for a significant part of the minute volume of blood circulation. it is believed that in land mammals, about a fifth of the volume of blood that passes through the heart passes through the kidneys. in adult mice, for example, minute volume is about 9%–22%. lymphatic system the kidney is well supplied with lymphatic vessels, which remove excess fluid with substances and macromolecules dissolved in it from the interstitium that fills the space between the tubules and blood vessels. the anatomy of the lymphatic system of the kidney is similar between mammals. lymphatics basically follow the path of blood vessels. the lymphatic system of the kidneys begins in the cortex with the initial blind-end intralobular lymphatic capillaries passing near the tubules and renal corpuscles, but the lymphatic vessels do not go inside the renal corpuscles. the intralobular lymphatic capillaries are connected to the arcuate lymphatics. the arcuate lymphatics pass into the interlobar lymphatics, which pass near the interlobar arteries. the arcuate and interlobar lymphatics are lymphatic precollectors. finally, the interlobar lymphatics join the collecting hilar lymphatics leaving the kidney through renal hilum. lymphatic vessels are usually absent in the medulla of the mammalian kidneys, and the role of lymphatic vessels is assumed to be performed by vasa recta. in some species, there may be differences in the anatomy of the lymphatic system of the kidney. for example, sheep lack lymphatics in the renal capsule, and rabbits lack interlobular lymphatics. most studies fail to detect lymphatic vessels in the renal medulla of animals, in particular, they are not found in sheep and rats. but some studies have found lymphatic vessels in the renal medulla of pigs and rabbits. depending on the species, there may or may not also be a connection between the lymphatics of the renal capsule and the internal renal lymphatic system. nerve supply the innervation of the kidney is provided by efferent sympathetic nerve fibers entering the kidney through the renal hilum, originating in the celiac plexus, and afferent, leaving the kidney to the spinal ganglion. there is no reliable evidence for the innervation of the kidney by parasympathetic nerves, while the existing evidence is controversial. efferent sympathetic nerve fibers reach the renal vasculature, renal tubules, juxtaglomerular cells, and the wall of the renal pelvis, all parts of the nephron are innervated by sympathetic nerves. nerve fibers pass through the connective tissue around the arteries and arterioles. in the medulla, the descending vasa recta are innervated as long as they contain smooth muscle cells. most afferent nerve fibers are located in the renal pelvis. the vast majority of nerves in the kidneys are unmyelinated. normal physiological stimulation of the efferent sympathetic nerves of the kidney is involved in maintaining the balance of water and sodium in the body. activation of the efferent sympathetic nerves of the kidney reduces its blood flow, and respectively, filtration and excretion of sodium in the urine, and also increases the rate of renin secretion. the afferent nerves in the kidney are also involved in maintaining balance. mechanosensory nerves of the kidney are activated by stretching of the tissue of the renal pelvis, which can occur with an increase in the rate of urine flow from the kidney, resulting in a reflex decrease in the activity of efferent sympathetic nerves. that is, activation of the afferent nerves in the kidney suppresses the activity of the efferent nerves. functions excretory function in mammals, nitrogenous metabolic products are excreted predominantly in the form of urea, which is the end product of mammalian metabolism and is highly soluble in water. urea is predominantly formed in the liver as a by-product of protein metabolism. most of the urea is excreted by the kidneys. blood filtration, as in other vertebrates, occurs in the renal glomeruli, where pressurized blood passes through a permeable barrier that filters out blood cells and large protein molecules, forming primary urine. filtered primary urine is osmotically and ionically the same as blood plasma. in the tubules of the nephron, substances useful for the body, dissolved in the primary urine, are subsequently reabsorbed, and the urine is being concentrated. osmoregulation mammalian kidneys maintain an almost constant level of plasma osmolarity. the main component of blood plasma, which determines its osmolarity, is sodium and its anions. the key role in maintaining a constant level of osmolarity is managed by the control of the ratio of sodium and water in the blood. drinking large amounts of water can dilute the blood plasma, in which case the kidneys produce more dilute urine than the plasma to keep the salt in the blood but to remove the excess water. if too little water is consumed, then urine is excreted more concentrated than blood plasma. the concentration of urine is provided by an osmotic gradient that increases from the border between the cortex and medulla to the top of the pyramid of the medulla. in addition to the kidneys, the hypothalamus and neurohypophysis are involved in the regulation of water balance through a feedback system. the osmoreceptors of the hypothalamus respond to an increase in the osmolarity of the blood plasma, as a result of which the secretion of vasopressin by the posterior pituitary gland is stimulated, and thirst also arises. the kidneys respond via receptors to increased levels of vasopressin by increasing water reabsorption, resulting in a decrease in plasma osmolarity due to its dilution with water. variation in the rate of water excretion is an important survival function for mammals that have limited access to water. the most prominent feature of the mammalian kidneys are the loops of henle, they are the most efficient way to reabsorb water and create concentrated urine, which allows you to save water in the body. after passing through the loop of henle, the fluid becomes hypertonic relative to the blood plasma. mammalian kidneys combine nephrons with short and long loops of henle. the ability to concentrate urine is determined mainly by the structure of the medulla and the length of the loops of henle. some desert animals have evolved the ability to concentrate urine much better than other animals. the longer loops in the australian hopping mouse make it possible to produce very concentrated urine and survive in conditions of water scarcity. endocrine function in addition to excretory, the kidneys also perform an endocrine function, they produce certain hormones. the juxtaglomerular cells of the kidneys produce renin, which is a key regulator of the renin–angiotensin system, which is responsible for blood pressure regulation. the production of erythropoietin by the kidneys is responsible for the differentiation of erythroid progenitor cells in the bone marrow into erythrocytes and is induced by hypoxia. thus, with a lack of oxygen, the number of red blood cells in the blood increases, and they are responsible for transporting oxygen. the kidneys are involved in the metabolism of vitamin d. in the liver, vitamin d is converted to calcifediol (25ohd), while the kidneys convert calcifediol to calcitriol (1,25(oh)2d), which is the active form of the vitamin and is essentially a hormone. vitamin d is involved in the formation of bones and cartilage, and also performs a number of other functions, for example, it is involved in the functioning of the immune system. blood pressure regulation some mammalian internal organs, including the kidneys and lung, are designed to function within normal blood pressure levels and normal blood volume levels, and blood pressure itself is also affected by changes in blood volume levels. therefore, maintaining a constant blood volume for mammals is a very important function of the body. the stable level of blood volume is influenced by the glomerular filtration rate, the function of individual parts of the nephron, the sympathetic nervous system and the renin-angiotensin-aldosterone system. in the walls of the afferent arterioles at the entrance to the renal glomeruli, there are juxtaglomerular cells. these cells are sensitive to changes in the minute volume of blood circulation, and to the composition and volume of the extracellular fluid, producing renin in response to changes in their level. once in the bloodstream, renin converts angiotensinogen to angiotensin i. angiotensin i is further cleaved by the angiotensin-converting enzyme to angiotensin ii, which is a potent vasoconstrictor that increases blood pressure. in addition to angiotensin ii, other biologically active substances can be formed in mammals. angiotensin ii can be cleaved to angiotensin iii, angiotensin iv and angiotensin (1-7). acid-base balance maintaining acid-base balance is vital because changes in ph levels affect virtually every biological process in the body. in a typical mammal, a normal average ph level is around 7.4, an elevated level is called alkalosis, and a lower level is called acidosis. as in the case of other vertebrates in mammals, the acid-base balance is maintained mainly by the bicarbonate buffer system (hco3-/co2), which allows maintaining a constant ph level of the blood and extracellular fluid. this buffer system is described by the following equation: hco 3 − + h + ↽ − − ⇀ h 2 co 3 ↽ − − ⇀ co 2 + h 2 o the regulation of the acid-base balance through the bicarbonate buffer system is provided by the lungs and kidneys. the lungs regulate co2 (carbon dioxide) level, while the kidneys regulate hco3- and h+ (bicarbonate and hydrogen ions). the kidneys play a key role in maintaining a constant level of acid-base balance in mammals. in the glomeruli, hco3- is completely filtered into primary urine. to maintain a constant ph, the kidneys reabsorb almost all of the hco3- from primary urine back into the bloodstream and secrete h+ into the urine, oxidizing the urine. reabsorption of hco3- occurs in the proximal tubule, in the ascending limb of the loop of henle, and to a lesser extent in the distal convoluted tubule of the nephron. h+ secretion is carried out mainly through na+/h+ exchangers in the tubules of the nephron. the collecting ducts are involved in the energy-dependent secretion of h+. when h+ ions enter the urine, they can combine with filtered hco3- to form carbonic acid h2co3, which is being converted into co2 and h2o (water) by the luminal carbonic anhydrase. the formed co2 diffuses into the cells of the tubules, where it combines with h2o with the help of cytosolic carbonic anhydrase and forms hco3-, which then returns to the bloodstream, and the formed h+ ion is secreted into the urine. some of the h+ ions are secreted at an energy cost through an atp-dependent mechanism. the excreted urine is slightly acidic. the excretion of h+ together with urine also occurs through buffer systems, in particular, nh4+ (ammonium). only a small amount of nh4+ is filtered through the glomerulus; most of the ammonium excreted is the result of h+ ion oxidation of nh3 (ammonia) formed in the cells of the proximal convoluted tubule, which is secreted into the lumen of the tubule either as nh3 or as nh4+. the formation of ammonia is also accompanied by the formation of new hco3-, which replenishes the extracellular buffer system. in the thick ascending tubule of the loop of henle, on the contrary, nh4+ is absorbed, which causes its accumulation in the interstitium. the final stage of urine oxidation occurs in the collecting ducts, where h+ ions are secreted with the involvement of atp, and nh3 is transported from the interstitium and secreted into the urine, where nh3 is oxidized by h+ to form nh4+. by regulating hco3- reabsorption and h+ secretion, the kidneys help maintain blood ph homeostasis. kidney development stages of kidney development main article: kidney development in mammals, the final kidney is the metanephric kidney, but kidneys development occurs in three stages with the development of three different types of kidney during embryonic period: pronephros, mesonephros and metanephros. all three types develop from the intermediate mesoderm sequentially in the cranio-caudal direction (in the direction from the side of the head to the tail of the body). first, the pronephros is formed, in mammals it is considered rudimentary, that is, it does not function. then, caudal to the pronephros, the mesonephros develops, which is the functioning kidney of the embryo. subsequently, the mesonephros degrades in females, and in males it participates in the development of the reproductive system. the third stage is the formation of a metanephros in the caudal part of the embryo, which