Proximal tubule#Brush border cell

The most distinctive characteristic of the proximal tubule is its luminal brush border.{{Citation needed|date=February 2021}}

===Brush border cell===

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The luminal surface of the epithelial cells of this segment of the nephron is covered with densely packed microvilli forming a border readily visible under the light microscope giving the brush border cell its name. The microvilli greatly increase the luminal surface area of the cells, presumably facilitating their reabsorptive function as well as putative flow sensing within the lumen.{{cite journal | vauthors = Wang T | title = Flow-activated transport events along the nephron | journal = Current Opinion in Nephrology and Hypertension | volume = 15 | issue = 5 | pages = 530–6 | date = September 2006 | pmid = 16914967 | doi = 10.1097/01.mnh.0000242180.46362.c4 | s2cid = 42761720 }} The microvilli are composed of actin filament bundles that have been visualized using confocal microscopy.{{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 }}

The cytoplasm of the cells is densely packed with mitochondria, which are largely found in the basal region within the infoldings of the basal plasma membrane. The high quantity of mitochondria gives the cells an acidophilic appearance. The mitochondria are needed in order to supply the energy for the active transport of sodium ions out of the cells to create a concentration gradient which allows more sodium ions to enter the cell from the luminal side. Water passively follows the sodium out of the cell along its concentration gradient.

Cuboidal epithelial cells lining the proximal tubule have extensive lateral interdigitations between neighboring cells, which lend an appearance of having no discrete cell margins when viewed with a light microscope.

Agonal resorption of the proximal tubular contents after interruption of circulation in the capillaries surrounding the tubule often leads to disturbance of the cellular morphology of the proximal tubule cells, including the ejection of cell nuclei into the tubule lumen.

This has led some observers to describe the lumen of proximal tubules as occluded or "dirty-looking", in contrast to the "clean" appearance of distal tubules, which have quite different properties.

Based on its appearance at low magnification, the proximal tubule can be divided into two sections: the proximal convoluted tubule (PCT), and the proximal straight tubule (PST).{{Cite book |title=Medical physiology |date=2017 |publisher=Elsevier |isbn=978-0-323-42796-8 |editor-last=Boron |editor-first=Walter F. |edition=3rd |series=Study smart with student consult |location=Philadelphia, PA |pages=727 |editor-last2=Boulpaep |editor-first2=Emile L.}} Differences in cell outlines exist between these segments, and therefore presumably in function too.{{Citation needed|date=February 2021}}

Based on ultrastructure, it can be divided into three segments, S1, S2, and S3.

File:Complex proximal tubule with acid base.svg

The pars convoluta (Latin "convoluted part") is the initial convoluted portion.{{Citation needed|date=February 2021}}{{Cite book |last=Wojciech |first=Pawlina |title=Histology A TEXT AND ATLAS |publisher=Wolters Kluwer Health |year=2016 |isbn=978-1-4698-8931-3 |pages=702}}

In relation to the morphology of the kidney as a whole, the convoluted segments of the proximal tubules are confined entirely to the renal cortex.{{Citation needed|date=February 2021}}

Some investigators on the basis of particular functional differences have divided the convoluted part into two segments designated S1 and S2.{{Citation needed|date=February 2021}}

The pars recta (Latin "straight part") is the following straight (descending) portion.{{Citation needed|date=February 2021}}

Straight segments descend into the outer medulla. They terminate at a remarkably uniform level and it is their line of termination that establishes the boundary between the inner and outer stripes of the outer zone of the renal medulla.{{Citation needed|date=February 2021}}

As a logical extension of the nomenclature described above, this segment is sometimes designated as S3.{{Citation needed|date=February 2021}}

The proximal tubule efficiently regulates the pH of the filtrate by secreting hydrogen ions (acid) into the tubule and reabsorbing approximately 80% of the filtered bicarbonate.{{Cite journal |last=Boron |first=Walter F. |date=September 2006 |title=Acid-Base Transport by the Renal Proximal Tubule |journal=Journal of the American Society of Nephrology |language=en |volume=17 |issue=9 |pages=2368–2382 |doi=10.1681/ASN.2006060620 |pmid=21170887 |s2cid=3122791 |issn=1046-6673|pmc=4699187 }}

Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries. This is driven by sodium transport from the lumen into the blood by the Na⁺/K⁺-ATPase in the basolateral membrane of the epithelial cells.

Sodium reabsorption is primarily driven by this P-type ATPase – 60–70% of the filtered sodium load is reabsorbed in the proximal tubule through active transport, solvent drag, and paracellular electrodiffusion. Active transport is mainly through the sodium/hydrogen antiporter NHE3.{{cite journal | vauthors = Aronson PS | title = Ion exchangers mediating NaCl transport in the renal proximal tubule | journal = Cell Biochemistry and Biophysics | volume = 36 | issue = 2–3 | pages = 147–53 | date = 2002 | pmid = 12139400 | doi = 10.1385/CBB:36:2-3:147 | s2cid = 24141102 }} Paracellular transport increases transport efficiency, as determined by oxygen consumed per unit of Na⁺ reabsorbed, thus playing a part in maintaining renal oxygen homeostasis.{{cite journal | vauthors = Pei L, Solis G, Nguyen MT, Kamat N, Magenheimer L, Zhuo M, Li J, Curry J, McDonough AA, Fields TA, Welch WJ, Yu AS | title = Paracellular epithelial sodium transport maximizes energy efficiency in the kidney | journal = The Journal of Clinical Investigation | volume = 126 | issue = 7 | pages = 2509–18 | date = July 2016 | pmid = 27214555 | pmc = 4922683 | doi = 10.1172/JCI83942 }}

Many types of medications are secreted in the proximal tubule. Further reading: Drugs secreted in the kidney

Most of the ammonium that is excreted in the urine is formed in the proximal tubule via the breakdown of glutamine to alpha-ketoglutarate.{{cite book|first1=Burton David|last1=Rose|first2=Helmut G|last2=Rennke|name-list-style=vanc|title=Renal pathophysiology : the essentials|year=1994|publisher=Williams & Wilkins|location=Baltimore|isbn=978-0-683-07354-6|page=[https://archive.org/details/renalpathophysio0000rose/page/132 132]|url-access=registration|url=https://archive.org/details/renalpathophysio0000rose/page/132}} This takes place in two steps, each of which generates an ammonium anion: the conversion of glutamine to glutamate and the conversion of glutamate to alpha-ketoglutarate. The alpha-ketoglutarate generated in this process is then further broken down to form two bicarbonate anions, which are pumped out of the basolateral portion of the tubule cell by co-transport with sodium ions.

File:Kidney cd10 ihc.jpg of the convoluted tubules and glomeruli with CD10]]

Proximal tubular epithelial cells (PTECs) have a pivotal role in kidney disease. Two mammalian cell lines are commonly used as models of the proximal tubule: porcine LLC-PK1 cells and marsupial OK cells.{{cite book | vauthors = Kruidering M, van de Water B, Nagelkerke JF | title = Methods for studying renal toxicity | journal = Archives of Toxicology. Supplement | volume = 18 | pages = 173–83 | date = 1996 | pmid = 8678793 | doi = 10.1007/978-3-642-61105-6 | url = https://books.google.com/books?id=IKf9CAAAQBAJ&pg=PA177 | series = Archives of Toxicology | isbn = 978-3-642-64696-6 | s2cid = 27034550 }}

Most renal cell carcinoma, the most common form of kidney cancer, arises from the convoluted tubules.{{cite journal | vauthors = Tomita Y | title = Early renal cell cancer | journal = International Journal of Clinical Oncology | volume = 11 | issue = 1 | pages = 22–7 | date = February 2006 | pmid = 16508725 | doi = 10.1007/s10147-005-0551-4 | s2cid = 28183020 }}

Acute tubular necrosis occurs when PTECs are directly damaged by toxins such as antibiotics (e.g., gentamicin), pigments (e.g., myoglobin) and sepsis (e.g., mediated by lipopolysaccharide from gram-negative bacteria). Renal tubular acidosis (proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of bicarbonate, glucose, amino acids, and phosphate.{{Citation needed|date=February 2021}}

PTECs also participate in the progression of tubulointerstitial injury due to glomerulonephritis, ischemia, interstitial nephritis, vascular injury, and diabetic nephropathy. In these situations, PTECs may be directly affected by protein (e.g., proteinuria in glomerulonephritis), glucose (in diabetes mellitus), or cytokines (e.g., interferon-γ and tumor necrosis factors). There are several ways in which PTECs may respond: producing cytokines, chemokines, and collagen; undergoing epithelial mesenchymal trans-differentiation; necrosis or apoptosis.{{Citation needed|date=February 2021}}

• Urinary pole
• Brush border
• List of distinct cell types in the adult human body

File:Gray1129.png|Distribution of blood vessels in cortex of kidney.

File:Glomerular Physiology.png|Glomerulus.

File:Tight junction blowup.jpg|TEM of negatively stained proximal convoluted tubule of Rat kidney tissue at a magnification of ~55,000x and 80KV with Tight junction.

File:Renal corpuscle-en.svg|Renal corpuscle

File:Kidney nephron molar transport diagram.svg|Diagram outlining movement of ions in nephron.

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{{reflist|2}}

• {{UCDavisOrganology|Urinary/mammal/cortex1/cortex6}} – "Mammal, kidney cortex (LM, Medium)"
• {{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 7/7ch03/7ch03p14 |chapter-url=http://humanphysiology.tuars.com/program/section7/7ch03/7ch03p14.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section7/7ch03/7ch03p14.htm|archive-date=2016-03-24}} – "The Nephron: Proximal Tubule, Pars Convoluta & Pars Recta"
• {{EmbryologySwiss|turinary/urinhaute02}}

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Category:Kidney anatomy