Materiały źródłowe

• #1 Hyponatremia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470386/

  Hyponatremia is defined as a serum sodium concentration of less than 135 mEq/L but can vary to a small extent in different laboratories. Hyponatremia is a common electrolyte abnormality caused by an excess of total body water when compared to total body sodium content. Edelman discovered that serum sodium concentration does not depend on total body sodium but the ratio of total body solutes (e.g., total body sodium and total body potassium) to total body water. Hyponatremia represents an imbalance in this ratio where total body water is more than total body solutes. […] Thirst stimulation, antidiuretic hormone (ADH) secretion, and handling of filtered sodium by kidneys maintain serum sodium and osmolality. Normal plasma osmolality is around 275 mOsm/kg to 290 mOsm/kg. To maintain normal osmolality, water intake should be equal to water excretion. The imbalance of water intake and excretion causes hyponatremia or hypernatremia. Water intake is regulated by the thirst mechanism, where osmoreceptors in the hypothalamus trigger thirst when body osmolality reaches 295 mOsm/kg. Water excretion is tightly regulated by antidiuretic hormone (ADH), synthesized in the hypothalamus, and stored in the posterior pituitary gland. Changes in tonicity lead to either enhancement or suppression of ADH secretion. Increased ADH secretion causes reabsorption of water in the kidney, and suppression causes the opposite effect.

• #2

  https://link.springer.com/article/10.1007/s10157-025-02624-9

  Hyponatremia is a water and electrolyte abnormality frequently observed in the general population that often is not appropriately diagnosed or effectively treated. […] Hyponatremia can result from various etiologies, ranging from the most common such as the syndrome of inappropriate antidiuresis (SIAD) and medication-induced hyponatremia, to the less common such as adrenal insufficiency and salt-losing nephropathy. […] Clinicians should promptly recognize hyponatremia in order to appropriately treat it, since not only acute moderate-to-severe symptomatic hyponatremia but also chronic mild symptomatic hyponatremia are associated with unfavorable outcomes. Therefore, this review details the pathophysiology, symptoms, adverse outcomes, and evaluation of hyponatremia to assist clinicians in clinical practice.

• #3 Hyponatremia – Sodium Disturbances – Electrolyte Disturbances – Electrolyte, Fluid, and Acid-Base Balance Disorders – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.19.1.3.1.

  Hyponatremia is defined as a serum [Na+] 135 mmol/L. […] In the majority of cases, hyponatremia is a consequence of water disturbances that result in a relative excess of body water compared with the body sodium content. The most frequent cause is impaired renal free water excretion due to inappropriate arginine vasopressin (AVP) hypersecretion caused by nonosmotic factors. […] Less frequently, the relative excess of body water may be due to excessive free water intake, which exceeds renal capacity for free water excretion. […] The most frequent cause of hypotonic hyponatremia is water retention due to syndrome of inappropriate antidiuresis (SIAD) (previously syndrome of inappropriate antidiuretic hormone secretion [SIADH]). […] Hypotonic hyponatremia with hypovolemia is caused by sodium and water loss that is partially replaced with fluids containing no electrolytes.

• #4 Hyponatremia | Diagnosis & Disease Information – Renal and Urology News

  https://www.renalandurologynews.com/ddi/hyponatremia/

  Hyponatremia is an electrolyte disorder characterized by serum sodium concentrations of less than 135 mEq/L. It usually occurs when an excessive amount of water is retained in cells relative to sodium. This may occur via ingestion of fluids or administration of intravenous fluids. A reduction in extracellular sodium may be the result of the following: An accumulation of extracellular solutes, such as glucose, cause water to shift from the cell; The body retains too much water; Sodium is lost; or Extracellular sodium shifts into the cell. […] Normally, reductions in extracellular sodium levels suppress the release of antidiuretic hormone (ADH), which in turn causes excretion of the excess fluid and corrects hyponatremia. Chronically decreased blood levels of sodium, however, indicate a problem with this corrective process, possibly as a result of the following: Ingesting more water than the kidneys can process; Renal failure; Reduced passing of glomerular filtrate to the distal nephron; and Inappropriate presence of ADH.

• #5 Hyponatremia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470386/

  Hyponatremia is defined as a serum sodium concentration of less than 135 mEq/L but can vary to a small extent in different laboratories. Hyponatremia is a common electrolyte abnormality caused by an excess of total body water when compared to total body sodium content. Edelman discovered that serum sodium concentration does not depend on total body sodium but the ratio of total body solutes (e.g., total body sodium and total body potassium) to total body water. Hyponatremia represents an imbalance in this ratio where total body water is more than total body solutes. […] Thirst stimulation, antidiuretic hormone (ADH) secretion, and handling of filtered sodium by kidneys maintain serum sodium and osmolality. Normal plasma osmolality is around 275 mOsm/kg to 290 mOsm/kg. To maintain normal osmolality, water intake should be equal to water excretion. The imbalance of water intake and excretion causes hyponatremia or hypernatremia. Water intake is regulated by the thirst mechanism, where osmoreceptors in the hypothalamus trigger thirst when body osmolality reaches 295 mOsm/kg. Water excretion is tightly regulated by antidiuretic hormone (ADH), synthesized in the hypothalamus, and stored in the posterior pituitary gland. Changes in tonicity lead to either enhancement or suppression of ADH secretion. Increased ADH secretion causes reabsorption of water in the kidney, and suppression causes the opposite effect.

• #6 Hyponatremia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242166-overview

  Hypo-osmolality (serum osmolality 275 mOsm/kg) always indicates excess total body water relative to body solutes or excess water relative to solute in the extracellular fluid (ECF), as water moves freely between the intracellular and the extracellular compartments. This imbalance can be due to solute depletion, solute dilution, or a combination of both. […] Under normal conditions, renal handling of water is sufficient to excrete as much as 15-20 L of free water per day. Further, the body’s response to a decreased osmolality is decreased thirst. Thus, hyponatremia can occur only when some condition impairs normal free-water excretion. […] Generally, hyponatremia is of clinical significance when it reflects a drop in the serum osmolality (ie, hypotonic hyponatremia), which is measured directly via osmometry or is calculated as 2(Na) mEq/L + serum glucose (mg/dL)/18 + BUN (mg/dL)/2.8. Note that urea is not an ineffective osmole, so when the urea levels are very high (as in azotemia), the measured osmolality should be corrected for the contribution of urea (measured serum osmolality BUN (mg/dL)/2.8).

• #7 Hyponatremia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hyponatremia_pathophysiology

  Hyponatremia is defined as serum sodium less than 135 mEq/L (mmol/L). Sodium is the major electrolyte which determines serum osmolality. Hyponatremia is a water balance disorder in which the ratio between sodium and water is disturbed. Water homeostasis is regulated mainly by two organs: hypothalamus by ADH secretion or thirst, kidney by water reabsorption or excretion. ADH is secreted due to alteration in serum osmolality or intravascular volume. Mechanisms in which different disorders cause hyponatremia involve ADH (secretion or action) and kidney function (absorption or excretion). ADH secretion is increased by increased osmolality of serum or decreased effective intravascular volume. […] Sodium is the main cation in the extracellular fluid, thus the plasma concentration of sodium is the determinant of tonicity and serum osmolality.

• #8 Hyponatremia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hyponatremia_pathophysiology

  Plasma water is regulated by sensory organs (baroreceptors and hypothalamus osmoreceptors), antidiuretic hormone (ADH or vasopressin, AVP), and the kidney. […] Osmoreceptors in the hypothalamus are sensitive to the increased or decreased tonicity of serum (magnocellular neurons). The primary brain osmoreceptors are located outside the blood-brain barrier in the lamina terminalis. Primary osmoreceptors are connected to brain areas responsible for ADH secretion and thirst by neuronal projections. Osmoreceptors can both stimulate and inhibit ADH secretion and thirst in response to hyper-and hypotonicity of serum, respectively. […] ADH secretion from hypothalamus through posterior pituitary is increased by: Angiotensin II (through activation of Renin-Angiotensin-Activation System), Sympathetic stimulation, Effective osmoles (Hypertonicity), Baroreceptor firing (effective intravascular volume), Right atrium stretching.

• #9 Hyponatremia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242166-overview

  Hypo-osmolality (serum osmolality 275 mOsm/kg) always indicates excess total body water relative to body solutes or excess water relative to solute in the extracellular fluid (ECF), as water moves freely between the intracellular and the extracellular compartments. This imbalance can be due to solute depletion, solute dilution, or a combination of both. […] Under normal conditions, renal handling of water is sufficient to excrete as much as 15-20 L of free water per day. Further, the body’s response to a decreased osmolality is decreased thirst. Thus, hyponatremia can occur only when some condition impairs normal free-water excretion. […] Generally, hyponatremia is of clinical significance when it reflects a drop in the serum osmolality (ie, hypotonic hyponatremia), which is measured directly via osmometry or is calculated as 2(Na) mEq/L + serum glucose (mg/dL)/18 + BUN (mg/dL)/2.8. Note that urea is not an ineffective osmole, so when the urea levels are very high (as in azotemia), the measured osmolality should be corrected for the contribution of urea (measured serum osmolality BUN (mg/dL)/2.8).

• #10 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Hyponatremia results from the inability of the kidney to excrete a water load or excess water intake. Water intake depends upon thirst mechanism. Thirst is stimulated by increase in osmolality. Thirst is sensed by osmoreceptors located in the hypothalamus and leads to the release of anti-diuretic hormone (vasopressin) from the posterior pituitary. Antidiuretic hormone acts on the V2 receptors located at the basolateral aspect of the collecting duct cells and leads to increased aquaporin expression on the luminal aspect of the collecting duct cells which increases water absorption and abolishes thirst. […] Hyponatremia occurs if there is persistent ADH stimulation which is seen in following situations. […] Normal but persistent ADH secretion-In volume depletion the effect of decreased volume counteracts the effect of hypoosmolality and ADH stimulation continues to occur. Effective arterial blood volume depletion occurs by two mechanisms: True volume depletion; and in edematous patients with heart failure or cirrhosis in whom tissue perfusion is reduced because of a low cardiac output or arterial vasodilation, respectively.

• #11 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  This enhances osmotic water reabsorption through the upregulation of the aquaporin-2 (AQP2) water channel. […] Even low doses of desmopressin can induce hyponatremia in susceptible patients with nocturnal polyuria because an advanced age is an important risk factor for hyponatremia. […] Oxytocin may also induce hyponatremia when it is used in obstetrics to induce abortion and to induce or augment labor. […] In brief, pharmacological doses of oxytocin can induce antidiuretic effects as a result of V2R stimulation and subsequent AQP2 upregulation. […] Hyponatremia is a common complication in cancer patients because SIAD is potentially caused by malignancies and it can be related to anticancer medical therapy as well. […] Previous studies have shown that SIADH underlies the mechanism of vincristine-associated hyponatremia.

• #12 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Hyponatremia results from the inability of the kidney to excrete a water load or excess water intake. Water intake depends upon thirst mechanism. Thirst is stimulated by increase in osmolality. Thirst is sensed by osmoreceptors located in the hypothalamus and leads to the release of anti-diuretic hormone (vasopressin) from the posterior pituitary. Antidiuretic hormone acts on the V2 receptors located at the basolateral aspect of the collecting duct cells and leads to increased aquaporin expression on the luminal aspect of the collecting duct cells which increases water absorption and abolishes thirst. […] Hyponatremia occurs if there is persistent ADH stimulation which is seen in following situations. […] Normal but persistent ADH secretion-In volume depletion the effect of decreased volume counteracts the effect of hypoosmolality and ADH stimulation continues to occur. Effective arterial blood volume depletion occurs by two mechanisms: True volume depletion; and in edematous patients with heart failure or cirrhosis in whom tissue perfusion is reduced because of a low cardiac output or arterial vasodilation, respectively.

• #13 Management of Hyponatremia: Focus on Psychiatric Patients

  https://www.uspharmacist.com/article/management-of-hyponatremia

  Hyponatremia, the most commonly encountered electrolyte disorder in clinical practice, is associated with increased mortality. […] Hyponatremia induced by SIADH (syndrome of inappropriate antidiuretic hormone secretion) and psychogenic polydipsia require significant pharmacist interventions and are frequently seen in psychiatric patients. […] The mechanism by which hyponatremia develops varies according to disease state, and arginine vasopressin (AVP) regularly plays a critical role in both hypervolemic and euvolemic hyponatremia. […] However, patients with hyponatremia are unable to suppress AVP due to true volume depletion, effective volume depletion, or an inappropriate increase in AVP secretion. […] In SIADH, AVP release is increased despite plasma osmolality, which can be due to various medications. […] The pathogenesis of psychogenic polydipsia is multifactorial, with an abnormal hypothalamic thirst center as a likely cause. […] Patients tend to have a difference in the set points of ADH and thirst suppression.

• #14 Antidepressants and the risk of hyponatremia: a Danish register-based population study | BMJ Open

  https://bmjopen.bmj.com/content/6/5/e011200

  Hyponatremia is one of the many well-known side effects of antidepressants. Even mild hyponatremia is associated with instability and falls, reduced cognitive function, osteoporosis and increased morbidity and mortality. The presence of hypotonic hyponatremia always implies excess of water, and hyponatremia essentially is a water balance disorder. In most cases of hypotonic hyponatremia, ADH secretion is increased due to one of the following reasons: (1) appropriate response to decreased effective plasma volume as in hypovolaemia, cirrhosis and heart failure; (2) ectopic production as seen in neoplastic diseases resulting in syndrome of inappropriate ADH (SIADH); or (3) syndrome of inappropriate antidiuresis (SIAD) either due to a drug induced increase in ADH production (SIADH) or an enhanced renal response to ADH, the nephrogenic syndrome of antidiuresis.

• #15 Management of Hyponatremia: Focus on Psychiatric Patients

  https://www.uspharmacist.com/article/management-of-hyponatremia

  Hyponatremia, the most commonly encountered electrolyte disorder in clinical practice, is associated with increased mortality. […] Hyponatremia induced by SIADH (syndrome of inappropriate antidiuretic hormone secretion) and psychogenic polydipsia require significant pharmacist interventions and are frequently seen in psychiatric patients. […] The mechanism by which hyponatremia develops varies according to disease state, and arginine vasopressin (AVP) regularly plays a critical role in both hypervolemic and euvolemic hyponatremia. […] However, patients with hyponatremia are unable to suppress AVP due to true volume depletion, effective volume depletion, or an inappropriate increase in AVP secretion. […] In SIADH, AVP release is increased despite plasma osmolality, which can be due to various medications. […] The pathogenesis of psychogenic polydipsia is multifactorial, with an abnormal hypothalamic thirst center as a likely cause. […] Patients tend to have a difference in the set points of ADH and thirst suppression.

• #16 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Abnormal ADH secretion e.g. Syndrome of inappropriate ADH release described below (SIADH). […] Pathogenesis of hyponatremia in SIADH: Plasma sodium concentration (PNa) is given by ratio of the body’s content of exchangeable sodium and potassium (NaE and KE) and total body water (TBW): PNa NaE + KE/TBW. TBW depends on urine volume. Urine volume cannot be increased in SIADH. This occurs because of defects in Antidiuretic hormone (ADH, arginine vasopressin) secretion. […] Patterns of ADH secretion: In normal individuals, plasma ADH levels is suppressed when the plasma osmolality is below 280mosmol/kg, thus ingested water is excreted and ADH levels increase as the plasma osmolality rises above 280mosmol/kg. […] ADH regulation is impaired in SIADH and four different patterns are seen: Type A there is unregulated release of ADH that has no relation to plasma osmolality. Plasma ADH levels are above that required for maximum antidiuresis, so urine osmolality is very high

• #17 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  The term SIAD was proposed by Dr. Robertson because plasma vasopressin levels were suppressed in a subgroup of patients who were diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). A diagnosis of SIADH can be made when unsuppressed levels of arginine vasopressin (AVP) are detected. However, in clinical practice, ‘SIADH’ is used interchangeably with ‘SIAD’ because the clinical features are identical and accurate measurement of plasma AVP levels is clinically impractical. […] The reason why a subset of hyponatremic patients with the SIADH phenotype shows suppressed plasma AVP levels was elucidated partly by Feldman et al. They described two infants whose clinical and laboratory findings were consistent with SIADH but had undetectable plasma AVP levels because of gain-of-function mutations in the vasopressin V2 receptor (V2R), and coined the term ‘nephrogenic syndrome of inappropriate antidiuresis (NSIAD)’. Thus, SIAD caused by renal water retention can be classified into SIADH (with an excess of plasma AVP) and NSIAD (with appropriately suppressed plasma AVP) according to different etiologies.

• #18 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Abnormal ADH secretion e.g. Syndrome of inappropriate ADH release described below (SIADH). […] Pathogenesis of hyponatremia in SIADH: Plasma sodium concentration (PNa) is given by ratio of the body’s content of exchangeable sodium and potassium (NaE and KE) and total body water (TBW): PNa NaE + KE/TBW. TBW depends on urine volume. Urine volume cannot be increased in SIADH. This occurs because of defects in Antidiuretic hormone (ADH, arginine vasopressin) secretion. […] Patterns of ADH secretion: In normal individuals, plasma ADH levels is suppressed when the plasma osmolality is below 280mosmol/kg, thus ingested water is excreted and ADH levels increase as the plasma osmolality rises above 280mosmol/kg. […] ADH regulation is impaired in SIADH and four different patterns are seen: Type A there is unregulated release of ADH that has no relation to plasma osmolality. Plasma ADH levels are above that required for maximum antidiuresis, so urine osmolality is very high

• #19 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Type B there is a modest and constant leak of ADH. […] Type C- there is downward resetting of osmostat. It is a variant of SIADH in which the plasma sodium concentration is normally regulated and is stable at a lower level (125 -135 meq/L) […] Type D- is the least common. Osmoregulation is normal (i.e. ADH secretion varies appropriately with the plasma osmolality), but the urine is concentrated even with suppressed ADH release. There are 3 mechanisms (a) germ cell mutation in which the V2 vasopressin receptor is activated. (b) Production of antidiuretic compound other than AVP and (3) a postreceptor defect in trafficking of aquaporin-2 water channels, which mediate ADH action.

• #20 Hyponatremia: A practical approach

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4192979/

  Type B there is a modest and constant leak of ADH. […] Type C- there is downward resetting of osmostat. It is a variant of SIADH in which the plasma sodium concentration is normally regulated and is stable at a lower level (125 -135 meq/L) […] Type D- is the least common. Osmoregulation is normal (i.e. ADH secretion varies appropriately with the plasma osmolality), but the urine is concentrated even with suppressed ADH release. There are 3 mechanisms (a) germ cell mutation in which the V2 vasopressin receptor is activated. (b) Production of antidiuretic compound other than AVP and (3) a postreceptor defect in trafficking of aquaporin-2 water channels, which mediate ADH action.

• #21 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  The term SIAD was proposed by Dr. Robertson because plasma vasopressin levels were suppressed in a subgroup of patients who were diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). A diagnosis of SIADH can be made when unsuppressed levels of arginine vasopressin (AVP) are detected. However, in clinical practice, ‘SIADH’ is used interchangeably with ‘SIAD’ because the clinical features are identical and accurate measurement of plasma AVP levels is clinically impractical. […] The reason why a subset of hyponatremic patients with the SIADH phenotype shows suppressed plasma AVP levels was elucidated partly by Feldman et al. They described two infants whose clinical and laboratory findings were consistent with SIADH but had undetectable plasma AVP levels because of gain-of-function mutations in the vasopressin V2 receptor (V2R), and coined the term ‘nephrogenic syndrome of inappropriate antidiuresis (NSIAD)’. Thus, SIAD caused by renal water retention can be classified into SIADH (with an excess of plasma AVP) and NSIAD (with appropriately suppressed plasma AVP) according to different etiologies.

• #22 Hyponatremia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hyponatremia

  Hyponatremia reflects an excess of total body water (TBW) relative to total body sodium content. […] In hypovolemic hyponatremia, both serum osmolality and blood volume decrease. Vasopressin (antidiuretic hormone [ADH]) secretion increases despite a decrease in osmolality to maintain blood volume. The resulting water retention increases plasma dilution and hyponatremia. […] Renal fluid losses resulting in hypovolemic hyponatremia may occur with mineralocorticoid deficiency, thiazide diuretic therapy, osmotic diuresis, or salt-losing nephropathy. […] In euvolemic (dilutional) hyponatremia, total body sodium and thus ECF volume are normal or near-normal; however, TBW is increased. […] The syndrome of inappropriate ADH (vasopressin) secretion is attributed to excessive vasopressin release.

• #23 Hyponatremia | Diagnosis & Disease Information – Renal and Urology News

  https://www.renalandurologynews.com/ddi/hyponatremia/

  Potential causes of hypovolemic hyponatremia include renal sodium loss due to diuretics, mineralocorticoid deficiency, nephropathy, metabolic alkalosis, or cerebral salt wasting. It also can be the result of nonrenal causes of fluid loss, such as vomiting, diarrhea, burns, pancreatitis, or trauma. Euvolemic hyponatremia may be due to glucocorticoid deficiency, hypothyroidism, stress, select medications and illicit drugs, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hypervolemic hyponatremia can be caused by renal failure, nephrotic syndrome, cirrhosis, and heart failure. […] Many conditions are associated with inappropriate ADH secretion and thus can result in hyponatremia. These include the following: Tumor-related conditions (cancers of the lung, pancreas, duodenum, ureter, bladder, and prostate, as well as lymphoma, thymoma, mesothelioma, and Ewing sarcoma); Lung problems (pneumonia, tuberculosis, aspergillosis, asthma, pneumothorax, cystic fibrosis, abscesses); Central nervous system problems (delirium tremens, seizures, Shy-Drager syndrome, Rocky Mountain spotted fever, lupus cerebritis, cavernous vein thrombosis, hydrocephalus, multiple sclerosis, schizophrenia, brain atrophy, encephalitis or meningitis, brain tumors or abscesses, head trauma, subdural hematoma, stroke, Guillain-Barr syndrome); Medication adverse effects (haloperidol, phenothiazines, opiates, selective serotonin reuptake inhibitors, tricyclic antidepressants, cyclophosphamide, vinca alkaloids, carbamazepine, clofibrate, sulfonylureas, arginine vasopressin); and Endocrine conditions (deficiency of glucocorticoids, myxedema).

• #24 Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0301/p299.html

  The most common classification system for hyponatremia is based on volume status: hypovolemic (decreased total body water with greater decrease in sodium level), euvolemic (increased total body water with normal sodium level), and hypervolemic (increased total body water compared with sodium). […] Severe symptomatic hyponatremia occurs when sodium levels decrease over less than 24 hours. Severe symptoms (e.g., coma, seizures) typically occur when the sodium level falls below 120 mEq per L, but can occur at less than 125 mEq per L. Severe symptomatic hyponatremia must be corrected promptly because it can lead to cerebral edema, irreversible neurologic damage, respiratory arrest, brainstem herniation, and death. […] Hypervolemic hyponatremia occurs when the kidneys cannot excrete water efficiently. In volume overload states, the effective arterial blood volume is decreased compared with venous volume, resulting in excess ADH secretion. The most common causes of hypervolemic hyponatremia are heart failure, cirrhosis, and kidney injury.

• #25 Hyponatremia – Sodium Disturbances – Electrolyte Disturbances – Electrolyte, Fluid, and Acid-Base Balance Disorders – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.19.1.3.1.

  Hyponatremia is defined as a serum [Na+] 135 mmol/L. […] In the majority of cases, hyponatremia is a consequence of water disturbances that result in a relative excess of body water compared with the body sodium content. The most frequent cause is impaired renal free water excretion due to inappropriate arginine vasopressin (AVP) hypersecretion caused by nonosmotic factors. […] Less frequently, the relative excess of body water may be due to excessive free water intake, which exceeds renal capacity for free water excretion. […] The most frequent cause of hypotonic hyponatremia is water retention due to syndrome of inappropriate antidiuresis (SIAD) (previously syndrome of inappropriate antidiuretic hormone secretion [SIADH]). […] Hypotonic hyponatremia with hypovolemia is caused by sodium and water loss that is partially replaced with fluids containing no electrolytes.

• #26 Hyponatremia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hyponatremia

  Hyponatremia reflects an excess of total body water (TBW) relative to total body sodium content. […] In hypovolemic hyponatremia, both serum osmolality and blood volume decrease. Vasopressin (antidiuretic hormone [ADH]) secretion increases despite a decrease in osmolality to maintain blood volume. The resulting water retention increases plasma dilution and hyponatremia. […] Renal fluid losses resulting in hypovolemic hyponatremia may occur with mineralocorticoid deficiency, thiazide diuretic therapy, osmotic diuresis, or salt-losing nephropathy. […] In euvolemic (dilutional) hyponatremia, total body sodium and thus ECF volume are normal or near-normal; however, TBW is increased. […] The syndrome of inappropriate ADH (vasopressin) secretion is attributed to excessive vasopressin release.

• #27 Hyponatremia – Sodium Disturbances – Electrolyte Disturbances – Electrolyte, Fluid, and Acid-Base Balance Disorders – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.19.1.3.1.

  Hypotonic hyponatremia with euvolemia, the most frequent type of hyponatremia, is caused by SIAD (see above), glucocorticoid deficiency, use of thiazide diuretics, prolonged strenuous exercise, primary polydipsia, long-term use of a low-sodium diet, hypothyroidism, increased sensitivity to AVP, or mutations of genes encoding V2 or aquaporin 2 receptors. […] Hypotonic hyponatremia with hypervolemia is caused by increased AVP secretion in patients with a relative decrease in effective intravascular volume (chronic heart failure [HF], cirrhosis with ascites, nephrotic syndrome with edema) or by excessive intake of fluids containing no electrolytes in patients with impaired free water excretion (acute kidney injury, advanced chronic kidney disease). […] Nonhypotonic (isotonic or hypertonic) hyponatremia, also called translocational hyponatremia, is caused by an increase in plasma concentrations of effective osmolytes leading to a shift of water from the ICF to the ECF and subsequent hyponatremia due to dilution. […] The most frequent cause is severe hyperglycemia. […] Pseudohyponatremia is a falsely low serum [Na+] caused by high plasma lipid or paraprotein levels.

• #28 Hyponatremia | Diagnosis & Disease Information – Renal and Urology News

  https://www.renalandurologynews.com/ddi/hyponatremia/

  Potential causes of hypovolemic hyponatremia include renal sodium loss due to diuretics, mineralocorticoid deficiency, nephropathy, metabolic alkalosis, or cerebral salt wasting. It also can be the result of nonrenal causes of fluid loss, such as vomiting, diarrhea, burns, pancreatitis, or trauma. Euvolemic hyponatremia may be due to glucocorticoid deficiency, hypothyroidism, stress, select medications and illicit drugs, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hypervolemic hyponatremia can be caused by renal failure, nephrotic syndrome, cirrhosis, and heart failure. […] Many conditions are associated with inappropriate ADH secretion and thus can result in hyponatremia. These include the following: Tumor-related conditions (cancers of the lung, pancreas, duodenum, ureter, bladder, and prostate, as well as lymphoma, thymoma, mesothelioma, and Ewing sarcoma); Lung problems (pneumonia, tuberculosis, aspergillosis, asthma, pneumothorax, cystic fibrosis, abscesses); Central nervous system problems (delirium tremens, seizures, Shy-Drager syndrome, Rocky Mountain spotted fever, lupus cerebritis, cavernous vein thrombosis, hydrocephalus, multiple sclerosis, schizophrenia, brain atrophy, encephalitis or meningitis, brain tumors or abscesses, head trauma, subdural hematoma, stroke, Guillain-Barr syndrome); Medication adverse effects (haloperidol, phenothiazines, opiates, selective serotonin reuptake inhibitors, tricyclic antidepressants, cyclophosphamide, vinca alkaloids, carbamazepine, clofibrate, sulfonylureas, arginine vasopressin); and Endocrine conditions (deficiency of glucocorticoids, myxedema).

• #29 Hyponatremia – Sodium Disturbances – Electrolyte Disturbances – Electrolyte, Fluid, and Acid-Base Balance Disorders – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.19.1.3.1.

  Hypotonic hyponatremia with euvolemia, the most frequent type of hyponatremia, is caused by SIAD (see above), glucocorticoid deficiency, use of thiazide diuretics, prolonged strenuous exercise, primary polydipsia, long-term use of a low-sodium diet, hypothyroidism, increased sensitivity to AVP, or mutations of genes encoding V2 or aquaporin 2 receptors. […] Hypotonic hyponatremia with hypervolemia is caused by increased AVP secretion in patients with a relative decrease in effective intravascular volume (chronic heart failure [HF], cirrhosis with ascites, nephrotic syndrome with edema) or by excessive intake of fluids containing no electrolytes in patients with impaired free water excretion (acute kidney injury, advanced chronic kidney disease). […] Nonhypotonic (isotonic or hypertonic) hyponatremia, also called translocational hyponatremia, is caused by an increase in plasma concentrations of effective osmolytes leading to a shift of water from the ICF to the ECF and subsequent hyponatremia due to dilution. […] The most frequent cause is severe hyperglycemia. […] Pseudohyponatremia is a falsely low serum [Na+] caused by high plasma lipid or paraprotein levels.

• #30 Hyponatremia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hyponatremia

  Hypervolemic hyponatremia is characterized by an increase in both total body sodium (and thus ECF volume) and total body water with a relatively greater increase in TBW. Various edematous disorders, including heart failure and cirrhosis, cause hypervolemic hyponatremia. […] The following factors contribute to hyponatremia: The antidiuretic effect of vasopressin on the kidneys, Direct impairment of renal water excretion by angiotensin II, Decreased glomerular filtration rate (GFR), Stimulation of thirst by angiotensin II.

• #31 Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0301/p299.html

  The most common classification system for hyponatremia is based on volume status: hypovolemic (decreased total body water with greater decrease in sodium level), euvolemic (increased total body water with normal sodium level), and hypervolemic (increased total body water compared with sodium). […] Severe symptomatic hyponatremia occurs when sodium levels decrease over less than 24 hours. Severe symptoms (e.g., coma, seizures) typically occur when the sodium level falls below 120 mEq per L, but can occur at less than 125 mEq per L. Severe symptomatic hyponatremia must be corrected promptly because it can lead to cerebral edema, irreversible neurologic damage, respiratory arrest, brainstem herniation, and death. […] Hypervolemic hyponatremia occurs when the kidneys cannot excrete water efficiently. In volume overload states, the effective arterial blood volume is decreased compared with venous volume, resulting in excess ADH secretion. The most common causes of hypervolemic hyponatremia are heart failure, cirrhosis, and kidney injury.

• #32 Hyponatremia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hyponatremia

  Hypervolemic hyponatremia is characterized by an increase in both total body sodium (and thus ECF volume) and total body water with a relatively greater increase in TBW. Various edematous disorders, including heart failure and cirrhosis, cause hypervolemic hyponatremia. […] The following factors contribute to hyponatremia: The antidiuretic effect of vasopressin on the kidneys, Direct impairment of renal water excretion by angiotensin II, Decreased glomerular filtration rate (GFR), Stimulation of thirst by angiotensin II.

• #33 Pathophysiology of Hyponatremia in Heart Failure| SAMSCA® (tolvaptan)

  https://www.samsca.com/hyponatremia-heart-failure/pathophysiology

  Reduced cardiac output in heart failure stimulates the release of vasopressin, resulting in elevated levels of circulating vasopressin. […] Because vasopressin reduces the excretion of free water, elevated levels of vasopressin may contribute to the development of hyponatremia in heart failure patients. […] Reduced cardiac output and decreased renal perfusion activates the renin-angiotensin-aldosterone system in heart failure patients. […] The excess of angiotensin II in heart failure causes the following which further exacerbate dilutional hyponatremia: systemic and arteriolar vasoconstriction, increase in aldosterone concentration, increased thirst. […] In heart failure, water and sodium retention occur in response to aldosterone.

• #34 Hyponatremia – Sodium Disturbances – Electrolyte Disturbances – Electrolyte, Fluid, and Acid-Base Balance Disorders – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.19.1.3.1.

  Hypotonic hyponatremia with euvolemia, the most frequent type of hyponatremia, is caused by SIAD (see above), glucocorticoid deficiency, use of thiazide diuretics, prolonged strenuous exercise, primary polydipsia, long-term use of a low-sodium diet, hypothyroidism, increased sensitivity to AVP, or mutations of genes encoding V2 or aquaporin 2 receptors. […] Hypotonic hyponatremia with hypervolemia is caused by increased AVP secretion in patients with a relative decrease in effective intravascular volume (chronic heart failure [HF], cirrhosis with ascites, nephrotic syndrome with edema) or by excessive intake of fluids containing no electrolytes in patients with impaired free water excretion (acute kidney injury, advanced chronic kidney disease). […] Nonhypotonic (isotonic or hypertonic) hyponatremia, also called translocational hyponatremia, is caused by an increase in plasma concentrations of effective osmolytes leading to a shift of water from the ICF to the ECF and subsequent hyponatremia due to dilution. […] The most frequent cause is severe hyperglycemia. […] Pseudohyponatremia is a falsely low serum [Na+] caused by high plasma lipid or paraprotein levels.

• #35 Hypoosmolar hyponatremia with concentrated urine | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/electrolyte-disorders/Chapter-536/hypoosmolar-hyponatremia-concentrated-urine

  Third space distribution of fluid is the key factor in the mechanism of hyponatremia due to nephrotic syndrome. Because of the low serum protein, oncotic pressure is reduced and fluid migrates out of the intravascular compartment, reducing the effective circulating volume. Again, the renin-angiotensin-aldosterone system responds by increasing sodium and water retention. […] In hepatic and renal failure, there is loss of protein (by nephrotic syndrome or by decreased synthesis). With loss of serum oncotic pressure, circulating arterial volume is decreased as fluid migrates into the interstitial compartment. In response to this, there is a hypersecretion of ADH, which leads to increased water retention. […] The pathophysiology of this is incompletely understood, even though we have known about this since the 1950s. It does not seem to be a problem with inappropriate ADH hypersecretion, according to the more recent reviews. The vasopressin levels are usually high in these people but the mechanism seems to be a matter of ADH-induced water retention, in response to a decreased cardiac output which causes decreased renal blood flow. […] Elevated vasopressin levels tend to result in water retention, and a dilutional hyponatremia develops. These patients have no way of increasing their water excretion in response to an increased water intake. The urinary mechanisms of solute excretion remain intact, hence the high urinary sodium.

• #36 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  Four major causes of SIAD are malignancies, pulmonary diseases, disorders of the central nervous system, and drugs. According to case reports, many medications are associated with hyponatremia. However, whether they all have significant cause-and-effect relationships is unclear because incidental coexistences need to be excluded in rare cases. Regarding the mechanisms of drug-induced hyponatremia, stimulation of AVP release and enhancement of AVP action in the kidney have been postulated. However, the evidence for the former was limited, and the mechanisms of the latter were elusive. […] AVP analogs include desmopressin and oxytocin and can induce hyponatremia by acting as V2R agonists. Desmopressin selectively binds the V2R in the kidney and stimulates adenylyl cyclase activity and cAMP production in collecting duct epithelial cells.

• #37 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  This suggests exaggerated free water reabsorption or a volume-expanded diluted state. […] In particular, thiazides may act directly on the collecting duct, where water permeability is increased by vasopressin-independent mechanisms. […] A subgroup of patients with TIH may carry a variant allele of the prostaglandin transporter SLCO2A1 gene that leads to a reduced ability to transport prostaglandin E2 across the apical cell membrane in the collecting duct. […] The final common pathway is AQP2 upregulation in the collecting duct, involving various drugs at different levels. Only a few drugs such as vincristine and ifosfamide were reported to stimulate AVP release (SIADH). Others can induce hyponatremia via nephrogenic antidiuresis (NSIAD). Recent in vitro studies have shown that haloperidol, sertraline, carbamazepine, and cyclophosphamide act directly on the V2R in the collecting duct and upregulate AQP2 via activation of the cAMP-PKA pathway. In the absence of AVP, these drugs can act as V2R agonists in the kidney and lead to water retention. Thiazide diuretics not only act on distal convoluted tubules to inhibit the NCC but also on collecting ducts to upregulate AQP2. These actions impair urinary dilution and enhance urinary concentration, respectively, resulting in hyponatremia.

• #38 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  Furthermore, animal studies have suggested that SIADH may result from a direct toxic effect of vincristine on the neurohypophysis and the hypothalamic system. […] The mechanism of anticonvulsant-associated hyponatremia has generally been considered inappropriate hypersecretion of AVP, but an experimental study has indicated a direct effect of carbamazepine on the kidney through V2R stimulation without evidence of the increased release of endogenous AVP. […] It has become clear that carbamazepine has a direct action on the collecting duct V2R, leading to AQP2 upregulation. […] The mechanisms of TIH are complicated and not fully understood at present. […] Thiazides inhibit the Na-Cl cotransporter (NCC) in the distal convoluted tubule, the cortical diluting segment of the nephron. Thus, urine dilution is impaired and water can be retained by thiazides.

• #39 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  This suggests exaggerated free water reabsorption or a volume-expanded diluted state. […] In particular, thiazides may act directly on the collecting duct, where water permeability is increased by vasopressin-independent mechanisms. […] A subgroup of patients with TIH may carry a variant allele of the prostaglandin transporter SLCO2A1 gene that leads to a reduced ability to transport prostaglandin E2 across the apical cell membrane in the collecting duct. […] The final common pathway is AQP2 upregulation in the collecting duct, involving various drugs at different levels. Only a few drugs such as vincristine and ifosfamide were reported to stimulate AVP release (SIADH). Others can induce hyponatremia via nephrogenic antidiuresis (NSIAD). Recent in vitro studies have shown that haloperidol, sertraline, carbamazepine, and cyclophosphamide act directly on the V2R in the collecting duct and upregulate AQP2 via activation of the cAMP-PKA pathway. In the absence of AVP, these drugs can act as V2R agonists in the kidney and lead to water retention. Thiazide diuretics not only act on distal convoluted tubules to inhibit the NCC but also on collecting ducts to upregulate AQP2. These actions impair urinary dilution and enhance urinary concentration, respectively, resulting in hyponatremia.

• #40 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  This suggests exaggerated free water reabsorption or a volume-expanded diluted state. […] In particular, thiazides may act directly on the collecting duct, where water permeability is increased by vasopressin-independent mechanisms. […] A subgroup of patients with TIH may carry a variant allele of the prostaglandin transporter SLCO2A1 gene that leads to a reduced ability to transport prostaglandin E2 across the apical cell membrane in the collecting duct. […] The final common pathway is AQP2 upregulation in the collecting duct, involving various drugs at different levels. Only a few drugs such as vincristine and ifosfamide were reported to stimulate AVP release (SIADH). Others can induce hyponatremia via nephrogenic antidiuresis (NSIAD). Recent in vitro studies have shown that haloperidol, sertraline, carbamazepine, and cyclophosphamide act directly on the V2R in the collecting duct and upregulate AQP2 via activation of the cAMP-PKA pathway. In the absence of AVP, these drugs can act as V2R agonists in the kidney and lead to water retention. Thiazide diuretics not only act on distal convoluted tubules to inhibit the NCC but also on collecting ducts to upregulate AQP2. These actions impair urinary dilution and enhance urinary concentration, respectively, resulting in hyponatremia.

• #41 Inflammation and hyponatremia: an underrecognized condition?

  https://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2013.56.12.519

  Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1 and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. […] The development of hyponatremia is associated with various inflammatory diseases including pneumonia, severe acute respiratory distress syndrome, tuberculosis, meningitis, encephalitis, human immunodeficiency virus infection, and malaria. However, the pathophysiology of hyponatremia diagnosed under these inflammatory conditions remains elusive. Recent research revealed that inflammatory cytokines such as IL-1 and IL-6 are involved in the development of hyponatremia associated with inflammatory conditions, and that this process is related to ADH secretion.

• #42 The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barré syndrome | Nefrología

  https://www.revistanefrologia.com/en-the-role-interleukin-6-in-pathogenesis-hyponatremia-associated-with-guillain-barre-articulo-X0211699512000467

  We read with great interest the contribution by Monzn et al. They reported a significant case of a man who had Guillain-Barr syndrome (GBS) with syndrome of inappropriate antidiuretic hormone (SIADH) and speculated that increased sensitivity to vasopressin in the renal tubule and a long-lasting hypo-osmolarity or antidiuretic substances might cause GBS-related SIADH. However, we would like to add a possible pathomechanism in the development of hyponatremia associated with GBS. […] According to a previous study by Maimone et al., interleukin (IL)-6, a multifunctional cytokine, might be implicated in the immunopathogenesis of GBS. […] Furthermore, Mastorakos et al. reported that plasma antidiuretic hormone levels were elevated after IL-6 injection in cancer patients, suggesting that IL-6 activated the magnocellular ADH-secreting neurons and that it might be involved in SIADH. […] Therefore, there is a possibility that IL-6 may play a central role in the pathogenesis of hyponatremia associated with GBS.

• #43 Inflammation and hyponatremia: an underrecognized condition?

  https://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2013.56.12.519

  Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1 and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. […] The development of hyponatremia is associated with various inflammatory diseases including pneumonia, severe acute respiratory distress syndrome, tuberculosis, meningitis, encephalitis, human immunodeficiency virus infection, and malaria. However, the pathophysiology of hyponatremia diagnosed under these inflammatory conditions remains elusive. Recent research revealed that inflammatory cytokines such as IL-1 and IL-6 are involved in the development of hyponatremia associated with inflammatory conditions, and that this process is related to ADH secretion.

• #44 The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barré syndrome

  http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0211-69952012000100018

  The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barr syndrome […] According to a previous study by Maimone et al., interleukin (IL)-6, a multifunctional cytokine, might be implicated in the immunopathogenesis of GBS. […] Therefore, there is a possibility that IL-6 may play a central role in the pathogenesis of hyponatremia associated with GBS.

• #45 Hyponatremia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242166-overview

  In the setting of an acute drop in the serum osmolality, neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space (ie, Starling forces). Swelling of the brain cells elicits the following two osmoregulatory responses: […] It inhibits arginine vasopressin secretion from neurons in the hypothalamus and hypothalamic thirst center. This leads to excess water elimination as dilute urine. […] There is an immediate cellular adaptation with loss of electrolytes, and over the next few days, a more gradual loss of organic intracellular osmolytes. […] Therefore, correction of hyponatremia must take into account the chronicity of the condition. Acute hyponatremia (duration 48 h) can be corrected more quickly than chronic hyponatremia. Most individuals who present with symptomatic hyponatremia (as opposed to those who develop hyponatremia in an inpatient setting) have had hyponatremia for some time, so their condition is chronic, and correction should proceed accordingly. Overly rapid correction of serum sodium levels in these individuals can precipitate a severe neurologic complication, ODS. Consequently, when the duration of hyponatremia is uncertain, the condition should be considered chronic.

• #46 Hyponatremia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242166-overview

  In the setting of an acute drop in the serum osmolality, neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space (ie, Starling forces). Swelling of the brain cells elicits the following two osmoregulatory responses: […] It inhibits arginine vasopressin secretion from neurons in the hypothalamus and hypothalamic thirst center. This leads to excess water elimination as dilute urine. […] There is an immediate cellular adaptation with loss of electrolytes, and over the next few days, a more gradual loss of organic intracellular osmolytes. […] Therefore, correction of hyponatremia must take into account the chronicity of the condition. Acute hyponatremia (duration 48 h) can be corrected more quickly than chronic hyponatremia. Most individuals who present with symptomatic hyponatremia (as opposed to those who develop hyponatremia in an inpatient setting) have had hyponatremia for some time, so their condition is chronic, and correction should proceed accordingly. Overly rapid correction of serum sodium levels in these individuals can precipitate a severe neurologic complication, ODS. Consequently, when the duration of hyponatremia is uncertain, the condition should be considered chronic.

• #47

  https://www.jci.org/articles/view/115292

  Osmotic injury induced by rapid correction of severe chronic hyponatremia has been implicated in the development of central pontine myelinolysis. […] It is concluded that: most of the change of brain osmolality in chronic hyponatremia can be accounted by the changes in organic osmolytes and brain electrolytes; and rapid correction of hyponatremia is associated with an overshoot of brain sodium and chloride levels along with a low organic osmolyte level. The high cerebral ion concentrations in the absence of adequate concentrations of organic osmolytes may be relevant to the development of central pontine myelinolysis.

• #48 Hyponatremia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242166-overview

  In the setting of an acute drop in the serum osmolality, neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space (ie, Starling forces). Swelling of the brain cells elicits the following two osmoregulatory responses: […] It inhibits arginine vasopressin secretion from neurons in the hypothalamus and hypothalamic thirst center. This leads to excess water elimination as dilute urine. […] There is an immediate cellular adaptation with loss of electrolytes, and over the next few days, a more gradual loss of organic intracellular osmolytes. […] Therefore, correction of hyponatremia must take into account the chronicity of the condition. Acute hyponatremia (duration 48 h) can be corrected more quickly than chronic hyponatremia. Most individuals who present with symptomatic hyponatremia (as opposed to those who develop hyponatremia in an inpatient setting) have had hyponatremia for some time, so their condition is chronic, and correction should proceed accordingly. Overly rapid correction of serum sodium levels in these individuals can precipitate a severe neurologic complication, ODS. Consequently, when the duration of hyponatremia is uncertain, the condition should be considered chronic.

• #49

  https://www.jci.org/articles/view/115292

  Osmotic injury induced by rapid correction of severe chronic hyponatremia has been implicated in the development of central pontine myelinolysis. […] It is concluded that: most of the change of brain osmolality in chronic hyponatremia can be accounted by the changes in organic osmolytes and brain electrolytes; and rapid correction of hyponatremia is associated with an overshoot of brain sodium and chloride levels along with a low organic osmolyte level. The high cerebral ion concentrations in the absence of adequate concentrations of organic osmolytes may be relevant to the development of central pontine myelinolysis.

• #50 Pathophysiology of Hyponatremia in Heart Failure| SAMSCA® (tolvaptan)

  https://www.samsca.com/hyponatremia-heart-failure/pathophysiology

  Reduced cardiac output in heart failure stimulates the release of vasopressin, resulting in elevated levels of circulating vasopressin. […] Because vasopressin reduces the excretion of free water, elevated levels of vasopressin may contribute to the development of hyponatremia in heart failure patients. […] Reduced cardiac output and decreased renal perfusion activates the renin-angiotensin-aldosterone system in heart failure patients. […] The excess of angiotensin II in heart failure causes the following which further exacerbate dilutional hyponatremia: systemic and arteriolar vasoconstriction, increase in aldosterone concentration, increased thirst. […] In heart failure, water and sodium retention occur in response to aldosterone.

• #51 Hypoosmolar hyponatremia with concentrated urine | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/electrolyte-disorders/Chapter-536/hypoosmolar-hyponatremia-concentrated-urine

  Third space distribution of fluid is the key factor in the mechanism of hyponatremia due to nephrotic syndrome. Because of the low serum protein, oncotic pressure is reduced and fluid migrates out of the intravascular compartment, reducing the effective circulating volume. Again, the renin-angiotensin-aldosterone system responds by increasing sodium and water retention. […] In hepatic and renal failure, there is loss of protein (by nephrotic syndrome or by decreased synthesis). With loss of serum oncotic pressure, circulating arterial volume is decreased as fluid migrates into the interstitial compartment. In response to this, there is a hypersecretion of ADH, which leads to increased water retention. […] The pathophysiology of this is incompletely understood, even though we have known about this since the 1950s. It does not seem to be a problem with inappropriate ADH hypersecretion, according to the more recent reviews. The vasopressin levels are usually high in these people but the mechanism seems to be a matter of ADH-induced water retention, in response to a decreased cardiac output which causes decreased renal blood flow. […] Elevated vasopressin levels tend to result in water retention, and a dilutional hyponatremia develops. These patients have no way of increasing their water excretion in response to an increased water intake. The urinary mechanisms of solute excretion remain intact, hence the high urinary sodium.

• #52 Pathophysiology of Hyponatremia in Heart Failure| SAMSCA® (tolvaptan)

  https://www.samsca.com/hyponatremia-heart-failure/pathophysiology

  Reduced cardiac output in heart failure stimulates the release of vasopressin, resulting in elevated levels of circulating vasopressin. […] Because vasopressin reduces the excretion of free water, elevated levels of vasopressin may contribute to the development of hyponatremia in heart failure patients. […] Reduced cardiac output and decreased renal perfusion activates the renin-angiotensin-aldosterone system in heart failure patients. […] The excess of angiotensin II in heart failure causes the following which further exacerbate dilutional hyponatremia: systemic and arteriolar vasoconstriction, increase in aldosterone concentration, increased thirst. […] In heart failure, water and sodium retention occur in response to aldosterone.

• #53 Pathophysiology of Hyponatremia in Heart Failure| SAMSCA® (tolvaptan)

  https://www.samsca.com/hyponatremia-heart-failure/pathophysiology

  Reduced cardiac output in heart failure stimulates the release of vasopressin, resulting in elevated levels of circulating vasopressin. […] Because vasopressin reduces the excretion of free water, elevated levels of vasopressin may contribute to the development of hyponatremia in heart failure patients. […] Reduced cardiac output and decreased renal perfusion activates the renin-angiotensin-aldosterone system in heart failure patients. […] The excess of angiotensin II in heart failure causes the following which further exacerbate dilutional hyponatremia: systemic and arteriolar vasoconstriction, increase in aldosterone concentration, increased thirst. […] In heart failure, water and sodium retention occur in response to aldosterone.

• #54 Hyponatremia in patients with cirrhosis – UpToDate

  https://www.uptodate.com/contents/hyponatremia-in-patients-with-cirrhosis

  Hyponatremia is a common problem in patients with advanced cirrhosis. The pathogenesis of hyponatremia in these patients is directly related to the hemodynamic changes and secondary neurohumoral adaptations that occur, resulting in an impaired ability to excrete ingested water. The severity of the hyponatremia is related to the severity of the cirrhosis. […] The pathogenesis, epidemiology, and special management considerations of hyponatremia in patients with cirrhosis are presented in this topic.

• #55 Hypoosmolar hyponatremia with concentrated urine | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/electrolyte-disorders/Chapter-536/hypoosmolar-hyponatremia-concentrated-urine

  Third space distribution of fluid is the key factor in the mechanism of hyponatremia due to nephrotic syndrome. Because of the low serum protein, oncotic pressure is reduced and fluid migrates out of the intravascular compartment, reducing the effective circulating volume. Again, the renin-angiotensin-aldosterone system responds by increasing sodium and water retention. […] In hepatic and renal failure, there is loss of protein (by nephrotic syndrome or by decreased synthesis). With loss of serum oncotic pressure, circulating arterial volume is decreased as fluid migrates into the interstitial compartment. In response to this, there is a hypersecretion of ADH, which leads to increased water retention. […] The pathophysiology of this is incompletely understood, even though we have known about this since the 1950s. It does not seem to be a problem with inappropriate ADH hypersecretion, according to the more recent reviews. The vasopressin levels are usually high in these people but the mechanism seems to be a matter of ADH-induced water retention, in response to a decreased cardiac output which causes decreased renal blood flow. […] Elevated vasopressin levels tend to result in water retention, and a dilutional hyponatremia develops. These patients have no way of increasing their water excretion in response to an increased water intake. The urinary mechanisms of solute excretion remain intact, hence the high urinary sodium.

• #56 Hypoosmolar hyponatremia with concentrated urine | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/electrolyte-disorders/Chapter-536/hypoosmolar-hyponatremia-concentrated-urine

  Third space distribution of fluid is the key factor in the mechanism of hyponatremia due to nephrotic syndrome. Because of the low serum protein, oncotic pressure is reduced and fluid migrates out of the intravascular compartment, reducing the effective circulating volume. Again, the renin-angiotensin-aldosterone system responds by increasing sodium and water retention. […] In hepatic and renal failure, there is loss of protein (by nephrotic syndrome or by decreased synthesis). With loss of serum oncotic pressure, circulating arterial volume is decreased as fluid migrates into the interstitial compartment. In response to this, there is a hypersecretion of ADH, which leads to increased water retention. […] The pathophysiology of this is incompletely understood, even though we have known about this since the 1950s. It does not seem to be a problem with inappropriate ADH hypersecretion, according to the more recent reviews. The vasopressin levels are usually high in these people but the mechanism seems to be a matter of ADH-induced water retention, in response to a decreased cardiac output which causes decreased renal blood flow. […] Elevated vasopressin levels tend to result in water retention, and a dilutional hyponatremia develops. These patients have no way of increasing their water excretion in response to an increased water intake. The urinary mechanisms of solute excretion remain intact, hence the high urinary sodium.

• #57 Hypoosmolar hyponatremia with concentrated urine | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/electrolyte-disorders/Chapter-536/hypoosmolar-hyponatremia-concentrated-urine

  Third space distribution of fluid is the key factor in the mechanism of hyponatremia due to nephrotic syndrome. Because of the low serum protein, oncotic pressure is reduced and fluid migrates out of the intravascular compartment, reducing the effective circulating volume. Again, the renin-angiotensin-aldosterone system responds by increasing sodium and water retention. […] In hepatic and renal failure, there is loss of protein (by nephrotic syndrome or by decreased synthesis). With loss of serum oncotic pressure, circulating arterial volume is decreased as fluid migrates into the interstitial compartment. In response to this, there is a hypersecretion of ADH, which leads to increased water retention. […] The pathophysiology of this is incompletely understood, even though we have known about this since the 1950s. It does not seem to be a problem with inappropriate ADH hypersecretion, according to the more recent reviews. The vasopressin levels are usually high in these people but the mechanism seems to be a matter of ADH-induced water retention, in response to a decreased cardiac output which causes decreased renal blood flow. […] Elevated vasopressin levels tend to result in water retention, and a dilutional hyponatremia develops. These patients have no way of increasing their water excretion in response to an increased water intake. The urinary mechanisms of solute excretion remain intact, hence the high urinary sodium.

• #58 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  Furthermore, animal studies have suggested that SIADH may result from a direct toxic effect of vincristine on the neurohypophysis and the hypothalamic system. […] The mechanism of anticonvulsant-associated hyponatremia has generally been considered inappropriate hypersecretion of AVP, but an experimental study has indicated a direct effect of carbamazepine on the kidney through V2R stimulation without evidence of the increased release of endogenous AVP. […] It has become clear that carbamazepine has a direct action on the collecting duct V2R, leading to AQP2 upregulation. […] The mechanisms of TIH are complicated and not fully understood at present. […] Thiazides inhibit the Na-Cl cotransporter (NCC) in the distal convoluted tubule, the cortical diluting segment of the nephron. Thus, urine dilution is impaired and water can be retained by thiazides.

• #59

  https://www.archivesofmedicalscience.com/Hyponatremia-in-patients-with-arterial-hypertension-pathophysiology-and-management,161578,0,2.html

  The pathogenesis of TIH is not fully understood. […] TIH shows increased water reabsorption in the collecting tubules, decreased free water excretion, increased translocation to the AQP-2 cell membrane and increased body weight due to increased water content in the body. […] Thus, a significant proportion of patients with TIH experience excessive water reabsorption, leading to profound hyponatremia accompanied by hypokalemia.

• #60

  https://www.archivesofmedicalscience.com/Hyponatremia-in-patients-with-arterial-hypertension-pathophysiology-and-management,161578,0,2.html

  The pathogenesis of TIH is not fully understood. […] TIH shows increased water reabsorption in the collecting tubules, decreased free water excretion, increased translocation to the AQP-2 cell membrane and increased body weight due to increased water content in the body. […] Thus, a significant proportion of patients with TIH experience excessive water reabsorption, leading to profound hyponatremia accompanied by hypokalemia.

• #61 Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury: a critical review | springermedizin.de

  https://www.springermedizin.de/mechanisms-of-hyponatremia-and-diabetes-insipidus-after-acute-sp/26308266

  The mechanism of hyponatremia after SCI is complex and unclear. […] Hyponatremia is often associated with diabetes insipidus, which refers to insufficient arginine vasopressin (AVP) secretion or defective renal response to AVP, with clinical manifestations of syndromes such hypoosmolality, polydipsia, and polydipsia. […] The therapeutic principles of CSWS and SIADH are in opposition to one another. It is not easy to identify the mechanism of hyponatremia in clinical practice, which makes selecting the treatment difficult. […] According to the existing theories, treatments for hyponatremia and diabetes insipidus together are contraindicated, whether the mechanism of hyponatremia is thought to be CSWS or SIADH. […] The mechanism of hyponatremia after SCI is generally considered to be related to central nervous system dysfunction, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSWS).

• #62 Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury: a critical review | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-023-00347-y

  The incidence of hyponatremia after spinal cord injury was reported to be between 25 and 80%. […] Hyponatremia is often associated with diabetes insipidus, which refers to insufficient arginine vasopressin (AVP) secretion or defective renal response to AVP, with clinical manifestations of syndromes such as hypoosmolality, polydipsia, and polydipsia. […] The mechanism of hyponatremia after SCI is complex and unclear. In addition to poor diet, application of diuretics and dehydrating agents, and combined craniocerebral trauma in early patients, hyponatremia after SCI is generally considered to be related to central nervous system dysfunction, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSWS). […] SIADH refers to hypervolemic hyponatremia that is caused by abnormally increased AVP secretion, which promotes renal water retention and sodium excretion and results in increased urinary sodium and water retention. CSWS refers to hypovolemic hyponatremia, which is caused by excessive renal sodium excretion that results from hypothalamic endocrine dysfunction.

• #63 Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury: a critical review | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-023-00347-y

  The incidence of hyponatremia after spinal cord injury was reported to be between 25 and 80%. […] Hyponatremia is often associated with diabetes insipidus, which refers to insufficient arginine vasopressin (AVP) secretion or defective renal response to AVP, with clinical manifestations of syndromes such as hypoosmolality, polydipsia, and polydipsia. […] The mechanism of hyponatremia after SCI is complex and unclear. In addition to poor diet, application of diuretics and dehydrating agents, and combined craniocerebral trauma in early patients, hyponatremia after SCI is generally considered to be related to central nervous system dysfunction, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSWS). […] SIADH refers to hypervolemic hyponatremia that is caused by abnormally increased AVP secretion, which promotes renal water retention and sodium excretion and results in increased urinary sodium and water retention. CSWS refers to hypovolemic hyponatremia, which is caused by excessive renal sodium excretion that results from hypothalamic endocrine dysfunction.

• #64 Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury: a critical review | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-023-00347-y

  These two theories for hyponatremia, SIADH and CSWS, are contradictory as follows: SIADH is hypervolemic hyponatremia that is caused by water retention, while CSWS is hypovolemic hyponatremia that is caused by excessive sodium excretion; SIADH is the hypersecretion of antidiuretic hormone which also known as arginine vasopressin (AVP), while CSWS is the hyposecretion of AVP. […] The therapeutic principles of CSWS and SIADH are in opposition to one another. […] According to the existing theories, treatments for both hyponatremia and diabetes insipidus are contraindicated, whether the mechanism of hyponatremia is thought to be CSWS or SIADH. […] The pathogenesis of diabetes insipidus remains unclear, and interpretation of some studies is not consistent with the physiological mechanism; and existing theories cannot guide clinical treatment, and dividing hyponatremia into CSWS and SIADH is contradictory to the treatment of diabetes insipidus. Thus, these findings suggest that our current understanding of the mechanisms of hyponatremia and diabetes insipidus after high acute cervical SCI is insufficient, and it is likely that there are other undetected pathogenetic mechanisms.

• #65 Risk factors and outcome of hyponatremia in patients with Guillain–Barré syndrome | Scientific Reports

  https://www.nature.com/articles/s41598-024-67427-6

  The objective of the present study was to evaluate the risk factors and outcomes associated with hyponatremia in patients with Guillain-Barr syndrome (GBS). […] Hyponatremia was significantly associated with older age (P=0.003), urinary retention (P0.0001), Hughes grade4 at admission and nadir (P=0.003 and P0.001, respectively), acute inflammatory demyelinating polyneuropathy subtype (P=0.017), sepsis (P=0.001), mechanical ventilator support (P=0.013), longer hospitalization length of stay (P0.0001), and inability to walk independently at 6 months (P0.001). […] Multivariate analysis performed to assess the risk factors of hyponatremia revealed that urinary retention (odds ratio [OR] 30.7, 95% confidence interval [CI] 3.6264.4; P=0.002) and mechanical ventilator support (OR 13.8, 95% CI 1.6118.0; P=0.017) were significant independent risk factors of hyponatremia.

• #66 Risk factors and outcome of hyponatremia in patients with Guillain–Barré syndrome | Scientific Reports

  https://www.nature.com/articles/s41598-024-67427-6

  Therefore, we demonstrate that, along with mechanical ventilator support, urinary retentionpossibly indicating autonomic dysfunctionis a risk factor of hyponatremia in GBS. Moreover, we confirm that hyponatremia is associated with poor outcome in GBS. […] Regarding the risk factors, previous studies have reported that disease severity and older age were associated with hyponatremia in GBS. […] Autonomic dysfunction was also associated with hyponatremia in GBS and was especially examined because of its potentially important role in the pathogenesis. […] We focused solely on urinary retention as a symptom of autonomic dysfunction. […] Hyponatremia has various causative factors such as drug-induced hyponatremia, hyponatremia due to inadequate intake, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and renal salt wasting (RSW).

• #67 Risk factors and outcome of hyponatremia in patients with Guillain–Barré syndrome | Scientific Reports

  https://www.nature.com/articles/s41598-024-67427-6

  We hypothesize that drug-induced factors are unlikely to be the primary cause of hyponatremia in this study. […] The complete elucidation of the mechanism through which autonomic dysfunction precipitates SIADH or RSW and subsequently induces hyponatremia in GBS remains elusive. […] One such hypothesized mechanism suggests that the abnormality of peripheral autonomic afferent fibers originating from vascular stretch receptors, as a component of autonomic dysfunction in GBS, could instigate hyponatremia mainly through SIADH. […] Another proposed mechanism posits that sympathoadrenal dysregulation, as a facet of autonomic dysfunction in GBS, might trigger excessive secretion of brain natriuretic peptide, culminating in disproportionate renal sodium excretion, thereby engendering hyponatremia mainly through RSW. […] We also demonstrated an independent association between mechanical ventilator support and hyponatremia in patients with GBS. […] Another noteworthy finding of our study is that hyponatremia was associated with poor outcome in patients with Guillain-Barr syndrome.

• #68 The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barré syndrome | Nefrología

  https://www.revistanefrologia.com/en-the-role-interleukin-6-in-pathogenesis-hyponatremia-associated-with-guillain-barre-articulo-X0211699512000467

  We read with great interest the contribution by Monzn et al. They reported a significant case of a man who had Guillain-Barr syndrome (GBS) with syndrome of inappropriate antidiuretic hormone (SIADH) and speculated that increased sensitivity to vasopressin in the renal tubule and a long-lasting hypo-osmolarity or antidiuretic substances might cause GBS-related SIADH. However, we would like to add a possible pathomechanism in the development of hyponatremia associated with GBS. […] According to a previous study by Maimone et al., interleukin (IL)-6, a multifunctional cytokine, might be implicated in the immunopathogenesis of GBS. […] Furthermore, Mastorakos et al. reported that plasma antidiuretic hormone levels were elevated after IL-6 injection in cancer patients, suggesting that IL-6 activated the magnocellular ADH-secreting neurons and that it might be involved in SIADH. […] Therefore, there is a possibility that IL-6 may play a central role in the pathogenesis of hyponatremia associated with GBS.

• #69 The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barré syndrome | Nefrología

  https://www.revistanefrologia.com/es-the-role-interleukin-6-in-articulo-X0211699512000467

  We read with great interest the contribution by Monzn et al.1 They reported a significant case of a man who had Guillain-Barr syndrome (GBS) with syndrome of inappropriate antidiuretic hormone (SIADH) and speculated that increased sensitivity to vasopressin in the renal tubule and a long-lasting hypo-osmolarity or antidiuretic substances might cause GBS-related SIADH. However, we would like to add a possible pathomechanism in the development of hyponatremia associated with GBS. […] According to a previous study by Maimone et al.,2 interleukin (IL)-6, a multifunctional cytokine, might be implicated in the immunopathogenesis of GBS. […] Therefore, there is a possibility that IL-6 may play a central role in the pathogenesis of hyponatremia associated with GBS.

• #70

  https://journals.lww.com/md-journal/fulltext/2016/03080/patient_with_severe_hyponatremia_caused_by_adrenal.20.aspx

  Hyponatremia may be one of the clinical manifestations of adrenal insufficiency (AI) and during the diagnostic workup of hyponatremic patients investigation of AI should be included. […] Clinician’s attention must focus on the underlying cause of AI which in this case was hidden in a miscommunication between hypothalamus and pituitary due to an ectopic posterior pituitary lobe and became apparent by a pituitary magnetic resonance imaging (MRI) scan. […] Secondary AI is related with hyponatremia through increased ADH secretion. […] Disruption of communication between hypothalamus and pituitary is a rare but considerable cause of AI. […] Hyponatremia caused by AI is explained by the dysfunction of hypothalamo-pituitary-adrenal axis. The electrolyte disturbance of hyponatremia in AI is due to diminished secretion of cortisol. Cortisol deficiency results in increased hypothalamic secretion of CRH. CRH plays the role of an additional ADH secretagogue.

• #71

  https://journals.lww.com/md-journal/fulltext/2016/03080/patient_with_severe_hyponatremia_caused_by_adrenal.20.aspx

  Hyponatremia may be one of the clinical manifestations of adrenal insufficiency (AI) and during the diagnostic workup of hyponatremic patients investigation of AI should be included. […] Clinician’s attention must focus on the underlying cause of AI which in this case was hidden in a miscommunication between hypothalamus and pituitary due to an ectopic posterior pituitary lobe and became apparent by a pituitary magnetic resonance imaging (MRI) scan. […] Secondary AI is related with hyponatremia through increased ADH secretion. […] Disruption of communication between hypothalamus and pituitary is a rare but considerable cause of AI. […] Hyponatremia caused by AI is explained by the dysfunction of hypothalamo-pituitary-adrenal axis. The electrolyte disturbance of hyponatremia in AI is due to diminished secretion of cortisol. Cortisol deficiency results in increased hypothalamic secretion of CRH. CRH plays the role of an additional ADH secretagogue.

• #72

  https://journals.lww.com/md-journal/fulltext/2016/03080/patient_with_severe_hyponatremia_caused_by_adrenal.20.aspx

  In conclusion, secondary AI is related with hyponatremia through increased ADH secretion. In the case of our patient, ectopic posterior pituitary lobe may have been both the cause of the disruption in the hypothalamus-pituitary communication resulting in inadequate ACTH production and AI and the origin of inappropriate ADH production clinically manifesting with hyponatremia.

• #73 Hyponatremia in the Elderly: Risk Factors, Clinical Consequences, and Management | Consultant360

  https://www.consultant360.com/articles/hyponatremia-elderly-risk-factors-clinical-consequences-and-management

  Alterations associated with the normal aging process may compromise homeostatic systems involved in the regulation of fluid balance including thirst perception that govern fluid intake, the kidney, regulation of secretion of arginine vasopressin (AVP) or antidiuretic hormone, atrial natriuretic hormone, and the reninangiotensinaldosterone system. […] Hyponatremia is usually defined as a serum sodium concentration of 135 mEq/L or less. It appears when there is an excess of water relative to sodium in the extracellular body fluid compartment and can be the consequence of either a decrease in extracellular sodium content (ie, sodium depletion) or an increase in extracellular water (ie, dilutional hyponatremia). In the elderly person, dilutional hyponatremia is the more common mechanism and most frequently is due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

• #74 Hyponatremia and Hypernatremia in the Elderly | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0615/p3623.html

  The ability to excrete a water load is delayed in the elderly. […] Other changes in renal physiology and anatomy that increase the elderly patient’s susceptibility to alterations of water imbalance include decreased renal mass, cortical blood flow and glomerular filtration rate, as well as impaired responsiveness to sodium balance. […] The elderly patient has a diminished reserve of water balance and an impaired regulatory mechanism. […] The impact of a lifetime of accumulated disease and comorbidities must also be duly considered in every clinical situation with an elderly patient, in addition to age-related physiologic changes.

• #75 Hyponatremia and Hypernatremia in the Elderly | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0615/p3623.html

  The ability to excrete a water load is delayed in the elderly. […] Other changes in renal physiology and anatomy that increase the elderly patient’s susceptibility to alterations of water imbalance include decreased renal mass, cortical blood flow and glomerular filtration rate, as well as impaired responsiveness to sodium balance. […] The elderly patient has a diminished reserve of water balance and an impaired regulatory mechanism. […] The impact of a lifetime of accumulated disease and comorbidities must also be duly considered in every clinical situation with an elderly patient, in addition to age-related physiologic changes.

• #76 Hyponatremia in the Elderly: Risk Factors, Clinical Consequences, and Management | Consultant360

  https://www.consultant360.com/articles/hyponatremia-elderly-risk-factors-clinical-consequences-and-management

  Advanced age itself may be a risk factor for hyponatremia. SIADH has been described in elderly individuals, generally older than age 80 years, in whom no identifiable cause for hyponatremia could be found, suggesting that there is an idiopathic form of SIADH that may represent the clinical expression of physiologic changes that take place in the regulation of water balance during aging. […] Almost all CNS disorders can lead to dysfunction of the hypothalamic system involved in the normal regulation of AVP secretion with resultant increased secretion of the hormone and consequent risk for water retention and hyponatremia. […] Malignancies can cause SIADH as a result of autonomous release of AVP from cancer tissue where it is synthesized, stored, and discharged in the absence of known stimuli.

• #77

  https://www.archivesofmedicalscience.com/Hyponatremia-in-patients-with-arterial-hypertension-pathophysiology-and-management,161578,0,2.html

  Hyponatremia is defined by a plasma sodium concentration lower than 135 mmol/l. […] In patients with arterial hypertension, the risk of hyponatremia is 1.5 times higher than in the general population. […] One of the causes of hyponatremia in patients with arterial hypertension is the use of thiazide or thiazide-like diuretics. […] The symptoms of hyponatremia are caused mainly by the swelling of cells in the central nervous system. […] In the present review paper, pathophysiology and management of hyponatremia in patients with arterial hypertension are discussed. […] From the pathophysiological point of view, the causes of hyponatremia are classified according to plasma osmolality and the patients hydration status. […] The incidence of various forms of hyponatremia was assessed by Fenske et al. in a study of 121 patients admitted to the hospital with a serum sodium concentration 130 mmol/l.

• #78

  https://www.archivesofmedicalscience.com/Hyponatremia-in-patients-with-arterial-hypertension-pathophysiology-and-management,161578,0,2.html

  The pathogenesis of TIH is not fully understood. […] TIH shows increased water reabsorption in the collecting tubules, decreased free water excretion, increased translocation to the AQP-2 cell membrane and increased body weight due to increased water content in the body. […] Thus, a significant proportion of patients with TIH experience excessive water reabsorption, leading to profound hyponatremia accompanied by hypokalemia.

• #79 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  Four major causes of SIAD are malignancies, pulmonary diseases, disorders of the central nervous system, and drugs. According to case reports, many medications are associated with hyponatremia. However, whether they all have significant cause-and-effect relationships is unclear because incidental coexistences need to be excluded in rare cases. Regarding the mechanisms of drug-induced hyponatremia, stimulation of AVP release and enhancement of AVP action in the kidney have been postulated. However, the evidence for the former was limited, and the mechanisms of the latter were elusive. […] AVP analogs include desmopressin and oxytocin and can induce hyponatremia by acting as V2R agonists. Desmopressin selectively binds the V2R in the kidney and stimulates adenylyl cyclase activity and cAMP production in collecting duct epithelial cells.

• #80 Hyponatremia | Diagnosis & Disease Information – Renal and Urology News

  https://www.renalandurologynews.com/ddi/hyponatremia/

  Potential causes of hypovolemic hyponatremia include renal sodium loss due to diuretics, mineralocorticoid deficiency, nephropathy, metabolic alkalosis, or cerebral salt wasting. It also can be the result of nonrenal causes of fluid loss, such as vomiting, diarrhea, burns, pancreatitis, or trauma. Euvolemic hyponatremia may be due to glucocorticoid deficiency, hypothyroidism, stress, select medications and illicit drugs, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hypervolemic hyponatremia can be caused by renal failure, nephrotic syndrome, cirrhosis, and heart failure. […] Many conditions are associated with inappropriate ADH secretion and thus can result in hyponatremia. These include the following: Tumor-related conditions (cancers of the lung, pancreas, duodenum, ureter, bladder, and prostate, as well as lymphoma, thymoma, mesothelioma, and Ewing sarcoma); Lung problems (pneumonia, tuberculosis, aspergillosis, asthma, pneumothorax, cystic fibrosis, abscesses); Central nervous system problems (delirium tremens, seizures, Shy-Drager syndrome, Rocky Mountain spotted fever, lupus cerebritis, cavernous vein thrombosis, hydrocephalus, multiple sclerosis, schizophrenia, brain atrophy, encephalitis or meningitis, brain tumors or abscesses, head trauma, subdural hematoma, stroke, Guillain-Barr syndrome); Medication adverse effects (haloperidol, phenothiazines, opiates, selective serotonin reuptake inhibitors, tricyclic antidepressants, cyclophosphamide, vinca alkaloids, carbamazepine, clofibrate, sulfonylureas, arginine vasopressin); and Endocrine conditions (deficiency of glucocorticoids, myxedema).

• #81 Hyponatremia and urinary retention in an eldery patient with type 2 diabetes | Cichocka | Clinical Diabetology

  https://journals.viamedica.pl/clinical_diabetology/article/view/76410

  Hyponatremia, defined as a serum sodium level 135 mmol/L, is the most prevalent fluid and electrolyte imbalance in clinical practice. […] Using both drugs together: duloxetine and indapamide were considered the most probable cause of hyponatremia and non-obstructive urinary retention. […] Duloxetine-related adverse reactions include hyponatremia (cases with a sodium level 110 mmol/L were also reported) and urinary retention as shown in the above mechanism. Pathological hyponatremia, whose mechanism is not fully understood, is not common and is estimated at 110 per 10,000 patients. It seems that it is caused by duloxetine-induced SIADH. […] Thiazide-like indapamide, as in the case of thiazide-type diuretics, is also a common cause of thiazide–induced hyponatremia (TIH), which usually occurs within the first two or three weeks following drug administration. However, it can occur at any stage of treatment and can progress rapidly in susceptible patients.

• #82 Omeprazole-induced and pantoprazole-induced asymptomatic hyponatremia: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02423-8

  Hyponatremia is the most common electrolyte disorder. Thiazides, antidepressants, antipsychotic drugs, and antiepileptic drugs are well-known causes of hyponatremia. Proton pump inhibitor use is a rare cause of hyponatremia and, when reported, it is due to one specific proton pump inhibitor, mostly omeprazole. […] The underlying pathophysiological mechanism of PPI-induced hyponatremia is not clearly understood. It is probably due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Salt-losing nephropathy caused by acute interstitial nephritis may play a role as well. […] We concluded that both omeprazole and pantoprazole caused mild hyponatremia in our patient and considered this to be a PPI class effect. […] In conclusion, whenever hyponatremia induced by a PPI is diagnosed, the clinician should be aware that switching to another PPI could also lead to hyponatremia.

• #83 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  This enhances osmotic water reabsorption through the upregulation of the aquaporin-2 (AQP2) water channel. […] Even low doses of desmopressin can induce hyponatremia in susceptible patients with nocturnal polyuria because an advanced age is an important risk factor for hyponatremia. […] Oxytocin may also induce hyponatremia when it is used in obstetrics to induce abortion and to induce or augment labor. […] In brief, pharmacological doses of oxytocin can induce antidiuretic effects as a result of V2R stimulation and subsequent AQP2 upregulation. […] Hyponatremia is a common complication in cancer patients because SIAD is potentially caused by malignancies and it can be related to anticancer medical therapy as well. […] Previous studies have shown that SIADH underlies the mechanism of vincristine-associated hyponatremia.

• #84 Pathophysiology of Drug-Induced Hyponatremia

  https://www.mdpi.com/2077-0383/11/19/5810

  Furthermore, animal studies have suggested that SIADH may result from a direct toxic effect of vincristine on the neurohypophysis and the hypothalamic system. […] The mechanism of anticonvulsant-associated hyponatremia has generally been considered inappropriate hypersecretion of AVP, but an experimental study has indicated a direct effect of carbamazepine on the kidney through V2R stimulation without evidence of the increased release of endogenous AVP. […] It has become clear that carbamazepine has a direct action on the collecting duct V2R, leading to AQP2 upregulation. […] The mechanisms of TIH are complicated and not fully understood at present. […] Thiazides inhibit the Na-Cl cotransporter (NCC) in the distal convoluted tubule, the cortical diluting segment of the nephron. Thus, urine dilution is impaired and water can be retained by thiazides.

• #85 Inflammation and hyponatremia: an underrecognized condition?

  https://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2013.56.12.519

  Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1 and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. […] The development of hyponatremia is associated with various inflammatory diseases including pneumonia, severe acute respiratory distress syndrome, tuberculosis, meningitis, encephalitis, human immunodeficiency virus infection, and malaria. However, the pathophysiology of hyponatremia diagnosed under these inflammatory conditions remains elusive. Recent research revealed that inflammatory cytokines such as IL-1 and IL-6 are involved in the development of hyponatremia associated with inflammatory conditions, and that this process is related to ADH secretion.

• #86 Inflammation and hyponatremia: an underrecognized condition?

  https://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2013.56.12.519

  Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1 and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. […] The development of hyponatremia is associated with various inflammatory diseases including pneumonia, severe acute respiratory distress syndrome, tuberculosis, meningitis, encephalitis, human immunodeficiency virus infection, and malaria. However, the pathophysiology of hyponatremia diagnosed under these inflammatory conditions remains elusive. Recent research revealed that inflammatory cytokines such as IL-1 and IL-6 are involved in the development of hyponatremia associated with inflammatory conditions, and that this process is related to ADH secretion.

• #87 Inflammation and hyponatremia: an underrecognized condition?

  https://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2013.56.12.519

  In conclusion, available data indicate that inflammatory cytokines such as IL-1 and IL-6 have an important role in the nonosmotic release of ADH. Under inflammatory conditions, this mechanism may be responsible for the development of hyponatremia. Understanding the physiological mechanisms of ADH release and antidiuresis during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid regimen with a suitable infusion rate will all be important aspects of future patient care.

• #88 Hyponatremia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hyponatremia_pathophysiology

  The most common cause of hyponatremia (euvolemic) due to either an increased level of ADH or gain-of-function mutation of the V2 receptor of ADH. […] Interleukin-6 (IL-6), which has been showed to be involved in the pathophysiology of COVID-19 and is released by monocytes and macrophages plays an important role in development of hyponatremia; it induces the non-osmotic release of vasopressin. […] Hyponatremia represents an excess of water relative to total body sodium, resulting from impaired water excretion by the kidneys or the depletion of sodium in excess of water.

• #89 Hyponatremia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470386/

  Hyponatremia is defined as a serum sodium concentration of less than 135 mEq/L but can vary to a small extent in different laboratories. Hyponatremia is a common electrolyte abnormality caused by an excess of total body water when compared to total body sodium content. Edelman discovered that serum sodium concentration does not depend on total body sodium but the ratio of total body solutes (e.g., total body sodium and total body potassium) to total body water. Hyponatremia represents an imbalance in this ratio where total body water is more than total body solutes. […] Thirst stimulation, antidiuretic hormone (ADH) secretion, and handling of filtered sodium by kidneys maintain serum sodium and osmolality. Normal plasma osmolality is around 275 mOsm/kg to 290 mOsm/kg. To maintain normal osmolality, water intake should be equal to water excretion. The imbalance of water intake and excretion causes hyponatremia or hypernatremia. Water intake is regulated by the thirst mechanism, where osmoreceptors in the hypothalamus trigger thirst when body osmolality reaches 295 mOsm/kg. Water excretion is tightly regulated by antidiuretic hormone (ADH), synthesized in the hypothalamus, and stored in the posterior pituitary gland. Changes in tonicity lead to either enhancement or suppression of ADH secretion. Increased ADH secretion causes reabsorption of water in the kidney, and suppression causes the opposite effect.

• #90 Hyponatremia – Wikipedia

  https://en.wikipedia.org/wiki/Hyponatremia

  The causes of and treatments for hyponatremia can only be understood by having a grasp of the size of the body fluid compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis of body fluid osmolality); conditions can cause that feedback system to malfunction (pathophysiology); and the consequences of the malfunction of that system on the size and solute concentration of the fluid compartments. […] Hyponatremia occurs 1) when the hypothalamic-kidney feedback loop is overwhelmed by increased fluid intake, 2) the feedback loop malfunctions such that ADH is always „turned on”, 3) the receptors in the kidney are always „open” regardless of there being no signal from ADH to be open; or 4) there is an increased ADH even though there is no normal stimulus (elevated serum sodium) for ADH to be increased.

• #91 Hyponatremia – Wikipedia

  https://en.wikipedia.org/wiki/Hyponatremia

  The causes of and treatments for hyponatremia can only be understood by having a grasp of the size of the body fluid compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis of body fluid osmolality); conditions can cause that feedback system to malfunction (pathophysiology); and the consequences of the malfunction of that system on the size and solute concentration of the fluid compartments. […] Hyponatremia occurs 1) when the hypothalamic-kidney feedback loop is overwhelmed by increased fluid intake, 2) the feedback loop malfunctions such that ADH is always „turned on”, 3) the receptors in the kidney are always „open” regardless of there being no signal from ADH to be open; or 4) there is an increased ADH even though there is no normal stimulus (elevated serum sodium) for ADH to be increased.

• #92 Hyponatremia – Wikipedia

  https://en.wikipedia.org/wiki/Hyponatremia

  Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. […] If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking (psychogenic polydipsia), 2) beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. „Impairment of urine diluting ability related to ADH” occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addison’s disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion (SIADH).

• #93 Hyponatremia – Wikipedia

  https://en.wikipedia.org/wiki/Hyponatremia

  Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. […] If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking (psychogenic polydipsia), 2) beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. „Impairment of urine diluting ability related to ADH” occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addison’s disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion (SIADH).

• #94 Hyponatremia – Wikipedia

  https://en.wikipedia.org/wiki/Hyponatremia

  Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. […] If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking (psychogenic polydipsia), 2) beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. „Impairment of urine diluting ability related to ADH” occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addison’s disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion (SIADH).

• #95 Hyponatremia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hyponatremia_pathophysiology

  The most common cause of hyponatremia (euvolemic) due to either an increased level of ADH or gain-of-function mutation of the V2 receptor of ADH. […] Interleukin-6 (IL-6), which has been showed to be involved in the pathophysiology of COVID-19 and is released by monocytes and macrophages plays an important role in development of hyponatremia; it induces the non-osmotic release of vasopressin. […] Hyponatremia represents an excess of water relative to total body sodium, resulting from impaired water excretion by the kidneys or the depletion of sodium in excess of water.

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