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KIDNEY DISEASES

Normal kidneys are a paired, continuously functioning organ. Constantly forming urine, they remove metabolic slags, regulate the water-salt exchange between blood and other tissues, participate in the regulation of blood pressure and acid-base blood balance, perform endocrine functions.

On the incision of the kidney, it is clearly seen how immediately under the thin connective tissue capsule there is a moderately dense cortical substance (having a thickness of 0.7–0.8 cm), and below it is a medulla represented by pyramids. The parenchyma of the cortical and medulla in one kidney is 1–1.5 million of the structural and functional units of the organ — the nephrons. Each nephron has several divisions: the renal corpuscle (glomerulus, surrounded by Bowman's capsule); proximal convoluted and proximal straight tubules; the loop of Henle {this loop descends from the cortical substance into the pyramid, the thin and distal straight canaliculi form the descending and ascending (back to the cortical substance) parts of the loop of Henle}; distal convoluted tubule; collective tubing extending into the pyramid.

Each nephron begins with a renal glomerulus having a vascular-epithelial structure. It consists of a bundle of capillaries forming several lobes and surrounded by a network of extracellular matrix and cells located in the central zone of the glomerulus. Because of its centro-lobular location, this zone is called the mesangium (capillaries are attached to this zone). A layer of visceral epithelial cells surrounds the outer surface of the capillaries. The layer of parietal epithelial cells forms a bag-like structure — the Bowman capsule surrounding the network of capillary loops. Parietal and visceral epithelial cells embryo and anatomically represent a single structure that forms Bowman's space. The capsule cavity opens into the proximal convoluted tubule. In it, the primary urine is filtered from the blood plasma.

The blood is delivered to the glomerulus through the carrying arteriole, which, penetrating the Bowman's capsule, breaks down into about 50 capillary loops, which are collected in the outgoing arteriole.

The capsule of the renal glomerulus is a sphere consisting of the basement membrane and the outer (parietal) leaflet of flattened epithelial cells containing bundles of actin filaments. The basement membrane of the capsule is multi-layered and consists of separate layers separated by light intervals. When moving to the vascular bundle, the basement membrane of the capsule is transformed into the glomerular basement membrane, and when moving to the urinary part, into the basement membrane of the proximal tubule.

The inner leaf of the capsule is formed by visceral epithelial cells — podocytes, highly specialized process cells. Differentiated podocytes are not capable of division and cannot be replaced in case of death.

Podocytes have numerous long primary processes that twist all capillary loops and give secondary short processes - “legs”, immersed in the glomerular basement membrane. The legs of all podocytes are closely intertwined, forming filtering slots, which are closed by the extracellular matrix structures - slit diaphragms. The slit diaphragms and the luminal surface of the podocytes are covered with a thick surface layer rich in sialoproteins, which create a high negative charge on the podocytes. In addition to creating a negative charge, podocytes synthesize most, if not all, of the components of the glomerular basement membrane.

The glomerular basement membrane is the main skeleton for the glomerular bundle. It is a continuous plate with a thickness of 240 to 340 nm. In the basement membrane, there are three layers. The thickest middle layer, lamina densa, has an electron density. The outer and inner layers have a more rarefied matrix (lamina rara externa and interna).

The endothelial cells of the capillaries of the renal glomerulus are structurally composed of a central portion containing the nucleus and a peripheral part, represented by a thin fenestrated leaflet. Unlike the fenestrated endothelium, other localizations of the pore of the glomerular endothelium (50–100 nm in diameter) do not have a diaphragm, i.e.
they are constantly open. Closed pores are found only on the terminal fragment of the efferent arteriole. The luminal surface of endothelial cells, as well as podocytes, is coated with polyanionic glycoproteins, providing a negative charge.

Thus, the capillary wall of the renal glomerulus, represented by the endothelial pores, the glomerular basement membrane and the slit diaphragms between the podocyte legs, is a filtration barrier. The barrier function of the capillary wall for macromolecules is based on their size, shape and charge. The filtration barrier is easily permeable to water, small molecules. Polyanionic molecules, such as plasma proteins, are repelled by an electronegative shield of the glomerular filter.

In addition to endothelium and podocytes, there is a third type of cells that is in close contact with the glomerular basement membrane - mesangial cells. Together with the mesangial matrix, they form a mesangium. Mesangial cells have a glandular structure. Their processes attach to the glomerular basement membrane and are in contact with the endothelium. Mesangial cells have close contacts between themselves and with other cells of the extracellular mesangium — Gurmatigtig cells and granular cells of the juxta-glomerular apparatus. Mesangial cells have receptors for angiotensin II, atriopeptin (atrial natriuretic protein) and vasopressin on the plasmolemle, and are capable of producing various vasoactive agents, including prostanoids. Vasoactive agents stimulate the contractile activity of mesangial cells, thereby reducing the surface area of ​​capillary loops and reducing the amount of filtration. Mesangium ensures uniform distribution of hydraulic pressure on the capillary wall and the successful functioning of the filtration barrier.

Mesangial cells are one of the main targets for many glomerular diseases of an immune and non-immune nature. In response to damage, they are able to synthesize numerous mediators, including cytokines and growth factors, determining further proliferative and reparative processes in the glomerulus.

Kidney disease is very complex. Conventionally, they can be divided into four groups depending on what morphological structure is affected to a greater degree - the glomeruli, tubules, stroma (interstitium) or blood vessels. Some structures of the kidneys seem to be more vulnerable to specific forms of damage. For example, glomerular diseases are most often immunologically related, and tubular (tubular) and interstitial lesions are often caused by toxic or infectious agents. The interdependence of the structures of the kidney leads to the fact that the damage of one of them almost always again causes the damage of others. Primary vascular disease, for example, causes damage to all structures that are dependent on renal blood flow. Severe glomerular damage switches blood flow to the peritubular vascular system. On the contrary, the destruction of the tubules causes an increase in pressure inside the glomeruli, which may be the cause of their atrophy. Thus, regardless of origin, in chronic kidney diseases there is a tendency to damage all the major structural components of the kidney, which leads to chronic renal failure.

The widespread use of renal biopsy has changed the perception of renal diseases, especially various types of glomerulonephritis. To clarify the morphological and immunological details using a number of methodological approaches. Thus, the complex periodic acid plus reagent — Schiff's dye (CHIC or PAS reaction) stains the basement membranes of the glomeruli and tubules, as well as the mesangial matrix; impregnation of sections with silver makes it possible to identify the basement membranes of the glomeruli and tubules; immunohistochemical methods are used to detect various types of immunoglobulins, antigens, complement, fibrin-related compounds and markers on the cell surface in sections of the kidney; electron microscopy reveals the details of glomerular lesions; other special histological stains make it possible to determine the presence of fibrin, amyloid and lipids.

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KIDNEY DISEASES

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