Urine Convoluted tubules

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. 

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... 

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. 

Only about 10% of the Na-i- filtered by the glomerulus is reabsorbed by the distal convoluted tubule (DCT) and therefore the capacity of the thiazide group of diuretics to influence the elimination of Na-H in the urine is limited compared to the loop agents. Thiazides can prevent the reabsorption of up to 5% of the total filtered Na+, whereas the equivalent figure for loop diuretics is about 20%. Thiazides can still produce a moderate naturesis and diuresis compared to carbonic anhydrase inhibitors and the K+-sparing agents. Most thiazides are ineffective at low glomerular filtration rates. They also hinder the ability of the kidneys to produce a dilute urine. 

Figure 12.4 Mechanism of action of Na+/K+symport inhibitors (thiazides) on the distal convoluted tubule. As in the other parts of the nephron, Na+movement is powered by the energy-requiring sodium pump (P) in the basolateral membrane which exchanges intracellular Na+for K-i-in the extracellular fluid (ECF). The transport of Na-rand Cl- into the cell from the filtrate against the prevailing electrochemical gradient is facilitated by the symporter (S). The Na-Hons are then transported by the pump mechanism described above and the Cl- ions diffuse passively Into the ECF through ion channels in the basolateral membrane. Thiazide diuretics inhibit the symporter by disabling the Cl- binding site with the loss of Na-rand Cl- in the urine.

Hydrochlorothiazide Inhibition of the Na/CI transporter in the distal convoluted tubule Modest increase in NaCI excretion some wasting hypokalemic metabolic alkalosis t decreased urine Ca Hypertension, mild heart failure, nephrolithiasis, nephrogenic diabetes insipidus Oral duration 8-12 h Toxicity Hypokalemic metabolic alkalosis, hyperuricemia, hyperglycemia, hyponatremia... 

The maintenance of the appropriate potassium levels in extracellular fluid is extremely important for the normal functioning of cardiac and skeletal muscle. Apparently, the regulation of intracellular potassium is of lesser importance. The control of potassium concentration in the extracellular fluid is affected by its migration in and out of the intracellular fluid and via excretion in the urine. The glomerular filtrate contains the same amount of potassium as plasma however, practically all of it is reabsorbed in the proximal convoluted tubule. In the distal tubule, however, as the sodium becomes reabsorbed under the influ-... 

Thiazides. Diuretics that act on the distal convoluted tubule and inhibit the sodium chloride symporter, leading to retention of water in the urine. An example is hydrochlorothiazide. 

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