Editing Nephron

{{Short description|Microscopic structural and functional unit of the kidney}}
{{About|the unit of the kidney|the journal|Nephron (journal)|the drug with trade name Nephron|Epinephrine}}
{{Infobox anatomy
| Name = Nephron
| Image = Kidney Nephron.svg
| Caption = Diagram (left) of a long ''juxtamedullary nephron'' and (right) of a short ''cortical nephron''. The left nephron is labelled with six named nephron segments. Collecting duct is the last part of the nephron.
| Width = 240
| Image2 =
| Caption2 =
| Precursor = [[Metanephric blastema]] ([[intermediate mesoderm]])
| System = [[Urinary system]]
| Artery =
| Vein =
| Nerve =
| Lymph =
}}

The '''nephron''' is the minute or microscopic structural and functional unit of the [[kidney]]. It is composed of a [[renal corpuscle]] and a [[Nephron#Renal tubule|renal tubule]]. The renal corpuscle consists of a tuft of [[capillary|capillaries]] called a [[glomerulus (kidney)|glomerulus]] and a cup-shaped structure called [[Bowman's capsule]]. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of [[epithelial cells]] with a [[Lumen (anatomy)|lumen]]. A healthy adult has 1 to 1.5 million nephrons in each kidney.<ref name="lote">{{cite book | vauthors = Lote CJ |title= Principles of Renal Physiology | edition = 5th |year=2012|publisher=Springer}}</ref>{{rp|22}} Blood is filtered as it passes through three layers: the [[endothelial cells]] of the capillary wall, its [[basement membrane]], and between the [[podocyte foot processes]] of the lining of the capsule. The tubule has adjacent [[peritubular capillaries]] that run between the descending and ascending portions of the tubule.<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> As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged (some are added, others are removed); first with the [[interstitial fluid]] outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—[[urine]]—exits: it is composed of water, [[metabolic waste]], and [[toxins]].

The interior of Bowman's capsule, called Bowman's space, collects the filtrate from the filtering capillaries of the [[glomerular tuft]], which also contains [[mesangial cell]]s supporting these capillaries. These components function as the [[Renal physiology#Filtration|filtration]] unit and make up the [[renal corpuscle]]. The filtering structure (glomerular filtration barrier) has three layers composed of [[endothelial cell]]s, a [[basement membrane]], and podocyte foot processes. The tubule has five anatomically and functionally different parts: the [[proximal tubule]], which has a convoluted section called the [[proximal convoluted tubule]] followed by a straight section (proximal straight tubule); the [[loop of Henle]], which has two parts, the descending loop of Henle ("descending loop") and the [[ascending loop of Henle]] ("ascending loop"); the [[distal convoluted tubule]] ("distal loop"); the [[connecting tubule]], and the last part of nephron the [[collecting duct]]s. Nephrons have two lengths with different urine-concentrating capacities: long juxtamedullary nephrons and short cortical nephrons.

The four mechanisms used to create and process the filtrate (the result of which is to convert blood to urine) are [[filtration]], [[reabsorption]], [[secretion]] and [[excretion]]. Filtration or [[Ultrafiltration (kidney)|ultrafiltration]] occurs in the glomerulus and is largely passive: it is dependent on the intracapillary blood pressure. About one-fifth of the plasma is filtered as the blood passes through the glomerular capillaries; four-fifths continues into the peritubular capillaries. Normally the only components of the blood that are not filtered into Bowman's capsule are [[blood proteins]], [[red blood cell]]s, [[white blood cell]]s and [[platelet]]s. Over 150 liters of fluid enter the glomeruli of an adult every day: 99% of the water in that filtrate is reabsorbed. Reabsorption occurs in the [[renal tubule]]s and is either passive, due to [[diffusion]], or active, due to pumping against a concentration gradient. Secretion also occurs in the tubules and collecting duct and is active. Substances reabsorbed include: [[water]], [[sodium chloride]], [[glucose]], [[amino acid]]s, [[Lactic acid|lactate]], [[magnesium]], [[calcium phosphate]], [[uric acid]], and [[bicarbonate]]. Substances secreted include [[urea]], [[creatinine]], [[potassium]], [[hydrogen]], and [[uric acid]]. Some of the [[hormones]] which signal the tubules to alter the reabsorption or secretion rate, and thereby maintain homeostasis, include (along with the substance affected) [[vasopressin|antidiuretic hormone]] (water), [[aldosterone]] (sodium, potassium), [[parathyroid hormone]] (calcium, phosphate), [[atrial natriuretic peptide]] (sodium) and [[brain natriuretic peptide]] (sodium). A countercurrent system in the [[renal medulla]] provides the mechanism for generating a hypertonic interstitium, which allows the recovery of solute-free water from within the nephron and returning it to the venous vasculature when appropriate.

Some diseases of the nephron predominantly affect either the glomeruli or the tubules. Glomerular diseases include [[diabetic nephropathy]], [[glomerulonephritis]] and [[IgA nephropathy]]; renal tubular diseases include [[acute tubular necrosis]] and [[polycystic kidney disease]].

== Structure ==
[[File:Physiology of Nephron.png|260px|thumb|right|Fig.1) Schematic diagram of the nephron (yellow), relevant circulation (red/blue), and the four methods of altering the filtrate.]]
The nephron is the functional unit of the kidney.<ref name="Pocock">{{cite book| vauthors = Pocock G, Richards CD |title=Human physiology : the basis of medicine|date=2006|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-856878-0|page=349|edition=3rd}}</ref>  This means that each separate nephron is where the main work of the kidney is performed.

A nephron is made of two parts:
* a [[renal corpuscle]], which is the initial filtering component, and
* a [[renal tubule]] that processes and carries away the [[Filtration|filtered fluid]].<ref name="tortora">{{Cite book|title=Principles of anatomy and physiology| vauthors = Tortora GJ, Derrickson BH |date=2010|publisher=John Wiley & Sons |isbn=978-0-470-23347-4|edition=12th|location=Hoboken, NJ|oclc=192027371}}</ref>{{rp|1024}}

=== Renal corpuscle ===
{{Main article|Renal corpuscle}}
[[File:Filtration barrier.svg|thumb|260px|Fig.2) Schematic of the glomerular filtration barrier (GFB).
A. The endothelial cells of the glomerulus; 1. endothelial pore (fenestra).<br /> B. [[Glomerular basement membrane]]: 1. lamina rara interna 2. lamina densa 3. lamina rara externa <br />
C. Podocytes: 1. enzymatic and structural proteins 2. filtration slit 3. diaphragm]]

The renal corpuscle is the site of the filtration of [[blood plasma]]. The renal corpuscle consists of the [[glomerulus (kidney)|glomerulus]], and the glomerular capsule or [[Bowman's capsule]].<ref name="tortora" />{{rp|1027}}

The renal corpuscle has two poles: a vascular pole and a tubular pole.<ref name="junqueiras">{{cite book | vauthors = Mescher AL |year=2016 |title=Junqueira's Basic Histology | edition = 14th  |publisher=Lange | isbn = 978-0-07-184268-6 }}</ref>{{rp|397}} The arterioles from the [[renal circulation]] enter and leave the glomerulus at the vascular pole. The glomerular filtrate leaves the Bowman's capsule at the renal tubule at the urinary pole.

===Glomerulus===
{{Main article|Glomerulus (kidney)|l1 = Glomerulus}}

The glomerulus is the network, known as a ''tuft'', of filtering [[capillary|capillaries]] located at the [[Renal corpuscle|vascular pole]] of the renal corpuscle in Bowman's capsule. Each glomerulus receives its blood supply from an [[afferent arterioles|afferent arteriole]] of the [[renal circulation]]. The glomerular blood pressure provides the driving force for water and solutes to be filtered out of the [[blood plasma]], and into the interior of [[Bowman's capsule]], called Bowman's space.

Only about a fifth of the plasma is filtered in the glomerulus. The rest passes into an [[efferent arteriole]]. The diameter of the efferent arteriole is smaller than that of the afferent, and this difference increases the hydrostatic pressure in the glomerulus.

===Bowman's capsule===
The [[Bowman's capsule]], also called the glomerular capsule, surrounds the glomerulus. It is composed of a visceral inner layer formed by specialized cells called [[podocyte]]s, and a parietal outer layer composed of [[simple squamous epithelium]]. Fluids from [[blood]] in the glomerulus are ultrafiltered through several layers, resulting in what is known as the filtrate.

The filtrate next moves to the renal tubule, where it is further processed to form [[urine]]. The different stages of this fluid are collectively known as the [[tubular fluid]].

===Renal tubule=== <!--Renal tubule redirects here-->
The renal tubule is a continuous and long pipe-like structure containing the [[tubular fluid]] filtered through the glomerulus.<ref>{{cite web | work = Ecology & Evolutionary Biology - University of Colorado at Boulder. | title = The Kidney Tubule I: Urine Production. | url = http://www.colorado.edu/eeb/web_resources/cartoons/nephrex1.html | access-date = March 6, 2007 | archive-url = https://web.archive.org/web/20071002180140/http://www.colorado.edu/eeb/web_resources/cartoons/nephrex1.html | archive-date=October 2, 2007 }}</ref> The filtrate passing through the renal tubule ultimately ends at the [[collecting duct system]].<ref>{{cite book| vauthors = Hook JB, Goldstein RS |title=Toxicology of the Kidney|publisher=Raven Press|year=1993|isbn=0-88167-885-6 |page=8 |url =https://books.google.com/books?id=61CAfmFDBrEC}}</ref>

The components of the renal tubule are:

# [[Proximal convoluted tubule]]: lies in the cortex and is lined by 'simple cuboidal epithelium with [[brush border]]s' which greatly increase surface area for absorption.
# [[Loop of Henle]]: lies in the medulla and is U-shaped (similar to a hair-pin)
#* [[Descending limb of loop of Henle]]: one segment of equal thickness
#* [[Ascending limb of loop of Henle]]: two segments of differing thickness (proximal portion lined by simple squamous epithelium is called the [[thin ascending limb of loop of Henle]], distal portion lined by simple cuboidal epithelium is called the [[thick ascending limb of loop of Henle]]).
# [[Distal convoluted tubule]]: lies in the cortex 
# [[Collecting tubule]]

The epithelial cells that form these nephron segments can be distinguished by the shapes of their actin cytoskeleton visualized by confocal microscopy of fluorescent phalloidin.<ref>{{cite journal |vauthors=Kumaran GK, Hanukoglu I |title=Identification and classification of epithelial cells in nephron segments by actin cytoskeleton patterns |journal=FEBS J |volume=287 |issue=6 |pages=1176–1194 |date=March 2020 |pmid=31605441 |pmc=7384063 |doi=10.1111/febs.15088 |url=https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15088}}</ref>

Blood from the efferent arteriole, containing everything that was not filtered out in the glomerulus, moves into the [[peritubular capillaries]], tiny blood vessels that surround the loop of Henle and the proximal and distal tubules, where the tubular fluid flows. Substances then reabsorb from the latter back to the blood stream.

The peritubular capillaries then recombine to form an efferent venule, which combines with efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

=== Difference in Length of Nephrons===
'''Cortical nephrons''' (the majority of nephrons) start high in the cortex and have a short loop of Henle which does not penetrate deeply into the medulla. Cortical nephrons can be subdivided into ''superficial cortical nephrons'' and ''midcortical nephrons''.<ref>{{cite book| title= Essentials of Human Physiology| vauthors = Nosek TM | chapter=Section 7/7ch03/7ch03p16 |chapter-url=http://humanphysiology.tuars.com/program/section7/7ch03/7ch03p16.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section7/7ch03/7ch03p16.htm|archive-date=2016-03-24}}</ref>

{{anchor|Juxtamedullary nephron}}
'''Juxtamedullary nephrons'''{{explain|reason=Juxtamedullary nephron redirects here, and nothing says what it is|date=August 2022}} start low in the cortex near the medulla and have a long loop of Henle which penetrates deeply into the renal medulla: only they have their loop of Henle surrounded by the [[Straight arterioles of kidney|vasa recta]]. These long loops of Henle and their associated vasa recta create a hyperosmolar gradient that allows for the generation of concentrated [[urine]].<ref>{{cite book | vauthors = Jameson JL, Loscalzo J |title=Harrison's Nephrology and Acid-Base Disorders|publisher=McGraw-Hill Professional|year=2010|isbn=978-0-07-166339-7|page=3|url=https://books.google.com/books?id=yoeXSV8O2wUC&pg=PA3}}</ref> Also the hairpin bend penetrates up to the inner zone of medulla.<ref>{{cite web|title=Regulation of Urine Concentration |url=http://www.cliffsnotes.com/study_guide/Regulation-of-Urine-Concentration.topicArticleId-277792,articleId-277776.html |work=Anatomy & Physiology |publisher=CliffsNotes |access-date=27 November 2012 |url-status=dead |archive-url=https://web.archive.org/web/20121025033759/http://www.cliffsnotes.com/study_guide/Regulation-of-Urine-Concentration.topicArticleId-277792%2CarticleId-277776.html |archive-date=25 October 2012 }}</ref>

Juxtamedullary nephrons are found only in birds and mammals, and have a specific location: ''medullary'' refers to the [[renal medulla]], while ''juxta'' (Latin: near) refers to the relative position of the [[renal corpuscle]] of this nephron  - ''near the medulla'', but still in the cortex.  In other words, a ''juxtamedullary nephron'' is a nephron whose renal corpuscle is near the medulla, and whose [[proximal convoluted tubule]] and its associated [[loop of Henle]] occur deeper in the medulla than the other type of nephron, the [[cortical nephron]].

The juxtamedullary nephrons comprise only about 15% of the nephrons in the human kidney.<ref name="lote" />{{rp|24}} However, it is this type of nephron which is most often depicted in illustrations of nephrons.

In humans, cortical nephrons have their renal corpuscles in the outer two thirds of the cortex, whereas juxtamedullary nephrons have their corpuscles in the inner third of the cortex.<ref name="lote" />{{rp|24}}

== Functions ==
[[File:2618 Nephron Secretion Reabsorption.jpg|thumb|Fig.3) Secretion and reabsorption of various substances throughout the nephron.]]
The nephron uses four mechanisms to convert blood into urine: filtration, reabsorption, secretion, and excretion.<ref name="junqueiras" />{{rp|395–396}} These apply to numerous substances. The structure and function of the epithelial cells lining the lumen change during the course of the nephron, and have segments named by their location and which reflects their different functions.

[[File:Kidney nephron molar transport diagram.svg|thumbnail|Fig.4) Diagram outlining movement of ions in nephron, with the collecting ducts on the right.]]
[[File:Complex proximal tubule with acid base.svg|thumb|Fig.5) Proximal tubule cell showing pumps involved in acid base balance, left is the lumen of tubule]]

===Proximal tubule===
The [[proximal tubule]] as a part of the nephron can be divided into an initial convoluted portion and a following straight (descending) portion.<ref name=boron743>{{cite book | vauthors = Boron WF |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |page=743 |isbn=978-1-4160-2328-9 |year=2005 }}</ref> Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including 80% of glucose, more than half of the filtered salt, water and all filtered [[organic compound|organic]] solutes (primarily [[glucose]] and [[amino acid]]s).<ref name="junqueiras" />{{rp|400–401}}

===Loop of Henle===
The [[loop of Henle]] is a U-shaped tube that extends from the proximal tubule. It consists of a descending limb and an ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla as the descending limb, and then returns to the cortex as the ascending limb to empty into the distal convoluted tubule. The primary role of the loop of Henle is to enable an organism to produce concentrated urine, not by increasing the tubular concentration, but by rendering the interstitial fluid hypertonic.<ref name="lote" />{{rp|67}}

Considerable differences aid in distinguishing the descending and ascending limbs of the loop of Henle. The [[Descending limb of loop of Henle|descending limb]] is permeable to water and noticeably less permeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the [[Hypertonicity|hypertonic]] [[interstitium]] of the renal medulla, water flows freely out of the descending limb by [[osmosis]] until the tonicity of the filtrate and interstitium equilibrate. The hypertonicity of the medulla (and therefore concentration of urine) is determined in part by the size of the loops of Henle.<ref name="lote" />{{rp|76}}

Unlike the descending limb, the [[Ascending limb of loop of Henle|thick ascending limb]] is impermeable to water, a critical feature of the [[countercurrent exchange]] mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows [[Hypotonicity|hypotonic]] since it has lost much of its sodium content. This hypotonic filtrate is passed to the [[distal convoluted tubule]] in the renal cortex.<ref name="lote" />{{rp|72}}

===Distal convoluted tubule===
The [[distal convoluted tubule]] has a different structure and function to that of the proximal convoluted tubule. Cells lining the tubule have numerous [[mitochondria]] to produce enough energy ([[adenosine triphosphate|ATP]]) for [[active transport]] to take place. Much of the ion transport taking place in the distal convoluted tubule is regulated by the [[endocrine system]]. In the presence of [[parathyroid hormone]], the distal convoluted tubule reabsorbs more calcium and secretes more phosphate. When [[aldosterone]] is present, more sodium is reabsorbed and more potassium secreted. Ammonia is also absorbed during the selective reabsorption. [[Atrial natriuretic peptide]] causes the distal convoluted tubule to secrete more sodium.

=== Connecting tubule ===
A part of Distal nephron. This is the final segment of the tubule before it enters the collecting duct system. Water, some salts and nitrogenous waste like urea and creatinine are passed out to collecting tubule.

=== Collecting duct system ===
{{main|Collecting duct system}}
[[File:Gray1133.png|thumbnail|Fig.6) Cross-sectional histologic preparation showing (b)small connecting tubules with simple columnar epithelium and (a) large connecting tubules with simple cuboidal epithelium.]]

Each distal convoluted tubule delivers its filtrate to a [[collecting duct system|system of collecting ducts]], the first segment of which is the [[connecting tubule]]. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's [[Countercurrent exchange#In the kidney|countercurrent multiplier system]].<ref name="lote" />{{rp|67}}

Because it has a different origin during the [[development of the urinary and reproductive organs]] than the rest of the nephron, the collecting duct is sometimes not considered a part of the nephron. Instead of originating from the metanephrogenic blastema, the collecting duct originates from the [[ureteric bud]].<ref name="mitchell">{{cite book | vauthors = Mitchell B, Sharma R |title= Embriology | edition = 2nd |year=2009|publisher=Churchill Livingstone Elsevier}}</ref>{{rp|50–51}}

Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of [[antidiuretic hormone]] (ADH). ADH affects the function of [[aquaporins]], resulting in the reabsorption of water molecules as it passes through the collecting duct. Aquaporins are membrane proteins that selectively conduct water molecules while preventing the passage of ions and other solutes. As much as three-quarters of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or diluted. An increase in ADH is an indication of [[dehydration]], while water sufficiency results in a decrease in ADH allowing for diluted urine.<ref name="junqueiras" />{{rp|406}}
[[Image:Kidney Nephron Cells.png|thumb|250px|Fig.7)
Cross-sectional diagram of the juxtaglomerular apparatus and adjacent structures: 1) top, yellow - distal convoluted tubule; 2) top, brown -macula densa cuboidal cells surrounding arterioles; 3) small blue cells - juxtaglomerular cells; 4) large blue cells - mesangial cells; 5) tan - podocytes lining [[Bowman's capsule]] adjacent to capillaries, and parietal layer of capsule, 6)center - five glomerular capillaries, and the 6)bottom, purple - exiting tubule. Structures (2), (3), and (4) constitute the juxtaglomerular apparatus.]]
Lower portions of the collecting organ are also permeable to [[urea]], allowing some of it to enter the medulla, thus maintaining its high concentration (which is very important for the nephron).<ref name="lote" />{{rp|73–74}}

Urine leaves the medullary collecting ducts through the [[renal papilla]]e, emptying into the [[Minor calyx|renal calyces]], the [[renal pelvis]], and finally into the [[urinary bladder]] via the [[ureter]].<ref name="junqueiras" />{{rp|406–407}}

=== Juxtaglomerular apparatus ===
{{main|Juxtaglomerular apparatus}}
The [[juxtaglomerular apparatus]] (JGA) is a specialized region associated with the nephron, but separate from it. It produces and secretes into the circulation the enzyme [[renin]] (angiotensinogenase), which cleaves [[angiotensinogen]] and results in the ten amino acid substance angiotensin-1 (A-1).  A-1 is then converted to angiotensin-2, a potent vasoconstrictor, by removing two amino acids: this is accomplished by angiotensin converting enzyme (ACE). This sequence of events is referred to as the [[renin–angiotensin system]] (RAS) or renin-angiotensin-aldosterone system (RAAS). The JGA is located between the thick ascending limb and the afferent arteriole. It contains three components: the [[macula densa]], [[juxtaglomerular cell]]s, and [[extraglomerular mesangial cell]]s.<ref name="junqueiras" />{{rp|404}}

==Clinical significance==
Patients in early stages of [[chronic kidney disease]] show an approximate 50% reduction in the number of nephrons, comparable to the nephron loss that occurs with [[Ageing|aging]] (between ages 18–29 and 70–75).<ref name="pmid30455427">{{cite journal | vauthors = Kuro-O M | title = The Klotho proteins in health and disease | journal = Nature Reviews. Nephrology | volume = 15 | issue = 1 | pages = 27–44 | date = January 2019 | pmid = 30455427 | doi = 10.1038/s41581-018-0078-3 | s2cid = 53872296 }}</ref>

Diseases of the nephron predominantly affect either the glomeruli or the tubules. Glomerular diseases include [[diabetic nephropathy]], [[glomerulonephritis]] and [[IgA nephropathy]]; renal tubular diseases include [[acute tubular necrosis]], [[renal tubular acidosis]], and [[polycystic kidney disease]].

== Additional images ==
<gallery>
File:Gray1129.png| Distribution of blood vessels in cortex of kidney. (Although the figure labels the efferent vessel as a ''[[vein]]'', it is actually an [[efferent arteriole|arteriole]].)
File:Gray1130.svg|[[Glomerulus]] is red; [[Bowman's capsule]] is white.
File:Kidney tubules.png|Kidney tissue
File:Glomerular Physiology.png|Glomerulus
File:Kidney Glomerulus Cell Types.png|This image shows the types of cells present in the glomerulus part of a kidney nephron. Podocytes, Endothelial cells, and Glomerular mesangial cell are present.
</gallery>

== See also ==
* [[Nephrology]]
* [[Urology]]

== References ==
{{Reflist}}

{{Urinary system anatomy}}
{{Renal physiology}}
{{Authority control}}

[[Category:Kidney anatomy]]