Kidney distal convoluted tubule

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 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. 

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. 

Thiazides inhibit NaCI reabsorption from the luminal side of epithelial cells in the DCT by blocking the Na+/Q transporter (NCC). In contrast to the situation in the TAL, in which loop diuretics inhibit Ca2+ reabsorption, thiazides actually enhance Ca2+ reabsorption. This enhancement has been postulated to result from effects in both the proximal and distal convoluted tubules. In the proximal tubule, thiazide-induced volume depletion leads to enhanced Na+ and passive Ca2+ reabsorption. In the DCT, lowering of intracellular Na+ by thiazide-induced blockade of Na+ entry enhances Na+/Ca2+ exchange in the basolateral membrane (Figure 15-4), and increases overall reabsorption of Ca2+. Although thiazides rarely cause hypercalcemia as the result of this enhanced reabsorption, they can unmask hypercalcemia due to other causes (eg, hyperparathyroidism, carcinoma, sarcoidosis). Thiazides are useful in the treatment of kidney stones caused by hypercalciuria. 

Approximately two thirds of kidney stones contain Ca2+ phosphate or Ca2+ oxalate. Many patients with such stones exhibit a defect in proximal tubular Ca2+ reabsorption that causes hypercalciuria. This can be treated with thiazide diuretics, which enhance Ca2+ reabsorption in the distal convoluted tubule and thus reduce the urinary Ca2+ concentration. Salt intake must be reduced in this setting, since excess dietary NaCI will overwhelm the hypocalciuric effect of thiazides. Calcium stones may also be caused by increased intestinal absorption of Ca2+, or they may be idiopathic. In these situations, thiazides are also effective, but should be used as adjunctive therapy with other measures. 

All of the thiazides can be administered orally, but there are differences in their metabolism. Chlorothiazide, the parent of the group, is not very lipid-soluble and must be given in relatively large doses. It is the only thiazide available for parenteral administration. Chlorthalidone is slowly absorbed and has a longer duration of action. Although indapamide is excreted primarily by the biliary system, enough of the active form is cleared by the kidney to exert its diuretic effect in the distal convoluted tubule. 

Although one thiazide diuretic may be 100 times more potent than another weight for weight, all these drugs have essentially the same properties. Their mechanism of action (inhibition of sodium and chloride reabsorption in the distal convoluted tubule of the kidney) is identical and they can therefore be dealt with as a group. Thiazidelike diuretics, structurally different from the thiazides, have similar actions. Thiazide and thiazide-like diuretics are listed in Table 1. 

Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine family, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is a mediator of inflammation and ischemic tissue injury in many organs. IL-18 is con-stitutively expressed by intercalated cells of the late distal convoluted tubule, fhe connecting tubule, and the collecting duct of the healthy human kidney [229]. It is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the... 

In the kidneys, PTH (1) induces 25-hydroxyvitamin D-la-hydroxylase, increasing the production of l,25(OH)2D, which stimulates intestinal absorption of both calcium and phosphate, (2) increases calcium reabsorption in the distal convoluted tubule of the nephron, (3) decreases reabsorption of phosphate by the proximal tubule, and (4) inhibits Na -H antiporter activity, which favors a mild hyperchloremic metabolic acidosis in hyperparathyroid states. 

In contrast to the calcium-conserving effect of PTH on the kidneys, PTH increases renal phosphate excretion at the proximal tubule by directly lowering the renal phosphate threshold. Approximately 6.5 g (210 mmol) of phosphate is filtered by the kidneys each day. Normally, 85% to 90% is reabsorbed by the renal tubules (proximal and distal convoluted tubule). PTH is one of the most important factors regulating the renal phosphate threshold and hence the serum phosphate concentration. 

Control of renin release from the Icidney is influenced by (1) specialized cells in the distal convoluted tubules called the macula densa function as cliemoreceptors for the concentration of sodium delivered to the distal tubules (2) juxtaglomerular cells functioning as mini pressure transducers sense the renal perfusion pressure in the kidney (3) the sympathetic nervous system that feeds the kidney and catecholamine release and (4) humoral factors such as potassium, atrial natriuretic peptides, and angiotensin II. All of these influences are involved in the normal control of salt and water balance and with diseases of the kidney. Secondary... 

The answer is c. (Murray, pp 505—626. Scriver, pp 4029—4240. Sack, pp 121-138. Wilson, pp 287-320.) Vasopressin, which is also called antidiuretic hormone, increases the permeability of the collecting ducts and distal convoluted tubules of the kidney and thus allows passage of water. Like the mineralocorticoid aldosterone, vasopressin results in an expansion of blood volume. However, the mode of action of aldosterone is different it causes sodium reabsorption, not water reabsorption. Sodium reabsorption indirectly leads to increased plasma osmolality and thus water retention in the blood. Cortisol is a glucocorticoid that potentiates catabolic metabolism chronically. Epinephrine stimulates catabolic metabolism acutely. Insulin acutely favors anabolic metabolism, in large part by allowing glucose and amino acid transport into cells. 

---