Hypoaldosteronism pathophysiology: Difference between revisions
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** Patients with adrenal dysfunction such as Addison's disease. Primary adrenal insufficiency or Addison's disease can be due to adrenal dysgenesis, Impaired steroidogenesis, and adrenal destruction. In these patients, the adrenal glands do not produce sufficient cortisol and aldosterone. | ** Patients with adrenal dysfunction such as Addison's disease. Primary adrenal insufficiency or Addison's disease can be due to adrenal dysgenesis, Impaired steroidogenesis, and adrenal destruction. In these patients, the adrenal glands do not produce sufficient cortisol and aldosterone. | ||
** Thus, in the above conditions there occurs deceased level of renin with decreased level of aldosterone. | ** Thus, in the above conditions there occurs deceased level of renin with decreased level of aldosterone. | ||
===Mineralocorticoid Resistance=== | |||
Mineralocorticoid resistance is characterized by a decrease in response to the hormone aldosterone. Mineralocorticoid resistance is also known as pseudohypoaldosteronism and can be further categorized into: | |||
* Pseudohypoaldosteronism type I: The decrease in response to aldosterone is due to heterozygous or homogenous inactivating mutations in the mineralocorticoid receptor. These patients are also resistant to mineralocorticoid therapy. | |||
* Pseudohypoaldosteronism Type II: This s an extremely rare disorder. It is speculated that these patients have mutations in the genes encoding for proteins of the serine threonine. which leads to decrease in response to aldosterone. | |||
==Pathophysiology== | ==Pathophysiology== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
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
[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.
Pathophysiology
Hypoaldosteronism is defined as decreased levels of the hormone aldosterone (Normal range: 1-21 ng/dL). Hypoaldosteronism from decreased aldosterone synthesis can be due to :
- Adrenal Insufficiency
- Enzyme deficiency: Aldosterone synthase, 21 hydroxylase, and 11B hydroxylase
- Renal disorders: Chronic renal failure and diabetic nephropathy
- Drugs inhibiting aldosterone effect: NSAID, spironolactone, and triamterene
Postadrenalectomy Hypoaldosteronism
Patients of Conn syndrome who are treated with spironolactone and later undergo sugery for tumor removal may develop hypoaldosteronism. In these patients there is chronic suppression of contralateral zona glomerulosa which may lead to decreased levels of aldosterone. [1][2][3][4][5][6]
Isolated Hypoaldosteronism
- In isolated hypoaldosteronism, there is selective deficiency of aldosterone with normal cortisol production. Isolated hypoaldosteronism may result from dysfunction of zona glomerulosa or aldosterone synthase deficiency.
- Aldosterone synthase is an enzyme involved in the synthesis of aldosterone. Patients with aldosterone synthase enzyme deficiency (type I and type II) results in defective conversion of deoxycorticosterone to aldosterone and subsequently abnormal levels of aldosterone.
- Certain drugs such as heparin sodium and nitric oxide have a direct suppressive effect on zona glomerulosa of adrenal cortex which may lead to decrease production of aldosterone, corticosterone and androgens.
Secondary Isolated Hypoaldosteronism
- Hyperreninemic hypoaldosteronism is seen in patients with severe illness such as sepsis, malignancy, heart failure, and liver cirrhosis.[7][8][9]
- During these stress inducing conditions, there occurs increased level of ACTH and cortisol. Under normal conditions, continuous ACTH secretion for > 96 hours leads to suppression of aldosterone synthase activity.
- Thus, chronically ill patients with prolonged ACTH secretion (>96 hours) have impaired aldosterone synthase activity and decreased levels of aldosterone. In response, the kidneys via its neurohormonal regulation leads to increased levels of renin and hence the term hyperreninemic hypoaldosteronism.
- In addition, cytokine release from chronic illness and increased levels of atrial natriuretic peptide (in patients with heart failure) also have an inhibitory effect on zona glomerulosa.
Hyporeninemic Hypoaldosteronism
- Hyporeninemic hypoaldosteronism is most commonly seen in:
- Patients with mild to moderate renal insufficiency. In patients with renal insufficiency, there may be atrophy of the juxtaglomerular apparatus (JGA) which leads to decreased sensing of sodium and blood pressure by the kidneys. Over time, this leads to inadequate renin production and release. There may also be decreased response of principal cells in the cortical collecting tubule to aldosterone.
- Patients with adrenal dysfunction such as Addison's disease. Primary adrenal insufficiency or Addison's disease can be due to adrenal dysgenesis, Impaired steroidogenesis, and adrenal destruction. In these patients, the adrenal glands do not produce sufficient cortisol and aldosterone.
- Thus, in the above conditions there occurs deceased level of renin with decreased level of aldosterone.
Mineralocorticoid Resistance
Mineralocorticoid resistance is characterized by a decrease in response to the hormone aldosterone. Mineralocorticoid resistance is also known as pseudohypoaldosteronism and can be further categorized into:
- Pseudohypoaldosteronism type I: The decrease in response to aldosterone is due to heterozygous or homogenous inactivating mutations in the mineralocorticoid receptor. These patients are also resistant to mineralocorticoid therapy.
- Pseudohypoaldosteronism Type II: This s an extremely rare disorder. It is speculated that these patients have mutations in the genes encoding for proteins of the serine threonine. which leads to decrease in response to aldosterone.
Pathophysiology
Pathogenesis
- 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].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
- Gene involved in the pathogenesis of hypoaldosteronism include mutation in CYP11B2 gene, which is located on chromosome 8q24.
- Mutation in CYP11B2 gene is transmitted in autosomal recessive pattern.
- The CYP11B2 gene encodes for the enzyme aldosterone synthase (previously known as corticosterone methyloxidase).
- Aldosterone synthase catalyses the conversion of 11 Deoxycorticosterone to aldosterone
| 11 Deoxycorticosterone | |||||||||||||||||||
| Corticosterone | |||||||||||||||||||
| 18 Hydroxycorticosterone | |||||||||||||||||||
| Aldosterone | |||||||||||||||||||
- Mutations in CYP11B2 can lead to:
- Type 1 aldosterone synthase deficiency: Patients have normal to decreased levels of 18-hydroxycorticosterone and undetectable levels of aldosterone.
- Type 2 aldosterone synthase deficiency: Patients have increased levels of 18-hydroxycorticosterone and normal to decreased levels of aldosterone.
- Aldosterone synthase is a member of the cytochrome P450 family of enzymes.
Associated Conditions
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ Kawasaki T, Uezono K, Ueno M, Noda Y, Kumamoto K, Kawano Y, Ogata M, Fukiyama K, Omae T, Bartter FC (1980). "Influence of unilateral adrenalectomy on renin-angiotensin-aldosterone system in primary aldosteronism". Jpn Heart J. 21 (5): 681–92. PMID 7001091.
- ↑ Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J (2009). "Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism". Ann. Intern. Med. 151 (5): 329–37. PMID 19721021.
- ↑ Huang WT, Chau T, Wu ST, Lin SH (2010). "Prolonged hyperkalemia following unilateral adrenalectomy for primary hyperaldosteronism". Clin. Nephrol. 73 (5): 392–7. PMID 20420801.
- ↑ Gadallah MF, Kayyas Y, Boules F (1998). "Reversible suppression of the renin-aldosterone axis after unilateral adrenalectomy for adrenal adenoma". Am. J. Kidney Dis. 32 (1): 160–3. PMID 9669438.
- ↑ Biglieri EG, Slaton PE, Silen WS, Galante M, Forsham PH (1966). "Postoperative studies of adrenal function in primary aldosteronism". J. Clin. Endocrinol. Metab. 26 (5): 553–8. doi:10.1210/jcem-26-5-553. PMID 4287160.
- ↑ Groth H, Vetter W, Stimpel M, Greminger P, Tenschert W, Klaiber E, Vetter H (1985). "Adrenalectomy in primary aldosteronism: a long-term follow-up study". Cardiology. 72 Suppl 1: 107–16. PMID 3902226.
- ↑ Kater CE, Biglieri EG, Brust N, Chang B, Hirai J (1982). "Regulation of the mineralocorticoid hormones in adrenocortical disorders with adrenocorticotropin excess". Clin Exp Hypertens A. 4 (9–10): 1749–58. PMID 6291814.
- ↑ Aguilera G, Fujita K, Catt KJ (1981). "Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin". Endocrinology. 108 (2): 522–8. doi:10.1210/endo-108-2-522. PMID 6256154.
- ↑ Singer DR, Shirley DG, Markandu ND, Miller MA, Buckley MG, Sugden AL, Sagnella GA, MacGregor GA (1991). "How important are suppression of aldosterone and stimulation of atrial natriuretic peptide secretion in the natriuretic response to an acute sodium load in man?". Clin. Sci. 80 (4): 293–9. PMID 1851063.