Difference between revisions of "Mesenteric ischemia pathophysiology"

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{{Mesenteric ischemia}}
 
{{Mesenteric ischemia}}
{{CMG}} {{AE}} {{FT}}
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{{CMG}}; {{AE}} {{FT}}
 
==Overview==
 
==Overview==
The factors that regulate the intestinal blood flow play a vital role in the development of mesenteric ischemia. Mucosa of the intestines has a high metabolic activity and accordingly a high blood flow requirement. The majority of blood supply of the intestine comes from the superior mesenteric artery, with a collateral blood supply from superior and inferior pancreaticoduodenal arteries (branches of the celiac artery) as well as the inferior mesenteric artery. The splanchnic circulation (arteries supplying the viscera) receives 15-35% of the cardiac output, making it sensitive to the effects of decreased perfusion. Mesenteric ischemia occurs when intestinal blood supply is compromised by more than 50% of the original blood flow without activation of adaptive responses. This can lead to disruption of mucosal barrier, allowing the release of bacterial toxins (present in the intestinal lumen) and vasoactive mediators which ultimately lead to complete necrosis (cell death) of the intestinal mucosa. This can further progress to  depression in myocardial activity, sepsis, multiorgan failure, and without prompt intervention, even death.<ref name="pmid9146713">{{cite journal| author=Rosenblum JD, Boyle CM, Schwartz LB| title=The mesenteric circulation. Anatomy and physiology. | journal=Surg Clin North Am | year= 1997 | volume= 77 | issue= 2 | pages= 289-306 | pmid=9146713 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9146713  }} </ref>
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The factors that regulate the [[intestinal]] blood flow play a vital role in the development of mesenteric ischemia. [[Mucosa]] of the [[intestines]] has a high metabolic activity and accordingly a high blood flow requirement. The majority of blood supply of the [[intestine]] comes from the [[superior mesenteric artery]], with a collateral blood supply from superior and inferior [[Pancreaticoduodenal artery|pancreaticoduodenal arteries]] (branches of the [[celiac artery]]) as well as the [[inferior mesenteric artery]]. The [[splanchnic]] circulation ([[arteries]] supplying the [[viscera]]) receives 15-35% of the [[cardiac output]], making it sensitive to the effects of decreased [[perfusion]]. Mesenteric ischemia occurs when [[intestinal]] blood supply is compromised by more than 50% of the original blood flow without activation of adaptive responses. This can lead to disruption of [[mucosal]] barrier, allowing the release of [[Bacterial toxin|bacterial toxins]] (present in the [[intestinal]] lumen) and [[vasoactive]] mediators which ultimately lead to complete [[necrosis]] (cell death) of the intestinal mucosa. This can further progress to  depression in [[myocardial]] activity, [[sepsis]], [[multiorgan failure]], and without prompt intervention, even death.
 +
 
 
==Pathophysiology==
 
==Pathophysiology==
  
 
=== '''Pathogenesis''' ===
 
=== '''Pathogenesis''' ===
Intestinal mucosal damage occurs in response to ischemic insult. In response to providing protection from ischemia, mesenteric vessels undergo intrinsic auto regulation, which is an adaptive response to ischemia. In order to compensate for the ischemia, there is vasoconstriction of mesenteric vessels resulting in increased tissue oxygen extraction along with vasodilation of the collateral vessels. Owing to this mechanism, intestine is able to compensate for around 75% reduction in blood flow.<ref name="pmid11464607">{{cite journal| author=Sánchez-Fernández P, Mier y Díaz J, Blanco-Benavides R| title=[Acute mesenteric ischemia. Profile of an aggressive disease]. | journal=Rev Gastroenterol Mex | year= 2000 | volume= 65 | issue= 3 | pages= 134-40 | pmid=11464607 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11464607  }} </ref><ref name="pmid27901324">{{cite journal| author=Savlania A, Tripathi RK| title=Acute mesenteric ischemia: current multidisciplinary approach. | journal=J Cardiovasc Surg (Torino) | year= 2017 | volume= 58 | issue= 2 | pages= 339-350 | pmid=27901324 | doi=10.23736/S0021-9509.16.09751-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27901324 }} </ref><ref name="pmid: 15772787">{{cite journal| author=Yasuhara H| title=Acute mesenteric ischemia: the challenge of gastroenterology. | journal=Surg Today | year= 2005 | volume= 35 | issue= 3 | pages= 185-95 | pmid=: 15772787 | doi=10.1007/s00595-004-2924-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15772787  }} </ref><ref name="Deitch2012">{{cite journal|last1=Deitch|first1=Edwin A.|title=Gut-origin sepsis: Evolution of a concept|journal=The Surgeon|volume=10|issue=6|year=2012|pages=350–356|issn=1479666X|doi=10.1016/j.surge.2012.03.003}}</ref><ref name="pmid7065183">{{cite journal| author=Kvietys PR, Granger DN| title=Relation between intestinal blood flow and oxygen uptake. | journal=Am J Physiol | year= 1982 | volume= 242 | issue= 3 | pages= G202-8 | pmid=7065183 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7065183  }} </ref><ref name="pmid6660300">{{cite journal| author=Granger DN, Granger HJ| title=Systems analysis of intestinal hemodynamics and oxygenation. | journal=Am J Physiol | year= 1983 | volume= 245 | issue= 6 | pages= G786-96 | pmid=6660300 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6660300  }} </ref>
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* [[Intestinal]] [[mucosal]] damage occurs in response to [[ischemic]] insult.  
 +
* In response to providing protection from [[ischemia]], mesenteric vessels undergo intrinsic [[autoregulation]], which is an adaptive response to [[ischemia]].  
 +
* In order to compensate for the [[ischemia]], there is [[vasoconstriction]] of mesenteric vessels resulting in increased tissue oxygen extraction along with [[vasodilation]] of the collateral vessels. Owing to this mechanism, intestine is able to compensate for around 75% reduction in blood flow.<ref name="pmid11464607">{{cite journal| author=Sánchez-Fernández P, Mier y Díaz J, Blanco-Benavides R| title=[Acute mesenteric ischemia. Profile of an aggressive disease]. | journal=Rev Gastroenterol Mex | year= 2000 | volume= 65 | issue= 3 | pages= 134-40 | pmid=11464607 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11464607  }} </ref><ref name="pmid27901324">{{cite journal| author=Savlania A, Tripathi RK| title=Acute mesenteric ischemia: current multidisciplinary approach. | journal=J Cardiovasc Surg (Torino) | year= 2017 | volume= 58 | issue= 2 | pages= 339-350 | pmid=27901324 | doi=10.23736/S0021-9509.16.09751-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27901324}} </ref><ref name="pmid: 15772787">{{cite journal| author=Yasuhara H| title=Acute mesenteric ischemia: the challenge of gastroenterology. | journal=Surg Today | year= 2005 | volume= 35 | issue= 3 | pages= 185-95 | pmid=: 15772787 | doi=10.1007/s00595-004-2924-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15772787  }} </ref><ref name="Deitch2012">{{cite journal|last1=Deitch|first1=Edwin A.|title=Gut-origin sepsis: Evolution of a concept|journal=The Surgeon|volume=10|issue=6|year=2012|pages=350–356|issn=1479666X|doi=10.1016/j.surge.2012.03.003}}</ref><ref name="pmid7065183">{{cite journal| author=Kvietys PR, Granger DN| title=Relation between intestinal blood flow and oxygen uptake. | journal=Am J Physiol | year= 1982 | volume= 242 | issue= 3 | pages= G202-8 | pmid=7065183 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7065183  }} </ref><ref name="pmid6660300">{{cite journal| author=Granger DN, Granger HJ| title=Systems analysis of intestinal hemodynamics and oxygenation. | journal=Am J Physiol | year= 1983 | volume= 245 | issue= 6 | pages= G786-96 | pmid=6660300 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6660300  }} </ref>
  
Disturbance in the following factors play a role in the development of mesenteric ischemia:<ref name="pmid6101568">{{cite journal| author=Granger DN, Richardson PD, Kvietys PR, Mortillaro NA| title=Intestinal blood flow. | journal=Gastroenterology | year= 1980 | volume= 78 | issue= 4 | pages= 837-63 | pmid=6101568 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101568  }} </ref>
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==== Factors contributing in the pathogenesis of mesenteric ischemia:<ref name="pmid6101568">{{cite journal| author=Granger DN, Richardson PD, Kvietys PR, Mortillaro NA| title=Intestinal blood flow. | journal=Gastroenterology | year= 1980 | volume= 78 | issue= 4 | pages= 837-63 | pmid=6101568 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101568  }} </ref><ref name="pmid9146713">{{cite journal| author=Rosenblum JD, Boyle CM, Schwartz LB| title=The mesenteric circulation. Anatomy and physiology. | journal=Surg Clin North Am | year= 1997 | volume= 77 | issue= 2 | pages= 289-306 | pmid=9146713 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9146713  }} </ref> ====
 +
* Mesenteric blood supply (general circulation)
  
(a) Mesenteric blood supply (General circulation)
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*Collateral circulation
 +
*Response of [[mesenteric]] vasculature to [[ischemia]]
 +
*[[Vasoactive]] and [[humoral]] factors
  
(b) Collateral circulation
+
===(A) Mesenteric blood supply (General circulation)===
 +
* The [[mesenteric]] circulation recevies approximately 25% of the resting and 35% of the [[postprandial]] [[cardiac output]].
 +
* Mucosal and [[submucosal]] layers of the [[intestine]] receive 70% of the [[mesenteric]] blood flow, with the rest supplying the [[muscularis]] and serosal layers.
  
(c) Response of mesenteric vasculature to autonomic stimuli
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* The arterial supply of the [[intestine]] originates from three major arteries which include [[superior mesenteric artery]], [[inferior mesenteric artery]], and [[celiac artery]]:<ref name="pmid11759648">{{cite journal| author=Kumar S, Sarr MG, Kamath PS| title=Mesenteric venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 345 | issue= 23 | pages= 1683-8 | pmid=11759648 | doi=10.1056/NEJMra010076 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11759648  }} </ref><ref name="pmid19491858">{{cite journal| author=Ha C, Magowan S, Accortt NA, Chen J, Stone CD| title=Risk of arterial thrombotic events in inflammatory bowel disease. | journal=Am J Gastroenterol | year= 2009 | volume= 104 | issue= 6 | pages= 1445-51 | pmid=19491858 | doi=10.1038/ajg.2009.81 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19491858  }} </ref><ref name="pmid6101568">{{cite journal| author=Granger DN, Richardson PD, Kvietys PR, Mortillaro NA| title=Intestinal blood flow. | journal=Gastroenterology | year= 1980 | volume= 78 | issue= 4 | pages= 837-63 | pmid=6101568 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101568  }} </ref>
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{| class="wikitable"
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! align="center" style="background:#4479BA; color: #FFFFFF;" | Arterial supply
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! align="center" style="background:#4479BA; color: #FFFFFF;" | Region supplied
 +
|-
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|[[Superior mesenteric artery]] ([[SMA]])
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|[[Small intestine]], [[proximal]] and mid [[colon]] up to the [[splenic flexure]].
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|-
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|[[Inferior mesenteric artery|Inferior mesenteric artery (IMA)]]
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|[[Hindgut]] starting from the [[splenic flexure]] to the [[rectum]].
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|-
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|[[Celiac artery|Celiac artery (CA)]]
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|[[Foregut]], [[hepatobiliary system]] and [[spleen]].
 +
|-
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! colspan="2" style="background:#4479BA; color: #FFFFFF;" |Venous drainage
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|-
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| colspan="2" |The venous system parallels the arterial branches and drains into the [[portal venous system]].
 +
|}
  
(d) Vasoactive and humoral factors
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[[Image: Colonic blood supply1.gif|thumb|center|300px|Blood supply to the intestines includes the celiac artery, superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and branches of the internal iliac artery (IIA). <br>Source: By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons]]
{{Family tree/start}}
 
{{Family tree | | | | A01 | | | |A01= Box 1 in Row 1}}
 
{{Family tree | | | | |!| | | | | }}
 
{{Family tree | | | | B01 | | | |B01= Box 2 in Row 2}}
 
{{Family tree | |,|-|-|^|-|-|.| | }}
 
{{Family tree | C01 | | | | C02 |C01= Box 3 in Row 3| C02= Box 4 in Row 4}}
 
{{Family tree/end}}
 
'''(a) Blood supply of the mesentery:'''
 
  
The arterial supply of the intestine originates from three major arteries:<ref name="pmid11759648">{{cite journal| author=Kumar S, Sarr MG, Kamath PS| title=Mesenteric venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 345 | issue= 23 | pages= 1683-8 | pmid=11759648 | doi=10.1056/NEJMra010076 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11759648  }} </ref><ref name="pmid19491858">{{cite journal| author=Ha C, Magowan S, Accortt NA, Chen J, Stone CD| title=Risk of arterial thrombotic events in inflammatory bowel disease. | journal=Am J Gastroenterol | year= 2009 | volume= 104 | issue= 6 | pages= 1445-51 | pmid=19491858 | doi=10.1038/ajg.2009.81 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19491858  }} </ref><ref name="pmid6101568">{{cite journal| author=Granger DN, Richardson PD, Kvietys PR, Mortillaro NA| title=Intestinal blood flow. | journal=Gastroenterology | year= 1980 | volume= 78 | issue= 4 | pages= 837-63 | pmid=6101568 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101568  }} </ref>
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'''Commonly affected arteries:'''<ref name="Wyers2010">{{cite journal|last1=Wyers|first1=Mark C.|title=Acute Mesenteric Ischemia: Diagnostic Approach and Surgical Treatment|journal=Seminars in Vascular Surgery|volume=23|issue=1|year=2010|pages=9–20|issn=08957967|doi=10.1053/j.semvascsurg.2009.12.002}}</ref>
* Superior mesenteric artery (SMA)
 
** Supplies the small intestine, proximal and mid colon upto the splenic flexure.
 
* Inferior mesenteric artery (IMA)
 
** Supplies hind gut starting from the splenic flexure to the rectum.
 
* Celiac artery (CA)
 
** Supplies the foregut, hepatobiliary system and spleen.
 
  
* The venous system parallels the arterial branches and drains into the portal venous system.
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* [[Embolus]] can typically lodge into points of normal [[anatomic]] narrowing.  
* The mesenteric circulation recevies approximately 25% of the resting and 35% of the postprandial cardiac output.
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* This makes [[superior mesenteric artery]] the most vulnerable site because of its relatively larger diameter (more blood flow) and low take off angle (more likely to from the [[aorta]].
* Mucosal and submucosal layers of the intestine receive 70% of the mesenteric blood flow, with the rest supplying the muscularis and serosal layers.
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*The majority of [[emboli]] lodge 3-10 cm distal to the origin of [[superior mesenteric artery]], classically sparing the proximal [[jejunum]] and [[colon]].
'''Commonly affected arteries:'''
 
* Embolus can typically lodge into points of normal anatomic narrowing.  
 
* This makes [[superior mesenteric artery]] the most vulnerable site because of its relatively larger diameter (more blood flow) and low take off angle (more likely to from the aorta.
 
*The majority of emboli lodge 3-10cm distal to the origin of [[superior mesenteric artery]], classically sparing the proximal jejunum and colon.
 
'''(b) Collateral circulation:'''
 
  
The role of collateral circulation in the development of mesenteric ischemia is as follows:<ref name="pmid9146714">{{cite journal| author=McKinsey JF, Gewertz BL| title=Acute mesenteric ischemia. | journal=Surg Clin North Am | year= 1997 | volume= 77 | issue= 2 | pages= 307-18 | pmid=9146714 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9146714  }} </ref><ref name="pmid21326561">{{cite journal| author=Walker TG| title=Mesenteric vasculature and collateral pathways. | journal=Semin Intervent Radiol | year= 2009 | volume= 26 | issue= 3 | pages= 167-74 | pmid=21326561 | doi=10.1055/s-0029-1225663 | pmc=3036491 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21326561  }} </ref><ref name="pmid3554567">{{cite journal| author=Fisher DF, Fry WJ| title=Collateral mesenteric circulation. | journal=Surg Gynecol Obstet | year= 1987 | volume= 164 | issue= 5 | pages= 487-92 | pmid=3554567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3554567  }} </ref><ref name="pmid4025549">{{cite journal| author=Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN| title=Characterization of segmental collateral blood flow in the small intestine. | journal=Am J Physiol | year= 1985 | volume= 249 | issue= 2 Pt 1 | pages= G228-35 | pmid=4025549 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4025549  }} </ref><ref name="pmid: 3738747">{{cite journal| author=Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN| title=Collateral blood flow in segmental intestinal ischemia: effects of vasoactive agents. | journal=Surgery | year= 1986 | volume= 100 | issue= 2 | pages= 157-66 | pmid=: 3738747 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3738747  }} </ref><ref name="pmid4025549">{{cite journal| author=Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN| title=Characterization of segmental collateral blood flow in the small intestine. | journal=Am J Physiol | year= 1985 | volume= 249 | issue= 2 Pt 1 | pages= G228-35 | pmid=4025549 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4025549 }} </ref>
+
===(B) Collateral circulation===
* Intestines receive collateral blood supply at all levels from the superior and inferior pancreaticoduodenal arteries, branches of the celiac artery, which provides protection from ischemia.  
+
The role of collateral circulation in the development of mesenteric ischemia is as follows:<ref name="pmid9146714">{{cite journal| author=McKinsey JF, Gewertz BL| title=Acute mesenteric ischemia. | journal=Surg Clin North Am | year= 1997 | volume= 77 | issue= 2 | pages= 307-18 | pmid=9146714 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9146714  }} </ref><ref name="pmid21326561">{{cite journal| author=Walker TG| title=Mesenteric vasculature and collateral pathways. | journal=Semin Intervent Radiol | year= 2009 | volume= 26 | issue= 3 | pages= 167-74 | pmid=21326561 | doi=10.1055/s-0029-1225663 | pmc=3036491 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21326561  }} </ref><ref name="pmid3554567">{{cite journal| author=Fisher DF, Fry WJ| title=Collateral mesenteric circulation. | journal=Surg Gynecol Obstet | year= 1987 | volume= 164 | issue= 5 | pages= 487-92 | pmid=3554567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3554567  }} </ref><ref name="pmid4025549">{{cite journal| author=Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN| title=Characterization of segmental collateral blood flow in the small intestine. | journal=Am J Physiol | year= 1985 | volume= 249 | issue= 2 Pt 1 | pages= G228-35 | pmid=4025549 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4025549  }} </ref><ref name="pmid: 3738747">{{cite journal| author=Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN| title=Collateral blood flow in segmental intestinal ischemia: effects of vasoactive agents. | journal=Surgery | year= 1986 | volume= 100 | issue= 2 | pages= 157-66 | pmid=: 3738747 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3738747  }} </ref>
* These arteries can compensate for 75% reduction in mesenteric blood flow for upto 12 hours, without substanial injury.
+
* [[Intestines]] receive collateral blood supply at all levels from the superior and inferior pancreaticoduodenal arteries, branches of the [[celiac artery]], which provide protection from [[ischemia]].
 +
* These arteries can compensate for 75% reduction in [[mesenteric]] blood flow for up to 12 hours, without substanial injury.
 +
*  An extensive [[collateral circulation]] protects the [[intestines]] from transient periods of inadequate [[perfusion]]. However, prolonged reduction in [[splanchnic]] blood flow leads to [[vasoconstriction]] in the affected [[vascular bed]], and eventually reduces collateral blood flow.  
 +
* The [[Superior mesenteric artery|SMA]] and [[Inferior mesenteric artery|IMA]] communicate via the marginal artery of Drummond and the meandering [[mesenteric artery]].
 +
* [[Collateralization]] between the [[Inferior mesenteric artery|IMA]] and [[systemic circulation]] occurs in the [[rectum]] as the [[Superior rectal plexus|superior rectal]] ([[Hemorrhoidal plexus|hemorrhoidal]]) vessels merge with the [[Middle rectal plexus|middle rectal]] vessels from the [[internal iliac arteries]].
 +
* The areas lacking this [[collateralization]] are prone toward [[ischemia]].
 +
===(C) Response of mesenteric vasculature to ischemia===
 +
* Mesenteric ischemia occurs when the blood supply to [[mesentery]] is reduced leading to disruption of [[cellular metabolism]] owing to [[oxygen]] and [[nutrient]] deficiency.<ref name="pmid26909235">{{cite journal| author=Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N et al.| title=Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities. | journal=World J Gastrointest Pathophysiol | year= 2016 | volume= 7 | issue= 1 | pages= 125-30 | pmid=26909235 | doi=10.4291/wjgp.v7.i1.125 | pmc=4753178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26909235 }} </ref><ref name="CorcosNuzzo2013">{{cite journal|last1=Corcos|first1=Olivier|last2=Nuzzo|first2=Alexandre|title=Gastro-Intestinal Vascular Emergencies|journal=Best Practice & Research Clinical Gastroenterology|volume=27|issue=5|year=2013|pages=709–725|issn=15216918|doi=10.1016/j.bpg.2013.08.006}}</ref>
 +
* In the first 4 hours following [[ischemia]], [[necrosis]] of the [[mucosal]] [[villi]] occurs.
 +
* Persistent [[ischemia]] for more than 6 hours results in transmural, mural or [[mucosal]] [[infarction]], ultimately leading to [[bowel perforation]].
 +
* Prolonged [[ischemia]] leads to progressive [[vasoconstriction]] of the mesenetric vessels which raises the pressure in them resulting in lowering the collateral flow.
 +
* This is followed by [[vasodilation]], trying to restore blood flow to the area of [[ischemic]] insult.
  
*  An extensive collateral circulation protects the intestines from transient periods of inadequate perfusion. However, prolonged reduction in splanchnic blood flow leads to vasoconstriction in the affected vascular bed, and eventually reduces collateral blood flow.  
+
==== The sequence of events that take place in the [[small intestine]] subsequent to decreased blood flow: ====
 +
<br><br>
 +
{{Family tree/start}}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= [[Ischemic]] insult
 +
| boxstyle_B02= text-align: Center;
 +
| boxstyle_B03= text-align: left;
 +
}}
 +
{{Family tree | | | | |!| | | | | }}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Decreased delivery of [[oxygen]] and nutrients
 +
| boxstyle_B02= text-align: Center;
 +
| boxstyle_B03= text-align: left;
 +
}}
 +
{{Family tree | | | | |!| | | | | }}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Disruption in cellular [[metabolism]]
 +
| boxstyle_B02= text-align: Center;
 +
| boxstyle_B03= text-align: left;
 +
}}
 +
{{Family tree | | | | |!| | | | | }}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Tissue injury due to [[hypoxia]] and [[reperfusion]]
 +
}}
 +
{{Family tree | | | | |!| | | | | }}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Full thickness [[necrosis]] of the [[bowel]]}}
 +
{{Family tree | | | | |!| | | | | }}
 +
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= [[Perforation]] of the [[bowel wall]]}}
 +
{{familytree/end}}
 +
<br>
  
* The SMA and IMA communicate via the marginal artery of Drummond and the meandering mesenteric artery.  
+
{| class="wikitable"
 +
! colspan="2" style="background:#4479BA; color: #FFFFFF;" |'''Post [[ischemic]] cellular changes''':
 +
|-
 +
! style="background:#4479BA; color: #FFFFFF;" |Time duration since [[ischemia]]
 +
! style="background:#4479BA; color: #FFFFFF;" |Pathological changes in the [[small intestine]]
 +
|-
 +
|3-4 hours
 +
|[[Necrosis]] of the [[mucosal]] [[villi]]
 +
|-
 +
|6 hours
 +
|Transmural, mural or [[mucosal]] infarction
 +
|-
 +
|1-4 days
 +
|[[Bowel]] [[hemorrhage]]
 +
|}
 +
'''[[Reperfusion]] injury:'''
 +
* Restoration of blood flow to the area of [[ischemic]] insult results in [[reperfusion]] injury.
 +
* This leads to release of [[oxygen free radicals]], toxic byproducts of [[ischemic]] injury and [[neutrophil]] activation.
 +
* [[Immune]] cells remove dead and damaged cells releasing [[cytokines]] such as [[TNF-alpha]].
 +
* Blood vessels become more permeable leading to [[edema]] of the [[small intestine]].
 +
* As the [[ischemia]] progresses from [[mucosa]] to all the layers beneath (transmural), it leads to breaks in the [[epithelial]] lining.
 +
* This allows [[bacteria]] in the [[intestinal]] lumen to enter into the [[peritoneal cavity]] causing [[peritonitis]].
 +
* If [[bacteria]] enter into the blood stream, it results in [[systemic inflammatory response syndrome]], which ultimately results in [[sepsis]] and [[septic shock]].
  
* Collateralization between the IMA and systemic circulation occurs in the rectum as the superior rectal (hemorrhoidal) vessels merge with the middle rectal vessels from the internal iliac arteries.
+
===(D) Vasoactive and humoral factors regulating the mesenteric blood flow===
* The areas lacking this collateralization are prone towards ischemia.
+
* [[Vasoactive]] and [[humoral]] factors control the regulation of [[vascular]] tone of [[mesenteric]] circulation in response to periods of stress such as [[systemic hypotension]] or [[postprandial]] state.
'''(c) Vasoactive and humoral factors regulating the mesenteric blood flow:'''
 
  
Mechansims that control the regulation of vascular tone of mesenteric circulation in response to periods of stress such as systemic hypotension or postprandial state.
+
* Physiologically [[mesenteric]] circulation is affected by:<ref name="pmid10052599">{{cite journal| author=Hansen MB, Dresner LS, Wait RB| title=Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease. | journal=Physiol Res | year= 1998 | volume= 47 | issue= 5 | pages= 307-27 | pmid=10052599 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10052599  }} </ref><ref name="pmid8370303">{{cite journal| author=Schoenberg MH, Beger HG| title=Reperfusion injury after intestinal ischemia. | journal=Crit Care Med | year= 1993 | volume= 21 | issue= 9 | pages= 1376-86 | pmid=8370303 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8370303  }} </ref><ref name="PatelKaleya1992">{{cite journal|last1=Patel|first1=Amit|last2=Kaleya|first2=Ronald N.|last3=Sammartano|first3=Robert J.|title=Pathophysiology of Mesenteric Ischemia|journal=Surgical Clinics of North America|volume=72|issue=1|year=1992|pages=31–41|issn=00396109|doi=10.1016/S0039-6109(16)45626-4}}</ref><ref name="pmid8703630">{{cite journal| author=Takala J| title=Determinants of splanchnic blood flow. | journal=Br J Anaesth | year= 1996 | volume= 77 | issue= 1 | pages= 50-8 | pmid=8703630 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8703630  }} </ref><ref name="pmid7386643">{{cite journal| author=Granger HJ, Norris CP| title=Intrinsic regulation of intestinal oxygenation in the anesthetized dog. | journal=Am J Physiol | year= 1980 | volume= 238 | issue= 6 | pages= H836-43 | pmid=7386643 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7386643 }} </ref><ref name="pmid4684756">{{cite journal| author=Granger HJ, Shepherd AP| title=Intrinsic microvascular control of tissue oxygen delivery. | journal=Microvasc Res | year= 1973 | volume= 5 | issue= 1 | pages= 49-72 | pmid=4684756 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4684756  }} </ref>
 +
** '''Intrinsic regulatory system''' that includes [[metabolic]] and [[myogenic]] factors.
 +
** '''Extrinsic regulatory system''' that includes [[neural]] and [[humoral]] factors.
 +
'''<u>Intrinsic regulation:</u>'''
  
Physiologically mesenteric circulation is affected by:<ref name="pmid10052599">{{cite journal| author=Hansen MB, Dresner LS, Wait RB| title=Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease. | journal=Physiol Res | year= 1998 | volume= 47 | issue= 5 | pages= 307-27 | pmid=10052599 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10052599  }} </ref><ref name="pmid8370303">{{cite journal| author=Schoenberg MH, Beger HG| title=Reperfusion injury after intestinal ischemia. | journal=Crit Care Med | year= 1993 | volume= 21 | issue= 9 | pages= 1376-86 | pmid=8370303 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8370303  }} </ref><ref name="PatelKaleya1992">{{cite journal|last1=Patel|first1=Amit|last2=Kaleya|first2=Ronald N.|last3=Sammartano|first3=Robert J.|title=Pathophysiology of Mesenteric Ischemia|journal=Surgical Clinics of North America|volume=72|issue=1|year=1992|pages=31–41|issn=00396109|doi=10.1016/S0039-6109(16)45626-4}}</ref><ref name="pmid8703630">{{cite journal| author=Takala J| title=Determinants of splanchnic blood flow. | journal=Br J Anaesth | year= 1996 | volume= 77 | issue= 1 | pages= 50-8 | pmid=8703630 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8703630  }} </ref><ref name="pmid7386643">{{cite journal| author=Granger HJ, Norris CP| title=Intrinsic regulation of intestinal oxygenation in the anesthetized dog. | journal=Am J Physiol | year= 1980 | volume= 238 | issue= 6 | pages= H836-43 | pmid=7386643 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7386643  }} </ref><ref name="pmid4684756">{{cite journal| author=Granger HJ, Shepherd AP| title=Intrinsic microvascular control of tissue oxygen delivery. | journal=Microvasc Res | year= 1973 | volume= 5 | issue= 1 | pages= 49-72 | pmid=4684756 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4684756  }} </ref>
+
'''(a) Metabolic factors:'''   
* Intrinsic regulatory system that includes metabolic and myogenic factors.
+
* Reduction in blood supply to the [[mesentery]] causes adaptive changes in the [[splanchnic]] circulation.   
* Extrinsic regulatory system that includes neural and humoral factors.
+
* A discrepancy between tissue oxyegn demand and supply raises the concentration of local [[metabolites]] such as [[hydrogen]], [[potassium]], [[carbon dioxide]], and [[adenosine]], resulting in [[vasodilation]], and [[hyperemia]].
'''Intrinsic regulation:'''
+
'''(b) Myogenic factors:'''
* Metabolic factors:  
+
* Myogenic theory suggests that arteriolar wall tension [[receptors]] act to regulate [[vascular resistance]] in accordance with the transmural pressure.  
** Reduction in blood supply to the mesentery causes adaptive changes in the splanchnic circulation.   
+
* An [[acute]] decrease in [[perfusion pressure]] is compensated for by a reduction in arteriolar wall tension, thereby maintaining [[splanchnic]] blood flow.
** A discrepancy between tissue oxyegn demand and supply raises the concentration of local metabolites such as hydrogen, potassium, carbon dioxide, and adenosine, resulting in vasodilation and hyperemia.  
+
'''<u>Extrinsic regulation:</u>'''
  
* Myogenic factors:
+
==== (a) [[Neural]] component: ====
** Myogenic theory suggests that arteriolar tension receptors act to regulate vascular resistance in accordance with the transmural pressure.
+
* The extrinsic [[neural]] component of [[splanchnic]] [[circulatory]] regulation comprises the alpha-activated [[vasoconstrictor]] fibers.  
** An acute decrease in perfusion pressure is compensated for by a reduction in arteriolar wall tension, thereby maintaining splanchnic blood flow.
+
* Intense activation of [[vasoconstrictor]] fibers through alpha-[[adrenergic]] stimulation results in [[vasoconstriction]] of small vessels and a decrease in [[mesenteric]] blood flow.  
'''Extrinsic regulation:'''
+
* After periods of prolonged [[Alpha adrenergic|alpha-adrenergic]] [[vasoconstriction]], blood flow increases, presumably through β-adrenergic stimulation, which acts as a protective response.  
* Neural component:  
+
* Although numerous types of neural stimulation (e.g. [[vagal]], [[cholinergic]], histaminergic, and [[sympathetic]]) can affect the blood supply of the gut, the [[adrenergic]] limb of the [[autonomic nervous system]] is the predominant neural influence on [[splanchnic]] circulation.
** The extrinsic neural component of splanchnic circulatory regulation comprises the alpha-activated vasoconstrictor fibers.  
 
** Intense activation of vasoconstrictor fibers through alpha-adrenergic stimulation results in vasoconstriction of small vessels and a decrease in mesenteric blood flow.  
 
** After periods of prolonged alpha-adrenergic vasoconstriction, blood flow increases, presumably through β-adrenergic stimulation, which acts as a protective response.  
 
** Although numerous types of neural stimulation (e.g. vagal, cholinergic, histaminergic, and sympathetic) can affect the blood supply of the gut, the adrenergic limb of the autonomic nervous system is the predominant neural influence on splanchnic circulation.
 
  
* Humoral component:  
+
==== (b) [[Humoral]] component: ====
** Numerous endogenous and exogenous humoral factors affect the splanchnic circulation.  
+
* Numerous [[endogenous]] and [[exogenous]] [[humoral]] factors affect the [[splanchnic]] circulation.  
** Norepinephrine and high doses of epinephrine produce intense vasoconstriction by stimulating the adrenergic receptors.  
+
* [[Norepinephrine]] and high doses of [[epinephrine]] produce intense [[vasoconstriction]] by stimulating the [[adrenergic]] receptors.  
** Other pharmacologic compounds that decrease splanchnic blood flow include:  
+
* Other pharmacologic compounds that decrease [[splanchnic]] blood flow include:  
*** Vasopressin
+
** [[Vasopressin]]
*** Phenylephrine
+
** [[Phenylephrine]]
*** Digoxin
+
** [[Digoxin]]
** Low-dose dopamine causes splanchnic vasodilation, whereas higher doses lead to vasoconstriction by stimulating alpha adrenergic receptors.
+
* Low-dose [[dopamine]] causes [[splanchnic]] [[vasodilation]], whereas higher doses lead to [[vasoconstriction]] by stimulating alpha [[adrenergic receptors]].
** Exogenous agents that increase mesenteric blood flow include:
+
* [[Exogenous]] agents that increase [[mesenteric]] blood flow include:
*** Papaverine
+
** [[Papaverine]]
*** Adenosine
+
** [[Adenosine]]
*** Dobutamine
+
** [[Dobutamine]]
*** Fenoldopam  
+
** [[Fenoldopam]]
*** Sodium nitroprusside
+
** [[Sodium nitroprusside]]
** In addition, numerous natural neurotransmitters can serve as splanchnic vasodilators, including acetylcholine, histamine, nitric oxide, leukotrienes, thromboxane analogues, glucagon, and a couple of gastrointestinal hormones.
+
* In addition, numerous natural [[neurotransmitters]] can serve as [[splanchnic]] [[vasodilators]], such as:
 +
** [[Acetylcholine]]
 +
** [[Histamine]]
 +
** [[Nitric oxide]]
 +
** [[Leukotrienes]]
 +
** [[Thromboxane]] analogues
 +
** [[Glucagon]]
 
{| class="wikitable"
 
{| class="wikitable"
! colspan="4" |Factors regulating mesenteric blood flow
+
! colspan="4" style="background:#4479BA; color: #FFFFFF;" |Factors regulating mesenteric blood flow
 
|-
 
|-
! colspan="4" |'''Extrinsic reguatory system'''
+
! colspan="4" style="background:#4479BA; color: #FFFFFF;" |'''Extrinsic reguatory system'''
 
|-
 
|-
! colspan="2" |'''Humoral (endogenous and exogenous)'''
+
! colspan="2" style="background:#4479BA; color: #FFFFFF;" |'''Humoral (endogenous and exogenous)'''
! colspan="2" |'''Neural component'''
+
! colspan="2" style="background:#4479BA; color: #FFFFFF;" |'''Neural component'''
 
|-
 
|-
|'''Decrease blood flow'''
+
! align="center" style="background:#4479BA; color: #FFFFFF;" |'''Decrease blood flow'''
|'''Increase blood flow'''
+
! align="center" style="background:#4479BA; color: #FFFFFF;" |'''Increase blood flow'''
|''Decrease blood flow''
+
! align="center" style="background:#4479BA; color: #FFFFFF;" |'''Decrease blood flow'''
|'''Increase blood flow'''
+
! align="center" style="background:#4479BA; color: #FFFFFF;" |'''Increase blood flow'''
 
|-
 
|-
 
|
 
|
* Epinephrine (high dose)
+
* [[Epinephrine]] (high dose)
* Norepinephrine (moderate to high dose)
+
* [[Norepinephrine]] (moderate to high dose)
* Dopamine (high dose)
+
* [[Dopamine]] (high dose)
* Phenylephrine
+
* [[Phenylephrine]]
* Vasopressin
+
* [[Vasopressin]]
* Angiotensin  
+
* [[Angiotensin]]
* Digoxin  
+
* [[Digoxin]]
 
|
 
|
* Epinephrine (low dose)
+
* [[Epinephrine]] (low dose)
* Norepinephrine (low dose)
+
* [[Norepinephrine]] (low dose)
* Dopamine (low dose)
+
* [[Dopamine]] (low dose)
* Dobutamine
+
* [[Dobutamine]]
* Sodium nitroprusside
+
* [[Sodium nitroprusside]]
* Papaverine
+
* [[Papaverine]]
* Nitric oxide
+
* [[Nitric oxide]]
* Acetylcholine  
+
* [[Acetylcholine]]
* Histamine
+
* [[Histamine]]
 
|
 
|
* Alpha-adrenergic receptors
+
* [[Alpha adrenergic|Alpha-adrenergic]] receptors
* Dopamenergic receptors
+
* [[Dopaminergic]] receptors
 
|
 
|
* Beta adrenergic receptors
+
* Beta [[adrenergic]] receptors
 
|-
 
|-
! colspan="4" |'''Intrinsic regulatory component'''
+
! colspan="4" style="background:#4479BA; color: #FFFFFF;" |'''Intrinsic regulatory component'''
 
|-
 
|-
| colspan="2" |'''Decrease blood flow'''
+
| colspan="2" style="background:#4479BA; color: #FFFFFF;" |'''Decrease blood flow (Myogenic factors)'''
| colspan="2" |'''Increase blood flow'''
+
| colspan="2" style="background:#4479BA; color: #FFFFFF;" |'''Increase blood flow (Metabolic factors)'''
 
|-
 
|-
 
| colspan="2" |
 
| colspan="2" |
 
* Arteriolar tension receptors
 
* Arteriolar tension receptors
 
| colspan="2" |
 
| colspan="2" |
* Hydrogen
+
* [[Hydrogen]]
* Potasssium
+
* [[Potassium]]
* Carbon dioxide
+
* [[Carbon dioxide]]
* Adenosine  
+
* [[Adenosine]]
 
|}
 
|}
'''Areas prone to ischemia:'''
+
===Areas prone to ischemia===
  
 
{| class="wikitable"
 
{| class="wikitable"
!Areas prone to ischemia  
+
! align="center" style="background:#4479BA; color: #FFFFFF;" | Areas prone to ischemia  
! colspan="3" |Blood supply
+
! style="background:#4479BA; color: #FFFFFF;" | Blood supply
 
|-
 
|-
|
+
|[[Splenic flexure]]
* Splenic flexure
+
|End arteries of [[superior mesenteric artery]]
| colspan="3" |End arteries of superior mesenteric artery
+
|-
 +
|Rectosigmoid junction
 +
|End arteries of [[inferior mesenteric artery]]
 
|-
 
|-
 +
|Middle segment of [[jejunum]]
 
|
 
|
* Rectosigmoid junction
 
| colspan="3" |End arteries of inferior mesenteric artery
 
 
|}
 
|}
* The watershed areas that lack collateralization are as follows:
 
  
* Splenic flexure
+
==== Watershed areas lacking collateralization: ====
** Supplied by the end arteries of SMA with no collateral circulation.
+
* [[Splenic flexure]]
 +
** Supplied by the end arteries of [[Superior mesenteric artery|SMA]] with no collateral circulation.
 
* Rectosigmoid junction
 
* Rectosigmoid junction
Supplied by the end arteries of IMA with no collateral circulation.
+
** Supplied by the end arteries of [[Inferior mesenteric artery|IMA]] with no collateral circulation.
  
'''Mechanism of ischemia:'''<ref name="pmid26909235">{{cite journal| author=Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N et al.| title=Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities. | journal=World J Gastrointest Pathophysiol | year= 2016 | volume= 7 | issue= 1 | pages= 125-30 | pmid=26909235 | doi=10.4291/wjgp.v7.i1.125 | pmc=4753178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26909235 }} </ref>
+
* Middle segment of [[jejunum]]<ref name="pmid9890114">{{cite journal| author=Cappell MS| title=Intestinal (mesenteric) vasculopathy. I. Acute superior mesenteric arteriopathy and venopathy. | journal=Gastroenterol Clin North Am | year= 1998 | volume= 27 | issue= 4 | pages= 783-825, vi | pmid=9890114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9890114 }} </ref>
 +
** This area is the farthest from collateral circulation and hence prone to [[ischemia]] as compared to other segments of [[jejunum]].
  
The sequence of events that take place in the small intestine subsequent to decreased blood flow:
+
===Pathogenesis of occlusive mesenteric ischemia:===
 +
<br><br>
  
{{Family tree/start}}
+
{{familytree/start|summary=Sample 1}}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Ischemic insult
+
{{familytree| | | | | | | | | |B01| | | | | | | | |B01= [[Vascular]] [[occlusion]]|}}
| boxstyle_B02= text-align: Center;
+
{{familytree| | | | | | | | | | |!| | | | | | | | |}}
| boxstyle_B03= text-align: left;
+
{{familytree| | | | | | | | | |C01| | | | | | | | |C01= Blood flow<metabolic demand|}}
}}
+
{{familytree| | | |,|-|-|-|-|-|-|+|-|-|-|-|-|-|-|.| |}}
{{Family tree | | | | |!| | | | | }}
+
{{familytree| | |D01| | | | |D02| | | | | | |D03|D01= [[Mucosal]] barrier disruption and [[bacterial]] translocation into the circulation|D02= Anaerobic [[glycolysis]] in [[mucosa]] and [[lactate]] production|D03= Activation of [[vascular]] and [[humoral]] factors leading to [[vasoconstriction]]|}}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Decreased delivery of oxygen and nutrients
+
{{familytree| | | |!| | | | | | |!| | | | | | | |!|}}
| boxstyle_B02= text-align: Center;
+
{{familytree| | |E01| | | | |E02| | | | | | |E03|E01= Systemic activation of [[inflammatory]] response|E02= [[Lactic acidosis]]|E03= [[Intestinal]] [[necrosis]]|}}
| boxstyle_B03= text-align: left;
+
{{familytree| | | |`|-|-|-|-|-|-|+|-|-|-|-|-|-|-|'| |}}
}}
+
{{familytree| | | | | | | | | | |!| | | | | | | | |}}
{{Family tree | | | | |!| | | | | }}
+
{{familytree| | | | | | | | | |F01| | | | | | | | |F01= [[Multiorgan failure]]|}}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Disruption in cellular metabolism
+
{{familytree/end}}
| boxstyle_B02= text-align: Center;
 
| boxstyle_B03= text-align: left;
 
}}
 
{{Family tree | | | | |!| | | | | }}
 
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Tissue injury due to hypoxia and reperfusion
 
}}
 
{{Family tree | | | | |!| | | | | }}
 
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Full thickness necrosis of the bowel
 
}}
 
{{Family tree | | | | |!| | | | | }}
 
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= Perforation of the bowel wall
 
}}
 
  
{{Family tree/end}}
+
===Pathogenesis of non-occlusive mesenteric ischemia:===
* Mesenteric ischemia occurs when the blood supply to mesentery is reduced leading to disruption of cellular metabolism owing to oxygen and nutrient deficiency.
+
<br><br>
* In the first 4 hours following ischemia, necrosis of the mucosal villi occurs.
+
{{familytree/start|summary=Sample 1}}
* Persistent ischemia for more than 6 hours results in transmural, mural or mucosal infarction, ultimately leading to bowel perforation.
+
{{familytree| | | | X01 | | | | | | | | | | | X02 |X01=[[Hypovolemia]]|X02= [[Cardiac failure]]|}}
* Prolonged ischemia leads to progressive vasoconstriction of the mesenetric vessels which raises the pressure in them resulting in lowering the collateral flow.
+
{{familytree| | | |`|-|-|-|-|-|-|v|-|-|-|-|-|-|-|'| |}}
* This is followed by vasodilation, trying to restore blood flow to the area of ischemic insult.
+
{{familytree| | | | | | | | | |A01| | | | | | | | |A01= [[Endogenous]] [[vasoconstriction]]|}}
{| class="wikitable"
+
{{familytree| | | | | | | | | | |!| | | | | | | | |}}
!Time duration dince ischemia
+
{{familytree| | | | | | | | | |B01| | | | | | | | |B01= [[Splanchnic]] [[vasoconstriction]]|}}
!Pathological changes in the small intestine
+
{{familytree| | | | | | | | | | |!| | | | | | | | |}}
|-
+
{{familytree| | | | | | | | | |C01| | | | | | | | |C01= Gut mucosal hypoperfusion|}}
|3-4 hours
+
{{familytree| | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|-|.| |}}
|Necrosis of the mucosal villi
+
{{familytree| | |D01| | | | | | | | | | | | | |D02|D01= Restoration of blood by [[vasodilation]] of collaterals|D02= Gut [[mucosal]] barrier disruption|}}
|-
+
{{familytree| | | |!| | | | | | | | | | | | | | |!|}}
|6 hours
+
{{familytree| | |E01| | | | | | | | | | | | | |E02|E01= [[Ischemia]]-reperfusion injury|E02= Increased [[mucosal]] [[perfusion]] to [[bacterial]] [[toxins]]|}}
|Transmural,mural or mucosal infarction
+
{{familytree| | | |`|-|-|-|-|-|-|v|-|-|-|-|-|-|-|'| |}}
|-
+
{{familytree| | | | | | | | | | |!| | | | | | | | |}}
|1-4 days
+
{{familytree| | | | | | | | | |F01| | | | | | | | |F01= Activation of [[inflammatory]] response|}}
|Bowel hemorrhage
+
{{familytree/end}}
|}
 
'''Response to ischemia:'''
 
* Restoration of blood flow to the area of ischemic insult resutls in reperfusion injury.
 
 
 
* This leads to release of oxygen free radicals, toxic byproducts of ischemic injury and neutrophil activation.
 
'''Post ischemic cellular changes''':
 
  
 
==Gross Pathology==
 
==Gross Pathology==
 
Gross pathology shows following changes:
 
Gross pathology shows following changes:
*Early stage of ischemia: Intestinal wall in congested.
+
*Early stage of [[ischemia]]
*Late stage of ischemia: Edematous, friable and hemorrhagic bowel wall.
+
**[[Intestinal wall]] in [[congested]].
 +
*Late stage of [[ischemia]]
 +
**[[Edema|Edematous]], friable and [[hemorrhagic]] [[bowel]] wall.
 +
 
 +
== Microscopic pathology ==
 +
Mesenteric ischemia is classified histopathologically into five grades:<ref name="pmid16332482">{{cite journal| author=Rosow DE, Sahani D, Strobel O, Kalva S, Mino-Kenudson M, Holalkere NS et al.| title=Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model. | journal=J Gastrointest Surg | year= 2005 | volume= 9 | issue= 9 | pages= 1262-74; discussion 1274-5 | pmid=16332482 | doi=10.1016/j.gassur.2005.07.034 | pmc=3807105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16332482  }} </ref>
 +
* Grade 1. Normal. [[Vascular]] [[congestion]] is absent, and both the villous architecture and [[Muscle|muscular]] layer are preserved. 
 +
 
 +
* Grade 2. Villous architecture is preserved, with some mucosal congestion and dilated [[Capillary|capillaries]]. 
 +
 
 +
* Grade 3. There is [[congestion]] of mucosa with loss of superficial [[Gland|glandular]] architecture, but deep villous architecture is preserved.
 +
 
 +
* Grade 4. [[Muscle|Muscular]] layer is preserved, but the mucosa is completely involved, with loss of all superficial and deep [[Gland|glandular]] architecture. 
 +
 
 +
* Grade 5. There is total loss of [[Gland|glandular]] architecture, and the muscularis propria shows degeneration, fragmentation, and [[Skeletal muscle|myocyte]] death, all of which indicate transmural [[infarction]].
  
 ==References==
+
==References==
  
 
{{Reflist|2}}
 
{{Reflist|2}}
  
[[Category:Needs content]]
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[[Category:Gastroenterology]]

Latest revision as of 00:53, 18 February 2018


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Overview

The factors that regulate the intestinal blood flow play a vital role in the development of mesenteric ischemia. Mucosa of the intestines has a high metabolic activity and accordingly a high blood flow requirement. The majority of blood supply of the intestine comes from the superior mesenteric artery, with a collateral blood supply from superior and inferior pancreaticoduodenal arteries (branches of the celiac artery) as well as the inferior mesenteric artery. The splanchnic circulation (arteries supplying the viscera) receives 15-35% of the cardiac output, making it sensitive to the effects of decreased perfusion. Mesenteric ischemia occurs when intestinal blood supply is compromised by more than 50% of the original blood flow without activation of adaptive responses. This can lead to disruption of mucosal barrier, allowing the release of bacterial toxins (present in the intestinal lumen) and vasoactive mediators which ultimately lead to complete necrosis (cell death) of the intestinal mucosa. This can further progress to depression in myocardial activity, sepsis, multiorgan failure, and without prompt intervention, even death.

Pathophysiology

Pathogenesis

Factors contributing in the pathogenesis of mesenteric ischemia:[7][8]

  • Mesenteric blood supply (general circulation)

(A) Mesenteric blood supply (General circulation)

Arterial supply Region supplied
Superior mesenteric artery (SMA) Small intestine, proximal and mid colon up to the splenic flexure.
Inferior mesenteric artery (IMA) Hindgut starting from the splenic flexure to the rectum.
Celiac artery (CA) Foregut, hepatobiliary system and spleen.
Venous drainage
The venous system parallels the arterial branches and drains into the portal venous system.
Blood supply to the intestines includes the celiac artery, superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and branches of the internal iliac artery (IIA).
Source: By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Commonly affected arteries:[11]

(B) Collateral circulation

The role of collateral circulation in the development of mesenteric ischemia is as follows:[12][13][14][15][16]

(C) Response of mesenteric vasculature to ischemia

The sequence of events that take place in the small intestine subsequent to decreased blood flow:



 
 
 
Ischemic insult
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decreased delivery of oxygen and nutrients
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disruption in cellular metabolism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tissue injury due to hypoxia and reperfusion
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full thickness necrosis of the bowel
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perforation of the bowel wall
 
 
 
 


Post ischemic cellular changes:
Time duration since ischemia Pathological changes in the small intestine
3-4 hours Necrosis of the mucosal villi
6 hours Transmural, mural or mucosal infarction
1-4 days Bowel hemorrhage

Reperfusion injury:

(D) Vasoactive and humoral factors regulating the mesenteric blood flow

Intrinsic regulation:

(a) Metabolic factors:

(b) Myogenic factors:

Extrinsic regulation:

(a) Neural component:

(b) Humoral component:

Factors regulating mesenteric blood flow
Extrinsic reguatory system
Humoral (endogenous and exogenous) Neural component
Decrease blood flow Increase blood flow Decrease blood flow Increase blood flow
Intrinsic regulatory component
Decrease blood flow (Myogenic factors) Increase blood flow (Metabolic factors)
  • Arteriolar tension receptors

Areas prone to ischemia

Areas prone to ischemia Blood supply
Splenic flexure End arteries of superior mesenteric artery
Rectosigmoid junction End arteries of inferior mesenteric artery
Middle segment of jejunum

Watershed areas lacking collateralization:

  • Splenic flexure
    • Supplied by the end arteries of SMA with no collateral circulation.
  • Rectosigmoid junction
    • Supplied by the end arteries of IMA with no collateral circulation.
  • Middle segment of jejunum[25]
    • This area is the farthest from collateral circulation and hence prone to ischemia as compared to other segments of jejunum.

Pathogenesis of occlusive mesenteric ischemia:



 
 
 
 
 
 
 
 
 
Vascular occlusion
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood flow<metabolic demand
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mucosal barrier disruption and bacterial translocation into the circulation
 
 
 
 
Anaerobic glycolysis in mucosa and lactate production
 
 
 
 
 
 
Activation of vascular and humoral factors leading to vasoconstriction
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Systemic activation of inflammatory response
 
 
 
 
Lactic acidosis
 
 
 
 
 
 
Intestinal necrosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiorgan failure
 
 
 
 
 
 
 
 

Pathogenesis of non-occlusive mesenteric ischemia:



 
 
 
Hypovolemia
 
 
 
 
 
 
 
 
 
 
Cardiac failure
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Endogenous vasoconstriction
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Splanchnic vasoconstriction
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gut mucosal hypoperfusion
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Restoration of blood by vasodilation of collaterals
 
 
 
 
 
 
 
 
 
 
 
 
 
Gut mucosal barrier disruption
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ischemia-reperfusion injury
 
 
 
 
 
 
 
 
 
 
 
 
 
Increased mucosal perfusion to bacterial toxins
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activation of inflammatory response
 
 
 
 
 
 
 
 

Gross Pathology

Gross pathology shows following changes:

Microscopic pathology

Mesenteric ischemia is classified histopathologically into five grades:[26]

  • Grade 2. Villous architecture is preserved, with some mucosal congestion and dilated capillaries
  • Grade 3. There is congestion of mucosa with loss of superficial glandular architecture, but deep villous architecture is preserved.
  • Grade 4. Muscular layer is preserved, but the mucosa is completely involved, with loss of all superficial and deep glandular architecture. 
  • Grade 5. There is total loss of glandular architecture, and the muscularis propria shows degeneration, fragmentation, and myocyte death, all of which indicate transmural infarction.

References

  1. Sánchez-Fernández P, Mier y Díaz J, Blanco-Benavides R (2000). "[Acute mesenteric ischemia. Profile of an aggressive disease].". Rev Gastroenterol Mex. 65 (3): 134–40. PMID 11464607. 
  2. Savlania A, Tripathi RK (2017). "Acute mesenteric ischemia: current multidisciplinary approach.". J Cardiovasc Surg (Torino). 58 (2): 339–350. PMID 27901324. doi:10.23736/S0021-9509.16.09751-2. 
  3. Yasuhara H (2005). "Acute mesenteric ischemia: the challenge of gastroenterology.". Surg Today. 35 (3): 185–95. PMID 15772787 : 15772787 . doi:10.1007/s00595-004-2924-0. 
  4. Deitch, Edwin A. (2012). "Gut-origin sepsis: Evolution of a concept". The Surgeon. 10 (6): 350–356. ISSN 1479-666X. doi:10.1016/j.surge.2012.03.003. 
  5. Kvietys PR, Granger DN (1982). "Relation between intestinal blood flow and oxygen uptake.". Am J Physiol. 242 (3): G202–8. PMID 7065183. 
  6. Granger DN, Granger HJ (1983). "Systems analysis of intestinal hemodynamics and oxygenation.". Am J Physiol. 245 (6): G786–96. PMID 6660300. 
  7. 7.0 7.1 Granger DN, Richardson PD, Kvietys PR, Mortillaro NA (1980). "Intestinal blood flow.". Gastroenterology. 78 (4): 837–63. PMID 6101568. 
  8. Rosenblum JD, Boyle CM, Schwartz LB (1997). "The mesenteric circulation. Anatomy and physiology.". Surg Clin North Am. 77 (2): 289–306. PMID 9146713. 
  9. Kumar S, Sarr MG, Kamath PS (2001). "Mesenteric venous thrombosis.". N Engl J Med. 345 (23): 1683–8. PMID 11759648. doi:10.1056/NEJMra010076. 
  10. Ha C, Magowan S, Accortt NA, Chen J, Stone CD (2009). "Risk of arterial thrombotic events in inflammatory bowel disease.". Am J Gastroenterol. 104 (6): 1445–51. PMID 19491858. doi:10.1038/ajg.2009.81. 
  11. Wyers, Mark C. (2010). "Acute Mesenteric Ischemia: Diagnostic Approach and Surgical Treatment". Seminars in Vascular Surgery. 23 (1): 9–20. ISSN 0895-7967. doi:10.1053/j.semvascsurg.2009.12.002. 
  12. McKinsey JF, Gewertz BL (1997). "Acute mesenteric ischemia.". Surg Clin North Am. 77 (2): 307–18. PMID 9146714. 
  13. Walker TG (2009). "Mesenteric vasculature and collateral pathways.". Semin Intervent Radiol. 26 (3): 167–74. PMC 3036491Freely accessible. PMID 21326561. doi:10.1055/s-0029-1225663. 
  14. Fisher DF, Fry WJ (1987). "Collateral mesenteric circulation.". Surg Gynecol Obstet. 164 (5): 487–92. PMID 3554567. 
  15. Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN (1985). "Characterization of segmental collateral blood flow in the small intestine.". Am J Physiol. 249 (2 Pt 1): G228–35. PMID 4025549. 
  16. Bulkley GB, Womack WA, Downey JM, Kvietys PR, Granger DN (1986). "Collateral blood flow in segmental intestinal ischemia: effects of vasoactive agents.". Surgery. 100 (2): 157–66. PMID 3738747 : 3738747 . 
  17. Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N; et al. (2016). "Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities.". World J Gastrointest Pathophysiol. 7 (1): 125–30. PMC 4753178Freely accessible. PMID 26909235. doi:10.4291/wjgp.v7.i1.125. 
  18. Corcos, Olivier; Nuzzo, Alexandre (2013). "Gastro-Intestinal Vascular Emergencies". Best Practice & Research Clinical Gastroenterology. 27 (5): 709–725. ISSN 1521-6918. doi:10.1016/j.bpg.2013.08.006. 
  19. Hansen MB, Dresner LS, Wait RB (1998). "Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease.". Physiol Res. 47 (5): 307–27. PMID 10052599. 
  20. Schoenberg MH, Beger HG (1993). "Reperfusion injury after intestinal ischemia.". Crit Care Med. 21 (9): 1376–86. PMID 8370303. 
  21. Patel, Amit; Kaleya, Ronald N.; Sammartano, Robert J. (1992). "Pathophysiology of Mesenteric Ischemia". Surgical Clinics of North America. 72 (1): 31–41. ISSN 0039-6109. doi:10.1016/S0039-6109(16)45626-4. 
  22. Takala J (1996). "Determinants of splanchnic blood flow.". Br J Anaesth. 77 (1): 50–8. PMID 8703630. 
  23. Granger HJ, Norris CP (1980). "Intrinsic regulation of intestinal oxygenation in the anesthetized dog.". Am J Physiol. 238 (6): H836–43. PMID 7386643. 
  24. Granger HJ, Shepherd AP (1973). "Intrinsic microvascular control of tissue oxygen delivery.". Microvasc Res. 5 (1): 49–72. PMID 4684756. 
  25. Cappell MS (1998). "Intestinal (mesenteric) vasculopathy. I. Acute superior mesenteric arteriopathy and venopathy.". Gastroenterol Clin North Am. 27 (4): 783–825, vi. PMID 9890114. 
  26. Rosow DE, Sahani D, Strobel O, Kalva S, Mino-Kenudson M, Holalkere NS; et al. (2005). "Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.". J Gastrointest Surg. 9 (9): 1262–74; discussion 1274–5. PMC 3807105Freely accessible. PMID 16332482. doi:10.1016/j.gassur.2005.07.034. 

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