Antidiuretic hormone tubules

Fig. 2. Schematic representation of relevant electrolyte transport through the renal tubule, depicting the osmolar gradient ia medullary iaterstitial fluid ia ywOj yW where represents active transport, —passive transport, hoth active and passive transport, and passive transport of H2O ia the presence of ADH, ia A, the cortex, and B, the medulla. An osmole equals a mole of solute divided by the number of ions formed per molecule of the solute. Thus one mole of sodium chloride is equivalent to two osmoles, ie, lAfNaCl = 2 Osm NaCl. ADH = antidiuretic hormone.

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. 

Diabetes insipidus Polyuria due to the failure of renal tubules to reabsorb water in response to antidiuretic hormone. 

Antidiuretic hormone promotes the reabsorption of water from the tubules of the kidney, or antidiuresis. Specifically, it acts on the collecting ducts and increases the number of water channels, which increases the diffusion coefficient for water. This results in the body s conservation of water and the production of a low volume of concentrated urine. The reabsorbed water affects plasma osmolarity and blood volume. This effect of ADH on the kidney occurs at relatively low concentrations. At higher concentrations, ADH causes constriction of arterioles, which serves to increase blood pressure. Antidiuretic hormone secretion is regulated by several factors ... 

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... 

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. 

Water. Water resorption in the proximal tubule is a passive process in which water follows the osmotically active particles, particularly the Na" ions. Fine regulation of water excretion (diuresis) takes place in the collecting ducts, where the peptide hormone vasopressin (antidiuretic hormone, ADH) operates. This promotes recovery of water by stimulating the transfer of aquaporins (see p. 220) into the plasma membrane of the tubule cells via V2 receptors. A lack of ADH leads to the disease picture of diabetes insipidus, in which up to 30 L of final urine is produced per day. 

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. 

Historically vasopressin and oxytocin, two nonapep-tides, were the first peptide neurohormones to be considered they are stored in the neurohypophysis and released into the bloodstream upon an appropriate stimulus. In the periphery, oxytocin stimulates the contraction of epididymal and uterine smooth muscle (see Chapter 62) and vasopressin (antidiuretic hormone) facilitates the reabsorption of water from the kidney tubules. In addition to these well-accepted roles as neurohormones, there is convincing evidence that these compounds function as neurotransmitters they both possess potent inhibitory actions on neurohypophyseal neurons. The significance of their neurotransmitter function is not yet clear. 

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via antidiuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

Antidiuretic hormone antagonists inhibit the effects of ADH in the collecting tubule. Conivaptan is a pharmacologic antagonist at Via and V2 receptors. Both lithium and demeclocycline appear to reduce the formation of cyclic adenosine monophosphate (cAMP) in response to ADH. 

Minocycline, 200 mg orally daily for 5 days, can eradicate the meningococcal carrier state, but because of side effects and resistance of many meningococcal strains, rifampin is preferred. Demeclocycline inhibits the action of antidiuretic hormone in the renal tubule and has been used in the treatment of inappropriate secretion of antidiuretic hormone or similar peptides by certain tumors (see Chapter 15). 

Water excretion is further controlled by the antidiuretic hormone from the posterior pituitary gland which acts to increase water resorption in the kidney through making the collecting tubule permeable to water for additional resorption beyond what took place in the tubule. The posterior pituitary gland secretes the hormone as a rapid and sensitive response... 

Water Intoxication. Ether an increased intake of water or a decreased output of water can cause an excess of body water. Because healthy kidneys have outstanding ability to increase water excretion, a condition of water intoxication usually occurs because of a disability to excrete water (hyponatremia). Frequently impairment may not be the result of disease or damage to the kidneys per se, but rather due to faulty processing of stimuli by the kidneys. Excessive renal reabsorption of water can result from the action of antidiuretic hormone (ADH) or by the excessive reabsorption of sodium in the proximal tubules. Under such conditions, the excretion of water and sodium will be low. Retention of salt and water causes an expansion of the ECF, usually resulting in edema and effusions. 

Even low-dose intravenous cyclophosphamide can cause a syndrome that resembles inappropriate secretion of antidiuretic hormone, with severe hyponatremia and symptoms of water intoxication (SEDA-19, 347 SEDA-21, 386). A direct effect on the renal tubules is likely, but no other nephrotoxic effects have been documented. 

Excessive retention of sodium ions in the body leads to increased release of antidiuretic hormone and a resulting increase in body water. Many diuretics such as chlorothiazide (i) and clopamide (2) inhibit sodium and chloride ion resorption in the kidney tubules and promote potassium depletion, whereas amiloride (J) and triamterene ( 4) diminish the excretion of potassium while causing a loss of sodium ions6. Other diuretics such as acetazolamide (5) and dichlorphenamide (6) inhibit the ion-exchange reaction catalysed by the zinc-containing enzyme carbonic an-hydrase. 

After several months of continuous therapy with lithium, diabetes insipidus and goiter may develop. The kidney tubules then become insensitive to the action of antidiuretic hormone, and its administration is ineffective. Either a dose reduction or discontinuation of the lithium corrects this side effect without leaving any residual pathology. In the... 

A key determinant of the final urine concentration is antidiuretic hormone (ADH also called vasopressin). In the absence of ADH, the collecting tubule (and duct) is impermeable to water, and dilute urine is produced. However, membrane water permeability of principal cells can be increased by ADH-induced fusion of vesicles containing preformed water channels with the apical membranes (Figure 15-6). ADH secretion is regulated by serum osmolality and by volume status. 

Polydipsia and polyuria are frequent but reversible concomitants of lithium treatment, occurring at therapeutic serum concentrations. The principal physiologic lesion involved is loss of the ability of the collecting tubule to conserve water under the influence of antidiuretic hormone, resulting in excessive free water clearance (nephrogenic diabetes insipidus). Lithium-induced diabetes insipidus is resistant to vasopressin but responds to amiloride. 

The principal and intercalated cells of the collecting tubule aie responsible for Na+- K+ exchange and for H+ secretion and K+ reabsorption, respectively. Stimulation of aldosterone receptors in the principal cells results in Na+ reabsorption and K+ secretion. Antidiuretic hormone (ADH, vasopressin) receptors promote the reabsorption of water from the collecting tubules and ducts (Figure 23.3). This action is mediated by cAMP. 

Vasopressin [vay soe PRESS in] (antidiuretic hormone, ADH), is structurally related to oxytocin (Figure 25.5). The chemically-synthesized nonapeptide has replaced that extracted from animal posterior pituitaries. Vasopressin has both antidiuretic and vasopressor effects. In the kidney it binds to the V2 receptor to increase water permeability and resorption in the collecting tubules. Thus the major use of vasopressin is to treat diabetes insipidus. It also finds use in controlling bleeding due to esophageal varices or colonic diverticula. Other effects of vasopressin are mediated by the Vi receptor, found in vascular smooth muscle, liver and other tissues. As might be expected the major toxicity is water intoxication and hyponatremia. Headache, bronchoconstriction and tremor also can occur. Caution must be used in treating patients with coronary artery disease, epilepsy and asthma. 

Figure 29.5. Schematic illustration of passive and active movement of electrolytes and water following glomerular filtration. Concentrations of tubular urine and peritubular fluid are given in milliosmoles per liter. Horizontal lines represent areas of increasing interstitial osmolarity. Tubule segments edged with thick black lines are either impermeable to water (loop of Henle) or display antidiuretic hormone-dependent water permeability (collecting duct).

Q8 Many of the symptoms of hypercalcaemia are non-specific. In excitable cells the membrane potential is stabilized (hyperpolarization) and the cells become less excitable fatigue, weakness, lethargy, confusion, anorexia, nausea and constipation are common. There are changes in the electrocardiogram (ECG), leading to heart block and other cardiac rhythm disturbances. A condition similar to diabetes insipidus also occurs with symptoms of polydipsia and polyuria. These symptoms are due to a reduction in the responsiveness of the renal tubules to antidiuretic hormone (ADH). 

An unexpected use for a tetracycline is in the treatment of chronic hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) when water restriction has failed. Demeclocycline produces a state of unresponsiveness to ADH, probably by inhibiting the formation and action of cyclic AMP in the renal tubule. It is effective and convenient to use in SIADH because this action is both dose-dependent and reversible. 

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. 

Water balance is controlled by vasopressin in addition to mechanisms that control Na and K balance. Vasopressin (Figure 10.16) stimulates the resorption of water by the kidney tubule. Vasopressin, also called antidiuretic hormone, is synthesized by the hypothalamus. The hormone is a nonapeptide. The two cysteine... 

Antidiuretic hormone (ADH) A vasopressin and promotes water reabsorption from the renal tubules to maintain water balance in the body fluids... 

Specific defects in particular functions of the nephrons can also be identified and evaluated. For example, assessment of the maximum concentrating capacity of the kidneys gives an estimate of antidiuretic hormone (ADH)-controUed reabsorption of solute-free water in the distal portion of the tubule. Pinpoint defects, caused by genetically determined deficiencies of specific tubular transport systems or ion channels and giving rise to characteristic biochemical disorders, are considered in Chapter 45. 

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