3.1 Anatomy

The blood flow to the splanchnic organs is derived from three main arterial trunks: the celiac, the superior mesenteric artery and the inferior mesenteric artery. The celiac artery supplies blood to the foregut (stomach and duodenum), the superior mesenteric artery supplies blood to the midgut (duodenum to transverse colon), and the inferior mesenteric artery is responsible for blood to the hindgut (transverse colon to the rectum). Each of these three arterial trunks supplies blood flow to its specific section of the gastrointestinal tract through a vast arcade network. This arcade system is an effective collateral circulation and is generally protective against ischemia, since blood can reach a specific segment of gut via more than one route. As shown in Figure 2, additional vascular protection is obtained from vascular connections between the three arterial systems. Communication between the celiac system and the superior mesenteric system generally occurs via the superior pancreaticoduodenal and the inferior pancreaticoduodenal arteries. The superior mesenteric and inferior mesenteric systems are joined by the arch of Riolan and the marginal artery of Drummond, vessels that connect the middle colic artery (a branch of the superior mesenteric artery) and the left colic artery (a branch of the inferior mesenteric artery). In addition, communication also exists between the inferior mesenteric artery and branches of the internal iliac arteries via the rectum. The caliber of these collateral connections varies considerably depending on the existence of vascular disease, but it is important to realize that in chronic states of vascular insufficiency, blood flow to an individual system can be maintained through these collateral connections even when an arterial trunk is completely obstructed. It is not uncommon to find one or even two arterial trunks completely occluded in the asymptomatic patient with chronic vascular disease. In fact, there are reports of occlusion of all three trunks in patients who are still maintaining their splanchnic circulation. However, in up to 30% of people, the collateral connections between the superior and inferior mesenteric arteries, via the arch of Riolan and the marginal artery of Drummond, can be weak or nonexistent, making the area of the splenic flexure particularly vulnerable to acute ischemia. This region of poor collateral circulation is often referred to as a "watershed area."

The mesenteric circulation receives approximately 30% of the cardiac output. Mesenteric blood flow is less in the fasting state and is increased with feeding. Blood flow through the celiac and superior mesenteric trunks is about equal (approximately 700 mL/min in the adult) and is twice the blood flow through the inferior mesenteric trunk. Blood flow distribution within the gut wall is not uniform, and it varies between the mucosa and the muscularis. The mucosa has the highest metabolic rate and thus it receives about 70% of the mesenteric blood flow. If one compares gut segments of equal weight, the small bowel receives the most blood, followed by the colon and then the stomach.

Much has been written on the control of gastrointestinal blood flow. Many factors are involved. A few important highlights of mesenteric vascular resistance will be discussed here. Vascular resistance is proportional to 1/r⁴ (where r = the radius of the vessel). Thus the smaller the artery, the greater its ability to effect vascular resistance. It is known that the majority of blood flow control occurs at the level of the arterioles, the so-called resistance vessels. Very little control of blood flow occurs at the level of the large arterial trunks. In fact, the diameter of these large arterial trunks can be compromised by 75% before blood flow is reduced. Additional control of blood flow occurs at the level of the precapillary sphincter. In the fasting state only one-fifth of capillary beds are open, leaving a tremendous reserve to meet increased metabolic demands.

Among the most important control mechanisms of splanchnic blood flow are the sympathetic nervous system, humoral factors and local factors. The sympathetic nervous system through a-adrenergic receptors plays an important role in maintaining the basal vascular tone and in mediating vasoconstriction. Beta-adrenergic activity appears to mediate vasodilation, and it appears that the antrum of the stomach may be particularly rich in these b receptors. Humoral factors involved in the regulation of GI blood flow include catecholamines, the renin-angiotensin system and vasopressin. These humoral systems may play a particularly important role in shock states and in some patients may play a role in the pathogenesis of nonocclusive ischemia. Local factors appear to be mainly involved in the matching of tissue blood flow to the metabolic demand. An increased metabolic rate may produce a decreased pO₂, increased pCO₂ and an increased level of adenosine, each of which can mediate a hyperemic response.

More recent and exciting research has identified the vascular endothelium as a source for potent vasoactive substances, such as nitric oxide (vasodilator) and endothelin (vasoconstrictor). Although these endothelial-derived substances may act systemically, it would appear that their major effect is local in a paracrine hormonal fashion. Although these vasoactive substances have the potential to dramatically alter mesenteric blood flow, their exact role in health and disease remains to be elucidated.

The integration of these control systems and their alteration by factors such as vascular disease, motor activity, intraluminal pressure and pharmaceuticals remains poorly understood. The key to our understanding and successful treatment of intestinal ischemia lies in a better knowledge of this physiology.

Intestinal ischemia occurs when the metabolic demand of the tissue supersedes the oxygen delivery. Obviously, many factors can be involved in this mismatch of oxygen need and demand. These include the general hemodynamic state, the degree of atherosclerosis, extent of collateral circulation, neurogenic/humoral/local control mechanisms of vascular resistance and abnormal products of cellular metabolism before and after reperfusion of an ischemic segment. Acute occlusion/hypoperfusion of a large mesenteric vessel usually results in transmural (gangrenous) ischemia of the small bowel and/or colon. On the other hand, acute occlusion of the intramural vessel(s) usually results in intramural (nongangrenous) ischemia. However, there are exceptions in both cases, depending on the severity of occlusion/hypoperfusion. As previously mentioned, the mucosa is the most metabolically active gut wall tissue layer and thus it is first tissue layer to demonstrate signs of ischemia. The earliest form of intestinal ischemia produces changes at the tip of the intestinal villi. With ongoing ischemia ultrastructural changes begin within 10 minutes and cellular damage is extensive by 30 minutes. Sloughing of the villi tips in the small bowel and the superficial mucosal layer of the colon is followed by edema, submucosal hemorrhage and eventual transmural necrosis.

The intestinal response to ischemia is first characterized by a hypermotility state. It is this intense motor activity that results in the patient experiencing severe pain, even though the ischemic damage may be limited to the mucosa at this stage. As the ischemia progresses, motor activity will cease and gut mucosal permeability will increase, leading to an increase in bacterial translocation. With transmural extension of the ischemia, the patient will develop visceral and parietal inflammation resulting in peritonitis.

An important factor often responsible for or aggravating intestinal ischemia is the phenomenon of vasospasm. It has been well demonstrated that both occlusive and nonocclusive forms of arterial ischemia can result in prolonged vasospasm, even after the occlusion has been removed or the perfusion pressure restored. This vasospasm may persist for several hours, resulting in prolonged ischemia. The mechanism responsible for this vasospasm is not clearly defined, but there is preliminary evidence that the potent vasoconstrictor endothelin may be involved. To date, many of the interventional techniques used in the treatment of acute mesenteric ischemia have been directed at counteracting this vasospasm.

A second factor that may be responsible for accentuating ischemic damage is reperfusion injury. This phenomenon has been well demonstrated in the laboratory, where it has been shown to be responsible for a greater degree of cellular damage than that brought about during the actual ischemic period. Parks and Granger have shown in an animal model that the injury after one hour of ischemia and three hours of reperfusion is more severe than that observed after four hours of continuous ischemia. The mechanism responsible for this reperfusion injury appears to be related to the release of harmful reactive oxygen metabolites, which are thought to be released from adhering polymorphonuclear leukocytes. It is not known what role ischemia reperfusion injury plays in humans with occlusive and nonocclusive disease.