Editing Kidney (section)

== Function ==
[[File:Kidney Nephron.png|thumb|The [[nephron]], 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 (mislabeled ''collection'' duct).]]
{{main|Renal physiology}}

The kidneys excrete a variety of waste products produced by [[metabolism]] into the urine. The microscopic structural and functional unit of the kidney is the [[nephron]]. It processes the blood supplied to it via filtration, reabsorption, secretion and excretion; the consequence of those processes is the production of [[urine]]. These include the nitrogenous wastes [[urea]], from protein [[catabolism]], and [[uric acid]], from [[nucleic 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 elaborate [[countercurrent 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, passive [[countercurrent exchange]] by the vessels carrying the blood supply to the nephron is essential for enabling this function.

The kidney participates in whole-body [[homeostasis]], regulating [[acid–base balance]], [[electrolyte]] concentrations, [[extracellular fluid volume]], and [[blood pressure]]. The kidney accomplishes these homeostatic functions both independently and in concert with other organs, particularly those of the [[endocrine system]]. Various endocrine hormones coordinate these endocrine functions; these include [[renin]], [[angiotensin II]], [[aldosterone]], [[antidiuretic hormone]], and [[atrial natriuretic peptide]], among others.

===Formation of urine===
[[File:Physiology of Nephron.png|thumb|260px|Four main processes are involved in the creation of [[urine]].]]

====Filtration====
Filtration, which takes place at the [[renal corpuscle]], is the process by which cells and large proteins are retained while materials of smaller molecular weights are<ref>{{cite book | vauthors = Hall JE |title=Guyton and Hall textbook of medical physiology |date=2016 |publisher=Elsevier Health Sciences |location=Philadelphia, PA |isbn=978-0-323-38930-3 |edition=13th | page = 1129 }}</ref> filtered from the blood to make an [[Ultrafiltration (kidney)|ultrafiltrate]] that eventually becomes urine. The adult human kidney generates approximately 180 liters of filtrate a day, most of which is reabsorbed.<ref>{{Cite book |last1=Alpern |first1=Robert J. |url=https://books.google.com/books?id=w5nEg7VLEQ4C&pg=1405 |title=Seldin and Giebisch's The Kidney: Physiology and Pathophysiology |last2=Caplan |first2=Michael |last3=Moe |first3=Orson W. |date=2012-12-31 |publisher=Academic Press |isbn=978-0-12-381463-0 |pages=1405 |language=en |access-date=2022-07-28 |archive-date=2023-07-22 |archive-url=https://web.archive.org/web/20230722105802/https://books.google.com/books?id=w5nEg7VLEQ4C&pg=1405 |url-status=live }}</ref> The normal range for a twenty four hour urine volume collection is 800 to 2,000 milliliters per day.<ref>{{cite web|url=https://www.mountsinai.org/health-library/tests/urine-24-hour-volume|title=Urine 24-hour volume|website=mountsinai|access-date=21 November 2022|archive-date=21 November 2022|archive-url=https://web.archive.org/web/20221121180728/https://www.mountsinai.org/health-library/tests/urine-24-hour-volume|url-status=live}}</ref> The process is also known as hydrostatic filtration due to the hydrostatic pressure exerted on the capillary walls.

====Reabsorption====
[[File:2618 Nephron Secretion Reabsorption.jpg|thumb|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.<ref name="2024-Kumaran">{{cite journal |vauthors=Kumaran GK, Hanukoglu I |title=Mapping the cytoskeletal architecture of renal tubules and surrounding peritubular capillaries in the kidney |journal=Cytoskeleton (Hoboken) |volume=81 |issue=4–5 |pages=227–237 |date=2024 |pmid=37937511 |doi=10.1002/cm.21809 |url=}}</ref> It is accomplished via selective [[Cell surface receptor|receptor]]s 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<sup>+</sup>/glucose cotransporter. A plasma level of 350&nbsp;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 in [[pellagra]].<ref name="Tao p 1">Le, Tao. ''First Aid for the USMLE Step 1'' 2013. New York: McGraw-Hill Medical, 2013. Print.</ref>

{| class="wikitable"
|-
! Location of Reabsorption !! Reabsorbed nutrient !! Notes
|-
| Early proximal tubule || Glucose (100%), amino acids (100%), bicarbonate (90%), Na<sup>+</sup> (65%), Cl<sup>−</sup> (65%), phosphate (65%) and H<sub>2</sub>O (65%) || 
* [[Parathyroid hormone|PTH]] will inhibit phosphate reabsorption.
* [[Angiotensin II|AT II]] stimulates Na<sup>+</sup>, H<sub>2</sub>O and HCO<sub>3</sub><sup>−</sup> reabsorption.
|-
| Thin descending loop of Henle || H<sub>2</sub>O || 
* Reabsorbs via medullary hypertonicity and makes urine hypertonic.
|-
| Thick ascending loop of Henle || Na<sup>+</sup> (10–20%), K<sup>+</sup>, Cl<sup>−</sup>; indirectly induces para cellular reabsorption of Mg<sup>2+</sup>, Ca<sup>2+</sup> || 
* This region is impermeable to H<sub>2</sub>O and the urine becomes less concentrated as it ascends.
|-
| Early distal convoluted tubule || Na<sup>+</sup>, Cl<sup>−</sup> || 
* PTH causes Ca<sup>2+</sup> reabsorption.
|-
| Collecting tubules || Na<sup>+</sup>(3–5%), H<sub>2</sub>O || 
* Na<sup>+</sup> is reabsorbed in exchange for K<sup>+</sup>, and H<sup>+</sup>, which is regulated by aldosterone.
* ADH acts on the V2 receptor and inserts [[aquaporins]] on the luminal side
|-
! colspan="3" |Examples of substances that are reabsorbed in the kidneys, and the hormones that influence those processes.<ref name="Tao p 1"/>
|}

====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 is ''excretion'': the ultrafiltrate passes out of the nephron and travels through a tube called the ''collecting duct'', which is part of the [[collecting duct system]], and then to the ureters where it is renamed ''urine''. 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 of [[hormones]], including [[erythropoietin]], [[calcitriol]], and [[renin]]. [[Erythropoietin]] (EPO) is released in response to [[Hypoxia (medical)|hypoxia]] (low levels of oxygen at tissue level) in the renal circulation. It stimulates [[erythropoiesis]] (production of red blood cells) in the [[bone marrow]]. [[Calcitriol]], the activated form of [[vitamin D]], promotes intestinal absorption of [[calcium]] and the renal [[reabsorption]] of [[phosphate]]. Renin is an [[enzyme]] which regulates [[angiotensin]] and [[aldosterone]] 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.<ref>{{Cite journal |last1=Hembree |first1=Wylie C |last2=Cohen-Kettenis |first2=Peggy T |last3=Gooren |first3=Louis |last4=Hannema |first4=Sabine E |last5=Meyer |first5=Walter J |last6=Murad |first6=M Hassan |last7=Rosenthal |first7=Stephen M |last8=Safer |first8=Joshua D |last9=Tangpricha |first9=Vin |last10=T’Sjoen |first10=Guy G |date=2017-11-01 |title=Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline |url=http://academic.oup.com/jcem/article/102/11/3869/4157558 |journal=The Journal of Clinical Endocrinology & Metabolism |language=en |volume=102 |issue=11 |pages=3869–3903 |doi=10.1210/jc.2017-01658 |pmid=28945902 |issn=0021-972X}}</ref> Monitoring kidney health is essential in adolescents undergoing such treatments to avoid potential long-term complications, especially in those with preexisting renal issues.

===Blood pressure regulation===
{{main|Blood pressure regulation|Renin–angiotensin system}}

Although the kidney cannot directly sense blood, long-term regulation of [[blood pressure]] predominantly depends upon the kidney. This primarily occurs through maintenance of the [[extracellular fluid]] compartment, the size of which depends on the plasma [[sodium]] concentration. Renin is the first in a series of important chemical messengers that make up the [[renin–angiotensin system]]. Changes in renin ultimately alter the output of this system, principally the hormones [[angiotensin II]] and [[aldosterone]]. Each hormone acts via multiple mechanisms, but both increase the kidney's absorption of [[sodium 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.

===Acid–base balance===
{{main|Acid–base homeostasis}}

The two organ systems that help regulate the body's acid–base balance are the kidneys and lungs. [[Acid–base homeostasis]] is the maintenance of [[pH]] around a value of 7.4. The lungs are the part of respiratory system which helps to maintain acid–base homeostasis by regulating [[carbon dioxide]] (CO<sub>2</sub>) 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 CO<sub>2</sub> and decreases the H<sup>+</sup> concentration, therefore increasing the pH. In basic conditions, the respiratory rate will slow down so that the body holds onto more CO<sub>2</sub> and increases the H<sup>+</sup> concentration and decreases the pH.<ref>{{Cite journal |last1=McNamara |first1=J. |last2=Worthley |first2=L.I.G. |date=September 2001 |title=Acid-Base Balance: Part I. Physiology |url=https://doi.org/10.1016/s1441-2772(23)00613-0 |journal=Critical Care and Resuscitation |volume=3 |issue=3 |pages=181–187 |doi=10.1016/s1441-2772(23)00613-0 |pmid=16573501 |issn=1441-2772|doi-access=free }}</ref>

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 CO<sub>2</sub> in the blood creates a gradient for CO<sub>2</sub> to move into the cell and push the reaction HCO<sub>3</sub> + H ↔ H<sub>2</sub>CO<sub>3</sub> ↔ CO<sub>2</sub> + H<sub>2</sub>O to the left. On the luminal side of the cell there is a H<sup>+</sup> pump and a H/K exchanger. These pumps move H<sup>+</sup> against their gradient and therefore require ATP. These cells will remove H<sup>+</sup> 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 HCO<sub>3</sub>/Cl exchanger and a Cl/K co-transporter (facilitated diffusion). When the reaction is pushed to the left it also increases the HCO<sub>3</sub> concentration in the cell and HCO<sub>3</sub> 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 HCO<sub>3</sub>/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.<ref>{{Cite journal |last1=Brown |first1=Dennis |last2=Bouley |first2=Richard |last3=Pǎunescu |first3=Teodor G. |last4=Breton |first4=Sylvie |last5=Lu |first5=Hua A. J. |date=2012-05-15 |title=New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells |journal=American Journal of Physiology-Cell Physiology |language=en |volume=302 |issue=10 |pages=C1421–C1433 |doi=10.1152/ajpcell.00085.2012 |issn=0363-6143 |pmc=3362000 |pmid=22460710}}</ref>

=== Regulation of osmolality ===
The kidneys help maintain the water and salt level of the body. Any significant rise in [[plasma osmolality]] is detected by the [[hypothalamus]], which communicates directly with the [[posterior pituitary gland]]. An increase in osmolality causes the gland to secrete [[antidiuretic 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.

===Measuring function===
{{main|Kidney function}}
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. The [[filtration 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 and [[mathematical model]]ling has been used to better understand kidney function at several scales, including fluid uptake and secretion.<ref>{{cite journal | vauthors = Weinstein AM | title = Mathematical models of tubular transport | journal = Annual Review of Physiology | volume = 56 | pages = 691–709 | year = 1994 | pmid = 8010757 | doi = 10.1146/annurev.physiol.56.1.691 }}</ref><ref name=SRT>{{cite journal | vauthors = Thomas SR |title=Modelling and simulation of the kidney |journal=Journal of Biological Physics and Chemistry |volume=5 |issue=2/3 |pages=70–83 |year=2005 |doi=10.4024/230503.jbpc.05.02}}</ref>