Proximal tubule
Encyclopedia
The proximal tubule is the portion of the duct
system of the nephron
of the kidney which leads from Bowman's capsule
to the loop of Henle
.
(or "striated border").
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 resorptive function as well a putative flow sensing within the lumen.
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 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.
Regarding ultrastructure
, it can be divided into three segments, S1, S2, and S3:
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".
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".
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.
Most of the ammonium that is excreted in the urine is formed in the proximal tubule via the breakdown of glutamine to alpha-ketoglutarate. 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 cotransport with sodium ions.
Proximal tubular epithelial cells (PTECs) have a pivotal role in kidney disease.
, the most common form of kidney cancer
, arises from the convoluted tubules.
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: producing cytokines, chemokines, and collagen
; undergoing epithelial mesenchymal transdifferentiation; necrosis or apoptosis
.
Duct (anatomy)
In anatomy and physiology, a duct is a circumscribed channel leading from an exocrine gland or organ.-Types of ducts:Examples include:-Duct system:...
system of the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
of the kidney which leads from Bowman's capsule
Bowman's capsule
The Bowman's 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 urine. A glomerulus is enclosed in the sac...
to the loop of Henle
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...
.
Structure and appearance
The most distinctive characteristic of the proximal tubule is its brush borderBrush border
A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...
(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 giving the brush border cell
Brush border
A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...
its name. The microvilli greatly increase the luminal
Luminal
Luminal may refer to:* A trade name for the anti-epileptic drug phenobarbital* Luminal , a 2004 film by Italian director Andrea Vecchiato starring Denis Lavant* In biology, pertaining to the lumen, the interior of a hollow structure...
surface area of the cells, presumably facilitating their resorptive function as well a putative flow sensing within the lumen.
The cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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
Agonal
Agonal may refer to:* Death rattle, deriving from the word agony* Agonist, as opposed to antagonist* Agonal respiration, abnormal breathing pattern...
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.
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
Ultrastructure
Ultrastructure is the detailed structure of a biological specimen, such as a cell, tissue, or organ, that can be observed by electron microscopy...
, it can be divided into three segments, S1, S2, and S3:
| Segment | Gross divisions | Ultrastructure divisions | Description |
| Proximal tubule | convoluted | S1 | Higher cell complexity |
| S2 | |||
| straight | |||
| S3 | Lower cell complexity | ||
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
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 that extend down between the pyramids. It contains the renal corpuscles and the renal tubules except for parts of...
.
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
Renal medulla
The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the arcuate arterioles. The arcuate arterioles each in turn branch into...
. 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
Peritubular capillaries
In the renal system, peritubular capillaries are tiny blood vessels that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron....
. 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 | transcellular transport Transcellular transport Transcellular transport involves the transportation of solutes by a cell through a cell. One classic example is the movement of glucose from the intestinal lumen to extracellular fluid by epithelial cells.... , which is then actively resorbed across the basolateral membrane via the Na/K/ATPase pump. The solutes are absorbed isotonic Isotonic The term isotonic may refer to;*Isotonic for the term associated with muscle contraction*An isotone in nuclear physics*Sports drinks are sometimes designed in an isotonic way to assist athletes rehydrate while balancing electrolytes... ally, in that the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate. >- | organic Organic compound An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the... solutes (primarily glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... and amino acid Amino acid Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen... s) |
100% | Glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... , amino acids, inorganic phosphate Phosphate A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in... , and some other solutes are reabsorbed via secondary active transport through cotransport channels Symporter A cotransporter is an integral membrane protein that is involved in secondary active transport. It works by binding to two molecules or ions at a time and using the gradient of one solute's concentration to force the other molecule or ion against its gradient.... driven by the sodium gradient out of the nephron. >- | potassium Potassium Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are... |
approximately 65% | >- | approximately 50% | >- | approximately 80% | Parathyroid hormone Parathyroid hormone Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids... reduces reabsorption of phosphate Phosphate A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in... in the proximal tubules, but, because it also enhances the uptake of phosphate from the intestine Intestine In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine... and bone Bone Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue... s 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 medications are secreted in the proximal tubule. Further reading: Table of medication secreted in kidneyMost of the ammonium that is excreted in the urine is formed in the proximal tubule via the breakdown of glutamine to alpha-ketoglutarate. 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 cotransport with sodium ions.
Pathophysiology in kidney disease
Malignant
Most renal cell carcinomaRenal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
, the most common form of kidney cancer
Kidney cancer
Kidney cancer is a type of cancer that starts in the cells in the kidney.The two most common types of kidney cancer are renal cell carcinoma and urothelial cell carcinoma of the renal pelvis...
, arises from the convoluted tubules.
Non-malignant
Acute tubular necrosisAcute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...
occurs when PTECs are directly damaged by toxins such as antibiotics (e.g., gentamicin
Gentamicin
Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
), pigments (e.g., myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
and sepsis (e.g., mediated by lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
from gram-negative bacteria). Renal tubular acidosis
Renal tubular acidosis
Renal tubular acidosis 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. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid...
(proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
, glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, amino acids, and phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
.
PTECs also participate in the progression of tubulointerstitial injury due to glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
, ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, interstitial nephritis
Interstitial nephritis
Interstitial nephritis is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules...
, vascular injury, and diabetic nephropathy
Diabetic nephropathy
Diabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
. In these situations, PTECs may be directly affected by protein (e.g., proteinuria in glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
), glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
(in diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
), or cytokines (e.g., interferon-γ and tumor necrosis factors
Tumor necrosis factors
Tumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...
). There are several ways in which PTECs may respond: producing cytokines, chemokines, and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
; undergoing epithelial mesenchymal transdifferentiation; necrosis or apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.