Zollinger-Ellison syndrome pathophysiology: Difference between revisions

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*[[Gastric acid|Acid]] [[secretion]] has 3 phases:<ref name="pmid15703599">{{cite journal| author=Schubert ML| title=Gastric secretion. | journal=Curr Opin Gastroenterol | year= 2003 | volume= 19 | issue= 6 | pages= 519-25 | pmid=15703599 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15703599  }} </ref>
*[[Gastric acid|Acid]] [[secretion]] has 3 phases:<ref name="pmid15703599">{{cite journal| author=Schubert ML| title=Gastric secretion. | journal=Curr Opin Gastroenterol | year= 2003 | volume= 19 | issue= 6 | pages= 519-25 | pmid=15703599 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15703599  }} </ref>


# Cephalic
:1. Cephalic


** Mediated by vagal stimulation during thinking, smelling, seeing, and smeeling food.
:*Mediated by [[Vagus nerve|vagal]] stimulation during thinking about, smelling, and seeing food.


2. Gastric
:2. Gastric


** The major mediator for acid secretion due to stomach distension and chemical effects related to the food.
:*The major mediator for acid secretion due to [[stomach]] distension and [[chemical]] effects related to the food.


3. Intestinal
:3. Intestinal


** Small mediator for acid secretion due to chemical effects of food
:*Small mediator for acid secretion due to chemical effects of food


* Acid secretion mediated by some pathways:<ref name="pmid16149129">{{cite journal| author=Geibel JP| title=Role of potassium in acid secretion. | journal=World J Gastroenterol | year= 2005 | volume= 11 | issue= 34 | pages= 5259-65 | pmid=16149129 | doi= | pmc=4622792 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16149129  }} </ref><ref name="pmid17928547">{{cite journal| author=Heitzmann D, Warth R| title=No potassium, no acid: K+ channels and gastric acid secretion. | journal=Physiology (Bethesda) | year= 2007 | volume= 22 | issue=  | pages= 335-41 | pmid=17928547 | doi=10.1152/physiol.00016.2007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17928547  }} </ref>
* Acid secretion mediated by some pathways:<ref name="pmid16149129">{{cite journal| author=Geibel JP| title=Role of potassium in acid secretion. | journal=World J Gastroenterol | year= 2005 | volume= 11 | issue= 34 | pages= 5259-65 | pmid=16149129 | doi= | pmc=4622792 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16149129  }} </ref><ref name="pmid17928547">{{cite journal| author=Heitzmann D, Warth R| title=No potassium, no acid: K+ channels and gastric acid secretion. | journal=Physiology (Bethesda) | year= 2007 | volume= 22 | issue=  | pages= 335-41 | pmid=17928547 | doi=10.1152/physiol.00016.2007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17928547  }} </ref>
** Parietal cells
**[[Parietal cell|Parietal cells]]
*** Contains the hydrogen-potassium-ATPase acid-secreting pump which controls acid secretion
*** Contains the hydrogen-potassium-ATPase acid-secreting pump which controls acid secretion
** Gastrin<ref name="pmid24279703">{{cite journal| author=Waldum HL, Hauso Ø, Fossmark R| title=The regulation of gastric acid secretion - clinical perspectives. | journal=Acta Physiol (Oxf) | year= 2014 | volume= 210 | issue= 2 | pages= 239-56 | pmid=24279703 | doi=10.1111/apha.12208 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24279703  }} </ref>
**[[Gastrin]]<ref name="pmid24279703">{{cite journal| author=Waldum HL, Hauso Ø, Fossmark R| title=The regulation of gastric acid secretion - clinical perspectives. | journal=Acta Physiol (Oxf) | year= 2014 | volume= 210 | issue= 2 | pages= 239-56 | pmid=24279703 | doi=10.1111/apha.12208 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24279703  }} </ref>
*** Major endocrine involves in acidic secretion
*** Main [[hormone]] involved in acid secretion
*** Gastrin-expressing cells (G cells) are located in antrum and responsible for gastrin secretion
***[[G cell|Gastrin-expressing cells (G cells)]] are located in the [[antrum]] and are responsible for [[gastrin]] [[secretion]].
*** Gastrin stimulates gastrin secretion from parietal cells by histamin release from enterochromaffin-like (ECL) cells.
***[[Gastrin]] stimulates [[gastrin]] [[secretion]] from [[Parietal cell|parietal cells]] by [[histamine]] release from [[Enterochromaffin cells|enterochromaffin-like (ECL) cells]].
*** Gastrin activates cholecystokinin CCK2 receptor and somatostatin-secreting D cells.<ref name="pmid2859810">{{cite journal| author=Soll AH, Amirian DA, Park J, Elashoff JD, Yamada T| title=Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture. | journal=Am J Physiol | year= 1985 | volume= 248 | issue= 5 Pt 1 | pages= G569-73 | pmid=2859810 | doi=10.1152/ajpgi.1985.248.5.G569 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2859810  }} </ref><ref name="pmid1373504">{{cite journal| author=Kopin AS, Lee YM, McBride EW, Miller LJ, Lu M, Lin HY et al.| title=Expression cloning and characterization of the canine parietal cell gastrin receptor. | journal=Proc Natl Acad Sci U S A | year= 1992 | volume= 89 | issue= 8 | pages= 3605-9 | pmid=1373504 | doi= | pmc=48917 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1373504  }} </ref>
***[[Gastrin]] activates [[Cholecystokinin receptor|cholecystokinin (CCK) 2 receptor]] and somatostatin-secreting D cells.<ref name="pmid2859810">{{cite journal| author=Soll AH, Amirian DA, Park J, Elashoff JD, Yamada T| title=Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture. | journal=Am J Physiol | year= 1985 | volume= 248 | issue= 5 Pt 1 | pages= G569-73 | pmid=2859810 | doi=10.1152/ajpgi.1985.248.5.G569 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2859810  }} </ref><ref name="pmid1373504">{{cite journal| author=Kopin AS, Lee YM, McBride EW, Miller LJ, Lu M, Lin HY et al.| title=Expression cloning and characterization of the canine parietal cell gastrin receptor. | journal=Proc Natl Acad Sci U S A | year= 1992 | volume= 89 | issue= 8 | pages= 3605-9 | pmid=1373504 | doi= | pmc=48917 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1373504  }} </ref>
* Acid secretion stimulates by histamine release, gastrin release, and acetyl choline release.<ref name="pmid7502535">{{cite journal| author=Sachs G, Prinz C, Loo D, Bamberg K, Besancon M, Shin JM| title=Gastric acid secretion: activation and inhibition. | journal=Yale J Biol Med | year= 1994 | volume= 67 | issue= 3-4 | pages= 81-95 | pmid=7502535 | doi= | pmc=2588922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7502535  }} </ref>.
* Acid secretion is stimulated by [[histamine]] release, [[gastrin]] release, and [[acetylcholine]] release.<ref name="pmid7502535">{{cite journal| author=Sachs G, Prinz C, Loo D, Bamberg K, Besancon M, Shin JM| title=Gastric acid secretion: activation and inhibition. | journal=Yale J Biol Med | year= 1994 | volume= 67 | issue= 3-4 | pages= 81-95 | pmid=7502535 | doi= | pmc=2588922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7502535  }} </ref>.
* Acid secretion inhibits by somatostatin secretion from oxyntic glands and antral D cells.
* Acid secretion is inhibited by somatostatin secretion from oxyntic glands and antral D cells.


===Pathogenesis===
===Pathogenesis===


* Embryologic endoderm produces enteroendocrine cells and these cells are consider as origin of gastrinomas.<ref name="pmid7904550">{{cite journal| author=Norton JA| title=Neuroendocrine tumors of the pancreas and duodenum. | journal=Curr Probl Surg | year= 1994 | volume= 31 | issue= 2 | pages= 77-156 | pmid=7904550 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7904550  }}</ref>
*[[Embryology|Embryologic]] [[endoderm]] produces [[enteroendocrine cells]] and these [[Cell (biology)|cells]] are considered as the origin of [[Gastrinoma|gastrinomas]].<ref name="pmid7904550">{{cite journal| author=Norton JA| title=Neuroendocrine tumors of the pancreas and duodenum. | journal=Curr Probl Surg | year= 1994 | volume= 31 | issue= 2 | pages= 77-156 | pmid=7904550 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7904550  }}</ref>
* Symptoms of Zollinger-Ellison syndrome is related to hypergastrinemia.<ref name="pmid17108778">{{cite journal| author=Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT| title=Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. | journal=Medicine (Baltimore) | year= 2006 | volume= 85 | issue= 6 | pages= 295-330 | pmid=17108778 | doi=10.1097/01.md.0000236956.74128.76 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17108778  }}</ref>
* Symptoms of Zollinger-Ellison syndrome are related to hypergastrinemia.<ref name="pmid17108778">{{cite journal| author=Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT| title=Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. | journal=Medicine (Baltimore) | year= 2006 | volume= 85 | issue= 6 | pages= 295-330 | pmid=17108778 | doi=10.1097/01.md.0000236956.74128.76 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17108778  }}</ref>
* Hypertrophy of gastrin mucosa results in hypergastrinemia.
*[[Hypertrophy (medical)|Hypertrophy]] of [[gastrin]] [[Mucous membrane|mucosa]] results in hypergastrinemia.
* Gastric acid secretion increase four to six four to six-fold.
*[[Gastric acid]] [[secretion]] increases four to six-fold.
* Hypergastrinemia results from increase activity of parietal cells and histamine-secreting enterochromaffin-like cells.
* Hypergastrinemia results from increase activity of parietal cells and histamine-secreting enterochromaffin-like cells.
*Gastric acid secretion overrides the mucosal defense of the [[gastric]] and [[duodenal]] wall which may cause [[ulceration]] and inactivation of [[pancreatic]] enzymes.
*Gastric acid secretion overrides the mucosal defense of the [[gastric]] and [[duodenal]] wall which may cause [[ulceration]] and inactivation of [[pancreatic]] enzymes.

Latest revision as of 01:55, 12 September 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2] Mohamad Alkateb, MBBCh [3]

Overview

Zollinger-Ellison syndrome results from increased levels of gastrin due to an existing gastrinoma in the duodenum or pancreas.

Pathophysiology

Physiology

1. Cephalic
  • Mediated by vagal stimulation during thinking about, smelling, and seeing food.
2. Gastric
  • The major mediator for acid secretion due to stomach distension and chemical effects related to the food.
3. Intestinal
  • Small mediator for acid secretion due to chemical effects of food

Pathogenesis

  • Embryologic endoderm produces enteroendocrine cells and these cells are considered as the origin of gastrinomas.[12]
  • Symptoms of Zollinger-Ellison syndrome are related to hypergastrinemia.[13]
  • Hypertrophy of gastrin mucosa results in hypergastrinemia.
  • Gastric acid secretion increases four to six-fold.
  • Hypergastrinemia results from increase activity of parietal cells and histamine-secreting enterochromaffin-like cells.
  • Gastric acid secretion overrides the mucosal defense of the gastric and duodenal wall which may cause ulceration and inactivation of pancreatic enzymes.
  • The majority of patients have large and multiple peptic ulcers located in distal duodenum and proximal jejunum.[14]
  • Inactivation of pancreatic enzymes leads to fat malabsorption and diarrhea.[15]
  • High gastric acid secretion does not reabsorb in small intestine and colon; therefore, it results in chronic diarrhea.[13]
  • Sodium and water do not reabsorb in presence of high volume of gastric acids which results in secretory diarrhea.
  • The major factors related to fat malabsorption are as following:[16]
    • Gastric mucosal damage
    • Inactivation of Pancreatic enzymes
    • Bile salts precipitation

Genetics

Associated Conditions

Gross Pathology

Microscopic Pathology

By Ed Uthman from Houston, TX, USA [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

References

  1. Schubert ML, Peura DA (2008). "Control of gastric acid secretion in health and disease". Gastroenterology. 134 (7): 1842–60. doi:10.1053/j.gastro.2008.05.021. PMID 18474247.
  2. Irving SA, Vadiveloo T, Leese GP (2015). "Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS)". Clin Endocrinol (Oxf). 82 (1): 136–41. doi:10.1111/cen.12559. PMID 25040647.
  3. Hegarty JP, Sangster W, Harris LR, Stewart DB (2014). "Proton pump inhibitors induce changes in colonocyte gene expression that may affect Clostridium difficile infection". Surgery. 156 (4): 972–8. doi:10.1016/j.surg.2014.06.074. PMID 25151556.
  4. Buendgens L, Bruensing J, Matthes M, Dückers H, Luedde T, Trautwein C; et al. (2014). "Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea". J Crit Care. 29 (4): 696.e11–5. doi:10.1016/j.jcrc.2014.03.002. PMID 24674763.
  5. Schubert ML (2003). "Gastric secretion". Curr Opin Gastroenterol. 19 (6): 519–25. PMID 15703599.
  6. Geibel JP (2005). "Role of potassium in acid secretion". World J Gastroenterol. 11 (34): 5259–65. PMC 4622792. PMID 16149129.
  7. Heitzmann D, Warth R (2007). "No potassium, no acid: K+ channels and gastric acid secretion". Physiology (Bethesda). 22: 335–41. doi:10.1152/physiol.00016.2007. PMID 17928547.
  8. Waldum HL, Hauso Ø, Fossmark R (2014). "The regulation of gastric acid secretion - clinical perspectives". Acta Physiol (Oxf). 210 (2): 239–56. doi:10.1111/apha.12208. PMID 24279703.
  9. Soll AH, Amirian DA, Park J, Elashoff JD, Yamada T (1985). "Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture". Am J Physiol. 248 (5 Pt 1): G569–73. doi:10.1152/ajpgi.1985.248.5.G569. PMID 2859810.
  10. Kopin AS, Lee YM, McBride EW, Miller LJ, Lu M, Lin HY; et al. (1992). "Expression cloning and characterization of the canine parietal cell gastrin receptor". Proc Natl Acad Sci U S A. 89 (8): 3605–9. PMC 48917. PMID 1373504.
  11. Sachs G, Prinz C, Loo D, Bamberg K, Besancon M, Shin JM (1994). "Gastric acid secretion: activation and inhibition". Yale J Biol Med. 67 (3–4): 81–95. PMC 2588922. PMID 7502535.
  12. Norton JA (1994). "Neuroendocrine tumors of the pancreas and duodenum". Curr Probl Surg. 31 (2): 77–156. PMID 7904550.
  13. 13.0 13.1 Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT (2006). "Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature". Medicine (Baltimore). 85 (6): 295–330. doi:10.1097/01.md.0000236956.74128.76. PMID 17108778.
  14. McGuigan JE, Wolfe MM (1980). "Secretin injection test in the diagnosis of gastrinoma". Gastroenterology. 79 (6): 1324–31. PMID 7439637.
  15. "Gastrinoma - StatPearls - NCBI Bookshelf".
  16. King CE, Toskes PP (1983). "Nutrient malabsorption in the Zollinger-Ellison syndrome. Normalization during long-term cimetidine therapy". Arch Intern Med. 143 (2): 349–51. PMID 6824402.
  17. Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR; et al. (2012). "Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)". J Clin Endocrinol Metab. 97 (9): 2990–3011. doi:10.1210/jc.2012-1230. PMID 22723327.
  18. Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT (2006). "Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature". Medicine (Baltimore). 85 (6): 295–330. doi:10.1097/01.md.0000236956.74128.76. PMID 17108778.
  19. Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT (2006). "Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature". Medicine (Baltimore). 85 (6): 295–330. doi:10.1097/01.md.0000236956.74128.76. PMID 17108778.
  20. Ito T, Igarashi H, Uehara H, Jensen RT (2013). "Pharmacotherapy of Zollinger-Ellison syndrome". Expert Opin Pharmacother. 14 (3): 307–21. doi:10.1517/14656566.2013.767332. PMC 3580316. PMID 23363383.
  21. Zhuang Z, Vortmeyer AO, Pack S, Huang S, Pham TA, Wang C; et al. (1997). "Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas". Cancer Res. 57 (21): 4682–6. PMID 9354421.
  22. Norton JA (1994). "Neuroendocrine tumors of the pancreas and duodenum". Curr Probl Surg. 31 (2): 77–156. PMID 7904550.
  23. 23.0 23.1 23.2 Cingam S, Karanchi H. PMID 28722872. Missing or empty |title= (help)

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