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Zollinger-Ellison syndrome results from increased levels of [[gastrin]] due to an existing [[gastrinoma]] in the [[duodenum]] or [[pancreas]]. | Zollinger-Ellison syndrome results from increased levels of [[gastrin]] due to an existing [[gastrinoma]] in the [[duodenum]] or [[pancreas]]. | ||
== | ==Physiology== | ||
* Chemotransmitters which are delivered to gastric mucosa have the main role for stimulation and inhibition of acid and pepsin production.<ref name="pmid18474247">{{cite journal| author=Schubert ML, Peura DA| title=Control of gastric acid secretion in health and disease. | journal=Gastroenterology | year= 2008 | volume= 134 | issue= 7 | pages= 1842-60 | pmid=18474247 | doi=10.1053/j.gastro.2008.05.021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18474247 }} </ref> | |||
*Gastric acid is responsible for protein digestion, absorption of calcium, iron, vitamin B12, thyroid hormones and some drugs ( itraconazole and ketoconazole).<ref name="pmid25040647">{{cite journal| author=Irving SA, Vadiveloo T, Leese GP| title=Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). | journal=Clin Endocrinol (Oxf) | year= 2015 | volume= 82 | issue= 1 | pages= 136-41 | pmid=25040647 | doi=10.1111/cen.12559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25040647 }} </ref> | |||
* Gastric acid is responsible for lowering gastric PH. | |||
* Acidic PH kills many microorganisms, reduces bacterial growth, prevents intestinal infection and bacterial peritonitis.<ref name="pmid25151556">{{cite journal| author=Hegarty JP, Sangster W, Harris LR, Stewart DB| title=Proton pump inhibitors induce changes in colonocyte gene expression that may affect Clostridium difficile infection. | journal=Surgery | year= 2014 | volume= 156 | issue= 4 | pages= 972-8 | pmid=25151556 | doi=10.1016/j.surg.2014.06.074 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25151556 }} </ref><ref name="pmid24674763">{{cite journal| author=Buendgens L, Bruensing J, Matthes M, Dückers H, Luedde T, Trautwein C et al.| title=Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. | journal=J Crit Care | year= 2014 | volume= 29 | issue= 4 | pages= 696.e11-5 | pmid=24674763 | doi=10.1016/j.jcrc.2014.03.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24674763 }} </ref> | |||
*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 | |||
*** Mediated by vagal stimulation during thinking, smelling, seeing, and smeeling food. | |||
** Gastric | |||
*** The major mediator for acid secretion due to stomach distension and chemical effects related to the food. | |||
** Intestinal | |||
*** 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> | |||
** Parietal cells | |||
*** 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> | |||
*** Major endocrine involves in acidic secretion | |||
*** Gastrin-expressing cells (G cells) are located in antrum and responsible for gastrin secretion | |||
*** Gastrin has effects on parietal cells | |||
*** Gastrin receptors | |||
*Zollinger-Ellison syndrome is a disorder where the production of increased levels of [[gastrin]] causes the [[stomach]] to release excess amounts of [[hydrochloric acid]]. [[Gastrin]] then results in an excessive production of acid which often may lead to [[peptic ulcers]] (in almost 95% of patients).<ref name="wikipedia">wikipedia.2015.https://en.wikipedia.org/wiki/Zollinger%E2%80%93Ellison_syndrome</ref> | *Zollinger-Ellison syndrome is a disorder where the production of increased levels of [[gastrin]] causes the [[stomach]] to release excess amounts of [[hydrochloric acid]]. [[Gastrin]] then results in an excessive production of acid which often may lead to [[peptic ulcers]] (in almost 95% of patients).<ref name="wikipedia">wikipedia.2015.https://en.wikipedia.org/wiki/Zollinger%E2%80%93Ellison_syndrome</ref> | ||
*Increased basal [[gastric acid]] output and hyperplasia of the fundic [[parietal cells]] occur as a result of excessive amounts of [[gastrin]] that secreted by the gastrinoma tumor cells. The excessive [[gastric acid]] output overrides the mucosal defense of the [[gastric]] and [[duodenal]] wall thereby causing [[ulceration]], and inactivation of [[pancreatic]] digestive enzymes which therefore results in fat [[malabsorption]] and [[diarrhea]]. Secretory nature of [[diarrhea]] is a result of the inhibition of absorption of [[sodium]] and water by the [[small intestine]]. <ref name="urlGastrinoma - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK441842/ |title=Gastrinoma - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref> | *Increased basal [[gastric acid]] output and hyperplasia of the fundic [[parietal cells]] occur as a result of excessive amounts of [[gastrin]] that secreted by the gastrinoma tumor cells. The excessive [[gastric acid]] output overrides the mucosal defense of the [[gastric]] and [[duodenal]] wall thereby causing [[ulceration]], and inactivation of [[pancreatic]] digestive enzymes which therefore results in fat [[malabsorption]] and [[diarrhea]]. Secretory nature of [[diarrhea]] is a result of the inhibition of absorption of [[sodium]] and water by the [[small intestine]]. <ref name="urlGastrinoma - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK441842/ |title=Gastrinoma - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref> | ||
Revision as of 16:06, 25 March 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.
Physiology
- Chemotransmitters which are delivered to gastric mucosa have the main role for stimulation and inhibition of acid and pepsin production.[1]
- Gastric acid is responsible for protein digestion, absorption of calcium, iron, vitamin B12, thyroid hormones and some drugs ( itraconazole and ketoconazole).[2]
- Gastric acid is responsible for lowering gastric PH.
- Acidic PH kills many microorganisms, reduces bacterial growth, prevents intestinal infection and bacterial peritonitis.[3][4]
- Acid secretion has 3 phases:[5]
- Cephalic
- Mediated by vagal stimulation during thinking, smelling, seeing, and smeeling food.
- Gastric
- The major mediator for acid secretion due to stomach distension and chemical effects related to the food.
- Intestinal
- Small mediator for acid secretion due to chemical effects of food
- Cephalic
- Acid secretion mediated by some pathways:[6][7]
- Parietal cells
- Contains the hydrogen-potassium-ATPase acid-secreting pump which controls acid secretion
- Gastrin[8]
- Major endocrine involves in acidic secretion
- Gastrin-expressing cells (G cells) are located in antrum and responsible for gastrin secretion
- Gastrin has effects on parietal cells
- Gastrin receptors
- Parietal cells
- Zollinger-Ellison syndrome is a disorder where the production of increased levels of gastrin causes the stomach to release excess amounts of hydrochloric acid. Gastrin then results in an excessive production of acid which often may lead to peptic ulcers (in almost 95% of patients).[9]
- Increased basal gastric acid output and hyperplasia of the fundic parietal cells occur as a result of excessive amounts of gastrin that secreted by the gastrinoma tumor cells. The excessive gastric acid output overrides the mucosal defense of the gastric and duodenal wall thereby causing ulceration, and inactivation of pancreatic digestive enzymes which therefore results in fat malabsorption and diarrhea. Secretory nature of diarrhea is a result of the inhibition of absorption of sodium and water by the small intestine. [10]
- The pathophysiology of ZES is the stimulatory action of gastrin on the parietal cells of the gastric antrum resulting in hyper-secretory acid milieu. [11]
- Majority of patients with ZES also develop peptic ulcers which are large and multiple in number, usually in the distal duodenum and proximal jejunum (which usually would be an uncommon location for ulcers arising due to Helicobacter pylori or by the use of nonsteroidal anti-inflammatory drugs). [11]
Genetics
- The primary causative lesion is assumed to develop sporadically in approximately 80% of the cases and in the rest of the recorded cases, this entity exists as a part of MEN-1; an autosomal dominant disorder characterized by tumors of the pituitary, the parathyroid, and the pancreas. [12]
- ZES occurs in 20–30% of patients as part of the Multiple Endocrine Neoplasia-type 1 syndrome (MEN1 which is an autosomal dominant disorder as a result of mutations in an 10-exon gene at chromosome 11q13. [13]
Associated Conditions
Gross Pathology
- Gross pathology presents as enlarged fundic mucosal folds with cerebriform pattern.
Microscopic Pathology
- A well-differentiated neuroendocrine tumor (NET) histologically typically shows an organ like arrangement of cells with nesting, trabecular, or gyriform patterns. [14]
- The tumor cells are usually round with regular bland nuclei which produce large number of secretory granules with diffuse immunoexpression of neuroendocrine markers where as, the poorly differentiated neuroendocrine tumor (NET) shows a atypical, sheet-like, diffuse and irregular nuclei, less cytoplasmic secretory granules, and limited biomarker immunoexpression. [14]
- Immunostaining for chromogranin A and synaptophysin is an important step in the diagnosis of neuroendocrine tumors. In order to differentiate from other neuroendocrine tumors gastrin immunostaining may be used. somatostatin scintigraphy is considered an effective localizing tool as gastrinomas tend to express a high density of somatostatin receptors. [14]
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Schubert ML (2003). "Gastric secretion". Curr Opin Gastroenterol. 19 (6): 519–25. PMID 15703599.
- ↑ Geibel JP (2005). "Role of potassium in acid secretion". World J Gastroenterol. 11 (34): 5259–65. PMC 4622792. PMID 16149129.
- ↑ 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.
- ↑ 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.
- ↑ wikipedia.2015.https://en.wikipedia.org/wiki/Zollinger%E2%80%93Ellison_syndrome
- ↑ "Gastrinoma - StatPearls - NCBI Bookshelf".
- ↑ 11.0 11.1 Epelboym I, Mazeh H (2014). "Zollinger-Ellison syndrome: classical considerations and current controversies". Oncologist. 19 (1): 44–50. doi:10.1634/theoncologist.2013-0369. PMC 3903066. PMID 24319020.
- ↑ 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.
- ↑ 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.
- ↑ 14.0 14.1 14.2 Cingam S, Karanchi H. PMID 28722872. Missing or empty
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