Gastroenterology and hepatology Flashcards
how do the areas of the GI tract affected by Crohn’s and UC differ?
Crohn’s- can affect anywhere from mouth to anus, transmural inflammation but discontinuous= skip lesions, commonly affects terminal ileum and prox colon
UC- always affects the rectum, and extends proximally, continuous distribution, although may not look this way as result of local tment, superficial inflammation (mucosa and SM) so no fissures, fistulae or strictures.
what term is used to diagnose ptnts in whom it is impossible to distinguish between UC and isolated colonic Crohn’s?
indeterminate colitis
microscopic appearance of Crohn’s?
non-caseating granuloma- differentiate from caseous in colonic TB, and TNF has major role
lymphoid hyperplasia and neutrophil aggregates
goblet cells present
transmural inflammation
microscopic appearance of UC?
crypt abscesses
goblet cell depletion
chronic inflammatory cell infiltrate in lamina propria
superficial inflammation
macroscopic appearance of UC?
erythematous and inflamed mucosa, bleeds easily (very friable)
mucus discharge
ulceration continuous
3 key features of colitis?
bloody diarrhoea (includ. nocturnal)
urgency- ?ptnt exerience of incontinence, not making toilet in time
tenesmus
macroscopic appearance of Crohn’s disease?
skip lesions
thickened bowel wall with strictures, repeated healing attempts cause extensive fibrosis and TGF-beta has key role.
deep ulcers and fissures, ulcers may appear as apthous ulcers- white spots
cobblestone appearance due to linear ulceration which is separated by normal mucosa
why do ptnts with UC experience urgency?
solid stools irritate inflamed mucosal lining producing pain, so rapid transit, BUT ptnts can have proximal constipation for which a laxative may have to be used as proximal transit slowed despite rapid transit distally in L sided disease (below splenic flexure), and relief may allow remission of L sided disease.
AXR appearance of UC?
thickened white line of bowel wall due to oedema, increasing distance between bowel loops
white protrusions of bowel- inflammatory ulcers and assoc. oedema, thick haustra= thumb printing due to mucosal thickening
lead pipe sign=featureless colon in longstanding UC with loss of normal haustral markings, so just air filled bowel
incidence of UC?
10-20 per 100,000 per year
prevalence= 100-200 per 100,000
how is severity of UC classified?
mild= less than 4 stools per day, no systemic upset moderate= 4 to 6 stools per day, minimal disturbance severe= more than 6 stools per day, with blood and systemic disturbance.
Truelove and Witts criteria:
mild=less than 4 motions per day, small amount rectal bleeding, apyrexial, HR less than 70, Hb more than 11g/dL, ESR less than 30mm/hr
moderate=4-6 motions, moderate PR bleeding, temp 37.1-37.8, HR 70-90, ESR less than 30, Hb 10.5-11
severe=more than 6 motions/day, large PR bleeding, temp more than 37.8, HR more than 90, Hb less than 10.5, ESR more than 30.
why do an AXR in suspected UC?
look for toxic megacolon
look at extent, absence of solid stool in inflamed colon
look for proximal constipation
define toxic megacolon
transverse colon more than 6cm in diameter with loss of haustration
indications for colonoscopy in UC?**
performed at later date to determine proximal extent, and screen for colorectal Ca
surveillence colonscopy starts after 10 yrs of disease
require yearly colonscopy if co-existing primary sclerosing cholangitis-non-malignant, non-bacterial inflammation, fibrosis, and strictures of intra- and extrahepatic bile ducts, due to higher risk of CR Ca.
what is important in management of ptnts with UC and primary sclerosing cholangitis?
must have yrly colonscopy as higher risk of bowel Ca development
PSC= cholestatic liver disease with biliary stricturing and dilatation
extra-intestinal manifestations of IBD related to disease activity?
erythema nodosum
apthous ulcers
episcleritis
acute arthropathy
why is LMWH given to pts with IBD?
IBD= pro-thrombotic state- risk of DVT and PE
and may treat colitis as helps with microvascular occlusion
why must frequent Us and Es be taken for ptnts given mesalazine as maintenance of remission in UC?
risk of interstitial nephritis
why can azathioprine not be used in acute flares of UC?
takes at least 6 wks for onset of action
MOA of ciclosporin?
calcineurin inhibitor- a protein required in activation of T cells which mediate an inflammatory response
a patient presents complaining of bleeding per rectum. what qns should be asked regarding the bleeding to differentiate between UC, colorectal Ca and diverticular disease?
pain?- all are painless, pain in diverticular disease only if acute diverticulitis, and in Ca if distally placed in rectum or in anal canal, causing tenesmus
blood relation to stools- mixed in with loose stools+mucus=UC, large volume in pan= diverticular disease, mixed in with stool, espec. if prox. tumour in Ca.
colour, volume
bleeding PR: timings, prev.episodes,progression?volume?colour?relation to stools?pain?other assoc. symptoms e.g. tenesmus, urgency, constipation.
assoc with diarrhoea-?mucus and waking up at night to open bowels-UC
Ca-?weight loss, tenesmus, diarrhoea and/or constipation
presentation of oesophageal hypermotility disorders e.g. Nutcracker oesophagus?
retrosternal chest pain, possible radiation to back, and persisting discomfort following acute episodes
dysphagia
heartburn
how are all oesophageal hypermotility disorders diagnosed?
manometry-pressure evaluation
definition of classical Barrett’s oesophagus?
columnar mucosa extending 3 or more cm into tubular oesophagus
=metaplasia=reversible change from 1 differentiated cell type to another fully differentiated cell type
incidence of adenocarcinoma of oesophagus in pts with barrett’s oesophagus?
1 in 100 pt yrs
definitive diagnosis of barrett’s oseophagus?
oesophageal biopsy via endoscopy
tment of barrett’s oesophagus?
lifestyle advice: lose weight, stop smoking, avoid alcohol, raised head of bed at night, eat small regular meals, avoid hot drinks, alcohol and eating within 3 hrs of going to bed, avoid drugs that affect oesophageal motility or damage the mucosa e.g. anticholinergics, nitrates, NSAIDs, bisphosphonates
LT PPI therapy
aspirin
must try and prevent progression to adenocarcinoma-5% lifetime risk in men and 3% in women, 40-50% of those with barrett’s and severe dysplasia go on to develop adenocarcinoma within 5 years.
when no dysplasia, if surveillence considered appropriate should be every 2-5 years depending on length of affected segment and presence if intestinal metaplasia
?over whether medical or surgical intervention can result in clinically meaningful regression of the barrett’s epithelium or reduce risk of subsequent malignancy.
low-grade dysplasia-after confirmation by 2 pathologists, surveillence every 6 months. may consider endoscopic radiofrequency ablation or photodynamic therapy. should allow regrowth of squamous epithelium.
photodynamic therapy- with laser +/- photosensitising agents to ablate dyslastic epithelium is being used, due to high mortality of surgery-7%.
Consider using radiofrequency ablation or photodynamic therapy alone for flat high-grade dysplasia.
Consider using endoscopic mucosal resection alone for localised lesions, use circumferential endoscopic mucosal resection with care because of the high incidence of stricture formation and consider following with an additional ablative therapy.
if suitable for surgery and wish to have this, oesophagectomy indicated in high grade dysplasia and intramucosal Ca.
if residual or recurrent disease, offer EMR or ablative therapy or both.
complication of achalasia?
squamous cell carcinoma of oesophagus, thought to be due to food stasis and mucosal irritation
aetiology of achalasia?
may be related to viruses or AI
known that myenteric plexus ganglion cells are reduced, and the non adrenergic non cholinergic inhibitory innervation to LOS, mainly via NO to cause relaxation, is impaired.
clinical features of achalasia?
dysphagia- both solids and liquids
regurgitation
weight loss
chest pain- linked to oesophageal spasm
findings of radiological investigation of achalasia?
CXR- may see air-fluid level due to dilated oesophagus
barium swallow- dilated oesophagus with reduced peristalsis
why is endoscopy performed in suspected achalasia?
to exclude mucosal pathology and pseudo-achalasia
what does oesophageal manometry reveal in achalasia?
raised LOS pressure and incomplete/absent sphincter relaxation
what is pseudo-achalasia?
oesophageal dilatation and dysphagia, usually due to malignant obstruction
complications of surgical myotomy for achalasia?
reflux
this is also a complication of endoscopic dilatation, which also poses the risk of perforation
define irritable bowel syndrome
a common recurrent chronic illness, characterised by abdominal pain/discomfort and disturbed bowel habit, but no recognised pathology or specific cause.
what are the Rome II diagnostic criteria for IBS?
at least 12 wks of abdo discomfort/pain in preceding yr with 2 or more of: relief by defecation, onset assoc. with change in stool frequency, onset assoc. with change in stool appearance.
symptoms supporting a diagnosis= abnormal stool frequency abnormal stool form difficulties in evacuation mucus passage bloating or feelings of distension
clinical features supporting IBS diagnosis?
Rome II criteria
long history with relapsing and remitting course
exacerbations triggered by life events
coexistence of anxiety or depression
assoc with symptoms in other organ systems
symptoms aggravated by eating
clinical features suggesting organic disease other than IBS?
onset in old age progressive deterioration fever weight loss rectal bleeding steatorrhoea dehydration
investigations in suspected IBS?
routine hamatology/BC
sigmoidoscopy with rectal biopsy (if diarrhoea)
if diarrhoea persistnet, serum B12, folic acid, iron studies, TFTs, coeliac Abs, LFTs, and stool microscopy
consider colonoscopy to exclude microscopic colitis
faecal urgency or incontinence suggest need for anorectal manometry
examples of alternative therapy in IBS tment?
physical therapy e.g. massage, acupuncture, reflexology, to work on tension release
meditation and hypnotherapy- produce focused relaxation which may facilitate cognitive behavioural change.
drugs used in IBS management?
antispasmodics for abdo pain e.g. mebeverine-synthetic anticholinergic, hyoscine butylbromide (buscopan)- anticholinergic/anti-muscarinic, MR peppermint oil capsules-local effect of colonic relaxation, and inhibits smooth muscle activity via interference with Ca2+, alverine citrate-spasmolytic.
antidiarrhoeal e.g. loperamide-synthetic opioid, and colestyramine-bile acid sequestrant
anticonstipation e.g. macrogols-osmotically acting laxative
antidepressants e.g. TCAs, SSRIs
considerations in management of diet in IBS pt?
pt may keep a food diary to detect food intolerance and eliminate these from diet, and speak to a dietician
exclusion diet- start off with bland diet for few days, slowly introd. favourite foods to identify a precipitating food.
illnesses which overlap with IBS?
fibromyalgia
chronic fatigue syndrome (ME)
how does recent rise in incidence of Crohn’s disease support role of enviromental factors in disease pathogenesis?
part. importance of smoking and diet
diet= some pts may have problems handling saturated FA
and smoking worsens disease possibly due to effect on microvasculature.
how do clinical features of Crohn’s differ from those of UC?
Crohns typically abdo pain and diarrhoea, may be weight loss, anorexia and fever, gross rectal bleeding and acute haemorrhage uncommon.
colonic crohn’s may present with bloody diarrhoea, but tenesmus less common than in UC as rectum less commonly affected.
gastroduodenal crohns can present as H.pylori -ve peptic ulcer disease.
EI manifestations of Crohn’s?
Eyes- scleritis, episcleritis, anter. uveitis
Joints- enteropathic arthritis assoc. with HLA-B27 and AS, typically large joints e.g. sacroileitis.
Skin- apthous ulceration, erythema nodosum, pyoderma gangrenosum-responds well to topical steroids and infliximab
metabolic bone disease- osteopenia with disease and as result of steroid tment of disease
venous and arterial VTE
GSs, fatty liver, AI hepatitis and primary sclerosing cholangitis
renal oxalate stones
when is MRI used in Crohn’s?
for imaging perianal or pelvic fistulating disease
micro and macroscopic evaluation favouring Crohn’s over UC?
transmural, granulomas, small-bowel disease, mainly R sided colonic disease, rectal sparing, fistulae (can be seen on US), perianal disease.
aim of crohn’s disease management?
NO CURE, so induce and maintain remission
indications for surgery in Crohn’s disease pts?
haemorrhage intra-abdominal masses obstruction as fibrotic strictures medically intractable fistulae toxic megacolon cancer
MOA of azathioprine?
pro-drug activated to 6-MP, which is a purine antagonist
elimination requires TPMT, so activity must be measured before commencing tment.
NICE recommendations for induction of remission in Crohns?
glucocorticosteroid e.g. prednisolone if 1st pres. or single inflammatory exacerbation in a yr
consider enteral nutrition as alternative in young if worried about growth retardation
consider adding azathioprine or 6-MP if 2 or more inflammatory exacerbations in 1 yr or can’t reduce steroid dose.
consider MTX if can’t take azathioprine or 6-MP
consdier infliximab or adalimumab if severe active disease not responding to conventional tments
NICE recommendations for remission maintenance in Crohns?
azathioprine or mercaptopurine
MTX considered only if needed to induce remission, or didn’t tolerate azathioprine or mercaptopurine for remission, or have CIs to these.
NICE recommendations for remission maintenance in Crohn’s after surgery?
azathioprine or mercaptopurine if adverse prognostic factors e.g. >1 resection, or previously debilitating/complicated disease e.g. abscesses, fistualising disease.
5-ASA tment may be considered e.g. mesalazine (pentasa).
investigations in Crohn’s?
FBC-?anaemia, leucocytosis, raised platelets-reactive to inflammation
iron, total iron binding capacity (TIBC), B12, folate
CRP-raised
LFTs- INR and albumin-lowered
low Ca2+, Mg2+, zinc- zinc important in tissue healing
Stools culture for C. difficile toxin and infectious cause of colitis
endoscopy-colonoscopy-allows mucosal biopsy and balloon dilatation of strictures
barium follow through- evaluate small bowel
USS- thickened bowel, fistulae and abscesses
CT- extraluminal features, blood flow
MRI- perianal or pelvic fistulating disease
NICE guidance for inducing remission in UC with proctitis and proctosigmoiditis?
proctitis and proctosigmoiditis: mild to mod 1st pres. or inflam. exacerbation, offer topical ASA alone- suppository or enema, or add an oral ASA to topical, or oral ASA alone although not as effective as 1st 2 options.
if unable to have aminosalicylate, consider topical corticosteroid or oral pred
if subacute pre, consider oral pred
NICE guidance for inducing remission in UC with L sided and extensive UC?
high induction dose of an oral ASA, and consider adding a topical ASA or oral beclometasone dipropionate
same for children and young people, but not high induction dose of oral ASA
oral pred if decline ASA/CI, or subacute UC
step 2 therapy in treating mild to mod UC?
consider adding oral pred to ASA in remission induction if no improvement within 4 wks, or worsening. stop becl dipro if adding pred.
consider adding oral tacrolimus to oral pred. if inadequate response to oral pred. after 2-4wks
NICE guidence for remission induction in acute severe UC?
IV corticosteroids, and assess likelihood for needing surgery
if not steroids, consider IV ciclosporin or surgery
NICE guidence for maintenance of remission in proctitis and proctosigmoiditis in UC?
topical ASA alone (daily or intermittent) or plus an oral ASA or just oral ASA although not as effective
NICE guidence for maintenance of remission in L sided and extensive in UC?
low maintenance dose of an oral ASA in adults
oral ASA in children and young adults
consider pt pref, ADRs and cost
oral ASA consider once daily dosing for increased effectiveness, but may be more ADRs.
when is oral azathioprine or mercaptopurine considered in UC?
as maintenance of remission after 2 or more inflammatory exacerbations in 12 mnths that require tment with systemic corticosteroids
or if remission not maintained by ASAs
also considered after single episode of acute severe UC for remission maintenance- consider ASAs if these are CI, not tolerated or declined.
difference between a suppository and enema for ASA administration in inducing remission in proctitis in UC?
suppository= solid placed into rectum, slowly dissolves enema= liquid or gas injected into rectum
MOA of mesalazine (an aminosalicylate)?
intestinal anti-inflammatory drug
inhibits leucocyte chemotaxis and cytokine prod. and scavengers for free radicals.
ADRs of mesalazine?
common= GI= diarrhoea, abdo pain, N+V, general=headaches, and skin= rash rare= leucopenia, thrombocytopenia, peripheral neuropathy, pancreatitis, lupus erythematosus type reactions, renal failure.
ADRs of azathioprine?
myelosuppression-leucopenia, anaemia, thrombocytopenia, neutropena nausea neoplasma e.g. NH lymphoma cholestasis-raised ALP, jaundice, LFT deterioration, liver impairment interstital nephritis hair loss myalgia arthralgia
why should pts with PSC have yrly abdo ultrasound
due to risk of malignant GB polyps/GB cancer e.g. cholangiocarcinoma- cancer of CBD.
azathioprine drug class?
antiproliferative immunosuppressant
symptoms and signs of toxic megacolon?
those assoc. with exacerbations of crohns and UC include abdo pain abdo tenderness diarrhoea, repeat, bloody distension fever tachycardia shock dehydration
define severe active Crohn’s disease necessitating anti TNF tment?
very poor general health and 1 or more of the following: severe abdominal pain, fever, weight loss and usually frequent (3-4) stools daily.
Crohn’s disease activity index (CDAI) of 300 or more, or a Harvey-Bradshaw score of 8-9 or above.
what is the Glasgow alcoholic hepatitis score (GAHS) used for?
to help in prognosticating pts with alcoholic liver disease predicts mortality based on age WCC blood urea nitrogen (BUN) bilirubin PT PT lab normal
9 or more is a predictor of mortality
(75% mortality at 28 days?, and anyone with alcoholic hepatitis 50% mortality at 28 days?)
components of tment in alcoholic liver disease (ALD)?
alcohol withdrawal
abstinence
nutrition- enteral preferred, parenteral- line sepsis, line thrombosis, electrolyte imbalance, mechanical trauma. also shouldn’t restrict protein despite fear over hepatic encephalopathy.
glucocorticoids- block inflammatory and cytotoxic pathways in alcoholic hepatitis
anti TNF alpha e.g. pentoxifylline, with elevated TNFalpha levels found to be predictive of poor survival in alcoholic hepatitis pts.
liver transplantation in decompensation
medications used for hepatic encephalopathy?
Rifaximin (antimicrobial) is recommended as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in adults.
?metronidazole?
what is calcineurin (inhibited by ciclosporin used in UC tment)?
a protein phosphatase involved in T cell activation
aim of a low residue diet in Crohn’s disease pts?
may help in inducing and maintaining remission as involves a diet that avoids high fibre foods as fibre can cause cramping, and lower fibre means less residue (undigested portion of food) so less stools.
Pts should avoid legumes, most raw fruit and veg, potato skins, milk, caffeine, most whole grain foods e.g. bread and pasta.
ideal marker of liver synthetic disruption to help determine timing/need for orthotopic liver transplantation?
PT
so do not correct elevated PT e.g. with FFP, unless pt actively bleeding.
indications for liver transplantation in CLD?
refractory ascites, hepatic encephalopathy and variceal bleeding (not effectively controlled by medical/endoscopic therapy) after 1st episode of SBP, as predoicts 50% 2 yr mortality. poor QOL e.g. pruritis, severe fatigue in cholestatic liver disease e.g. PBC Child-Pugh score >7= score of 1-3 given for 5 variables, with 3 being most severe=total bilirubin, serum albumin, PT, ascites and hepatic encephalopathy, with class C=score 10-15, with 45% 1 yr survival, and MELD score (model for endstage liver disease- determines % mortlaity in CLD without transplant)= indicators for need of referral.
other than low PLTs, why do many pts in hospital have some degree of abdominal bruising?
result of SC VTE prophylaxis injections e.g. dalteparin
contraindications to liver transplantation?
active sepsis
advanced CP disease
extrahepatic/extensive intrahepatic malignancy
active alcohol dependency or substance abuce- most programmes require 6 mnths abstinence prior to transplantation for alcoholic cirrhosis.
psychosocial factors that impair pt’s ability to comply with immunosuppressive tment
HIV was previously but now improved ART and comparable graft survival so may be considered, although reduced post transplant outcomes.
what does a Glasgow Alcoholic Hepatitis Score (GAHS) of 9 or more indicate?
50% mortality at 28 days
indicates need for steroids to treat hepatits
if score less than this, consider general factors in pt management- alcohol abstinence, adequate E + D, fluid intake, education on alcohol withdrawal and abstinence, ref to alcohol liason team, discuss need for physio/OT if necessary.
common drug now used to prevent recurrent episodes of overt hepatic encephalopathy?
rifaximin from rifamycin class of antibacterials, and inhibits RNA polymerase. may inhibit division of urea-deaminating bacteria, so reducing NH3 production.
excreted in the faeces
post liver transplant complications?
rejection- hyperacute- treat with re-transplant, acute- hgih dose IS, chronic- adjust IS but graft failure usual.
technical problems- VC thrombosis, haemorrhage, anastamotic leak
drug effect- increase infections, and ISs can cause hepatotoxic effects
INFECTION e.g. EBV reactivation
what is pabrinex?
indicated for severe depletion or malabsorption of water soluble vitamins B and C part. in alcoholism
(Parenteral thiamine)
how is hepatic encephalopathy assessed for?
hepatic flap?
AMT: is pt orientated to person, time and place
are there symptoms of drowsiness, confusion, or is pt unresponsive?
Pt may have positive Babinski test- big toe DF and fanning of the toes.
characteristic appearance on biopsy of primary sclerosing cholangitis?
onion skin fibrosis around the bile ducts
risk factors for non-alcoholic fatty liver disease?
obesity
HTN
hyperlipidaemia
type 2 DM
considered the liver component of the metabolic syndrome, and insulin resistance is universal.
management of NAFLD?
weight loss
good BP, lipid and diabetes control
exercise
pts most at risk of NAFLD progression following assoc. inflammation?
diabetics
how is NAFLD diagnosis confirmed?
fatty liver on USS
how is liver fibrosis enhanced by insulin resistance?
induces connective tissue GF
give 2 reasons for thrombocytopenia in liver disease?
reduced thrombopoietin prod which is dependent on functional liver cell mass and is required for platelet production
and portal hypertension leads to splenomegaly, causing sequestratioin of platelets by the spleen.
