Hyponatremia in pregnancy
Nadia Barghouthi, Jessica Perini in Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Nonpregnant state, maintenance of serum osmolality and sodium:Under nonpregnant conditions, serum osmolality is maintained within a narrow range of 275–295 mOsm/L.Any changes in serum osmolality are sensed by osmoreceptors which respond to correct the change.An increase in serum osmolality by 1–2% results in the release of ADH from the posterior pituitary, which acts on the Arginine Vasopressin Receptor 2 (AVPR2) on the basolateral membrane of the collecting ducts in the kidneys. This leads to the upregulation of aquaporin 2 channels and increased water absorption by the kidneys.Any increase in serum osmolality also stimulates the thirst center in the hypothalamus, resulting in water intake to assist in correction of the hypertonic state.4
Replacement therapy in adult hypopituitarism
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Central DI is rapidly detected in the postoperative phase if urine volume, urinary osmolality (specific gravity), and serum sodium (urea) concentrations are monitored. This monitoring needs to be performed several times during the first postoperative day. DI after surgery or trauma to the pituitary or hypothalamus may be transient, permanent, or triphasic. Transient DI usually has an abrupt onset and then resolves within a few days. This is the most common pattern of postoperative and posttraumatic DI. Permanent or prolonged DI is less common and has also an abrupt early onset. In the triphasic form, there is an immediate onset of DI lasting a few days followed by an interphase during which urine osmolality rises and serum osmolality decreases, sometimes producing a period of hypotonic hyponatremia (SIADH), which then turns into a more prolonged or permanent period of DI. These first and last periods need treatment with desmopressin, whereas the interphase period is treated with water deprivation or with vaptans, a vasopressin receptor 2 antagonist. The mechanism for the triphasic postoperative response has been explained by a direct trauma toward the posterior pituitary that inhibits the secretion of the AVP. This is then followed by a period when the stored AVP in the neurons is passively released. Because this release is not regulated serum osmolality may either normalize or become too low due to excess AVP (SIADH). When the neurons have emptied their AVP content, a DI develops again. All patients undergoing surgery close to the hypothalamic-pituitary area should be monitored for DI in the postoperative phase, and if DI occurs, treatment and monitoring during the following days should be done in such manner that a transient period of SIADH can be detected and managed. Because postoperative DI may be a self-limiting condition, patients may be advised to omit one dose of desmopressin on a regular basis particularly in the time period (months) after surgery to determine whether polyuria returns.
The pharmacotherapeutic options in patients with catecholamine-resistant vasodilatory shock
Published in Expert Review of Clinical Pharmacology, 2022
Timothy E. Albertson, James A. Chenoweth, Justin C. Lewis, Janelle V. Pugashetti, Christian E. Sandrock, Brian M. Morrissey
The endogenous hormone vasopressin circulates in the blood after it is released from the posterior pituitary gland. VP mainly ensures osmoregulation by its effect on the arginine vasopressin receptor 2 (AVPR2) located primarily in the distal convoluted tubules promoting water retention. The antidiuretic hormone effect is normally the major effect of VP, but in shock conditions, even higher circulatory levels of VP are naturally released. These higher levels also stimulate arginine vasopressin receptor 1a (AVPR1a) generating powerful vasoconstriction. Potentially when VP is given exogenously, it maintains better kidney perfusion than exogenous NE because there are more AVPR1a receptors in the glomerular efferent than afferent arterioles [21]. In addition, the stimulation of arginine vasopressin receptor 1b (AVPR1b) by VP generates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary resulting in release of cortisol from the adrenal gland. The higher levels of ACTH generated by VP release generate increased natural levels of endogenous cortical steroids in shock patients.
Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic diabetes insipidus
Published in Journal of Receptors and Signal Transduction, 2022
Arginine vasopressin receptor 2 (AVPR2) is a type of GPCR and is mainly expressed in the basolateral membrane of the collecting duct cells of the human kidney [4]. AVPR2s mediate body water homeostasis throughout the water reabsorption from urine to the bloodstream via arginine vasopressin hormone (AVP). The binding of AVP to the AVPR2 stimulates adenylyl cyclase (AC) via Gαs protein and consequently cAMP/PKA-mediated trafficking of aquaporin water channel 2 (AQP2) into the apical membrane is promoted which allows water reabsorption from urine [5]. AVPR2 mutations cause X-linked congenital Nephrogenic Diabetes insipidus (NDI) which is a rare disease characterized by the inability of the affected patients to concentrate their urine [5,6]. While several episodes of dehydration which is caused by water losses can result in growth and mental retardation in infants, constant urination and thirstiness can affect the quality of daily life in adults [2]. To date, more than 250 different AVPR2 mutations which mostly effect intracellular trafficking of the receptor have been reported to cause NDI [2]. Also, it is known that wild-type AVPR2 signaling occurs with coupling with Gαs but some studies showed that this coupling could be biased to Gαq/11 by activating PLCβ and somehow, mutations can cause biased receptors [7–9]. Investigation of biased receptors is important to elucidate the relationship between the receptor conformational change and downstream signaling which can affect the pathophysiology of NDI. Also, computational techniques such as in-silico analyzes contribute significantly to the understanding of the structural insights of GPCR trafficking including AVPR2 as well as many other proteins [10–15].
Related Knowledge Centers
- Adenylyl Cyclase
- Collecting Duct System
- Distal Convoluted Tubule
- G Protein
- Nephron
- Protein
- Vasopressin
- Vasopressin Receptor
- G Protein-Coupled Receptor
- Gs Alpha Subunit