Ulcerative Colitis Fatma Otman Cellular Pathology Biology Essay

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Ulcerative colitis is an idiopathic chronic inflammatory disease of the rectum and the colon that follows a course of relapse and remission. It is an inflammatory bowel disease, which is characterized by mucosal inflammation with crypt abscesses, ulcers and pseudopolyp formation. The chronic inflammation is limited to mucosa, sometime that is extended to submucosa. Ulcerative colitis is a condition that starts at the rectum and ends at some point in the colon. The affected area is continuous; there is no area of normal tissues between the affected areas. It is sometime definite diagnosis of ulcerative or Crohn's can be established in which case the term an indeterminate colitis is used.

Epidemiology: - Ulcerative colitis affects about 1 in 1000 people in the Western world. First pack incidence between the age of 10-40 year's, but may affect people of any age and second peak incidence at average of 60 year's (Bimodal distribution). The disease affects females and males. The geographic distribution of ulcerative colitis is the highest incidence in The United Status, Canada, The United Kingdom. Higher incidence is seen in northern locations compared to southern locations in Europe and the United Status. The prevalence of ulcerative colitis is greater among Ashkenazi Jews and decreases progressively in other person of Jewish descent, non-Jewish Caucasians, Africans, Hispanics and Asians, because genetic susceptibility is a factor associated with ulcerative colitis..

Mortality: - The effect of ulcerative colitis on mortality is unclear. Some studies confirm that, mortality of patient with ulcerative colitis is only 12% (Viscido et al, 2001). Although, mortality from ulcerative colitis is decreased during the past 50 year's (Sonnenbery,2007). Therefore, it is thought that the disease primarily affects quality of life not life span.

Causes and risk factors: - Causes of ulcerative colitis is still unknown. There are many factors including:

*Genetic factors suggesting that the disease arise from combination of multiple genes abnormalities, for example p35 gene mutation,15% increased risk in 1st degree relative (Medicine, 2010).

*Environmental factors include the following: Firstly, diet has been hypothesized to play role in pathogenesis of ulcerative colitis, for example a diet with low in dietary fibre may affect ulcerative colitis incidence. Secondly, breast feeding has been reported of protection in development of inflammatory bowel disease ( Klement et al., 2004).

*Auto immune disease, some sources list ulcerative colitis as an autoimmune disease duo to malfunction of the immune system (Odze, 2003). However, surgical removal of the large intestine often cures the disease, including the manifestation outside the digested system. This suggest that the cause of the disease is in colon itself and not in the immune system or some other part of body (e Medicine, 2009).

*Alternative theories suggesting that the symptoms of the disease may be caused by toxic effect of hydrogen sulphide in the intestine in patient with ulcerative colitis. It may be caused by occlusion of in the capillaries of sub epithelial lining, and infiltration of the lamina propria with plasma cells.

* Appendectomy prior to age 20 for appendicitis and tobacco use both are protective against development of ulcerative colitis.

*Psychological factors and socioeconomic factors, clinical exacerbation has been found to be facilitated by life stress in ulcerative colitis (Novack et al., 2006)

Types of ulcerative colitis: The different types of ulcerative colitis are classified according to the location and extent of inflammation.

*Ulcerative proctitis refers to inflammation that is limited to the rectum (Rectal bleeding).

*Procoto-sigmoiditis involves inflammation of the rectum and sigmoid colon (Rectal bleeding).

*Left side colitis involves inflammation that starts at rectum and extends up the left colon (Bloody diarrhea, abdomen cramp, weight loss).

*Pancolitis refers to inflammation affecting the entire colon (Bloody diarrhea, abdominal pain, weight loss, fever and night sweating).

*Fulminated colitis is rare, however it is severe form of pancolitis (Dehydration, severe abdominal pain, bloody diarrhea and shock. They are at risk of developing toxic megacolon (Marked dilation of colon duo to severe inflammation), resulting in colon rupture (Perforation, peritonitis , abscesses and massive haemorrhage).

Ulcerative colitis is divided into four stages according to gross pathology:-

*Acute stage is involved mucosal surface, which is wet and glaring from blood and mucus, often is associated with petechial haemorrhage.

*Chronic stage shows various sized of irregular ulcers and elevated sessile reddish nodules (pseudopolyps).In this stage raise suspicion of carcinoma (1% of all colorectal carcinoma).

*More advanced stage is involved entire bowel, shows fibrotic, narrowed and shortened.

*Quiescent stage shows no ulceration, but the mucosa shows atrophy or sometimes appears grossly normal. It may be extensive submucosal fat deposition.

Intestinal symptoms:- The most common symptoms of ulcerative colitis are bloody diarrheal and abdominal pain. Patient also may experience anaemia, fatigue, weight loss, loss of appetite, rectal bleeding, loss of body fluid and nutrition.

Extra-intestinal symptoms:- These include the following: aphtous ulcer of mouth, eye disease ( Iritis or uveitis), arthritis ( ankylosing spondylitis), erythema nodosum, deep venous thrombosis, autoimmune haemolytic anaemia, clubbing and primary sclerosing cholangitis.

Differentiation diagnosis:-

*Crohn's disease, infective colitis, *pseudomembranuos colitis, ischemic colitis (elderly people), tuberculosis, colorectal adenocarcinoma.

Routine investigation:- The initial diagnostic workup for ulcerative colitis includes the following.

*A complete blood count is done to check anaemia (iron deficiency anaemia), which is hypochromic microcytic anaemia ( low MCH, low MCV, low haemoglobin).

*Elevated of white blood cells, it is more than normal range ( 4.300-10.800 cells/cmm).

*Thrombocytosis is high platelets count, it is more than normal range ( 150-400x 10/ L).

*Erythrocyte sedimentation rate is elevated =(≥ 18 mm/ hr).

*C-reactive protein is acute phase protein that is produced by liver during inflammation. It is elevated= (≥ 10mg/l).

*Electrolytes analysis and renal function test are done, because chronic diarrhea may be associated with hypokalemia, hypomagnesaemia and pre renal failure.

*Liver function tests are performed to screen for bile duct involvement.

*Stool culture to exclude parasites and infective causes.

Diagnostic procedures for ulcerative colitis:- There are include the following.

Endoscopy and biopsies:- The best test for diagnosis of ulcerative colitis remains endoscopy.

*Full colonoscopy is extended from anus to the caecum, also entry into terminal ileum is attempted only if diagnosis of ulcerative colitis is unclear and to differentiate between ulcerative colitis and Crohn's disease, because in some cases of ulcerative colitis may be involve terminal ileum. Endoscopic finding in ulcerative colitis include the following: loss of vascular appearance of the colon, erythematic or redness of the mucosa and friability of the mucosa, superficial ulceration and pesudopolyps. Biopsies of mucosa are taken from different parts of colon to definitively diagnosis of ulcerative colitis and differentiated from crohn's disease. The histology finding in ulcerative colitis typically involves distortion of crypt architecture, inflammation of crypts (cryptitis), frank crypt abscesses, haemorrhage and inflammatory cells in lamina propria (lymphocytes, plasma cells). Acute stage shows accumulation of neutrophil at base of crypts ( crypt abscesses). No granuloma is important criterion in differential diagnosis with crohn's disease. Mucosal capillary are dilated. Inflammation may remain above muscularis mucosa or extend to submucosa. Glands are progressive destroyed, marked decrease in cytoplasm, mucus, atrophic changes and regenerative changes, also manifested by nuclear enlargement and increased mitotic activity. Other feature shows, ulcer is covered by non specific granulation tissue, pseudopolyps( largely granulation tissues mixed with inflamed and hyperaemic mucosa.

*Flexible sigmoidoscopy is extended from anus to sigmoid colon.

*Abdomen X rays are quick, cheap, non invasive and an x ray of abdomen that is indicated in acute abdomen conditions such as intestinal obstruction, perforation, dilation (Toxic megacolonic).

*Trans-abdominal ultrasound is a non-invasive modality that may be helpful in the diagnosis of inflammatory bowel disease, but it can not be used to distinguish between ulcerative colitis and crohn's disease. It is used for diagnosing biliary complication.

*CT has limited role in the diagnosis of uncomplicated ulcerative colitis, however CT plays an excellent modality in the diagnosis of complication associated with disease.

*Barium enema is special type of x ray that uses barium sulphate and air to outline the lining of rectum and colon. The result can show polyp, tumour, diverticulitis. Today, the uses of barium enema are rare due to the uses of endoscopy for diagnosing. There is contraindication of using barium enema in acute abdomen as complication of UC.

*Radio-nuclide studies are useful in depicting disease activity and the extent of disease and in monitoring the response to therapy. It is useful in case of fulminant colitis

* Serology test is performed in approximately 20% of cases of UC, overlapping symptoms, radiographic and histological features make the differential diagnosis difficult. It is important to accurately differentiate between two diseases ulcerative colitis and Crohn's disease, because the management of patient are different and ulcerative colitis is more risk for malignancy. The use of an inflammatory bowel disease serology panel that should be included the following, Perinuclear anticytoplasmic antibodies (PANCA) and Saccharyomyces cerevisiac IgA nd IgG antibodies (ASCA). Because, PANCA is prevalent in ulcerative colitis and ASCA is more prevalent in Crohn's disease. ASCA represent the immunologic marker corrected with Crohn's disease, because their high specificity (80-95%).

*Immunohistochemistry assessment of ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis related dysplasia. Strong immunoreactivity for p53 that suggested diagnosis of dysplasia, also suggested Ki67 staining above basal two third of the crypt in high grade dysplasia (HGD).

Complication:- There is significantly increased risk of colorectal cancer in patient with ulcerative colitis after 10 year's if involvement in the splenic flexure, however those with only procotitis or rectosigmoid it is usually have no increased risk. It is recommended that patient have screening by colonoscopies with random biopsies to look for dysplasia after eight year's of disease activity.

Treatment:- The standard treatment for ulcerative colitis is depended on the extent of involvement and disease severity. The goal is to induce remission initially with medication, followed by the administration of maintenance medication to prevent a relapse of the disease.

*Dietary modification: Diet rich of fibres, avoiding dairy products, avoiding raw vegetates and fruit, because they cause injury to inflamed mucosa of colon.

*Supplement treatment: Iron tables for treatment of anaemia, multivitamin.

*Anti diarrheal drugs: Such as Immodium, a doctor must closely monitor the person taking these anti-diarrheal drugs to avoid precipitating toxic megacolon.

*Anti-inflammatory drugs: Such as aminosalicytates, corticosteroids and immunosuppressive drugs. Also anti tumour necrosis factor ( Infliximabe).

*Surgical treatment: Surgical treatment can be emergency operation and elective operation. Emergency operation is performed in cases of haemorrhage, frank perforation, sever colitis or toxic megacolon and elective operation is performed in cases of patient is not response to treatment and documented or strongly suspected carcinoma. There are different types of surgical approaches such as proctocolectomy with ileostomy, Ileoanal anatomises and continent ileostomy.

Some investigations are used for monitor of inflammatory bowel disease:-

*Concentration of tumour necrosis factor alpha in stool is used as a marker of intestine inflammation in both ulcerative colitis and crohn's disease.

*Measurement level of neutrophli binding by immunoglobulin and titres of antineutrophli immunoglobulin in serum from patient with ulcerative colitis and patient with ulcerative colitis post colectomy by using a fixed neutrophil enzyme linked immunosorbent assay.

*Measurement of nitric oxide in ulcerative colitis patient during colonoscopy, gas was aspirated from different parts of the colon and immediately analyzed by a chemiluminescence technique.