fundamental in the establishment of a nephrological diagnosis, in deciding questions about the prognosis, methods of treatment and control of therapy.

Thermography, ultrasound examinations, radionuclide renography, scanning and scintigraphy are also widely used in nephrology.

An artificial kidney apparatus is used to treat renal failure. Kidney transplantation is of great importance both for studying the problem of tissue compatibility and for developing practical methods of replacement therapy.

As you know, the nephron is the structural and functional unit of the kidney. He has a high level of specialization. As part of the nephron, a renal glomerulus with a Shumlyansky-Bowman capsule and a system of renal tubules are isolated.

The kidney contains 1.2-1.3 million glomeruli, each of which contains about 50 capillary loops with anastomoses. Thus, the renal glomerulus is regarded as a conglomerate of capillary loops. In its composition, juxtamezangial and peripheral (urinary) zones are distinguished. The peripheral part of the capillary is covered with the glomerular basement membrane (GBM), a layer of podocytes and protrudes into the urinary space.

The most complex and functionally important structure of the renal capillary is the mesangium. The mesangial matrix fills the space between the mesangial cell and the perimesangial GBM. A small part of the mesangium is located under the endothelium. With electron microscopy, the mesangial matrix resembles the material of the basement membrane and differs from it in the pattern of the tissue and the presence of bundles of thin fibers enclosed in a fibrous mesh. The mesangial matrix consists mainly of microfibrils, forming a tightly interwoven three-dimensional network, and is an important component of the mesangial contractile system. The latter performs a skeletal function (the role of the trunk), and it is also a complex functional component of the glomerulus. Here are the receptors closely associated with the juxtaglomerular apparatus (JGA).

So, the structure of the nephron is very complex and highly subordinated to its differentiated function.



FEATURES OF THE KIDNEY BLOOD SYSTEM (Renal Pathology)

In the kidney, two functionally different circles of blood circulation are distinguished: large (cortical) and small (juxtamedullary). The cortical circle is represented by the vessels of the cortical substance (interlobular arteries, bringing arterioles and the “miraculous network” of the bulk of glomeruli, efferent vessels and post-glomerular capillary and venous networks of the cortex). Juxtamedullary, a shortened circle of blood circulation, is associated with a special structure and originality of the function of the YUGA. Usually, up to 90% of blood flows through the cortical pathway, and about 10% through the juxtamedullary pathway.

Renal blood flow is not very sensitive to fluctuations in systemic arterial pressure – within the systolic blood pressure from 80 to 180 mm Hg. it remains constant.

According to modern concepts, stable renal blood flow is the basis of their renal homeostatic functions. Falling blood pressure below 60 mm Hg. Art. leads to the termination of glomerular filtration processes.

The lymphatic system of the kidneys is functionally subordinate to the reabsorption work of the tubules and is the second link in renal reabsorption. This system carries out the transport of reabsorbed components, primarily proteins and water. In 1 minute, 1 ml of lymph is formed in the kidneys, i.e. as much as secondary urine. Adequate lymphatic drainage ensures both normal excretory (diuretic) renal function and renal metabolism.

In terms of its functional characteristics, the kidney is the most important organ of homeostasis. They, in particular, are involved in the regulation of the following processes.

  1. Maintaining the constancy of the volume of the liquid, its osmotic concentration and ionic composition (the main parameters of water-salt metabolism).
  2. Maintaining the constancy of the CBS.
  3. Excretion of products of nitrogen metabolism and foreign substances (actually excretory function).
  4. Economy or excretion, depending on the composition of the internal environment of the body, of various organic and inorganic compounds – glucose, amino acids, ions.
  5. Metabolism of proteins, lipids and carbohydrates.
  6. Splitting and excretion of biologically active substances (including hormones).
  7. Endocrine function of the kidneys (non-excretory) is associated with the presence of the renin-angiotensin system, the kallikrein-kinin system, the renal prostaglandin system (A-1 and E-2), the vitamin D system, erythropoietins and erythropoiesis inhibitors, as well as with the production of urokinases – activators fibrinolysis.

In the kidneys, the production of the Grolman antipressor factor was also detected.

How are the kidneys capable of performing such complex homeostatic functions? With the help of active renal processes (glomerular filtration, reabsorption and secretion in the renal tubules, synthesis of new compounds).

Glomerular filtration – 1 min. about 1200 ml of blood passes through the kidneys and 120 ml of filtrate is formed (in newborns –

4 times less, and only after 2 years the adult level is reached).

In principle, the filtration process is determined by physical factors: hydrostatic capillary pressure, equal to approximately 106 mm Hg. Art., intrarenal pressure – 15 mm Hg. Art. and colloidal osmotic blood pressure – 26 mm Hg. Art. Pressure gradient – effective filtration pressure – approx.

65 mmHg Art. It is essential that its constancy is maintained due to the myogenic regulation of blood flow in the glomerular arteriole.

Substances with a molecular weight of up to 5000 are filtered without hindrance; with a relative molecular weight of more than 70,000, filtration through an intact glomerulus does not occur.

An increase in sympathetic activity with fear, pain, physical exertion, progressive heart failure causes

increases resistance in the renal vessels and reduces renal blood flow, as well as glomerular filtration due to the effect of catecholamines on efferent arterioles.

What are the violations of glomerular filtration processes? Both a decrease and an increase in its volume are possible. The decrease is most clinically significant, probably due to a drop in systemic blood pressure (collapse, shock, heart failure). Under such conditions, the hydrostatic pressure in the bringing arteriole of the glomeruli decreases, which leads to a decrease in the effective filtration pressure and to a limitation of the filtration area. In cases of shock, the pain component is of additional importance in reducing filtration. In violation of cardiac activity, along with a drop in hydrostatic pressure, congestion develops, which leads to an increase in intrarenal pressure.

In the pathogenesis of a decrease in glomerular filtration, the narrowing of the renal artery is also important in connection, for example, with sclerotic disorders, since this reduces the volume of renal blood flow. Filtration also decreases with an increase in the oncotic pressure of blood plasma, for example, with dehydration or parenteral administration of protein preparations. Disorders of urine outflow (strictures of the ureters or urethra, prostate hypertrophy, kidney stones), leading to an increase in intrarenal pressure, also reduce filtration. Damage to the filter membrane is also important in inflammatory and immune diseases. Moreover, due to the depolymerization of the basic substance, permeability increases with the development of hematuria and proteinuria,

In all cases, when glomerular filtration decreases, the activity of the excretory function of the kidneys decreases and retention azotemia develops.

An increase in the volume of glomerular filtration is also possible. In fever, due to reflexive restriction of blood circulation in the periphery of the body, renal blood flow and, accordingly, filtration increase. An increase in filtration due to a drop in oncotic pressure is noted when a large amount of fluid is injected into the body or when blood is thinned during the edema subsidence.

MECHANISMS OF REABSORPTION AND SECRETION IN THE RENAL TUBULES (Renal Pathology)

Filtration of all low molecular weight components of blood in the kidneys has led to the creation of mechanisms capable of reabsorbing all compounds valuable for the body from primary urine. The processes occurring in the tubules are extremely complex and have so far been described only schematically. The cells of the renal tubules have specialized systems of active transport and carry various substances from the blood into the lumen of the nephron (secretion), as well as in the opposite direction (reabsorption), against a high concentration and electrochemical gradient with the consumption of significant amounts of energy and oxygen.

As a result of active absorption of most of the osmotically active components of the filtrate through the tubule walls, water moving due to diffusion is reabsorbed, i.e. passively.

For quantitative characterization of the fate of various substances

in the nephron, they are compared with the release of substances that are completely filtered in the glomeruli and are subsequently completely excreted in the secondary urine.

Clearance – coefficient of blood purification from various substances –

the concept is, to a certain extent, conditional. In quantitative terms, it is characterized by the volume of blood plasma, completely cleared by the kidneys from one or another substance in 1 min. Based on the principle of clearance, the functional state of the kidneys, renal blood flow, glomerular filtration, tubular secretion, processes of osmotic concentration and dilution, transport of electrolytes, etc. are determined. substances completely excreted during a single passage through the kidneys. The inulin clearance determines the glomerular filtration volume and is equal to approximately 120 ml / min. The clearance of para-amino hippuric acid is used to assess the effective renal plasma flow and is equal to 600-650 ml / min.

Tubular secretion – the ability of renal tubular cells to transfer from the blood to the lumen of the tubules by means of carriers against a concentration gradient of various substances. Assessed by the method of maximum tubular secretion of para-amino hippuric acid. In the proximal part of the nephron, metabolites are predominantly secreted, in the distal part – ions K, H, NH4.

Tubular reabsorption is the ability of renal tubular cells to be reabsorbed from the lumen of the nephron into the blood. In the proximal section, all biologically important organic substances are reabsorbed, glucose, amino acids, protein, urea, lactate, bicarbonate, as well as inorganic ones – Pi, Cl, K, 75% Na. Here Na and other osmotically active substances are absorbed with an equivalent amount of water (isoosmotic to blood plasma). In the loop of Henle and the distal tubules, the inorganic components of the filtrate 1/4 Na, Mg, 1/2 Ca are reabsorbed.

The volume of water reabsorbed in the tubules is calculated as the difference between the value of glomerular filtration for 1 min and minute diuresis. When calculating the percentage of reabsorbed water, the volume of water reabsorption is related to the amount of glomerular filtration. Under normal conditions, water reabsorption is about 99%.

GENERAL MECHANISMS OF DISORDERS OF TUBULE REABSORPTION AND SECRETION (Renal Pathology)

  1. Overstrain of reabsorption processes and depletion of enzyme systems due to an excess of reabsorbable substances in the primary urine (exceeding the “renal threshold”).
  2. Primary drop in the activity of tubular apparatus enzymes due to a hereditary defect or under the action of inhibitors.
  3. Violation of the structure of the tubules (degeneration, necrosis) with a decrease in blood supply or toxic damage.

IMPAIRMENT OF Glucose Reabsorption (Renal Pathology)

Filtered glucose is almost completely reabsorbed by the cells of the proximal tubules and is usually excreted in the urine in small amounts. During reabsorption, glucose combines with the carrier (it is phosphorylated) and is transported through the basal part of the cell into the blood. The role of sodium ions and, accordingly, the Na-pump is essential.

With hyperglycemia accompanying diabetes mellitus, the blood glucose level exceeds the level of the “renal threshold” 8 mmol / l, a lot of glucose is filtered through the glomeruli, and the enzyme systems are not able to provide complete reabsorption. Glucosuria develops. True, in advanced cases of diabetes mellitus, glucosuria may not be due to kidney damage (angiopathy) and a decrease in filtration. A hereditary defect in the enzymatic systems of glucose reabsorption manifests itself in the form of renal diabetes mellitus, a dominantly inherited disease, in which glucosuria develops against the background of normal or even low blood glucose levels. Glucosuria can be a consequence of damage to the epithelium of the tubules in renal ischemia or poisoning with mercury-containing drugs or lysol.

IMPAIRMENT OF PROTEIN REABSORPTION (Renal Pathology)

Primary urine can contain up to 0.3 g / l of protein, and in just a day, up to 50 g of protein is filtered through the glomeruli. There is practically no protein in the final urine. The protein is reabsorbed in the proximal tubules by pinocytosis, is partially broken down, and then low molecular weight components enter the blood. The mechanisms of protein reabsorption are poorly understood. It is known, in particular, the essential importance of hemodynamics. The appearance of protein in the urine is referred to as proteinuria (albuminuria is more common). Temporary low proteinuria up to 1 g / l can occur in healthy individuals after intense prolonged physical work. Persistent and higher proteinuria is a sign of kidney disease. According to the mechanism of development, it is conventionally divided into glomerular and tubular (glomerular and tubular). For glomerular proteinuria

due to an increase in the permeability of the filtering membrane, protein in large quantities enters the cavity of the Shumlyansky-Bowman capsule, which exceeds the reabsorption capabilities of the tubular apparatus. If the glomeruli are damaged, moderate proteinuria develops. True, the degree of proteinuria does not reflect the severity of kidney disease. Tubular proteinuria is associated with impaired protein reabsorption against the background of damage to the tubular epithelium (amyloidosis, sublimate necronephrosis) or with impaired lymphatic drainage. Massive proteinuria is observed in nephrotic syndrome, when both the glomeruli and tubules are damaged.



TRANSPORTATION OF ELECTROLYTES IN NEPHRON (Renal Pathology)

The cells of the proximal nephron reabsorb most of the components of the ultrafiltrate, but the leading role in this process belongs to the reabsorption of sodium with concomitant anions. It is sodium reabsorption that is the most significant kidney function in terms of volume and energy costs. Sodium reabsorption largely determines the total amount of urine excreted, the participation of the kidneys in the regulation of water in the body, osmotic concentration, the ionic composition of the blood and other vital indicators. The kidneys filter 1200 g of sodium per day, and the excretion does not exceed 5-10 g. The reabsorption of sodium in various parts of the nephron has pronounced features. So, in the proximal regions, where up to 75% of filtered sodium is reabsorbed, its reabsorption is an active process, but it is carried out against a low gradient. The reabsorption of sodium in the distal regions is carried out against a high concentration gradient, which causes the excretion of urine, which contains almost no sodium ions. Distal sodium reabsorption has been found to be regulated by aldosterone, a hormone of the adrenal cortex. The biochemical mechanisms of active transport of sodium ions remain largely unclear. A certain value is attached to Mg-dependent ATPase, SDH, alpha-ketoglutarate dehydrogenase.

Disorders of sodium ion reabsorption can develop when aldosterone production is reduced either under the action of inhibitors (osmotic diuretics), or when the sensitivity of the renal epithelium to aldosterone is reduced. Under such conditions, along with sodium ions, water is also lost with the possible development of dehydration.

The release of potassium ions is about 10% of that filtered in the glomeruli, and potassium ions are not only reabsorbed, but also partially secreted in the distal tubules.

OSMOTIC DILUTION AND CONCENTRATION OF URINE (Renal Pathology)

Depending on the state of the body’s water balance, the kidneys can excrete both diluted and highly concentrated urine. In the process of osmotic concentration of urine, all parts of the tubules, vessels of the medulla, interstitial tissue, functioning as a single multiplying system, take part. In this case, intensive water reabsorption is carried out; urine comes out with a high concentration of excreted substances.

From 120 ml of filtrate, 119 ml are reabsorbed in 1 min. Up to 85% of this amount is reabsorbed in the proximal tubules following osmotically active substances (Na, glucose, etc.), which is defined as “obligatory reabsorption” of water. About 15% is reabsorbed in the distal and collecting ducts –

“optional reabsorption”.

The level of compulsory reabsorption may fall when the reabsorption of sodium or glucose ions is impaired (polyuria in diabetes mellitus, the appointment of osmotic diuretics aldoctan). Facultative water reabsorption is suppressed with a lack of ADH or the absence of a reaction of the renal epithelium to the latter (forms of diabetes insipidus).

The kidneys are able to excrete urine 4 times more hypertonic and 6 times more hypotonic than blood plasma with fluctuations in the relative osmotic concentration of 1002-1035. A decrease in the ability of the kidneys to concentrate urine is expressed in the form of hypostenuria or isostenuria. Hypostenuria is a condition in which the maximum osmotic concentration of urine is lower than that of blood plasma (severe tubular damage). This maximum concentration of urine is 240-250 mmol / l (relative – 1005-1008).

Isotenuria is a condition in which the maximum concentration of urine becomes equal to the osmotic concentration of blood plasma. Complete cessation of osmotic concentration is noted. The maximum osmotic concentration is 270-330 mmol / l (relative – 1010-1012).

Daily diuresis in healthy adults is about 70% of exogenously introduced water. The minimum volume of urine required to excrete toxins is 500 ml. The volume of fluid consumed should not be less than 800 ml per day. Diuresis in adults ranges from 800 ml to 1500 ml per day. In a one-year-old child, it does not exceed 500 ml and by the age of eight it reaches 1000 ml. Polyuria – excretion of a daily amount of urine of more than 2000 ml, oliguria – 400-500 ml, anuria – up to 200 ml.

In the pathogenesis of disorders of urine excretion, the state of nervous and humoral regulation is of great importance. Emotional factors can change diuresis, and the activation of excitation processes in the cerebral cortex leads to polyuria, and inhibition

niya – to oliguria. Polyuria and oliguria can be obtained by conditioned reflex or by hypnotic suggestion.

Quite often, in conditions of pathology, reflex painful anuria occurs. Reflex inhibition of urination is possible from various reflexogenic zones (skin, intestines, bladder, ureters). In pathogenesis, the reno-renal reflex is of particular importance, when trauma or other damage to one kidney causes temporary anuria of the other, intact. In this case, due to the activation of the sympathoadrenal system, the tone of the renal arterioles increases, which leads to a decrease in glomerular filtration.

Hormonal influences are important – thyroxine increases glomerular filtration and, like glucocorticoids, increases urine output.

GENERAL ETIOLOGY OF KIDNEY DISEASES (Renal Pathology)

RISK FACTORS

1. Factors disrupting the nervous and humoral regulation of the kidneys.

As already mentioned, a change in the ratio of excitatory and inhibitory processes under the influence of psychotraumas affects diuresis. Hemorrhages, tumors and trauma to the skull, leading to damage to the hypothalamus and pituitary gland, are reflected in the condition of the kidneys.

2. Factors leading to impaired blood supply to the kidneys –

thrombosis and embolism of renal vessels, their sclerosis, as well as shock conditions, severe injuries, prolonged compression syndrome. In the latter cases, the development of the mechanism of “centralization of blood circulation” is important.

3. Biological factors – viral infection (measles, chickenpox, hepatitis), bacterial (streptococci, staphylococci), leptospirosis can lead to the development of nephritis. Quite frequent kidney damage in severe infections and intoxications – sepsis, cholera.

4. Immunogenic factors are especially important in the development of glomerulonephritis.

5. A number of toxic factors adversely affect the kidneys (salts of heavy metals – arsenic, lead, ethylene glycol, dichloroethane, methanol; organic poisons – mushroom, snake; drugs – sulfonamides, butadione, D-penicillamine, antibiotics, X-ray contrast compounds, aminazine, PASK , cytostatics).

Medicinal nephropathies develop with the appointment of therapeutic doses of drugs, especially with an overdose, can often be a symptom of a systemic drug disease. The action of drugs is realized by immune or metabolic mechanisms. In the pathogenesis of nephropathy, the leading role is played by hypersensitivity (sensitization) to drug antigens, which causes immunocomplex, cellular, antibody damage to the renal tissue. Metabolic drug nephropathies with a nephrotoxic effect can be realized directly (damage to the convoluted tubules) or indirectly (through dyselectrolythemia, hemolysis, hemodynamic and microcirculation disorders, purine metabolism, etc.). Sulfanilamide kidney –

a type of acute renal failure caused by blockade of the kidneys with fast-acting sulfonamides (sulfadimezine, norsulfazole, streptocid). Acetylated metabolic products (their crystals) lead to blockage of the tubules and further to anuria. For prevention, it is recommended to drink plenty of moderately alkaline drink.

6. Factors leading to a violation of the outflow of urine – urolithiasis, compression of the ureters, etc.

7. Congenital developmental defects – hypoplasia, polycystic.

8. Hereditary fermentopathies.

The kidneys react to almost any stimulus (irritant), any violation of homeostasis (fluctuations in blood pressure, infection, immunogenic factors, inflammation), and in most cases they react in a rather stereotypical and non-specific manner. Because of this “renal response”, a wide variety of kidney diseases present with the same symptoms – hematuria, proteinuria, and nephrotic symptoms. In any pathological process, the glomeruli, the tubulo-interstitial apparatus, and the vessels are involved. Of course, the ratio of the severity of the lesions is different.

All manifestations of kidney disease are reduced to the following main syndromes: urinary, nephrotic, hypertensive, edematous and (finally) renal failure.

URINARY SYNDROME (Renal Pathology)

The most common manifestation of kidney disease. It is characterized by the development of hematuria and proteinuria. There are many algorithms for establishing the nature of hematuria. There are painless and painless forms. There are also types of hematuria by origin: renal, pelvic, ureteral, gallbladder, etc. The painful form is associated with kidney injury, renal colic with the identification of calculi in kidney stones. Painful sensations are possible with hematuria in patients with sickle-cell anemia, with polycystic disease, a combination with leukocyturia, bacteriuria is not excluded.

The painless form of hematuria is more common with glomerulonephritis, with tumors. Less often, coagulation defects are important in the treatment with heparin, cytostatics. In addition, renal vascular anomalies (arteriovenous shunts), systemic vasculitis, amyloidosis, and diabetic nephropathy are possible.

According to modern concepts (B.I.Shulutko, 1983; L. Simpson et al., 1987), hematuria has a capillary-tubular mechanism and the main place of erythrocyte exit – peritubular capillaries. Indirectly in favor of this mechanism (along with the unconditional proximity of the tubules and capillaries) are early changes in the capillaries both in nephritis and in borderline arterial hypertension. The study of hematuria leads to the conclusion: to diagnose causing

her neck disease is possible only with the help of a puncture biopsy. It is important to note that hematuria is a non-specific syndrome. If we recognize the proposed (capillary-tubular) mechanism of renal hematuria, then, obviously, there is no need to talk about glomerular or tubular hematuria. It is also obvious: the nature of hematuria in nephropathies, its relation to the defeat of one or another part of the nephron must be determined, focusing not on the nature of hematuria, but on the accompanying symptoms.

The diagnostic value of proteinuria – a formidable symptom of many kidney diseases – is ambiguous. Quantitative and qualitative analysis of urine proteins is important to determine both the nature and location of the lesion. A correct explanation of proteinuria is possible only with a sufficiently complete knowledge of its mechanisms, the topography of the existing barriers to the path of plasma and tissue proteins into urine. Albumin, normally negatively charged, is repelled by the negatively charged glomerular glycocalyx. Depending on the pH value, albumin can change its charge; loss of glycocalyx can lead to increased filtration of albumin. Allocate glomerular, tubular and mixed proteinuria; overflow proteinuria, secretory and histuria. Glomerular type of proteinuria is selective, non-selective and mixed.

NEPHROTIC SYNDROME (Renal Pathology)

This syndrome is understood as a symptom complex in which proteinuria is more than 3 g / day, hypoproteinemia (less than 60 g / l), hypercholesterolemia and edema. Nephrotic syndrome is a common manifestation of many very dissimilar, fundamentally different diseases. These include: damage to the glomeruli, (glomerulonephritis, lipoid nephrosis, heroin nephropathy, diabetes mellitus, sickle cell anemia, drug kidney damage.Selective proteinuria is caused by invisible (inaccessible to modern research methods) damage, possibly a change in the electric charge of the membrane and protein conformation ; nonselective – more gross damage to the glomerular basement membrane.

PAIN SYNDROME (Renal Pathology)

The renal tissue does not have pain sensitivity, since it lacks pain receptors. The appearance of pain is due to stretching of the renal capsule or pelvis due to inflammatory or congestion. Pain is usually localized in the lumbar and hypochondrium regions, radiating down the ureter, into the bladder, urethra, testicles. Very intense pain – renal colic. The intensity of pain may not correspond to the degree of anatomical changes. The cause of renal colic is most often an acute violation of the outflow of urine as a result of blockage of the renal pelvis or ureter with a stone, sometimes a blood or purulent clot.

URINARY DISORDER SYNDROME (Renal Pathology)

N 1-1.5; 2 liters or more – polyuria; up to 500 – oliguria; 100-200 or less – anuria, dysuria – frequent painful urination, sometimes accompanied by impaired urine outflow. Normally, in the daytime is allocated 2 / 3 – 3 / 4 daily amount of urine; the predominance of nocturnal diuresis – nocturia.

PADDER SYNDROME

Renal edema can occur very quickly and spread evenly throughout the body. Small swelling (pastiness) primarily appears in the area of ​​the loose connective tissue of the face on the eyelids and under the eyes. Renal edema is mobile and soft. There are frequent cerebral edema, accompanied by headaches, convulsive seizures, transient loss of vision (amaurosis); organs of the gastrointestinal tract (vomiting, diarrhea). The main mechanism of renal edema is sodium and water retention in the body. Edema develops when the pressure in the interstitial fluid rises above a certain “threshold” level, while the extensibility of the interstitial space increases sharply. It is also important to increase the hydrostatic pressure in the capillaries and increase the permeability of the capillary wall. A decrease in the release of sodium ions with kidney damage can be associated either with a decrease in the amount of sodium ions filtered in the glomeruli, or with an increase in its reabsorption in the tubules. The loss of protein in the urine leads to a decrease in the content of total protein in the blood plasma (hypoproteinemia), a decrease in the amount of albumin (hypoalbuminemia), this leads to a drop in oncotic pressure, the release of part of the fluid from the vascular space into the interstitial space. At the same time, the volume of circulating blood is liquefied, volumetric receptors are irritated, and through the renin-angiotensin system, the production of aldosterone in the adrenal glands is activated, and the secretion of ADH increases. Aldosterone increases the reabsorption of sodium ions in the renal tubules, ADH promotes fluid retention. Similar results are obtained with a decrease in glomerular filtration, which leads to a decrease in the flow of sodium ions into the distal nephron. The distal parts are in contact with the JUA, in which, under the influence of a decrease in the combination of sodium and chlorine ions in the liquid of the distal tubule, renin production is activated.

ARTERIAL HYPERTENSION SYNDROME

This is a condition when the systolic pressure exceeds 140 mm Hg. Art., and diastolic – 90 mm Hg. Art. Renal hypertension – secondary arterial hypertension caused by organic kidney disease. Renal hypertension associated with diffuse renal lesions (10-15%) and renovascular hypertension (2-5%) are distinguished.

1) Renal hypertension (renal parenchymal) often develops in chronic pyelonephritis, acute and chronic glomerulonephritis, in connection with systemic vasculitis (periarteritis nodosa, systemic lupus erythematosus). In the pathogenesis: a) sodium and water retention; b) activation of pressor systems (renin-angiotensin and sympathoadrenal); c) decreased function of the kidney depressor systems (renal prostaglandins and kallikrein-kinin system).

Against the background of a decrease in blood formation in the kidneys, the level of glomerular filtration decreases and sodium retention increases (hypervolemia, an increase in BCC, an increase in sodium in the vascular wall with an increase in sensitivity to the pressor effects of angiotensin and catecholamines in acute glomerulonephritis, acute and chronic renal failure).

The activation of the renin-angiotensin system is associated with a decrease in renal perfusion due to diffuse narrowing of arterioles and interlobular arteries. An increase in the activity of the sympathoadrenal system is due to impaired excretion of hormones and their active metabolites due to impaired renal excretory function.

2) Renovascular hypertension (vasorenal) – symptomatic hypertension caused by narrowing of one or both renal arteries. The most common causes: vasoconstriction of the kidneys against the background of atherosclerosis and fibromuscular hyperplasia, less often – arteritis, traumatic aneurysm, malformations. Pathogenesis: disorders of the renal vessels lead to a decrease in the main blood flow in them, cause ischemic damage to the organ, activation of the renin-angiotensin-aldosterone system and an increase in blood pressure. The asymmetry of blood pressure, resistance to drug therapy is characteristic.

LIPOID NEPHROSIS

Diffuse lesions of a non-immune nature of the epithelial lining of glomerular capillaries are responsible for 70-80% of all cases of nephrotic syndrome in children and approximately 20% in adults. The etiology and pathogenesis are not yet known. Apparently, there is a genetically determined defect in podocytes, which, under unknown circumstances, can manifest itself as an independent pathology (HLA – B12 Ag). Modern approaches associate lipoid nephrosis with the presence of a selective capillary permeability defect. A defect in the electrostatic functional barrier of the capillary wall is noted. Obviously, the breakthrough of the barrier can be triggered by any non-specific reasons. There are no visible changes in the glomerular structures. The peak incidence is at 3 years of age. An advanced nephrotic syndrome develops clinically.



GLOMERULONEPHRITIS

According to modern concepts, this is a genetically determined immune-mediated inflammation with a predominant initial lesion of the glomeruli and the subsequent involvement of all renal structures in the pathological process. The relationship between glomerulonephritis (GN) and a specific phenotype of the HLA system has been established. GN can be considered as a pathological process localized in an initially defective organ and realized under the influence of various (possibly nonspecific) stimuli. The classification of GN is carried out according to the morphological principle, however, with an immunological criterion.

  1. Immunocomplex GN:
    1. Mesangial-proliferative GN, including acute GN, JgA-nephropathy (Berger’s disease), JgG and JgM mesangial nephritis.
    2. Membranous GN.
    3. Membranous-proliferative GN.
  2. GN with an antibody mechanism:
    1. Extracapillary GN
    2. Gupasture’s Syndrome.

In the etiology of GN, play a role: microbes – nephrogenic streptococci, staphylococcus white, bovine corynebacterium, enterococcus, typhoid salmonella, treponema pale, diplococcus; viruses – cytomegalovirus, herpes virus, hepatitis B, Epstein-Barr; couple-

zites – malarial plasmodium, schistosome, toxoplasma; medicines, poisons, foreign serum; endogenous antigens – nuclear, brush border, thyroglobulin, immunoglobulins, tumor and embryonic carcinomatous.

In pathogenesis, an immune response takes place, which is carried out by intermolecular interactions of the antigen and components

MHC (large histocompatibility complex). The combination of an antigen and a complex molecule is recognized by the T-lymphocyte receptor. The antigen, the complex-coding molecule and the T-lymphocyte receptor provide an independent specificity of the immune response. This is followed by passive import of immune complexes (IC) into the glomerulus and their deposition, circulation of antibodies reacting with a structural antigen or with a “trigger” non-glomerular autologous or exogenous antigen, which induces the formation of immune deposits in the kidney tissue. A variant of the reaction with a fixed antigen of the basement membrane itself is possible, the so-called anti-GBM-antibody GN. The occurrence of glomerular and tubulo-interstitial lesions is due to either the participation of killer T cells, or a macrophage reaction, or other mechanisms.

The influence of the antigen is superimposed on the genetic predisposition (the antigen itself is endo or exogenous). Then

a normal immune reaction is formed with the formation of IC, which triggers microcirculation disorders with the development of microthrombosis and micronecrosis (i.e., nonspecific inflammation). Under the influence of chemotactic factors, polymorphonuclear leukocytes are concentrated in the glomerulus, moreover, exfoliating the endothelium, opsonizing and phagocytizing IK, they release prostaglandins, leukotrienes, histamine, cationic proteins, coagulation factors, enzymes from the phospholipids of cell membranes. The result is damage to the glomeruli, depolymerization of GBM glycoproteins, an increase in the permeability of the latter, with possible damage to it as well.

The problem of chronic GBV (CGN) is central to nephrology. CGN is diagnosed in about a third of nephrological patients, which is a common cause of renal failure.

Acute GBV (OHN). Its main culprit is group A streptococcus. Evidence of the involvement of streptococcus in OGN is the presence of a nephritogenic antigen as a specific component of streptococcus and the stimulation of autoantigenic reactivity by streptococcal infection. According to the pathogenesis, OGN is a classic example of immunocomplex inflammation. In 90% of patients, the level of JgG and JgM increases, 93% have hypocomplementemia, 60% have cryoglobulins containing antibodies to some forms of autologous JgG and circulating IC; the number of the latter correlates with the severity of the disease and the presence of visible deposits in the tissue of not only the kidney, but also the spleen.

Renal failure is a potentially reversible rapid cessation of renal excretory function with a retention of metabolic products in the blood, usually excreted in the urine. It is divided into prerenal (general hemodynamic disorders), renal (ischemic or toxic damage to the renal parenchyma) and postrenal (obstruction of urine outflow)

The prerenal form of acute renal failure develops against the background of conditions associated with a decrease in cardiac output, cardiogenic shock, cardiac tamponade, arrhythmias, heart failure, pulmonary embolism; conditions associated with the phenomena of dilatation – sepsis, anaphylactic shock; conditions associated with a decrease in the volume of circulating

blood – burns, blood loss, dehydration, diarrhea, cirrhosis, nephrotic syndrome, peritonitis.

Renal in 75% of cases is due to acute tubular necro-

zom against the background of ischemic or toxic kidney damage,

in 25% – acute post-streptococcal GN, systemic vasculitis. With it, a decrease in glomerular filtration is noted.

Postrenal is associated with the action of mechanical factors (ureteral stones, tumors, catheter obstruction, ureteral stricture, prostate hypertrophy, inflammatory edema) or with functional disorders (spinal cord disease, diabetic nephropathy, pregnancy, prolonged use of ganglion blockers).

Acute renal failure is one of the most formidable nephrological syndromes occurring with severe damage not only to the kidneys, but also to the body as a whole. Main reasons –

shock, nephrotoxic lesions and obstruction, in some cases –

hypovolemia and cardiogenic disorders. The main mechanism of pathogenesis is ischemia of the renal tissue, tubules, epithelium and interstitium. When blood pressure falls below 70 mm Hg. Art. filtration is disturbed, which leads to spasm of the renal vessels and activation of the juxtaglomerular circulation. Possible toxic damage to the renal structures. The pathogenetic basis of the disease is acute tubular necrosis, which causes mechanical obstruction of the tubules by desquamated epithelium. It manifests itself as anuria. The leading pathogenetic factors are water-electrolyte disturbances, metabolic acidosis, CO 2 accumulation , increased pulmonary ventilation, lung damage with the development of pathological respiration.

Chronic renal failure basically has a pronounced morphological equivalent – nephrosclerosis, i.e. is the outcome of most kidney disease. For its development are important: all forms of GN, tubulo-interstitial diseases (pyelonephritis and interstitial nephritis), systemic diseases with kidney damage, dysmetabolic diseases (amyloidosis, diabetic nephropathy and gout), vascular diseases, obstructive lesions – tumors, obstruction of the ureters.

The pronounced manifestation of renal failure is azotemia, i.e. increased accumulation of urea, amino nitrogen, uric acid, methylguanine, creatinine in the blood.

Stages: latent, azotemic and uremic.

All types of renal failure are accompanied by severe disorders of the homeostatic functions of the kidneys, characterized by the following indicators.

  1. Falling clearance.
  2. A sharp decrease or even cessation of urine flow (oligoanuria).
  3. Violation of the concentrating ability of the kidneys with the development of hypostenuria and isostenuria.
  4. Azotemia is a consequence of impaired renal excretory function in relation to nitrogen metabolism products.
  5. Violation of the electrolyte composition of blood plasma.
  6. Development of excretory non-gas acidosis.

The consequence of renal failure is uremia – a very complex in genesis and extremely severe in clinical terms syndrome. It includes not only deep impairment of kidney function, but also disorders of the functions of several organs and systems. The body also develops humoral changes, primarily from the side of the blood. The pathogenesis of uremia is not limited to the accumulation of slag products of nitrogen metabolism.

Of great importance are violations of the electrolyte balance of the blood – hyperkalemia, hyponatremia, hypocalcemia, etc. In hyperkalemia, not only the electrical, but also the mechanical activity of the myocardium changes. Conduction processes fade up to complete blockade. In severe cases, cardiac arrest is possible. Vascular disorders are associated not only with hyperkalemia, but also with hypervolemia, azotemic intoxication.

As a rule, there is anemia, due primarily to a violation of the formation of erythropoietins.

Due to the discrepancy between the intake and excretion of water, overhydration often develops, with it, edema is likely, followed by a breakdown in the functions of the brain and the formation of a coma. The main mechanism of acidosis is associated with the accumulation of sulfuric, phosphoric and a number of organic acids in the blood, since they are excreted only by the kidneys. The clinical manifestations of acidosis are shortness of breath and even pathological types of breathing (Kussmaul). Often, uremia is complicated by pulmonary edema. Liver damage

to one degree or another it is observed almost constantly, since the liver and kidneys – the main organs of homeostasis – unite

in a harmonious system by the commonality of a number of functions and features of blood circulation, refer to the so-called “shock organs”, and in renal failure suffer together.

In acute renal failure and uremia, the main method of pathogenetic therapy is extrarenal blood purification (extracorporeal hemodialysis). In peritoneal hemodialysis, the peritoneum is used as a semipermeable membrane, and the abdominal cavity is washed with a specially formulated sterile solution. In an artificial kidney apparatus, a semi-permeable membrane is made of tubes or sheets mounted in a chamber. The outside of the chamber is washed with dialysis fluid.

In some cases, hyperbaric oxygenation is used, which reduces the activity of immune reactions, slowing down the extinction of renal function.

Repeated use of hemodialysis can buy time to restore normal kidney function. With progressive failure and the development of irreversible disorders, only kidney transplantation can save the patient’s life. In our time, considerable experience of successful kidney transplantation has been accumulated, however, its widespread use is limited by a common problem – how to overcome histone incompatibility?