Lecture 8 - Inflammatory Bowel Disease Flashcards
2 types of inflammatory bowel diseases? Describe each.
- Crohn’s disease: transmural inflammation anywhere in the GIT from mouth to anus
- Ulcerative colitis: inflammation of mucosa and submucosa of colon ONLY (superficial)
Is IBD the same as IBS?
Nope, that is irritable bowel syndrome that is functional but there is no actual inflammation of the gut
Define IBD.
Chronic lifelong disease characterized by inflammation of the GIT with acute flare-ups alternating with remission
Number of patients affected in the US? Are there more males or females affected?
1.6 M, which is increasing with time
Same number of males and females affected
Age distribution of patients with IBD?
Bimodal: 15-30 and 50-70
What races are more affected by IBD?
Caucasians and jews
How does smoking affect the risk of developing IBD?
- Increases risk of Crohn’s disease
- Decreases risk of ulcerative colitis
What % of IBD patients have a 1st degree relative with the disease?
5-10%
Where does ulcerative colitis always start? Describe it.
Rectum and then is continuous up to a certain random point of the colon
Describe the distribution of the GIT inflammation in CD?
Patchy and can include fistulae with other abdominal organs and strictures (narrowing) of the bowel because of the transmural nature of the inflammation, which can cause obstruction => constipation, vomiting, pain
What do ulcers look like in CD patients?
White patches in mucosa
How do we classify the extent of UC?
Depending on how far from the rectum the inflammation extends to:
- Proctitis: only in rectum
- Left-sided: extends past rectum to splenic flexure max
- Universal: past splenic flexure
7 GI symptoms of IBD?
Diarrhea Abdominal pain Mucus/Pus/Blood Tenesmus Urgency Incontinence Rectal pain
3 symptoms specific to CD?
Intra-abdominal abscess
Perianal abscess
Fistula (bowel-skin; bowel-viscus)
5 systemic symptoms of IBD?
Fever Weight loss Fatigue Anemia Electrolyte abnormalities
What is tenesmus? Why does IBD cause this?
A continual or recurrent inclination to evacuate the bowels
Rectum loses its compliance due to the inflammation and need to release gas and/or stool very often (cannot tell the difference between the 2)
Why does diarrhea happen in IBD?
- Inflamed mucosa cannot reabsorb water from feces
2. Inflamed mucosa leaks fluids and nutrients
Why is urgency a symptom of IBD?
Due to:
- Cramping due to inflammation
- Fluid nature of the feces which is harder to contain
- Tenesmus
What are 4 systems that have extra-intestinal symptoms of IBD?
- Joints
- Skin
- Occular
- Hepatobiliary
Describe the joint symptoms of IBD.
- Parallels IBD: peripheral arthritis
2. Independent of IBD: axial arthritis
Describe the skin symptoms of IBD.
- Parallels IBD: erythema nodosum
2. Independent of IBD: pyoderma gangenosum
Describe the occular symptoms of IBD.
- Parallels IBD: episcleritis and scleritis
2. Independent of IBD: uveitis
Describe the hepatobiliary symptoms of IBD.
Independent of IBD: primary sclerosing cholangitis (PSC)
When is inflammatory pain the worst during the day?
Morning and night when body is resting
Describe the pathogenesis of IBD.
- Genetic predisposition: hundreds of genes linked to IBD
- Immunoregulatory defect of the mucosal immune system
- Environmental triggers: luminal bacteria (gut microbiome is different with less anti-inflammatory and more pre-inflammatory bacteria AND reduced diversity) and infection
How does taking antibiotics affect the GIT and IBD?
It affects the mucosa and could increase IBD risks:
- In children , with abx use in the 1st year of life
- In adults, with abx use 2-5 years before diagnosis
How does excessive hygiene affect IBD?
Excessive hygiene => lack of early childhood exposure to infectious agents => suppresses the natural development of the immune system/normal gut microbiota (TH1 response not well developed) => increased risk of immunological disease later in life, like IBD (TH2 response like allergies)
6 environmental factors causing increased risk of CD?
Cigarette smoking Appendectomy +/- ↑ Dietary animal protein NSAID and aspirin use Psychosocial stress, Depression Oral contraceptive use ↓ soluble fiber (fruits/vegetables) in pediatric and adult population
How does the genetic predisposition of IBD work?
These genes may be responsible for abnormalities in the mucosal immune system: overproduction of pro-inflammatory cytokines, underproduction of anti-inflammatory or regulatory cytokines
And then a triggering event takes place that irritates the GI tract, setting the chronic inflammatory process in motion (generally believed to be bacteria)
5 environmental factors causing increased risk of UC?
Dietary arachidonic acid
Dietary linoleic acid (sunflower oil, corn oil..)
NSAID use
Psychosocial stress, Depression
Postmenopausal hormone use
↓ omega-3 fatty acid/ DHA (cold water fatty fish: salmon, bluefin tuna, sardines, shellfish, and herring)
2 environmental factors causing decreased risk of CD?
Dietary Fiber
Vitamin D
3 environmental factors causing decreased risk of UC?
Dietary n-3 fatty acids
Cigarette smoking
Appendectomy < age 20
What is a common thread in the environmental factors of IBD? Examples?
These are from the Western world (including processed food, high protein, high fat, low fiber) and there is a higher prevalence of IBD in westernized countries, urbanized regions (because of stress and pollution)
E.g. incidence of IBD has recently increased in Japan that is westernized and young immigrants’ risk of developing it increase when they move to a western country
Describe the gut barrier and how it works.
One cell layer of epithelial cells attached by tight junctions which are exposed to trillions of organisms and that needs to:
- Allow for minimal penetration of bacteria
- Efficiently kill the invading bacteria
- Carry out a controlled inflammatory response that is self-limited and without sequelae
% of body lymphocytes in the GIT?
70%
What is the interaction between microbiome and intestinal mucosa critical for?
Critical role in the maturation of the immune system
Difference between microbiota and microbiome?
Microbiota: community of microorganism
Microbiome: community of microorganisms AND all of their related genomes
How does the GIT epithelium shape the microbiota?
It produces nutrients/mucus, and antimicrobial peptides
How do we call the microbiota in IBD?
Dysbiotic microbiota
Do insoluble fiber (cereals, whole grain, bran) affect the risk of CD?
NOPE
How to make the IBD diagnosis?
- History
- Physical exam
- Labs, Imaging studies (CTScan , MRI-E)
- Colonoscopy prior to or soon after starting therapy to determine:
a. Extent, severity of disease, exam of TI (r/o CD)
b. Histological confirmation (granulomas 30% CD) - Rule out other causes of colitis
Morphology of UC on colonoscopy?
Rectum involved Ileum not involved Diffuse (confluent) Loss of normal vascular pattern Granular, friable mucosa Superficial ulcers Pseudopolyps common PSC more common
Morphology of CD on colonoscopy?
Rectum typically spared Ileal disease is common Segmental disease Aphthoid, deep linear ulcers Cobblestoning Stricture, Fistulas Perianal disease
7 goals of treating IBD?
Induce and maintain remission Clinical remission Mucosal healing on endoscopy/imaging Prevent complications of CD (stricture, fistula, abscess, perforation) Prevent hospitalization Prevent surgery Prevent IBD-Colorectal cancer
First treatment to relieve patients of their symptoms? Downside?
Steroids to calm down inflammation
Downside: lots of side effects so this is not a long-term treatment
How to treat patients with mild IBD symptoms? Describe this treatment.
Mesalamine (5-ASA): topical or oral administration
- Acts as topical anti-inflammatory for the GIT
- Safe and well tolerated
- Also used to treat nephritis, pancreatitis, pericarditis, penumonitis, and pleuritis
- Downside: lots of big pills to take
Can drugs cure IBD?
NOPE
What does the choice of treatment for IBD depend on?
Extent and severity of disease
Definition of chronic disease?
3 weeks+
What is C. Difficile?
Bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon
What is the association between C. Diff and UC?
C. Diff can unmask IBD and IBD patients will have a higher incidence of C. Diff
How does UC appear histologically?
- Marked chronic inflammation
- Glandular atrophy with crypt architectural distortion
- Hypertrophy of muscularis mucosa
What is pyoderma gangenosum? Treatment?
Deep ulcers that develop at trauma areas or where prior surgery was done (independent symptoms of IBD)
Treatment = topical agents (steroids, cromolyn, tacrolimus), oral agents (steroids, dapsone), and anti-TNF (anti-tumor necrosis factor, for intestinal and extra-intestinal manifestations)
How can we sometimes treat uncontrollable UC?
Iliostomy = surgical operation in which a piece of the ileum is diverted to an artificial opening in the abdominal wall after the colon has been removed
What is toxic megacolon?
Distention of the colon caused by severe inflammation of the gut causing increased risk of perforation => requires immediate surgery
When should a colectomy be performed on patients with UC?
- Disease is refractory to medical treatment
- Toxic colon and/or spontaneous perforation
- Colon cancer
What is the association between colorectal cancer and UC?
Risk is increased after 7 to 10 years of disease
What is primary sclerosing cholangitis (PSC)? What can it progress to? Increases risk of what? Treatment?
Cholesthatic disease causing stricture and dilation of bile duct (string of pearls appearance) causing stasis of the bowels and jaundice
Can progress to liver cirrhosis
Increases risk of cholangiocarcinoma (bile duct cancer)
Treatment: supportive until liver transplant is needed
What does low albumin level indicate?
- Malnutrition, and/or
2. Inflammatory state
What is gastroparesis?
Disease in which stomach is unable to empty properly and is often a complication of poorly controlled diabetes
What is uveitis?
Eye inflammation (independent of IBD)
What is erythema nodosum?
Acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs (parallels IBD)
How does CD appear histologically? What to notes?
Granulomas (circulatory groupings of inflammatory cells and rimmed by lymphocytes)
BUT, not present in all patients(only in 30%)
What is perianal disease?
Complication of CD because the inflammation is transmural and in the anal canal it’ll create a tunnel out to the skin (fistula) through which pus seeps or to the fat (gets infected and forms an abcess)
Fistulae can even reach bladder causing recurring UTIs
How to cure UC? Does this work for CD?
Total colectomy
CD: Surgery is needed to treat complications, but is not curative
