Mammalian kidney

Mammalian kidney
Unipapillary, multilobar, smooth, bean-shaped camel kidney, in which the renal papillae are completely fused into the renal crest.
Details
Precursor	Ureteric bud, metanephrogenic blastema
System	Urinary system and endocrine system
Artery	Renal artery
Vein	Renal vein
Nerve	Renal plexus
Lymph	Collecting lymphatic vessels
Anatomical terminology

The mammalian kidneys are the paired organ of the urinary system of mammals, which is a type of metanephric kidney. The kidney in mammals is usually bean-shaped, located retroperitoneally on the back (dorsal) wall of the body. Each kidney consists of a renal capsule, peripheral cortex, internal medulla, calices, and renal pelvis, although the calices or renal pelvis may be absent in some species. Urine is excreted from the kidney through the ureter. The structure of the kidney may differ between species depending on the environment, in particular on its aridity. The cortex is responsible for filtering the blood, this part of the kidney is similar to the typical kidneys of less developed vertebrates.Nitrogen-containing waste products are excreted by the kidneys in mammals mainly in the form of urea.

Depending on the species, the kidneys can be unilobar (single lobe) or multilobar, unipapillary (single papilla), with several papillae or multipapillary, may be smooth-surfaced or lobulated, also the kidneys may be reniculate, which are found mainly in marine mammals. The simplest type of kidney in mammals is the unipapillary kidney with single lobe. The human kidney is an example of the mammalian kidney.

The cortex and medulla of the kidney contain nephrons. In mammals, the nephron consists of the renal glomerulus inside Bowman's capsule, the proximal convoluted tubule, the proximal straight tubule, the loop of Henle, and the distal convoluted tubule. The nephrons can be classified as nephrons with a short loop and a long loop of Henle. Blood that enters the kidneys is filtered through the renal glomeruli into Bowman's capsule to form primary urine. Then it enters the tubules, which concentrate it. Amongst the vertebrates, only mammals and birds have kidneys that can produce urine more concentrated (hypertonic) than the blood plasma, but only in mammals do all nephrons have the loop of Henle.

The kidneys of mammals are vital organs that maintain water, electrolyte and acid-base balance in the body, excrete nitrogenous waste products, regulate blood pressure and participate in bone formation. The processes of blood plasma filtration, tubular reabsorption and tubular secretion occur in the kidneys, and urine formation is a result of these processes. The kidneys produce renin and erythropoietinhormones, and are involved in the conversion of vitamin D to its active form. Mammals are the only class of vertebrates in which only the kidneys are responsible for maintaining the homeostasis of the extracellular fluid in the body. The function of the kidneys is regulated by the autonomic nervous system and hormones.

Structure

Didactic model of the mammalian kidney: 1 — fibrous capsule, 2 — cortex, 3 — renal pyramid of the medulla, 4 — renal column of the cortex, 5 — nephron, 6 — renal papilla, 7 — minor renal calyx, 8 — major renal calyx, 9 — renal pelvis, 10 — ureter, 11 — renal artery, 12 — renal vein, 13 — interlobar artery, 14 — renal lobe, 15 — arcuate artery, 16 — interlobular artery.

Location and form

In mammals, kidneys are usually bean-shaped; the shape is unique to mammals (fish, for example, has elongated kidneys). Kidneys are located retroperitoneally on the posterior (dorsal) wall of the body. One of the key factors that determine the shape and morphology of the kidneys in mammals is their mass. The concave part of the bean-shaped kidneys is called the renal hilum, through which the renal artery and nerves enter the kidney. The renal vein, collecting lymphatic vessels and ureter exit the kidney through the renal hilum. In the body, the kidney is surrounded by a mass of adipose tissue.

General structure

The outer layer of each kidney is made up of a fibrous sheath called a renal capsule. The peripheral layer of the kidney is represented by the cortex, and the inner layer is represented by the medulla. The medulla consists of pyramids (also called malpighian pyramids), ascending with their base to the cortex and forming together with it the renal lobe. The pyramids are separated from each other by renal columns (Bertin's columns) formed by cortical tissue. The tips of the pyramids end with the renal papillae, from which urine is excreted into the calyces, pelvis, ureter, and, in most species, directly into the bladder, after which it is excreted through the urethra.

Parenchyma

The parenchyma, being a functional part of the kidneys, is visually divided into cortex and medulla. The cortex and medulla are based on nephrons together with an extensive network of blood vessels and capillaries, as well as collecting ducts, into which nephrons empty, and renal interstitium. There is a blood-filtering part of the nephron in the cortex — the renal corpuscle, from which the renal tubule extends to the medulla into the loop of Henle, then the tubule returns back to the cortex and with its distal end flows into its collecting duct that is common to several nephrons. The collecting ducts descend again into the medulla and fuse to wider collecting ducts which pass through the inner medulla.

The ratio of cortex to medulla varies between species, in domesticated animals the cortex usually occupies a third or fourth part of the parenchyma, while in desert animals with long loops of Henle it is only a fifth part.

Cortex

Structurally, the cortex consists of cortical labyrinth and medullary rays. The cortical labyrinth contains interlobular arteries, vascular networks formed by afferent and efferent arterioles, renal corpuscles, proximal convoluted tubules, macula densa, distal convoluted tubules, connecting tubules and the initial parts of the collecting ducts. The proximal convoluted tubules predominate in the cortical labyrinth. The continuous layer of the cortex lying above the medullary rays is called the cortex corticis. Some mammals have nephrons whose loops of Henle do not reach the medulla; such nephrons are called cortical nephrons. The medullary rays of the cortex contain the proximal straight tubules, the cortical part of the thick ascending limb of the loops of Henle, and the cortical part of the collecting ducts. The cortex is divided into lobules, each of which is a medullary ray in conjunction with connected to it nephrons, and interlobular arteries that pass between the lobules.

Medulla

The medulla in mammals is divided into outer and inner regions. The outer region consists of short loops of Henle and collecting ducts, while the inner region consists of long loops and collecting ducts. The outer region is also subdivided into outer (lying directly under the cortex) and inner stripes. The stripes differ in that the outer stripe contain proximal straight tubules, while the inner strite contain thin descending limbs of the loop of Henle (a section of the nephron following the proximal straight tubule).

The ratio of the outer and inner medulla

Most mammalian species have nephrons with both short and long loops of Henle, while some species may have only one type. For example, mountain beavers have only nephrons with a short loop, and, accordingly, there is no inner medulla in the kidney. Dogs and cats, on the other hand, have only long-loop nephrons. The ratio of nephrons with short loops of Henle to those with long loops also varies between species.

Structural differences between species

Buffalo kidneys

Structurally, kidneys vary between mammals. What structural type a particular species will have depends generally on the body mass of the animals. Small mammals have unilobar kidneys with a compact structure and a single renal papilla, while larger animals have multilobar kidneys, such as those of bovines, but bovine kidneys are also externally lobulated (visually divided into lobes). By itself, the lobe is equivalent to a simple unipapillary kidney, as in rats or mice. Bovine kidneys also lack renal pelvis, urine from the major calices is excreted directly into the ureter.

Kidneys can be unipapillary, as in rats and mice, with few renal papillae, as in spider monkeys, or with many, as in pigs and humans. Most animals have single renal papilla. In some animals, such as horses, the tips of the renal pyramids fuse with each other to form a common renal papilla, called the renal crest. The renal crest usually appears in animals larger than the rabbit.

Horse kidneys

In marine mammals, otters and bears, the kidneys are reniculate, consisting of small reniculi, each of which is comparable to a simple unilobar kidney. Marine mammal kidneys can have hundreds of reniculi, each with its own cortex, medulla, and calyx. In manatees, which are also marine mammals, the kidneys are actually multilobar, since the cortex is continuous.

The size of the kidneys increases with the mass of mammals, and the number of nephrons in the kidneys between mammals increases allometrically. In mice, the kidneys are approximately 1 cm (0.4 in) long, weighing 400 mg, with 16,000 nephrons, while in the killer whale, the kidney length exceeds 25 cm (10 in), the mass is approximately 4.5 kg (10 lb), with the number of nephrons of the order of 10,000,000. At the same time, killer whale kidneys are reniculate, and each reniculus is comparable to the kidney of mice. Reniculate kidneys probably increase the number of nephrons by the addition of individual reniculi without the need to increase the length of the tubules. An alternative adaptation mechanism is an increase in the diameter of the renal glomeruli in large mammals (and, accordingly, an increase in the length of the tubules), like in elephants, in which the glomerulus diameter can be 2 times larger than that of killer whales.

Microanatomy

By microanatomic structure, the kidney can be divided into several main elements: interstitium, renal corpuscles, tubules, and vasculature. The interstitium is the cells and extracellular matrix in the space between the glomeruli, vessels, tubules, and collecting ducts. Due to the lack of a basement membrane, the lymphatic capillaries are also considered part of the interstitium. The nephron, together with the collecting duct that continues it, is called the uriniferous tubule.

Approximately 18–26 different cell types have been described in mammalian kidneys, with a large variation in the range due to a lack of consensus on what counts as a particular cell type, and likely to species differences. At least 16 different cell types make up the renal tubules. The tubules themselves are divided into at least 14 segments, which differ in cell types and functions. The normal functioning of the kidneys is provided by the complex of epithelial, endothelial, interstitial and immune cells.

Blood supply

Equine kidney blood supply

Blood enters the kidney through the renal artery, which in the multilobar kidney branches in the area of the renal pelvis into large interlobar arteries that pass through the renal columns. The interlobar arteries branch at the base of the pyramid, giving rise to arcuate arteries, from which the interlobular arteries extend into the cortex. The interlobar arteries supply the pyramids and the adjacent cortex with an extensive network of blood vessels. The cortex itself is heavily permeated with arteries, while there are no arteries in the medulla. The venous flow of blood runs back parallel to the arteries. In some species, in the cortex there are veins isolated from the arteries under the capsule, which in humans are called stellate veins. These veins flow into the interlobular veins. The renal portal system is absent in mammals, with the exception of monotremes. Mammals are the only class of vertebrates (with exception of some species) that does not have a renal portal system.

The vascular glomeruli of nephrons receive blood from afferent arterioles, which originate in the interlobular arteries with intermediate formation of prearterioles. Each afferent arteriole divides into several renal glomeruli. Then these glomeruli join into the efferent arteriole, into which filtered blood goes from the nephrons. In nephrons with a long loop of Henle, the efferent arterioles branch, forming straight vessels called vasa recta, descending into the medulla. The descending vasa recta, ascending vasa recta vessels, and the loop of Henle together form the countercurrent system of the kidney. In the afferent arteriole, blood is supplied at high pressure, which promotes filtration, and in the efferent arteriole, it is at low pressure, which promotes reabsorption.

Despite their small size, the kidneys of mammals account 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:

${\displaystyle {\ce {HCO_3^- + H+ <=> H2CO3 <=> CO2 + H2O}}}$

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

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 is a permanent kidney.

Metanephros development

The metanephros develops from the ureteric bud, which is an outgrowth on the caudal part of the nephric duct, and the metanephrogenic blastema, which is part of the intermediate mesoderm surrounding the ureteral bud. The development of metanephros begins with the induction of a metanephrogenic blastema by the ureteric bud. While the kidney develops, the metanephrogenic blastema and ureteric bud reciprocally induce each other. Growing into the mesoderm, the ureteric bud branches and transforms into a tree structure that will eventually become the ureter, renal pelvis, major and minor calyces, renal papillae, and collecting ducts. At the same time, at the tips of the collecting ducts, the mesoderm differentiates into epithelial cells that form nephron tubules (processes of epithelialization and tubulogenesis occur). Vascular system of the kidney is also developed with the development of nephrons, with large vessels branching from the dorsal aorta.

In some mammals, kidney organogenesis ends before birth, while in others it may continue for some time into the postpartum period (for example, in rodents it ends about a week after birth). When the formation of new nephrons (nephrogenesis) ends, the number of nephrons in the kidney becomes final. Thus, after suffering damage, the kidneys of adult mammals cannot regenerate by forming new nephrons.

Bibliography

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