Mesenteric ischemia 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.

# Historical Perspective
In 1843, Tiedemann described mesenteric occlusion and bowel infarction, followed by Virchow who added two more patients to the literature. In 1921, Klein wrote a thesis on embolism and thrombosis, in which he pointed out a relationship between SMA stenosis and episodic abdominal pain. In 1936, Dunphy was the first one to establish an association between mesenteric artery occlusion and bowel infarction. In 1971, the first book written on all aspects of mesenteric ischemia named "Vascular Disorders of the Intestines" was published and edited by Boley, Schwartz, and Williams.

# Classification
Mesenteric ischemia (MI) is classified into various subdivisions based on the difference in pathogenesis and treatment of each type. MI is primarily classified into acute and chronic, on the basis of severity; occlusive and non occlusive based on their pathophysiology.

# Pathophysiology
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.

# Causes
Narrowing of the arteries that supply blood to the intestine causes mesenteric ischemia. The arteries that supply blood to the intestines travel straight 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 can 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.

# Differentiating Mesenteric Ischemia from Other Diseases
Mesenteric ischemia must be differentiated from other diseases that cause abdominal pain, diarrhea, nausea and vomiting, such as ischemic colitis, inflammatory bowel disease, and irritable bowel syndrome.

# Epidemiology and Demographics
The incidence rate of mesenteric ischemia secondary to superior mesenteric artery occlusion is 8.6/100 000/year. 70% of SMA occlusion is caused by embolism and 30% by thrombosis. The annual incidence of mesenteric ischemia is approximately 5.5% per 100,000 individuals. The incidence of mesenteric ischemia increases with age and the median age at diagnosis is 70 years. Mesenteric ischemia affects men and women equally.

# Risk Factors
Risk factors causing mesenteric ischemia can be divided based on the underlying etiology. Conditions posing a significant risk towards the development of mesenteric ischemia either by interrupting the blood flow through the artery or vein supplying the small intestine (e.g thromboembolism) 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.

# Screening
There is insufficient evidence to recommend routine screening for mesenteric ischemia.

# Natural History, Complications, and Prognosis
If left untreated, 99% of patients with mesenteric ischemia may progress to develop intestinal gangrene, septic shock and subsequently multiorgan failure. The progressive phases of mesenteric ischemia include hyperactive phase, paralytic phase and shock phase. The prognosis mostly depends on prompt diagnosis and timely medical/surgical intervention depending on the underlying etiology. Poor prognostic factors include signs such as tachypnea, tachycardia, hypotension and altered mental status. Common complications of mesenteric ischemia include bowel infarction, perforation, sepsis, peritonitis, septic shock, and multiorgan failure.

# Diagnosis

## Diagnostic Study of Choice:
The definitive diagnosis of mesenteric ischemia relies mainly on the imaging studies of which the most accurate is high resolution computed tomographic angiography. It not only demonstrates the site of occlusion in the vessels but also guides about making  the correct choice of treatment. It has a sensitivity of 94% and a specificity of 95%.

## History and Symptoms
The hallmark of mesenteric ischemia symptoms  is 'abdominal pain out of proportion to the examination findings'. A positive history of chronic cardiovascular disorder, old age and abdominal pain is suggestive of mesenteric ischemia. The most common symptoms of mesenteric ischemia include excruciating abdominal pain, bloody diarrhea, and nausea/vomiting. Symptoms of chronic mesenteric ischemia caused by atherosclerosis include abdominal pain after eating and diarrhea, while that of acute mesenteric ischemia due to an embolus include diarrhea, sudden severe abdominal pain, and vomiting.

## Physical Examination
Physical examination of patients with mesenteric ischemia can be normal in early stages or there may be mild abdominal distension in the absence of peritonitis which presents as rebound tenderness and guarding. As the ischemia progresses to involve all the layers of the intestine (transmural infarction), abdomen becomes distended, peritoneal signs develop and bowel sounds become absent.  A feculent odor to the breath may also be noticed. Signs of dehydration and shock may also appear if not treated in time.

## Laboratory Findings
No specific biomarker for the diagnosis of mesenteric ischemia has been identified to date. However, certain biomarkers are released into circulation as a result of ischemic injury to the intestine, which can be detected in the blood.

## Electrocardiogram

## X-ray
Plain radiographs such as X-ray abdomen can be helpful in ruling out other important causes of acute abdomen such as perforation. The sensitivity of this test is limited because it can show normal findings in as many as 25% of cases of mesenteric ischemia.

## Ultrasound
Duplex ultrasonograghy is often used for the evaluation of abdominal pain. However, in case of acute mesenteric ischemia its sensitivity is relatively reduced as compared to other radiological tests owing to its diagnostic limitation by the presence of air-filled distended bowel loops. Its primary clinical application is in the diagnosis of high grade arterial stenosis.

## CT scan
Computerised axial tomographic angiography should be performed as soon as possible in order to diagnose mesenteric ischemia becasue of its ability to define the arterial anatomy and demonstrate the site of occlusion.

## MRA
Magnetic Resonance Angiography(MRA) is another investigation which helps diagnose mesenteric ischemia. However, its clinical application is limted as compared to computed tomography angiography because the latter is readily available and less cost effective.

## Other Imaging Findings

## Other Diagnostic Studies
Although computed tomography angiography remains the diagnostic test of choice for mesenteric ischemia. However, there are newer diagnostic studies which may be helpful in making the diagnosis of mesenteric ischemia and include functional studies such as tonometry, spectroscopic oximetry and MR flow.

# Treatment

## Medical Therapy
Mesenteric ischemia is a medical emergency that requires prompt treatment. The mainstay of treatment is surgery if bowel necrosis or gangrene has occurred , whereas medical therapy is considered initially for hemodynamically stable patients.

## Surgery
Surgery in mesenteric ischemia is done to resect the ischemic bowel in order to prevent the complications. However, in case of acute embolic type of mesenteric ischemia, early laparotomy and surgical resection is the mainstay of treatment.

## Primary Prevention
In order to prevent mesenteric ischemia, the risk factors should be controlled avidly. Healthy life style changes and screening of comorbidities posing a risk to developing mesenteric ischemia are the most important factors.

## Secondary Prevention
Effective measures to prevent recurrence of mesenteric ischemia include screening by duplex ultrasonography, nutritional and life style modification, and drug therapy.