Proximal tubule

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Proximal Convoluted Tubule
Gray1128.png
Scheme of renal tubule and its vascular supply. (1st convoluted tubule labeled at center top.)
Histology-kidney.jpg
1 Glomerulus, 2 proximal tubule, 3 distal tubule
Latin tubulus contortus proximalis
Gray's subject #253 1223
Precursor Metanephric blastema
Dorlands/Elsevier t_22/12830072

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The proximal tubule is the portion of the duct system of the nephron leading from Bowman's capsule to the loop of Henle.

Structure and appearance

The most distinctive characteristic of the proximal tubule is its brush border (or "striated border").

Brush border cell

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. The microvilli greatly increase the luminal surface area of the cells, presumably facilitating their resorptive function. The infolded membranes forming the microvilli are the site of numerous sodium pumps.

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 proximal tubule. 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 contents 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.

Divisions

The proximal tubule as a part of the nephron can be divided into two sections, pars convoluta and pars recta. Differences in cell outlines exist between these segments, and therefore presumably in function too.

Alternatively, regarding ultrastructure, it can be divided into three segments, S1, S2 and S3:

Segment Gross divisions Ultrastructure divisions Description
Proximal tubule convoluted S1[1] Higher cell complexity[1]
S2[1]
straight
S3[1] Lower cell complexity[1]

Pars convoluta

The "Pars convoluta" is the initial convoluted portion.

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.

Some investigators on the basis of particular functional differences have divided the convoluted part into two segments designated '"S1" and "S2".

Pars recta

The "Pars recta" is the following straight (descending) portion.

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.

As a logical extension of the nomenclature described above, this segment is sometimes designated as "S3".

Absorption

The proximal tubule regulates the pH of the filtrate by exchanging hydrogen ions in the interstitium for bicarbonate ions in the filtrate; furthermore, it is responsible for secreting organic acids, such as creatinine and other bases, into the filtrate.

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 antiporter. This is the most important transport mechanism in the PCT.

Substance % of filtrate reabsorbed Comments
salt and water approximately two-thirds Much of the mass movement of water and solutes occurs through the cells, passively across the lumenal membrane via transcellular transport, which is then actively resorbed across the basolateral membrane via the Na/K/ATPase pump. The solutes are absorbed isotonically, in that the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate.
organic solutes (primarily glucose and amino acids) 100% Glucose, amino acids, inorganic phosphate, and some other solutes are reabsorbed via secondary active transport through cotransport channels driven by the sodium gradient out of the nephron.
potassium approximately 65%
urea approximately 50%
phosphate approximately 80% Parathyroid hormone reduces reabsorption of phosphate in the proximal tubules, but because it also enhances the uptake of phosphate from the intestine and bones into the blood, the responses to PTH cancel each other out, and the serum concentration of phosphate remains approximately the same.

Secretion

Many types of medication are secreted in the proximal tubule. Further reading: Table of medication secreted in kidney

Pathophysiology in kidney disease

Proximal tubular epithelial cells (PTECs) have a pivotal role in kidney disease.

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.

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 - by producing cytokines, chemokines and collagen; undergoing epithelial mesenchymal transdifferentiation; necrosis or apoptosis.

See also

Additional images

References

  1. 1.0 1.1 1.2 1.3 1.4 Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3.  Page 743

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This article was originally based on an entry from a public domain edition of Gray's Anatomy. As such, some of the information contained herein may be outdated. Please edit the article if this is the case, and feel free to remove this notice when it is no longer relevant.

Cost Effectiveness of Proximal tubule

| group5 = Clinical Trials Involving Proximal tubule | list5 = Ongoing Trials on Proximal tubule at Clinical Trials.govTrial results on Proximal tubuleClinical Trials on Proximal tubule at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Proximal tubule | list6 = US National Guidelines Clearinghouse on Proximal tubuleNICE Guidance on Proximal tubuleNHS PRODIGY GuidanceFDA on Proximal tubuleCDC on Proximal tubule


| group7 = Textbook Information on Proximal tubule | list7 = Books and Textbook Information on Proximal tubule


| group8 = Pharmacology Resources on Proximal tubule | list8 = AND (Dose)}} Dosing of Proximal tubuleAND (drug interactions)}} Drug interactions with Proximal tubuleAND (side effects)}} Side effects of Proximal tubuleAND (Allergy)}} Allergic reactions to Proximal tubuleAND (overdose)}} Overdose information on Proximal tubuleAND (carcinogenicity)}} Carcinogenicity information on Proximal tubuleAND (pregnancy)}} Proximal tubule in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Proximal tubule


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Proximal tubule | list9 = AND (pharmacogenomics)}} Genetics of Proximal tubuleAND (pharmacogenomics)}} Pharmacogenomics of Proximal tubuleAND (proteomics)}} Proteomics of Proximal tubule


| group10 = Newstories on Proximal tubule | list10 = Proximal tubule in the newsBe alerted to news on Proximal tubuleNews trends on Proximal tubule</small>


| group11 = Commentary on Proximal tubule | list11 = Blogs on Proximal tubule

| group12 = Patient Resources on Proximal tubule | list12 = Patient resources on Proximal tubuleDiscussion groups on Proximal tubulePatient Handouts on Proximal tubuleDirections to Hospitals Treating Proximal tubuleRisk calculators and risk factors for Proximal tubule


| group13 = Healthcare Provider Resources on Proximal tubule | list13 = Symptoms of Proximal tubuleCauses & Risk Factors for Proximal tubuleDiagnostic studies for Proximal tubuleTreatment of Proximal tubule

| group14 = Continuing Medical Education (CME) Programs on Proximal tubule | list14 = CME Programs on Proximal tubule

| group15 = International Resources on Proximal tubule | list15 = Proximal tubule en EspanolProximal tubule en Francais

| group16 = Business Resources on Proximal tubule | list16 = Proximal tubule in the MarketplacePatents on Proximal tubule

| group17 = Informatics Resources on Proximal tubule | list17 = List of terms related to Proximal tubule


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