The proximal tubule is the segment of the

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

s which begins from the renal pole of the

Bowman's capsule Bowman's capsule (or the Bowman capsule, capsula glomeruli, or glomerular capsule) is a cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of blood to form u ...

to the beginning of

loop of Henle In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its ...

. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straight tubule (PST).

Structure

The most distinctive characteristic of the proximal tubule is its luminal

brush border A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and thei ...

Brush border cell

The luminal surface of the

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

cells of this segment of the nephron is covered with densely packed

microvilli Microvilli (singular: microvillus) are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, ...

forming a border readily visible under the

light microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsc ...

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. The

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

of the cells is densely packed with

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

, 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 A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

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 The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lu ...

, 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. Regarding ultrastructure, it can be divided into three segments, ''oS1, S2, and S3'': Complex proximal tubule with acid base

Proximal convoluted tubule (''pars convoluta'')

The ''pars convoluta'' (Latin "convoluted part") 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 The renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections (cortical columns) that extend down between the pyramids. It ...

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

Proximal straight tubule (''pars recta'')

The ''pars recta'' (Latin "straight part") is the following straight (descending) portion. Straight segments descend into the outer

medulla Medulla or Medullary may refer to: Science * Medulla oblongata, a part of the brain stem * Renal medulla, a part of the kidney * Adrenal medulla, a part of the adrenal gland * Medulla of ovary, a stroma in the center of the ovary * Medulla of t ...

. 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.

Functions

Absorption

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. 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 Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via th ...

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 Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...

electrodiffusion Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) of ...

. Active transport is mainly through the sodium/hydrogen

antiporter An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membr ...

NHE3. Paracellular transport increases transport efficiency, as determined by oxygen consumed per unit of Na⁺ reabsorbed, thus playing a part in maintaining renal oxygen homeostasis.

Secretion

Many types of

medications A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and re ...

are secreted in the proximal tubule. ''Further reading:

Table of medication secreted in kidney This is a table of medications that are Clearance (pharmacology), secreted in the kidney. Acid medication are, because of pH partition, secreted to a higher extent when urine is basic. In the same way, basic medications are secreted to a higher ext ...

'' Most of the

ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaterna ...

that is excreted in the urine is formed in the proximal tubule via the breakdown of

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

to alpha-ketoglutarate. This takes place in two steps, each of which generates an ammonium anion: the conversion of glutamine to

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

and the conversion of glutamate to alpha-ketoglutarate. The alpha-ketoglutarate generated in this process is then further broken down to form two

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochemi ...

anions, which are pumped out of the basolateral portion of the tubule cell by co-transport with sodium ions.

Clinical significance

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

cell lines An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...

are commonly used as models of the proximal tubule: porcine LLC-PK1 cells and marsupial

OK cells OK cells (short for opossum kidney cells) are a marsupial cell line used in medical research to model proximal tubule epithelial cells of the kidney. Characteristics The cell line was derived from the kidney of an adult female North American opos ...

Cancer

Most

renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, re ...

, the most common form of

kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include sp ...

, arises from the convoluted tubules.

Other

Acute tubular necrosis occurs when PTECs are directly damaged by toxins such as antibiotics (e.g.,

gentamicin Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not ...

), pigments (e.g.,

myoglobin Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglob ...

) and sepsis (e.g., mediated by

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O- antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the out ...

from gram-negative bacteria).

Renal tubular acidosis Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate p ...

(proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

, and

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

. PTECs also participate in the progression of tubulointerstitial injury due to

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

interstitial nephritis Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubul ...

, vascular injury, and

diabetic nephropathy Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...

. In these situations, PTECs may be directly affected by protein (e.g., proteinuria in

(in

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

), or cytokines (e.g.,

interferon-γ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

and

tumor necrosis factors The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular pro ...

). There are several ways in which PTECs may respond: producing

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition ...

, and

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...

; undergoing epithelial mesenchymal trans-differentiation; necrosis or

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...

Additional images

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

tissue at a magnification of ~55,000x and 80KV with

Tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

. File:Renal corpuscle-en.svg, Renal corpuscle File:Kidney nephron molar transport diagram.svg, Diagram outlining movement of ions in nephron.

References

External links

* – "Mammal, kidney cortex (LM, Medium)" * – "The Nephron: Proximal Tubule, Pars Convoluta & Pars Recta" * {{DEFAULTSORT:Proximal Convoluted Tubule Kidney anatomy