IBD Flashcards
what is IBD?
Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders that involve chronic inflammation of your digestive tract.
what are the different types of IBD?
- crohn’s disease and ulcerative colitis
what is the definition of Chron’s Disease?
chronic inflammatory and ulcerating condition of the GI tract that can affect anywhere from the mouth to the anus
(most common in the terminal ileum and the colon)
who is more likely to get Crohn’s Disease?
- young patients
- more common in males
what is the presentation of Crohn’s Disease?
- abdominal pain
- small bowel obstruction
- diarrhoea
- bleeding PR
- anaemia
- weight loss
what are changes in histology?
granuloma formation, lamina propria plasma cells and lymphocytes, neutrophillic inflammation
what is the pathology of Crohn’s Disease?
- segmental disease
- ileal and/or colonic chronic active mucosal inflammation
- transmural inflammation
- deep knife-like fissuring ulcers
- granulomas, 50%, non-caseating
what are the malabsorption complications of Crohn’s Disease?
- malabsorption
- -iatrogenic (short bowel syndrome)
- -hypoproteinemia, vitamin deficiency
- -gallstones (interrupted enterohepatic ciruclation)
what are the fitula complications of Crohn’s Disease?
- vesicocolic
- enterocolic
- gastrocolic
- recto vaginal
- tuboovarian abscess
- bind loop syndrome
what are the anal disease complications of Crohn’s Disease?
- sinuses
- fissures
- skin tags
- abscesses
- perineum fall apart
what intractable disease complications are of Crohn’s Disease?
- failure to tolerate or respond to medial therapy
- continuous diarhoea or pian
- may require surgery
give examples of environmental triggers f Crohn’s Disease
- smoking
- NSAIDs
- infectious agents
- vasculitis
- sterile environment theory
describe the immune response involved in Crohn’s disease?
- persistent activation of T cells and macrophages
- excess proinflammatory cytokine production
what is the definition of ulcerative colitis?
- chronic inflammatory disorder confined to colon and rectum
- mucosal and submucosal inflammation
who is more likely to get ulcerative colitis?
- young patients
- males
where is ulcerative colitis?
colon and rectum
what is the clinical presentation of ulcerative colitis??
diarrhoea, mucus and blood PR
what are the changes in histology for ulcerative colitis
- massive influx of inflammatory cells
- basal lymphoplasmacytic infiltrate with irregular shaped branching crypts
- acute cryptitis
- absecesses
- excess fibrin
management of ulcerative colitis/
- does not respond to medical therapy
- subtotal colectomy
where is inflammation confined to in ulcerative colitis?
mucosa and submucosa
give a pathological summary of ulcerative colitis
- continuous, diffuse disease
- rectal involvement
- superficial ulceration and inflammation
- chronic active colitis
- cryptitis
- crypt abscess
- no granulomas
intractable disease complications of ulcerative colitis
- continuous diarrhoea
- flares may be due to intercurrent infection by enteric bacteria or CMV
- total colectomy
what are the toxic megacolon complications of ulcerative colitis?
- acute or acute on chronic fulinmant colitis
- colon swells up to massive size
- will rupture unless removed
- emergency colectomy
how can complications of ulcerative colitis lead to colorectal carcinoma?
- chronic inflammation leads to epithelial dysplasia and the carcinoma
- risk increased if
- pancolitis
- disease longer than 10 years
- requires surveillance
give a summary of complications of ulcerative colitis
- blood loss
- electrolyte disturbance
- anal fissures
- eyes: uveitis
- liver: primary sclerosing cholangitis
- joints: arthritis
skin, erythema ?
why do you get ulcerative colitis?
- genetic defects
- aberrant immune response
- environmental factors
describe the immune response of ulcerative colitis
- persistent activation of T-cells and macrophages
- autoantibodies present
- excess proinflammatory cytokine production
explain the pathogenesis of ID
the genetic predisposition + mucosal immune system + environmental triggers
what is the IBD gene?
NOD2/CARD15 (IBD-1)
what chromosome is the disease susceptibility gene located?
16q12
what does the gene encode?
a protein involved in bacterial recognition
describe the innate immunity involved in IBD
- tight junctions regulate epithelial permeability
- hydrophobic mucus protects the epithelial cell layer
- defensins (catatonic anti-microbial peptides) can be activated
- NOD2 contributes to normal mucosal defences
describe the adaptive immunity involved in IBD
- T lymphocytes are critical to the orchestration of adaptive mucosal immunity
- ## normal conditions are characterised by a balance between effector and regulatory T cell responses
what happens if there is an overreactive effector T-cell response?
inflammation/disease
what happens if there is an absence of regulatory T cells?
uncontrolled inflammation/aggressive disease
what T helper cells mediate Crohn’s disease?
Th1
what T helper cells mediate ulcerative colitis?
mixed Th1/Th2 and NKTC
what are the main symptoms of UC?
- diarrhoea and bleeding
- increased bowel frequency
- urgency
- tenesmus
- lower abdo pain (esp LIF)
how would you determine the severity of UC?
- Truelove and Witt criteria >6 bloody stools/24 hours \+ 1 or more of fever tachycardia anaemia elevated ESR
what tests would you do for UC?
- bloods (CRP, albumin)
- plain AXR
- endoscopy
- histology
why would you do a plain AXR in UC?
- to see stool distribution, mucosal oedema/thumb printing or toxic megacolon
why would you do an endoscopy in UC?
- to define extent
- confluent inflammation
- loss of vessel pattern
- granular mucosa
- contact bleeding
what are histological signs of UC?
- crypt distortion
- absence of goblet cells
what are some extra-intestinal manifestations of UC?
- skin
- joints
- eyes
- deranged LFTs
- oxalate renal stones
what is Primary Sclerosing Cholangitis (PSC)?
chronic inflammation of biliary tree
what are signs of PSC?
- most asymptomatic OR itch, rigors
- cholestatic LFTs
- 15% get cholangiocarcinoma
what is cholestasis?
a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts
describe the distribution of Crohn’s disease
- can affect any region of GI tract
- skip lesions
- transmural inflammation
what are signs and symptoms of peri-anal disease?
- recurrent abscess formation
- pain
- fistula with persistent leakage
- damaged sphincters
what are the disease phenotypes of Crohn’s disease?
- stenosis
- inflammation
- fistula
what are symptoms of Crohn’s disease in the small intestine?
- abdominal cramps (peri-umbilical)
- diarrhoea, weight loss
what are symptoms of Crohn’s disease in the colon?
- abdominal cramps (lower abdomen)
- diarrhoea with blood
- weight loss
what are symptoms of Crohn’s disease in the mouth?
- painful ulcers
- swollen lips
- angular chielitis
what are symptoms of Crohn’s disease in the anus?
- peri-anal pain
- absecess
what blood tests would you do for Crohn’s disease?
CRP, albumin, platelets, B12, ferritin
what are endoscopic signs of Crohn’s disease?
cobblestoning, thickened walls, fissures
what are endoscopic signs of ulcerative colitis?
- ulceration
- loss of haustra
- crypt distortion
- pseudopolyps
what are some of the aims of IBD therapy?
- control inflammation and heal mucosa
- restore normal bowel movement
what is the lifestyle advice for therapy?
- smoking aggravates Crohn’s
- diet not implicated in pathoogenesis but can induce symptoms
what drug types would you give to a patient with ulcerative colitis?
- 5ASA (mesalazine)
- steroids
- immunosuppressants
- anti-TNF therapy
what drug types would you give a patient with Crohn’s disease?
- steroids
- immuosuppressants
- anti-TNF therapy
what is the mechanism of action of 5ASA?
- anti-inflammatory
- reduces risk of colon cancer
what are side effects of 5ASA?
- diarrhoea
- idiosyncratic nephritis
what are the pros and cons of oral 5ASA?
- prodrugs
- pH dependent release
- dealyed release
what are the pro and cons of topical 5ASA?
- suppositories coat <20cm but have better mucosal adherence than enemas
- enemas. reflex contraction aids proximal spread of foam or liquid enemas
- <10% enemas remain in the rectum
give some examples of 5ASA drugs
- sulphasalazine
- balsalazide
- mezavant
- asacol salofalk
- pentasa
describe mechanism of corticosteroids
- systemic anti-inflammatory properties
- eg prednisolone, budesonide
- to induce remission
- short course of high dose initially then reduce over 6-8 weeks
what are the musculoskeletal side effects of steroids?
avascular necrosis
osteoporosis
what are the cutaneous side effects of steroids?
- acne
- thinning of skin
what are the metabolic side effects of steroids?
- weight gain
- diabetes
- hypertension
give examples of immunosuppressive drugs used in the maintenance therapy of Crohn’s
- azathioprine/mercaptopurine
- methotrexate
what is the mechanism of action of Azathioprine?
- slow onset
- TPMT activity contributes to toxicity
- avoid co-prescription of allopurinol
- regular blood monitoring required
what are side effects of Azathioprine?
- pancreatitis
- leucopaenia
- hepatitis
what is Tumour Necrosis Factor alpha?
proinflammatory cytokine
name antibodies to TNF
- chimeric (infliximab)
- humanised (adalimumab)
how is infliximab administered?
IV infusion
how is adalimumab administered?
S/C injection
what is the mechanism of action of anti-TNF therapy?
- promote apoptosis of activated T-lymphocytes
when would you use ant-TNF therapy?
as part of long term strategy, including immune suppression, surgery (Crohn’s), supportive therapy
why would you perform an elective operation for Crohn’s disease?
- resection
- strictuoplasty
- fistulas
- anal disease
why would you perform an elective operation for UC?
- proctocolectomy with end ileostomy
- proctocolectomy with ileorectal anastomosis
