In humans, thekidneys are two reddish-brown bean-shaped blood-filteringorgans[1] that are a multilobar, multipapillary form ofmammalian kidneys, usually without signs of external lobulation.[2][3] They are located on the left and right in theretroperitoneal space, and in adult humans are about 12 centimetres (4+1⁄2 inches) in length.[4][5] They receive blood from the pairedrenal arteries; blood exits into the pairedrenal veins. Each kidney is attached to aureter, a tube that carries excretedurine to thebladder.
The kidney participates in the control of the volume of variousbody fluids, fluidosmolality,acid-base balance, variouselectrolyte concentrations, and removal oftoxins. Filtration occurs in theglomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-freewater,sodium,bicarbonate,glucose, andamino acids. Examples of substances secreted arehydrogen,ammonium,potassium anduric acid. Thenephron is the structural and functional unit of the kidney. Each adult human kidney contains around 1 million nephrons, while a mouse kidney contains only about 12,500 nephrons. The kidneys also carry out functions independent of the nephrons. For example, they convert a precursor ofvitamin D to its active form,calcitriol; and synthesize thehormoneserythropoietin andrenin.
The word “renal” is an adjective meaning “relating to the kidneys”, and its roots are French or late Latin. Whereas according to some opinions, "renal" should be replaced with "kidney" in scientific writings such as "kidney artery", other experts have advocated preserving the use of "renal" as appropriate including in "renal artery".[8]
Structure
Image showing the humantrunk with positions of the organs. The kidneys are at thevertebral level of T12 to L3.
In humans, the kidneys are located high in theabdominal cavity, one on each side of thespine, and lie in aretroperitoneal position at a slightly oblique angle.[9] The asymmetry within the abdominal cavity, caused by the position of theliver, typically results in the right kidney being slightly lower and smaller than the left, and being placed slightly more to the middle than the left kidney.[10][11][12] The left kidney is approximately at the vertebral levelT12 toL3,[13] and the right is slightly lower. The right kidney sits just below thediaphragm and posterior to theliver. The left kidney sits below the diaphragm and posterior to thespleen. On top of each kidney is anadrenal gland. The upper parts of the kidneys are partially protected by the 11th and 12thribs. Each kidney, with its adrenal gland is surrounded by two layers of fat: theperirenal fat present between renal fascia and renal capsule andpararenal fat superior to therenal fascia.
The superior pole of the right kidney is adjacent to the liver. For the left kidney, it is next to thespleen. Both, therefore, move down upon inhalation.
A Danish study measured the median renal length to be11.2 cm (4+7⁄16 in) on the left side and10.9 cm (4+5⁄16 in) on the right side in adults. Median renal volumes were146 cm3 (8+15⁄16 cu in) on the left and134 cm3 (8+3⁄16 cu in) on the right.[17]
The functional substance, orparenchyma, of the human kidney is divided into two major structures: the outerrenal cortex and the innerrenal medulla. Grossly, these structures take the shape of eight to 18 cone-shapedrenal lobes, each containing renal cortex surrounding a portion of medulla called arenal pyramid.[18] Between the renal pyramids are projections of cortex calledrenal columns.
The tip, orpapilla, of each pyramid empties urine into aminor calyx; minor calyces empty intomajor calyces, and major calyces empty into therenal pelvis. This becomes the ureter. At the hilum, the ureter and renal vein exit the kidney and the renal artery enters. Hilar fat and lymphatic tissue with lymph nodes surround these structures. The hilar fat is contiguous with a fat-filled cavity called therenal sinus. The renal sinus collectively contains the renal pelvis and calyces and separates these structures from the renal medullary tissue.[19]
The kidneys possess no overtly moving structures.
Normal adult right kidney as seen onabdominal ultrasound with a pole to pole measurement of 9.34 cm
ACT scan of the abdomen showing the position of the kidneys. The left cross-section in the upper abdomen shows theliver on the left side of scan (right side of body). Center: cross-section showing the kidneys below the liver and spleen. Right: further cross-section through the left kidney.
Image showing the structures that the kidney lies near
Cross-section through acadaveric specimen showing the position of the kidneys
The kidneys receive blood from therenal arteries, left and right, which branch directly from theabdominal aorta. The kidneys receive approximately 20–25% ofcardiac output in adult human.[18][20][21] Each renal artery branches into segmental arteries, dividing further intointerlobar arteries, which penetrate the renal capsule and extend through the renal columns between the renal pyramids. The interlobar arteries then supply blood to thearcuate arteries that run through the boundary of the cortex and the medulla. Each arcuate artery supplies severalinterlobular arteries that feed into theafferent arterioles that supply the glomeruli.
Blood drains from the kidneys, ultimately into theinferior vena cava. After filtration occurs, the blood moves through a small network of small veins (venules) that converge intointerlobular veins. As with the arteriole distribution, the veins follow the same pattern: the interlobular provide blood to thearcuate veins then back to theinterlobar veins, which come to form therenal veins which exit the kidney.
Nephrons, the urine-producing functional structures of the kidney, span the cortex and medulla. The initial filtering portion of a nephron is therenal corpuscle, which is located in the cortex. This is followed by arenal tubule that passes from the cortex deep into the medullary pyramids. Part of the renal cortex, amedullary ray is a collection of renal tubules that drain into a singlecollecting duct.[citation needed]
Renalhistology is the study of themicroscopic structure of the kidney. The adult human kidney contains at least 26 distinctcell types,[25] including epithelial, endothelial, stromal and smooth muscle cells. Distinct cell types include:
In humans, about 20,000 protein coding genes are expressed in human cells and almost 70% of these genes are expressed in normal, adult kidneys.[26][27] Just over 300 genes are more specifically expressed in the kidney, with only some 50 genes being highly specific for the kidney. Many of the corresponding kidney specific proteins are expressed in the cell membrane and function as transporter proteins. The highest expressed kidney specific protein isuromodulin, the most abundant protein in urine with functions that prevent calcification and growth of bacteria. Specific proteins are expressed in the different compartments of the kidney withpodocin andnephrin expressed in glomeruli, Solute carrier family proteinSLC22A8 expressed in proximal tubules,calbindin expressed in distal tubules andaquaporin 2 expressed in the collecting duct cells.[28]
The mammalian kidney develops fromintermediate mesoderm.Kidney development, also callednephrogenesis, proceeds through a series of three successive developmental phases: the pronephros, mesonephros, and metanephros. The metanephros are primordia of the permanent kidney.[29]
Function
Thenephron, shown here, is the functional unit of the kidneys. Its parts are labelled except the (gray)connecting tubule located after the (dark red) distal convoluted tubule and before the large (gray) collecting duct (mislabeledcollection duct).
The kidneys excrete a variety of waste products produced bymetabolism into the urine. The microscopic structural and functional unit of the kidney is thenephron. It processes the blood supplied to it via filtration, reabsorption, secretion and excretion; the consequence of those processes is the production ofurine. These include the nitrogenous wastesurea, from proteincatabolism, anduric acid, fromnucleic acid metabolism. The ability of mammals and some birds to concentrate wastes into a volume of urine much smaller than the volume of blood from which the wastes were extracted is dependent on an elaboratecountercurrent multiplication mechanism. This requires several independent nephron characteristics to operate: a tight hairpin configuration of the tubules, water and ion permeability in the descending limb of the loop, water impermeability in the ascending loop, and active ion transport out of most of the ascending limb. In addition, passivecountercurrent exchange by the vessels carrying the blood supply to the nephron is essential for enabling this function.
Four main processes are involved in the creation ofurine.
Filtration
Filtration, which takes place at therenal corpuscle, is the process by which cells and large proteins are retained while materials of smaller molecular weights are[30] filtered from the blood to make anultrafiltrate that eventually becomes urine. The adult human kidney generates approximately 180 liters of filtrate a day, most of which is reabsorbed.[31] The normal range for a twenty four hour urine volume collection is 800 to 2,000 milliliters per day.[32] The process is also known as hydrostatic filtration due to the hydrostatic pressure exerted on the capillary walls.
Reabsorption
Secretion and reabsorption of various substances throughout the nephron
Reabsorption is the transport of molecules from this ultrafiltrate and into the peritubular capillary network that surrounds the nephron tubules.[33] It is accomplished via selectivereceptors on the luminal cell membrane. Water is 55% reabsorbed in the proximal tubule. Glucose at normal plasma levels is completely reabsorbed in the proximal tubule. The mechanism for this is the Na+/glucose cotransporter. A plasma level of 350 mg/dL will fully saturate the transporters and glucose will be lost in the urine. A plasma glucose level of approximately 160 is sufficient to allow glucosuria, which is an important clinical clue to diabetes mellitus.
Amino acids are reabsorbed by sodium dependent transporters in the proximal tubule.Hartnup disease is a deficiency of the tryptophan amino acid transporter, which results inpellagra.[34]
Reabsorbs via medullary hypertonicity and makes urine hypertonic.
Thick ascending loop of Henle
Na+ (10–20%), K+, Cl−; indirectly induces para cellular reabsorption of Mg2+, Ca2+
This region is impermeable to H2O and the urine becomes less concentrated as it ascends.
Early distal convoluted tubule
Na+, Cl−
PTH causes Ca2+ reabsorption.
Collecting tubules
Na+(3–5%), H2O
Na+ is reabsorbed in exchange for K+, and H+, which is regulated by aldosterone.
ADH acts on the V2 receptor and insertsaquaporins on the luminal side
Examples of substances that are reabsorbed in the kidneys, and the hormones that influence those processes.[34]
Secretion
Secretion is the reverse of reabsorption: molecules are transported from the peritubular capillary through the interstitial fluid, then through the renal tubular cell and into the ultrafiltrate.
Excretion
The last step in the processing of the ultrafiltrate isexcretion: the ultrafiltrate passes out of the nephron and travels through a tube called thecollecting duct, which is part of thecollecting duct system, and then to the ureters where it is renamedurine. In addition to transporting the ultrafiltrate, the collecting duct also takes part in reabsorption.
Hormone secretion
The kidneys are essential for more than just filtration; they also secrete several important hormones that play pivotal roles in regulating various physiological processes.The kidneys secrete a variety ofhormones, includingerythropoietin,calcitriol, andrenin.Erythropoietin (EPO) is released in response tohypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulateserythropoiesis (production of red blood cells) in thebone marrow.Calcitriol, the activated form ofvitamin D, promotes intestinal absorption ofcalcium and the renalreabsorption ofphosphate. Renin is anenzyme which regulatesangiotensin andaldosterone levels.
Erythropoietin (EPO): Produced in response to low oxygen levels, EPO stimulates red blood cell production in the bone marrow. Impaired EPO production, particularly in chronic kidney disease, can lead to anemia and cardiovascular complications.
Renin: Secreted in response to low blood pressure or sodium levels, renin initiates the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid balance. Dysregulation of RAAS is linked to hypertension and cardiovascular diseases.
Calcitriol: The active form of vitamin D, calcitriol helps regulate calcium and phosphate metabolism, supporting bone health and calcium absorption in the intestines. Impaired calcitriol synthesis can lead to bone mineralization issues in chronic kidney disease.
Hormonal interventions, including the introduction of therapies - such as gender-affirming treatments - may alter renal function, estrogen and testosterone and affect kidney function, electrolyte balance, and glomerular filtration rate.[35] Monitoring kidney health is essential in adolescents undergoing such treatments to avoid potential long-term complications, especially in those with preexisting renal issues.
Although the kidney cannot directly sense blood, long-term regulation ofblood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of theextracellular fluid compartment, the size of which depends on the plasmasodium concentration. Renin is the first in a series of important chemical messengers that make up therenin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormonesangiotensin II andaldosterone. Each hormone acts via multiple mechanisms, but both increase the kidney's absorption ofsodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure.
The two organ systems that help regulate the body's acid–base balance are the kidneys and lungs.Acid–base homeostasis is the maintenance ofpH around a value of 7.4. The lungs are the part of respiratory system which helps to maintain acid–base homeostasis by regulatingcarbon dioxide (CO2) concentration in the blood. The respiratory system is the first line of defense when the body experiences and acid–base problem. It attempts to return the body pH to a value of 7.4 by controlling the respiratory rate. When the body is experiencing acidic conditions, it will increase the respiratory rate which in turn drives off CO2 and decreases the H+ concentration, therefore increasing the pH. In basic conditions, the respiratory rate will slow down so that the body holds onto more CO2 and increases the H+ concentration and decreases the pH.[36]
The kidneys have two cells that help to maintain acid-base homeostasis: intercalated A and B cells. The intercalated A cells are stimulated when the body is experiencing acidic conditions. Under acidic conditions, the high concentration of CO2 in the blood creates a gradient for CO2 to move into the cell and push the reaction HCO3 + H ↔ H2CO3 ↔ CO2 + H2O to the left. On the luminal side of the cell there is a H+ pump and a H/K exchanger. These pumps move H+ against their gradient and therefore require ATP. These cells will remove H+ from the blood and move it to the filtrate which helps to increase the pH of the blood. On the basal side of the cell there is a HCO3/Cl exchanger and a Cl/K co-transporter (facilitated diffusion). When the reaction is pushed to the left it also increases the HCO3 concentration in the cell and HCO3 is then able to move out into the blood which additionally raises the pH. The intercalated B cell responds very similarly, however, the membrane proteins are flipped from the intercalated A cells: the proton pumps are on the basal side and the HCO3/Cl exchanger and K/Cl co-transporter are on the luminal side. They function the same, but now release protons into the blood to decrease the pH.[37]
Regulation of osmolality
The kidneys help maintain the water and salt level of the body. Any significant rise inplasma osmolality is detected by thehypothalamus, which communicates directly with theposterior pituitary gland. An increase in osmolality causes the gland to secreteantidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.
Various calculations and methods are used to try to measure kidney function.Renal clearance is the volume of plasma from which the substance is completely cleared from the blood per unit time. Thefiltration fraction is the amount of plasma that is actually filtered through the kidney. This can be defined using the equation. The kidney is a very complex organ andmathematical modelling has been used to better understand kidney function at several scales, including fluid uptake and secretion.[38][39]
Medical terms related to the kidneys commonly use terms such asrenal and the prefixnephro-. Theadjectiverenal, meaning related to the kidney, is from theLatinrēnēs, meaning kidneys; the prefixnephro- is from theAncient Greek word for kidney,nephros (νεφρός).[40] For example, surgical removal of the kidney is anephrectomy, while a reduction in kidney function is calledrenal dysfunction.
Kidney stones (nephrolithiasis) are a relatively common and particularly painful disorder. A chronic condition can result in scars to the kidneys. The removal of kidney stones involvesultrasound treatment to break up the stones into smaller pieces, which are then passed through the urinary tract. One common symptom of kidney stones is a sharp to disabling pain in the middle and sides of the lower back or groin.
Innephrotic syndrome, theglomerulus has been damaged so that a large amount ofprotein in the blood enters theurine. Other frequent features of the nephrotic syndrome include swelling, low serum albumin, and high cholesterol.
Generally, humans can live normally with just one kidney, as one has more functioning renal tissue than is needed to survive. Only when the amount of functioning kidney tissue is greatly diminished does one developchronic kidney disease.Renal replacement therapy, in the form ofdialysis orkidney transplantation, is indicated when theglomerular filtration rate has fallen very low or if the renal dysfunction leads to severe symptoms.[41]
Dialysis is a treatment that substitutes for the function of normal kidneys. Dialysis may be instituted when approximately 85%–90% of kidney function is lost, as indicated by a glomerular filtration rate (GFR) of less than 15. Dialysis removes metabolic waste products as well as excess water and sodium (thereby contributing to regulating blood pressure); and maintains many chemical levels within the body. Life expectancy is 5–10 years for those on dialysis; some live up to 30 years. Dialysis can occur via the blood (through acatheter orarteriovenous fistula), or through theperitoneum (peritoneal dialysis) Dialysis is typically administered three times a week for several hours at free-standing dialysis centers, allowing recipients to lead an otherwise essentially normal life.[42]
Duplex kidneys, or double kidneys, occur in approximately 1% of the population. This occurrence normally causes no complications, but can occasionally cause urinary tract infections.[43][44]
Renal agenesis. Failure of one kidney to form occurs in approximately one in 750 live births. Failure of both kidneys to form used to be fatal; however, medical advances such as amnioinfusion therapy during pregnancy and peritoneal dialysis have made it possible to stay alive until a transplant can occur.
Ureteropelvic Junction Obstruction or UPJO; although most cases are congenital, some are acquired.[45]
Diagnosis
Many renal diseases are diagnosed on the basis of a detailedmedical history, andphysical examination.[46] The medical history takes into account present and past symptoms, especially those of kidney disease; recent infections; exposure to substances toxic to the kidney; and family history of kidney disease.
Kidney function is tested by usingblood tests andurine tests. The most common blood tests arecreatinine,urea andelectrolytes. Urine tests such asurinalysis can evaluate for pH, protein, glucose, and the presence of blood. Microscopic analysis can also identify the presence ofurinary casts and crystals.[47] Theglomerular filtration rate (GFR) can be directly measured ("measured GFR", or mGFR) but this rarely done in everyday practice. Instead, special equations are used to calculate GFR ("estimated GFR", or eGFR).[48][47]
Imaging
Renal ultrasonography is essential in the diagnosis and management of kidney-related diseases.[49] Other modalities, such asCT andMRI, should always be considered as supplementary imaging modalities in the assessment of renal disease.[49]
Biopsy
The role of the renal biopsy is to diagnose renal disease in which the etiology is not clear based upon noninvasive means (clinical history, past medical history, medication history, physical exam, laboratory studies, imaging studies). In general, a renal pathologist will perform a detailed morphological evaluation and integrate the morphologic findings with the clinical history and laboratory data, ultimately arriving at a pathological diagnosis. A renalpathologist is a physician who has undergone general training in anatomic pathology and additional specially training in the interpretation of renal biopsy specimens.
Ideally, multiple core sections are obtained and evaluated for adequacy (presence of glomeruli) intraoperatively. A pathologist/pathology assistant divides the specimen(s) for submission for light microscopy, immunofluorescence microscopy and electron microscopy.
The pathologist will examine the specimen using light microscopy with multiple staining techniques (hematoxylin and eosin/H&E, PAS, trichrome, silver stain) on multiple level sections. Multiple immunofluorescence stains are performed to evaluate for antibody, protein and complement deposition. Finally, ultra-structural examination is performed with electron microscopy and may reveal the presence of electron-dense deposits or other characteristic abnormalities that may suggest an etiology for the patient's renal disease.
In the majority of vertebrates, themesonephros persists into the adult, albeit usually fused with the more advancedmetanephros; only inamniotes is the mesonephros restricted to the embryo. The kidneys offish andamphibians are typically narrow, elongated organs, occupying a significant portion of the trunk. The collecting ducts from each cluster of nephrons usually drain into anarchinephric duct, which ishomologous with thevas deferens of amniotes. However, the situation is not always so simple; incartilaginous fish and some amphibians, there is also a shorter duct, similar to the amniote ureter, which drains the posterior (metanephric) parts of the kidney, and joins with the archinephric duct at thebladder orcloaca. Indeed, in many cartilaginous fish, the anterior portion of the kidney may degenerate or cease to function altogether in the adult.[50]
In the most primitive vertebrates, thehagfish andlampreys, the kidney is unusually simple: it consists of a row of nephrons, each emptying directly into the archinephric duct. Invertebrates may possess excretory organs that are sometimes referred to as "kidneys", but, even inAmphioxus, these are never homologous with the kidneys of vertebrates, and are more accurately referred to by other names, such asnephridia.[50] Inamphibians, kidneys and theurinary bladder harbour specializedparasites,monogeneans of the family Polystomatidae.[51]
The kidneys ofreptiles consist of a number of lobules arranged in a broadly linear pattern. Each lobule contains a single branch of the ureter in its centre, into which the collecting ducts empty. Reptiles have relatively few nephrons compared with other amniotes of a similar size, possibly because of their lowermetabolic rate.[50]
Birds have relatively large, elongated kidneys, each of which is divided into three or more distinct lobes. The lobes consists of several small, irregularly arranged, lobules, each centred on a branch of the ureter. Birds have small glomeruli, but about twice as many nephrons as similarly sized mammals.[50]
The human kidney is fairly typical of that ofmammals. Distinctive features of the mammalian kidney, in comparison with that of other vertebrates, include the presence of the renal pelvis and renal pyramids and a clearly distinguishable cortex and medulla. The latter feature is due to the presence of elongatedloops of Henle; these are much shorter in birds, and not truly present in other vertebrates (although the nephron often has a shortintermediate segment between the convoluted tubules). It is only in mammals that the kidney takes on its classical "kidney" shape, although there are some exceptions, such as the multilobedreniculate kidneys ofpinnipeds andcetaceans.[50]
Evolutionary adaptation
Kidneys of various animals show evidence of evolutionaryadaptation and have long been studied inecophysiology andcomparative physiology. Kidney morphology, often indexed as the relative medullary thickness, is associated with habitataridity among species of mammals[52] and diet (e.g., carnivores have only long loops of Henle).[39]
Society and culture
Significance
Egyptian
Inancient Egypt, the kidneys, like the heart, were left inside the mummified bodies, unlike other organs which were removed. Comparing this to the biblical statements, and to drawings of human body with the heart and two kidneys portraying a set of scales for weighing justice, it seems that the Egyptian beliefs had also connected the kidneys with judgement and perhaps with moral decisions.[53]
Hebrew
According to studies in modern and ancient Hebrew, various body organs in humans and animals served also an emotional or logical role, today mostly attributed to thebrain and theendocrine system. The kidney is mentioned in several biblical verses in conjunction with the heart, much as thebowels were understood to be the "seat" of emotion – grief, joy and pain.[54] Similarly, theTalmud (Berakhoth 61.a) states that one of the two kidneys counsels what is good, and the other evil.
In the sacrifices offered at the biblicalTabernacle and later on at the temple inJerusalem, the priests were instructed[55] to remove the kidneys and the adrenal gland covering the kidneys of the sheep, goat and cattle offerings, and to burn them on the altar, as the holy part of the "offering for God" never to be eaten.[56]
India: Ayurvedic system
In ancient India, according to theAyurvedic medical systems, the kidneys were considered the beginning of the excursion channels system, the 'head' of theMutra Srotas, receiving from all other systems, and therefore important in determining a person's health balance and temperament by the balance and mixture of the three 'Dosha's – the three health elements: Vatha (or Vata) – air, Pitta –bile, and Kapha –mucus. The temperament and health of a person can then be seen in the resulting color of the urine.[57]
Modern Ayurveda practitioners, a practice which is characterized as pseudoscience,[58] have attempted to revive these methods in medical procedures as part of AyurvedaUrine therapy.[59] These procedures have been called "nonsensical" by skeptics.[60]
Medieval Christianity
The Latin termrenes is related to the English word "reins", a synonym for the kidneys inShakespearean English (e.g.Merry Wives of Windsor 3.5), which was also the time when theKing James Version of theBible was translated. Kidneys were once popularly regarded as the seat of theconscience and reflection,[61][62] and a number of verses in the Bible (e.g. Ps. 7:9, Rev. 2:23) state that God searches out and inspects the kidneys, or "reins", of humans, together with the heart.[63]
History
Kidney stones have been identified and recorded about as long as written historical records exist.[64] The urinary tract including the ureters, as well as their function to drain urine from the kidneys, has been described byGalen in the second century AD.[65]
The first to examine the ureter through an internal approach, called ureteroscopy, rather than surgery wasHampton Young in 1929.[64] This was improved on byVF Marshall who is the first published use of a flexibleendoscope based onfiber optics, which occurred in 1964.[64] The insertion of a drainage tube into therenal pelvis, bypassing the uterers and urinary tract, callednephrostomy, was first described in 1941. Such an approach differed greatly from theopen surgical approaches within the urinary system employed during the preceding two millennia.[64]
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