Distal tubule water reabsorption

Non-plant reference [Vasopressin] (lOkDa 9aa 2 Cys 1 S-S peptide) Animals ex posterior pituitary nephrogenic diabetes insipidus from V2 VAS-R mutation 5.8Xn VAS-R agonist [kidney distal tubule water reabsorption per aquaporins, vasoconstrictor]... 

Diuretic-induced hyponatremia occurs more frequently in patients treated with thiazide diuretics than in patients who are receiving loop diuretics. In addition to causing extracellular volume depletion and nonosmotic stimulation of ADH, thiazides interfere with urinary dilution and water excretion by blocking tubular sodium and potassium reabsorption in the distal tubule. Water is then retained in excess of sodium by virtue of nonosmotic release of ADH and excretion of urine with a concentration of sodium and potassium that exceeds that of the plasma. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Thiazides and related diuretics inhibit the reabsorption of sodium and chloride ions in the ascending portion of the loop of Henle and the early distal tubule of the nephron. This action results in the excretion of sodium, chloride, and water. 

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

In order to make adjustments in the water load, the reabsorption of the remaining 20% of the filtered water from the distal tubule and the collecting duct is physiologically controlled by antidiuretic hormone (ADH), also referred to as vasopressin. Antidiuretic hormone, synthesized in the hypothalamus and released from the neurohypophysis of the pituitary gland, promotes the... 

Water reabsorption and regulation of blood pressure Approximately 7-7.51 of fluid passes from the distal convoluted tubule into the collecting duct each day substantially more than the 1.51 of fluid which are excreted as urine. Reabsorption of water occurs... 

Kidney medulla From the metabolic point of view the kidney is virtually two organs, the cortex and the medulla. The cortex contains the glomeruli, through which the blood is filtered, the proximal tubules and part of the distal tubules, from which ions and molecules are reabsorbed. The cortex is well supplied with blood so that ATP is generated by the oxidation of fuels. The medulla is metabolically quite different. Here the ATP is required for the reabsorption of ions from the loop of Henle. Some ATP is generated by anaerobic glycolysis, since the supply of blood, and therefore of oxygen, to the medulla is much poorer than to the cortex. This reflects control of the uptake of water and Na+ ions into the blood by the counter current mechanism. This depends on a slow flow of the blood in the capillaries. 

The smallest functional unit of the kidney is the nephron. In the glomerular capillary loops, ultrafiltration of plasma fluid into Bowman s capsule (BC) yields primary urine. In the proximal tubules (pT), approx. 70% of the ultrafiltrate is retrieved by isoosmotic reabsorption of NaCl and water. In the thick portion of the ascending limb of Henle s loop (HL), NaCl is absorbed unaccompanied by water. This is the prerequisite for the hairpin countercurrent mechanism that allows build-up of a very high NaQ concentration in the renal medulla In the distal tubules (dT), NaCl and water are again jointly reabsorbed. At the end of the nephron, this process involves an aldosterone-controlled exchange of Na+ against 1C or H. In the collecting tubule (C), vasopressin (antidiuretic hormone, ADH) increases the epithelial permeability for water, which is drawn into the hyperosmolar milieu of the renal medulla and thus retained in the body. As a result, a concentrated urine enters the renal pelvis. 

Thiazide diuretics (benzothiadia-zines) include hydrochlorothiazide, benzthiazide, trichlormethiazide, and cyclothiazide. A long-acting analogue is chlorthalidone. These drugs affect the intermediate segment of the distal tubules, where they inhibit a Na+/Ch cotransport, Thus, reabsorption of NaQ and water is inhibited. Renal excretion of Ca decreases, that of Mg + increases. Indications are hypertension, cardiac failure, and mobilization of edema. 

The permeability properties of the distal convoluted tubule are regulated by antidiuretic hormone (ADH, or vasopressin). In hypotonic conditions, ADH secretion by the posterior pituitary is suppressed and the distal convoluted tubule is impermeant to water. Conversely, in hypertonic or volume-contracted states, ADH is released by the posterior pituitary and increases the permeability and water reabsorption by the distal convoluted tubule. 

Mechanism of Action A sulfonamide derivative that acts as a thiazide diuretic and antihypertensive. As a diuretic, blocks reabsorption of water and the electrolytes sodium and potassium at cortical diluting segment of distal tubule. As an antihypertensive, reduces plasma and extracellular fluid volume, decreases peripheral vascular resistance (PVR) by direct effect on blood vessels. Therapeutic Effect Promotes diuresis, reduces BP. 

Mechanism of Action A potassium-sparing diuretic that interferes with sodium reabsorption by competitively inhibiting the action of aldosterone in the distal tubule, thus promoting sodium and water excretion and increasing potassium retention. Therapeutic Effect Produces diuresis lowers BP diagnostic aid for primary aldosteronism. 

Mechanism of Action A posterior pituitary hormone that increases reabsorption of water by the renal tubules. Increases water permeability at the distal tubule and collecting duct. Directly stimulates smooth muscle in the GI tract. Therapeutic Effect Causes peristalsis and vasoconstriction. 

As is evident from the major difference between the GFR and the rate of urine production, the majority of the water in the filtrate is reabsorbed into the blood in the capillaries, by osmosis through the wall of the tubule and the interstitial fluid. This reabsorption of water occurs mostly in the proximal tubule, although some is also reabsorbed in the distal tubule and collecting duct. 

Distal tubular resorption occurs with many lipid-soluble or nonionized drugs. Reabsorption in the distal tubule can occur by active transport with saturation and competition, or by passive diffusion. Water is reabsorbed, thus producing a high concentration in the urine and a concentration gradient that favors drug resorption. 

Acts on the distal tubules to increase potassium excretion, hydrogen ion excretion, and sodium reabsorption and subsequent water retention... 

Thiazide Diuretics. Thiazide drugs share a common chemical nucleus as well as a common mode of action. These drugs act primarily on the early portion of the distal tubule of the nephron, where they inhibit sodium reabsorption. By inhibiting sodium reabsorption, more sodium is retained within the nephron, creating an osmotic force that also retains more water in the nephron. Since more sodium and water are passed through the nephron, where they will ultimately be excreted from the body, a diuretic effect is produced. Thiazides are the most frequently used type of diuretic for hypertension. Specific types of thiazide drugs are listed in Table 21-3. 

Inhibit reabsorption of Na+ and Cl in distal tubule, resulting in retention of water. 

Four factors contribute to the ability to concentrate urine (1) Active reabsorption of Na+, K+, and CF without water reabsorption by the thick ascending limb of the loop of Henle results in interstitial hypertonicity and hypoosmotic tubular fluid. (2) Selective permeability to water, but not small electrolytes, in the descending thin limb of the loop of Henle allows passive reabsorption of water, facilitated by interstitial hypertonicity. (3) Relatively low medullary blood flow maintains medullary hypertonicity, allowing continued elaboration of concentrated urine. (4) In the presence of ADH, the distal tubule and collecting ducts are permeable to water so that water may diffuse out of the tubular lumen into the medullary, and papillary inter-stitium. Because of the ability of the thick ascending limb of the loop of Henle to move solutes but not water into the medullary interstitium, the medullary, and papillary interstitium are hyperosmotic and hypertonic compared to plasma and cortical interstitium (Figure 29.5). 

Q6 Thiazide diuretics are moderately powerful diuretic agents acting on the distal tubule of the nephron. They reduce reabsorption of sodium chloride and water by blocking the electroneutral sodium chloride (NaCl) transporter system at the luminal border of the distal tubular cells. In addition there are direct relaxant effects on vascular smooth muscle which reduces BP. Diuretics help patients in heart failure by reducing peripheral oedema and decreasing blood volume, which in turn reduces BP. In this way both preload and afterload are decreased and the work of the heart is diminished. 

Desmopressin replacement therapy is the first choice. Thiazide diuretics (and chlortalidone) also have paradoxical antidiuretic effect in diabetes insipidus. That this is not due to sodium depletion is suggested by the fact that the nondiuretic thiazide, diazoxide (see Index), also has this effect. It is probable that changes in the proximal renal tubule result in increased reabsorption and in delivery of less sodium and water to the distal tubule, but the mechanism remains incompletely elucidated. Some cases of the nephrogenic form, which is not helped by antidiuretic hormone, may be benefited by a thiazide. 

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