Inflammatory bowel disease - B. Pharma 2nd Semester Pathophysiology notes pdf

Inflammatory bowel disease

Content

·         Inflammatory bowel disease

·         Etiology

·         Pathophysiology

OBJECTIVES

By the end of this session the students will be able to

•       Define inflammatory bowel disease

•       Explain the  etiology of inflammatory bowel disease

•       Describe  the pathophysiology of inflammatory bowel disease

Inflammatory bowel disease

Inflammatory bowel disease describes two major chronic nonspecific inflammatory disorders of the gastro intestinal tract

•       They are:

•       Crohn’s disease(CD)

•       Ulcerative colitis(UC)

•       Main difference between Crohn's disease and UC is the location and nature of the inflammatory changes

•        Crohn's can affect any part of the gastrointestinal tract, from mouth to anus , although a majority of the cases start in the terminal ileum

•        Ulcerative colitis, in contrast, is restricted to the colon and the rectum

Ulcerative colitis and Crohn's

Etiology of Inflammatory bowel disease

Epidemology of Inflammatory bowel disease

	Ulcerative colitis	Crohn’s disease
Incidence (US)	11/100 000	7/100 000
Age of onset	15-30 & 60-80	15-30 & 60-80
Male:female ratio	1:1	1,1-1,8:1
Smoking	May prevent disease	May cause disease
Oral contraceptive	No increased risk	Relative risk 1,9
Appendectomy	Not protective	Protective
Monozygotic twins	8% concordance	67% concordance

INFLAMMATORY RESPONSE

•       Inflammatory response with IBD may indicate abnormal regulation of the normal immune response or an autoimmune reaction to self-antigens - microflora of the gastrointestinal tract may provide an environmental trigger to activate inflammation

•       Crohn’s disease has been described as “a disorder mediated by T lymphocytes which arises in genetically susceptible individuals as a result of a breakdown in the regulatory constraints on mucosal immune responses to enteric bacteria”

INFECTIOUS FACTORS

•       Microorganisms are a likely factor in the initiation of inflammation in IBD  -  Patients with inflammatory bowel diseases have increased numbers of surface-adherent and intracellular bacteria

•       Suspect infectious agents include the measles virus, protozoans, mycobacteria, and other bacteria

•       Bacteria elaborate peptides (e.g., formyl-methionylleucyl-phenylalanine) that have chemotactic properties - influx of inflammatory cells with subsequent release of inflammatory mediators and tissue destruction

GENETIC FACTORS

•       Genetic factors predispose patients to inflammatory bowel diseases, particularly Crohn’s disease - studies of monozygotic twins, there has been a high concordance rate, with both individuals of the pair having an IBD (particularly Crohn’s disease) -  first-degree relatives of patients with IBD had a 13-fold increase in the risk of disease

•       Other investigators - genetic markers  - more  frequent in those with IBD (particularly major histocompatability complex, HLA-DR2 for ulcerative colitis and HLA-A2 for Crohn’s disease)

IMMUNOLOGICAL MECHANISMS

•       Inflammatory process is a component of wound healing, the inflamed mucosa activates the typical inflammation –associated genes and genes associated with wound healing

•       Pro-inflammatory antigenic triggers in the intestinal lumen activate macrophages and t-helper lymphocytes to release inflammatory mediators

Pathophysiology of Inflammatory bowel disease

Ulcerative colitis:

•       UC is confined to be in rectum and colon and affects the mucosa and the sub mucosa - some instances, a short segment of terminal ileum may be inflamed

•       Primary lesion of uc occurs in the crypts of the mucosa (crypts of liberkhun) in the form of crypt abscess

•       Necrosis of the epithelium occurs and visible only in microscope

•       Other typical ulceration patterns include a “collar button ulcer”, which results from extensive sub mucosal undermining at the ulcer edge which results in diarrhea and bleeding

•       UC complications can be local (colon/rectum) or systemic

•       Complications could be minor, serious or life threatening

•       Minor complication occurs in the majority of ulcerative colitis patients. They include: hemorrhoids, anal fissures or perirectal abscesses

•       Major complication is toxic megacolon (1-3%), massive colonic hemorrage

•       Risk of colon cancer begins to increase after 10-15 years of uc diagnosis

Ulcerative colitis – microscopic features

•       Process  is  limited  to  the  mucosa  and submucosa  with  deeper  layer  unaffected

•       Two major  histologic  features:

 - the  crypt  architecture  of  the  colon is distorted

 - some  patients  have  basal  plasma  cells  and multiple  basal  lymphoid  aggregates

•       40-50% of patients have disease limited to the rectum and rectosigmoid

•       30-40% of patients have disease extending beyond the sigmoid

•       20% of patients have a total colitis

•       Proximal spread occurs in continuity without areas of uninvolved mucosa

Symptoms of Ulcerative colitis

Crohn’s disease:

•       Target point for CD- terminal ileum

•       About two-thirds of patients have some colonic involvement, and 15% to 25% of patients have only colonic disease

•       Bowel wall injury is extensive and the intestinal lumen is often narrowed

•       Mesentery first becomes thickened and edematous and then fibrotic

•       Ulcers tend to be deep and elongated and extend along the longitudinal axis of the bowel, atleast into the submucosa

•       “Cobblestone” appearance of the bowel wall results from deep mucosal ulceration intermingled with nodular submucosal thickening

•       Fistula formation is common and occurs much more frequently than with ulcerative colitis

•       Fistulae often occur in the areas of worst inflammation, where loops of bowel have become matted together by fibrous adhesions

•       Nutritional deficiencies are common with Crohn’s disease

•       Weight loss, growth failure in children, iron deficiency anemia, vitamin B12 deficiency, folate deficiency, hypoalbuminemia, hypokalemia, and osteomalacia

Sign & Symptoms of Crohn’s disease

Dignosis of Crohn’s disease

•       The first clue in the diagnosis of IBD are the symptoms:

•       Unrelenting diarrhea

•       Blood or mucus in the stool (more common with ulcerative colitis than Crohn’s disease)

•       Fever

•       Abdominal pain

TESTS :

•        Complete blood cell (CBC) count,

•       Electrolyte panel, and

•        Liver function tests (LFT)

•       Fecal occult blood test (also called stool gaiac or hemoccult test)

OTHER TESTS

ü  X-RAY

ü  BARIUM ENEMA

ü  COLONOSCOPY

ü  ENDOSCOPY

ü  SIGMOIDOSCOPY

Comparision of  Ulcerative colitis & Crohn’s disease

Features	Ulcerative colitis	Crohn’s
Abdominal pain	Variable	Common
Depth of inflammation	Mucosal	Transmural
Diarrhea	Severe	Less severe
Fistula and sinus tracts	Rare	Common
Distribution	Diffuse, contiguous spread; always involves rectum; spares proximal gastrointestinal tract	Segmental, noncontiguous spread (“skip lesions”); less common rectal involvement; occurs in entire GIT

Clinical Features of  Ulcerative colitis & Crohn’s disease

	UC	Crohn’s disease
Blood in stool	Yes	Occasionally
Mucus	Yes	Occasionally
Systemic symptoms	Occasionally	Frequently
Pain	Occasionally	Frequently
Abdominal mass	Rarely	Yes
Perineal disease	No	Frequently

SUMMARY

•       Inflammatory bowel disease describes two major chronic nonspecific inflammatory disorders of the gastro intestinal tract ulcerative colitis and crohns disease

•       Major causes of inflammatory bowel disease are infectious agents, environmental factors, genetics, diet

•        UC is confined to be in rectum and colon and affects the mucosa and the sub mucosa by release of inflammatory cells

•       Ulcers in crohn’s tend to be deep and elongated and extend along the longitudinal axis of the bowel, into the submucosa