Hyponatremia pathophysiology: Difference between revisions
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'''Pathogenesis:''' | '''Pathogenesis:''' | ||
* '''Decreased renal excretion of water''' is the most cases of hyponatremia, secondary to persistent action of ADH or gain of function mutation of the V2 receptor of ADH. | * '''Decreased renal excretion of water''' is the most cases of hyponatremia, secondary to persistent action of ADH or gain-of-function mutation of the V2 receptor of ADH. | ||
* '''Blood sampling''' from a vein that is being infused with hypotonic medications. | * '''Blood sampling''' from a vein that is being infused with hypotonic medications. | ||
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}}</ref>) | }}</ref>) | ||
* '''Excess water intake''' is a rare cause of hyponatremia.In psychogenic polydipsia, ingesting large volumes (>15-20 L/day) of water results in hyponatremia, in spite of normal renal function and diluting ability. | * '''Excess water intake''' is a rare cause of hyponatremia.In psychogenic polydipsia, ingesting large volumes (>15-20 L/day) of water results in hyponatremia, in spite of normal renal function and diluting ability. | ||
* '''Medications''' | * '''Medications''' cause hyponatremia with different mechanisms like interfering with urinary dilution (thiazide diuretics and nonsteroidal anti-inflammatory drugs [NSAIDs]), increasing ADH secretion or persisting ADH effect. | ||
* '''Clinical disorders''' ( congestive heart failure, nephrotic syndrome, cirrhosis) with the reduction in effective arterial blood volume, resulting in persistent ADH activity despite hypo-osmolar plasma. | * '''Clinical disorders''' ( congestive heart failure, nephrotic syndrome, cirrhosis) with the reduction in effective arterial blood volume, resulting in persistent ADH activity despite hypo-osmolar plasma. | ||
* '''Hormonal''' like cortisol which has an inhibitory effect on ADH release | * '''Hormonal''' like cortisol which has an inhibitory effect on ADH release.Adrenal insufficiency causes increased ADH level. | ||
* '''Volume loss''' like GI loss, renal loss and insensible loss cause solute and water loss simultaneously which leads to the rise in ADH secretion. | * '''Volume loss''' like GI loss, renal loss and insensible loss cause solute and water loss simultaneously which leads to the rise in ADH secretion. | ||
* '''Acute or chronic renal failure''' results in reduced functional nephron mass, decreased glomerular filtration rate, and therefore decreased capacity for water excretion. | * '''Acute or chronic renal failure''' results in reduced functional nephron mass, decreased glomerular filtration rate, and therefore decreased capacity for water excretion. | ||
Revision as of 20:27, 3 May 2018
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Hyponatremia Microchapters |
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Hyponatremia pathophysiology On the Web |
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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]
Overview
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
Blo [Disease or malignancy nme] 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.
Pathophysiology
Sodium is the main cation in the extracellular fluid, thus the plasma concentration of sodium is determinant of tonicity and serum osmolality.
The osmotic gradient of solutes that do not cross cell membranes constitutes serum Tonicity [1] which determines the distribution of water in the body.
Plasma tonicity = (Extracellular solute + Intracellular solute) / TBW
Serum or plasma osmolality measures different solutes in plasma. It helps to evaluate the etiology of hyponatremia and screen other solutes in serum.
Serum Osmolality = (2 x (Na + K)) + (BUN (mg/dL) / 2.8) + (glucose (mg/dL) / 18) + (Ethanol (mg/dL) /3.7) [2]
Normal Range= 275–295 mosm /kg (mmol /kg)
| Normal range | Osmolality versus Osmolarity | |
|---|---|---|
| Sodium‡ | 135-145 mEq/L |
(one liter of plasma equals to one kilogram of plasma thus plasma osmolarity and plasma osmolality would be the same but osmolality is independent of temperature and pressure so it's the more stable unite of measurment) |
| Potassium‡ | 3.5-5.1 mEq/L | |
| Blood Urea Nitrogen | 7-20 mg/dL (2.5-7.1 mmol/L) | |
| Glucose | 70-100 mg/dL ( 3.9-5.5 mmol/L) | |
‡ Mmol and Meq are the same for univalent ions like sodium, potassium
mOsmol/kg = n x mmol/L, for Na+, Cl-, Ca2+, urea, and glucose, 1 mmol/L equals 1 mOsmol/kg because n=1 , for NaCl n=2
Plasma water is regulated by sensory organs (baroreceptors and hypothalamus osmoreceptors), antidiuretic hormone (ADH or vasopressin), and the kidney.
Osmoreceptors in the hypothalamus are sensitive to the increased tonicity of serum.
ADH secretion from hypothalamus through posterior pituitary is increased by [4] [5]:
- ↑ Angiotensin II (activation of Renin-Angiotensin-Activation System)
- ↑ Sympathetic stimulation
- ↑ Effective osmoles (Hypertonicity)
- ↓ Baroreceptor firing ( ↓effective intravascular volume)
- ↓ Right atrium stretching
ADH increases renal free water reabsorption from the collecting tubules which results in correction of plasma sodium toward the normal range. The vasopressin type 2 (V2) receptor in the basolateral membrane of the collecting tubule acts as the antidiuretic effect of ADH. Binding of ADH to V2 receptor [6][7] intensifies the action of intracellular cyclic adenosine monophosphate (cAMP) which results in insertion of water channel (aquaporin 2) into the luminal membrane and increasing the numbers of aquaporin-2 mRNA level [8].As plasma water increases, plasma sodium concentration, osmolality, and ADH secretion decrease and the collecting tubule becomes impermeable to water.
Hyponatremia is defined as serum sodium less than 135 mEq/L (mmol/L).Hyponatremia is a water balance disorder which represents an imbalance in a ratio where total body water is more than total body solutes( total body sodium and total body potassium).
Pathogenesis:
- Decreased renal excretion of water is the most cases of hyponatremia, secondary to persistent action of ADH or gain-of-function mutation of the V2 receptor of ADH.
- Blood sampling from a vein that is being infused with hypotonic medications.
- Older techniques (e.g., flame photometry) for sodium measurement, high levels of protein or triglyceride can cause false hyponatremia (Pseudohyponatremia).
- Hyperglycemia can cause hyponatremia, osmotic water movement from cells into the blood, resulting in a relative decrease in serum sodium concentration in the absence of hypo-osmolality.
(for each 100-mg/dL increase in glucose concentration above 100 mg/dL The sodium concentration should be increased by approximately 1.6 to 2 mmol/L [9])
- Excess water intake is a rare cause of hyponatremia.In psychogenic polydipsia, ingesting large volumes (>15-20 L/day) of water results in hyponatremia, in spite of normal renal function and diluting ability.
- Medications cause hyponatremia with different mechanisms like interfering with urinary dilution (thiazide diuretics and nonsteroidal anti-inflammatory drugs [NSAIDs]), increasing ADH secretion or persisting ADH effect.
- Clinical disorders ( congestive heart failure, nephrotic syndrome, cirrhosis) with the reduction in effective arterial blood volume, resulting in persistent ADH activity despite hypo-osmolar plasma.
- Hormonal like cortisol which has an inhibitory effect on ADH release.Adrenal insufficiency causes increased ADH level.
- Volume loss like GI loss, renal loss and insensible loss cause solute and water loss simultaneously which leads to the rise in ADH secretion.
- Acute or chronic renal failure results in reduced functional nephron mass, decreased glomerular filtration rate, and therefore decreased capacity for water excretion.
Hyponatremia represents as 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.
Hypotonic (dilutional) hyponatraemia is classified by the extracellular volume status into hypo-, eu- and hyper-volemic hyponatremia.
| Term | Definitions[10][11][12] |
|---|---|
| Hyponatremia | Hyponatremia is defined as a serum sodium concentration < 135 mEq/L. |
| Hypotonic hyponatremia | Hyponatremia with low osmolality (hypotonic hyponatremia) is defined as hyponatremia with a serum osmolality below 280 mOsm/kg. |
| Hypertonic hyponatremia | Hyponatremia with high osmolality (hypertonic hyponatremia) is defined as hyponatremia with a serum osmolality greater than 295 mOsm/kg. |
| Isotonic hyponatremia | Hyponatremia with normal osmolality (Isotonic hyponatremia) is defined as hyponatremia with a serum osmolality ranging between 280-295 mOsm/kg. |
| Hyponatremia based on ECF volume | |
| Hypovolemic hyponatremia | Hyponatremia plus decreased extracellular cellular fluid volume. Usually diagnosed by history and physical examinationshowing water depletion plus spot urine sodium <20 to 30 mmol/L, unless kidney is the source of sodium loss. |
| Euvolemic hyponatremia | Hyponatremia plus normal extracellular cellular fluid volume. Majority of cases are of this type. Usually diagnosed by spot urine sodium ≥ 20 to 30 mmol/L, unless secondarily sodium depleted. |
| Hypervolemia hyponatremia | Hyponatremia plus increased extracellular cellular fluid volume. Usually diagnosed by history and physical examinationshowing water retention plus spot urine sodium <20 to 30 mmol/L |
Genetics
- Nephrogenic SIAD (syndrome of inappropriate anti diuresis) [13] : Gain-of-function mutations of the V2 vasopressin receptor gene (AVPR2) causes hyponatremia.
- Pseudohypoaldosteronism
- Aldosterone Biosynthetic Defects
- Gittleman syndrome
- Bartter syndrome
Associated Conditions
- Fanconi syndrome
- Renal tubular acicosis
References
- ↑ Sperelakis, Nick (2012). Cell physiology sourcebook : essentials of membrane biophysics. London, UK Waltham, MA, USA: Elsevier/Academic Press. ISBN 978-0-12-387738-3.
- ↑ Purssell, Roy A.; Pudek, Morris; Brubacher, Jeffrey; Abu-Laban, Riyad B. (2001). "Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap". Annals of Emergency Medicine. 38 (6): 653–659. doi:10.1067/mem.2001.119455. ISSN 0196-0644.
- ↑ Erstad BL (2003). "Osmolality and osmolarity: narrowing the terminology gap". Pharmacotherapy. 23 (9): 1085–6. PMID 14524639.
- ↑ G. L. Robertson (1987). "Physiology of ADH secretion". Kidney international. Supplement. 21: S20–S26. PMID 3476800. Unknown parameter
|month=ignored (help) - ↑ L. Share (1967). "Vasopressin, its bioassay and the physiological control of its release". The American journal of medicine. 42 (5): 701–712. PMID 5337374. Unknown parameter
|month=ignored (help) - ↑ Holmes, Cheryl L; Landry, Donald W; Granton, John T (2003). Critical Care. 7 (6): 427. doi:10.1186/cc2337. ISSN 1364-8535. Missing or empty
|title=(help) - ↑ Holmes, Cheryl L; Landry, Donald W; Granton, John T (2003). Critical Care. 7 (6): 427. doi:10.1186/cc2337. ISSN 1364-8535. Missing or empty
|title=(help) - ↑ Kwon, Tae-Hwan; Hager, Henrik; Nejsum, Lene N.; Andersen, Marie-Louise E.; Fr[oslash]ki[aelig ]r, J[oslash]rgen; Nielsen, S[oslash]ren (2001). "Physiology and pathophysiology of renal aquaporins". Seminars in Nephrology. 21 (3): 231–238. doi:10.1053/snep.2001.21647. ISSN 0270-9295.
- ↑ S. M. Lauriat & T. Berl (1997). "The hyponatremic patient: practical focus on therapy". Journal of the American Society of Nephrology : JASN. 8 (10): 1599–1607. PMID 9335390. Unknown parameter
|month=ignored (help) - ↑ Laczi, F. (2008). "[Etiology, diagnostics and therapy of hyponatremias]". Orv Hetil. 149 (29): 1347–54. doi:10.1556/OH.2008.28409. PMID 18617466. Unknown parameter
|month=ignored (help) - ↑ Douglas, I. (2006). "Hyponatremia: why it matters, how it presents, how we can manage it". Cleve Clin J Med. 73 Suppl 3: S4–12. PMID 16970147. Unknown parameter
|month=ignored (help) - ↑ Verbalis, JG.; Goldsmith, SR.; Greenberg, A.; Korzelius, C.; Schrier, RW.; Sterns, RH.; Thompson, CJ. (2013). "Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations". Am J Med. 126 (10 Suppl 1): S1–42. doi:10.1016/j.amjmed.2013.07.006. PMID 24074529. Unknown parameter
|month=ignored (help) - ↑ Powlson, Andrew S.; Challis, Benjamin G.; Halsall, David J.; Schoenmakers, Erik; Gurnell, Mark (2016). "Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2". Clinical Endocrinology. 85 (2): 306–312. doi:10.1111/cen.13011. ISSN 0300-0664.