Zollinger-Ellison syndrome pathophysiology: Difference between revisions
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==Pathogenesis== | ==Pathogenesis== | ||
* Symptoms of Zollinger-Ellison syndrome is related to hypergastrinemia.<ref name=" | * 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> | ||
* 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> | |||
* Hypertrophy of gastrin mucosa results in hypergastrinemia. | * Hypertrophy of gastrin mucosa results in hypergastrinemia. | ||
* Gastric acid secretion increase four to six four to six-fold. | * Gastric acid secretion increase four to six 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 | *The majority of patients have large and multiple peptic ulcers located in distal duodenum and proximal jejunum.<ref name="pmid7439637">{{cite journal| author=McGuigan JE, Wolfe MM| title=Secretin injection test in the diagnosis of gastrinoma. | journal=Gastroenterology | year= 1980 | volume= 79 | issue= 6 | pages= 1324-31 | pmid=7439637 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7439637 }}</ref> | ||
* | *Inactivation of pancreatic enzymes lead to fat [[malabsorption]] and [[diarrhea]].<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> | ||
==Genetics== | ==Genetics== | ||
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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 stimulates gastrin secretion from parietal cells by histamin release from enterochromaffin-like (ECL) cells.
- Gastrin activates cholecystokinin CCK2 receptor and somatostatin-secreting D cells.[9][10]
- Parietal cells
- Acid secretion stimulates by histamine release, gastrin release, and acetyl choline release.[11].
- Acid secretion inhibits by somatostatin secretion from oxyntic glands and antral D cells.
Pathogenesis
- Embryologic endoderm produces enteroendocrine cells and these cells are consider as origin of gastrinomas.[12]
- Symptoms of Zollinger-Ellison syndrome is related to hypergastrinemia.[13]
- Hypertrophy of gastrin mucosa results in hypergastrinemia.
- Gastric acid secretion increase four to six 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 lead to fat malabsorption and diarrhea.[15]
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. [16]
- 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. [17]
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. [18]
- 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. [18]
- 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. [18]
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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Norton JA (1994). "Neuroendocrine tumors of the pancreas and duodenum". Curr Probl Surg. 31 (2): 77–156. PMID 7904550.
- ↑ 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.
- ↑ McGuigan JE, Wolfe MM (1980). "Secretin injection test in the diagnosis of gastrinoma". Gastroenterology. 79 (6): 1324–31. PMID 7439637.
- ↑ "Gastrinoma - StatPearls - NCBI Bookshelf".
- ↑ 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.
- ↑ 18.0 18.1 18.2 Cingam S, Karanchi H. PMID 28722872. Missing or empty
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