Acute pancreatitis pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
=== 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 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 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 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. | ||
===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]]. | 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]]. | ||
=== 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> | |||
* CFTR | |||
* PRSS-1 | |||
* SPINK-1 | |||
* Chymotrypsin C | |||
* Claudin-2 | |||
* Calcium sensing receptors | |||
=== Associated Conditions === | |||
The most common conditions associated with acute pancreatitis include: | |||
* 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== | ||
Revision as of 17:36, 25 November 2016
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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]
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
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 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.
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.
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:[1]
- CFTR
- PRSS-1
- SPINK-1
- Chymotrypsin C
- Claudin-2
- Calcium sensing receptors
Associated Conditions
The most common conditions associated with acute pancreatitis include:
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.