Gastroenterology Flashcards
Which enzyme is responsible for the conversion of trypsinogen to trypsin?
Enterokinase secreted by enterocytes
Cleaves –> trypsin which allows the conversion of pancreatic enzymes to their active form in the duodenum
Which protein is responsible for the transport of fructose across the luminal membrane?
Fructose - GLUT-5
Glucose/galactose/Na - SGLT1
What two sugars make up the disaccharides sucrose and lactose
Sucrose - glucose and fructose
Lactose - galactose and glucose
Which of the following is NOT a characteristic of osmotic diarrhoea?
a. Na >70 mEq/L
b. stops with gut rest
c. Reducing substances present
A = A, Na >70 mEq
A 15 year old with Crohn’s disease begins azathioprine therapy for maintenance.
Testing reveals they are heterozygous for a mutated TPMT allele.
What complication would they most be at risk for?
Answer: most at risk for myelosuppression
TPMT: thiopurine methyltransferase
Thiopurines: AZA, 6-MP, thioguanine
4-11% heterozygous for mutant allele
1/300 homozygous for mutant or compound heterozygote
Remainder wild-type
Other risks include hepatitis and pancreatitis
Which IBD medication may rarely be associated with interstitial nephritis?
5-ASA, mesalazine
List the monitoring required if using anti-TNF alpha therapy in inflammatory bowel disease:
TB: history, CXR, quantiferon gold
Varicella titers
Hepatitis B screening
Imaging if suspected fistulising disease in Crohn’s (most difficult to treat, suggest higher induction doses and longer duration of treatment)
Which of the following EIMs (extra-intestinal manifestations) is LEAST likely to correlate with intestinal disease activity in IBD?
a. pyoderma gangrenosum
b. erythema nodosum
c. ankylosing spondylitis
d. peripheral arthritis
e. anaemia
Answer = C ankylosing spondylitis
Correlates well with intestinal disease: erythema nodosum, peripheral arthritis, anaemia, sweet syndrome, episcleritis
May correlate: pyoderma gangrenosum
Does not correlate: primary sclerosing cholangitis, ankylosing spondylitis, sacroileitis
Sweet’s syndrome: acute, febrile, neutrophilic dermatosis assoc w/ IBD, 40 cases reported
More likely in Crohn’s than UC, more likely if colitis exists in either type
Which of the following EIMs (extra-intestinal manifestations) is more likely to be associated with ulcerative colitis than Crohn’s?
a. peripheral arthritis
b. erythema multiforme
c. primary sclerosing cholangitis
d. episcleritis
Primary sclerosing cholangitis more likely in UC
All others more common in CD
Pyoderma gangrenosum us more common in UC also
Ocular, axial and aphthous complications more likely in CD
In which form of inflammatory bowel disease is pANCA more likely to be present?
more common present in UC
pANCA - anti neutrophil cytoplasmic antibody 60-70% UC cases, if present in CD more likely to have a UC phenotype
ASCA - antisaccharomyces cerevisiae antibody - 60-70% of CD patients
Describe the classic endoscopic/histopathological findings of ulcerative colitis
Diffuse, continue inflammation becoming less severe as progresses proximally in the colon
Colon has a friable, granular appearance
May progress to ulceration, but only as deep as the muscularis mucosa
Extensive ulceration with patches of spared mucosa may give rise to ‘inflammatory pseudopolyps’
Rectal sparing and backwash ileitis may be seen
Describe the classic endoscopic/histopathological findings of crohn’s disease
Discontinuous inflammation - ‘skip lesions’
Creeping fat - extension of fat towards the antimesteric surface
Aphthous ulcers –> deep linear/serpiginous ulcers that have oedematous, hyperaemic mucosal edges (gives ‘cobblestoning’ appearance
What is the underlying gene mutation present in Wilson’s Disease?
ATP7B mutation
In the hepatocyte, the ATB7B protein either packages copper with caeruloplasmin for transport in plasma or excretes it in the bile
regarding ALT/AST, which is more specific for damage to hepatocytes?
= ALT
ALT stands for = always liver trauma
AST = all stuff (liver, heart, RBCs, kidney, pancreas, lungs, RBC, WBC)
You review a patient in clinic who has severely reduced function of the bilirubin glucuronosyl transferase enzymes and an serum bilirubin of approximately 300
What is the diagnosis/prognosis?
Most likely Crigler Najjar Type 1
Likely to require liver transplantation once older (BSA/mass will become too low for phototherapy)
Name the medications with may induce the enzyme GGT
Carbamazepine
Frusemide
OCP
MTx
Phenobarbitol
Phenytoin
Valproate
What is the clinical significance of the triangular cord sign?
Suggestive of extra hepatic biliary atresia
Triangular cord sign - echogenic cord at the bifurcation of the portal vein
○ Located at the porta hepatis - this is a deep fissure in the inferior surface of the liver through which all neurovascular structures enter or leave the liver (except the hepatic veins) - common hepatic ducts, hepatic artery, portal vein
○ The triangular cord sign is a triangular echogenic cord of fibrous tissue representing the ductal remnant of the extra-hepatic bile duct
Describe the management of cerebral oedema secondary to acute liver failure
QuadH
Hyperventilation
Hypothermia
Hypernatraemia
Haemofiltration
Other Mx of acute liver failure
- PPI
- Coagulopathy
- Sepsis cover
- IV dextrose (avoid protein, fructose galactose until metabolic diagnosis excluded)
- Inotropic support
You review a 14 year old male patient.
They have a mild transaminitis and a very high bilirubin. Imaging has excluded an obstructive cause?
Which intrahepatic cause is most likely and what biochemical test could you use to prove the diagnosis?
This is suggestive but not pathognomonic for Wilsons Disease
Low ceruloplasmin could be used to confirm the diagnosis
Note ceruloplasmin may be artificially elevated by hepatic conditions and lowered by malnutrition
Describe the first line therapy for Wilson’s Disease
1st line: D-penicillamine
Promotes urinary copper excretion
Highly toxic, 30% will discontinue due to effects
-worsening of neurological symptoms
- immunological manifestations such as drug induced lupus and nephrotic syndrome
- skin: urticaria, cutis laxa, elastosis perforans serpignosa
2nd line is trientine dihydrochloride
- Similar MOA, less morbid
what is the syndrome?
what are the features + inheriance?
Peutz-jeghers
Autosomal dominant
Mucosal pigmentation of the lips, buccal mucosa, skin around the eyes nostrils, hands, feet and perianal region
Recurrent bowel intussusception may result in multiple resections
You are in gastroenterology clinic and are reviewing a patient with a large number of intestinal polyps.
In addition to this finding, the patient also has white papules in their mouth and on their hands and macrocephaly.
The diagnosis is:
a) FAP
b) Cowden disease
c) Bannayan-Riley-Ruvalcaba
d) IBD
The presence of white papules in the mouth and trichilemmoma (benign tumour of the hair follicle sheath often seen on the face) with intestinal polyps suggests Cowden syndrome, part of the Juvenile polyposis syndrome/PTEN hamartoma group. Other features include macrocephaly, acral keratoses and increased risk of thyroid, breast and endometrial cancer.
The other disorder in this group (also a PNET hamartoma thing) is Bannayan-Riley-Ruvalcaba, which is associated with macrocephly, intellectual disability and freckling of the penis.
FAP is associated with hundreds of polyps but may also have extra-intestinal features such as exostosis, eye lesions, desmoid tumours and dental abnormalities.
IBD can cause inflammatory polyps.
Which childhood cancers are FAP patients at risk of developing?
Hepatoblastoma - take a family history!
In children with very early onset inflammatory bowel disease, mutations affecting the immune system are common
In a 9 month old diagnosed with IBD, mutations in the gene for which receptor are commonly found?
Interleukin 10
definition of VEO-IBD
<6 years
which form of IBD can EEN be used to induce remission?
Crohn’s
name some agents used for maintenance in Crohn’s
5 ASA
Azathioprine/6MP
MTx
Infliximab/adalimumab
Name some agents used for maintenance in UC
5ASA
Azathioprine
Infliximab
what are the possible adverse effects of azathioprine
Bone marrow toxicity - higher risk of TPMT deficient
Liver dysfunction
Pancreatitis
Risk of EBV/VZV
Lymphoma
Sun related skin damage
adverse effects of methotrexate
Nausea - 25%
Liver toxicity
Bone marrow suppression
Infections
Lung fibrosis
patient on infliximab presents with lymphadenopathy and hepatosplenomegaly
what are you worried about?
risk of hepatosplenic t cell lymphoma with anti-TNF biologics
which form of IBD is associated with sclerosing cholangitis?
UC
which serological marker of coeliac disease is the most specific for coeliac disease
IgA endomyseal - just
IgA TTG is a close second
which serological marker of coeliac disease is the most specific?
anti-endomyseal
outline the pathobiology of coeliac disease
Gluten - family of proteins in wheat, barley, rye and spelt
Gluten - complex mixture of hundreds of proteins, predominantly glutenin
Limited degradation of gliadin by pepsin and TTG in the small intestine produces deamidated gliadin peptides (DPGS)
These bind to certain HLA haplotypes - DQ2 or DDQ8 leading to a gluten specific T cell response
what HLA types are associated with coeliac disease
People with coeliac disease are known to have one of either HLA DQ 2.5 (commonest), HLA DQ8 (less common) or HLA DQ2. 2 (least common)
https://www.coeliac.org.uk/information-and-support/coeliac-disease/about-coeliac-disease/causes/genetics/#:~:text=People%20with%20coeliac%20disease%20are,you%20will%20definitely%20develop%20it.
what findings on histology are suggestive of coeliac disease?
Intraepithelial lymphocyte count >30 per 100 enterocytes
Villous atrophy
Crypt hyperplasia
what foods does a patient with coeliac disease need to eliminate?
wheat, barley and rye
oats ok for 95%
