Inflammatory Bowel disease SR-f

Cont

LECTURE 14

• Crohn disease and ulcerative colitis are chronic relapsing inflammatory disorders of unknown orgin, collectively known as idiopathic inflammatory bowel disease (IBD), which share many common features.

IBD• Inflammatory• Chronic • Relapsing• Autoimmune ?• Idiopathic

They result from an abnormal local immune response against the normal flora of the gut, and probably against some self antigens, in genetically susceptible individuals.

The pathogenesis of IBD involves genetic susceptibility, failure of immune regulation, and triggering by microbial flora.

Crohn Disease“terminal ileitis” or “regional enteritis

•A systemic inflammatory disease with predominant intestinal involvement.

• When fully developed , Crohn disease is characterized by:

• Sharply limited transmural involvement of the bowel by an inflammatory process with mucosal damage

• Presence of noncaseating granulomas• Fistula formation

Common symptoms of Crohn's disease:

•abdominal pain•diarrhoea•weight loss

Less common symptoms include:• poor appetite• fever, • night sweats• rectal pain/rectal bleeding

Extraintestinal symptoms

Some patients with Crohn's disease also develop symptoms outside of the gastrointestinal tract; these symptoms include:

• arthritis• skin rash• inflammation of the iris of the eye.

Ulcerative

Colitis

• Ulcerative Colitis is an ulceroinflammatory disease affecting the colon, which is

limited to the mucosa and submucosa, except in the most severe cases.

• It begins in the rectum and extends

proximally in a continuous fashion sometimes involving the entire colon.

Epidemiology

• More common in USA & Western countries. The incidence has risen in recent decades. More common among whites. No sex predilection. A peak incidence between ages 20-25 years. Has a familial association.

Morphology• Gross:• Rectum & Sigmoid --may involve entire colon.• The lesions are continuous.• inflammatory destruction of the mucosa with

macroscopic appearance of :• Hyperemia, edema, and granularity with

friability and easy bleeding.

• With severe active disease:• Extensive and broad based ulceration in the

distal colon.• Pseudopolyps• Toxic megacolon

• A diffuse, predominantly mononuclear inflammatory infiltrate in the lamina propria and Crypt abscesses.

Complications:Perforation, peritonitis, abscess

• Toxic megacolon

• Venous thrombosis

• Carcinoma

Clinical features• Bloody mucoid diarrhea• Cramps• Tenesmus• Colicky lower abdominal pain• Fever • Weight loss

Extra-intestinal symptoms

• Migratory polyarthritis, • sacroilitis, • ankylosing spondilitis, • uveitis, • erythema nodosum and • hepatic involvement (pericholangitis and

primary sclerosing cholangitis).

Diagnosis•Endoscopy•Biopsy

Comparison of CD &UC• Crohn disease and ulcerative colitis differ in

many respects, including the natural history of the disease, pathological aspects, and in the types of therapies and responses to treatment.

Comparisons of various factors in Crohn's disease and ulcerative colitis

Crohn's Disease Crohn's Disease Ulcerative Colitis Ulcerative Colitis

Involves terminal ileum Involves terminal ileum Commonly Commonly Seldom Seldom

Involves colon? Involves colon?

Involves rectum? Involves rectum?

Usually Usually

Seldom Seldom

Always Always

Usually Usually

Bile duct involvement? Bile duct involvement? Not associated Not associated Higher rate of Primary Higher rate of Primary sclerosing cholangitis sclerosing cholangitis

Distribution of Disease Distribution of Disease Patchy areas of Patchy areas of inflammation inflammation

Continuous area of Continuous area of inflammation inflammation

Endoscopy Endoscopy Linear and serpiginous Linear and serpiginous (snake-like) ulcers (snake-like) ulcers

Continuous ulcer Continuous ulcer

Depth of inflammation Depth of inflammation May be transmural, deep May be transmural, deep into tissues into tissues

Shallow, mucosal Shallow, mucosal

FistulaeFistulae, , abnormal abnormal passageways between passageways between

organs organs

Commonly Commonly Seldom Seldom

Biopsy Biopsy Can have Can have granulomagranulomata ta Crypt abscesses and Crypt abscesses and cryptitis cryptitis

Surgical cure ?Surgical cure ?

Smoking Smoking

Often returnsOften returns following removal of following removal of

affected part affected part

Higher risk for smokers Higher risk for smokers

Usually cured by Usually cured by removal of colon, removal of colon,

Lower risk for smokers Lower risk for smokers

Autoimmune disease Autoimmune disease Generally regarded as Generally regarded as an autoimmune an autoimmune

disease disease

No consensus No consensus

Cancer risk? Cancer risk? Lower than ulcerative Lower than ulcerative colitis colitis

Higher Higher than Crohn's than Crohn's

Comparisons of various factors in Crohn's disease and UC (Cont.)

Features UC CD

Morphologic

Distribution Diffuse,mucosal &submucosal, left sided

Focal, trans-

mural, right sided

Mucosal atrophy Marked Minimal

Cytoplasmic mucin ↓ Preserved

Lymphoid aggregate Rare Common

Edema Minimal marked

Features UC CDMorphologic

Hyperemia Extreme Minimal

Granuloma Absent 60% present

Fissuring Absent Present

Crypt abscess Common Rare

Lymph nodes Reactive Granulomas

Acute Appendicitis The appendix is a normal true diverticulum of

the cecum that is prone to acute and chronic inflammation. Acute appendicitis is most common in adolescents and young adults, but may occur in any age group. The lifetime risk for

appendicitis is 7%; males are affected slightly more often than

females.

• Despite the prevalence of acute appendicitis, the diagnosis can be difficult to confirm preoperatively and may be confused with mesenteric lymphadenitis, acute salpingitis, ectopic pregnancy, mittelschmerz (pain caused by minor pelvic bleeding at the time of ovulation), and Meckel diverticulitis.

Pathogenesis Acute appendicitis is thought to be initiated by

progressive increases in intraluminal pressure that compromise venous outflow. In 50% to 80% of cases, acute appendicitis is associated

with overt luminal obstruction, usually caused by a small stone-like mass of stool, or fecalith, or, less commonly, a gallstone, tumor, or mass of worms (oxyuriasis vermicularis).

• Ischemic injury and stasis of luminal contents, which favor bacterial proliferation, trigger inflammatory responses including tissue edema and neutrophilic infiltration of the lumen, muscular wall, and periappendiceal soft tissues.

MorphologyIn early acute appendicitis subserosal vessels are

congested and there is a modest perivascular neutrophilic infiltrate within all layers of the wall.

The inflammatory reaction transforms the normal glistening serosa into a dull, granular, erythematous surface.

• Diagnosis of acute appendicitis requires neutrophilic infiltration of the muscularis propria.

• In more severe cases a prominent neutrophilic exudate generates a serosal fibrinopurulent reaction. As the process continues, focal abscesses may form within the wall (acute suppurative appendicitis).

• Further appendiceal compromise leads to large areas of hemorrhagic ulceration and gangrenous necrosis that extends to the

serosa creating acute gangrenous appendicitis, which is often followed by rupture and suppurative peritonitis.

Clinical Features

• Typically, early acute appendicitis produces periumbilical pain that ultimately localizes to the right lower quadrant, followed by nausea, vomiting, low-grade fever, and a mildly elevated peripheral white cell count

Charles Heber Mc Burney

American surgeon

• Regrettably, these signs and symptoms are often absent, creating difficulty in clinical diagnosis. In some cases, a retrocecal appendix may generate right flank or pelvic pain, while a malrotated colon may give rise to appendicitis in the left upper quadrant. In other cases the peripheral leukocytosis may be minimal or, alternatively, so great that other causes are considered.

• The diagnosis of acute appendicitis in young children and the very elderly is particularly problematic, since other causes of abdominal emergencies are prevalent in these populations, and the very young and old are

also more likely to have atypical clinical presentations.

• Given these diagnostic challenges, it should be no surprise that even highly skilled surgeons remove normal appendices. This is preferred to delayed resection of a diseased appendix, given the significant morbidity and mortality associated with appendiceal perforation. Other complications of appendicitis include pyelophlebitis, portal venous thrombosis, liver abscess, and bacteremia.