ABSTRACT
Hyponatraemia has indeed been extensively studied from multiple angles, including volume status, tonicity, and aetiology; however, the specific consideration of the osmolar gap (OG) within the context of hyponatraemia and its potential impact on their overall outcomes received limited attention in research. The current study represents an effort to address this gap in our understanding. This prospective exploratory study was conducted on adults aged 14 years and older at the Indus Hospital, Karachi, from 2017 to 2020. The study involved categorising severity of hyponatraemia and volume status. The osmolar gap (OG) was calculated and categorised as either increased (OG>10) or normal (OG<10). Among the 262 patients included in the study, there were 139 females and 123 males. Elevated OG was observed in 141(53.8%) patients. There were 28 (10.7%) recorded fatalities and majority of these individuals had an elevated OG. These findings underscore the importance for clinicians to consider the osmolar gap when managing patients with hyponatraemia.
Subject(s)
Hyponatremia , Humans , Hyponatremia/epidemiology , Hyponatremia/physiopathology , Female , Male , Adult , Middle Aged , Prospective Studies , Osmolar Concentration , Aged , Young Adult , Pakistan/epidemiology , AdolescentABSTRACT
PURPOSE OF REVIEW: To provide a contemporary overview of the pathophysiology, evaluation, and treatment of hyponatremia in heart failure (HF). RECENT FINDINGS: Potassium and magnesium losses due to poor nutritional intake and treatment with diuretics cause an intracellular sodium shift in HF that may contribute to hyponatremia. Impaired renal blood flow leading to a lower glomerular filtration rate and increased proximal tubular reabsorption lead to an impaired tubular flux through diluting distal segments of the nephron, compromising electrolyte-free water excretion. Hyponatremia in HF is typically a condition of impaired water excretion by the kidneys on a background of potassium and magnesium depletion. While those cations can and should be easily repleted, further treatment should mainly focus on improving the underlying HF and hemodynamics, while addressing congestion. For decongestive treatment, proximally acting diuretics such as sodium-glucose co-transporter-2 inhibitors, acetazolamide, and loop diuretics are the preferred options.
Subject(s)
Heart Failure , Hyponatremia , Humans , Hyponatremia/therapy , Hyponatremia/physiopathology , Hyponatremia/etiology , Heart Failure/physiopathology , Heart Failure/complications , Heart Failure/therapy , Diuretics/therapeutic use , Disease ManagementABSTRACT
The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore, arginine vasopressin, which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low versus high [Na+], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9-mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis.
Subject(s)
Fibroblast Growth Factor-23 , Sodium , Humans , Fibroblast Growth Factor-23/genetics , Fibroblast Growth Factor-23/metabolism , Hyponatremia/physiopathology , Renal Insufficiency, Chronic/physiopathology , Sodium/metabolism , Sodium/pharmacology , Cell Line, Tumor , Cell Line , Animals , Mice , Mice, Inbred C57BL , Arginine Vasopressin/metabolism , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , RatsABSTRACT
Observational hemodialysis (HD) studies report an association between hyponatremia and increased mortality. As volume overload is also associated with mortality, we wished to determine whether hyponatremia is linked to increased extracellular water (ECW). We measured ECW, total body water (TBW) and body composition predialysis with multifrequency bioimpedance, arm strength with pinch gauge and hand grip strength (PS, HGS), standard biochemistry profiles, comorbidity and clinical frailty scores (CFS). We reviewed 324 patients, 195 (60.2%) male, mean age 62.3 ± 15.6 years. Thirty-eight (11.7%) patients were hyponatremic (sodium ≤135 mmol/L), ECW/height2 was not different, but ECW/TBW (0.409 ± 0.016 vs. 0.402 ± 0.016, p < 0.01), C reactive protein (CRP) (9(4-6) vs. 5(2-12) g/L, p < 0.05), CFS (5(4-6) vs. 4(3-6), p < 0.05) were higher in hyponatremic patients, whereas appendicular lean mass index (8.6 ± 1.7 vs. 9.4 ± 1.8 kg/m2, p < 0.01), serum albumin (36.3 ± 5.5 vs. 38.8 ± 5.0 g/L, p < 0.01) and PS (3.7(2.7-4.7) vs. 4.7 (3.2-6.5) kg, p < 0.05)) were lower. Both serum sodium, and serum sodium after adjustment for glucose were associated with serum creatinine (ß 4.26, (95% confidence limits [CL] 1.9-6.7), ß 3.98 (CL 1.6-6.4), both p = 0.001, respectively) and negatively with CRP (ß -0.76, [CL] -1.5 to -0.5), ß -0.72 (CL -1.44 to -0.12), p = 0.036, p = 0.046, respectively) in a multivariable model. Hyponatremic HD patients did not simply have an increased ECW, as the increased ECW/TBW and ECW/ICW ratios were more likely secondary to loss of muscle mass and strength, associated with increased CRP and reduced albumin, suggesting that hyponatremia is associated with inflammation, loss of muscle mass and increasing frailty.
Subject(s)
Body Water , Hyponatremia/complications , Hyponatremia/physiopathology , Renal Dialysis/methods , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/physiopathology , Water-Electrolyte Imbalance/physiopathologyABSTRACT
BACKGROUND: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. METHODS: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. RESULTS: Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). CONCLUSIONS: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.
Subject(s)
Graft Rejection/complications , Hyponatremia/complications , Kidney Transplantation , Transplant Recipients/statistics & numerical data , Adult , Cohort Studies , Female , Graft Rejection/physiopathology , Humans , Hyponatremia/physiopathology , Kidney/physiopathology , Male , Middle Aged , Prospective Studies , Survival Analysis , SwitzerlandABSTRACT
OBJECTIVES: Although new-born screening (NBS) for classical congenital adrenal hyperplasia (C-CAH) has been available for decades, it is not widely implemented. We assessed the usefulness of introducing NBS for C-CAH, by analyzing presenting status of infants with C-CAH, over the past two decades, in Sri Lanka. METHODS: This retrospective clinic-based study, from the largest tertiary children's hospital in Sri Lanka, analyzed initial presenting features of children with C-CAH from 1999 to 2018, in the absence of NBS for CAH, and included gender-based comparisons. RESULTS: Features suggestive of impending adrenal-crisis were seen at initial presentation in >80 % (dehydration 70%, hyponatremia 65%, hyperkalemia 47%, vomiting 45%, hypoglycemia 22%, collapse 20%). Hyperpigmentation was seen in 78%, and consanguinity in 27%. There were fewer affected males (n = 12) compared to females (n = 28). Most girls (96%) had virilized genitalia, and 16 faced uncertainty about gender at birth. Median age at diagnosis was 20 days. More than 70% of children had SW-CAH (males = 9 and females = 20). There were fewer males with SW-CAH, and all had features of impending adrenal crisis, including severe hyponatremia in 50%, while 62% of girls also developed hyponatremia and 33% had hyperkalemia, prior to treatment. Treatment of SW-CAH was initiated at a median age of 30 days in boys, and 10 days of age in girls. CONCLUSION: Many boys and girls with C-CAH from Sri Lanka presented late with impending adrenal crisis. Males were diagnosed later, and some possibly succumbed to C-CAH undiagnosed. These findings support including CAH in NBS programs to avert preventable childhood morbidity and mortality.
Subject(s)
Adrenal Hyperplasia, Congenital/diagnosis , Hyperkalemia/physiopathology , Hyperpigmentation/physiopathology , Hyponatremia/physiopathology , Vomiting/physiopathology , Adolescent , Adrenal Hyperplasia, Congenital/epidemiology , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Neonatal Screening , Prognosis , Retrospective Studies , Sri Lanka/epidemiology , Young AdultABSTRACT
Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.
Subject(s)
Apelin/analogs & derivatives , Apelin/metabolism , Arginine Vasopressin/adverse effects , Diuresis , Hyponatremia/pathology , Hyponatremia/physiopathology , Amino Acid Sequence , Animals , Apelin/administration & dosage , Apelin/blood , Apelin Receptors/metabolism , Arginine Vasopressin/blood , Blood Glucose/metabolism , Blood Pressure/drug effects , Cell Line , Colforsin/pharmacology , Cyclic AMP/biosynthesis , Deamino Arginine Vasopressin/pharmacology , Disease Models, Animal , Diuresis/drug effects , Electrolytes/blood , Half-Life , Hyponatremia/blood , Hyponatremia/urine , Kidney Tubules, Collecting/drug effects , Kidney Tubules, Collecting/metabolism , Kidney Tubules, Collecting/physiopathology , Male , Mice , Models, Biological , Myocardial Contraction/drug effects , Peptides/chemistry , Peptides/pharmacology , Phosphorylation/drug effects , Rats, Sprague-Dawley , Tolvaptan/pharmacologySubject(s)
Adrenal Insufficiency/complications , Adrenal Insufficiency/diagnosis , Cathartics/adverse effects , Hyponatremia/etiology , Abdominal Pain/etiology , Cathartics/administration & dosage , Cathartics/therapeutic use , Humans , Hyponatremia/diagnosis , Hyponatremia/physiopathology , Magnetic Resonance Imaging/methods , Male , Middle AgedABSTRACT
SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.
Subject(s)
Adrenal Insufficiency/physiopathology , COVID-19/physiopathology , Hyponatremia/physiopathology , Hypotension/physiopathology , Acidosis/blood , Acidosis/physiopathology , Acidosis/therapy , Adrenal Insufficiency/blood , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/drug therapy , COVID-19/blood , Fluid Therapy , Glucocorticoids/therapeutic use , Humans , Hydrocortisone/blood , Hyponatremia/blood , Hyponatremia/therapy , Hypophosphatemia/blood , Hypophosphatemia/physiopathology , Hypophosphatemia/therapy , Hypotension/therapy , Male , Middle Aged , Pituitary-Adrenal Function Tests , Prednisolone/therapeutic use , SARS-CoV-2 , Vomiting/physiopathology , Water-Electrolyte Imbalance/blood , Water-Electrolyte Imbalance/physiopathology , Water-Electrolyte Imbalance/therapyABSTRACT
Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1th through April 31th, 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa <135 mmol/L), eunatremic (SNa 135-145 mmol/L), or hypernatremic (SNa >145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52-77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291.
Subject(s)
COVID-19/mortality , Hospital Mortality/trends , Hypernatremia/physiopathology , Hyponatremia/physiopathology , Registries/statistics & numerical data , SARS-CoV-2/isolation & purification , Aged , COVID-19/epidemiology , COVID-19/virology , Female , Follow-Up Studies , Global Health , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Retrospective Studies , Survival RateABSTRACT
Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.
Subject(s)
Ascites/metabolism , Hypertension, Portal/metabolism , Hyponatremia/metabolism , Liver Cirrhosis/metabolism , Renin-Angiotensin System/physiology , Vasopressins/metabolism , Acute Kidney Injury/metabolism , Acute Kidney Injury/physiopathology , Acute-On-Chronic Liver Failure/metabolism , Acute-On-Chronic Liver Failure/physiopathology , Albumins/therapeutic use , Antidiuretic Hormone Receptor Antagonists/therapeutic use , Ascites/physiopathology , Fluid Therapy , Hepatic Encephalopathy/metabolism , Hepatic Encephalopathy/physiopathology , Hepatorenal Syndrome/metabolism , Hepatorenal Syndrome/physiopathology , Humans , Hypertension, Portal/physiopathology , Hyponatremia/physiopathology , Hyponatremia/therapy , Liver Cirrhosis/physiopathology , Liver Transplantation , Saline Solution, Hypertonic/therapeutic use , Splanchnic Circulation/physiology , Tolvaptan/therapeutic use , Vasodilation/physiologyABSTRACT
Hyponatremia is a common condition affecting hospitalized and ambulatory patients as well. The clinical spectrum of hyponatremia can range from asymptomatic laboratory findings to severely symptomatic conditions such as acute epileptic seizures. Etiologies of hyponatremia include excessive intake of solute-free fluids, side-effects of medication, diseases associated with hypervolemic states such as congestive heart failure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH).As hyponatremia can be a potentially life-threatening condition, it requires an efficient management with the goal of identifying the etiology and to subsequently provide adequate treatment, while avoiding treatment-related adverse effects such as overcorrection and pontine myelinolysis. This article summarizes the pathophysiology and differential diagnosis, as well as useful diagnostic tests and therapy of hyponatremia in a practice-oriented manner.
Subject(s)
Hyponatremia , Diagnosis, Differential , Heart Failure , Humans , Hyponatremia/diagnosis , Hyponatremia/physiopathology , Hyponatremia/therapy , Inappropriate ADH SyndromeABSTRACT
Volume and electrolyte evaluation and management is seen frequently in primary care practices. Some of the most common abnormalities encountered in outpatient practices are prerenal azotemia, dysnatremias, and altered potassium levels. Perturbations in volume or electrolyte concentrations can lead to serious organ dysfunction as well as hemodynamic collapse. This review focuses on the maintenance and regulation of intravascular volume and electrolytes, specifically sodium and potassium.
Subject(s)
Azotemia/physiopathology , Kidney/physiology , Water-Electrolyte Imbalance/physiopathology , Water-Electrolyte Imbalance/therapy , Blood Urea Nitrogen , Body Water/physiology , Creatinine/blood , Humans , Hyperkalemia/physiopathology , Hyperkalemia/therapy , Hypernatremia/physiopathology , Hypernatremia/therapy , Hypokalemia/physiopathology , Hypokalemia/therapy , Hyponatremia/physiopathology , Hyponatremia/therapy , Primary Health CareABSTRACT
Intravenous fluids are frequently used in hospitalized children. Hypotonic fluids have been the standard of care in pediatrics for many years. This might be explained by the empiricism of early recommendations favoring fluids with dextrose, but an insufficient amount of sodium. The risk of hyponatremia (<135mmol/L) might be increased by the occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in the course of common acute diseases (e.g., bronchiolitis, acute gastroenteritis, encephalitis, meningitis) in children. Severe hyponatremia (<130mmol/L) is often associated with neurologic complications leading to sequelae or even death. Over the last few years, hyponatremia induced by hypotonic fluids has been increasingly reported, and significant progress has been made in the understanding of cerebral edema and osmotic demyelination. Several randomized clinical trials have shown weak but significant evidence that isotonic fluids were superior to hypotonic solutions in preventing hyponatremia. However, clinical practices have not changed much in France, as suggested by the analysis of intravenous fluids ordered from the Assistance Publique-Hôpitaux de Paris (AP-HP) central pharmacy (PCH) in 2017. Therefore, it would be advisable that national guidelines be released under the French Health Authorities regarding the safe infusion of infants and children.
Subject(s)
Fluid Therapy/adverse effects , Hyponatremia/etiology , Hypotonic Solutions/adverse effects , Child , Child, Preschool , Fluid Therapy/methods , France , Hospitalization , Humans , Hyponatremia/mortality , Hyponatremia/physiopathology , Hyponatremia/prevention & control , Infant , Isotonic Solutions , Practice Guidelines as Topic , Practice Patterns, Physicians' , Risk Factors , Severity of Illness IndexABSTRACT
OBJECTIVE: Hyponatremia is a common electrolyte disorder in patients with stroke, which leads to various fatal complications. We performed a systematic review and meta-analysis to investigate the outcomes of acute stroke patients with hyponatremia. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library databases for relevant literature in English published up to March 2020. Two review authors independently screened and selected the studies by assessing the eligibility and validity based on the inclusion criteria. Mortality at 90 days was set as the primary end point, and in-hospital mortality and length of hospital stay were set as the secondary end points. We conducted the data synthesis and analyzed the outcomes by calculating the odds ratio (OR) and mean difference. RESULTS: Of 835 studies, 15 studies met the inclusion criteria (n = 10,745). The prevalence rate of stroke patients with hyponatremia was 7.0-59.2%. They had significantly higher 90-day mortality (OR, 1.73; 95% confidence interval (CI), 1.24-2.42) and longer length of hospital stay (mean difference, 10.68 days; 95% CI, 7.14-14.22) than patients without hyponatremia. Patients with hyponatremia had a higher tendency of in-hospital mortality than those without hyponatremia (OR, 1.61; 95% CI, 0.97-2.69). CONCLUSIONS: The development of hyponatremia in the clinical course of stroke is associated with higher short-term mortality and a longer hospital stay. Although the causal relationship is unclear, hyponatremia could be a significant predictor of poor outcomes after stroke.
Subject(s)
Hyponatremia/etiology , Sodium/blood , Stroke/complications , Water-Electrolyte Balance , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Hospital Mortality , Humans , Hyponatremia/mortality , Hyponatremia/physiopathology , Length of Stay , Male , Middle Aged , Risk Assessment , Risk Factors , Stroke/mortality , Stroke/physiopathology , Stroke/therapy , Time Factors , Treatment Outcome , Young AdultABSTRACT
RATIONALE: Hyponatremia occurs frequently in the hospital setting and may be attributable to a host of etiologies. Drugs are frequently implicated. Trimethoprim-sulfamethoxazole (TMP/SMX) represents a well-recognized pharmacologic precipitant of drug-induced hyponatremia, with several reports extant in the retrievable literature. Nephrologists thus debate the mechanisms giving rise to TMP/SMX-induced hyponatremia and the precise mechanism by which treatment with TMP/SMX generates reductions of serum sodium concentration remain controversial. The agent has a well-known effect of antagonizing the effects of aldosterone upon the distal nephron. Renal salt wasting and the syndrome of inappropriate antidiuretic hormone secretion represent implicated mechanistic intermediaries in TMP/SMX-induced hyponatremia. PATIENT CONCERNS: The patient endorsed no explicit concerns. DIAGNOSES: We describe the case of an 83-year-old female clinically diagnosed with pneumonia found to have an initial serum sodium in the range of 130 to 134âmEq/L consistent with mild hyponatremia upon admission. Sputum cultures grew Achromobacter xylosoxidans susceptible to TMP/SMX. The patient's serum sodium concentration precipitously decline following institution of treatment with TMP/SMX to 112 to 114âmEq/L during the course of 5 days. INTERVENTIONS: Severe hyponatremia proved recalcitrant to initial therapy with supplemental salt tabs and standard doses of the vasopressin receptor antagonist tolvaptan. OUTCOMES: Escalating doses of tolvaptan increased the patient's sodium to 120 to 124âmEq/L. The patient was transferred to another hospital for further management. During her stay, the patient did not exhibit frank or obvious clinical features consistent with hyponatremia nor readily appreciable evidence of volume depletion. LESSONS: TMP/SMX represents a frequent, though underreported cause of hyponatremia in the hospital setting several authors believe natriuresis may represent the most common mechanism underlying TMP/SMX-induced hyponatremia. Evidence implicating natriuresis to be mechanistic in TMP/SMX-induced hyponatremia include clinically appreciable hypovolemia and resolution of hyponatremia with oral or intravenous salt repletion. Salt repletion failed to monotherapeutically enhance our patient's hyponatremiadisfavoring renal salt wasting as originately mechanistic. Contemporaneous refractoriness of serum sodium to fluid restriction nor standard doses of tolvaptan confounded our initial attempts to mechanistically attribute the patient's hyponatremia to a specific cause. Clinical euvolemia and rapid response of hyponatremia to exceptionally high doses of tolvaptan strongly favors syndrome of inappropriate antidiuretic hormone to represent the chief mechanism by which TMP/SMX exacerbates hyponatremia.
Subject(s)
Achromobacter denitrificans , Anti-Bacterial Agents/adverse effects , Gram-Negative Bacterial Infections/drug therapy , Hyponatremia/chemically induced , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Diagnosis, Differential , Female , Gram-Negative Bacterial Infections/blood , Gram-Negative Bacterial Infections/complications , Humans , Hyponatremia/complications , Hyponatremia/physiopathology , Hyponatremia/therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
OBJECTIVE: In this study, we examined the effect of acute hyponatremia associated with vasopressin (AVP) on the responses of the isolated rat's MCAs and PAs to acidosis, nitric oxide donor (SNAP) and to endothelium-dependent vasodilator ATP. METHODS: The studies were performed on isolated, perfused and pressurized MCAs and PAs in control conditions and during AVP-associated hyponatremia. Hyponatremia was induced in vitro by lowering Na+ concentration from 144 to 121 mmol/L in intra- and extravascular fluid in the presence of AVP. RESULTS: Parenchymal arterioles showed greater response to an increase in H+ and K+ ions concentration and to ATP in comparison with MCAs in control normonatremic conditions. Both PAs and MCAs constricted in response to acute hyponatremia associated with AVP. Interestingly, disordered regulation of vascular tone was observed in PAs but not in MCAs. The abnormalities in the regulation comprised a significant reduction of PA response to acidosis and the absence of the response to the administration of SNAP or ATP. CONCLUSIONS: Arginine vasopressin-associated hyponatremia leads to constriction and dysregulation of PAs which may impair neurovascular coupling.
Subject(s)
Arterioles/physiopathology , Brain/blood supply , Brain/physiopathology , Hyponatremia/physiopathology , Acidosis/physiopathology , Acute Disease , Adenosine Triphosphate/pharmacology , Animals , Arginine Vasopressin/administration & dosage , Arginine Vasopressin/physiology , Arterioles/drug effects , Disease Models, Animal , Humans , Hyponatremia/etiology , In Vitro Techniques , Male , Middle Cerebral Artery/drug effects , Middle Cerebral Artery/physiopathology , Nitric Oxide Donors/pharmacology , Rats , Rats, Wistar , S-Nitroso-N-Acetylpenicillamine/pharmacology , Vasoconstriction/drug effects , Vasoconstriction/physiologyABSTRACT
Clinical symptoms of active tuberculosis (TB) can range from a simple cough to more severe reactions, such as irreversible lung damage and, eventually, death, depending on disease progression. In addition to its clinical presentation, TB has been associated with several other disease-induced systemic complications, such as hyponatremia and glucose intolerance. Here, we provide an overview of the known, although ill-described, underlying biochemical mechanisms responsible for the clinical and systemic presentations associated with this disease and discuss novel hypotheses recently generated by various omics technologies. This summative update can assist clinicians to improve the tentative diagnosis of TB based on a patient's clinical presentation and aid in the development of improved treatment protocols specifically aimed at restoring the disease-induced imbalance for overall homeostasis while simultaneously eradicating the pathogen. Furthermore, future applications of this knowledge could be applied to personalized diagnostic and therapeutic options, bettering the treatment outcome and quality of life of TB patients.
Subject(s)
Glucose Intolerance/etiology , Hyponatremia/etiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/physiopathology , Diagnosis, Differential , Glucose Intolerance/physiopathology , Humans , Hyponatremia/physiopathology , Precision Medicine , Tuberculosis, Pulmonary/diagnosisABSTRACT
A 57-year-old woman presented with severe lethargy, dizziness and nausea 1 week after transsphenoidal resection of a growth hormone secreting pituitary adenoma. She was found to have severe hyponatremia of 115 mmol/L. Importantly, she was neurologically intact and clinically euvolaemic. Her fluid intake was restricted and her sodium levels increased to 131 mmol/L over 4 days. She made a full recovery.She was diagnosed with isolated second-phase diabetes insipidus, a state of symptomatic hypoosmolar hyponatremia that usually occurs 7-10 days after transsphenoidal surgery. The sodium levels improve with fluid restriction.
Subject(s)
Adenoma/surgery , Drinking Water , Hyponatremia , Hypophysectomy , Pituitary Neoplasms/surgery , Postoperative Complications , Water-Electrolyte Imbalance/therapy , Adenoma/metabolism , Adenoma/pathology , Diet Therapy/methods , Dizziness/diagnosis , Dizziness/etiology , Female , Humans , Hyponatremia/blood , Hyponatremia/etiology , Hyponatremia/physiopathology , Hyponatremia/therapy , Hypophysectomy/adverse effects , Hypophysectomy/methods , Lethargy/diagnosis , Lethargy/etiology , Middle Aged , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Postoperative Complications/blood , Postoperative Complications/physiopathology , Postoperative Complications/therapy , Sphenoid Bone/surgery , Treatment OutcomeABSTRACT
Retrospective single institution observational study.The aim of the present study was to analyze the influence of early extensive posterior decompression on complications in patients with severe traumatic cervical spinal cord injury (tcSCI).Cervical SCI is associated with a high prevalence of hyponatremia and cardiopulmonary dysfunction. However, very few studies have focused on this exploration to reduce the incidence of SCI early complications.We reviewed the medical records of consecutive patients undergoing extensive posterior decompression within 24âh for severe tcSCI (American Spinal Injury Association Impairment Scale [AIS] A to C) admitted between January 2009 and January 2018. The data collected retrospectively included age, gender, mechanism, and level of SCI, AIS grade, fracture or dislocation, electrolyte, and cardiopulmonary complications.Of the 97 enrolled patients, the baseline AIS grade was AIS A in 14, AIS B in 31, and AIS C in 52. Improvement of at least two AIS grades was found in 26 (26.8%), and improvement of at least one grade was found in 80.4% of patients at discharge. Twenty-nine (29.9%) patients had mild hyponatremia, 8 (8.2%) had moderate hyponatremia, and 3 (3.1%) had severe hyponatremia during hospitalization. The incidences of hyponatremia, hypotension, and tracheotomy were 41.2%, 13.4%, and 6.2%, respectively. The mean forced vital capacity (FVC) on admission and at discharge was 1.34â±â0.46âL and 2.21â±â0.41âL (Pâ<â.0001), respectively. Five patients developed pneumonia.Our results suggest that early expansive posterior decompression significantly reduces the incidence of hyponatremia, hypotension, and tracheotomy by promoting recovery of spinal cord function after severe tcSCI.