Hypoaldosteronism pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
===Physiology===
===Physiology===
*The [[juxtaglomerular apparatus]] of the [[macula densa]] primarily senses the [[concentration]] of [[Blood plasma|plasma]] [[sodium]] and [[renal]] [[perfusion pressure]].  
*The [[juxtaglomerular apparatus]] of the [[macula densa]] primarily senses the [[concentration]] of [[Blood plasma|plasma]] [[sodium]] and [[renal]] [[perfusion pressure]].<ref name="pmid12208992">{{cite journal |vauthors=Schnermann J, Levine DZ |title=Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide |journal=Annu. Rev. Physiol. |volume=65 |issue= |pages=501–29 |year=2003 |pmid=12208992 |doi=10.1146/annurev.physiol.65.050102.085738 |url=}}</ref><ref name="pmid17280552">{{cite journal |vauthors=Castrop H |title=Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine |journal=Acta Physiol (Oxf) |volume=189 |issue=1 |pages=3–14 |year=2007 |pmid=17280552 |doi=10.1111/j.1748-1716.2006.01610.x |url=}}</ref>
** In response to low [[plasma]] [[sodium]] concentration or decreased [[renal]] [[perfusion pressure]], the [[juxtaglomerular apparatus]] secretes [[renin]].  
** In response to low [[plasma]] [[sodium]] concentration or decreased [[renal]] [[perfusion pressure]], the [[juxtaglomerular apparatus]] secretes [[renin]].  
** On secretion, [[renin]] cleaves [[angiotensinogen]] (produced by [[liver]]) to [[angiotensin I]].  
** On secretion, [[renin]] cleaves [[angiotensinogen]] (produced by [[liver]]) to [[angiotensin I]].  

Revision as of 15:10, 1 September 2017

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

Overview

Hypoaldosteronism is defined as decreased levels of the hormone aldosterone or a resistance of the target tissue to the actions of aldosterone. Hypoaldosteronism from decreased production is seen in conditions such as congenital isolated hypoaldosteronism, primary adrenal insufficiency, diabetic nephropathy, critical illness, and drugs such as ACE inhibitors, NSAIDs and calcineurin inhibitors. Resistance of the target tissue to the actions of aldosterone is seen with mineralocorticoid receptor defects (seen in pseudohypoaldosteronism) and with drugs such as potassium-sparing diuretics and trimethoprim. Hypoaldosteronism results in reduced reabsorption of sodium in the principal cells of cortical collecting tubules (CCT). This leads to decreased excretion of potassium (hyperkalemia) and mild non-anion gap metabolic acidosis. On gross pathology, adrenal glands may be irregularly shrunken or hyperplastic.

Pathophysiology

Physiology


Source:By A. Rad (me) (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons


Pathogenesis

Hyporeninemic Hypoaldosteronism

Hyperreninemic Hypoaldosteronism

Isolated Hypoaldosteronism

Postadrenalectomy Hypoaldosteronism

Postadrenalectomy hypoaldosteronism is seen in patients with Conn syndrome who undergo surgery for tumor removal:[7][8][9][10][11][12][13]

Mineralocorticoid Resistance

Mineralocorticoid resistance is characterized by a decrease in response to the hormone aldosterone. In mineralocorticoid resistance the level of aldosterone may be normal or supranormal. It is due to this reason mineralocorticoid resistance is also known as pseudohypoaldosteronism. Mineralocorticoid resistance can be further categorized into:[14][15][16]

  • Pseudohypoaldosteronism type I:
    • The decrease in response to aldosterone is due to heterozygous or homozygous inactivating mutations in the mineralocorticoid receptor. These patients are also resistant to mineralocorticoid therapy.
  • Pseudohypoaldosteronism Type II:
    • This is an extremely rare disorder. It is speculated that these patients have mutations in the genes encoding proteins of the serine threonine kinase family (WKNK1 or WNK4 kinases). Pseudohypoaldosteronism Type II is characterized by low or low-normal plasma renin activity and aldosterone concentrations, leading to hyperkalemia and metabolic acidosis with normal renal function. Pseudohypoaldosteronism type II is also known as Gordon’s syndrome.
  • Pseudohypoaldosteronism type III:
    • This condition presents with transient mineralocorticoid resistance. Pseudohypoaldosteronism type III is seen in patients with underlying renal conditions with decreased GFR. The exact cause is unknown but is thought to be related to increased levels of TGF-β.

Genetics


 
 
 
11 Deoxycorticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Corticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
18 Hydroxycorticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aldosterone
 
 
 


Associated Conditions

Gross Pathology

Image courtesy: PathologyOutlines.com
Image courtesy: PathologyOutlines.com

Microscopic Pathology

Image courtesy: PathologyOutlines.com
Image courtesy: PathologyOutlines.com

References

  1. Schnermann J, Levine DZ (2003). "Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide". Annu. Rev. Physiol. 65: 501–29. doi:10.1146/annurev.physiol.65.050102.085738. PMID 12208992.
  2. Castrop H (2007). "Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine". Acta Physiol (Oxf). 189 (1): 3–14. doi:10.1111/j.1748-1716.2006.01610.x. PMID 17280552.
  3. White PC (1994). "Disorders of aldosterone biosynthesis and action". N. Engl. J. Med. 331 (4): 250–8. doi:10.1056/NEJM199407283310408. PMID 8015573.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Yorke E, Stafford S, Holmes D, Sheth S, Melck A (2015). "Aldosterone deficiency after unilateral adrenalectomy for Conn's syndrome: a case report and literature review". Int J Surg Case Rep. 7C: 141–4. doi:10.1016/j.ijscr.2015.01.013. PMC 4336421. PMID 25604311.
  14. CHEEK DB, PERRY JW (1958). "A salt wasting syndrome in infancy". Arch. Dis. Child. 33 (169): 252–6. PMC 2012226. PMID 13545877.
  15. Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001). "Human hypertension caused by mutations in WNK kinases". Science. 293 (5532): 1107–12. doi:10.1126/science.1062844. PMID 11498583.
  16. Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Matsuo H, Murata T, Nomura S, Asano T, Kawaguchi H, Nonoyama S, Rai T, Sasaki S, Uchida S (2013). "Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension". Cell Rep. 3 (3): 858–68. doi:10.1016/j.celrep.2013.02.024. PMID 23453970.

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