Extracellular Fluid Volume Depletion Research Articles

Dyselectrolytemia in Children With Severe Pneumonia: A Prospective Study.

Background Pneumonia is a condition characterized by inflammation of the lung parenchyma. It is one of the leading causes of mortality in children below five years of age. While predominantly prevalent in developing countries, it is also associated with significant healthcare-associated costs in developed countries. Among the many risk factors for childhood pneumonia, incomplete immunization, nonexclusive breastfeeding for less than six months, delayed weaning, poor household air quality, malnutrition, and low birth weight are the most commonly found. Electrolyte disturbances, also known as dyselectrolytemia, have been associated with a broad spectrum of acute infections, including pneumonia, particularly hyponatremia. It occurs in the majority of community-acquired pneumonia. Hyper- and hypokalemia are less frequently occurring electrolyte disturbances. Electrolyte disturbances are due to impairment of the intrarenal mechanism of urine dilutiondue to extracellular fluid volume depletion and inappropriate secretion of antidiuretic hormone. The central nervous system is imminently affected by acute hyponatremia. This condition frequently culminates in cerebral edema, a result of the rapid fluid shift, and causes sudden fatality. Aim of the study This study aims to study dyselectrolytemia in children with severe pneumonia. Objectives The study objectives are to assess dyselectrolytemia in children with severe pneumonia and to correlate dyselectrolytemia with morbidity and hospital stay. Methodology This prospective study was conducted on 80 children in the age group of two months up to five years who visited our tertiary care center and had severe pneumonia. We evaluated the extent of dyselectrolytemia in our study population by analyzing the frequency correlation of different kinds of electrolyte imbalances. We also analyzed the correlation between morbidity and hospital stay. Results Out of 80 children in this study with severe pneumonia, 47 (59%) had electrolyte imbalance. Among the patients with electrolyte imbalance, 31 (39%) patients had hyponatremia followed by hypokalemia in 12 (15%) patients, hypernatremia in 3 (4%) patients, and hyperkalemia in 1 (1%) patient. Among the 17 (21%) children with pneumonia requiring ICU admission, 16 (94%) had dyselectrolytemia and 4 (24%) experienced fatal outcomes. Conclusions The majority of the children who were admitted to the ICU had severe pneumonia along with electrolyte imbalance. This necessitates the monitoring of the electrolyte and nutritional status of the patients with pneumonia. Providing proper nutrition advice for children with pneumonia may reduce morbidity and mortality. Early detection and treatment of electrolyte imbalances in pneumonia cases can decrease prolonged hospital stays, ICU admissions, and the need for mechanical ventilation, ultimately contributing to a reduction in morbidity and mortality.

THU293 Enhancement Of Best Practices In Diabetic Ketoacidosis Management Using Standardized Order-sets vs Individual Practitioner Orders

Abstract Disclosure: C. Yim: None. Q. Li: None. T.G. Arnason: None. Diabetic ketoacidosis (DKA) is a hyperglycemic emergency occurring in diabetics due to insulin deficiency. This results in urinary losses of water and electrolytes (sodium, potassium, chloride) and ultimately extracellular fluid volume depletion. Hallmark features of DKA include ketoacidosis, arterial pH < 7.3, bicarbonate <15 mmol/L and an anion gap of >12 mmol/L. The 2018 Diabetes Canada (DC) guidelines outline the key steps of DKA management including fluid resuscitation, resolution of ketoacidosis, correction of electrolytes and management of precipitating factors. Its detailed algorithm identifies three pillars to DKA treatment: IV fluids, serum potassium and acidosis. A 2016 DKA outcome audit at the Royal University Hospital (RUH) in Saskatoon identified that practitioners diverged considerably from (2013) Canadian Diabetes Association guidelines. Subsequently, two standardized preprinted DKA order sets were developed incorporating the 2018 DC recommendations for i) INITIAL and ii) MAINTENANCE DKA management. Their rollout overlapped with annual academic half day sessions on DKA management for postgraduate year 1 residents in internal medicine. These order-sets were initially implemented at RUH in November 2018 and subsequently adopted by some practitioners at St. Paul’s Hospital (SPH). To ensure the order-sets were promoting improved outcomes and adhering to best practices, a retrospective chart review was conducted of all adult DKA admissions at RUH and SPH from Nov. 13, 2018 to December 31, 2020. In total, 279 hospital admissions were reviewed: 99 used practitioners’ own orders, 115 used both initial and maintenance order-sets, 26 used only the initial order-set and 38 used only the maintenance order-set. Use of the INITIAL order set significantly improved compliance (p < 0.0001) with DC 2018 guidelines for recommended insulin dose and timing, fluid resuscitation as well as potassium, sodium and dextrose replacement. Use of the MAINTENANCE order set consistently enhanced outcomes for intravenous fluid selection, subcutaneous insulin overlap, and ensuring a closed anion gap at transition (p < 0.0001). Additionally, the chart review revealed that there were hospital differences for uptake of order sets and compliance to DC 2018 guidelines. There was a significant uptake of order sets at RUH versus SPH (p < 0.0001). RUH consistently met outcomes for appropriate insulin dosing, potassium and dextrose replacement (p < 0.0001). RUH also consistently overlapped IV and SC insulin and ensured a closed insulin gap. The anion gap remained consistently closed post-transition at RUH versus SPH (p = 0.035). These results suggest that utilization of a DKA order set does significantly promote adherence to key best practices outlined in the DC 2018 guidelines. Presentation: Thursday, June 15, 2023

Changes in Serum Electrolytes Following Permanent or Temporary Ileostomy

Background: Patients with ileostomies are well known to be susceptible to extracellular fluid volume depletion as a result of fluid and solute losses that are greater than intake. However, electrolyte disorders accompanying these episodes of volume depletion are not well delineated. Objective: To find out serum electrolytes changes observed in patients undergone permanent or temporary ileostomy. Method: This prospective observational study was carried out in the Department of Colorectal Surgery, BSMMU, Dhaka, from January 2018 to December 2018. Fifty patients underwent permanent or temporary ileostomy and postoperatively treated with intravenous fluid and electrolytes at least up to 3rd POD along with gradual resumption of oral intake or ileostomy feeding and managed at least for 5 days were included in this study. Electrolyte was measured preoperatively and 3rd and 5th POD and observed the changes. Result: Males were predominant than females (1.17:1). Most of the patients were in age group 31 – 40 years. Mean age was 42.4±12.5 years. Serum sodium (Na) and serum potassium (K) were reduced at POD 3 and at POD 5 compared to pre-operative level. Serum sodium concentration was 136.6±3.75 mmol/L pre operatively and reduced to 135.1 ±2.98 mmol/L at 3rd POD and 134.8±3.04 mmol/L at 5th POD. Similarly, serum potassium concentration was 4.0±0.49 mmol/L pre operatively and reduced to 3.8±0.70 mmol/L at 3rd POD and 3.8±0.50 mmol/L at 5th POD. Both serum Na and serum K level reduced significantly in POD 3 and in POD 5 in comparison to pre-operative values (p<0.05). Regarding serum Cl and serum HCO3 level no statistically significant difference were observed (p>0.05). Conclusion: Serum sodium and potassium concentration reduced statistically significantly after permanent ileostomy. Bangladesh Med Res Counc Bull 2021; 47(1): 78-81

Salt sensitivity of volume and blood pressure in a mouse with globally reduced ENaC γ-subunit expression.

The epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding subunits of ENaC results in early postnatal mortality. Here, we present the initial characterization of a mouse with dramatically suppressed expression of the ENaC γ-subunit. We used this hypomorphic (γmt) allele to explore the importance of this subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ-subunit expression in γmt/mt mice was markedly suppressed in the kidney and lung, whereas electrolytes resembled those of littermate controls. Aldosterone levels in γmt/mt mice exceeded those seen in littermate controls. Quantitative magnetic resonance measurement of body composition revealed similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. γmt/mt mice exhibited a more rapid decline in body water and lean tissue mass in response to a low-Na+ diet than the controls. Replacement of drinking water with 2% saline selectively and transiently increased body water and lean tissue mass in γmt/mt mice relative to the controls. Lower blood pressures were variably observed in γmt/mt mice on a high-salt diet compared with the controls. γmt/mt also exhibited reduced diurnal blood pressure variation, a "nondipping" phenotype, on a high-Na+ diet. Although ENaC in the renal tubules and colon works to prevent extracellular fluid volume depletion, our observations suggest that ENaC in other tissues may participate in regulating extracellular fluid volume and blood pressure.NEW & NOTEWORTHY A mouse with globally suppressed expression of the epithelial Na+ channel γ-subunit showed enhanced sensitivity to dietary salt, including a transient increase in total body fluid, reduced blood pressure, and reduced diurnal blood pressure variation when given a dietary NaCl challenge. These results point to a role for the epithelial Na+ channel in regulating body fluid and blood pressure beyond classical transepithelial Na+ transport mechanisms.

Hyponatremia in children with acute respiratory infections: A reappraisal.

Hyponatremia (<135 mmol/L), typically associated with an elevated anti-diuretic hormone level, is common among children admitted with bronchiolitis, pneumonia, or pulmonary exacerbation of cystic fibrosis. The main consequences of acute hyponatremia include cerebral edema and Ayus-Arieff pulmonary edema. A widespread belief is that, in children with pneumonia or bronchiolitis, hyponatremia results from inappropriate anti-diuresis. By contrast, the pathogenic role of extracellular fluid volume depletion or decreased effective circulating blood volume is underscored. Considering the prevalence of hyponatremia, sodium determination is advised on admission in children diagnosed with bronchiolitis, pneumonia, or pulmonary exacerbation of cystic fibrosis. There is no necessity to do anything beyond reassessing the appropriateness of fluid therapy in cases with mild (130-134 mmol/L) hyponatremia. In children with sodium <130 mmol/L, the underlying etiology is sometimes evident from history and physical findings. Given that clinical assessment of fluid volume status is difficult in hyponatremia, further laboratory evaluation is often required in these patients. An increase in sodium level ≤6 mmol/L per day is currently considered the therapeutic goal in all cases. Emergency correction with a 2 mL/kg body weight bolus of 3.0% saline over 10-15 min intravenously is advised in cases with severe symptoms due to hyponatremia and in cases with symptoms, even if mild, due to a rapid-onset (<48 h) of hyponatremia (two additional doses are administered if the patient's condition does not improve).

WATER-ELECTROLYTE DISTURBANCES POSTRESUSCITATION ACUTE MYOCARDIAL INFARCTION AND THEIR VALUE IN DISORDERS OF SYSTEMIC HEMODYNAMICS

Purpose. The establishment of the role of water and electrolyte disorders in the pathogenesis postresuscitation hemo circulatory disorders after removal from the clinical death caused by acute myocardial infarction. Materials and methods. In experiments with 158 dogs studied under Nembutal anesthesia recovery processes of life after 5 minutes of clinical death caused by myocardial infarction. Results. It is found that dogs in the early postresuscitative after myocardial infarction occurs movement of sodium ions in the red blood cells, which is accompanied by gipoosmiey blood plasma and interstitial fluid. This causes the movement of water in the cell sector, which leads to the development of hypovolemia and drop in cardiac output. Movement of potassium and calcium ions from cell sector into the extracellular defines violation of myocardial, vascular tone, and increases the risk of arrhythmia postresuscitation myocardial infarction. Сonclusion. In postresuscitative in dogs undergoing clinical death with acute myocardial infarction, there is a redistribution of electrolytes sector body. During the first 9 hours after resuscitation sodium and calcium concentration in the cell sector increase and decrease in the extracellular. Changes in the potassium content of the opposite. By the end of 1st day recovery period increases plasma sodium concentration, and the corresponding potassium and calcium indicators reduced. The osmolarity of the extracellular space is reduced by 5 min postresuscitative period and increases toward the end of 1 day. It is associated with similar changes in sodium concentration. sodium retention in the cell movement causes the space portion therein, and development of extracellular fluid volume depletion, which leads to a decrease in venous return and cardiac output drop. In the interval of 9–24 hours after resuscitation begins a long period of stabilization of the circulatory system. This is due to the normalization of the water distribution sector, which leads to the restoration of intravascular volume and resolution of hemodynamic disturbances.

Hyperglycemic Emergencies in Adults

Hyperglycemic Emergencies in Adults

Type 1 Diabetes in Children and Adolescents

Type 1 Diabetes in Children and Adolescents

Renal effects of carprofen and etodolac in euvolemic and volume-depleted dogs

To determine the effects of carprofen and etodolac on renal function in euvolemic dogs and dogs with extracellular fluid volume depletion induced via administration of furosemide. 12 female Beagles. Dogs received a placebo, furosemide, carprofen, etodolac, furosemide and carprofen, and furosemide and etodolac. The order in which dogs received treatments was determined via a randomization procedure. Values of urine specific gravity, various plasma biochemical variables, glomerular filtration rate (GFR [urinary clearance of creatinine]), and renal plasma flow (urinary clearance of para-aminohippuric acid) were determined before and after 8 days of drug administration. A washout time of approximately 12 days was allowed between treatment periods. Administration of furosemide, furosemide and carprofen, and furosemide and etodolac caused changes in urine specific gravity and values of plasma biochemical variables. Administration of carprofen or etodolac alone did not have a significant effect on renal plasma flow or GFR. Concurrent administration of furosemide and carprofen or furosemide and etodolac caused a significant decrease in GFR. After 12-day washout periods, mean values of GFR were similar to values before drug administration for all treatments. Results indicated GFR decreased after 8 days of concurrent administration of furosemide and carprofen or furosemide and etodolac to dogs. Administration of preferential cyclooxygenase-2 inhibitors to dogs with extracellular fluid volume depletion or to dogs treated with diuretics may transiently impair renal function.

Hyponatremia in a patient with scleroderma renal crisis: a potential role of activated renin-angiotensin system

BackgroundScleroderma renal crisis is an important complication of scleroderma (systemic sclerosis) that is associated with significant morbidity and mortality. On the other hand, hyponatremia has never been reported in patients with scleroderma renal crisis.Case presentationA 66-year-old man with scleroderma was admitted to our hospital for an evaluation of renal dysfunction and extreme hypertension. The laboratory evaluation revealed remarkably high plasma renin activity in association with microangiopathic hemolytic anemia, and the anti-RNA polymerase III antibody assessment was positive. The patient was diagnosed with scleroderma renal crisis and was started treatment with enalapril maleate, an angiotensin-converting enzyme inhibitor. During hospitalization, the patient developed symptomatic hyponatremia three times and each laboratory analysis revealed improperly high levels of antidiuretic hormone without signs of extracellular fluid volume depletion as well as remarkably high plasma renin activities and angiotensin levels. However, hyponatremia has not been demonstrated to occur as a result of combined therapy with candesartan cilexetil, an angiotensin II receptor blocker, and aliskiren fumarate, a direct renin inhibitor. The plasma renin activities and angiotensin levels were normalized and the renal function was maintained after treatment.ConclusionsTo our best knowledge, this is the first documented case of scleroderma renal crisis complicated with hyponatremia. This report also suggests that the activated renin-angiotensin system may play a role in the development of hyponatremia and that hyponatremia should be taken into consideration as a rare but possible complication associated with screloderma renal crisis.

Laxative Abuse, Eating Disorders, and Kidney Stones: A Case Report and Review of the Literature

Kidney stones are listed among the complications of eating disorders; however, very few cases have been reported. We present an additional case of nephrolithiasis associated with laxative abuse, including detailed results of the patient's urine metabolic profiles, in a patient with idiopathic hypercalciuria. We review the literature and provide an explanation for the paucity of cases of nephrolithiasis associated with these disorders. Despite low urine volumes resulting from extracellular fluid volume depletion and hypocitraturia resulting from hypokalemia, both of which would tend to favor the formation of kidney stones, most patients with eating disorders are likely to be protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion and increased proximal tubular sodium reabsorption. However, patients with underlying idiopathic hypercalciuria who develop eating disorders may be at increased risk of stone formation in the setting of low urine volume and therefore high supersaturation of calcium oxalate and phosphate.

Renal salt-wasting syndrome in children with intracranial disorders

Hypotonic hyponatremia, a serious and recognized complication of any intracranial disorder, results from extra-cellular fluid volume depletion, inappropriate anti-diuresis or renal salt-wasting. The putative mechanisms by which intracranial disorders might lead to renal salt-wasting are either a disrupted neural input to the kidney or the elaboration of a circulating natriuretic factor. The key to diagnosis of renal salt-wasting lies in the assessment of extra-cellular volume status: the central venous pressure is currently considered the yardstick for measuring fluid volume status in subjects with intracranial disorders and hyponatremia. Approximately 110 cases have been reported so far in subjects ≤18 years of age (male: 63%; female: 37%): intracranial surgery, meningo-encephalitis (most frequently tuberculous) or head injury were the most common underlying disorders. Volume and sodium repletion are the goals of treatment, and this can be performed using some combination of isotonic saline, hypertonic saline, and mineralocorticoids (fludrocortisone). It is worthy of a mention, however, that some authorities contend that cerebral salt wasting syndrome does not exist, since this diagnosis requires evidence of a reduced arterial blood volume, a concept but not a measurable variable.

A SPAK Isoform Switch Modulates Renal Salt Transport and Blood Pressure

The renal thick ascending limb (TAL) and distal convoluted tubule (DCT) play central roles in salt homeostasis and blood pressure regulation. An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1. Here, we show that a kidney-specific SPAK isoform, which lacks the kinase domain, inhibits phosphorylation of NCC and NKCC2 by full-length SPAK invitro. Kidney-specific SPAK is highly expressed along the TAL, whereas full-length SPAK is more highly expressed along the DCT. As predicted from the differential expression, SPAK knockout in animals has divergent effects along TAL and DCT, with increased phosphorylated NKCC2 along TAL and decreased phosphorylated NCC along DCT. In mice, extracellular fluid volume depletion shifts SPAK isoform abundance to favor NaCl retention along both segments, indicating that a SPAK isoform switch modulates sodium avidity along the distal nephron.

Diagnostic Value of Urinary Sodium, Chloride, Urea, and Flow

Up to 30% of hospitalized critically ill patients may have a rise in serum creatinine concentration. In addition to history and physical examination, there is diagnostic value in assessing urinary electrolytes, solute excretion, and urine flow in these patients. The correct interpretation of these urinary parameters can avoid unnecessary volume overload and mechanical ventilation, risk factors for increased mortality in patients with rising serum creatinine. The present article also discusses the role of arterial underfilling in causing prerenal azotemia in the presence of an increase in total body sodium and extracellular fluid expansion. As with extracellular fluid volume depletion, arterial underfilling secondary to impaired cardiac function or primary arterial vasodilation can delay or prevent recovery from ischemic or toxic acute tubular necrosis. The present brief review discusses the various aspects of the correct interpretation of urinary electrolytes, solute excretion, and urine flow in the setting of a rising serum creatinine concentration.

Prerenal azotemia from excessive sweating in an adult with a cystic fibrosis gene mutation

We present the case of a 58-year-old male with chronic kidney disease who was admitted to the hospital multiple times with extracellular fluid volume depletion and prerenal azotemia. Some episodes were associated with gastrointestinal fluid losses and others with profuse diaphoresis in the absence of gastrointestinal fluid losses. At the age of 57 years, a common cystic fibrosis transmembrane conductance regulator protein mutation and a family history of cystic fibrosis were documented. We hypothesize that the abnormal cystic fibrosis transmembrane conductance regulator resulted in repeated bouts of excessive sweating, extracellular fluid volume depletion, and acute renal failure. This case is unique because of the prolonged period of time over which multiple documented episodes of prerenal acute renal failure occurred and because of the onset of the episodes in adulthood.

Thiazide Effects and Adverse Effects

One of the longest-running debates in clinical medicine shows no sign of disappearing; just when it seems that thiazides have reassumed their role as front-line drugs to treat hypertension,1 new concerns emerge,2–4 leading some to question their role once again.5 Thiazides are effective antihypertensives with long track records and low cost. The major concerns about their use arise from their tendency to cause hypokalemia, impair glucose tolerance, increase serum cholesterol, and increase serum uric acid. Few medical controversies have generated as much heat, with well-established camps staking out positions that appear resistant to change.6–9 The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the largest study of antihypertensive monotherapy ever performed,10 was intended to identify the best first-line treatment for high-risk hypertensive individuals; however, despite its size and the numerous resulting publications, its implications and authority continue to be disputed. The goal of this review is not take sides in this debate but rather to inject a distinct, and sometimes neglected, perspective; during the past 15 years, remarkable developments in molecular biology and human genetics have provided substantial insights into the pathogenesis of hypertension and mechanisms and adverse effects of diuretics. Diuretic proponents and antagonists alike often neglect these developments when addressing the topic; it is the purpose of this Brief Review to integrate these developments into the debate with the goal of generating questions that can be addressed scientifically. Thiazide diuretics were developed during the 1950s, when chemists and physiologists at Merck Sharpe and Dohme tested derivatives of sulfonamide-based carbonic anhydrase inhibitors, with the goal of discovering drugs that enhance the excretion of sodium with chloride rather than sodium bicarbonate.* Although these drugs lower arterial pressure effectively, the mechanisms have long perplexed investigators.11 Thiazides reduce cardiac output acutely by reducing extracellular …

Handling of water and electrolytes in the healthy old

SummaryThis paper reviews the handling of water and electrolytes by the ageing kidney and the clinical consequences in everyday clinical practice. Normal physiology in the adult kidney is discussed, followed by description of the main physiological changes (adaption) that occur as the kidney ages. Clearly, successful management of the elderly patient requires a knowledge of these changes, which result in: (i) increased tendency for volume depletion and dehydration; (ii) decreased ability to tolerate a volume load; (iii) increased propensity for potassium disturbances (hypo- and hyperkalaemia); (iv) diminished production of renin and blunted physiological response to the effects of aldosterone and antidiuretic hormone; (v) increased tendency to lower levels of phosphate; and (vi) tendency for the development of hypocalcaemia and hypomagnesaemia. A brief review of the role of extracellular fluid volume depletion and other factors contributing to acute renal failure in elderly patients is also presented.

Acute Electrolyte and Acid-Base Disorders in Patients With Ileostomies: A Case Series

Patients with ileostomies are well known to be susceptible to extracellular fluid volume depletion as a result of fluid and solute losses that are greater than intake. However, electrolyte and acid-base disorders accompanying these episodes of volume depletion are not well delineated. Case series. 7 patients with hospitalization because of acute acid-base disturbances at an academic medical center. In all patients, serum and urine creatinine and electrolytes were measured. In 2 patients, arterial blood pH and Pco(2) and ileal drainage electrolytes also were measured. 2 patients presented with severe metabolic alkalosis, and the remaining 5 patients had low serum total carbon dioxide values in association with hyperkalemia. All 7 had acute renal failure. Pathophysiological characteristics, diagnosis, and management of these disorders are discussed, along with considerations for long-term management of fluid and electrolyte balance. This report illustrates electrolyte and acid-base disorders encountered in patients with ileostomies from our clinical experience. We have no data about the incidence of these disorders. Patients with ileostomies can develop diverse and potentially life-threatening acute electrolyte and acid-base disorders when ileostomy drainage increases. Either metabolic acidosis or metabolic alkalosis can occur, depending on the nature and duration of the losses. These cases emphasize the need to be aware of the variety of acute electrolyte and acid-base disorders that can occur in this group of patients and to intervene rapidly when they develop.

Low-dose desmopressin infusion: renal action in healthy women in moderate salt retention and depletion, and interactions with prostanoids

Studies were carried out to evaluate the influence of variations in sodium balance on the renal response to low-dose infusion of 1-desamino-8- D -arginine vasopressin (dDAVP), and the functional interaction between dDAVP and renal prostanoids. The studies were performed on healthy women in conditions of extracellular fluid volume expansion (SR group, n =9) and depletion (SD2 group, n=6), respectively. The study protocol included hypotonic polyuria (induced by oral water load) and subsequent antidiuresis (induced by low-dose infusion of dDAVP). Three 60-min clearance (cl.) periods were performed during polyuria (cl. P), early (cl. A1) and late (cl. A2) antidiuresis. The urinary concentrations of prostaglandin (PG) E 2 and the stable metabolites of PGI 2 and thromboxane (Tx) A 2, 6-keto-PGF 1α (6KPGF) and TxB 2, were estimated. Paired renal functional explorations were performed in salt retention and salt depletion both in absence and presence of indomethacin (SR.I and SD2.I groups). In both paired and unpaired studies, the early and late effects of dDAVP on the functional excretory variables and the excretion of prostanoids were assessed as percentage variations, (A1−P)% P and (A2−A1)% A1. (I) dDAVP in salt retention and depletion. During early infusion dDAVP produced in both conditions a significant reduction in urinary flow rate, creatinine cl., absolute and fractional excretions of sodium, chloride and potassium; during late infusion dDAVP was effective in inducing a further significant reduction in urinary flow rate. In salt retention compared to depletion the early reductions in sodium and chloride (absolute and fractional) excretions were significantly lower. (II) Indomethacin pretreatment. During early infusion the dDAVP-induced reductions in the urinary flow rate and 6KPGF excretion were enhanced in both conditions. In salt depletion the dDAVP effects in reduction of creatinine cl. and urinary electrolyte excretions were also enhanced. During late infusion the antidiuretic effect of dDAVP was suppressed in salt retention, while in salt depletion creatinine cl., the urinary excretions of electrolytes and both 6KPGF and TxB 2 showed increases significantly different from the dDAVP effects in the absence of indomethacin. In conclusion, (a) the salt-retaining effect of dDAVP was less effective in salt retention compared to depletion. (b) Indomethacin pretreatment affected the renal action of dDAVP in a time-dependent pattern. The early effects in both conditions were consistent with an inhibited synthesis of modulator PGs. On the contrary, the late effects were consistent with the occurrence, at least in salt depletion, of an escape from dDAVP renal action. This escape phenomenon probably depended on a partial regression of the pharmacological inhibition of the modulating PGs.

In Situ Demonstration of Angiotensin-Dependent and Independent Pathways for Hyperaldosteronism During Chronic Extracellular Fluid Volume Depletion

In Situ Demonstration of Angiotensin-Dependent and Independent Pathways for Hyperaldosteronism During Chronic Extracellular Fluid Volume Depletion