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Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency.

To clarify the mechanism underlying abnormal vasopressin (AVP) secretion in glucocorticoid deficiency, we examined the response of AVP secretion to osmotic stimulus produced by 5% saline infusion and analyzed the possible causative factors in seven patients with hypoosmolal hyponatremia resulting from adrenal insufficiency. In all patients, urinary sodium excretion persisted with urine osmolality exceeding plasma osmolality, and plasma AVP levels relative to plasma osmolality were elevated. Blood urea nitrogen, plasma creatinine, and PRA ranged from low to normal. All patients had nausea or vomiting, three had hypotension, and two had hypoglycemia; however, the primary cause of increased AVP secretion was attributed to none of these stimuli. After 5% saline infusion, patterns of changes in plasma AVP levels in individual patients were variable: levels decreased with increasing plasma osmolality in two patients and remained unchanged in the other five patients. Despite hyponatremia and absence of hypovolemia, thirst was present in the five patients, who responded normally to questions. This abnormality in AVP secretion and thirst was corrected after glucocorticoid replacement with normalization of plasma sodium concentrations and osmolality. Thus, glucocorticoid deficiency in man results in a clinical picture almost indistinguishable from that of the syndrome of inappropriate secretion of antidiuretic hormone. Persistent AVP secretion in this pathological state is due to a loss of hypotonic suppression of the osmostat for AVP release, which may be occasioned primarily by glucocorticoid deficiency per se and aggravated secondarily by multiple nonosmotic stimuli including nausea, hypotension, and hypoglycemia.

Adrenal Insufficiency↗

Chronic hypernatremia due to impaired osmoregulated thirst and vasopressin secretion.

We report the case of a young man who became adipsic following a subarachnoid hemorrhage and subsequently had two episodes of life-threatening hypernatremia. Investigations demonstrated that he had defective osmoregulated thirst and AVP release, but normal AVP responses to hypotension and nausea. There is also evidence that he had intact baroregulated thirst. We discuss the results of our investigations in the context of current models of hypothalamic-neurohypophysial function.

Adult↗

The interaction of meal-related, rhythmic and homeostatic mechanisms and the generation of thirst and drinking.

One of the primary goals of the study of thirst is to understand why drinking occurs under ad libitum or natural conditions. An appreciation of the experimental strategies applied by physiologists studying thirst from different perspectives can facilitate progress toward understanding the natural history of drinking behavior. Drinking research carried out using three separate perspectives-homeostatic, circadian rhythms, and food-associated-generates types of information about the mechanisms underlying drinking behavior. By combining research strategies and methods derived from each of these approaches, it has been possible to gain new information that increases our appreciation of the interactions between homeostatic mechanisms and circadian rhythms in the modulation of water intake and how these might be related to drinking associated with food intake under near natural conditions.

Animals↗

Thirst and renal excretion of water and electrolytes during pyrogen fever in dogs.

Body temperature, water intake, urine output, sodium and potassium excretion, osmolal and free water clearance, plasma osmolality, sodium and potassium concentrations and osmotic thirst were examined in conscious dogs during pyrogen fever and compared to those found under control conditions. Arterial blood pressure and central venous pressure were also measured in some experiments. Administration of pyrogen produced transient but significant decreases in urine output and striking increases in the spontaneous water intake in some of the experiments in the phase of increasing fever. Arterial blood pressure decreased, whetreas central venous pressure increased at this stage of fever. No significant changes in renal excretion of solutes and free water as well as sodium and potassium were found. Plasma osmolality and sodium concentration increased and potassium concentration decreased unsignificantly both in control and pyrogen experiments. The main finding was that the thirst threshold to osmotic stimuli increased markedly during the phase of stabilized fever may be caused by significant increase in internal body temperature.

Animals↗

Parallel effects of DOCA on salt appetite, thirst, and blood pressure in sheep.

Salt appetite was quantified in sheep by measuring the relative amounts of high-salt (266 meq/kg) and low-salt (6 meq/kg) pelleted alfalfa that they ate. Given a choice of these two foods, normal sheep ate twice as much low-salt as high-salt pellets. Following DOCA administration the sheep rapidly developed an increased salt appetite, and after 10 days they ate approximately three times as much high-salt as low-salt pellets. Their choice rapidly reverted to control values after the end of the DOCA treatment. The changes in salt appetite were accompanied by changes in thirst and mean arterial pressure. We hypothesize that these effects of DOCA reflect changes that parallel those this mineralocorticoid causes in the hypothalamic regulatory centers for salt appetite, thirst, and blood pressure.

Animals↗

[Marked hypernatremia in suprasellar germinoma lacking a sense of thirst].

We here report a 17-year-old high school boy having suprasellar germinoma who presented marked hypernatremia probably due to damages of both the osmoregulation and thirst centers. He was in good health until July, 1996, when he noticed slight general malaise and complained of dryness of the mouth, but without polyuria. He was found to have hypernatremia of mild degree (serum Na 151 mEq/l), but dropped out from the follow-up. In April, 1997, he was admitted to our hospital with complaints of general malaise and weakness of the upper and lower extremities. Serum Na was high at 202 mEq/l with a plasma osmolality of 390 mOsm/kg H2O. He completely lacked a sense of thirst and polydipsia/polyuria. Computed tomography and magnetic resonance imaging indicated a suprasellar tumor, possibly a germinoma. Hypernatremia was first treated with intravenous infusion of a half-normal saline solution, followed by immediate polyuria of 3 to 6 l/day. Subsequently, nasal administration of desamino-D-arginine vasopressin (DDAVP) induced stabilization of serum Na to a range between 140 and 160 mEq/l. The tumor disappeared following steroid pulse therapy and irradiation of 50 Gy to the brain. At the time of discharge, he and his family were instructed to record the urine volume, amount of water intake, body weight and amount of DDAVP used. The patient was instructed to drink water corresponding to the urine volume while maintaining the dose of DDAVP. One year after treatment, the water balance reverted to a positive direction, leading to a normal range of serum Na probably because of partial recovery of the osmoreceptors and/or trained drinking habit. This case illustrates the so-called adipsic hypernatremia which is attributed to partial osmoreceptor destruction by a suprasellar germinoma.

Adolescent↗

Scalp recorded direct current potential shifts associated with quenching thirst in humans.

As an indicator of cortical excitability, direct current (DC) potentials were recorded from thirsted subjects before, during and after drinking 400 ml of water. Self-rated thirst was distinctly reduced after drinking. Compared with control conditions in which the subjects remained thirsty, during drinking a widespread negative potential shift occurred averaging over -70 microV at Cz. At the transition from the consumatory phase to the postconsumption phase, a slow positive potential shift commenced that was most pronounced over the anterior cortex (averaging over +40 microV at Fz) and persisted for more than 3 min after drinking. Control conditions excluded muscle activity, ocular movements, and changes in body fluid and serum osmolality as possible non-neuronal sources of the DC-potential changes. The sequence of negative and positive potential shifts associated with drinking indicates a coordinate regulation of cortical excitability that may facilitate consumatory behavior and its context-dependent encoding into memory.

Adult↗

Self-care strategies to reduce fluid intake and control thirst in hemodialysis patients.

The purpose of this pilot study was to describe how often hemodialysis (HD) patients used particular self-care strategies to reduce fluid intake or relieve thirst, how effective each strategy was perceived to be, and whether they planned to use that strategy in the future. A cross-sectional descriptive design was used. The sample of 20 participants from one Midwest dialysis unit verbally responded to the self-care items that were presented. Most of these patients reported they regularly avoided the sun, took medications with mealtime fluid, limited salt on their foods, avoided salty foods, stayed busy, stayed away from fast food restaurants, drank ice-cold drinks, and drank only when thirsty to reduce fluid intake and relieve thirst. They also planned to use these strategies in the future. Interestingly, the strategies perceived as most effective--measuring daily allotted fluids in a pitcher to drink from all day, spacing liquids over the entire day, and measuring the amount of fluid they drank--were not the same as those they used most. Replication of these findings with larger samples is strongly recommended.

Adult↗

Common aspects of the cerebral regulation of thirst and renal sodium excretion.

It has been shown that several mammalian species increase the excretion of sodium in urine as they become dehydrated. This dehydration-induced natriuresis occurs despite simultaneous hypovolemia, and it can be blocked by an experimentally-induced reduction in the sodium concentration of CSF, or by ablation of the periventricular tissue in the vicinity of the lamina terminalis. These two experimental procedures also disrupt thirst and vasopressin secretion. There may therefore be common features involved in the central control of osmoregulatory thirst, vasopressin secretion and sodium excretion. Experimental evidence in sheep suggests that whenever the tonicity of body fluids increases, a centrally mediated natriuretic mechanism is engaged. This cerebral natriuretic mechanism may contribute along with other influences such as the extracellular fluid volume, aldosterone and atrial natriuretic peptide, to determine the rate of sodium excretion by kidneys. The efferent pathway from brain to kidney mediating osmoregulatory natriuresis is not known. It is probably hormonal, because renal denervation does not disrupt such natriuresis.

Animals↗

Motivational control of instrumental performance following a shift from thirst to hunger.

Thirsty rats were trained to press a lever for either a sucrose solution or saline before performance was tested in extinction while the animals were either hungry alone or experiencing both hunger and a sodium appetite. Reinforcer-specific motivational control was observed in that the animals trained with the sucrose solution pressed more than those trained with the saline when they were tested hungry, but not when they were tested under combined hunger and sodium appetite. In order to assess the role of a Pavlovian incentive process in this effect, thirsty animals received non-contingent pairings of one stimulus with the sucrose solution and another with saline in the second experiment. In an extinction test the sucrose stimulus augmented lever pressing relative to the saline stimulus when the animals were hungry, but not when they were thirsty. In the subsequent experiments the contribution of the Pavlovian process was equated by giving concurrent training with both incentives. Lever pressing and chain pulling were reinforced concurrently, one with the sucrose solution and the other with saline, while the animals were thirsty. Once again, the animals pressed more in extinction if this action had been trained with the sucrose solution rather than the saline, but only if they were hungry rather than thirsty. Thus, instrumental performance across a thirst-to-hunger shift can also be controlled by an instrumental incentive process. The direct engagement of the instrumental process by this motivational shift contrasts to the absence of such control following a hunger-to-thirst transition (Dickinson & Dawson, 1987a), a fact attributed to the asymmetrical motivational interactions produced by water and food deprivation.

Animals↗

Brain mechanisms and drinking: the role of lamina terminalis-associated systems in extracellular thirst.

Concomitants associated with alterations in body fluid balance serve as stimuli to appraise the brain of the momentary status of body salt and water. Extracellular fluid osmolality and the peptide ANG II have been identified as the humoral components that act as stimuli to trigger central receptors related to cellular and extracellular thirst, respectively. In the case of extracellular thirst, information about pressure/volume status is also obtained from systemic vascular receptors. It is proposed that peripherally-derived neural information is integrated with ANG II-related input within structures located in periventricular tissue of the AV3V.

Angiotensin II↗

[Analysis of the impulse activity of the cerebral neurons in rabbits with artificial thirst].

Neuronal impulse activity of various brain structures was studied in rabbits in conditions of artificial thirst elicited by intrabrain injection of 0.3-0.5 M NaCl solution (from 5 to 8 mcl). Specific organization was revealed of the impulse flow at drinking motivational excitation, i.e., domination on interval histograms of certain intervals (20-40 and 100-200 ms). Comparative analysis of activity patterns of both different and the same neurones in conditions of natural and artificial thirst showed a resemblance of dominating intervals values that testifies to specificity of the observed neural activity characteristics, reflecting drinking motivational excitation. Thus, an interval code is found corresponding to drinking motivational state. P. K. Anokhin's notions about anticipating reflection of reality find their expression in anticipating reactions of brain neuronal activity.

Animals↗

[Thirst and fluid metabolism in old age].

Water balance depends on an intact regulating mechanism for volume and osmolality. While thirst has a very important function in osmoregulation, in repletion of volume deficits it is of little importance. A thirst deficit is common in old persons and often a cause of dehydration in geriatric patients. Diagnosis, treatment and prevention of dehydration are discussed.

Aged↗

The clinical physiology of water metabolism. Part I: The physiologic regulation of arginine vasopressin secretion and thirst.

Water balance is tightly regulated within a tolerance of less than 1 percent by a physiologic control system located in the hypothalamus. Body water homeostasis is achieved by balancing renal and nonrenal water losses with appropriate water intake. The major stimulus to thirst is increased osmolality of body fluids as perceived by osmoreceptors in the anteroventral hypothalamus. Hypovolemia also has an important effect on thirst which is mediated by arterial baroreceptors and by the renin-angiotensin system. Renal water loss is determined by the circulating level of the antidiuretic hormone, arginine vasopressin (AVP). AVP is synthesized in specialized neurosecretory cells located in the supraoptic and paraventricular nuclei in the hypothalamus and is transported in neurosecretory granules down elongated axons to the posterior pituitary. Depolarization of the neurosecretory neurons results in the exocytosis of the granules and the release of AVP and its carrier protein (neurophysin) into the circulation. AVP is secreted in response to a wide variety of stimuli. Change in body fluid osmolality is the most potent factor affecting AVP secretion, but hypovolemia, the renin-angiotensin system, hypoxia, hypercapnia, hyperthermia and pain also have important effects. Many drugs have been shown to stimulate the release of AVP as well. Small changes in plasma AVP concentration of from 0.5 to 4 muU per ml have major effects on urine osmolality and renal water handling.

Adolescent↗

[Anti-thirst action of propranolol].

A reduction of the thirst was observed one hour after intramuscolar injection of 0.3 mg/kg propranolol in the rat; this effect was not observed with higher doses. According to work hypotheses, small doses could act blocking renal beta-adrenergic receptors: the stopped renin emission reduces angiotensin production that is the basic factor of thirst. The AA hypothesize that the lack of the effect in response to higher doses of propranolol can be explained through a different action of this drug which antagonizes the first one.

Animals↗

Osmoreceptor mediation of thirst and vasopressin secretion in the dog.

Water deprivation leads to depletion of both the intracellular and extracellular compartments. The resulting cellular dehydration and extracellular dehydration stimulate thirst and the secretion of vasopressin. The cellular stimulus is thought to arise from a change in volume and hence in the hydration status of specific osmoreceptor cells located in the anterior hypothalamus. Thus, reduction in cell volume because of either water deprivation or administration of hyperosmolar solutions of solutes that cannot penetrate cell membranes would stimulate thirst and vasopressin secretion, whereas an increase in cell volume caused by water intake would inhibit these responses. An alternative theory proposes that receptors in the region of the third cerebral ventricle that are sensitive to the concentration of sodium in cerebrospinal fluid are responsible for stimulating the responses to cellular dehydration. Both theories must account for the fundamental observation that NaCl, which does not penetrate cells, and urea, which does, are both excluded from the brain by the blood-brain barrier, and thus both solutes cause cerebral dehydration. However, NaCl stimulates drinking and vasopressin secretion but urea does not. The periventricular sodium receptor theory is not compatible with this observation. An osmoreceptor theory is compatible with the data if it is assumed that the receptors reside outside the blood-brain barrier, for example, in a circumventricular organ.

Animals↗

[A coherent analysis of the neocortical electrical activity on the cessation of a thirst dominant].

During learning of an animal to goal-directed discontinuation of the thirst dominant, the stable temporary connection established between the center where the dominant focus has been created and the center related to the goal-directed blinking reaction. Study of the spatio-temporal relations of neocortical biopotentials in rabbits learned to goal-directed behaviour showed that in the motivation state of thirst induced by water deprivation the level of coherence of the electrical activity in the low-frequency range increased between the frontal cortex (the swallowing center) and the blinking cortical center. The observed changes testify to the readiness of certain structures of the dominant constellation for realization of the temporary connection. Analysis of the EEG recorded in three successive 5-sec intervals which preceded blinking revealed a certain dynamics of changes in coherent characteristics. These findings reflect a functional ambiguity and phase course of the processes which accompany preparation for a goal-directed reaction. The blinking reaction occurs at the background of increasing correlation between electrical processes in symmetrical points of the cortical blinking center in the right and left hemispheres.

Acoustic Stimulation↗

[The thermal activity of the rabbit brain in motivational states of hunger or thirst].

Motivational states of hunger or thirst in rabbits were produced by the relevant deprivation of different duration (24 and 48 h). The distribution of brain thermal fields was studied by the method of thermoencephaloscopy. The thermal asymmetry was observed in the states of thirst and hunger the temperature of the left hemisphere being higher. Generalization of the brain temperature reaction depended on the level of motivational excitation. The interhemispheric brain asymmetry with higher temperature in the left hemisphere in the states of food and drinking deprivation had a pronounced trace effect, i.e., persisted for some time after satisfaction of the corresponding need. Evidently, the interhemispheric asymmetry with higher temperature of the left hemisphere reflects its predominant activation in the studied states.

Animals↗