—  SHORT COURSE #44  —

Non-Neoplastic Disorders of the Intestines

Case 7 - Ischemic Injury

Laura W. Lamps, M.D.
Audrey J. Lazenby, M.D.
Joel K. Greenson, M.D.


Clinical Presentation:
This 38 year old female presented with hematochezia.


Case 7 - Figure 1 - Low magnification shows superficial mucosal erosion and hemorrhage, accompanied by gland withering and marked lamina propria fibrosis.
Case 7 - Figure 2 - High magnification emphasizes gland withering and lamina propria fibrosis.


Endoscopic Findings:
Diagnosis: At endoscopy, an edematous mass was seen at the splenic flexure.

Diagnosis :
Ischemic colitis

General Comments:
"Ischemic colitis" is a histologic description of a pattern of injury for which there is a host of etiologies. Ischemia can give rise to a wide range of clinical presentations and pathologic changes. While many cases of ischemia occur in older patients with known cardiovascular disease, ischemic colitis can also be seen in younger people such as long distance runners and women taking oral contraceptives. Rendering this diagnosis should not be the end point of the biopsy evaluation, but rather should initiate a thorough search for potential etiologic factors.

Pathologic features:
Pathologic features are similar regardless of underlying cause of ischemia. Grossly, ischemia tends to show geographic areas of ulceration with pseudomembranes. This is often accompanied by marked submucosal edema, a finding that gives rise to the "thumbprinting" seen on barium enemas. Endoscopically this submucosal edema can be prominent enough to appear mass-like. The watershed areas around the splenic flexure are the most common sites for ischemic lesions of the colon, however, nearly any site can be ischemic, even the proximal rectum.

Acute ischemic lesions of the colon show necrosis of the superficial portion of the mucosa that often spare the deeper portion of the colonic crypts. The remaining crypts usually have an atrophic or withered appearance which may show striking cytologic atypia. Care should be taken to avoid overcalling these reactive changes dysplastic. Other findings in ischemia include pseudomembranes, hemorrhage into the lamina propria, and hyalinization of the lamina propria. A trichrome stain can be used to highlight the hyalinization of the lamina propria. Cryptitis and crypt abscesses can be seen, but these are usually not prominent. These lesions may regress on their own or lead to perforation and/or stricture formation. The chronic phase of ischemia may be much harder to diagnose, as the only histologic finding may be areas of submucosal fibrosis and stricture that is rather non-specific.

Pathogenesis:
While lack of blood flow to the mucosa is the underlying mechanism of disease, there is a long list of possible causes. Anything from occlusion of a major blood vessel to low-flow states secondary to hypovolemia may cause colonic necrosis (see table below). Many drugs have been associated with ischemic appearing lesions, including oral contraceptives, cocaine, narcotics, and amphetamines. In some instances the drug may induce vasospasm (i.e. cocaine) while in other cases the medication may lead to thrombosis. Enterohemorrhagic strains of E. coli (such as E. coli O157:H7) also cause an ischemic type colitis, presumably due to the numerous fibrin thrombi that develop during this toxin-mediated infection. Mechanical obstruction may also lead to ischemia secondary to compression/obstruction of blood vessels. Vasculitis due to collagen vascular disease or CMV may also cause ischemia. Ischemic colitis is well described following even moderately strenuous long distance running or cycling. It is thought that visceral blood flow falls to 20-50% of baseline during exercise, and that these effects may be exacerbated by the ingestion of large quantities of NSAIDS as many athletes do.

CAUSES OF COLONIC ISCHEMIA (table adapted from Pat Dean M.D.)
  1. Arterial Occlusion
    1. Superior mesenteric artery (usually due to atherosclerosis with thrombosis)
    2. Inferior mesenteric artery (often following surgical intervention)
  2. Small vessel disease
    1. Diabetes mellitus
    2. Amyloidosis
    3. Radiation vasculopathy
    4. Vasculitides
    5. Infectious causes
  3. Venous occlusion
    1. Thrombogenic factors
      1. Hypercoagulability
      2. Portal hypertension
      3. Idiopathic states (e.g. idiopathic myointimal hyperplasia)
    2. Mechanical conditions
      1. Direct extrinsic pressure (e.g., tumor compression)
      2. Prolapse
    3. Non-occlusive factors
      1. Shock
      2. Dehydration/hypovolemia
      3. Exercise-related diversion of blood flow
      4. Drugs and medications
      5. Diverticular disease
      6. Hirshsprung's disease


Differential diagnosis:
Ischemic colitis may mimic pseudomembranous colitis, ulcerative colitis, Crohn's disease, and other acute self limited colitides. Differentiating ischemia from C. difficile colitis can be difficult, as both may present with pseudomembranous colitis. The presence of a hyalinized lamina propria and atrophic crypts are specific findings in ischemia that are not seen in C. difficile colitis. In addition the pseudomembranes tend to be diffuse in C. difficile and patchy in ischemia. The presence of an ischemic appearing lesion with pseudomembranes in the right colon should also make one think of enterohemorrhagic E. coli, especially if fibrin thrombi are present. Marked architectural distortion, cryptitis, apthoid ulcers, and pseudomembranes may all be features of ischemia. Focality of the injury mitigates against ulcerative colitis, which is, of course, usually diffuse. Healed ischemic lesions may form strictures that mimic Crohn's disease. Clinical and radiographic features may prove invaluable in sorting out the differential.

Natural History and Treatment:
Disease course and therapeutic intervention are dependent on the underlying cause of ischemia. The sequelae of ischemic injury are very variable, ranging from focal areas of acute mucosal necrosis that may be transient and only require supportive care to full-blown gangrene of the gut that may be fatal despite emergency surgery.

References:
  1. Gandhi SK, Hanson MM, Vernava AM, Kaminski DL, Longo WE: Ischemic Colitis. Dis Colon Rectum 39:88-100, 1996.

  2. Deana DG, Dean PJ: Reversible ischemic colitis in young women. Association with oral contraceptive use. Am J Surg Pathol 19:454-462, 1995.

  3. Haggitt RC: Differential diagnosis of colitis. In Goldman H, Appelman HD, Kaufman N (eds): Gastrointestinal Pathology, 1st ed. Baltimore, Williams and Wilkins, 1990, pp 342-348.

  4. Dignan CR, Greenson JK: Can Ischemic Colitis be Differentiated from Clostridium Diffficile Colitis in Biopsy Specimens? Am J Surg Pathol 21:706-710, 1997.

  5. Boutros HH, Pautler S, Chakrabarti S. Cocaine-induced ischemic colitis with small vessel thrombosis of colon and gallbladder. J Clin Gastroenterol 1997;24:49-53.

  6. Johnson TD, Berenson MM. Methamphetamine-induced ischemic colitis. J Clin Gastroenterol 1991;13:687-9.

  7. Moses FM. Gastrointestinal bleeding and the athlete. Am J Gastroenterol 1993;88:1157-59.

  8. Griffin PM, Olmstead LC, Petras RE. Escherichia coli 0157:H7-associated colitis: a clinical and histological study of 11 cases. Gastroenterol 1990; 99:142-49.

  9. Cohen MB, Giannella RA. Hemorrhagic colitis associated with Escherichia coli 0157:H7. Adv Int Med 1991;37:173-195.