Diuresis

DIURESIS. Contents: Physiology of D. Definition of the concept and the role of D. in the organism

375 Work of the kidney and its consumption of oxygen

385 Pathological physiology and clinic of D. Quantitative and qualitative disorders of D.

3S5 Pathological forms of disorders of D. . . .

387 Physiology of diuresis. Definition of the concept and the role of D. in the organism. Diuresis (from the Greek dia- through and ouron- urine), urination, the most important excretory process in the organism, in the narrow sense means the formation and excretion of urine by renal tissue. In the broader understanding, however, D. is the result of complex physiol. processes of metabolism (water, salt, nitrogenous, pigmentary, etc.), the final stage of which is proper urination. Thus, in the process of diuresis renal factors are difficult to separate from extrarenal factors; taking the latter into account, the concept of D. becomes less defined; meanwhile, it is in this sense that it is increasingly applied in clinical practice and even in physiology, since understanding and evaluation of proper urination are almost impossible without simultaneous consideration of the state of general circulation and chemical shifts in the blood and tissues. The physiol. role of the kidneys as an excretory organ and of diuresis as the most important excretory act is not only extremely great but also very multifaceted. Of all the end products of metabolism in the organism, the kidney (during diuresis) excretes the most complex and at the same time most toxic nitrogenous wastes, pigments, and under pathological conditions also ketone bodies, bile acids, path. pigments, and in some cases even the paired compounds formed in it (e.g. hippuric acid). Thanks to the excretion of salt and other electrolytes or their retention in the body during D., the most important biological property of blood and the internal (tissue) medium of the human organism and warm-blooded animals is maintained - their isotonicity. All these solid substances can only be eliminated in aqueous solutions, consequently the excretion of water, which is at the same time a constant product of oxidative processes in the cell, is the third most important function of the kidney during diuresis. Finally, with the help of D., the basic physico-chem. properties of blood plasma as a colloidal system with buffer properties (see) are maintained - the constancy of its active reaction (see), its normal alkaline reserve, the specific osmotic pressure of its proteins. The quantitative limits of the kidney's accommodation in terms of excreting various components of urine are very considerable: the amount of water excreted by the kidneys per day, as is known, can vary from minimal figures to 15-20 liters and more, sodium chloride varies within the range of 0 to 30-40 g, etc. Development of the doctrine of D. The question of proper urine formation is the most thoroughly studied chapter of the doctrine of D. Schematically, all existing theories of D. can be grouped into three: 1) the theory of filtration of urine under the influence of blood pressure (Ludwig), 2) the theory of secretion of urine by the kidney (as a gland) in the glomeruli and tubules (Bowman-Heidenhain), 3) the theory of filtration of preformed urine in the glomeruli and active reabsorption in the tubules (Ribbert-Cushny). Bowman described in detail the relationships existing between Malpighian glomeruli and tubules, and on the basis, admittedly speculative, analysis of the hist. structure of the kidney, created the first scientific theory of urination. 'Why should there be such a magnificent apparatus [i.e. the glomerulus] at the end of the urinary tubule if not to supply the water necessary for the excretion and dissolution of the solid components of urine excreted by the renal epithelium?' (Bowman; 1842). However, Bowman's view was not confirmed by experiment, which is why in the following 30 years in physiology the filtration theory of D. proposed by Ludwig (1844) was established and became dominant. Through numerous studies by his students, variations in D. were established under the influence of transection of the renal nerves (Ustimovich), the spinal cord, as well as after compression of a large number of large arteries (Goll). From this it was concluded (Ludwig) that urine with all its components is filtered from the glomeruli into Bowman's capsule under the influence of blood pressure, and during further passage through the tubules it becomes concentrated due to the absorption (diffusion) of an excess amount of water back into the blood [more accurately - into the lymph (Zavarykin)]. The greatest difficulties in such reasoning were the need to explain the different concentrations of salts and urea in the blood and urine, as well as the different concentrating ability of the kidney with respect to individual components of urine. All this was later taken into account by Ludwig himself, which is why further studies in his laboratory (Ustimovich, Hermann) concerned the influence on renal secretion of substances subject to excretion, and led to the conclusion that to the influence of blood pressure on the intensity of D. is added an additional factor - the content in the blood of 'urine-forming' (harnfahige) substances. Thus, to purely mechanical factors were added chemical ones. Heidenhain (1874) found it easy to show that the work of the heart (resp. blood pressure) is insufficient to explain the enormous concentrating, osmotic work performed by the kidney, and that the process of D. cannot be exhausted by simple phenomena of filtration and diffusion. He also expressed the assumption that among the factors created by circulation, not the height of blood pressure but the acceleration of blood flow in the glomeruli is accompanied by an increase in D. At the same time it was established (I. P. Pavlov) that when large amounts of water are absorbed from the stomach, strong diuresis occurs without a simultaneous increase in blood pressure. All this, along with the experimental data below on the excretion of dyes by the glomeruli, led Heidenhain to assert that the glomeruli during D. excrete only water and in part easily soluble sodium chloride, while the epithelium of the convoluted tubules and the wide loops of Henle were ascribed the secretion of solid components (first of all urea), dissolved in minimal amounts of water, with the epithelium both in Bowman's capsule and in the urinary tubules possessing, according to Heidenhain, active secretory ability to selectively excrete solid components of urine in different concentrations. Of the numerous studies conducted to confirm and prove the secretory theory, the most important should be recognized: 1. Heidenhain's own observations on deposits of indigo carmine in the renal epithelium 10 minutes after injection of a 1% solution of the dye into the blood with the spinal cord transected, i.e. under maximum unfavorable conditions for D. After an hour the dye was already found in the lumen of the ascending parts of the loops and the insertional sections. Heidenhain believed that this experiment provided direct proof of the secretory ability of the renal epithelium, sometimes even without urination. 2. Observations of Nussbaum on the frog kidney, which has valuable features of structure for studying D. in that its blood supply occurs separately from two systems: a. renalis supplies the glomeruli, while v. porta renalis supplies the tubules. These experiments showed that after ligation of a. renalis and after the resulting atrophy of the glomeruli 2-3 days later, upon subsequent injection of urea into the vein or lymph, diuresis again occurs at about 74% of the normal amount. When indigo carmine was injected in a similar experiment, it appeared in the lumen of the tubule although diuresis did not occur. Less convincing are the observations of Lindemann, who attempted to cause embolism of the glomeruli by injecting oils into a. renalis and create conditions similar to Nussbaum's experiment. The data of these experiments the majority of followers of the secretory theory tend to consider exclusively as proof of the ability of the urinary tubules to true secretion. Similar experiments were later repeated with other dyes, and according to Gurchvich, the dye accumulates inside the cells in special vacuoles (resp. on granules) and when a certain concentration is reached in the cells, it is released from them with the help of these devices into the lumen of the tubule (see also Glands). Lindemann created a similar concept of so-called tonoplasts - intracellular formations which in his opinion are the actual carriers of the specific secretory function of the cells of the renal epithelium - nephrocytes. Magnus, attempting to expand the circle of evidence in favor of the secretory theory, established that an increase in arterial pressure in the kidneys, as well as an increase in blood mass through transfusion, leads to an outflow of fluid into the tissues but is not accompanied by diuresis. The latter occurs, however, if chemical changes in the composition of the blood are caused, for example by the introduction of salt and especially Na₂SO₄. Its completion the secretory theory found in the teaching of Putter (1926) on the 'three glands' in the kidneys (Drei-Drüsentheorie). On the basis of a comparative-physiological study of D. in the phylogenetic series, Putter asserts that the glomerular epithelium is predominantly a water gland, the ascending wide loop of Henle serves for the excretion of salt ('salt gland'), and the convoluted tubules of the first and second order excrete (actively eliminate) urea, uric acid, paired compounds, and under path. conditions - sugar. The function of the third gland, the most complex, is peculiar only to the kidney of higher animals. While acknowledging the presence of absorption in the kidneys, Putter attributes it only to the descending loop of Henle.

However, numerous studies have shown that the same facts that are explained by the secretory theory can also receive a different interpretation. Moreover, the facts themselves are sometimes more complex than Heydenhain and his followers assumed. Thus, it has been proven that after injection, indigo carmine appears not only in the tubules but also in the epithelium of Bowman's capsule and in the glomerular filtrate, albeit in very high dilution (direct study of the punctate of capsular fluid by Wearn and Richards). Histological examination of the kidney after injection of carmine (Mb 11 endorif, Suzuki) revealed its preliminary appearance in the lumen of the tubules, and then in the epithelium, which speaks in favor of the reabsorption of these dyes from the lumen of the tubules. Finally, staining of the tubule epithelium with indigo carmine is also obtained on an excised kidney, which has undoubtedly lost its viability (Jacoby, Sobieranski). Both of the above doctrines of diuresis thus attribute to the glomeruli the role of water excretion. But the mechanism of its excretion, as well as the quantity and purpose of the fluid excreted by the glomeruli, remains controversial. The question of the secretory or filtratory role of the epithelium of Bowman's capsule also remains unexplained. However, the center of gravity of the disagreement lies not in this, but in determining the function of the tubules, in resolving the dispute whether absorption or excretion is their main task. Cishny recently (1920) brilliantly analyzed all the facts currently known regarding D. and was able to show that all of them can find their explanation from the point of view of ultrafiltration of preformed urine through Bowman's capsule and absorption of an excessive amount of fluid, as well as some salts, along the path of the filtrate, i.e., in the tubules. This so-called filtration-reabsorption theory returns the doctrine of diuresis to physicochemical concepts in a modernized sense. In the glomeruli, according to Cishny, ultrafiltration occurs, during which the protein-free part of the plasma is filtered through Bowman's capsule and undergoes further transformation into urine as it passes through the tubules. The rate of flow of capsular fluid into the tubules is determined by the speed of filtration and the resistance offered by the ureters. The concentration of urine requires the expenditure of a corresponding amount of work (osmotic work), which is why the process of reabsorption should be considered not as passive diffusion (Ludwig), but as active resorption (Cishny). Direct experimental evidence in favor of resorption in the tubules can be provided by the experiments of Richards and Wearn, who, using the finest technique, obtained filtrate from individual Bowman's capsules of the frog kidney, in which they managed to detect, along with salt and urea, also glucose in amounts corresponding to the concentration of these substances in the blood. The urine collected from the same kidney, however, was free of sugar and contained, as is usually observed in frogs, urea and salt in a lower dilution. Furthermore, chemical studies of the kidney of warm-blooded animals—separately the medullary and cortical substance—revealed the presence of sugar in the former and its absence in the latter. Finally, in birds (for example in geese), during direct collection of urine from the ureter, D. many times exceeding the normal norm (up to 2¹/₂ liters per day; A. M. Levin, Sharpe, Orbeli) was repeatedly observed. The latter observations can only be explained by the failure of reabsorption from the cloaca. Particularly interesting in terms of reabsorption are the long-term chronic observations from Orbeli's laboratory (Michelson, Rozhdestvensky, Storch and Danilov) on dogs with separately diverted ureters (operation according to Orbeli) and with decortication or removal of the medullary substance of one kidney, observations that confirmed—as such crude interventions allow—the possibility of resorption of large amounts of fluid in the tubules and clarified the place and mechanism of absorption of individual components of urine. To the logical evidence in favor of reabsorption and against the specifically secretory nature of the renal epithelium belongs the reference to the embryogenesis of the kidney, which occupies a special place among other secretory organs in its origin from mesoderm (Mollendorff). Nevertheless, admitting the possibility of filtration to explain its mechanism, it is currently impossible to limit oneself to only hydrostatic factors (blood pressure, blood flow rate, etc.); one must also take into account the peculiarities of the structure of the glomerulus and the properties of the plasma giving off the filtrate. Histologically, the glomeruli are not a bare capillary network directly surrounded by the inner layer of Bowman's capsule—between them lie loose syncytial cells filling all the free space between the capsule and the glomerulus (Mollendorff). Thus, from the physicochemical point of view, the glomeruli represent an extremely complex membrane, and therefore the filtration occurring here is determined not by simple physical factors alone, but is connected with phenomena of osmosis, swelling, deswelling and probably also adsorption. In recent times (1928/29), the school of Hober, studying the physicochemical properties of the renal epithelium, came to the conclusion that the passage of individual components of urine through the glomeruli depends on the solubility of these substances in lipoids: in other words, the cell membrane, due to its structure, selectively promotes or hinders the excretion of endogenous or exogenous (dyes) substances. Furthermore, the proteins of the plasma that give off its water to the urine have their own colloid-osmotic pressure, which retains water with a certain force. The magnitude of the force that must be overcome to press out the filtrate is determined by Starling, Schade and Gover as 25-30 mm Hg, by Krogh as 33-35 mm. In this connection, it is interesting to note that the minimum pressure at which D. is still possible has long been determined as 40-30 mm (Ustimovich, Gruetner). The possibility of forming concentrated urine from the capsular filtrate, from the point of view of the reabsorption theory, implies the exudation through the glomeruli of significant amounts of fluid many times exceeding the volume of the excreted urine. Thus, 1 liter of urine should theoretically be formed from 83 liters of filtrate, which in turn requires the passage of 90 liters of plasma through the glomeruli. The different concentration of dense substances in the urine is explained by the fact that for individual components of plasma there is a threshold (Schwelle), below which they do not appear in the urine. Those substances that do not have such a threshold are excreted completely. These are sulfates, creatinine, iodides, which are excreted in parallel with their concentration in the blood. According to these views, sugar is completely resorbed in the tubules, sodium chloride is also subject to significant absorption, urea, uric acid, phosphates are absorbed in smaller quantities, i.e., they have a lower threshold of excretion. All these positions have recently been confirmed in the experiments of Richards and Plant (Plant). The work of the kidney and its oxygen consumption. Attempts have repeatedly been made, based on the lowering of the freezing point (D) in urine and blood, to make a mathematical calculation of the work performed by the kidney in the formation of a unit volume of urine. According to these calculations, for the formation of, for example, 200 cm³ of urine with D-2.3°, the work of the kidney is 42.91 kg m (Dreser, Galeotti). However, these figures in no way correspond to the actually expended energy, as can be judged at least by the amount of oxygen consumed by the functioning kidney (Barcroft, Brodie). More precise ideas about the work performed in the kidney can be obtained only by calculating the concentration work for each component of the urine separately. For the formation of 1 liter of normal urine, according to calculations based on the latest formulas by Hill and Donann, it is necessary to expend at least 500 kg/m, however, such calculations will remain incomplete until the essence of the urine formation process is known in all details. The oxygen consumption in kidneys, both at rest and functioning, is, by general admission, significantly higher than the average consumption of many other organs. For a dog it is, according to various authors, 0.008-0.075 cm³ per 1 g of substance and 1 minute of time, and with certain types of intense D. up to 0.3 cm³. A regular relationship between oxygen consumption and carbon dioxide excretion cannot be noted. With certain types of D., but undoubtedly not with all, oxygen consumption sharply increases. In accordance with the abundant oxygen consumption, the blood supply to the kidneys is also located. According to approximate calculations, based on research with blood clocks, the entire mass of blood in the body should pass through the kidneys in 5-8 minutes (on average 2 cm³ of blood per 1 min. per 1 g of substance). For a human, the blood irrigation of the kidneys (per day) is thus 700-860 liters. The rate of blood flow through the kidneys is relatively less than through other organs—a fact of no small importance if one considers the peculiarities of the renal-capillary system.

Here, as is known, the blood passes twice through the capillary bed with interpolated vasa efferentia. Meanwhile, the question of whether all nervous and exogenous factors that influence the afferent arterioles also exert the same influence on the efferent vessels has not yet been sufficiently clarified. Moreover, direct observation (Richard) has also proven that at rest, not all glomeruli participate in renal circulation, and only when salt, urea, and sugar are infused, as well as when medicinal substances (nitroglycerin, caffeine) are administered, do numerous reserve glomeruli come into play. Similar observations have been made by Krogh on the capillary networks of many other areas of the body (see Capillaries). In any case, it is necessary to take into account the firmly established fact that an increase or decrease in blood pressure in the glomeruli is accompanied by a corresponding strengthening or weakening of diuresis (Holl, Richard and Plent). In the same sense, although less distinctly, acceleration and deceleration of blood flow through the glomeruli have an effect. All this refers, of course, to physiological conditions when normal blood supply and venous circulation in the kidney are preserved and there are no difficulties in blood outflow (see also below - pathology of diuresis). Chemical composition of blood and D. The chemical composition of blood plasma is one of the main factors determining D. Fluctuations in the content of individual normal plasma ingredients, as well as the appearance of new substances unusual for the blood, can serve as a reason for enhanced D. The simplest and at the same time most common irritant is water. Its excess (hydremic plethora) is usually accompanied by enhanced D., although the question of whether hydremia is a consequence, cause, or accompanying factor in D. has not yet been fully clarified. For example, it deserves attention that in some oligurias, the retention of even very large amounts of water in the body is not accompanied by dilution of the blood and at the same time does not cause edema. The introduction of even very large amounts of water into the body is accompanied only by a short-term hydremia, after which the water goes into the tissues, so that it then appears again in the blood during the onset of D. On the other hand, after the introduction of certain salts into the blood or after bloodletting, hydremia occurs due to increased water intake from the tissues, which is not always accompanied by D. All this indicates that it is not the quantitative content of water, but the qualitative changes it causes in the blood plasma (e.g., decrease in osmotic and colloid-osmotic pressure) and tissues that determine diuresis. In addition, the degree of preliminary saturation of tissues with water (dry and 'wet' nutrition) has a significant influence on the diuretic outcome of water load. Enhancement of D. is observed, however, without an increase in water content in the plasma, but only in connection with fluctuations in the content of electrolytes (chlorides, sulfates, Na, K, Ca) or other soluble substances (urea, glucose) in it. In this connection, Magnus created the concept of the so-called threshold (Schwelle), the exceeding of which in the blood substances begin to act diuretically. The excretion of these substances is carried out either by enhanced D., i.e., an increase in the amount of water excreted by the kidneys, or by increasing the concentration of these substances in the urine. However, in relation to the classic irritant of D.- salt, it has been established that the introduction of hypo- and isotonic solutions leads to as intense D. as the injection of hypertonic solutions; in other words, the osmotic moment by no means plays a decisive role. The view of Starling about a regular increase in blood supply, resp. acceleration of blood flow in the kidney during salt D. has also not found confirmation. Therefore, supporters of the secretory theory consider salt D. as a result of specific irritation of the kidney's secretory apparatus, and the filtration-reabsorption theory- as D. from dilution (Verdünnungsdiurese). In the latter sense, the cause of the enhanced release of water by the plasma is the decrease in its colloid-osmotic pressure after the infusion of a salt solution, as well as the acceleration of the filtrate flow through the tubules, which is necessarily accompanied by a decrease in reabsorption. Dilution, in turn, leads to a weakening of the reabsorptive capacity of lymph and blood from the tubular epithelium. Direct evidence in favor of such an interpretation can be found in the observation that salt diuresis is significantly lower when colloids (gelatin, gum arabic) are added to the administered salt solution. The decrease in colloid-osmotic pressure during dilution from salt introduction apparently also explains the well-known fact that salt D. is preserved even at minimal blood pressure figures-13-12 mm Hg, when under normal conditions D. is no longer obtained. The influence of extrarenal factors in salt D. is most clearly demonstrated by the different diuretic effect from the administration of the same amount of salt to people or animals previously on a poor or rich salt diet.-Urea is the second main substance that physiologically causes D. Until recently, the only generally recognized point of application of its diuretic action was the kidney. The above observations of Nussbaum, phylogenetic comparisons of Pütter and many others led to the assertion that urea is a specific secretory irritant for the tubular epithelium and in particular that it is excreted by the convoluted tubules of the first and second order. The reabsorption theory, however, explains the same diuretic action by the low threshold of urea excretion, i.e., the difficulty of its reabsorption in the tubules. Therefore, the cat's kidney, which has the ability to concentrate urea strongly in the urine (up to 12%), excretes the urea load without excessive D. Only in the mentioned sense does urea retain the property of a tubular diuretic substance. Like urea, sugar is also osmotically highly active, an excess of which in the blood leads to significant D. The diuretic effect of glucose is particularly evident with its parenteral administration; in pathological hyperglycemias polyuria and glycosuria (see) are also caused by nervous and hormonal influences. Diuresis and acid-base balance. In the regulation of the active reaction of the blood and acid-base balance in the body, the most prominent role, along with the lungs, belongs to the kidney. In the normal state, the kidney excretes acidic urine (pH=4.7-6.5), while in the blood the reaction is steadily maintained at a slightly alkaline level (pH=7.1-7.3). In the urine, therefore, a certain excess of acidic valences is continuously excreted, which are constantly formed in the body as a result of the oxidative processes occurring in it. Minor shifts in the urine reaction in the acidic direction indicate that there are weak acids and their salts in it: essentially, the matter comes down to replacing the existing relationship in the blood between its buffer substances, acidic and basic phosphates * PO₄* = i, in the direction of a sharp predominance in the urine of acidic sodium phosphate (9:1), i.e., predominance of anions over cations. Nevertheless, under pathological conditions and during acid loads, significant amounts of acids can be removed from the body by means of D., although most often they are previously neutralized by blood buffers or ammonia. By general consent, urine acquires its acidic reaction only in the tubules; the pH of glomerular fluid, as shown by direct studies of Wearn and Richards, is close to the pH of the blood. Supporters of the secretory theory attribute to the tubular epithelium the ability to convert acidic NaH₂PO₄ into slightly alkaline Na₂HPO₄ with the return of the cation Na back into the blood. The theory of reabsorption, however, explains the acidic reaction of urine by the reverse reabsorption of the cation Na from the tubule lumen together with HCO₃ and the leaving in the urine of the anion PO₄, which, along with sulfates, as well as creatinine and urea, has a low threshold of excretion. That is why with abundant and rapid D. the pH of urine approaches the neutral point, and conversely, with artificial increase in pressure in one of the ureters (resp. slowed passage through the tubules), the urine obtained from it is more acidic than from the other kidney. Extrarenal regulators of D. To the extrarenal factors of D., regulating its quality and quantity, should be attributed the nervous and endocrine systems and their common executive organ-tissues (in this case, mainly connective tissue), united by Volhard in the concept of 'pronephros' (Vorniere). The influence of the central nervous system was first clearly demonstrated by Claude Bernard, who obtained sharp D. after a prick in the floor of the fourth ventricle along the median line, between the nuclei of the p. acusticus and p. vagus. This water prick of C. Bernard, as later research showed, is essentially a water-salt prick, since during it D. is accompanied by the excretion of very large amounts of NaCl. Centrifugal pathways carrying inhibitory D. impulses to the kidneys are, by general consent, the p. splanchnicus and to some extent the abdominal sympathetic nerve.

However, even among supporters of the secretory theory, the question of whether true secretory nerve fibers for the kidneys exist, supposedly located in the branches of the vagus nerve (Asher), remains disputed. Observations of recent years seem to return the entire question of the doubtful secretory innervation of the kidneys exclusively to fluctuations in renal blood supply under the influence of nerve irritations, and this alone tends to explain fluctuations in diuresis under the influence of nerve impulses, localizing the center of these influences in the gray tubercle (N. Sirotinin). New studies on the regulatory influence of the midbrain on vegetative functions have revealed the appearance of enhanced D. upon irritation in the area of the gray tubercle, when polyuria was accompanied by excretion of urine with low specific gravity and with a small chloride content. Finally, the influence of the cerebral cortex on D. has been established - irritation with a weak faradic current in the area of the gyri sigmoidei leads to polyuria, while extirpation of this area leads to weakening and then enhancement of D. (Bechterev and Karpinsky). At the same time, it would be a considerable schematization to consider D. as a simple (double) dependence between the central nervous system (resp. afferent nerves) and the kidneys. Thus, the aforementioned water-salt injection of Claude Bernard leads to significant dilution of blood (a fall in chlorides and proteins), which is also observed after kidney extirpation. Thus, in addition to the kidneys, the tissues (more details - see Metabolism, water and mineral) must be recognized as points of application of this injection. How unclear the question of the own innervation of the excretory apparatus of the kidneys is, is evidenced by observations on kidneys completely devoid of nerves or even transplanted: D. continues and apparently undergoes regulation by the humoral route through the blood irrigating the kidney (Oehme); such observations are explained by the fact that hormonal factors also participate in the regulation of D. The regulatory influence of the hypophysis (its posterior lobe) on D. is well known. Extracts from it (pituitrin) contain substances with a two-phase diuretic and antidiuretic effect. The latter clearly predominates and is mainly reduced to a sharp retention of water in the body, accompanied by pronounced hydremia, and in severe degrees - also by the picture of water poisoning (water intoxication Rowntree). Sodium chloride is excreted in absolutely normal, and relatively even increased, amounts. This effect of pituitrin is particularly pronounced in diabetes insipidus; the mechanism of this action is as complex as the aforementioned nerve influences mentioned above, and the question of whether the kidneys or tissues are the physiological point of application of pituitrin remains controversial (see also Hypophysis, Metabolism, water). In any case, there is a huge amount of observations speaking in favor of both renal and extrarenal action of pituitrin. - The thyroid gland also plays a significant role in the regulation of water-salt metabolism, resp. in D. The strong diuretic effect of thyroxine was clinically first noted in patients with cardiac edema and myxedema (Eppinger). Subsequently, it was confirmed also in renal edemas, mainly nephrotic, and to a lesser degree also in healthy individuals. The mechanism of action of thyroxine is not entirely clear - it manifests itself by the removal of sodium chloride from the tissues, the result of which is polyuria and disappearance of edemas. It must therefore be assumed that the secretion of the thyroid gland has an exclusively extrarenal effect. Pharmacodynamics of diuresis. Injection of adrenaline in humans leads to a prolonged decrease, and then a transient increase in D. with a decrease in the amount of table salt excreted. Many were inclined to attribute these changes in D. to the sympathicotropic effect of adrenaline on the renal vessels. However, it must be noted that the delay in D. from adrenaline injection ceases significantly later than the increase in blood pressure. In addition, adrenaline delays the absorption of fluids from the subcutaneous tissue and serous cavities, i.e., its vascular effect also has an extrarenal influence on water-salt metabolism. - Among pharmacological vegetative poisons, atropin, according to old observations, decreases diuresis, which was attempted to be explained by paralysis of secretory fibers (n. vagi). However, the existence of the latter, as well as the constancy of the antidiuretic effect of atropin, is doubtful. Pilocarpin moderately or significantly decreases D. Due to the simultaneous presence of strong sweating and salivation, the evaluation of its antidiuretic effect is very difficult. It is also necessary to mention the possibility of influence of the aforementioned vagotropic poisons on the musculature of the ureter and thus indirectly on D. Ergotamine, paralyzing n. sympathicus, according to some observations also has a braking effect on D. All the listed pharmacological substances through the vegetative nervous system exert diverse influence on the executive instruments in the body, therefore the diuretic (or antidiuretic) effect of these poisons can show significant fluctuations depending on the nature of nutrition, resp. on the state of the tissue depots of the body (Hecht, Nobel). On the influence on diuresis of various diuretic substances - see Diuretics. Pathological physiology and clinic of diuresis. Quantitative and qualitative disorders of D. Pathogenetically, disorders of D. can be, like the excretion of urine itself, conditioned by renal and extrarenal factors, but in their clinical manifestation these disorders manifest themselves as changes in the quantity or quality of diuresis. Quantitative changes in D. (polyuria, oliguria) in various diseases sometimes show only external similarity, reflecting in essence extremely diverse processes. And even normaluria often represents only a transitional stage of some pathological process to an increase or decrease in D. The nature of such pseudonormaluria is clarified by the parallel study of the dense components of urine, the amount of which is found to be sharply decreased. It can be definitely stated that there are almost no constant quantitative changes in D. characteristic of this or that pathological process in the kidneys, and that most often, depending on the stage in which this disease is studied, a fluctuation of D. in one direction or the other is found. Experimental observations in toxic nephropathies in most cases confirm this position. Thus, in early or terminating nephritis, as well as in the early stage of mercuric or chromic poisoning, polyuria is observed, which, then passing through the stage of normal diuresis (of course not always detectable), can pass into severe oliguria. Polyuria is often observed simultaneously with a decrease in the excretion of dense substances (in nephrosclerosis, hypertrophy of the prostate), and therefore it tends to be considered as a compensatory phenomenon ('compensatory, forced polyuria'). The complexity of explaining compensatory polyuria follows, however, from the well-known fact that in the initial stage of a shrunken kidney, when the ability to concentrate and excrete sodium chloride is still fully preserved, polyuria is already observed. A distinction is made between polyuria with relative and absolute increase or decrease in the excretion of dense substances, resp. with high and low specific gravity of urine. In pathological polyurias, the specific gravity is often fixed at low figures and does not increase even during dry eating (hyposthenuria) or else does not respond to any influence: under all conditions, urine of a certain specific gravity (1.007-1.010) is excreted - a phenomenon designated by the name isosthenuria [see also Kidneys, functional diagnosis (there also curves)]. Polyuria with relatively or absolutely sufficient excretion of salts is observed in the salt and sugar injection of Claude Bernard, in uranium poisoning, in diabetes mellitus, in some forms of tbc of the kidneys and pyelitis, in convalescents, as well as in the diuretic effect of some diuretics, primarily thyroxine, mercury and its derivatives (novasurol, salyrgan). Polyuria with excretion of liquid urine most often accompanies all kinds of mechanical difficulties in urination (hypertrophy of the prostate, narrowing of the urethra), a shrunken kidney in an advanced degree, and initial forms of acute nephritis; this also includes especially nervous forms of polyuria (see below) in diabetes insipidus, nervous polydipsia, as well as in angina pectoris, epilepsy, migraine, etc. In many cases, polyuria is pathogenetically not connected with kidney diseases and is caused by damage to the regulating devices of water-salt metabolism (see Diabetes insipidus to Diabetes mellitus). Similar to polyuria, the decrease in D. - oliguria - can occur with excretion of urine of high or low specific gravity, resp. with abundant or insignificant excretion of dense substances. Thus, in the acute stage of diffuse glomerulonephritis, in nephroses with edemas, in cardiac stagnations, concentrated urine is often excreted. In deeper lesions of the larger arterial branches and in the terminal stages of a shrunken kidney, oliguria with excretion of typical hypo- and isosthenuric urine is often observed.

If in glomerular lesions (glomerulonephritis and nephrosclerosis, accompanied by a sharp disturbance of blood circulation in the kidneys) there are, for obvious reasons, all grounds for a decrease in D., then oliguria in tubular processes is not a consequence of kidney disease alone and is largely due to extrarenal changes (see below). The highest degree of disturbance of D., absence of urine formation - true anuria - is observed both as a result of severe kidney lesions (on the basis of poisoning with sublimate, cantharidin) and as a result of acute circulatory disturbances caused by infectious, toxic and nervous factors. Of particular interest from a pathogenetic point of view are transient anurias after removal of one kidney - reno-renal reflexes (see also Anuria). In addition to quantitative changes in D., a large number of deviations from the normal excretion of individual components of urine are observed in clinical practice, e.g., hyperchloruria, hypochloruria, phosphaturia (see), oxaluria, as well as the excretion during D. of unusual pathological products, such as glycosuria, albuminuria (see), indicanuria, urobilinuria. All these pathological forms of D. are symptoms, sometimes main ones, of complex disturbances of intermediate metabolism and can be considered only in close connection with the pathology of metabolism (see). Pathological forms of disturbances of D. For clinical practice, it is of great interest to distinguish, even if schematically, individual pathological forms of D., united by a common pathogenesis, e.g.: pathological D. in disorders of 'general and local (renal) circulation, in inflammatory and toxic lesions of the kidney, in nervous (resp. reflex) influences on the kidney, in mechanical difficulties of urine outflow, in fever, depending on the nature of nutrition, etc. Already under physiological conditions, the importance of adequate blood supply to the kidney and a certain level of blood pressure for D. is extremely great, which has been repeatedly emphasized above; mild disturbances of circulation in the kidney (venous congestion or vasoconstrictive ischemia) lead to a decrease in the amount of urine and the appearance of protein in it, as for example in orthostatic (or march) albuminuria. With more severe degrees of venous congestion (hep cyanoticum), albuminuria is joined by oliguria, a decrease in the absolute amount of excreted NaCl, and in severe cases, the excretion of nitrogenous products also falls. Similar data are also obtained in experimental compression of the renal vein, resp. difficulty in blood outflow from the kidney (Rowntree). The urine excreted in this case is of high or normal specific gravity and is strongly saturated with pigments. The disturbances of D. in congestive kidney are apparently due to oxygen starvation of its parenchymal elements; therefore, this pathological D. is easily eliminated when blood circulation improves, resp. when compensation occurs (see also Heart defects). Clinically, an increase in general blood pressure with preserved normal venous outflow does not directly lead to pathological changes in D. The latter occurs in the later stages of hypertension (see), when it is complicated by arteriolosclerosis of the kidneys or in cases of hypertension with acute pathological renal processes (glomerulonephritis). Here the disturbances of D. are due to pathological changes in the kidneys. In actual kidney diseases, usually subdivided (to some extent artificially) into glomerular, tubular and vascular, or inflammatory, toxic and sclerotic, certain regular disturbances of D. can also be noted. Acute diffuse glomerulonephritides are accompanied by a decrease in the excretion of water and nitrogenous products of metabolism; to a lesser extent, these glomerular lesions affect the chloride-excretory function. As a result, in acute glomerulonephritis, D. is quantitatively decreased; the excreted urine is of low specific gravity and is significantly pigmented. Most researchers tend to the view that the main cause of pathological D. in acute glomerulonephritis is a disturbance of the blood supply to the kidneys: deterioration of blood flow in them due to ischemia of the glomeruli and their inflammatory changes. In nephroses, the chloride-excretory function of the kidneys suffers first, which also leads to water retention. It must be borne in mind, however, that, especially in these processes, the harmful agents affecting the kidney also find extrarenal application, and therefore it is extremely difficult to delimit what is the cause of the retention of NaCl in the body - a change in the permeability of the walls of blood vessels, pathological changes in blood proteins and tissues, or the tubular apparatus of the kidneys itself. Nitrogenous products are excreted in amounts close to normal. Quantitatively, D. in pronounced nephrosis is decreased; the urine is light, of normal specific gravity with a low chloride content. Finally, in nephroscleroses and chronic glomerulonephritides with a tendency to shrinkage, in processes accompanied by obliteration of the glomeruli with subsequent death of the tubules, a sharp decrease in the excretion of nitrogenous products, and subsequently also NaCl, is observed. As the process develops, the limits of kidney accommodation also decrease sharply, so that the polyuria observed in the initial stages can turn into oliguria. The kidney undergoes deep structural changes and excretes urine close in composition to plasma - of low specific gravity, light (for details see Nephritis, Nephrosis, Nephroscleroses, Kidneys). However, the data presented do not make it possible to genetically link certain changes in D. with specific morphological changes of individual elements of renal tissue, all the more so since their function, as indicated above, cannot yet be considered fully clarified. Disorders of the nervous regulation of D. can be of central and peripheral origin. The former, according to Feil (W. H. Veil), either have as their basis lesions in the region of the gray tuber - and then are accompanied by polyuria with the excretion of urine poor in table salt (hyperchloremia - hypochloruria) - or the medulla oblongata in the region of the bottom of the IV ventricle is affected (similar to the Claude-Bernardian puncture) and along with polyuria, a large amount of NaCl is excreted in the urine (hypochloremia - hyperchloruria). Both of these forms are clinically observed in diabetes insipidus, although it should be noted that the second form apparently occurs extremely rarely. Reflex forms of disturbance of D. arise as a result of reflex influences from pathologically altered organs, most often in some way connected with the kidney. The best known are reflex influences from the prostate gland, the urinary bladder, from one kidney to the other (reno-renal reflex); in mild cases, polyuria is usually observed, while in some more severe cases, complete anuria may also occur. Disturbances of D. in angina pectoris, migraine, epilepsy, etc., should also be considered reflex; the acute polyurias that arise with the excretion of urine of low specific gravity (urina spastica) are due in part to acute vaso-motor disturbances of renal circulation. Mechanical difficulties in urine outflow in hydronephrosis, hypertrophy of the prostate, diseases of the urinary tract - in the initial stage, as a rule, lead to increased D. with the excretion of urine of low specific gravity and with a low content of urea and NaCl. Only in far advanced or severe cases does oliguria and anuria occur. Pathogenetically, these forms are extremely close to the described reflex disturbances of D., complicated by purely mechanical difficulties of urine outflow. Finally, a number of extrarenal diseases affecting organs and tissues in some way connected with the regulation of water and salt metabolism - are accompanied by disturbances of D., e.g.: oliguria - in cirrhotic and especially parenchymal changes in the liver, in reduced absorption in the gastro-intestinal tract (e.g., narrowing of the pylorus), in diarrhea, increased sweating, formation of cavity exudates; increased retention of chlorides, along with a decrease in the amount of urine, in febrile diseases (especially in lobar pneumonia). In addition, the saturation or depletion of tissues with water and salts, depending on the nature of previous nutrition, and in a more pronounced degree, e.g., in the formation of edema or in cachexia - are also accompanied by quantitative or qualitative changes in D. (on the pathogenesis of these disturbances of D. - see Metabolism, water and salt).