Distal convoluted tubule

The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.

Distal convoluted tubule
Kidney nephron
Kidney nephron ("1st proximal convoluted tubule", "2nd distal convoluted tubule")
Gray1132
Section of cortex of human kidney.
Details
PrecursorMetanephrogenic blastema
Identifiers
Latintubulus contortus distalis
FMA17721
Anatomical terminology

Physiology

It is partly responsible for the regulation of potassium, sodium, calcium, and pH.

On its apical surface (lumen side), cells of the DCT have a thiazide-sensitive Na-Cl cotransporter and are permeable to Ca, via the TRPV5 channel. On the basolateral surface (peritubular capillary side) there is an ATP-dependent Na/K antiporter pump, a secondary active Na/Ca transporter, and an ATP dependent Ca transporter. The basolateral ATP dependent Na/K pump produces the gradient for Na to be absorbed from the apical surface via the Na/Cl symporter, and for Ca to be reclaimed into the blood by the Na/Ca basolateral antiporter.

  • It regulates pH by absorbing bicarbonate and secreting protons (H+) into the filtrate, or by absorbing protons and secreting bicarbonate into the filtrate.
  • Sodium and potassium levels are controlled by secreting K+ and absorbing Na+. Sodium absorption by the distal tubule is mediated by the hormone aldosterone. Aldosterone increases sodium reabsorption. Sodium and chloride (salt) reabsorption is also mediated by a group of kinases called WNK kinases. There are 4 different WNK kinases, WNK1, WNK2, WNK3, and WNK4.
  • It also participates in calcium regulation by reabsorbing Ca2+ in response to parathyroid hormone.[1] PTH effect is mediated through phosphorylation of regulatory proteins and enhancing the synthesis of all transporters within the distal convoluted tubule.
  • Arginine vasopressin receptor 2 is also expressed in the DCT.

Clinical significance

Thiazide diuretics inhibit Na+/Cl reabsorption from the DCT by blocking the thiazide-sensitive Na-Cl cotransporter.

By inhibiting the transporter, thiazide diuretics increase the gradient potential for Na. This increases the activity of the basolateral Na/Ca antiport and causes the increase in calcium reclamation associated with thiazide diuretics.

Histology

The DCT is lined with simple cuboidal cells that are shorter than those of the proximal convoluted tubule (PCT). The lumen appears larger in DCT than the PCT lumen because the PCT has a brush border (microvilli). DCT can be recognized by its numerous mitochondria, basal infoldings and lateral membrane interdigitations with neighboring cells.

The point where DCT contacts the cortical thick ascending limb of the loop of Henle is called macula densa. It has tightly packed columnar cells which display reversed polarity and may monitor the osmolarity of blood.

Histologically, cells of the DCT can be differentiated from cells of the proximal convoluted tubule:

Characteristic PCT DCT
Apical brush border Usually present Not present
Eosinophilicity More Less
Cytoplasm More Less
Readily discernible nuclei Less likely More likely

Additional images

Histology-kidney

1 Glomerulus, 2 proximal tubule, 3 distal tubule

Gray1133

Transverse section of pyramidal substance of kidney of pig, the bloodvessels of which are injected.

Renal corpuscle-en

Renal corpuscle

Kidney nephron molar transport diagram

Diagram outlining movement of ions in nephron.

References

  1. ^ MedEd at Loyola mech/cases/case24/kidney.htm

External links

  • Histology image: 35_19 at the University of Oklahoma Health Sciences Center
  • Essentials of Human Physiology by Thomas M. Nosek. Section 7/7ch03/7ch03p18.
  • Essentials of Human Physiology by Thomas M. Nosek. Section 7/7ch07/7ch07p14.
  • Histology image: 16004loa – Histology Learning System at Boston University
  • Histology image: 16007loa – Histology Learning System at Boston University
Ascending limb of loop of Henle

Within the nephron of the kidney, the ascending limb of the loop of Henle is a segment of the loop of Henle downstream of the descending limb, after the sharp bend of the loop. This part of the renal tubule is divided into a thin and thick ascending limb; the thick portion is also known as the distal straight tubule, in contrast with the distal convoluted tubule downstream.

Bendroflumethiazide

Bendroflumethiazide (INN), formerly bendrofluazide (BAN), trade name Aprinox, is a thiazide diuretic used to treat hypertension.

Bendroflumethiazide is a thiazide diuretic which works by inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT). Water is lost as a result of more sodium reaching the collecting ducts. Bendroflumethiazide has a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide currently is in hypertension (part of the effect is due to vasodilation).

Connecting tubule

In the kidney, the connecting tubule (CNT, or junctional tubule, or arcuate renal tubule) is a tubular segment of the renal collecting duct system that connects the distal convoluted tubule to the cortical collecting duct.

Extraglomerular mesangial cell

Extraglomerular mesangial cells (also known as Lacis cells, Polkissen cells, or Goormaghtigh cells) are light-staining pericytes in the kidney found outside the glomerulus, near the vascular pole. They resemble smooth muscle cells and play a role in renal autoregulation of blood flow to the kidney and regulation of systemic blood pressure through the renin–angiotensin system. Extraglomerular mesangial cells are part of the juxtaglomerular apparatus, along with the macula densa cells of the distal convoluted tubule and the juxtaglomerular cells of the afferent arteriole.

The specific function of extraglomerular mesangial cells is not well understood, although it has been associated with the secretion of erythropoietin and secretion of renin. They are distinguished from intraglomerular mesangial cells, which are situated between the basement membrane and the epithelial cells within the glomerulus.

Gitelman syndrome

Gitelman syndrome is an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. The disorder is caused by genetic mutations resulting in improper function of the thiazide-sensitive sodium-chloride symporter (also known as NCC, NCCT, or TSC) located in the distal convoluted tubule of the kidney. This symporter is a channel responsible for the transport of multiple electrolytes such as sodium, chloride, calcium, magnesium, and potassium.

Gitelman syndrome was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. Bartter syndrome is also an autosomal recessive hypokalemic metabolic alkalosis, but it derives from a mutation to the NKCC2 found in the thick ascending limb of the loop of Henle.

Juxtaglomerular apparatus

The juxtaglomerular apparatus (also known as the juxtaglomerular complex) is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to (juxta-) the glomerulus.

The juxtaglomerular apparatus consists of three types of cells:

the macula densa, a part of the distal convoluted tubule of the same nephron

juxtaglomerular cells, (also known as granular cells) which secrete renin

extraglomerular mesangial cells

Juxtaglomerular cell

The juxtaglomerular cells (JG cells, or granular cells) are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells mainly in the walls of the afferent arterioles, and some in the efferent arterioles, that deliver blood to the glomerulus. In synthesizing renin, they play a critical role in the renin–angiotensin system and thus in autoregulation of the kidney.

Juxtaglomerular cells secrete renin in response to a drop in pressure detected by stretch receptors in the vascular walls, or when stimulated by macula densa cells. Macula densa cells are located in the distal convoluted tubule, and stimulate juxtaglomerular cells to release renin when they detect a drop in sodium concentration in tubular fluid. Together, juxtaglomerular cells, extraglomerular mesangial cells and macula densa cells comprise the juxtaglomerular apparatus.

In appropriately stained tissue sections, juxtaglomerular cells are distinguished by their granulated cytoplasm.

The juxtaglomerular cell is a cell that is located near the glomerulus, hence its name.

Similar to cardiac tissue, juxtaglomerular cells harbor β1 adrenergic receptors. When stimulated by epinephrine or norepinephrine, these receptors induce the secretion of renin. These cells also respond directly to a decrease in systemic blood pressure which is manifested as a lower renal perfusion pressure.

Loop of Henle

In the kidney, the loop of Henle (English: ) (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 discoverer, the German anatomist Friedrich Gustav Jakob Henle, the loop of Henle's main function is to create a concentration gradient in the medulla of the kidney.By means of a countercurrent multiplier system, which uses electrolyte pumps, the loop of Henle creates an area of high urea concentration deep in the medulla, near the papillary duct in the collecting duct system. Water present in the filtrate in the papillary duct flows through aquaporin channels out of the duct, moving passively down its concentration gradient. This process reabsorbs water and creates a concentrated urine for excretion.

Macula densa

In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal tubule, at the point where the thick ascending limb meets the distal convoluted tubule. The macula densa is the thickening where the distal tubule touches the glomerulus.

The cells of the macula densa are sensitive to the concentration of sodium chloride in the distal convoluted tubule. A decrease in sodium chloride concentration initiates a signal from the macula densa that has two effects:

(1) it decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return the glomerular filtration rate (GFR) toward normal, and

(2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin.As such, an increase in sodium chloride concentration would result in vasoconstriction of afferent arterioles, and reduced paracrine stimulation of juxtaglomerular cells. This demonstrates the macula densa feedback, where compensatory mechanisms act in order to return GFR to normal.

The release of renin is an essential component of the renin–angiotensin–aldosterone system (RAAS), which regulates blood pressure and volume.

Metolazone

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

Nephron

The nephron (from Greek νεφρός – nephros, meaning "kidney") is the 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 an encompassing Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 0.8 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged (some are added, others are removed); first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

The interior of Bowman's capsule, called Bowman's space, collects the filtrate from the filtering capillaries of the glomerular tuft, which also contains mesangial cells supporting these capillaries. These components function as the filtration unit and make up the renal corpuscle. The filtering structure (glomerular filtration barrier) has three layers composed of endothelial cells, a basement membrane, and podocytes (foot processes). The tubule has five anatomically and functionally different parts: the proximal tubule, which has a convoluted section the proximal convoluted tubule followed by a straight section (proximal straight tubule); the loop of Henle, which has two parts, the descending loop of Henle ("descending loop") and the ascending loop of Henle ("ascending loop"); the distal convoluted tubule ("distal loop"); the connecting tubule, and the collecting ducts. Nephrons have two lengths with different urine concentrating capacities: long juxtamedullary nephrons and short cortical nephrons.

The four mechanisms used to create and process the filtrate (the result of which is to convert blood to urine) are filtration, reabsorption, secretion and excretion. Filtration occurs in the glomerulus and is largely passive: it is dependent on the intracapillary blood pressure. About one-fifth of the plasma is filtered as the blood passes through the glomerular capillaries; four-fifths continues into the peritubular capillaries. Normally the only components of the blood that are not filtered into Bowman's capsule are blood proteins, red blood cells, white blood cells and platelets. Over 150 liters of fluid enter the glomeruli of an adult every day: 99% of the water in that filtrate is reabsorbed. Reabsorption occurs in the renal tubules and is either passive, due to diffusion, or active, due to pumping against a concentration gradient. Secretion also occurs in the tubules and is active. Substances reabsorbed include: water, sodium chloride, glucose, amino acids, lactate, magnesium, calcium phosphate, uric acid, and bicarbonate. Substances secreted include urea, creatinine, potassium, hydrogen, and uric acid. Some of the hormones which signal the tubules to alter the reabsorption or secretion rate, and thereby maintain homeostasis, include (along with the substance affected) antidiuretic hormone (water), aldosterone (sodium, potassium), parathyroid hormone (calcium, phosphate), atrial natriuretic peptide (sodium) and brain natriuretic peptide (sodium). A countercurrent system in the renal medulla provides the mechanism for generating a hypertonic interstitium, which allows the recovery of solute-free water from within the nephron and returning it to the venous vasculature when appropriate.

Some diseases of the nephron predominantly affect either the glomeruli or the tubules. Glomerular diseases include diabetic nephropathy, glomerulonephritis and IgA nephropathy; renal tubular diseases include acute tubular necrosis and polycystic kidney disease.

Renal glucose reabsorption

Renal glucose reabsorption is the part of kidney (renal) physiology that deals with the retrieval of filtered glucose, preventing it from disappearing from the body through the urine.

If glucose is not reabsorbed by the kidney, it appears in the urine, in a condition known as glucosuria. This is associated with diabetes mellitus.Firstly, the glucose in the proximal tubule is co-transported with sodium ions into the proximal convoluted tubule walls via the SGLT2 cotransporter. Some (typically smaller) amino acids are also transported in this way.

Once in the tubule wall, the glucose and amino acids diffuse directly into the blood capillaries along a concentration gradient. This blood is flowing, so the gradient is maintained.

Lastly, sodium/potassium ion active transport pumps remove sodium from the tubule wall and the sodium is put back into the blood. This maintains a sodium concentration gradient in the proximal tubule lining, so the first step continues to happen.

Gliflozins such as canagliflozin inhibit renal glucose reabsorption, and are used in diabetes mellitus to lower blood glucose.

Renal sodium reabsorption

Renal reabsorption of sodium (Na+) is a part of renal physiology. It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide.

It is very efficient, since more than 25,000 mmoles/day of sodium is filtered into the nephron, but only ~100 mmoles/day, or less than 0.4% remains in the final urine.

Sodium-chloride symporter

The sodium-chloride symporter (also known as Na+-Cl− cotransporter, NCC or NCCT, or as the thiazide-sensitive Na+-Cl− cotransporter or TSC) is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from the tubular fluid into the cells of the distal convoluted tubule of the nephron. It is a member of the SLC12 cotransporter family of electroneutral cation-coupled chloride cotransporters. In humans, it is encoded by the gene SLC12A3 (solute carrier family 12 member 3) located in 16q13.A loss of NCC function causes Gitelman syndrome, an autosomic recessive disease characterized by salt wasting and low blood pressure, hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Over a hundred different mutations in the NCC gene have been identified.

Tubular fluid

Tubular fluid is the fluid in the tubules of the kidney. It starts as a renal ultrafiltrate in the glomerulus, changes composition through the nephron, and ends up as urine leaving through the ureters.

Tubule

A tubule is:

a small tube or fistular structure

a minute tube lined with glandular epithelium

any hollow cylindrical body structure

a minute canal found in various structures or organs of the body

a slender elongated anatomical channel

Definition: A minute tube, especially as an anatomical structure.

Urinary cast

Urinary casts are microscopic cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy.

They form via precipitation of Tamm–Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH). Tamm–Horsfall protein is particularly susceptible to precipitation in these conditions.

Casts were first described by Henry Bence Jones (1813–1873).As reflected in their cylindrical form, casts are generated in the small distal convoluted tubules and collecting ducts of the kidney, and generally maintain their shape and composition as they pass through the urinary system. Although the most common forms are benign, others indicate disease. All rely on the inclusion or adhesion of various elements on a mucoprotein base—the hyaline cast. "Cast" itself merely describes the shape, so an adjective is added to describe the composition of the cast. Various casts found in urine sediment may be classified as follows.

Vasopressin receptor 2

Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs type of G proteins, which stimulate adenylate cyclase.

AVPR2 is expressed in the kidney tubule, predominantly in the membrane of cells of the distal convoluted tubule and collecting ducts, in fetal lung tissue and lung cancer, the last two being associated with alternative splicing. AVPR2 is also expressed outside the kidney, and, when stimulated, can cause the release of Von Willebrand Factor from the Weibel-Palade Bodies in the endothelial cells of the vasculature. Because Von Willebrand Factor helps to stabilize circulating levels of factor VIII, the vasopressin analog, desmopressin can be used to stimulate the AVPR2 receptor and increase levels of circulating factor VIII. This is useful in the treatment of hemophilia A as well as Von Willebrand disease.

In the kidney, AVPR2's primary property is to respond to arginine vasopressin by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of AVPR2 is lost, the disease nephrogenic diabetes insipidus (NDI) results.

Zona glomerulosa

The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (glomus is Latin for "ball").

In response to increased potassium levels, renin or decreased blood flow to the kidneys, cells of the zona glomerulosa produce and secrete the mineralocorticoid aldosterone into the blood as part of the renin–angiotensin system. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry. However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca2+ channels signal that can be controlled by angiotensin II and extracellular potassium, the 2 major regulators of aldosterone production. Aldosterone regulates the body's concentration of electrolytes, primarily sodium and potassium, by acting on the distal convoluted tubule of kidney nephrons to: increase sodium reabsorption, increase potassium excretion, increase water reabsorption through osmosis.

The enzyme aldosterone synthase (also known as CYP11B2) acts in this location The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors and it was suggested that the expression of proteins like the neuronal cell adhesion molecule (NCAM) in the cells of the zona glomerulosa reflects the regenerative feature of these cells, which would lose NCAM immunoreactivity after moving to the zona fasciculata. However, together with other data on neuroendocrine properties of zona glomerulosa cells, NCAM expression may reflect a neuroendocrine differentiation of these cells. Voltage-dependent calcium channels have been detected in the zona glomerulosa of the human adrenal, which suggests that calcium-channel blockers may directly influence the adrenocortical biosynthesis of aldosterone in vivo.

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