Distal convoluted tubule

Potassium-Sparing Diuretics. Potassium-sparing diuretics act on the aldosterone-sensitive portion of cortical collecting tubules, and partially in the distal convoluted tubules of the nephron. The commonly used potassium-sparing diuretics are triamterene, amiloride, and spironolactone (Table 3). Spironolactone is a competitive aldosterone receptor antagonist, whereas triamterene and amiloride are not (44,45). 

Electroneutral NaCl transport in the distal convoluted tubule is inhibited by the class of thiazide diuretics (chlorothiazide, hydrochlorothiazide, metolazone, chlorthalidone, and others). Thiazides interfere with the Cl binding site of NCC, and cause a relatively small... 

Til tee successive tubule portions contribute to the ASDN the late portion of the distal convoluted tubule, the connecting tubule, and the collecting duct. The recent observation that collecting duct-specific inactivation of aENaC in the mouse kidney does not impair sodium and potassium balance, suggests that the more proximal nephron segments (late distal convoluted tubule, connecting tubule) are mainly important for-achieving sodium and potassium balance. 

The thiazide sensitive NaCI cotransporter (NCC) is the major pathway of NaCI entry in the distal convoluted tubule. Like NKCC2, NCC contains 12 putative transmembrane domains and long intracellular amino-and carboxy-tails. NCC and NKCC as well as the KC1 cotransporter KCC are members of the same gene family and have considerable homology. 

Tyrosine hydroxylase 1 Thiazide diuretics, a group of drugs with moderate diuretic activity, includes hydrochlorothiazide, chlorthalidone, and xipamide. They decrease active reabsorption of sodium and accompanying chloride by binding to the chloride site of the electroneutral Na+/CF cotransport system in the distal convoluted tubule and inhibiting its action. 

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

Prolonged administration of loop diuretics can lead to a second type of diuretic resistance. Enhanced delivery of sodium to the distal tubule can result in hypertrophy of distal convoluted cells.17 Subsequently, increased sodium chloride absorption occurs in the distal tubule which diminishes the effect of the loop diuretic on sodium excretion. Addition of a distal convoluted tubule diuretic, such as metolazone or hydrochlorothiazide, to a loop diuretic can result in a synergistic increase in urine output. There are no data to support the efficacy of one distal convoluted tubule diuretic over another. The common practice of administering the distal convoluted tubule diuretic 30 to 60 minutes prior to the loop diuretic has not been studied, although this practice may first inhibit sodium reabsorption at the distal convoluted tubule before it is inundated with sodium from the loop of Henle. 

The posterior pituitary is innervated by direct nervous stimulation from the hypothalamus, resulting in the release of specific hormones. The hypothalamus synthesizes two hormones, oxytocin and vasopressin. These hormones are stored in and released from the posterior pituitary lobe. Oxytocin exerts two actions (1) it promotes uterine contractions during labor, and (2) it contracts the smooth muscles in the breast to stimulate the release of milk from the mammary gland during lactation. Vasopressin is an antidiuretic hormone (ADH) essential for proper fluid and electrolyte balance in the body. Specifically, vasopressin increases the permeability of the distal convoluted tubules and collecting ducts of the nephrons to water. This causes the kidney to excrete less water in the urine. Consequently, the urine becomes more concentrated as water is conserved. 

Hydrochlorothiazide has its proposed site of action at the distal convoluted tubule or, more specifically, at the early portion of the distal tubule. Hydrochlorothiazide inhibits the reabsorption of Na and Cl. It also promotes the reabsorption of Ca back into the blood, but inhibits the re absorption of Mg from the renal tubular fluid. The K-sparing diuretic agents (spironolactone, triamterene, and amiloride) have their site of action in the nephron at the late distal tubule and the collecting duct. These diuretic agents only cause a mild natriuretic effect... 

The answers are 373-d, 374-c, 375-a. (Kut ung, pp 253— 254, 256-257.) The urinary excretion pattern of electrolytes for the thiazide diuretic agents (e.g., hydrochlorothiazide) shown in the table that accompanies the question is represented by choice a. These drugs block the reabsorption of Na and Cl at the early distal convoluted tubule of the nephron. In addition, they promote the excretion of K and Mg. At high doses, the thiazide diuretics (especially hydrochlorothiazide) may cause a... 

The K-sparing group of diuretics produce their diuretic response by reduction of the reabsorption of Na in the later distal convoluted tubule and the collecting duct. They cause an increase in the urinary excretion of NaCl and possibly bicarbonate, while they reduce the excretion of K. The K-sparing diuretic agents do not appear to have any significant effect on the excretion of Mg and Ca ions. 

Strategies are available to overcome diuretic resistance (Table 75-5), a common problem in patients with ARF. Agents from different pharmacologic classes, such as diuretics that work at the distal convoluted tubule (thiazides) or the collecting duct (amiloride, triamterene, spironolactone), may be synergistic when combined with loop diuretics. Metolazone is commonly used because, unlike other thiazides, it produces effective diuresis at GFR less than 20 mL/min. 

Except for its lower protein concentration, glomerular filtrate at the top of the nephron is chemically identical to the plasma. The chemical composition of the urine is however quantitatively very different to that of plasma, the difference is due to the actions of the tubules. Cells of the proximal convoluted tubule (PCT) are responsible for bulk transfer and reclamation of most of the filtered water, sodium, amino acids and glucose (for example) whereas the distal convoluted tubule (DCT) and the collecting duct are concerned more with fine tuning the composition to suit the needs of the body. 

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... 

Thick ascending limb This limb is also impermeable to water. It contains ion pumps to pump electrolytes actively into the interstitium. The main pump is the Na+/2C1 /K+ co-transporter. Fluid leaving this limb is, therefore, hypotonic and passes into the distal convoluted tubule. 

PCT is proximal convoluted tubule, DL is descending limb of the loop of Henle, Thin AL is thin ascending limb of the loop of Henle, Thick AL is thick ascending limb of the loop of Henle, DCT is distal convoluted tubule and CD is collecting duct. (This figure is reproduced with permission from Fundamental Principles and Practice of Anaesthesia, P. Hutton, G. Cooper, F. James and J. Butterworth. Martin-Dunitz 2002 pp. 487, illustration no. 25.16.)... 

Hemoglobinuria and hematin casts in the distal convoluted tubules and tubular lumens located in the medulla and papilla were reported in rats after a single dermal exposure to 107.1 mg/kg liquid phenol (Conning and Hayes 1970). These phenomena are probably related to red blood cell lysis and increased glomerular filtration of hemoglobin. Hemoglobinuria is characteristic of lethal or near-lethal exposures by the dermal route. 

Lasilix containing furosemide is classified as a loop diuretic and acts by inhibiting re-absorption from the ascending part of the loop of Henle. Thiazide diuretics, such as bendroflumethiazide, act by inhibiting re-absorption at the beginning of the distal convoluted tubule. 

Thiazide diuretics act on the beginning of the distal convoluted tubule by inhibiting sodium re-absorption. Thiazide diuretics are indicated in hypertension, and at higher doses to relieve oedema caused by heart failure. Thiazide diuretics lead to hyponatraemia and hypokalaemia. They may cause hypercalcaemia and are therefore avoided in patients with this condition. 

A nephron, showing the major sites and percentage (in braces) of sodium absorption along with other features of solute transport. The filtered load = GFR (180 L/day) Xplasma Na+ (140 mEq/L) or 25,200 mEq/day. About 1% of this amount is excreted in voided urine. Sites where tubular fluid is isosmotic, hypertonic, or hypotonic relative to plasma are shown. POT, proximal convoluted tubule LH, loop of Henle DOT, distal convoluted tubule CCD, cortical collecting duct TAL, thick ascending loop. 

Sodium reabsorption continues in the distal convoluted tubule, which accounts for some 6 to 8% of the transport of sodium. The entry of Na+ across the apical cell membrane is mediated by Na+-Cl cotransport (Fig. 21.4). This protein is a distinct gene product that differs from the Na -K+-2C1 cotransporter in thick ascending limbs. 

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