Inlammatory Bowel Disorders Flashcards
What is inflammatory bowel disease?
A structural problem with physical abnormalities in the GI tract. It is a chronic condition resulting from inappropriate mucosal immune activation.
What is it irritable bowel syndrome?
A functional GI problem with no structural abnormalities. It is characterised by abdominal pain and altered bowel habits
What gender is IBP more prevalent in and what age group?
- more prevalent in women
- high prevalence in youth and middle aged people
What are the pathogenesis (causes) of IBS?
1) stress
2) diet
3) abnormal GI motility
4) Visceral hypersensitivity
5) infection
6) overgrowth of intestinal flora
How is IBS diagnosed?
1) if the individual has experienced discomfort for 3 days per month for over 3 months
2) if there’s a change in stool frequency/form
3) if the individual has any food allergies/intolerances resulting in bacterial growth
How is IBS treated?
1-psychotherapy (antidepressants) 2-dietary fibre supplements 3-loperamide or laxatives 4-antibiotics 5-analgesics
What are the 2 most common IBD’s?
Ulcerative Collitis (UC) and Crohn’s disease
Where do Crohn’s disease and UC exist?
CD - any area in the GI tract
UC - Limited to the colon and rectum
What type of inflammation does CD cause?
Transmural inflammation
What type of inflammation does UC cause?
mucosal and submucosal inflammation
What type of lesions are caused by crohns and ulcerative?
CD- skip lesions
UC- continuous lesions
What are the symptoms of Crohn?
- pain
- diarrhoea
- weight loss
- anaemia
What are the symptoms of UC?
- bloody diarrhoea
- colicky
- abdominal pain
- urgency
- fever
Which of the 2, UC or CD, can lead to relapse in 50% of patients?
Ulcerative Colitis
What is a colectomy?
Removal of the colon
What are the pathogenesis of IBD?
1) genetic factors
2) mucosal immune responses
3) epithelial defects
4) microbiota
What is the role of TH1 cells?
- activate macrophages
- cause inflammation of the mucosa through release of TNF (tumour necrosis factors)
What is the role of TH17 cells?
-stimulated by IL-23 and activate neutrophils causing inflammation.
What is the role of TH2 cells?
-Secrete IL-13 found in the mucosa of ulcerative collitis patients.
What is used to support the theory that TH1 and TH17 cells play a role in UC?
The effectiveness of anti-TNF therapy on UC patients and the protective role that IL-23R polymorphisms have on UC patients.
What can happen if there are defects in the intestinal epithelial tight junction barrier?
Can activate innate and adaptive mucosal immunity and sensitize subjects to the disease
What polymorphism is associated with the intestinal epithelial tight junction barrier defect?
NOD2 polymorphism
What does a mutation of the organic cation transporter SLC22A4 in Crohn disease suggest?
That defects in transepithelial transport may be related to this mutation
What is the effect of the ATG16L1 polymorphism on Crohn disease patients?
it means they carry abnormal production of defensins (antibacterial peptides), which leads to defective ant-microbial function
What happens to the microbiota of IBD patients?
-the diversity of the microbiota is reduced (less range of bacteria).
-Bacterial strands
associated with a role
in mucosal protection
are lost.
What are microbiota alterations associated with?
genetic polymorphisms
What is chronic inflammation?
inflammation of prolonged duration (weeks/months) in which inflammation, tissue injury and attempts at repairs coexist in varying combinations
Causes of chronic inflammation?
1-persistent infections
2-immune-mediated inflammatory disease
3-immune reaction against individual’s tissues (autoimmune disease)
4-Unregulated immune-reactions against microbes
5-mmune-response against harmless environmental substances
6-prolonged exposure to toxic agents.
What type of immune response is IBD?
An unregulated immune-reaction against microbes
How is IBD diagnosed?
1-stool tests
2-blood tests (mainly for inflammatory markers)
3-GI investigations: radiology, imaging and endoscopy
2 groups of drugs used to treat IBD?
1- DMARDs (Disease Modifying Anti-rheumatic Drugs)
2-Immunosuppressant drugs
Examples of DMARDs
5 Aminosalicylic acid (5ASA)
Methotexate
Examples of immunosuppressant drugs?
- glucocorticoids
- azathioprine
- ciclosporin
- biologicals
What is the mechanism of action of 5ASA?
- free radicals inhibit prostaglandin and leukotrienes production.
- they decrease neutrophil chemotaxis
what are the side effects to using 5ASA?
- diarrhoea
- salicylate sensitivity
- interstitial nephritis
Effect of 5ASA on UC?
- less flare ups (less inflammatory responses)
- reduced risk of colorectal cancer
Effect of 5ASA on chron’s disease?
-used after surgery to reduce chances of relapse
Mechanism of action of methotrexate (MTX)?
folic acid antagonist (cytotoxic) and immunosuppressant activity.
Effect of MTX on CD and UC?
- induces remission and maintains it in CD.
- Has no role in UC.
Side effects to using MTX?
- bone marrow depression
- develop intolerance to the drug
- diarrhoea
- stomatitis
- GI epithelium damaged
Mechanism of action of glucocorticoids?
- reduce transcription of genes encoding COX-2, phospholipase A, pro-inflammatory cytokines and iNOS.
- has immunosuppressive effect
side effects to Glucocorticoids?
- prolongesd use can result in -glaucoma, cataracts, osteoporosis, infections, diabetes mellitus.
Mechanism of action of azathioprine?
interferes with purine synthesis (cytotoxic).
When metabolised to mercatopurine (a purine analogue), it inhibits DNA synthesis.
Also inhibits both cell-mediated and antibody-mediated immune reactions.
Effect of azathioprine in CD?
induces remission and maintains remission for up to 4 years. Used after surgery as well.
Effect of azathioprine in UC?
used to maintain remission for up to 4 years.
Side effects of Azathioprine?
- Depression of the bone marrow
- nausea
- vomitting
- skin eruptions
- mild hepatotoxicity
Mechanism of action of cyclosporin in treatment of IBD?
inhibits IL-2 gene transcription hence decreasing the activation of clonal proliferation T-cells. This reduces the induction of cytotoxic T-cells, reduces the function of the effector T-cells, and reduces the T-cell-dependent B-cell responses.
(so overall reduces autoimmune response)
When is Cyclosporin used in UC treatment?
if the condition is severe it is ‘typically used only as a rescue therapy’
side effects of using Cyclosporin?
- infections
- hepatotoxicity
- hypertension
- renal impairment
Mechanism of action of biologics?
- directs monoclonal antibodies against TNF
- has immunosuppressant activity
- induces remission is steroids and immunomodulators are ineffective.
problem with using biologics?
very costly-both drug and clinical administration
side effects of using biologics?
- risk of infections (TB)
- psoriasis (rarely)
- hypersensitivity
- GI symptoms
- increased risk of developing lymphoma (rarely)
Examples of biologics?
- infliximab
- adalimumab
