Mesenteric ischemia pathophysiology

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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

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  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. 
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  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. 
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  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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