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{{Acute pancreatitis}}
{{Acute pancreatitis}}
{{CMG}}; {{AE}} {{RT}}; {{TarekNafee}}


{{CMG}}; {{AE}} {{RT}}
==Overview==
The pathophysiology of acute pancreatitis involves [[Acute inflammation of pancreas|acute inflammation]] and [[edema]] of the [[pancreas]]. The process is mediated by the abnormal activation of [[trypsinogen]] to [[trypsin]] inside the pancreas, and the involvement of other mediators such as [[cathepsin]], [[lysosomal enzymes]], and caspases. Intrapancreatic activation of [[amylase]] and [[lipase]] is what causes [[necrosis]] of pancreatic cells. 
 
==Pathophysiology==


==Overview==
=== Pathogenesis ===
* The two types of [[pancreatitis]] are mild pancreatitis and severe pancreatitis, which are separated based on whether their predominant response to cell injury is [[inflammation]] or [[necrosis]], respectively. 
* In mild [[pancreatitis]] there is [[inflammation]] and [[edema]] of the pancreas. 
* In severe pancreatitis, there are additional features of [[necrosis]] and secondary injury to extrapancreatic organs. 
* Both types share a common mechanism of abnormal inhibition of secretion of [[zymogens]] and inappropriate activation of [[pancreatic]] [[zymogens]] inside the [[pancreas]], most notably [[trypsinogen]].  Normally, [[trypsinogen]] is activated to [[trypsin]] in the [[duodenum]] where it assists in the digestion of proteins. 
* During an [[acute pancreatitis]] episode there is co-localization of [[lysosomal enzymes]], specifically [[cathepsin]] with [[trypsinogen]]. 
* [[Cathepsin]] activates [[trypsinogen]] to trypsin leading to further activation of other molecules of [[trypsinogen]] and immediate pancreatic cell death according to either the [[necrosis]] or [[apoptosis]] mechanism (or a mix between the two). 
* The balance between these two processes is mediated by [[caspases]] which regulate [[apoptosis]] and have important anti-necrosis functions during pancreatitis: preventing [[trypsinogen]] activation, preventing [[ATP]] depletion through inhibiting poly ADP-ribose polymerase, and by inhibiting the inhibitors of [[apoptosis]] (IAPs).  If, however, the [[caspases]] are depleted due to either [[chronic]] [[ethanol]] exposure or through a severe insult then [[necrosis]] can predominate.
 
==== Transient Obstruction of Pancreatic Ducts ====
* The aforementioned [[inflammatory]] process which primarily manifests as oversecretion of [[zymogens]] and activation of [[trypsinogen]] in the [[pancreas]] is often a result of transient obstruction of the pancreatic ducts.
* This obstruction is the triggering insult which is the underlying mechanism for the most common cause of [[acute pancreatitis]] - migrating [[gallstones]] or sludge.
* Other causes of transient obstruction include:
** Dysfunctional [[sphincter of Oddi]]
** Pancreas divisium, though the association of these disorders with acute pancreatitis has come into question in the absence of underlying [[genetic]] disease.<ref name="pmid22982183">{{cite journal| author=Coté GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L et al.| title=Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis. | journal=Gastroenterology | year= 2012 | volume= 143 | issue= 6 | pages= 1502-1509.e1 | pmid=22982183 | doi=10.1053/j.gastro.2012.09.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22982183  }}</ref><ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>
 
==== Alcoholism ====
* Alcohol is proposed to have a direct, toxic effect on the [[pancreas]].
* It is metabolized by the [[pancreas]] and may result in [[oxidative stress]] and induce the release of pancreatic enzymes. This excessive release may result in auto-digestion of the gland.
* Additionally, alcohol may result in activation of pancreatic [[Stellate cell|stellate cells]] which are primarily responsible for [[fibrosis]] of the gland and weakening of the intracellular membranes, which results in anatomical changes in the [[pancreas]], further predisposing to [[pathological]] auto-digestion.<ref name="pmid21091991">{{cite journal| author=Apte MV, Pirola RC, Wilson JS| title=Mechanisms of alcoholic pancreatitis. | journal=J Gastroenterol Hepatol | year= 2010 | volume= 25 | issue= 12 | pages= 1816-26 | pmid=21091991 | doi=10.1111/j.1440-1746.2010.06445.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21091991  }}</ref><ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>


==== Hypertriglyceridemia ====
* [[Triglyceride]] rich [[lipoproteins]] are primarily comprised of [[chylomicrons]] and [[VLDL|VLDLs]]. These molecules are large and in abundance in conditions of [[Hypertriglyceridemia (patient information)|hypertriglyceridemia]].
* These molecules have been postulated to occlude [[pancreatic]] [[capillaries]] and result in subsequent [[acinar]] pancreatic structural changes.
* Additionally, this triggers the release of pancreatic [[lipases]] to catabolize the lipid rich molecules.
* It results in increased local [[oxidative stress]] which further contributes to the [[inflammatory response]] in the pancreas, resulting in the symptomatology of acute pancreatitis. <ref name="pmid22276267">{{cite journal| author=Kota SK, Kota SK, Jammula S, Krishna SV, Modi KD| title=Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 1 | pages= 141-3 | pmid=22276267 | doi=10.4103/2230-8210.91211 | pmc=3263185 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22276267  }} </ref><ref name="pmid12488710">{{cite journal| author=Yadav D, Pitchumoni CS| title=Issues in hyperlipidemic pancreatitis. | journal=J Clin Gastroenterol | year= 2003 | volume= 36 | issue= 1 | pages= 54-62 | pmid=12488710 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12488710  }} </ref><ref name="pmid9013278">{{cite journal| author=Kimura W, Mössner J| title=Role of hypertriglyceridemia in the pathogenesis of experimental acute pancreatitis in rats. | journal=Int J Pancreatol | year= 1996 | volume= 20 | issue= 3 | pages= 177-84 | pmid=9013278 | doi=10.1007/BF02803766 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9013278  }} </ref><ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>


==Pathophysiology==
==== Post ERCP Pancreatitis ====
The two types of pancreatitis are mild pancreatitis and severe pancreatitis, which are separated based on whether their predominant response to cell injury is inflammation or necrosis, respectively. In mild pancreatitis there is inflammation and edema of the pancreas. In severe pancreatitis there are additional features of necrosis and secondary injury to extrapancreatic organs.  Both types share a common mechanism of abnormal inhibition of secretion of [[zymogens]] and inappropriate activation of pancreatic zymogens inside the pancreas, most notably [[trypsinogen]].  Normally, trypsinogen is activated to [[trypsin]] in the duodenum where it assists in the digestion of proteins.  During an acute pancreatitis episode there is colocalization of lysosomal enzymes, specifically [[cathepsin]], with trypsinogen.  Cathepsin activates trypsinogen to trypsin leading to further activation of other molecules of trypsinogen and immediate pancreatic cell death according to either the necrosis or apoptosis mechanism (or a mix between the two). The balance between these two processes is mediated by [[caspases]] which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing ATP depletion through inhibiting polyADP-ribose polymerase, and by inhibiting the inhibitors of apoptosis (IAPs).  If, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate.
* The mechanism by which post-[[ERCP]] [[pancreatitis]] (PEP) occurs is not fully understood.
* However, it is proposed that mechanical, [[chemical]], [[allergic]], and thermally induced [[trauma]] to the pancreatic orifice and duct are the underlying causes.  
* Instrumental manipulation of the pancreatic orifices, as well as [[chemical]] and [[allergic]] damage due to contrast injection contribute to the pathogenesis.<ref name="pmid8122635">{{cite journal| author=Sherman S| title=ERCP and endoscopic sphincterotomy-induced pancreatitis. | journal=Am J Gastroenterol | year= 1994 | volume= 89 | issue= 3 | pages= 303-5 | pmid=8122635 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8122635 }} </ref><ref name="pmid15139506">{{cite journal| author=George S, Kulkarni AA, Stevens G, Forsmark CE, Draganov P| title=Role of osmolality of contrast media in the development of post-ERCP pancreatitis: a metanalysis. | journal=Dig Dis Sci | year= 2004 | volume= 49 | issue= 3 | pages= 503-8 | pmid=15139506 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15139506  }}</ref>
* Additionally, [[cauterization]] of the [[superficial]] and [[intraluminal]] pancreatic structures may result in thermal damage.<ref name="pmid9869722">{{cite journal| author=Ratani RS, Mills TN, Ainley CC, Swain CP| title=Electrophysical factors influencing endoscopic sphincterotomy. | journal=Gastrointest Endosc | year= 1999 | volume= 49 | issue= 1 | pages= 43-52 | pmid=9869722 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9869722 }}</ref>
* These [[iatrogenic]] traumatic and toxic influences may, again, stimulate the fibrogenic pancreatic [[Stellate cell|stellate cells]] to initiate a cascade of events responsible for activation of [[zymogens]] and autodigestion of the pancreas.<ref name="pmid21869870">{{cite journal| author=Baillie J| title=Management of Post-ERCP Pancreatitis. | journal=Gastroenterol Hepatol (N Y) | year= 2011 | volume= 7 | issue= 6 | pages= 390-2 | pmid=21869870 | doi= | pmc=3151411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21869870  }}</ref><ref name="pmid19590651">{{cite journal| author=Matsubayashi H, Fukutomi A, Kanemoto H, Maeda A, Matsunaga K, Uesaka K et al.| title=Risk of pancreatitis after endoscopic retrograde cholangiopancreatography and endoscopic biliary drainage. | journal=HPB (Oxford) | year= 2009 | volume= 11 | issue= 3 | pages= 222-8 | pmid=19590651 | doi=10.1111/j.1477-2574.2008.00020.x | pmc=2697892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19590651 }} </ref><ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>


===Microscopic Pathology===
===Microscopic Pathology===
The acute pancreatitis (acute hemorrhagic pancreatic necrosis) is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessels necrosis - hemorrhage. These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces. Necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. It is possible to find calcium precipitates (hematoxylinophilic). Digestion of vascular walls results in thrombosis and hemorrhage. Inflammatory infiltrate is rich in [[neutrophils]]. Photos at: [http://www.pathologyatlas.ro/Acute%20Pancreatitis.html Atlas of Pathology]
*The [[acute pancreatitis]] (acute [[hemorrhagic]] pancreatic [[necrosis]]) is characterized by:
**[[Acute inflammation of pancreas|Acute inflammation]] and [[necrosis]] of [[pancreas]] [[parenchyma]]
**Focal [[enzymatic]] [[necrosis]] of [[pancreatic]] fat  
**Vessel necrosis  
**Hemorrhage
 
*These are produced by intrapancreatic activation of [[pancreatic enzymes]].  
**[[Lipase]] activation produces the [[necrosis]] of fat tissue in [[pancreatic]] [[interstitium]] and peripancreatic spaces.  
 
*[[Necrotic]] [[fat cells]] appear as:
**Shadows
**Contours of cells
**Lacking the [[nucleus]] with pink, finely granular [[cytoplasm]]
*[[Calcium]] precipitates ([[hematoxylinophilic]]).  
*Digestion of [[vascular]] walls results in [[thrombosis]] and [[hemorrhage]].  
*[[Inflammatory]] infiltrate is rich in [[neutrophils]].
 
=== Genetics ===
Several [[genes]] have been proposed to play a role in the [[pathogenesis]] of [[acute pancreatitis]]. While the exact role of every implicated [[genetic mutation]] is not fully understood, the following genes have been associated with the development of [[acute pancreatitis]]:<ref name="pmid23622139">{{cite journal| author=Whitcomb DC| title=Genetic risk factors for pancreatic disorders. | journal=Gastroenterology | year= 2013 | volume= 144 | issue= 6 | pages= 1292-302 | pmid=23622139 | doi=10.1053/j.gastro.2013.01.069 | pmc=3684061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23622139  }}</ref><ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>
* [[CFTR]]
* [https://en.wikipedia.org/wiki/Trypsin_1 PRSS-1]
* [https://en.wikipedia.org/wiki/SPINK1 SPINK-1]
* [https://en.wikipedia.org/wiki/Chymotrypsin-C Chymotrypsin C]
* [https://en.wikipedia.org/wiki/CLDN2 Claudin-2]
* [https://en.wikipedia.org/wiki/Calcium-sensing_receptor Calcium sensing receptors]
 
=== Associated Conditions ===
The most common conditions associated with acute pancreatitis include:<ref name="acutepancreatitis">{{cite journal
| last      = Forsmark
| first      = Chris E.
| last2      = Vege
| first2    = Santhi Swaroop
| last3      = Wilcox
| first3    = Mel
| date      = November 17,2016
| title      = Acute Pancreatitis
| url        = http://www.nejm.org/doi/full/10.1056/NEJMra1505202
| journal    = The New England Journal of Medicine
| volume    =
| issue      =
| pages      = 1972 - 1981
| doi        = 10.1056/NEJMra1505202
| pmc        =
| pmid      =
| access-date = November 25,2016
| name-list-format = vanc
}}</ref>
* [[Alcoholism]]<ref name="pmid21029787">{{cite journal| author=Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR et al.| title=Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. | journal=Clin Gastroenterol Hepatol | year= 2011 | volume= 9 | issue= 3 | pages= 266-73; quiz e27 | pmid=21029787 | doi=10.1016/j.cgh.2010.10.015 | pmc=3043170 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21029787  }}</ref>
* [[Smoking]]<ref name="pmid210297872">{{cite journal| author=Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR et al.| title=Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. | journal=Clin Gastroenterol Hepatol | year= 2011 | volume= 9 | issue= 3 | pages= 266-73; quiz e27 | pmid=21029787 | doi=10.1016/j.cgh.2010.10.015 | pmc=3043170 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21029787  }}</ref>
* Obsesity<ref name="pmid21904207">{{cite journal| author=Hong S, Qiwen B, Ying J, Wei A, Chaoyang T| title=Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis. | journal=Eur J Gastroenterol Hepatol | year= 2011 | volume= 23 | issue= 12 | pages= 1136-43 | pmid=21904207 | doi=10.1097/MEG.0b013e32834b0e0e | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21904207  }}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]; Tarek Nafee, M.D. [3]

Overview

The pathophysiology of acute pancreatitis involves acute inflammation and edema of the pancreas. The process is mediated by the abnormal activation of trypsinogen to trypsin inside the pancreas, and the involvement of other mediators such as cathepsin, lysosomal enzymes, and caspases. Intrapancreatic activation of amylase and lipase is what causes necrosis of pancreatic cells.

Pathophysiology

Pathogenesis

Transient Obstruction of Pancreatic Ducts

  • The aforementioned inflammatory process which primarily manifests as oversecretion of zymogens and activation of trypsinogen in the pancreas is often a result of transient obstruction of the pancreatic ducts.
  • This obstruction is the triggering insult which is the underlying mechanism for the most common cause of acute pancreatitis - migrating gallstones or sludge.
  • Other causes of transient obstruction include:
    • Dysfunctional sphincter of Oddi
    • Pancreas divisium, though the association of these disorders with acute pancreatitis has come into question in the absence of underlying genetic disease.[1][2]

Alcoholism

  • Alcohol is proposed to have a direct, toxic effect on the pancreas.
  • It is metabolized by the pancreas and may result in oxidative stress and induce the release of pancreatic enzymes. This excessive release may result in auto-digestion of the gland.
  • Additionally, alcohol may result in activation of pancreatic stellate cells which are primarily responsible for fibrosis of the gland and weakening of the intracellular membranes, which results in anatomical changes in the pancreas, further predisposing to pathological auto-digestion.[3][2]

Hypertriglyceridemia

Post ERCP Pancreatitis

  • The mechanism by which post-ERCP pancreatitis (PEP) occurs is not fully understood.
  • However, it is proposed that mechanical, chemical, allergic, and thermally induced trauma to the pancreatic orifice and duct are the underlying causes.
  • Instrumental manipulation of the pancreatic orifices, as well as chemical and allergic damage due to contrast injection contribute to the pathogenesis.[7][8]
  • Additionally, cauterization of the superficial and intraluminal pancreatic structures may result in thermal damage.[9]
  • These iatrogenic traumatic and toxic influences may, again, stimulate the fibrogenic pancreatic stellate cells to initiate a cascade of events responsible for activation of zymogens and autodigestion of the pancreas.[10][11][2]

Microscopic Pathology

Genetics

Several genes have been proposed to play a role in the pathogenesis of acute pancreatitis. While the exact role of every implicated genetic mutation is not fully understood, the following genes have been associated with the development of acute pancreatitis:[12][2]

Associated Conditions

The most common conditions associated with acute pancreatitis include:[2]

References

  1. ↑ Coté GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L; et al. (2012). "Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis". Gastroenterology. 143 (6): 1502–1509.e1. doi:10.1053/j.gastro.2012.09.006. PMID 22982183.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Forsmark CE, Vege SS, Wilcox M (November 17,2016). "Acute Pancreatitis". The New England Journal of Medicine: 1972–1981. doi:10.1056/NEJMra1505202. Retrieved November 25,2016. Check date values in: |access-date=, |date= (help)
  3. ↑ Apte MV, Pirola RC, Wilson JS (2010). "Mechanisms of alcoholic pancreatitis". J Gastroenterol Hepatol. 25 (12): 1816–26. doi:10.1111/j.1440-1746.2010.06445.x. PMID 21091991.
  4. ↑ Kota SK, Kota SK, Jammula S, Krishna SV, Modi KD (2012). "Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review". Indian J Endocrinol Metab. 16 (1): 141–3. doi:10.4103/2230-8210.91211. PMC 3263185. PMID 22276267.
  5. ↑ Yadav D, Pitchumoni CS (2003). "Issues in hyperlipidemic pancreatitis". J Clin Gastroenterol. 36 (1): 54–62. PMID 12488710.
  6. ↑ Kimura W, Mössner J (1996). "Role of hypertriglyceridemia in the pathogenesis of experimental acute pancreatitis in rats". Int J Pancreatol. 20 (3): 177–84. doi:10.1007/BF02803766. PMID 9013278.
  7. ↑ Sherman S (1994). "ERCP and endoscopic sphincterotomy-induced pancreatitis". Am J Gastroenterol. 89 (3): 303–5. PMID 8122635.
  8. ↑ George S, Kulkarni AA, Stevens G, Forsmark CE, Draganov P (2004). "Role of osmolality of contrast media in the development of post-ERCP pancreatitis: a metanalysis". Dig Dis Sci. 49 (3): 503–8. PMID 15139506.
  9. ↑ Ratani RS, Mills TN, Ainley CC, Swain CP (1999). "Electrophysical factors influencing endoscopic sphincterotomy". Gastrointest Endosc. 49 (1): 43–52. PMID 9869722.
  10. ↑ Baillie J (2011). "Management of Post-ERCP Pancreatitis". Gastroenterol Hepatol (N Y). 7 (6): 390–2. PMC 3151411. PMID 21869870.
  11. ↑ Matsubayashi H, Fukutomi A, Kanemoto H, Maeda A, Matsunaga K, Uesaka K; et al. (2009). "Risk of pancreatitis after endoscopic retrograde cholangiopancreatography and endoscopic biliary drainage". HPB (Oxford). 11 (3): 222–8. doi:10.1111/j.1477-2574.2008.00020.x. PMC 2697892. PMID 19590651.
  12. ↑ Whitcomb DC (2013). "Genetic risk factors for pancreatic disorders". Gastroenterology. 144 (6): 1292–302. doi:10.1053/j.gastro.2013.01.069. PMC 3684061. PMID 23622139.
  13. ↑ Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR; et al. (2011). "Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis". Clin Gastroenterol Hepatol. 9 (3): 266–73, quiz e27. doi:10.1016/j.cgh.2010.10.015. PMC 3043170. PMID 21029787.
  14. ↑ Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR; et al. (2011). "Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis". Clin Gastroenterol Hepatol. 9 (3): 266–73, quiz e27. doi:10.1016/j.cgh.2010.10.015. PMC 3043170. PMID 21029787.
  15. ↑ Hong S, Qiwen B, Ying J, Wei A, Chaoyang T (2011). "Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis". Eur J Gastroenterol Hepatol. 23 (12): 1136–43. doi:10.1097/MEG.0b013e32834b0e0e. PMID 21904207.

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