Course:SOMBlock3IQ1/Week 1/Case 10
[edit] Large Intestine
[edit] What is the histology of the large intestine?
Mucosa of colon is relatively "smooth" with no plicae and villi. Crypts of Lieberkuhn (deep straight glands) extend to the muscularis mucosa. Well-developed lymphatic nodules lie in the lamina propria. Lumen is lined with simple columnar epithelium composed of absorptive columnar and numerous goblet cells.
In the ascending, transverse, and descending colon, the circular muscle layer is overlaid by three long nonoverlapping bands of longitudinal muscle oriented at 120° to each other, known as the taeniae coli.
As one moves into the sigmoid colon and rectum, the intestine becomes completely enveloped by longitudinal muscle that is important to the specialized functions of this region, which include serving as a reservoir and participating in defecation. The lumen of the rectum is also partially occluded by transverse folds, again formed by muscular contraction, which act as shelves to retard the passage of fecal material.
Ross and Lange, CT
[edit] What is the gross structure of the large intestine?
Cecum, ascending, and transverse are all retroperitoneal. Descending is intraperitoneal.
[edit] What is the physiology?
The functions of the colon are quite distinct from those of the small intestine. Thus, while the colon does engage in some limited digestion and salvage of nutrients from undigested residues, with the cooperation of its endogenous flora, the primary functions of the colon are to extract and reclaim water from the intestinal contents, and to process the feces for elimination. As a result, even in the fasted state, the motility functions of the colon are considerably more biased toward mixing the contents and retaining them for prolonged periods, and the colon does not participate in the MMC. On the other hand, periodically, large propulsive contractions sweep through the colon, transferring its contents to the rectum and ultimately promoting the urge to defecate.
Lange, CT
[edit] What is the relationship between the immune system and the large intestine?
[edit] Ulcerative colitis
[edit] What is the relationship between joint pain and ulcerative colitis?
[edit] What is the pathophysiology of ulcerative colitis?
UC is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. About 40 to 50% of patients have disease limited to the rectum and rectosigmoid, 30 to 40% have disease extending beyond the sigmoid but not involving the whole colon, and 20% have a total colitis. Proximal spread occurs in continuity without areas of uninvolved mucosa. When the whole colon is involved, the inflammation extends 1 to 2 cm into the terminal ileum in 10 to 20% of patients. This is called backwash ileitis and is of little clinical significance.
With mild inflammation, the mucosa is erythematous and has a fine granular surface that looks like sandpaper. In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated (Fig. 276-1). In long-standing disease, inflammatory polyps (pseudopolyps) may be present as a result of epithelial regeneration.
Histologic findings correlate well with the endoscopic appearance and clinical course of UC. The process is limited to the mucosa and superficial submucosa, with deeper layers unaffected except in fulminant disease. In UC, two major histologic features are indicative of chronicity and help distinguish it from infectious or acute self-limited colitis. First, the crypt architecture of the colon is distorted; crypts may be bifid and reduced in number, often with a gap between the crypt bases and the muscularis mucosae. Second, some patients have basal plasma cells and multiple basal lymphoid aggregates. Mucosal vascular congestion with edema and focal hemorrhage, and an inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells, and macrophages may be present. The neutrophils invade the epithelium, usually in the crypts, and give rise to cryptitis and, ultimately, to crypt abscesses.
Lange, CT
[edit] What is the etiology of ulcerative colitis?
Inflammatory bowel disease (IBD) is an idiopathic and chronic intestinal inflammation. Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of IBD. The incidence of IBD varies within different geographic areas. Northern countries, such as the United States, United Kingdom, Norway, and Sweden, have the highest rates. The incidence rates of UC and CD in the United States are about 11 per 100,000 and 7 per 100,000, respectively (Table 276-1).
The peak age of onset of UC and CD is between 15 and 30 years. A second peak occurs between the ages of 60 and 80. The male to female ratio for UC is 1:1 and for CD is 1.1 to 1.8:1. A two- to fourfold increased frequency of UC and CD in Jewish populations has been described in the United States, Europe, and South Africa. Furthermore, disease frequency differs within the Jewish populations. The prevalence of IBD in Ashkenazi Jews is about twice that of Israeli-born, Sephardic, or Oriental Jews. The prevalence decreases progressively in non-Jewish Caucasian, African-American, Hispanic, and Asian populations. Urban areas have a higher prevalence of IBD than rural areas, and high socioeconomic classes have a higher prevalence than lower socioeconomic classes.
IBD runs in families. If a patient has IBD, the lifetime risk that a first-degree relative will be affected is 10%. If two parents have IBD, each child has a 36% chance of being affected. In twin studies, 67% of monozygotic twins are concordant for CD and 20% are concordant for UC, whereas 8% of dizygotic twins are concordant for CD and none are concordant for UC. Anatomic site and clinical type of CD is also concordant within families.
Lange
[edit] What is the difference between Crohn disease and ulcerative colitis?
Unlike UC, CD is a transmural process. Endoscopically, aphthous or small superficial ulcerations characterize mild disease; in more active disease, stellate ulcerations fuse longitudinally and transversely to demarcate islands of mucosa that frequently are histologically normal. This "cobblestone" appearance is characteristic of CD, both endoscopically and by barium radiography. As in UC, pseudopolyps can form in CD.
Active CD is characterized by focal inflammation and formation of fistula tracts, which resolve by fibrosis and stricturing of the bowel. The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstructions. Projections of thickened mesentery encase the bowel ("creeping fat"), and serosal and mesenteric inflammation promote adhesions and fistula formation.
The earliest lesions in CD are aphthoid ulcerations and focal crypt abscesses with loose aggregations of macrophages, which form noncaseating granulomas in all layers of the bowel wall from mucosa to serosa (Fig. 276-4). Granulomas can be seen in lymph nodes, mesentery, peritoneum, liver, and pancreas. Although granulomas are a pathognomonic feature of CD, they are rarely found on mucosal biopsies. Surgical resection reveals granulomas in about half of cases. Other histologic features of CD include submucosal or subserosal lymphoid aggregates, particularly away from areas of ulceration, gross and microscopic skip areas, and transmural inflammation that is accompanied by fissures that penetrate deeply into the bowel wall and sometimes form fistulous tracts or local abscesses.
Lange, CT
[edit] How does prednisone function?
Prednisone is the most commonly-prescribed oral corticosteroid. The drug is metabolized in the liver to its active form, prednisolone. Relative to hydrocortisone, prednisone is roughly 4 times as potent as a glucocorticoid. Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At a molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately protein synthesis to achieve the steroid's intended action. Such actions may include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses.
[edit] What are the small, palpable effusions on the wrist?
[edit] What is the distinction between infection and inflammation?
[edit] How is ulcerative colitis diagnosed?
[edit] What are the diagnostic tests?
[edit] What are the differentials?
Diverticulitis can be confused with CD clinically and radiographically. Both diseases cause fever, abdominal pain, tender abdominal mass, leukocytosis, elevated ESR, partial obstruction, and fistulas. Perianal disease or ileitis on small-bowel series favors the diagnosis of CD. Significant endoscopic mucosal abnormalities are more likely in CD than in diverticulitis. Endoscopic or clinical recurrence following segmental resection favors CD. Diverticular-associated colitis is similar to CD, but mucosal abnormalities are limited to the sigmoid and descending colon.
Ischemic colitis can be chronic and diffuse as in UC, or segmental as in CD. Colonic inflammation due to ischemia may resolve quickly or may persist and result in transmural scarring and stricture formation. Patients usually present with sudden onset of left lower quadrant pain, urgency to defecate, and the passage of bright red blood per rectum. Endoscopic examination often demonstrates a normal-appearing rectum and a sharp transition to an area of inflammation in the descending colon and splenic flexure.
Solitary rectal ulcer syndrome is uncommon and can be confused with IBD. It occurs in persons of all ages and may be caused by impaired evacuation and failure of relaxation of the puborectalis muscle. Ulceration may arise from anal sphincter overactivity, higher intrarectal pressures during defecation, and digital removal of stool. The ulceration, which can be as large as 5 cm in diameter, is usually seen anteriorly or anteriorlaterally 3 to 15 cm from the anal verge. Biopsies can be diagnostic.
Lange
[edit] What are the complications?
[edit] What are the different kinds of diarrhea? Implications for inflammatory bowel disease?
[edit] What is the natural history of inflammatory bowel disease?
[edit] What is the treatment for ulcerative colitis?
[edit] Additional Notes
[edit] Learning Objectives
1. Describe the role of the colon in the reclaiming of fluid and electrolytes. 2. Describe the role of the colon in forming and storing of feces. 3. Describe the colonic mucosal immune system. 4. Describe the evaluation of bloody diarrhea. 5. Explain the pathophysiology of diarrhea in inflammatory bowel disease. 6. List the risk factors for the development of inflammatory bowel disease. 7. List the epidemiology of inflammatory bowel disease. 8. Compare and contrast the current hypotheses on the etiology of Crohn's disease and ulcerative colitis. 9. Compare and contrast the clinical, endoscopic, and histologic differences between ulcerative colitis and Crohn's disease. 10. List the therapeutic approaches to the management of inflammatory bowel disease. 11. Compare and contrast the natural history of ulcerative colitis and Crohn's disease. 12. List the extra-intestinal manifestations of inflammatory bowel disease. 13. List the risk factors for and describe the pathophysiology of colorectal cancer in inflammatory bowel disease.
[edit] Class notes
Histology of Large Intestine: No villi; crypts Goblet cells increase distally Significant lymphatic tissue Tenia colia – outer layer of longitudinal muscle Lymphatic begins extensively in lamina propria before extending into submucosa (hence less ability to metastasis
Anatomy: Ascending, Transverse, Descending Colon Multiple haustration Also includes appendix, rectum and anal canal Appendages – sacs of fat along tenia Vascularization innervations: superior (beginning), inferior mesenteric Innervations: vagus, superior mesenteric ganglion (later of transverse), inferior mesenteric ganglion (descending), pudendal nerve (anal), and enteric
Function: Absorb water and electrolytes, make waste,
Cells: Goblet cells, absorptive cells (brush border) and enterocytes
Lymphatic: GALT continues with that of the terminal ileum; more extensively developed Immunosuprresive response to train our body to react or not to react to certain bacteria flora Different countries sensitizes to be resilient to certain bacteria
Pathophysiology to Ulcerative Colitis: Disease inflammation of the mucosa Balance between immune response and suppression Begins with rectum and moves proximally Crohn’s spotted lesion and extends deeper (transmural – meaning through all the layer – disease)
Key Findings: Histological: Crypts distorted and reduced in numbers, often times with a gap between , vascular congestion in mucosa, pseudopolyps develops when mucosa regenerates, crypt abscess when neutrophils invade layer
Gross: pseudo polyps, red granular bits (sand-paper look)
Differential: ulcerative colitis is confined to colon Different causes of diarrhea: Secretory, Motility, Inflammatory, Osmotic
IBD: have all of them Cytokine release causes change, motility mucosa gets destroyed transit time increases, osmotic and secretory changes Look in: see blood, touch scope bleeding, ulcerations, mucus, but diagnosis isn’t clear until biopsy
Diarrhea losing more blood and water as the disease increases in severity HIV associated because of link with bloody stool; immune response with mucosa
Etiology:
Unregulated CD4
Combination of host factors and exogenous factor
Combination of immune regulation and environmental factors
Risk Factors: Peak onset between 20-40 years and another at 60 for UC Non smoking associated with UC, but ex-smoking at higher risk than never smoking Incidence UC 11/100000 and for CD 7/100000 Incidence of UC and CD increasing within recent decades 2-4 fold increase within Jewish population Apendectomy decreases risk for UC If both parents IBD, child has 36% increased risk Dizygotic twins have normal rate, monozygotic 30-50%
Smoking positive for UC, bad for Crohn’s
Crohn’s vs. Ulcerative Granulomas (accumulation of macrophages) none Entire GI tract from mouth to anus Begins in rectum, only in colon Involves liver and pancreas Spotted Blockage of bile duct Responds to antibiotics does not Poor response to surgery good response to surgery
Extracolonic manifestation of Ulcerative Erthythema nodosum – attack in correlation with bowel activity; skin lesions; lesions are usually hot, red tender nodules, found on anterior surface of calves, legs and thighs Uvelitis Sclerosing cholangitis Skin lesions – pyoderma gangrenosum, erythema nodosum, apthous stomatitis (white plaques) Anemia (can be a cause of ulcers in the mouth, iron deficiency because of blood lose) Malnutrition and growth retardation Bone and joint lesions Palpable effusion on wrist – from erthymthema nodosum If you were to drain, no lymphocytes Swelling due to overproduction of immune cells to that area
Treatment Initial is with corticosteroid and anti-inflammatory agents Prednisone Mechanism: decreased lymphatic response, inhibition of mediators in inflammation Side effects: headache, nausea, worsening of colitis
Be careful of anti diarrheas; paralyses peristalsis leading to toxic megacolon - massive dilation of colon and can eventually explode!
Patients also take folate acid to boost production of RBC
Immune response of small bowel: inflicimab treats autoimmune disorders
Disease progression/Natural History
Toxic megacolon Proferation Hemorrhoids Fistules (more common in Crohns) Mucosa becomes atrophic and entire colon can shortenin Terminal iliatis Shock (failure of tissue perfusion reflected by low BP) Massice hemmorahge
IBD UC
One attack with no reoccurance, however sometimes will be people will go for years; attacks may be precipitated by stress Develop pseudopolyps, develop dysplasia carcinoma in situ carcinoma from UC is rapidly metastitis, multicenteric (more than one location) Carcinoma’s often infiltrative Carcinoma more common in UC than Crohn’s Carcinoma in UC develops after time (8-10 yrs) Surgery curative – remove entire colon
IBD CD Transmural (spread into all layers) Skip lesions Surgery not-curative (50% patients with come for surgery and of those 50% will get operated on again, of those, 50% will get operated on again….) For surgery of CD operate on complications of disease only: obstruction, internal fistuli, perforation, abscess. Only take out the part that is grossly affected