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 structu ...

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s which begins from the renal (tubular) 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 Renal tubule, tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of b ...

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 it ...

. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s capsule abruptly transition to proximal tubule epithelial cells (PTECs). The proximal tubule 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 microvillus-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and th ...

Brush border cell

The luminal surface of the

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cells of this segment of the nephron is covered with densely packed microvilli 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 spectrum, visible light and a system of lens (optics), lenses to generate magnified images of small objects. Optical microscopes ...

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 microvilli are composed of actin filament bundles that have been visualized using confocal microscopy. The

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

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 us ...

, 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 in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...

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

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). Differences in cell outlines exist between these segments, and therefore presumably in function too. Based on

ultrastructure Ultrastructure (or ultra-structure) is the architecture of cells and biomaterials that is visible at higher magnifications than found on a standard optical light microscope. This traditionally meant the resolution and magnification range of a c ...

, it can be divided into three segments, ''S1, 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. I ...

. 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. 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 In the renal system, peritubular capillaries are tiny blood vessels, supplied by the efferent arteriole, that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron. Peritubular capillaries ...

. This is driven by sodium transport from the lumen into the blood by the Na⁺/K⁺-ATPase in the

basolateral membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...

of the epithelial cells. Sodium reabsorption is primarily driven by this

P-type ATPase The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases are α-helical bundle primary transporters named based upon thei ...

– 60–70% of the filtered sodium load is reabsorbed in the proximal tubule through active transport,

solvent drag Solvent drag, also known as bulk transport, refers to solutes in the ultrafiltrate that are transported back from the renal tubule by the flow of water rather than specifically by ion pumps or other membrane transport proteins. Page 791 This is ...

, and paracellular

electrodiffusion Molecular diffusion is the motion of atoms, molecules, or other particles of a gas or liquid at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid, size and density (or their product, ...

. Active transport is mainly through the sodium/hydrogen

antiporter An antiporter (also called exchanger or counter-transporter) is an integral membrane protein that uses secondary active transport to move two or more molecules in opposite directions across a phospholipid membrane. It is a type of cotransporte ...

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 Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

are secreted in the proximal tubule. ''Further reading: Drugs secreted in the kidney'' Most of the

ammonium Ammonium is a modified form of ammonia that has an extra hydrogen atom. It is a positively charged (cationic) polyatomic ion, molecular ion with the chemical formula or . It is formed by the protonation, addition of a proton (a hydrogen nucleu ...

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; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

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 bioche ...

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 that 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.

Cancer

Most renal cell carcinoma, 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, a lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include ...

, 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 aminoglycoside 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 amo ...

), pigments (e.g.,

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

) and sepsis (e.g., mediated by

lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

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 ...

(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 sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

, and

phosphate Phosphates are the naturally occurring form of the element phosphorus. 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 orthop ...

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

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 ...

, interstitial nephritis, vascular injury, and diabetic nephropathy. In these situations, PTECs may be directly affected by protein (e.g., proteinuria in glomerulonephritis),

(in

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

), or cytokines (e.g., interferon-γ and

tumor necrosis factors The tumor necrosis factor (TNF) superfamily is a protein superfamily of transmembrane protein#Classification by topology, type II transmembrane proteins containing TNF homology domain and forming Protein trimer, trimers. Members of this superfa ...

). 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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

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 addit ...

, and

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

; undergoing epithelial mesenchymal trans-differentiation; necrosis or

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

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 Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

. 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