Mesenteric vascular disease
Mesenteric vascular disease encompasses a family of diseases in which the end result is ischaemic injury to the small or large bowel. Early recognition and appropriate management offers the best outcome, but this is not easily achieved because in the early stages the presentations are vague and non-specific.
The intestinal tract has a generous overlapping blood supply. The three main vessels supplying circulation to the bowel include the coeliac axis (CA), the superior mesenteric artery (SMA) and the inferior mesenteric artery (IMA). Important collateral vessels emanate from the hypogastric vessels at the level of the sigmoid colon. The CA communicates with the SMA system via the pancreaticoduodenal loop and, to a lesser extent, from the dorsal pancreatic artery. The SMA communicates with the IMA system via the marginal artery (and sometimes a separate collateral, the arc of Riolan, at the base of the mesentery) between the left branch of the middle colic artery and the left colic artery.
In general, acute occlusion of any of the three main mesenteric vessels may lead to acute bowel infarction. Gradual occlusion of any one, two or even three of these vessels can occur without injury, depending on the efficacy of the collateral circulation.
Acute mesenteric ischaemia
Aetiology and pathology
The main blood supply to the intestine is via the SMA. Inadequate intestinal perfusion is due to either a lowflow state or to focal vascular occlusion. Non-occlusive intestinal ischaemia results from inadequate perfusion secondary to hypotension, spasm or intestinal distension. In patients with underlying atherosclerosis and in whom other organ systems are already impaired, a vicious cycle may be initiated. Occlusive vascular diseases include SMA embolism, thrombosis and venous thrombosis. Mesenteric embolus is uncommon. Acute thrombosis certainly occurs, but the relationship between the vascular and the intestinal lesion is not clearcut. However, stenoses and even complete occlusion of the mesenteric vessels can be found in asymptomatic individuals.
The early phase of acute intestinal ischaemia leads to intense loss of circulating blood volume and metabolic acidosis. At this early stage the acute process is still reversible. Vasoactive substances released in response to intestinal ischaemia further diminish perfusion. Partial reduction of molecular oxygen results in the production of oxygen free radicals. These superoxide radicals lead to increased vascular permeability and mucosal injury, and are central to the reperfusion injury. The intestinal mucosa is uniquely rich in the enzyme xanthine oxidase, which contributes to superoxide production. This particularly applies to the phase of reperfusion when the intestinal mucosa is flooded with oxygen. Thus tissue damage tends to occur during reperfusion rather than during the period of ischaemia. Later in the course, mucosal disruption and bacterial invasion develop with endotoxin release, septicaemia and shock, indicating an irreversible injury.
Patients are usually elderly with associated cardiac or peripheral vascular disease. They present with severe central abdominal pain that is often out of proportion to the objective abdominal signs. A history of chronic intestinal ischaemia may be present. Superior mesenteric artery thrombosis is distinguishable from embolism by the more insidious onset of symptoms. Vomiting and diarrhoea may be present. Bloody diarrhoea is evident only late, when mucosal infarction has occurred. Peritoneal irritation indicates full-thickness bowel infarction and the process becomes irreversible.
Non-occlusive mesenteric ischaemia is diagnosed with increasing frequency in intensive care unit settings among critically ill patients with a low blood flow state. This entity should be suspected in anyone with abdominal pain following a prolonged episode of hypotension.
The white blood cell count usually is elevated. It may be used as an indicator to monitor the progress of the disease. Serum phosphate levels, while not specific for bowel ischaemia, may be elevated and these may precede irreversible ischaemic injury. Metabolic acidosis is a late finding and suggests bowel necrosis. In the early stages, the patient appears sicker and in more pain than is suggested by the physical examination. Within a very short period (hours to 1–2 days), the damage progresses and the patient becomes desperately ill with ileus, peritonism and dehydration. Hypovolaemic and septic shock develops and multi-organ failure ensues.
In the early stages, plain radiograph of the abdomen may appear normal. Later, features of ileus develop and air may appear in the portal vein and the liver. In patients with doubtful clinical features who are haemodynamically stable, visceral angiography of the CA, SMA and IMA via the femoral artery is helpful. With thromboembolism, a sharp cut-off is present at the site of obstruction. A normal mesenteric angiogram, however, does not exclude ischaemia, because approximately one-third of cases are ‘non-occlusive’ in nature and are due to a low-flow state.
Vigorous replacement of water and electrolytes is initiated with balanced saline or colloid solution. Adequacy of replacement is monitored by serial measurements of the urine output, vital signs and central venous or wedged pulmonary arterial pressure.
Blood culture is taken and broad-spectrum antibiotics covering Gram-negative organisms and anaerobes are commenced. This will usually be a second- or third- generation cephalosporin together with metronidazole.
Correction of metabolic acidosis
Metabolic acidosis is due to a combination of low tissue perfusion, absorption of products of tissue necrosis, and impaired respiratory exchange. Restoration of circulating blood volume will help to correct acid-base equilibrium. Occasionally, bicarbonate therapy may be necessary.
Continuous infusion with heparin is given for thromboembolic disease to prevent clot extension and to counteract disseminated intravascular coagulation. This therapy is interrupted during surgery.
If clot is demonstrated within the mesenteric system and signs of irreversible ischaemia (i.e. peritonism) are absent, lysis may be performed with fibrinolytic agents infused via a catheter placed in the SMA immediately proximal to the occlusion. Streptokinase is commonly used but there are problems with anaphylaxis, febrile reactions and bleeding. Newer agents such as recombinant tissue plasminogen activator (rTPA) or anisoylated plasminogen streptokinase activator complex (APSAC) may be more efficacious. Clinical reports on these agents are awaited.
Angiographic catheter infusion of papaverine is best for non-occlusive mesenteric ischaemia and, less often, for embolic disease. Epidural block may also help relieve the reflex component of the vasospasm.
This remains the standard surgical treatment when the diagnosis of acute mesenteric ischaemia is suspected or made. Once the metabolic defects are brought under control, swift surgical action is taken, unless the clinical condition has progressed beyond salvage and is preterminal.
The diagnosis is usually obvious, with the characteristic ‘musty’ smell of ischaemic bowel. Thrombosis of the SMA occurs at the origin and produces ischaemia throughout the midgut from the ligament of Treitz to the splenic flexure of the colon. Emboli usually lodge at or distal to the origin of the middle colic artery from the SMA, thus sparing the proximal jejunum and sometimes the right transverse colon. Small emboli may migrate peripherally to cause segmental damage.
A number of surgical options are available.
First, the abdomen can be closed without further action. This procedure is adopted if a large length of intestinal tract is dead such that the patient will be committed to long-term parenteral nutrition and there are severe co-morbid factors.
Second, the infarcted bowel can be resected and both bowel ends exteriorised. This is the safest option and allows inspection of both bowel ends for their viability. Anastomosis and restoration of continuity of bowel is deferred for 4–6 months to allow restoration of health and maturation of intra-abdominal adhesions. Occasionally, a primary anastomosis is performed if viability is assured. In these latter cases, or in cases in which viability is uncertain, the use of a second-look laparotomy may maximise intestinal salvage. The re-exploration is planned and done 24–48 hours later, regardless of apparent clinical improvement. Support with parenteral nutrition is invaluable.
Third, revascularisation of the bowel may be undertaken. Embolectomy for embolic disease or aortomesenteric bypass grafting for arterial thrombosis may be performed. The need for small bowel resection often may be avoided by re-evaluating the viability of the bowel 15–30 minutes after restoration of blood flow. Such operations are technically difficult and the results are variable. Reperfusion of ischaemic bowel also imposes a heavy physiological burden on the patient.
Post-operatively, intensive care with cardiovascular and respiratory monitoring is important. Fluid replacement, antibiotics and inotropic agents are continued. Central intravenous lines, urethral catheter and nasogastric tube are in place. Often a period of assisted ventilation is continued.
Mesenteric infarction is associated with mortality of between 90% and 100%. Embolic disease has a better outcome than thrombotic disease as it tends to present more acutely and earlier. Non-occlusive mesenteric ischaemia tends to have a poor prognosis because of the severity of the underlying illness that precipitates the ischaemic event.
Mesenteric venous thrombosis
Mesenteric venous thrombosis accounts for less than 10% of cases of mesenteric infarction. Approximately 20% are idiopathic but the underlying causes include portal hypertension, haematological diseases, malignancy, inflammatory bowel disease, sepsis, reactions to oral contraceptives and trauma.
Mesenteric venous thrombosis is insidious in onset with vague abdominal discomfort, distension, altered bowel habits and nausea. Later, features of an acute abdomen with tenderness and guarding, and leucocytosis may appear. This is differentiated from arterial occlusion by one of the associated diseases that is commonly present.
A plain radiograph of the abdomen usually shows features of an ileus with dilated loops of small bowel and air-fluid levels. Gas is usually present in the large bowel as well. Mesenteric angiography is less useful; the features include prolongation of the arterial phase, nonopacification of the superior mesenteric vein and visible contrast within the bowel lumen. Diagnostic peritoneal lavage may reveal serosanguineous fluid. In practice, the diagnosis is made at surgery. Operative findings include the presence of a congested, cyanotic, oedematous bowel with pulsatile mesenteric arteries.
Treatment includes fluid resuscitation, antibiotics and prompt surgical intervention. With venous infarction, the damage is often limited and a segmental resection with primary end-to-end anastomosis is performed. A short bowel syndrome is less likely to occur than with arterial occlusion. Anticoagulation therapy is initiated during or immediately after surgery, initially with heparin and subsequently converted to Warfarin. Recurrences occur in 20% of patients and, therefore, anticoagulation therapy is continued for 6 months post-operatively.
Short bowel syndrome
Intestinal failure results from reduction in the amount of functioning gut to below the minimal amount necessary for adequate digestion and absorption of nutrients. A major cause is short bowel syndrome secondary to major resections of the small bowel. The outlook for these patients has improved dramatically with the advent of total parenteral nutrition (TPN) and home parenteral nutrition (HPN).
The length of normal small bowel measured at surgery is variable but is about 350 cm. In general, loss of more than 50–70% or a remaining length of less than 100 cm of small bowel results in significant malabsorption and malnutrition.
Loss of intestinal length leads to a loss of mucosal absorptive surface and an associated shortened transit time. There is a reduced interaction between the nutrients, the biliary and pancreatic secretions, and the intestinal mucosa. Carbohydrate absorption is usually less affected than protein or fat absorption. Fat absorption is most severely affected.
Bile salts are resorbed only by the ileum, and approximately 100 cm of distal ileum is necessary for complete bile salt resorption.With less than 100 cm of ileum, enterohepatic circulation of bile salts is impaired, leading to fat malabsorption and steatorrhoea, which in turn leads to malabsorption of the fat-soluble vitamins A, D, E and K.
Loss of ileum is more disabling than an equal loss of jejunum. The ileum is the selective site for resorption of bile salts as well as the intrinsic factor-bound vitamin B12. The jejunum has a lesser potential for adaptation than the ileum. Motility in the ileum is also slower than in the jejunum, allowing more time for absorption. Loss of jejunum leads to a reduction in several enterohormones. Lactose intolerance may also be noted. Absorption of minerals and electrolytes is disturbed.
The residual small bowel undergoes adaptation, which is most pronounced within the first 6 months. However, adaptive change is a slow process and may continue for up to 3 years after resection. The adaptive changes include cellular hyperplasia, increases in villous height and crypt depth, intestinal lengthening and dilatation, increased absorptive ability and activity of brush border enzymes, and increased transit time. Enteral feeding stimulates intestinal adaptation and should be introduced as soon as the clinical situation allows. Patients maintained on TPN alone do not undergo adaptation as readily.
The following factors may influence the outcome.
- Extent of resection of small bowel.
- Site of resection. Jejunal resections are better tolerated than ileal resections.
- Age of the patient. Younger patients adapt better both physically and mentally than older patients.
- Presence of stomach or colon. Diarrhoea is lessened if the stomach and colon are intact; however, unabsorbed bile salts following massive ileal resection may have a choleretic effect on the colon, causing diarrhoea and fluid-electrolyte loss.
- Presence of ileocaecal valve. The ileocaecal valve reduces bacterial colonisation of the ileum from the colon and slows intestinal transit.
- Health of the residual bowel. Absorption and adaptive potential of the remaining bowel is impaired by the presence of any residual disease.
After massive bowel loss, the immediate problems are dehydration and electrolyte imbalance. These problems may last for several weeks and intravenous fluid replacement is needed to keep apace with ongoing losses (diarrhoea, fistula or stoma effluent), as well as daily maintenance needs. Assessment of fluid and electrolyte balance is made by clinical examination, fluid-balance charts, and biochemical analysis of urine and serum electrolytes, as well as electrolyte analysis of other losses (fistula or stoma effluent). In the short term, TPN is usually necessary while intestinal recovery and adaptation occur.
Enteric feeding is commenced as soon as the clinical condition allows. If massive bowel resection has been performed, enteric feeding through a thin silastic naso-enteric tube may be preferred. Initially, a solution of 5% dextrose with half normal saline is used. When the patient's fluid status stabilises, one of the defined formula diets may be initiated. These contain glucose or other simple sugars, amino acids and peptides, electrolytes, small amounts of fats, vitamins and trace elements. These formulae are hyperosmolar and should be diluted initially to avoid bloating or worsening diarrhoea. Monthly injections of vitamin B12 may be necessary. Glutamine infusions or enteral supplements produce mucosal growth. Additional nutritional needs are supplemented with TPN, and additional fluids and electrolytes are replaced as necessary. Nutritional support is instituted early in the treatment of short bowel syndrome. It prevents malnutrition and improves survival. As adaptation occurs, the enteral intake is increased and the TPN tapered. This phase may take several weeks to a year. In others, a more prolonged HPN may be necessary.
Antidiarrhoeal agents, such as loperamide or codeine are added in increasing dosages tailored to the response. Liquid preparations generally are more readily absorbed and work better. Bulking agents such as Metamucil® may also be used. If bile salt malabsorption is a problem, cholestyramine can be added. Gastric secretion is decreased with H2 antagonists (cimetidine or ranitidine) or proton pump inhibitors (omeprazole). Somatostatin and its analogues (e.g. octreotide) help to reduce diarrhoea or fistula output. Somatostatin acts by slowing intestinal transit, thus improving absorption and by suppressing gastric acid and pancreatic fluid secretion.
Chronic mesenteric vascular disease
Aetiology and pathology
Chronic mesenteric vascular disease or ‘intestinal angina’ is poorly defined and poorly understood. The clinical studies on this disease are limited but there is underlying atheromatous occlusion of the visceral arteries. There is poor correlation between angiographic findings and clinical symptoms. Because of the rich collateral network, high-grade arterial stenosis may be present without any symptoms of ischaemia.
The presenting symptoms are variable but include postprandial pain, weight loss and malabsorption. The patient often refuses to eat because of fear of subsequent pain, which occurs soon after a meal and lasts for several hours.
Surgery should be considered only when the clinical presentation is typical of intestinal ischaemia and there is angiographic evidence of critical stenosis in two of the three vessels. The favoured surgical option is bypass grafting with prosthetic grafts or with autogenous vein grafts. Some early success has been reported following percutaneous transluminal angioplasty. If symptoms recur following a previously successful angioplasty, a favourable outcome may be expected from surgical reconstruction. However, technical failure in the mesenteric circulation could be catastrophic. For this reason, angioplasty should be used only where facilities for immediate operation are available.
Aetiology and pathology
The colon has a generous overlapping blood supply with contributions from the SMA, IMA and hypogastric arteries. All parts of the colon are susceptible to ischaemia. However, two regions are anatomically vulnerable: ‘Griffith’s point', at the splenic flexure corresponding to the junction of the SMA and the IMA; and ‘Sudeck's critical point’, in the midportion of the sigmoid colon corresponding to the junction of the IMA and hypogastric arteries.
Occlusive events and low-flow states both have been associated with ischaemic colitis.
- Surgery: aortic surgery with ligation of a patent IMA or colonic surgery.
- Hypotension or low-flow states from any cause.
- Underlying diseases such as atherosclerosis, vasculitis and polycythaemia.
- Medications such as oral contraceptives, antihypertensive agents, vasopressors and digoxin.
The severity of ischaemic colitis will depend on the duration of reduction in blood flow, the adequacy of collateral circulation and, if the mucosal barrier is disrupted, the concentration of colonic bacteria in the colon. Distension of the involved colon will further impair the transmural blood flow.
Three phases of ischaemic colitis have been described (Phases of ischaemic colitis).
The clinical features depend on the phase of the disease. Common symptoms include left iliac fossa pain if the left colon is the site affected. There may be bloody diarrhoea and often fever and abdominal distension. The patient usually is not grossly ill or shocked.
Laboratory tests and angiography usually are not helpful. Barium enema has been a useful tool in diagnosis, by demonstrating ‘thumbprinting’ in the early stages (Early ischaemic colitis with ‘thumbprinting’ in the splenic flexure.) and later with mucosal ulceration and strictures. CT scan may also be helpful by showing mucosal oedema, thickening and associated inflammatory changes. A limited colonoscopy performed in the unprepared large bowel during the acute phase is particularly useful with the more severe disease where barium enema is contraindicated. Biopsy may be helpful in differentiating the disease from inflammatory bowel disease.
In the acute phase, clinical and early endoscopic evaluation will distinguish ischaemic colitis from inflammatory bowel disease or diverticulitis. The treatment for the most part is expectant and will include bowel rest, intravenous fluid replacement and combination antibiotics that cover for Gram-negative organisms and anaerobes. When a protracted course is suspected, TPN may be helpful. Most patients will recover spontaneously. Progression to gangrene or perforation is rare. Fibrous stricture is a late and unpredictable event.
Surgery is rarely necessary in ischaemic colitis. Specific indications for surgery include peritonitis, perforation and sepsis. A wide resection of non-viable colon is performed with exteriorisation of the proximal colon as a stoma. The distal part of the large bowel is either stapled or oversewn, or exteriorised as a mucous fistula. Primary anastomosis is unsafe in this acute setting with unprepared bowel. Post-operative progression of the ischaemia may compromise the anastomosis as well.
Surgery is generally not indicated for strictures without clinical symptoms of obstruction. Obstructing strictures may require resection. Occasionally, resection for strictures is indicated because malignancy cannot be ruled out.
Ischaemic colitis following aortic surgery
Ischaemic colitis following aortic surgery is unique because the most likely aetiology is a sudden loss of blood flow from ligation of a patent IMA. The incidence of ischaemic colitis is higher following emergency than elective repair of abdominal aortic aneurysm (see Disorders of the arterial system). Other factors include duration of cross-clamping of the aorta, hypotension, presence of hypogastric blood flow, collateral circulation and cholesterol emboli. The mortality of clinical ischaemia following elective aortic aneurysm surgery is around 20% and is much higher after emergency operation.
Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesenteric ischemia: a clinical review. Arch Intern Med. 2004 May 24;164(10):1054-62.
Horgan PG, Gorey TF. Operative assessment of intestinal viability. Surg Clin North Am. 1992;72:143-155.Chou CK, Mak CW, Tzeng WS, Chang JM. CT of small bowel ischemia. Abdom Imaging. 2004 Jan-Feb;29(1): 18-22.