Sandbox:Feham

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

Overview

Mesenteric ischemia is a type of intestinal ischemia primarily affecting the small intestine. It is one of the life-threatening gastrointestinal vascular emergencies which requires prompt surgical/medical intervention depending upon the underlying cause.

It can be divided into occlusive/non-occlusive, arterial or venous, localized/generalized and superficial or transmural.

Overview

The anatomy and physiology of the small intestine plays a vital role in the develpoment of mesenteric ischemia. Intestinal muscosa has a high metabolic rate 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. This can lead to disrutpion of mucosal barrier, allowing the release of bacterial toxins and vasoactive mediators which ultimately lead to complete necrosis(cell death) of the intestinal mucosa. This can further progress to myocaridal depression, sepsis, multiorgan failure and without prompt intervention, even death.

Pathophysiology

Pathogenesis: Development of mesenteric ischemia depends on three major factors:

(a) Mesenteric vascular anatomy and physiology

(b) Collateral circulation

(c) Factors regulating the splanchnic circulation

Mesenteric vascular anatomy and physiology: The arterial supply of the intestine originates from three major arteries:

• Superior mesenteric artery- supplies the small intestine, proximal and mid colon upto the splenic flexure.
• Inferior mesenteric artery- supplies hind gut starting from the splenic flexure to the rectum.
• Celiac artery- supplies the foregut, hepatobiliary system and spleen.

• The venous system parallels the arterial branches and drains into the portal venous system.
• The mesenteric circulation recevies approximately 25% of the resting and 35% of the postprandial cardiac output.
• 70% of the mesenteric blood flow is directed to the mucosal and submucosal layers of the intestine with the rest supplying the muscularis and serosal layers.

Which arteries are mostly affected?

• Embolus can typically lodge into points of normal anatomic narrowing, making superior mesenteric artery the most vulnerable site because of its relatively large diameter and low take off angle 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.

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 and can compensate for 75% reduction in mesenteric blood flow for upto 12 hours, without substanial injury.

Factors regulating the splanchnic circulation: Physiologic characteristics of the splanchnic circulation can be divided into two categories:

• Intrinsic pathway(metabolic and myogenic factors)
• Extrinsic pathway(neural and humoral factors)

The pathophysiology of mesenteric ischemia can be explained on the basis of etiology:

• Acute mesenteric arterial embolism: Attributes to 50% cases of mesenteric ischemia.
• Mesenteric embolus can oringinate from the left atrium, associated with cardiac arrythmias such as atrial fibrillation.
• Recent myocardial infarction resulting in segmental wall motion abnormality leading to poor ejaction fraction and embolus formation.
• Infective endocarditis: vegetations on the cardiac valves resulting in turbulence in blood flow predisposing to formation of emboli into the blood stream.
• Embolus can typically lodge into points of normal anatomic narrowing, making superior mesenteric artery the most vulnerable because of its relatively large diameter and low take off angle 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.
• Acute mesenteric arterial thrombosis:
• 25% cases of mesenteric ischemia result from mesenteric arterial thrombosis.
• Most likely due to underlying atherosclerosis(plaque formation) leading to stenosis.
• An underlying plaque(fatty streak) in the superior mesenteric artery leads to critical stenosis over the years forming collaterals.
• It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
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• Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
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Genetics

• [Disease name] is transmitted in [mode of genetic transmission] pattern.
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Gross Pathology

• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Risk Factors

Common Risk Factors

The following conditions pose a signifiacnt risk towards the development of mesenteric ischemia either by interrupting the blood flow through the artery or vein supplying the small intestine (e.g.thromboemboli) or by reducing the blood supply (e.g. vasoconstriction). Also, there are certain life-style related risk factors which predominantly cause mesenteric ischemia in the older age group.

Risk factors
Occlusive	Embolic	Atrial fibrillation
		Cardiac arrhythmia
		Valvular heart disease
		Infective endocarditis
		Recent myocardial infarction
		Ventricular aneurysm
		Aortic atherosclerosis
	Thrombotic	Advanced age
		Low cardiac output states
		Peripheral arterial disease
		Traumatic injury
		Inherited thrombophilia- Factor V Leidin mutation Prothrombin G20210A mutation Protein S deficiency Antithrombin III deficiency Activated protein C resistance Anti-phospholipid syndrome Myeloproliferative disorders(JAK2 V617F) mutation.
		Acquired thrombophilia- malignancy, oral contraceptives intake.
Non-occlusive		Heart failure
		Aortic insufficiency
		Septic shock
		Vasoconstrictive drugs: Digoxin Alpha-adrenergic agonists
		Cocaine abuse or ergot poisoning
		Hemodialysis
Other causes		Lifestyle related risk factors: High cholesterol levels History of smoking Immobility Recent surgery Less common risk factors: Fibromuscular dysplasia Beta receptor blocking agents Hepatitis

• Common risk factors in the development of mesenteric ischemia include:
  • Occlusive causes
    • Embolic causes:
    • Atrial fibrillation
    • Cardiac arrhythmias
    • Valvular heart diseases
    • Infective endocarditis
    • Recent myocardial infarction
    • Ventricular aneurysm
    • Aortic atherosclerosis
    • Aortic aneurysm
  • Thrombotic causes:
    • Advanced age
    • Low cardiac output states
    • Traumatic injury
    • Peripheral artery disease
• Non-occlusive causes:
  • Heart failure
  • Aortic insufficiency
  • Septic shock
  • Vasoconstrictive drugs(e.g. Digoxin, alpha-adrenergic agonists)

• • Cocaine abuse or ergot poisoning

• • Hemodialysis

Less Common Risk Factors

• Less common risk factors in the development of mesenteric ischemia include:
  • Fibromuscular dysplasia
  • Hepatitis
  • Beta recpetor blocking agents
  • Polyarteritis nodosa

Causes

Narrowing of the arteries that supply blood to the intestine causes mesenteric ischemia. The arteries that supply blood to the intestines run directly from the aorta. Mesenteric ischemia is often seen in people who have hardening of the arteries in other parts of the body (for example, those with coronary artery disease or peripheral vascular disease). The condition is more common in smokers and in patients with high blood pressure or blood cholesterol. Mesenteric ischemia may also be caused by an embolus that suddenly blocks one of the mesenteric arteries. The emboli usually come from the heart or aorta. These clots are more commonly seen in patients with arrhythmias, such as atrial fibrillation. They can be broadly classified into four categories:

• Arterial thrombosis
• Arterial embolism
• Venous thrombosis
• Non-occlusive ischemia

Classification based on etiology
Etiology	Cause	Incidence	Examples
Occlusive causes	Aterial embolism	50-70%	Superior mesenteric artery obstruction (most common cause) Arrhythmia Myocardial infarction Infective endocarditis Valvular heart diseases Ventricular aneurysms History of embolic events Recent angiography
	Arterial thrombosis	15-25%	Atherosclerosis Advanced age Prlonged hypotension Hypercoagulabilty states Peripheral arterial disease Traumatic injury
	Venous thrombosis	5%	Right-sided heart failure Previous deep venous thrombosis (20-40% risk) Primary clotting disorder Pancreatitis Polycythemia Sickle cell anemia Recent abdominal surgery or infection
Non-Occlusive causes	Non-occlusive ischemia	20-30%	Low cardiac output states(most commom cause) Hypovolemia Vasoconstrictive drugs (Digoxin, alpha-adrernergic agonists) Septic schock Aortic insufficiency Cocaine abuse or ergot poisoning