coeliac and inflammatory bowel disease Flashcards
what is coeliac disease
gluten sensitive enteropathy or coeliac spruce
AI mediated disease of SI triggered by gluten in genetically predisposed individuals leads too malabsorption
cessation of symptoms when no gluten in diet
what is gluten
compound of wheat, rye and barely left behind after washing off the starch
consists of gliadin and glutenins
what are the genetic abnormalities of coeliac disease
ass with HLA-DQ2 and HLA-DQ8 in 95/5%
genes located on Chr 6p21
others being investigated
strong hereditary predisposition affecting 10% first degree relatives
who gets coeliac disease
Western Europe and USA, esp Irish and Scandanavian
inc in africa and asia
lots have it undiagnosed
high prevalence in downs syndrome, T1 DM, AI hepatitis, thyroid gland abnormalities
bimodal presentation in childhood and late 30s, 20% over 60
how does gluten cause coeliac disease
gluten in wheat and small bowel mucosa tissue transglutaminase dominates glutamine in gliadin neg charged protein IL-15 Natural killer Tc ells and intraepithelial T lymphocytes tissue destruction and villous atrophy
what does wheat do to the small bowel mucosa
inflammation and flat lining (crypts but loss of villi)
what are the types of coeliac disease
malabsorption leads to symptoms
asymptomatic coeliac disease - blood test
classical and atypical CD
symptoms of classic CD with GI symptoms
diarrhoea (smelly, bulky, rich in fat) flatulence in some borborygmus weight loss in kids - fail to thrive weakness and fatigue sev abdo pain IBS like symptoms
classic presentation of ssteatorhoea
bulky pale offensive stool
rich in fat
atypical CD due to extra intestinal symptoms
anaemia
osteopenia and osteoporosis
muscle weakness, pins and needles, loss of balance
itchy skin conditions eg dermatitis
lack of periods, delayed periods, infertility in women and infertility and impotence in men
bleeding disorders due to vit K deficiency
atypical presentation of CD
emaciation
pot belly due to gaseous distension
muscle wasting
osteoporosis
investigations for CD
general - FBC, U and Es, LFTs
serology - TTGA, endomysial IgA (CT covering smooth muscle fibres), deaminated gliadin peptide (IgA and G). gluten free disease
can be neg in 6.4-9%
genetics and +TTGA to avoid biopsy in kids
duodenal biopsy
how do routine coeliac disease tests work
assess tissue damage
overreaction of immune system - antibodies to protein involved in damaged eg TTGA (tissue transglutaminase), endomysium and deaminated gliadin peptide
microscopic features of coeliac disease
at least 4 biopsies sampled from duodenum at upper GIT endoscopy as can be patchy
there is
villous hypertrophy, crypt hyperplasia, inc lymphocytes in lamina propria/chronic inflammation, intraepithelial lymphocytes, recovery of villous atrophy on gluten free diet
what is villous atrophy
chronic inflammation (packed full of blue cells) crypt hyperplasia to replace villi
complications of coeliac disease
enteropathy associated T-cell lymphoma
high risk of adenocarcinoma in SB and other organs (LB, Yes, panc)
ass dermatitis hepetiformis
infertility and miscarriage
refractory coeliac disease despite sticking to diet
may be reduced by diet
what constitutes IBD
Crohn's disease UC Diverticular disease ischaemic colitis drug induced colitis infective colitis CD and UC - idiopathic IBD (important to differentiate - surgery and treatment differs) overlap in presentation, features and treatment
what is Crohn’s disease
idiopathic chronic IBD often complicated by fibrosis and obstructive symptoms
can affect any part of GIT mouth to anus
what is the epidemiology of CD
high prevalence in west, inc by jewish origin
inc in africa, South America and Asia
bimodal pres in teens/20s and 60/70s
what causes CD
exact unknown
genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psych
defects in mucosal barrier allowing pathogens and antigens to induce unregulated inflammatory reaction
what are the genetics of CD
strong evidence for it
first degree relatives 13-18%, 50% in MZ twins
polygenic
NOD2, also CARD15 on Chr16 encodes proteins ass to uncontrolled inflammation to luminal contents and microbes
is there an infectious cause of CD
60-65% mycobacterium para-TB was investigated, not proven
other infectious organisms implicated inc measles, psuedomas and listeria
environmental factors implicated in Crohn’s disease
improved hygiene hypothesis - reduces enteric infection in those susceptible, less reg processes so immune response not limited on infection leading to mucosal damage
migration from low risk pop to high risk
cigarette smoking doubles
clinical features of CD
chronic indolent course punctuated by periods of remission and relapses
abdo pain, received by opening bowels
prolonged diarrhoea (not bloody, blood if colon involved)
loss of weight
low grade fever
distribution of CD
SB alone - 40%
LB alone - 30%
both - 30%
what are the morphologic features of CD
fat wrapping serosa (can aid to demarcate the extent of disease)
affects bowel segmentally to give rise to skip lesions
ulceration of mucosa giving rise to cobblestone pattern
strictures
microscopic appearance of CD
transmural or full thickness inflammation of bowel wall
mixed acute and chronic inflammation eg polymorphs and lymphocytes
preserved crypts
mucosal ulceration
fissuring ulcers
granulomas
fibrosis of wall
complications of CD
intra-abdo abscess
deep ulcers - fistula
sinus tract - blind ended tract ends in cul de sac
obstruction due to adhesions, strictures (fibrosis)
perianal fistula and sinuses
risk of adenocarcinoma, not as high as UC
what is UC
chronic IBD
only affects large bowel from rectum to caecum
inflammatory process confined to mucosa and submucosa except in severe cases
epidemiology of UC
more common in west, higher prevalence in jewish
less freq in africa, south America and Asia
arise at any age but rare before 10, peaks at 20-25 with smaller peals at 55-65
what causes UC
unknown
similar to CD multiple factors implicated
genetic predisposition not as well defined (high incidence in first degree relative and twins)
HLA-B27 in most pts but not a cause
no specific infective agent
env factors - smoking protective, NSAIDs exacerbate, vits A and E found in low levels in UC
clinical features of UC
intermittent attacks of bloody diarrhoea mucoid diarrhoea abdo pain low grade fever weight loss
macroscopic features of UC
LB, rectum to caecum
rectum only (proctitis), LHS bowel (splenic flexure to rectum) or whole (total colitis)
no ulcers in early disease
diffuse mucosal involvement (haemorrhagic)
chronicity - mucosa flat with shortening of bowel
microscopic features of UC
inflammation confined to mucosa
diffuse mixed acute and chronic inflammation
crypt architecture distorted
quiescent UC mucosa may be atrophic with little/few inflammatory cells in lamina propria
complications of UC
lead to surgery refractory medical treatment toxic megacolon (dilated, ill, bloody diarrhoea, abdo distension, electrolyte imbalance with hypoproteinanaemia) refractory bleedoing dysplasia or adenocarcinoma unremitting UC after 8/10 years - annual colonoscopy
what are the extra intestinal manifestations of UC and CD
ocular - uveitis, irisitis, episcleritis
cutaneous - erythema nodosum, pyoderma gangrenosum
arthropathies - ankylosing spondylitis
hepatic - screlosing cholangitis
investigations into UC and CD
FBC, U and Es, LFTAs inflammatory markers like CRP faecal calprotectin endoscopy and biopsies radiological imaging barium studies, MRI, USS, CT
why is it important to differentiate between UC and CD
pouch after surgery in UC but not CD due to risk of recurrence
pouch from SB as stool reservoir after removing large bowel
what is fissuring
deep crevices
same as transmural
what are granulomas
collections of lymphoid cells
known as granulomatous inflammation
ass to CD
layers of SB
submucosa mucosa muscularis mucosa circular muscularis propria longitudinal muscularis propria villi attached to crypts, attached to mucosa
