The mesenteric arterial bed receives 10% to 35% of total cardiac output. Diseases of this extensive arterial bed can be a cause of significant mortality and morbidity. Ischemia of the mesenteric vasculature is caused by a reduction in the blood flow either from a systemic low flow state or from local impairment of the flow. Sudden onset of intestinal hypoperfusion from occlusive or nonocclusive obstruction of arterial or venous blood flow causes acute mesenteric ischemia. Chronic mesenteric ischemia is the result of episodic or constant intestinal hypoperfusion usually among patients with systemic atherosclerosis.

Mesenteric circulation has numerous variations in its blood supply to the visceral organs. Delineation and understanding of these various patterns of mesenteric circulation is important. Fortunately, with the advent of current imaging technology and digital angiography, it is now quite possible to accurately study the major vessels, pathologies, and aberrations of these vessels as well their branches, and the collaterals in every patient.

Embryology

The mesenteric vessels arise from the primitive ventral segmental arteries. All but three of these segmental arteries regress as development proceeds.¹ The 10th, 13th, and 21st or 22nd artery give rise to the celiac, superior mesenteric, and inferior mesenteric artery (IMA) to supply the foregut, midgut, and the hindgut, respectively. Figure 31.1 shows the embryologic origin of mesenteric arteries.

Arterial Supply of the Intestines

Arterial supply of the mesenteric bed is characterized by a unique, well-developed network of collateral circulation. Presence of this collateral network is protective to a great extent against transient perturbation in the vascular supply of the intestines. Ischemia can develop even in the background of this rich collateral network if the insult persists for a prolonged period or if the insult affects a large area of vasculature.^2,3

The blood supply predominantly occurs through three major branches of the abdominal aorta. Figure 31.2 shows the splanchnic arteries and the collateral circulation.

Celiac Axis

Celiac axis (CA) is the largest of the three arteries, and originates anteriorly from the aorta. After origin, it trifurcates into common hepatic, splenic, and left gastric arteries. The common hepatic artery may provide significant collateral flow to the intestine through its first branch, the gastroduodenal artery as well as the anterior and posterior pancreaticoduodenal arcades.

Superior Mesenteric Artery

The superior mesenteric artery (SMA) arises anteriorly, 1 to 3 cm distal to the celiac artery, and forms a more acute angle. It courses almost parallel to the aorta proximally before curving toward the right lower quadrant terminating as the ileocolic artery. It also gives rise to the inferior pancreaticoduodenal artery, several ileal and jejunal branches, the middle colic artery, and the right colic artery. The middle colic artery supplies the proximal to midtransverse colon, and the right colic artery supplies mid to distal ascending colon. The ileocolic artery supplies the distal ileum, cecum, and the proximal ascending colon.

Inferior Mesenteric Artery

The IMA artery is smaller in caliber, originates from the infrarenal aorta 5 to 8 cm distal to the SMA. It gives rise to left colic artery, the sigmoid arteries, and the hemorrhoidal arteries. It provides perfusion to the distal transverse colon, descending colon, and the rectum. The superior hemorrhoidal artery, the continuation of the IMA descends into the pelvis between the layers of the mesentery of the sigmoid colon, form a series of loops around the lower end of the rectum, and communicate with the middle hemorrhoidal branches of the internal iliac artery, and with the inferior hemorrhoidal branches of the internal pudendal artery.

Collateral Circulation: Three major collateral networks in the mesenteric arterial circulation are responsible for rendering splanchnic bed relatively resistant to ischemic insult unless two of the three mesenteric arteries are simultaneously diseased. The CA and the SMA via superior and inferior pancreaticoduodenal arteries, the SMA and IMA via middle colic and left colic arteries (primarily anastomose through the marginal artery of Drummond and the Arc of Riolan), and the IMA and internal iliac artery via superior hemorrhoidal artery and middle rectal arteries comprise these collateral networks. Symptomatic manifestations of intestinal ischemia depend on the site of stenoses in relation to these collateral networks. If stenosis is mainly before the collateral network, patient may not develop symptoms at all. However, if stenoses occur either after the collateral network or both before and after the collateral network, symptoms develop readily.

Regulation of mesenteric vascular tone can be either by intrinsic autoregulation or by extrinsic control. Following sudden fall in intestinal hypoperfusion, direct arterial smooth muscle relaxation ensues. Metabolic response to adenosine and other metabolites of ischemia are the proposed mechanism of this arteriolar relaxation.^4,5 Autoregulation continues to maintain intestinal perfusion across the range of mean arterial pressure of 50 to 75 mm Hg. A broad array of neurohumoral factors such as gastrin, glucagon, and secretin as well as other vasoactive petides such as bradykinin, serotonin, histamine, and prostaglandins are thought to contribute to the regulation of the mesenteric blood supply. Autonomic nervous system, renin angiotensin system, and vasopressin all play important roles in the control of splanchnic blood supply. Sudden reduction in blood supply to the intestine initiates the changes associated with organ ischemia, and compromises the mucosal barrier function. Because of extensive collateral network, and efficient oxygen extraction, intestine can sustain substantial ischemic injury for several hours. Following restoration of blood supply, reperfusion injury can cause further deleterious effects catalyzed by oxygen-free radicals and other toxins. Following brief period of ischemia, reperfusion injury causes most of the damage, whereas after prolonged ischemia, hypoxic damage predominates. Both reperfusion injury and prolonged ischemia result in loss of cellular integrity, and eventual cell necrosis.

Mesenteric ischemia can be acute or chronic.

Acute Mesenteric Ischemia: Table 31.1 enlists various risk factors of mesenteric ischemia. Acute mesenteric ischemia accounts for 60% to 70% of mesenteric ischemia. The diagnosis of acute mesenteric ischemia maybe present in up to 1 in every 1000 patients admitted to acute care hospitals and is bound to increase as our aging population is on the rise. Advanced age, low cardiac output state, atherosclerotic cardiovascular disease, recent myocardial infarction, cardiac arrhythmias, valvular heart disease, and intra-abdominal neoplasms are specific risk factors for acute mesenteric ischemia.² Formation of oxygen-free radicals during ischemia causes injury to the bowel wall, and allows systemic release of endotoxins from the infarcted bowels. The endotoxemia thus ensued following restoration of flow can lead to DIC, shock, adult respiratory distress syndrome (ARDS), and even multiorgan system failure. Acute mesenteric ischemia carries a mortality rate up to 60% among hospitalized patients.²

Arterial Embolism

Embolization to the SMA is the most frequent cause of acute mesenteric ischemia. In response to acute occlusion, concomitant vasoconstriction may further compromise arterial perfusion, thus exacerbating the ischemic insult. Because of larger caliber and narrow angle at the take-off at its origin, SMA is more susceptible to embolization unlike IMA, which is of smaller caliber and thus is very rarely affected by arterial emboli.^6,7,8,9 Typically, the emboli originate in the heart in an akinetic or aneurysmal left ventricular apex following an infarction, in the left atrial appendage in atrial fibrillation, and in valve cusps with vegetations in infective endocarditis. Rarely, a paradoxical embolism from the venous thrombus may cross an unrecognized right to left shunt (generally, a patent foramen ovale). Occasionally, atheromatous aortic arch with mobile plaques either spontaneously or with catheter manipulation in the aorta during an endovascular procedure may contribute to SMA embolism. Emboli usually become lodged at major branch points within the SMA where the distal vessel tends to taper. This is typically just beyond the origin of the middle colic artery, although emboli at more distal branch points have been identified. Proximal SMA perfusion maybe maintained, ensuring viability of the jejunum and resulting in a clear demarcation of the affected intestinal segment at the time of laparotomy. In about 15% of patients, emboli may occlude the SMA at its origin, and in 20%, emboli may affect multiple vascular beds.^2,6 Figure 31.3 shows appearance of small intestine during acute mesenteric ischemia. Figures 31.4 and 31.5 depict surgical procedures for acute mesenteric ischemia. Figure 31.6 shows an angiogram showing acute SMA occlusion from an embolus.

Arterial Thrombosis

Thrombosis of the mesenteric arteries occurs at the ostia (aorto-ostial), or very proximal segments of the mesenteric arteries. Thrombosis of the residual lumen of the diseased mesenteric artery may occur during a period of relative hypotension, or reduced flow.¹⁰ Dehydration may also precipitate thrombosis in elderly patients.¹¹ Sometimes, intramural hemorrhage into an atheromatous plaque may lead to complete occlusion of the vessel lumen. Although atherosclerosis is the commonest cause of mesenteric arterial thrombosis, arterial dissection either as a result of extension of an aortic dissection or localized dissection (spontaneous or iatrogenic) may also cause thrombosis. Fibromuscular dysplasia (FMD) and Takayasu’s arteritis may also cause thrombosis of the mesenteric arteries. Rarely, arterial thrombosis may occur with underlying hypercoagulable state.¹²

Mesenteric Venous Thrombosis

Although this chapter focuses on arterial diseases, mesenteric venous thrombosis (MVT) is an important cause of mesenteric ischemia, and will be briefly discussed here. The development of thrombus in the portal and superior mesenteric venous system may induce intestinal ischemia. Hypercoagulable state, traumatic injury, smoking, portal hypertension, splenectomy, malignancies of the portal region, obstruction of the venous flow, and intra-abdominal infection are risk factors commonly associated with mesenteric vein thrombosis.^13,14 In contrast to other etiologies of acute mesenteric ischemia, patients with MVT are typically younger, between the ages of 30 and 60 years, and predominantly women. Inherited hypercoagulable states account for the majority of cases of venous thrombosis. Activated protein C resistance, prothrombin 20210 A gene mutation, deficiencies of protein C & S, antithrombin III deficiency, and antiphospholipid antibody syndrome (APS) are present in that order. Among the acquired hypercoagulable state, paroxysmal nocturnal hemoglobinuria and myeloproliferative syndromes are commonly associated with MVT.¹⁴ The primary pathophysiologic process associated with venous thrombosis is an increase in portal and mesenteric venous pressure. This increased hydrostatic pressure leads to luminal fluid sequestration and bowel wall edema. The resultant relative hypovolemia and hemoconcentration lead to vasoconstriction and ultimately infarction. The arterial response to venous thrombosis may persist well after the venous obstruction has been corrected. Figure 31.7 shows normal mesenteric venous circulation and Figure 31.8 shows a computed tomography (CT) of abdomen with MVT.

Nonocclusive Mesenteric Ischemia

Hypoperfusion of the mesenteric vascular bed and resultant reactive vasoconstriction among patients with advanced atherosclerotic vascular disease leads to nonocclusive mesenteric ischemia (NOMI). Low output cardiac state following a large myocardial infarction or an episode of congestive heart failure, hypovolemia following blood loss or diuretic use, cardiac arrhythmias, sepsis, aortic insufficiency, drugs such as digoxin and alpha adrenergic agonists (pseudoephedrine, amphetamines), cocaine use, postcardiac surgery, especially those requiring long aortic cross-clamp time or inotropic support, and postdialysis are associated with NOMI.^15,16,17,18 NOMI can also occur as a result of mesenteric arterial spasm following repair of aortic coarctation and revascularization procedures for chronic mesenteric ischemia.

Chronic Mesenteric Ischemia

Chronic mesenteric ischemia refers to episodic or constant intestinal hypoperfusion that usually develops among patients with mesenteric atherosclerotic disease.¹⁹ Patients typically develop abdominal pain (intestinal angina) within 1 hour of eating that lasts typically 1 to 2 hours. Larger and fatty meals tend to worsen symptoms readily.²⁰ Typically, patients will have marked weight loss as they develop fear of food, and want to eat frequent small meals to avoid worsening of their pain. Disease of other vascular trees such as coronary and peripheral arteries often coexist, and risk factors of systemic atherosclerosis including diabetes, hypertension, and smoking are often present.^21,22 Figure 31.9 shows mesenteric stenosis causing chronic mesenteric ischemia. Figure 31.10 depicts development of collaterals in splanchnic artery occlusions.

Unusual Causes of Chronic Mesenteric Ischemia

mechanical causes

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  Mesenteric Arterial Dissection: The causes of spontaneous arterial dissection of the splanchnic arteries are uncertain. Atherosclerosis, cystic medial necrosis, and primary muscular dysplasia are thought to be contributory. Dissection can present either as intra-abdominal hemorrhage (abdominal apoplexy) or mesenteric ischemia.²³

  
  
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  Median Arcuate Ligament Syndrome: Median arcuate ligament syndrome is caused by compression of the celiac or SMA by the median arcuate ligament of the diaphragm. Two anatomic variants have been described.²³ In one, CA alone is compressed; in the other, both CA and SMA are compressed. It occurs in young individuals, mostly women. The pain produced by celiac compression could be ischemic or neural in origin caused by fibrosis of celiac ganglion.^23,24 In many patients, this syndrome progresses to thrombosis of celiac artery. Median arcuate ligament syndrome is unusual in that only one mesenteric artery needs to be involved to produce symptoms. The classical presentations are upper abdominal pain on eating, with associated weight loss, and a loud epigastric systolic bruit. The bruit occurs throughout systole, and the initial part of diastole. During inspiration, the bruit is loudest owing to caudal displacement of aorta and CA with the celiac band moving in cranial direction. Angiography, especially lateral aortography, shows compression of CA by the median arcuate ligament during deep expiration and is diagnostic. Compression of CA by the arcuate ligament produces a concave defect in the superior aspect of the celiac trunk just beyond its origin. This defect often increases with expiration, and decreases or disappears with inspiration. Duplex ultrasonography can measure blood flow in the SMA and CA. Contrast-induced CT scan and MR angiogram may also be used to demonstrate a compression. Surgery is the treatment of choice for median arcuate ligament syndrome. Division of the obstructing diaphragmatic fibers and denervation of the celiac ganglion is the most commonly performed operative procedure. Endovascular treatment maybe used in conjunction with surgical procedure. Balloon dilation of the CA or SMA or arterial reconstruction following surgical division may offer more symptomatic relief compared to surgical division alone.^23,25 Figures 31.11, 31.12, 31.13 and 31.14 show relation of median arcuate ligament to the celiac and SMA.

  
  
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  Retroperitoneal Fibrosis: Retroperitoneal fibrosis is a rare disorder characterized by inflammatory and fibrotic changes of the retroperitoneal space. It has been associated with the use of methysergide, an antimigraine agent.²⁶ Rarely, this can occur with inflammatory aneurysms. Ureteral obstruction is a common finding in this disorder. Although arterial obstruction is rare, obstruction of the abdominal aorta or its branches (celiac or mesenteric arteries) can occur and cause chronic intestinal ischemia.²⁷ Surgical resection of the fibrotic tissue to relieve the arterial obstruction maybe attempted in symptomatic patients, though maybe technically difficult.

  
  
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  Neurofibromatosis: Neurofibromatosis (Von Recklinghausen’s disease) is an autosomal dominant, neurocutaneous disorder and characterized by café-au-lait spots, mental retardation, seizure disorder, and multiple neurofibromas. Intimal and adventitial layers of the vascular system are distorted by presence of neurofibromas within these layers. This may eventually lead to vascular compromise, and thereby intestinal ischemia.²⁸

  
  
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  Radiation: Exposure to radiation therapy leads to chronic fibrosis and cicatrisation (formation of scar tissue) of the mural and extramural tissue, and thereby can cause obstruction of one of the splanchnic vessels leading to mesenteric ischemia.²³

drugs

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  Digitalis: Digitalis, a cardiac glycoside, produces contraction of vascular smooth muscles in vitro and in vivo. Thus, among patients with preexisting mesenteric atherosclerosis, digitalis-induced vasoconstriction may lead to mesenteric ischemia, particularly NOMI.^29,30

  
  
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  Cocaine: It is a sympathomimetic and local anesthetic alkaloid. A very popular recreational drug, and at present widely abused, it can cause numerous cardiovascular and cerebrovascular complications such as myocardial infarction, stroke, and arrhythmia by causing arterial vasoconstriction.³¹ By similar mechanism, cocaine causes intestinal vasoconstriction and ischemia regardless of its mode of administration.³²

  
  
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  Ergotamines: The ergot alkaloids, especially ergotamine are potent arterial vasoconstrictors. Chronic and repetitive use of ergot alkaloids may thus lead to intense intestinal vasoconstriction and subsequent mesenteric ischemia.³³

  
  
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  Vasopressors: Alpha adrenergic agonists such as ephedrine, pseudoephedrine, amphetamines, and vasopressin can cause vasoconstriction and intestinal ischemia.^34,35

clinical features. Accurate diagnosis of acute mesenteric ischemia remains a clinical challenge while early and prompt diagnosis is the key to improving patient survival. Table 31.2 describes clinical features of four major causes of acute mesenteric ischemia. Heightened awareness and adequate knowledge of the varied clinical presentations while maintaining a high index of suspicion play vital roles in making an expedient diagnosis of acute mesenteric ischemia.

Rapid onset of severe periumbilical abdominal pain, often out of proportion to physical findings, is the commonest presentation of acute mesenteric ischemia. This apparent inconsistency between the presenting symptoms and paucity of physical findings, which has been a major hurdle in making an accurate diagnosis, is unfortunately the sine qua non of acute mesenteric ischemia.^2,9 Unlike most of the atherosclerotic vascular disease, mesenteric ischemia does not predominate in men. Among patients with arterial embolism and thrombosis causing mesenteric ischemia, the symptom onset is drastic. However, among patients with MVT, symptoms are more insidious in onset. Several clues to the etiology of ischemia maybe present. Acute abdominal pain followed by rapid and forceful bowel evacuation strongly suggests SMA emboli. Acute abdominal pain that develops after percutaneous arterial interventions in which catheters traverse the visceral aorta or abdominal pain among patients with risk factors of systemic emboli such as atrial fibrillation or recent myocardial infarction should suggest mesenteric emboli as the cause of acute intestinal ischemia.²¹ A history of abdominal pain for several months followed by acute worsening suggests mesenteric artery thrombosis. Patients with NOMI may not present with abdominal pain in up to 25% of cases, and may present as unexplained abdominal distension and gastrointestinal bleeding. Nausea and vomiting, and less commonly diarrhea maybe seen. In patients with NOMI, the clinical picture maybe overshadowed by the precipitating disorders such as hypotension, congestive heart failure, arrhythmia, and hypovolemia.^8,15 The stool may contain occult blood in up to 75% of the patients, and bloody diarrhea is not uncommon. Feculent breath may herald intestinal necrosis. Unexplained abdominal distention may herald intestinal infarction and maybe present early in the course. Mental confusion maybe present in the elderly.³⁶

When physical findings suggestive of an acute intra-abdominal catastrophe are present, bowel infarction may have already ensued, and the chances of survival for these elderly patients are already compromised. Abdominal examination maybe normal initially or reveal only abdominal distension. But as the disease progresses, abdomen becomes grossly distended, bowel sounds become absent, and peritoneal signs develop.

Laboratory Testing

A complete blood count with differential, electrolyte panel, coagulation studies, liver function tests, and an amylase level should be drawn in any patient suspected of having an acute abdominal pain. The findings of leucocytosis, metabolic acidosis, and elevated amylase level are associated with more advanced ischemia and most likely, nonviable bowel. Significant base deficit can occur early in patients with SMA occlusion and intestinal infarction without hypotension. This can occur within 8 to 16 hours of symptom onset, and may precede the physical findings, laboratory data, and radiologic studies suggestive of intestinal infarction. Conditions other than SMA occlusion causing abdominal pain do not cause the base deficit unless associated with cardiogenic shock.³⁷ Serum lactate level is also very helpful in diagnosis in case of intestinal ischemia. Elevated serum lactate level is found in one study to be 100% sensitive, and 42% specific for intestinal ischemia/infarction.³⁸ Serum D-dimer levels maybe elevated in patients with acute ischemia and maybe a useful marker, although nonspecific.³⁹ Alpha-glutathione S-transferase (alpha-GST) and intestinal fatty acid-binding protein (I-FABP) are found to be elevated inpatients with ischemia, and may prove to be useful in diagnosing mesenteric ischemia and infarction.^40,41

Plain Radiography

Plain abdominal x-rays may be normal in early ischemia. Later in the course of ischemia, x-rays may show formless loops of bowel, ileus, or thickening of the bowel wall with “thumbprinting,” suggestive of submucosal edema. Any radiological findings are late signs of ischemia, and portend an ominous outcome.⁴² Figure 31.15 shows radiographic pictures of acute mesenteric ischemia.