Water and Electrolyte Disturbances in Diabetes Insipidus & Their Biochemical Relationship

to create guidelines for an early approach. Likewise, we have to recognize the degree of complications in water disorders in this disease which is what causes the specific symptomatology of the patients. (5-7) The aim of our article is to identify the hydroelectrolytic disorders of diabetes insipidus and to relate them to their clinical manifestations, diagnosis and treatment. ABSTRACT


INTRODUCTION
Diabetes insipidus is a syndrome characterized by elimination of large volumes of dilute urine.This disorder has multiple etiologies, but it is grouped in 2 possible anatomical sites associated with it which are the central nervous system (CNS) and the kidney.(1,2) When we speak of diabetes insipidus in the CNS we refer to the insufficiency of the neurohypophysis to sustain the adequate capacity of secretion of the antidiuretic hormone, also called vasopressin (AVP), which in the literature is called neurogenic or central diabetes insipidus.Likewise, when the kidney is the anatomical site affected by its inability to sustain thewater balance, it is called nephrogenic diabetes insipidus.(1-4) Table 1 shows the different causes depending on the anatomical site affected.The prevalence of this disease is not very precise due to the lack of epidemiological information since it is established as an uncommon syndrome in some countries.It is estimated that there are 1:25000 cases without being able to differentiate between male and female sex.Globally, central diabetes insipidus is more frequent due to genetic manifestations at early ages and the hereditary pattern of AVP gene mutations.
(5,6) However, more studies should be carried out to track intrahospital cases in our countries and to find the most frequent etiology in order to create guidelines for an early approach.Likewise, we have to recognize the degree of complications in water disorders in this disease which is what causes the specific symptomatology of the patients.(5-7) The aim of our article is to identify the hydroelectrolytic disorders of diabetes insipidus and to relate them to their clinical manifestations, diagnosis and treatment.

THE ACTION OF ANTIDIURETIC HORMONE AT THE PHYSIOLOGICAL AND BIOCHEMICAL LEVEL
AVP is a peptide composed of nine amino acids with a ring structure and disulfide bond between its components.This compound is synthesized at the level of the magno cellular neurons located in the supraoptic and paraventricular nuclei of the hypothalamus; and its synthesis is accompanied by the specific binding protein (neurophysin II).(7-9) Then, AVP binds to this protein and is transported by the axons of the hypophyseal-hypothalamic fascicle to the neurohypophysis, where subsequently the hormonal complexes are stored in the form of granules until their utilization.(10-13) Additionally, an intracellular calcium entry must occur in order to stimulate the membrane potential and generate the exocytosis process for AVP to go out to perform its functions.This hormone has 3 important receptors:  V1a: This receptor is located in vascular smooth muscle, platelets, hepatocytes and myometrium, for which functions such as vasoconstriction (associated with Gq protein increasing the intracellular calcium level), platelet aggregation, glycogenolysis and uterine contraction have been demonstrated.
 V1b: Found at the corticotropic level, it contributes to increased ACTH secretion.
 V2: found in the distal nephrons of the kidney; its main action is to regulate the effects of AVP in relation to osmolality, which is why it is called antidiuretic AVP is an important hormone in the conservation of body water through the reduction of urine output.Its antidiuretic effect is given by the reabsorption of water at the level of the collecting tubule of the nephron by means of the V2 receptor of AVP at the renal level; this generates the increase of water permeability at the level of the collecting tubule where a water channel called aquaporin-2 (AQ2) is involved, this is found at the level of the apical membranes.(12,13) This effect is initiated by the binding of AVP with the V2 receptor, triggering activation of the adenylate cyclase system by means of the GS protein and increasing cAMP levels.(13,14) The latter, in turn, increases the synthesis of protein kinase A, which is responsible for phosphorylating the AQ2 aqueous channel so that it inserts into the tubular cell membrane, which is normally impermeable to water, becoming permeable.Thus, under the osmotic gradient of sodium, water moves transcellularly, enters the cell through AQ2 and exits to the interstitium through another type of aquaporins.(8,9) At the end of the AVP effect, endocytosis of the aqueous channel occurs, again restoring water impermeability in the luminal membrane of the nephron.

WATER-ELECTROLYTE DISORDER IN DIABETES INSIPIDUS
The control of osmolality (tonicity) and extracellular volume has a close and fundamental relationship to maintain normal cell structure and functionality.Therefore, it is fundamental within the physiology of water balance to comment on the relationship between water and sodium.(15-18) The tonicity of the extracellular fluid is regulated at its maximum expression by excretion and intake of water, while the extracellular volume is regulated by sodium through its intake and excretion.The management of plasma tonicity and intravascular volume is given by the integration of the endocrine, nervous and behavioral systems of the person (Figure 1).( 19) Regulation of antidiuretic hormone secretion and serum osmolality.Taken from: Authors.AVP, secreted from the posterior pituitary system, is the hormone responsible for regulating tonicity, being stimulated by the increase in plasma tonicity.Likewise, to maintain volume homeostasis it must be regulated mainly by the Renin-Angiotensin-Aldosterone System (RAS) associated with AVP and also receives contributions from natriuretic peptide.(17)(18)(19) We must take into account that its half-life in the circulation is around 5 minutes, so its response to osmotic stimuli is fast.Also, it is secreted when we have abrupt decreases in volumes and intravascular pressure, through the baroreceptor pathways of the carotid sinus and the different volume receptors at the level of the pulmonary veins and the atria.(20,21) However, these stimuli are not isolated, but act synergistically.One of the situations most related to AVP release is the sensation of thirst, which is regulated by hypothalamic and cortical neurons (18,19).Thirst has an osmotic threshold above the threshold for AVP release.Therefore, elevated AVP levels have been found before the onset of thirst, which allows water intake to be delayed and regulated by homeostatic mechanisms before hyperosmolar situations.Subsequently, vasopressin secretion is decreased prior to water intake to prevent hyponatremia and even the thirst stimulus is decreased prior to water intake to avoid excessive drinking.
(1,18) However, all the regulations of the physiology of the water balance deteriorate in patients with diabetes insipidus, so there is evidence of decreased secretion, relative deficit or resistance in the renal action of AVP.(22,23) This generates a decrease in urinary concentration (urinary density <1005 in uroanalysis) since there is no water reabsorption mechanism at the level of the collecting tubule and clinically Corresponding Author: Alyi Alejandro Arellano it is classified with an increase in the amount of urine excreted in 24 hours.Likewise, hyperosmolar states above 300 mosm/kg are evidenced causing activation of the central thirst system, clinically evidenced as polydipsia (increased thirst).Likewise, patients within the syndrome present a characteristic dysnatremia such as hypernatremia (21)(22)(23).This always develops in three situations: When there is a decrease in free water intake in relation to body water losses; secondly, when there is a net gain of sodium and, finally, when there is a loss of free water or with low ion concentrations, which is the case in patients with diabetes insipidus with sodium levels above 150 mEq/L.The clinical and biochemical criteria for diabetes insipidus are listed in Table 2. Table 2. Clinical and biochemical characteristics of diabetes insipidus in symptomatic patients.Performed by the authors.

TREATMENT
The basis of treatment is based on the main alteration of the affected anatomical site, so it is divided into whether it is diabetes insipidus of central or nephrogenic origin.Central Diabetes Insipidus (DIC) In this case, we have a relative deficit or decreased secretion of AVP, so patients present with some degree of dehydration or hemodynamic decompensation.Water intake should always be established in conscious patients or in the case of unconscious patients, water resuscitation with isotonic solutions and close monitoring of vital signs should be performed.Likewise, AVP supplementation should be performed.(23,24) We have 2 drugs recommended for this pathology: 1. Desmopressin: It is a synthetic analogue of AVP with a longer duration and little effect on the V1a receptor, so that at recommended doses it does not generate vasoconstriction.However, its use can generate dilutional hyponatremia and aqueous intoxication, due to the potent effect at the V2 receptor level.If the patient tolerates the drug, we can obtain an increase in urinary density, a decrease in urinary volume, sodium returns to physiological levels and plasma osmolality returns to normal (23,24).2. Vasopressin: It is the direct derivative of AVP with a shorter half-life, but with more side effects because it activates all receptors.Another situation that limits its use is its high costand availability, which is why it is only used in intensive care units (23-25).Nephrogenic Diabetes Insipidus (DIN) This entity is suspected in patients without central nervous system alterations who present symptoms and do not respond to DIC management.In these patients, sodium restriction and control of dietary protein intake are performed in order to reduce the osmolar load at the kidney level and water excretion.Likewise, the patient must maintain an optimal hydric intake to maintain his hemodynamic status (17,19) Likewise, the literature recommends the use of NSAIDs because they decrease the glomerular filtration rate, generate an increase in the osmotic gradient and this leads to a decrease in urine production.However, we must take into account the gastrointestinal side effects of these drugs (23)(24)(25).

CONCLUSION
Diabetes insipidus is a disease caused by the relative or insufficient decrease of AVP that generates inability to concentrate urine or AVP is unable to perform its function at the renal level.Hypernatremia is the most characteristic electrolyte alteration of this pathology associated with the hyperosmolar dehydration that is caused, so patients show polydipsia, polyuria and intense thirst.We must take into account the pathophysiology of the disease to perform the excellent hydroelectrolytic correction depending on its etiology and to be able to generate a better quality of life for these patients.Blood biochemistry will always be a good complementary help to differentiate this syndrome from other etiology of hypernatremia.

The Antimicrobial of Selenium Nanoparticles and Combination with Cinnamon Oil Against Salmonella Typhi Which Cause Diarrhea in Human 492 Volume 03 Issue 09 September Corresponding Author: Alyi Alejandro Arellano
hormone.