Gastroenterology Flashcards
Which gene and chromosome is associated with Wilson’s disease?
13q14.3 chromosome
ATP7B gene
Autosomal recessive
Carrier 1:90
How do Wilson’s Disease present?
Liver disease, coombs negative Haemolysis, tubular nephropathy, Kayser Flescher rings, Neuropsychiatric disorder
Presents typically 5 and above (need accumulation of copper for damage)
Most asymptomatic family screening
How do you diagnose Wilson’s disease?
Serum (liver) copper, Ceuroplasmin (copper carrying protein) - the lab measures the free amount of Ceuroplasm (thus, low Caeroplasmin and high copper means Wilsons), measure baseline 24 hours urinary copper excretion (and then give Pencillamine and if significant elevation -> Wilson’s disease)
ATP7 is the enzyme that attaches copper to caeroplasmin, and thus when the body isn’t able to do this , you have low levels of caeruplasmin
How do you treat Wilson’s disease?
D- Penicillamine as first line
2nd line is Trientine
(lifelong)
How does Bacillus Cereus infection present - in A) vomitting and B) diarrheal type?
Vomitting - undercoocked rice, and vomiting 1–5 hours after consumption
Diarrhea - various foods - has an 8- to 16.5-hour incubation time
How does Clostridium Perfrigens present?
Poor prepared meat and poultry - GI symptoms within 6-24 hours
Which Pathogen can act very quickly (within 30mins to cause GI symptoms)?
Staph Aureus - Foods that are frequently incriminated in staphylococcal food poisoning include meat and meat products; poultry and egg products; salads such as egg, tuna, chicken, potato, and macaroni; bakery products such as cream-filled pastries, cream pies, and chocolate eclairs; sandwich fillings; and milk and dairy products.
Heat resistant Toxin produced by Staph
Where is the APC gene and what role does it play?
It is found on chromosome 5 and mutations lead to adenomatosis polyposis coli (FAP).
It is normally a tumour suppressor gene
100% of patients will develop malignancy
What other malignancy is FAP associated with?
Hepatoblastoma
Other rare cancers; cortical dysplasia - seizure, congenital hypertrophy of retinal pigmented epithelium
What is Turcot syndrome?
Autosomal recessive + Colonic polyps + CNS tumours
What is Peutz Jeghers syndrome characterised by?
Lip freckling + gastric polyps
What is syndrome caused by germline mutations int he Serine Threonine Kinase tumour suppressor gene on chromosome 19p13.3?
Peutz Jeghers syndrome
How is Calprotectin produced?
It is present in the cytoplasm of neutrophils - it is not degraded by intestinal enzymes or bacteria
Good screening test for GI inflammation
What are GI complications fo CF?
DIOS (15%) Rectal prolapse (~20%) increased risk of GI tract tumours Fibrosing colonopathy CF associated liver disease (spectrum of disease upto cirrhosis)
3 other syndromes associated with exocrine pancreatic insufficiency?
And describe their characteristics
Shwachman-Diamond syndrome - Triad of Pancreatic insufficiency, bone marrow dysfunction and skeletal abnormalities (OP, dysplasias)
Pearson syndrome - Pancreatic fibrosis, vacoulated erythropoetic precursors, no skeletal abnormalities
Johnson-Blizzard syndrome - EPI, hypoplasia of nasal alae
How do you test for Exocrine pancreatic insufficiency?
72 hour faceal fat or faecal elastase (false positive with diarrhea)
Risk factors for TPALD?
- Prematurity and LBW
- Primary GI disease
- Lack of enteral nutrition
- Catheter related blood stream infections
- Small bowel bacterial overgrowth
Fish oil is omega- _
AND
Soy oil is omega- _
Fishoil - Omega 3 FA
Soy oil - omega 6 FA
What is the effect seen with GLP-2 analagogues (Teduglutide)?
It is a trophic hormone normally secreted by enteroendocrine cells -
It is shown to increase villous height in SBS patients and increase serum citrulline levels
SPINK 1 associated with ________
Familial pancreatitis
NOTCH 2 and JAG1 associated with _______
Allagile syndrome
SERPINA 1 associated with ________
A1AT deficiency
STK11 associated with _________
Peutz Jeghers
UGTP81 associated with ___________
Gilberts
SBDS associated with ______
Schwaman Diamond Syndrome
What is the rule of 4-4-9?
Carbohydrates = 4kcal/gram Protein = 4kcal/gram Fat = 9kcal/gram
Lactose = ______ + _______ (broken down by _______)
Glucose + Galactose (by lactase)
Breath test for carbohydrate malabsorption peaks at ______ hours. An earlier peak at 1 hour may suggests…
Breath test for carbohydrate malabsorption peaks at 2-4 hours. An earlier peak at 1 hour may suggest bacterial overgrowth or intestinal pathology
Glucose and galactose are transported by which transporter?
SGLT1 which requires Na and ATP
Fructose is transported by _______ and ________ across the basolateral membrane
Fructose is transported by GLUT2 (also transports glucose) and GLUT5
Transported via passive diffusion across the apical membrane
How does Mycophenolate mofetil work?
Prevents guanosine nucleotide synthesis preventing proliferation of T and B cells
Massive hepatic haemangiomas are associated with _________.
This is in relation to tumour expressing __________ which acts to _______
Associated with hypothyroidism.
The tumour expresses type 3 iodothyronine deiodinase which results in an increased rate of inactivation of thyroid hormone
The _ _ variant of A1AT overwhelmingly associated with liver disease
The ZZ variant
MM normal
Crigler-Najjar Syndrome 1 is due to ________
Absent enzyme that conjugates bilirubin - also UGTA1A gene
In Crigler-Najjar Syndrome 2 - the bilirubin levels are responsive to treatment with ______
Phenobarbitol because it increases the activity of the enzyme
IL-__ deficiency in VEO-IBD seen with significant perianal disease
IL-10
Which extra-manifestinal are more common in Crohns Disease than ulcerative colitis?
Erythema nodosum
Which bacteria can mimic RIF pain/appendicitis?
Yersinia enterocolitca
Also presents with erythema nodosum
Which is the investigation of choice when looking for fructose intolerance?
Serum Aldolase B enzyme measurement
What are the two chelating agents used for copper?
Pencillamine and Trientine
How do you treat hyperammonia?
Sodium Benzoate
Goat’s milk is deficient in _______
Folate
______ mutation increases the likelihood of developing Crohn’s disease
NOD2
Most common food associated with EI?
Cow’s milk
What is the recommended treatment for EI?
PPI, Elimination diet, swallowed corticosteroids
Difference between Type I and Type II and Type III Progressive familial intrahepatic cholestasis
Type I and II - normal GGT
What does bowel histopathology with Rotavirus show?
Histopathology of rotavirus-induced gastroenteritis show that the jejunal and duodenal mucosa appear to have patchy irregularities, which consists of shortening and blunting of the villi, and increased infiltration of the lamina propria with mononuclear cells.
In faecal screen:
Fat globules = ___________________
Fatty acid crystals = ________________
Fat globules = intraluminal problem e.g. failure of enzyme process or bile to suspend fats = maldigestion
Fatty acid crystals = mucosal/brush border problem (fatty acid not absorbed) = malabsorption
___________ is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities
Aagenaes syndrome
Affected patients usually present with episodic cholestasis with elevation of serum aminotransferase, alkaline phosphatase, and bile acid levels. Between episodes, the patients are usually asymptomatic and biochemical indices improve.
Generalized hypotonia with psychomotor retardation. Abnormal head shape and unusual facies, hepatomegaly, renal cortical cysts, stippled calcifications of the patellas and greater trochanter, and ocular abnormalities. Hepatic cells on ultrastructural examination show an absence of peroxisomes.
Which syndrome?
Zellweger (cerebrohepatorenal) syndrome
What is the pathophysiology behind neonatal haemachromatosis?
This is an alloimmune disorder with maternal antibodies directed against the fetal liver. Liver injury results in decreased hepatic hepcidin expression and thus dysregulation of placental iron flux
Affected patients present with steatorrhea, pruritus, vitamin D-deficient rickets, gradually developing cirrhosis, and low γ-glutamyl transpeptidase (GGT) levels
PFIC 1
The mutation for PFIC 1 occurs on chromosome __ and the pattern of inheritance is _______. This has an impact on _________
Chromosome 18q21 and inheritance is autosomal recessive. This affects protein FIC1 which is responsible for ATP dependent aminophospholipid flippase
What are some differences in presentation fo PFIC 1 and PFIC 2?
PFIC 2 presents with rapidly progressive cholestatic giant cell hepatitis, growth failure, pruritus.
Key differences are that PFIC 2 is rapidly progressive and PFIC 1 has impact on colon and thus you have more diarrhea
In contrast to PFIC I and PFIC 2, patients with PFIC type 3 (MDR3 disease) have _________
High levels of GGT
It is more often later-onset cholestasis, portal hypertension, minimal pruritus, intraductal and gallbladder lithiasis
How does benign recurrent intrahepatic cholestasis (BRIC) type I present?
Recurrent bouts of cholestasis, jaundice, and severe pruritus. Same mutation that involves PFIC1 but has
non-sense, frame shift, and deletional mutations cause PFIC type I; missense and split-type mutations result in BRIC type I
___________ is characterized by an elevated serum bile acid concentration, pruritus, failure to thrive, and coagulopathy
Familial hypercholanemia is characterized by an elevated serum bile acid concentration, pruritus, failure to thrive, and coagulopathy
___________ is characterized by an elevated serum bile acid concentration, pruritus, failure to thrive, and coagulopathy
Familial hypercholanemia is characterized by an elevated serum bile acid concentration, pruritus, failure to thrive, and coagulopathy
SGLT1 helps absorb ______________
glucose and galactpse
How does congenital sucrase-isomaltase deficiency present?
Infant begins to have diarrhea after starting fruits and juices
What is the genetic manifestation of glucose/galactose malabsorption?
Autosomal recessive disorder with SGLT1 gene anomaly (found on chromosome 22)
Hereditary fructose intolerance is caused by deficiency in which enzyme and what is the genetic basis?
It is caused by deficiency of Aldolase B which is important in conversion of fructose 1-P into glyceraldehyde (issue inside the hepatocytes)
Autosomal recessive condition
How is the digestion of MCT different to LCT?
You don’t need emulsification process and also MCT’s goes straight into the blood stream.
LCT’s get absorbed as chylomicrons through the lymphatics
Low albumin, low lymphocyte count and low IgG? + diarrhea/oedema
Primary intestinal lymphangiectasia
Which stool test helps look for protein losing enteropathy?
Alpha-1 antitrypsin
How do you treat protein losing enteropathy?
Treat underlying condition
Alter diet to MCT rich diet to put less pressure on lymphatic pressures
Can also use Octreotide to reduce pressures
What are non-GI manifestations of Coeliac disease?
Dermatitis Herpetiformis Dental enamel hypoplasia Delayed puberty Osteopenia/Osteoporosis Fe Deficiency Epilepsy with occipital calcifications
What are some associated conditions with Coeliac deficiency?
Down syndrome Turner syndrome Williams Syndrome T1DM Thyroiditis
Most sensitive serology test for coeliac?
Most specific serology test for coeliac?
Sensitive - tTG IgA
Specific - EMA IgA, DGP IgA and then tTG IgA
DQ _ found in 95% of coeliac patients and DQ _ in remaining
DQ 2 found in 95% of coeliac patients and DQ 8 i n remaining
Present in 30-40% of general population - used to rule out but not rule in
___% of people can be serology negative and still have Coeliac disease
5%
How does Schwannman diamond syndrome cause pancreatic insufficiency?
Acinar cell failure -parenchymal fatty infiltration of the pancreas
__________ is caused by a gene mutation in UBR1 gene and is associated with pancreatic failure; other clinical signs associated with this are imperforate anus, hypoplastic alae nasi, hypothyroidism, ectodermal scalp defect, deafness
Johanson Blizzard syndrome
No haematological or skeletal anomalies
_______ is associated with defects in acinar and duct cell function leading to pancreatic insufficiency. Other clinical signs can be refractory sideroblastic anaemia.
This is a mitochondrial disease
Pearson marrow pancreas syndrome
Most common cause of recurrent pancreatitis is genetic - what is the causative gene?
PRSS1 (autosomal dom) - 80%
SPINK1 is the autosomal recessive - less common
Why does coeliac disease reduce pH?
Lactose fermentation (secondary lactose intolerance) thus stool pH is low
That’s why carbohydrate malabsorption reduce stool pH
Estimated caloric requirements;
Neonate - XX kcal/kg/day,
6yo - XX kcal/kg/day,
12yo - XX kcal/kg/day.
Carbs = Xcal/g Protein = Xcal/g Fat = Xcal/g
Neonate - 100kcal/kg/day,
6yo - 75kcal/kg/day,
12yo - 50kcal/kg/day.
Carbs = 4 cal/g Protein = 4 cal/g Fat = 9cal/g
What is Sandifer syndrome?
Sandifer syndrome is a condition that involves spasmodic torsional dystonia with arching of the back and rigid opisthotonic posturing, associated with symptomatic gastroesophageal reflux, esophagitis, or hiatal hernia
How does PPI work?
Irreversibly bind to and inhibit the parietal cell enzyme hydrogen potassium stimulated ATPase “gastric proton pump”
How does erythromycin work to help with gastric motility?
Antidopaminergic effects and motilin agonist
How does Baclofen work for dysmotility?
Cholinergic agent - GABA receptor agonist
What is achalasia?
Reduction in inhibitory ganglion cells in the myenteric cells - reduced NO (increased collagen and lymphocytes)
Which syndrome?
Achalasia + ACTH insensitivity + Alacrima = ______
Allgrove syndrome
Hypophosphatemic rickets + deafness + vitiligo + achalasia = ______ which syndrome?
Rozychi
Which infective disease can cause achalasia?
Chagas disease
What are pathognemonic findings for EO?
- rings “trachialisation” of the oesophagus
- Furrows
- There may be white exudate
- Crepe paper like mucosa
- Or normal in 1/3 of the cases
When eliminating food in EO; which food do you eleminate first?
First eliminate Dairy and Gluten - 43% efficacy
Then you eliminate legumes and egg as well - 64% efficacy in children
First line treatment for H Pylori treatment?
Amoxi- Clarithro - PPI
Use metro instead of Clarithromycin if there is resistance
Confirmation of clearance with hydrogen breath test
What is the most common type of oesophageal fistula?
Type C - Oesophagus dead end; distal oesophagus connected to trachea (84%)
Second most common - Type A - both dead end
Vascular malformation occur in ___% of ToF
18%
Which genetic condition does Hirschsprung disease commonly occur in?
including trisomy 21, Joubert syndrome, Goldberg-Shprintzen syndrome, Smith-Lemli-Opitz syndrome, Shah-Waardenburg syndrome, cartilage-hair hypoplasia, multiple endocrine neoplasm 2 syndrome, neurofibromatosis, neuroblastoma, congenital hypoventilation (Ondine’s curse)
+ increased familial incidence
What is the histopathological findings in Hirschprung disease?
Observed histologically is an absence of Meissner’s and Auerbach’s plexuses and hypertrophied nerve bundles with high concentrations of acetylcholinesterase between the muscular layers and in the submucosa
What is the Curriano triad?
Currarino triad must be considered, which includes anorectal malformations (ectopic anus, anal stenosis, imperforate anus), sacral bone anomalies (hypoplasia, poor segmentation), and presacral anomaly (anterior meningoceles, teratoma, cyst).
- Often detected when investigating for Hirschprung disease in older children
What is the diagnosis?
Normal ganglion on the rectal suction biopsy, normal ACTHe activity, but absence of recto-sphinteric reflex on anal manometry
Internal anal sphincter achalasia
Which variants of Protease inhibitor phenotype gives you liver disease?
PiZZ and PiSZ
How does alpha 1 antitrypsin deficiency present?
11% have neonatal cholestasis +/- acholic stools
25% develop early liver failure and cirrhosis
Assoc with biliary atresia
Increased risk of HCC
What do you see in histopath for A1 antitrypsin def?
Period acid Schiff +ve diastase resistance globules in ER of hepatocytes
Low elastase in stool means?
Pancreatic insufficiency
What is the specific gene involved in Lynch syndrome?
MLH1 or MSH2 gene
Autosome dominant
What is the specific gene in Peutz Jeghers?
STK11
What is the second most common cancer in Lynch syndrome after cololncancer?
Endometrial cancer
If a button battery is in the _______ the it needs to be taken out ASAP
Oesophagus!
if in stomach we normally repeat XRAY in 24 hours, to check it is moving out of the stomach. If it isn’t -> endoscopy
Most common side effects with Sulfalazine?
Rash
Most common side effect of Mesalazine?
Elevated creatine, renal function issues, LFT rise and pancreatitis
Gold standard diagnosis of CMV colitis is________
colonic biopsies - you see Apoptosis
Primary sclerosing cholangitis is more in ______
More common in males, ulcerative colitis
Uveitis, arthritis and erythema nodosum is more common in ______
Crohn’s disease!
Anti-LMK 1 and Anti-LMK 3 and Anti-LC 1 are associated with _______
Type 2 Autoimmune hepatitis
What antibodies are associated with Type 1 autoimmune hepatitis?
ANA, Anti-SM, Antiactin antibody
Which form of autoimmune hepatitis is more severe?
Type 2
Several human leukocyte antigen class II molecules―particularly DR_, DR_, and DR_ isoforms―confer susceptibility to autoimmune hepatitis
DR 3, DR 4, DR 7
What are some extrahepatic manifestations of Autoimmune hepatitis?
Extrahepatic manifestations can include arthritis, vasculitis, nephritis, thyroiditis, Coombs-positive anemia, and rash
AMA +ve might also be seen in
Primary biliary cholangitis
What are the most common drugs that can induce pancreatitis?
Valproic acid
6MP
Azathioprine
Aspiriginase
What are the symptoms of Thiamin (B1 deficiency)?
o May have ptosis and atrophy of optic nerve
o Hoarseness secondary paralysis of laryngeal nerve characteristic
o Later: Raised ICP, meningismus, coma
o Severe deficiency -> beriberi disease
- Wet beriberi= undernourished, pale, edematous child with dyspnoea, vomiting and tachycardia, urine has albumin and casts
- Dry beriberi= plump, pale flabby, listless with dyspnoea, tachycardia and hepatomegaly
Low RBC transkelotase activity is best indicator of body tissue ___________
Thiamine deficiency
Which vitamin deficiency is associated with cheilosis and glossitis
Riboflavin (B2)
Which vitamin B deficiency?
classic triad of dermatitis, diarrhoea and dementia
Niacin - B3
Normal milk/formula/ breast milk has how many calories?
20kcal/30mL or 67kcal/100mL
The ____ acts as the major haematopoeitic organ until week 6, after which the bone marrow takes over
The liver
The pancreases starts excreting insulin from week __
Week 10
Gut rotation normally begins around week __ and ends week ___.
Normally the caudal portion (forms the cecum) of the midgut rotates ___degrees _____.
The most common type of malrotation involves failure of the cecum to move into the _________
Week 5 - Week 12
The Caecum rotates 270 degrees counterclockwise
Failure of caecum to move to RLQ
ATP7 A =
ATP7 B =
ATP7 A = Menke’s
ATP7 B = Wilson’s
As per guidelines, first line treatment for Wilson’s in an asymptomatic person?
ZInc salts
Coca Cola breaks down….
Fruit and vegetable bezoars
What drugs in Crohn’s disease cause mucosal healing?
EEN
Prednisolone
Infliximab
All of the above used for induction
Ways to differentiate osmotic vs secretory diarrhea?
Osmotic = loosing water alongside electrolytes
Secretory = “loosing serum”. Affected by feeds
Stool osmolal gap=
Stool Osm - (2x (Na+K))
If >100 = osmotic (losing electrolytes)
<100 = secretory
Simple way:
- 2 x (serum sodium + potassium)
- If >250 = secretory
- If <200 = osmotic
Most infectious agents cause secretory diarrhea, but in what instance can it cause osmotic diarrhea?
In salmonella and malabsorption disorders = you get osmotic diarrhea because losing nutrients and water
Which hormone is inappropriately high in PWS?
Grehlin
What is the role of gastrin?
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility
Which cells release acid?
Parietal cells
What is the role of secretin and CCK?
Secretin stimulates the flow of bile from the liver to the gallbladder. CCK stimulates the gallbladder to contract, causing bile to be secreted into the duodenum, as shown below.
In the pancreas, secretin stimulates the secretion of bicarbonate (HCO3), while CCK stimulates the secretion of digestive enzymes
Released by duodenum in response to chyme
What is the step up with medications UC and CD?
UC: Mesalazine -> azathioprine (steroid sparing)-> Infliximab (reserved for steroid requiring disease)
CD: Azathioprine -> Methotrexate (steroid sparing) -> Infliximab (reserved for steroid requiring disease)
EPCAM gene occurs in ….
Lynch syndrome
MYO5B is associated with…
PFIC, microvillous inclusion disease
What is the mechanism of action of cholestyramine?
Increased excretion of bile salts through he gut. Binds to the bile salts and prevent them from being absorbed in the ileum.
90% of bile salts are reabsorbed through the ____ as urobilogen
Ileum
Name the important channels:
Channels on the apical enterocyte absorption:
- _____ - sodium cotransporter - absorbs glucose and galactose
- ______ - absorbs fructose
Channels on the basolateral enterocyte membrane:
- ________ - glucose, galactose, fructose
- ________ - fructose
Channels on the apical enterocyte absorption:
- SGLT2 - sodium cotransporter - absorbs glucose and galactose
- GLUT 5 - absorbs fructose
Channels on the basolateral enterocyte membrane:
- GLUT 2 - glucose, galactose, fructose
- GLUT 5 - fructose
Liver histology =
Periductal fibrosis of liver = _______
Proliferation of bile ducts = _________
Paucity of bile ducts = __________
Periportal fibrosis = ___________
PAS negative staining = ________
Periductal fibrosis of liver = Primary sclerosing cholangitis
Proliferation of bile ducts = Biliary atresia
Paucity of bile ducts = Alagilles syndrome
Periportal fibrosis = NAFD
PAS negative staining = A1AT
ABCB4 gene is associated with ______
PFIC type 3
What do pareital cells secrete?
Intrinsic factor and hydrochloric acid
What do chief cells secrete?
Pepsinogen
What do G cells secrete?
G-cells are enteroendocrine cells which produce gastrin.
Gastrin causes stimulation of acid secretion from gastric parietal cells and stimulation of mucosal growth in the acid-secreting part of the stomach
Is Sucrose a reducing sugar or not a reducing sugar?
Sucrose is not
Most of the others are
Crypt lesions are seen in _______
Ulcerative colitis
Granulomas on bowel biopsy are seen in _______
Crohn’s disease
