Sandbox:Saeedeh

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Saeedeh Kowsarnia M.D.[2]

Synonyms and keywords:

Historical Perspective

[Disease name] was first discovered by [name of scientist], a [nationality + occupatiGIon], in [year]/during/following [event].

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].≤

Classification

Hyponatremia is defined as serum sodium less than 135 mEq/L (mmol/L).Hyponatremia is a water balance disorder which represents an imbalance in this ratio where total body water is more than total body solutes( total body sodium and total body potassium).

Hyponatremia is classified based on serum sodium level:

• Mild : serum sodium 130– 135 mmol/L
• Moderate : serum sodium ≤125–129 mmol/L
• Severe: serum sodium <124 mmol/L

Classification based on duration:

• Hyperacute: develops in a few hours,excess water intake/impaired water excretion,runners,users of the recreational drug (Ecstasy)

• Acute: rapid onset <48 hours(some litreture )
• Chronic: gradual onset >48 hours, caused by chronic disease (including cardiac,renal, hepatic and other conditions)

Classification based on volume status		Causes
Hypovolemic Hyponatremia	total body water ↓ total body sodium ↓↓	GI loss:Vomiting, diarrhea, tube drainage Insensible loss:Sweating, burns Salt-wasting nephropathy: Inappropriate loss of Na+-Cl– in the urine Third spacing of fluids :Pancreatitis, hypoalbuminemia Cerebral salt-wasting syndrome :Stroke ,SAH (urinary salt wasting, brain natriuretic peptide ↑) Mineralocorticoid deficiency:Addison disease Excessive diuretic administration
Hypervolemic Hyponatremia	total body water ↑↑ total body sodium ↑	Acute/chronic kidney injury/disease:(low sodium levels in advanced kidney disease or dialysis patients due to relatively higher water versus salt intake and poor excretion due to underlying kidney disease) Congestive heart failure Cirrhosis Nephrotic syndrome Iatrogenic
Euvolemic Hyponatremia	total body water ↑ total body sodium ↔	Drugs:Vasopressin, diuretics, antidepressants, opioids SIADH: Malignancy, central nervous system (CNS) disorders, pulmonary disease, or drugs, postoperative nausea, pain,stress,Neoplasia (common),trauma,pregnancy High fluid intake: Physical activity, surgery, primary polydipsia, potomania (caused by a low intake of solutes with relatively high fluid intake) Medical testing (excess fluid intake) :Colonoscopy or cardiac catheterization Hypothyroidism Glucocorticoid deficiency Iatrogenic

There is no established system for the classification of [disease name].

OR

[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].

OR

[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3]. [Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].

OR

Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

If the staging system involves specific and characteristic findings and features: According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

The staging of [malignancy name] is based on the [staging system].

OR

There is no established system for the staging of [malignancy name].

Pathophysiology

Sodium is the main cation in the extracellular fluid; thus the plasma concentration of sodium is the determinant of serum osmolality. Hyponatremia represents as an excess of water relative to total body sodium, arising as a result of impaired water excretion by the kidneys or the depletion of sodium in excess of water.

Hypotonic (dilutional) hyponatraemia is classified by the extracellular volume status into hypo-, eu- and hyper-volemic hyponatremia.

Following the onset of hyponatraemia, water moves into the brain down an osmotic gradient leading to swelling of the brain (cerebral oedema). A few hours after the onset of hyponatraemia, the brain undergoes a process of volume adaptation, in which intracellular and extracellular solutes are extruded,inducing water loss and ameliorating brain swelling

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Causes

• SIADH/SIAD: the most common cause of hyponatremia (Euvolemic)

It includes all mutations result in activation of ADH receptors in kodney,caused antidiuresis state.

Diagnostic criteria of SIADH/SIAD
serum sodium <135 mEq/L Plasma osmolality <275 mOsm/kg , ( NL=275–295 mOsm/kg) urine concentration UOsm >100mOsm/kg H2O, (NL=500-800 mOsm/kg H2O) Urine sodium >30 (20-40) mmol/L, with normal salt and water intake, (NL=20 mEq/L)† Clinical euvolemia Exclusion of glucocorticoid deficiency or hypothyroidism

† Mmol and Meq are the same for univalent ions like sodium

Pseudohyponatremia
Hyperlipidemia Hyperglycemia Obstructive jaundice Patients with plasma cell dyscrasia Patients who are treated with Mannitol, Glycerol, IVIG Patients who underwent irrigation with hypotonic fluids()

• Drugs:

Drug Mechanisms	Drug Classification
Increase ADH secretion	Antidepressants:Tricyclic antidepressants (amitryptiline, protriptyline, desipramine),Selective serotonin reuptake inhibitors, Monoamine oxidase inhibitors Antipsychotic drugs: Phenothiazines (thioridazine, trifluoperazine), Butyrophenones (haloperidol) Antiepileptic drugs: Carbamazepine,oxcarbazepine,sodium valproate Anticancer agents: Vinca alkaloids (vincristine, vinblastine), Platinum compounds (cisplatin, carboplatin) Alkylating agents: Intravenous, cyclophosphamide, melphalan, ifosfamide Miscellaneous: Methotrexate, interferon,levamisole, pentostatin, monoclonalantibodies, MDMA, Nicotine Opiates
Increase ADH effect	Antiepileptic drugs: Carbamazepine,lamotrigine Antidiabetic drugs: Chlorpropamide,tolbutamide Anticancer agents: Alkylating agents (intravenous cyclophosphamide) NSAIDS
Drugs affecting water and sodium homeostasis	Diuretics:Thiazides,Indapamide,Amiloride,Loop diuretics
Reset omostat ‡	Antidepressants: Venlafaxine Antiepileptic drugs:Carbamazepine

‡ Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating ((Page name)) from Other Diseases

Pseudohyponatremia

• Hyperosmolar
  • Hyperglycemia
  • Mannitol
  • Severe azotemia
• Normoosmolar
  • Hyperlipidemia
  • Hyperproteinemia

Primary Polydypsia	SIADH	CSWǂ Syndrom

ǂ cerebral salt-wasting syndrome

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

Epidemiology and Demographics

Hyponatremia is found in 15–30% of hospitalized patients .7.7 % in outpatients with electrolyte disorders.Severe hyponatremia < 125 mmol/L occurs in 1–2% of patients. Prevalence of hyponatremia in patients admitted to ICUs is 25–30% , neurosurgical units 50% of patients with SAH (subarachnoid hemorrhage) , 20% of patients hospitalized for CHF(heart failure). 50% of nursing home residents had at least one episode of hyponatremia over a 12-month of study.

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.

OR.

In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

OR

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.

Patients of all age groups may develop [disease name].

OR

The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.

OR

[Disease name] commonly affects individuals younger than/older than [number of years] years of age.

OR

[Chronic disease name] is usually first diagnosed among [age group].

OR

[Acute disease name] commonly affects [age group].

There is no racial predilection to [disease name].

OR

[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

[Disease name] affects men and women equally.

OR

[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

The majority of [disease name] cases are reported in [geographical region].

OR

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

Risk Factors

amiodarone-induced SIADH was masked by tolvaptan therapy before LVAD implantation.

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnosis

Diagnostic Criteria

Characteristics	Hypervolemic Hyponatremia	Euvolemic Hyponatremia	Hypovolemic Hyponatremia
Total body water	↑↑	↑	↔
Serum sodium level	↑	↔	↓↓
Plasma Osmolality, mOsm/kg	< 280	<280	≥ 280
Urine Osmolality, mOsm/L	> 100	> 100	> 500
Urine sodium level, mEq/L	< 20 or >20	> 20	< 10 or > 20
Differentiation of causes	>20 mEq/L urinary sodium: Acute or chronic renal failure Fluid overload Psychogenic polydipsia <20 mEq/L urinary sodium: Heart failure Cirrhosis Nephritic syndrome	SIADH/SIAD Adrenal insufficiency Hypothyroidism Drugs	<10 mEq/L urinary sodium: Diuretics Extrarenal loss such as diarrhea, vomiting Severe hyperglycemia Third spacing of fluids >20 mEq/L urinary sodium: Adrenal insufficiency Renal bicarbonate loss(renal tubal acidosis, metabolic alkalosis) Renal sodium loss (cerebral salt wasting, salt-wasting nephropathy) Diuretics

Corrected serum Na⁺ = measured Na⁺ + 2.4 × ([glucose  – 100 mg/dL] /100 mg/dL)

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

History and Symptoms

The severity of neurological symptoms due to sodium deficiencies is related to the degree of cerebral edema caused by electrolyte and fluid imbalances and is correlated with the rate at which hyponatremia develops and the extent of the hyponatremia.

• headache, nausea, vomiting, muscle cramps, disorientation, depressed reflexes, seizures and coma.
• No signs or symptoms Difficulty concentrating Anorexia Headaches Irritability Restlessness Unstable gait and/or falls Nausea and/or vomiting Fatigue Disorientation and/or confusion Seizures Coma Respiratory arrest

The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [ 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Treatment

Symptomatic
Asymptomatic

Medical Therapy

Disorders	Treatment
Primary polydipsia	Fluid restriction
Hypovolemia	Volume expansion
Heart failure	Fluid restriction V2 receptor antagonists Loop diuretics ACE inhibitors
Liver cirrhosis	Loop diuretics V2 receptor antagonists
Cortisol deficiency	Glucocorticoids
SIADH/SIAD	Treat underlying cause if possible Fluid restriction Loop diuretics: low dose Furosemide Salt tablets Urea Increase dietary solute intake V2 receptor antagonists:Vaptans Demeclocycline
Renal insufficiency	Fluid restriction
Potomania	Increased dietary solute intake

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR   The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

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