M104 T1 L12 Flashcards
What is celiac disease otherwise known as?
celiac sprue
gluten-sensitive enteropathy
What main three substances is gluten commonly found in?
wheat, rye, and barley
What two substances does gluten consist of?
gliadin and glutenins
What genes are associated with Coeliac Disease?
HLA - DQ2 gene (95%)
HLA - DQ8 gene (5%)
Which chromosome are the HLA – DQ2 & - DQ8 genes located?
CMS 6p21
Is Coeliac disease hereditary?
yes - it has a strong hereditary predisposition
affects 10% of first degree relatives
Globally, where is Coeliac disease most prevalent?
Western Europe
the USA, especially for those of Irish / Scandinavian descent
Globally, where is Coeliac disease increasing in prevalence?
Africa and Asia
Is Coeliac disease a well diagnosed condition?
no - a lot of patients in the community are undiagnosed
it requires a high index of suspicion
What conditions have a high prevalence of coeliac disease?
Down’s syndrome
Type I diabetes mellitus
auto-immune hepatitis
thyroid gland abnormalities
What percentage of patients with coeliac disease are older than 60?
approx 20%
How does gluten cause coeliac disease?
Gluten (from diet) + small bowel mucosa produces tissue transglutaminase
this diamidates glutamine in gliadin, producing a negatively charged protein, IL – 15
NK cells + Intraepithelial T lymphocytes results in tissue destruction and villous atrophy
What is transglutaminase otherwise known as?
meat glue
What is the role of IL – 15?
it stimulates CD8 T cell and NK cells
What types of coeliac disease are there symptoms wise? (ACA)
Asymptomatic (detected by a blood test)
Classical coeliac disease
Atypical coeliac disease
What are the symptoms of coeliac disease caused by?
the flat mucosa not absorbing nutrients
What are the symptoms of Classical Coeliac Disease?
Diarrhoea Flatulence (28%) Borborygmus Weight loss (45%) Weakness & fatigue (80%) Severe abdominal pain IBS-like symptoms
What are the symptoms of Atypical Coeliac Disease?
Anaemia (15%)
Osteopenia and osteoporosis
Muscle weakness, pins and needles, loss of balance (minority)
Itchy skin conditions (minority)
Lack of periods (delayed in teens)
infertility and impotence
Bleeding disorders (due to Vitamin K deficiency)
What is an example of an Itchy skin condition?
dermatitis herpetiformis
What are the features of an atypical presentation of coeliac disease?
Emaciation
Pot belly due to gaseous distention
Muscle wasting
Osteoporosis
What are the general investigations for coeliac disease?
FBC, U&Es, LFTs
What are the serological investigations for coeliac disease?
the presence of TTGA
the presence of Endomysial IgA
Deamidated gliadin peptide IgA & IgG (new)
For monitoring compliance to gluten free diet
Sero-negative coeliac disease
HLA DQ2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies
Duodenal biopsies
How do routine coeliac disease tests work?
They assess tissue damage
When the small bowel is exposed to gluten there is overreaction of the immune system to produce antibodies to the proteins involved in tissue damage
What proteins involved in tissue damage have antibodies produced for them?
Tissue transglutaminase
Endomysium
Deamidated gliadin peptide
Where and how many biopsies should be sampled from the intestines?
At least four from the duodenum at upper GIT endoscopy as changes can be patchy
What are the microscopic features of Coeliac disease?
Villous atrophy
Crypt hyperplasia
Increase in lymphocytes in the lamina propria / chronic inflammation
Increase in intraepithelial lymphocytes
Recovery of villous atrophy on gluten-free diet
What are the complications of coeliac disease?
Enteropathy associated T-cell lymphoma
High risk of adenocarcinoma of small bowel and other organs
May be associated with dermatitis hepetiformis
Infertility and miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
In what organs is there a high risk of adenocarcinomas developing as a complication of coeliac disease?
the SI
the large bowel
the oesophagus
the pancreas
What may reduce risk of complications for coeliac disease?
a gluten free diet
What conditions come under IBD?
CD, UC Diverticular disease Ischaemic colitis Drug-induced colitis – NSAIDs Infective colitis idiopathic inflammatory disease
Why is it important to distinguish CD from UC?
they have different complications and different surgical procedures
What is Crohn’s disease complicated by?
fibrosis and obstructive symptoms
What parts of the GI tract can Crohn’s disease affect?
any part of the GIT from mouth to anus
What is the global spread of Crohn’s disease?
has a high prevalence in the Western world
has an increasing incidence in Africa, South America and Asia
Bimodal presentation with peaks in the teens-20s and 60-70 year olds
What group is Crohn’s disease especially high in?
in patients of Jewish origin
What is the cause of CD?
exact cause is unknown
there are – all have been implicated
Defects in mucosal barriers allow pathogens and other antigens to induce an unregulated inflammatory reaction
What are the factors that potentially contribute to CD?
genetic, infectious, dietary, immunologic, smoking, environmental, vascular (GIDISEV)
NSAIDs and psychological factors
What are the genetics of CD?
genetic predisposition is highly probable
No classical Mendelian inheritance but polygenic
What are the genes that could lead to a genetic predisposition towards CD?
NOD2 gene
CARD15 gene on cms 16
What does the CARD15 on cms 16 code for?
a protein associated with uncontrolled inflammatory response to luminal contents and microbes
What is the increased risk first degree relatives have of developing CD?
13-18% increased risk of with a 50% concordance in monozygotic twins
Is there a possible infectious cause of CD?
bc granulomas are present in 60-65% of patients, mycobacterium para-tuberculosis was extensively investigated as a possible cause but never proven
What infectious organisms have been implicated as possible infectious causes of CD?
mycobacterium para-tuberculosis
measles virus
pseudomonas
listeria
What are the dangerous effects of listeriosis?
fever, meningitis
miscarriage, premature birth
How is listeriosis spread?
by eating food contaminated with listeria
What groups of people does listeriosis primarily affect?
pregnant women, newborns
the elderly, people with weakened immune systems
What environmental factors are implicated in Crohn’s Disease?
Improved Hygiene Hypothesis
Migration from a low risk population to high risk population increases the risk of developing CD
Cigarette smoking doubles the risk of developing CD
What does the Improved Hygiene Hypothesis state?
that improved hygiene in susceptible individuals reduces enteric infections
this reduces the ability of the GIT mucosa to develop regulatory processes that would normally limit immune response to pathogens which cause self-limiting infections
What are the clinical features of CD?
Chronic, indolent course punctuated by periods of remission and relapses
Abdominal pain, relieved by opening bowels
Prolonged non-bloody diarrhoea
Blood may be present if the colon is involved
Loss of weight, low grade fever
What is the distribution of CD?
Small bowel alone – 40%
Large bowel alone – 30%
Small and large bowel – 30%
What are the morphological features of CD?
Fat wrapping of the serosa
skip lesions
cobblestone pattern (caused by mucosal ulceration)
strictures (fibrosis)
What does fat wrapping of the serosa involve?
fat deposition on the anterior surface which is usually fat-free
What is the effect of fat wrapping in Crohn’s disease at the time of a surgery
it can assist the surgeon to demarcate the extent of the disease in the small bowel
What are the microscopic appearances of CD?
Transmural / full thickness inflammation of the bowel wall
Mixed acute and chronic inflammation i.e. polymorphs and lymphocytes
Preserved crypt architecture
Mucosal ulceration
Fissuring ulcers (deep crevices)
Granulomas (collection of macrophages) present in 60 - 65%
Fibrosis of the wall
What are the complications of CD?
Intra-abdominal abscesses
Deep ulcers lead to fistula = communication between two mucosal surfaces
Sinus tract = blind ended tract ends in a “cul de sac”
Obstruction due to adhesions
Obstruction due strictures caused by increased fibrosis
Perianal fistula and sinuses
Risk of adenocarcinoma, but not as high as in UC
What is the difference between UC and CD?
unlike CD, UC’s inflammatory process is confined to the mucosa and sub-mucosa except in severe cases
What is the epidemiology of UC?
More common in Western countries with higher prevalence in patients of Jewish descent
Less frequent in Africa, Asia and South America
Can arise at any age but rare before the age of 10
Peaks between 20-25 years with a smaller peak in 55-65 year olds
What causes UC?
unknown but multiple factors are implicated
Genetic predisposition not as well defined as in CD
High incidence in first degree relatives and high concordance in twins
no specific infective agent has been identified
What gene is commonly identified in most patients with UC?
HLA-B27 identified in most patients with UC, but not thought to be an aetiological factor
How do environmental factors affect UC?
Smoking is protective in UC -; cessation of smoking may trigger UC or activate disease in remission
NSAIDs exacerbates UC
Antioxidants Vitamins A & E are found in low levels in UC
What are the clinical features of UC?
Intermittent attacks of bloody diarrhoea Mucoid diarrhoea Abdominal pain Low grade fever Loss of weight
What areas are affected by UC?
the large bowel from rectum to the caecum
the rectum only - proctitis
left sided bowel only - splenic flexure to rectum
whole large bowel - total colitis
What are the macroscopic features of UC?
there are no ulcers on endoscopic examination in early disease, despite the term ‘ulcerative’
there is diffuse mucosal involvement which appears haemorrhagic
with chronicity, the mucosa becomes flat with shortening of the bowel
What are the microscopic features of UC?
Inflammation confined to the mucosa
Diffuse mixed acute & chronic inflammation
Crypt architecture distortion
In quiescent (inactive) UC, the mucosa may be atrophic with little or few inflammatory cells in the lamina propria
What are the complications of UC?
Toxic megacolon
Refractory bleeding
Dysplasia / adenocarcinoma in patients at risk
What are symptoms of a toxic megacolon?
Patient very ill
Bloody diarrhoea
Abdominal distention
Electrolyte imbalance with hypoproteinaemia
What patients are at risk of dysplasia or adenocarcinoma complications of UC?
patients who have had UC at an early age
patients with total unremitting UC
After how many years will a UC patient require annual screening colonoscopy?
after 8-10 years
What are the extra-intestinal manifestations of CD & UC? (OCAH)
Ocular
Cutaneous
Arthropathies
Hepatic
What are examples of ocular manifestations of CD & UC?
uveitis, iritis, episcleritis
What are examples of cutaneous manifestations of CD & UC?
erythema nodosum
pyoderma gangrenosum
What is an example of arthropathies manifestations of CD & UC?
ankylosing spondylitis
What is an example of hepatic manifestations of CD & UC?
screlosing cholangitis
What are the investigations in CD & UC?
FBC, U & Es, LFTs Inflammatory markers – CRP Faecal Calprotectin Endoscopy, biopsies Radiological imaging
What inflammatory marker is tested for when investigating CD & UC?
C reactive protein
What radiological imaging methods are used to investigate CD & UC?
Barium studies
MRI, USS, CT Scan
What are the differences in presentation between CD & UC?
Bleeding: CD - occasional, UC - very common
Obstruction: CD - common, UC - uncommon
Fistula: CD - common, UC - none
Weight loss: CD - common, UC - uncommon
Perianal disease: CD - common, UC - rare
Distribution: CD - entire GIT, skip lesions / UC - large bowel only, continuous
What are the differences in pathology between CD & UC?
CD - full thickness, UC - mucosa only
CD - fissuring ulcers, UC - no ulcers early stages
CD - granulomas 60 -65%, UC - no granulomas
CD - crypt architecture preserved, UC - crypt architecture distortion
What are the differences in radiology between CD & UC?
CD - skip lesions, fistula abscess, fibrotic strictures UC - continuous process
What are the differences in cancer risk between CD & UC?
CD - increased
UC - much higher 1% at 10yrs of diagnosis
What are the differences in the effect of smoking between CD & UC?
CD - makes it worse
UC - makes it better
Why is a pouch created after surgery in UC patients?
as a stool reservoir following the surgical removal of the large bowel
What is a pouch created from for UC patients?
from the small bowel
What is a pouch not created for CD patients?
bc of the risk of recurrence
