GIT pathophysiology (IBD) and pharmacology

Question 1

What is IBD

Answer 1

•The inflammatory bowel diseases(IBD)are defined as chronic intestinal inflammation that results from immunological abnormalities and triggered by genetic and environmental factors
• Two forms:
– Ulcerative colitis (UC) and 
– Crohn’s disease (CD),
IBD is an idiopathic disease

Question 2

Ulcerative colitis vs. Crohn’s disease

Answer 2

Both are chronic inflammatory diseases of the bowel differentiated by: Location of the inflammation in the GIT and, Nature of the alterations in the intestinal wall.
• IBD can be debilitating and sometimes leads to life-threatening complications.

Question 3

Ulcerative colitis

Answer 3

Ulcerative colitis is an IBD that causes long-lasting inflammation and sores (ulcers) in the innermost lining of large intestine (colon & rectum).

• Superficial affecting last part of large intestine
• lost of haustra, ulceration, crypt disortion, thinned walls, pseudopolyps

Question 4

Crohn’s disease

Answer 4

Crohn’s disease is an IBD that cause chronic inflammation that often spreads deep into affected tissues (transmural) – fistula formation.

• affects deep and non-specific area that is affected
• Thickened wall by gathering more immune cells, fat wrapping, fissure, cobblestonning

Question 5

2 most important parts of GIT

Answer 5

Stomach = impotant for digestion

Small intestine = absorption

Question 6

Signs /symptoms

Answer 6

• Abdominal pain and cramping
• Reduced appetite
• Unintended weight loss
• Diarrhoea
• Blood in stool
• Unexplained fever lasting > 1-2 days
Extraintestinal manifestations of IBD can involve the musculoskeletal, dermatologic, hepatopancreatobiliary, ocular, renal, & pulmonary systems;

Question 7

Diagnosis

Answer 7

• Clinical signs
• Haematology, Endoscopy, Radiology
• Need to exclude enteric infections!

Question 8

Aetiology **

Answer 8

• The exact cause of IBD is unclear (an idiopathic disease)
• Four main factors influence the disease:
– Hostgeneticsusceptibility
– Adysregulatedimmuneresponse,
– Impairment of intestinal epithelial barrier function,and – Environmental factors

Question 9

Risk factors

Answer 9

• Age
– Usually diagnosis < age 30 years, sometimes 50s or 60s.
• Family history
– Higher risk if close relative with IBD
• Cigarette smoking (nicotine)
– Smoking has been shown to help patients with ulcerative colitis!
• Nonsteroidal anti-inflammatory medications
– May increase the risk of developing IBD or worsen disease in people who have IBD.
– Role of housekeeping PG
• Geography
– Higher incidence in urban area, industrialized
– Country, Northern climate

Question 10

Pathogenesis of IBD

Answer 10

• Disturbance in the balance between gut commensal bacteria & host response in the intestinal mucosa.
• Epithelial cells play a prominent role in the pathogenesis of IBD.

Physical barrier > immune system >

Question 11

IBD drug treatment

Answer 11

• There is no cure for IBD
• The goal of IBD treatment is to reduce the inflammation.
• Understand & maintain links between diet & the immune system & bacteria in the GIT (microbiome).
• Treatment leads to:
– symptom relief
– long-term remission and
– reduced risks of complications.

Question 12

• Drug therapy or surgery

Answer 12

• 1. Anti-inflammatory drugs:
– Aminosalicylates, corticosteroids.
• 2. Immunomodulators (immunesuppressors)
– Azathioprine , mercaptopurine
– Cyclosporine
• 3. Biological therapy (TNF-a inhibitors)

Question 13

Targeting tumour necrosis factor (TNF)

Answer 13

TNF-specific antibodies may alleviate disease by simultaneously suppressing several pro-inflammatory pathways in patients with IBD.

Question 14

Stem Cell Therapy for IBD?

Answer 14

• Stem-cell therapy through hematopoietic stem cells (HSCs) or mesenchymal stem /stromal cells (MSCs) is a promising therapeutic option for severe refractory cases especially when surgery is not feasible.
– InHSCtransplantation,theobjectiveistodestroythe‘autoreactive’ immune cells responsible for disease chronicity, and to re-establish gut tolerance to gut microbes
.
– InperianalCrohn’s disease(CD),the objective is to deposit MSCs locally in fistulising tracts to down-regulate the local immune response and induce wound healing.

Question 15

Fecal microbiota transplantation (FMT)

Answer 15

• Also known as stool transplant, it works by introducing fecal bacteria (stool) from an healthy individual into the affected patient to restore the colonic microflora.
• Originally used to treat patients suffering Clostridium difficile infection (CDI)
• Recently being used in patients with IBD to treat the symptoms. Very early stages, but the preliminary data shows interesting results, even without knowing how it works! Speculation on restoring the “normal dialog” between gut microbes and immune system.