Urine Antidiuretic hormones

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

Syndrome of inappropriate antidiuretic hormone is defined by water retention, dilutional hyponatraemia and decreased volume of highly concentrated urine. There are several causes which can result in SIADH, neoplasms ectopic secreting AVP, ectopic release of AVP by various diseases or drugs, exogenous administration of AVP, desmopressin, lysipressin or large doses of OT (iatrogenic SLADH). 

X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the gene for the vasopressin V2 receptor leading to an insensitivity of the kidney for the antidiuretic hormone arginine vasopressin (AVP). The main symptom of the disease is diuresis, i.e., the production of a large amount of diluted urine. Due to the massive loss of water, the patients suffer from thirst and are in danger of dehydration. The disease usually becomes evident shortly after birth. 

Vasopressin and its derivatives are used in die treatment of diabetes insipidus, a disease resulting from die failure of the pituitary to secrete vasopressin or from surgical removal of die pituitary. Diabetes insipidus is characterized by marked increase in urination (as much as 10 L in 24 hours) and excessive tiiirst by inadequate secretion of die antidiuretic hormone or vasopressin. Treatment with vasopressin therapy replaces die hormone in the body and restores normal urination and thirst Vasopressin may also be used for die prevention and treatment of postoperative abdominal distention and to dispel gas interfering with abdominal roentgenography. 

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. 

Antidiuretic hormone (ADH), also referred to as vasopressin, has two major effects, both of which are reflected by its names (1) antidiuresis (decrease in urine formation by the kidney) and (2) vasoconstriction of arterioles. 

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 ... 

Li+ also inhibits several hormone-stimulated adenylate cyclases which, in some cases, appear to be related to side effects of Li+ therapy. For instance, Li+ inhibits the hydro-osmotic action of vasopressin, the antidiuretic hormone which increases water resorption in the kidney [136]. This effect is associated with polyuria, a relatively harmless side effect sometimes experienced with Li+ treatment, which arises from the inability of the kidney to concentrate urine. Li+ has been shown to inhibit vasopressin-stimulated adenylate cyclase activity in renal epithelial cells. Additionally, Li+ is reported to enhance the vasopressin-induced synthesis of prostaglandin E2 (PGE2) in vitro in kidney. PGE2 inhibits adenylate cyclase activity by stimulation of Gj, and, therefore, this effect may contribute to the Li+-induced polyuria. 

Common laboratory tests are used to classify the cause of ARF. Functional ARF, which is not included in this table, would have laboratory values similar to those seen in prerenal azotemia. However, the urine osmolality-to-plasma osmolality ratios may not exceed 1.5, depending on the circulating levels of antidiuretic hormone. The laboratory results listed under acute intrinsic renal failure are those seen in acute tubular necrosis, the most common cause of acute intrinsic renal failure. 

FIGURE 78-1. Diagnostic algorithm for the evaluation of hyponatremia. (CHF, congestive heart failure EABV, effective arterial blood volume SIADH, syndrome of inappropriate antidiuretic hormone UNa, urine sodium concentration Uosm, urine osmolality.)... 

The function of the loop of Henle is to enable production of a concentrated urine. It does this by generating a hypertonic interstitium, which provides a gradient for water reabsorption from the collecting duct. This, in turn, occurs under the control of antidiuretic hormone (ADH). There are several important requirements without which this mechanism would not work. These include the differential permeabilities of the two limbs to water and solutes and the presence of a blood supply that does not dissipate the concentration gradients produced. This is a simplified description to convey the principles. 

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. 

Ethanol is a diuretic. This effect may be caused by its ability to inhibit secretion of antidiuretic hormone from the posterior pituitary, which leads to a reduction in renal tubular water reabsorption. The large amount of fluid normally consumed with ethanol also contributes to increased urine production. 

Case reports have indicated an association between SSRIs and the syndrome of inappropriate secretion of antidiuretic hormone. Symptoms include lethargy, headache, hyponatremia, increased urinary sodium excretion, and hyperosmotic urine. Acute treatment of this syndrome should consist of discontinuation of the drug as well as restriction of fluid intake. Patients experiencing severe confusion, convulsions, or coma should receive intravenous sodium chloride. Elderly persons may he at a higher risk for developing this syndrome. 

The antidiuretic hormone is an octapeptide released from the posterior lobe of pituitary gland. It is used in the treatment of diabetes insipidus. ADH reduces the total urine volume and absence of this hormone cause diabetes insipidus. ADH acts on collecting duct cells to increase their water permeability. It acts on V2 receptors in collecting duct and regulate their water permeability through cAMP production. 

An 87-year-old woman received intra-articular betamethasone (Diprophos) 7 mg on three occasions for painful knee joints over 6 months. Six weeks after the last injection she developed diffuse pain and contractures in the legs, fatigue, nausea, abdominal pain, and weight loss of 6 kg. Both knee joints were tender but there was no effusion. Her serum sodium concentration was 123 mmol/1, serum osmolality 254 mosmol/kg, urine sodium 136 mmol/1, and urinary osmolality 373 mosmol/kg. The syndrome of inappropriate antidiuretic hormone secretion was diagnosed, but despite treatment she remained drowsy and hyponatremic. About a week later, she developed hypotension and symptoms of an acute abdomen. Further investigations showed that her basal cortisol concentration was low (36 nmol/1) but it increased to 481 nmol/1 after a short tetracosactide test, consistent with acute adrenal crisis. She recovered rapidly after treatment with oral hydrocortisone, but still required glucocorticoid substitution several months later. 

Diabetes insipidus A disease marked by increased urination (polyuria) and excessive thirst (polydipsia) due to inadequate production of antidiuretic hormone (ADH) and/or a decrease in the renal response to ADH. 

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. 

The fluid flows from the nephron into the collecting duct system. This segment of the nephron is crucial to the process of water conservation. In the presence of antidiuretic hormone (ADH also called vasopressin), these ducts become permeable to water and facilitate its reabsorption, thus concentrating the urine and reducing its volume. Conversely, when the organism must eliminate excess water, such as after excess fluid drinking, the production of ADH is... 

Any significant rise or drop in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. A rise in osmolality causes the gland to secrete antidiuretic hormone, resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels. 

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).

In laboratory animals, papillary necrosis due to non-narcotic analgesic has been extremely difficult to produce. However, papillary necrosis has been demonstrated following administration of 2-bromoethylamine 2-bromoethylamine has been used to demonstrate the role of urinary concentrating mechanisms in the etiology of 2-bromoethylamine-induced papillary necrosis. Maneuvers that produce large volumes of dilute urine, such as diuretic therapy, lack of antidiuretic hormone (Brattleboro rats), or volume expansion with 5% glucose, prevent papillary necrosis due to... 

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