Gastroenterology 1 - Upper GI Issues Flashcards
Where is gastrin produced?
In the G cells of the antrum of the stomach. Stimulates H+ production in parietal cells, and production of somatostatin in D-cells, which inhibits gastrin production from G-cells.
Gastrin is stimulated by digested protein and amino acids.
Where is somatostatin secreted in the stomach and it’s function?
Released by D-cells in the antrum and body - inhibits G-cell production of gastrin, and inhibits the production of histamine from ECL cels in the body. Inhibits the production of H+ by parietal cells in a paracrine manner.
Is stimulated by ACh release from post ganglionic vagus nerves.
What is the histamine in the stomach?
released by ECL cells in the body, and acts on parietal cells to release H+ via H2 receptors. Stimulated by ACh and inhibited by somatostatin
What are features of peptide hormones in the stomach?
Gastrin and CCK
Produced in response to triggers, and produced as preprohormones - secretory granules in the golgi apparatus
several sized versions are produced with differing actions
What is the rate limiting step in H+ secretion in the stomach?
H/K/ATPase pump
Increases in what conditions have been associated with PPI use in case control studies?
Pneumonia - RR 1.89
Gastroenteritis (campylobacter, salmonella) - RR2.9
Osteoporosis OR1.44
What is the odds ratio for C. difficile infection in PPI treated patients?
OR 1.47-2.85, p
Is there an interaction between clopodigrel and PPIs?
Conflicting data - 2C19 interaction in vitro ? significant clinically?
post hoc analyses have shown no conclusive link
What is the proposed theoretical mechanism for increased CVD in PPI?
ADMA destruction inhibited by PPIs - which decreases NO production and decreased vascocontstriction
What are causes of hypergastrinaemia?
Prolonged acid suppression (PPI, ranitidine)
Atrophic gastritis - pernicious anaemia, Hpylori
Vagotomy, SB resection
Gastrin secreting tumours
Renal failure
Hypercalcaemia
Hyperlipidaemia (artefact)
What are features of ZES?
1/3 of patients have MEN1: hyperparathyroisism, pancreatic and pituitary tumours.
Chromosome 11q13 - 90% have positive genetic test.
Where are tumours found in ZES, and what are lab findings?
90% in the head of pancreas/duodenal area, 10% in the tail of pancreas.
fasting gastrin >1000, secretin provocation, gastrin >200, hypersecretion BAO >10mEq/hr
Gatate PET-CT is new standard.
Where do parasympathetic fibres originate?
vagal and sacral (Craniosacral)
Where do the sympathetic fibres originate?
thoracic and lumbar spine
What segments of the GIT are innervated by the SNS/pSNS?
Vagus innervates the oesophagus to upper 1/3 large intestine
Sympathetic - whole gut
Pelvic - large intestine
What is the intrinsic nervous system in the gut?
mysenteric plexus - as many neurons as the CNS
peristalsis controlled by ‘pacemaker cells’ - interstitial cells of Cajal
What are properties of slow wave conduction in the GUT?
Slow waves propagate without decrement in regions with ICC, but decay in regions without ICC
What are adult disorders of gut motility associated with loss of ICC?
Slow transit constipation, chronic idiopathic constipation Internal anal sphincter achalasia Gastroparesis (idiopathic/diabetic) Afferent loop syndrome Megacolon/megaduodenum Paraneoplastic dysmotility Crohn's disease Chaga's disease Achalasia of LES
What are causes of acute pancreatitis?
Alcohol Gallstones Infection Drugs Metabolic Post ERCP Ischaemia Pancreas divisum
What are causes of chronic pancreatitis?
Alcohol genetic Duct obstruction Tropical Systemic disease Autoimmune Idiopathic
What is the appropriate management of microlithiasis/sludge?
Appropriate to proceed to lap chole - decreased future risk of pancreatitis
What are important metabolic causes of pancreatitis?
increased chylomicrons and triglycerides increase the risk of pancreatitis
What is the effect of statins and fibrates upon the risk of pancreatitis?
Statins reduce the risk of pancreatitis in patients with hypercholesterolaemia.
Fibrates possibly increase the risk of pancreatitis in patients with hypertriglyceridaemia.
What is the effect of smoking and alcohol upon chronic pancreatitis?
smoking cessation reduces rates of pancreatic calcification at 6 years.
alcohol cessation has no impact upon calcification at this time
What is the optimal treatment strategy for post ERCP pancreatitis?
Can use NSAIDs periprocedurally to reduce risk (RR 0.36) of post ERCP pancreatitis - no AEs detected in study
What are causes of inherited pancreatitis?
Hereditary pancreatitis SPINK1 mutation CF gene mutations Varian common chromotrypsin C Autoimmune pancreatitis
What are features of autoimmune pancreatitis?
Autosomal dominant 80% penetrance Recurrent mild attacks from age 5 Chromosome 7q35, with 20 variants Trypsinogen gene PRSS1 Increased risk of cancer Genetic testing is available
What are features of SPINK1 mutation in chronic pancreatitis?
recently described mutation in patients with chronic pancreatitis and normal trypsinogen levels.
1/4 of adolescent patients with no FHx
most common missense mutation at codon 34
What is the relationship between CFTR gene mutations and idiopathic chronic pancreatitis?
RR 3.0 in patients with CFTR gene mutations
5T allele intron 8
also assoc with male infertility
mild mutations may be factor in other causes of pancreatitis
What is the relationship between variant common chymotrypsin C
Cofactor only Increases risk of pancreatitis along with: EtOH smoking CFTR SPINK1
What are features of autoimmune pancreatitis?
Rare, mild recurrent attacks May present with mass - DDx - Cancer Associated with Sjogren's, PBC, RA Raised serum IgG Responds to steroids, both histologically and clinically
What are features of necrotising pancreatitis?
Traditional treatment = early surgery and necrosectomy
Recent RCT showed that there were lower major complications in those treated with percutaneous radiological drainage first, followed by necrosectomy if needed
What are features of helicobacter pylori and cag a?
Cag A +ve = more virulence
assoc w Vac A - Vaculolating cytotoxin
Clinically = more duodenal ulcers, worse gastritis, higher risk of relapse, ? less cancer (assoc with atrophic gastritis and IM)
What are features of antrum-predominant gastritis?
associated with Vac A positive H. pylori.
Gastric histo:
Chronic inflammation and polymorph activity,
increased acid output,
Duodenal histo
gastric metaplasia and active chronic inflammation,
with risk of duodenal ulceration
What are features of pan-gastritis?
Gastric histo:
Chronic inflammation, polymorph activity, atrophy and intestinal metaplasia
Reduced acid output
Normal duodenal pathology
Risk of gastric ulcration
What is the rate of reinfection following h. pylori elimination?
1% / year
verify eradication with breath test
What are symptoms of eosinophilic oesophagitis?
Dysphagia Food impaction Chest pain Heart burn Abdominal pain refractory GORD
What are typical histological findings in oesophagitis?
> =15 eosinophils per HPF on histology
basal zone hyperplasia
dilated intercellular spaces
What are features of eosinophilic oesophagitis?
Th2 driven - ? asthma like
assoc with carbamazepine hypersensitivity syndrome
young men, dysphagia, food impaction and heartburn
What is current treatment of EoE?
Empiric Six food elimination diet - histological remission in 81%
Compliance is difficult
most common triggers are milk and wheat
(milk, wheat, egg, soy, peanuts, seafood)
Can do guided diet by skin prick testing - less accurate (histologic remission in 65%)
Four food elimination diet also possible (milk, wheat, eggs and soy)
What are other investigation options for EoE other than Bx?
Oesophageal string test is a possible method of Dx EoE
What are features of PPI responsive oesophageal eosinophilia
Typical EoE symptoms and histology
do not have GERD on endoscopy/pH monitoring
Exhibit clinical and histological response to PPIs
What are possible mechanisms for PPI responsive EoE?
PPIs may have anti-oxidant, inhibitory neutrophil function, decrease CK pdn by endo/epithelial cells, decrease adhesion molecule production by endothelial cells and neutrophils
may have Ix negative GERD (NERD) or respond to anti-inflammatory effects of PPIs
What are current Mx guidelines for EoE?
trial of PPI for 2 months, even if Sx suggest EoE vs GORD
4 food elimination diet as effective as 6 food - with better compliance
Should assess success at symptomatic improvement at 6 weeks.
How is achalasia diagnosed?
On barium swallow - bird beak sign with lack of gastric bubble.
On manometry, failure of LES relaxation on swallow.
What is the treatment of achalasia?
Surgery - modified heller myotomy - mortality 0.3%, response 85% at 5 years
Botulinum toxin - similar efficacy to dilatation, safe, but requires multiple treatments, 12/12 duration
Dilatation, pneumatic - perforation rate 5%, mort 0.2%, response 65% at 5 years, no longer performed
POEM - endoscopic myotomy, also an option
What are causes of malabsorption?
Luminal phase:
- enzyme deficiency - chronic pancreatitis
- nutrient consumption - bacteria o’growth (Vit b12)
Mucosal phase - coeliac disease
Post-absorptive phase - lymphangectasia
What are causes of vitamin B12 Deficiency?
Dietary - vegans Gastric: - pernicious aneamia - atrophic gastritis - gastrectomy Small bowel: - bacterial overgrowth - pancreatic insufficiency - crohn's disease - blocking agents - e.g. neomycin
What is HLA types are associated with coeliac disease?
HLA DQ2, DQ8
95% of patients with coeliac disease are positive for these - useful rule out test.
What are histological features in coeliac disease?
villous atrophy
crypt hyperplasia
increased intraepithelial lymphocytes
What diseases are associated with coeliac disease?
Dermatitis herpetiformis
Autoimmune conditions - IDDM, hypothyroidism, IgA deficiency
Down snydrome
What are characteristics of coeliac serology?
Anti-gliadin Abs: IgA, IgG traditionally used Endomysial Abs - IgA Tissue transglutaminase Ab - IgA - most accurate test - may be used with endomysial Ab Deamindated anti gliadin Ab - IgG antibody, useful in IgA deficiency - Not quite as Sn as TTG
What are the relative Sn and Sp of Ab in Coeliac Disease?
IgA Gliadin Sn 85, Sp 90 IgG Gliadin Sn 75, Sp 80 EMA Sn 95, Sp 100 tTG Sn 95, Sp 100 Deaminated gliadin Sn 90, Sp 100
What is the Dx approach for coeliac disease?
Histology is still required for diagnosis
Indeterminate cases:
-HLA typing
- Exclude other causes of villous atrophy
(bact overgrowth, giardiasis, lymphoma, gastroenteritis, CVID, norovirus, NSAIDs, MMF and olmesartan)
Recheck after gluten challenge
What are features of lymphocytic duodenosis?
AKA Marsh 1
>25 IELS/100 enterocytes
Normal architecture
10-20% part of spectrum of gluten sensitivity
Also NSAIDs, H. pylori, Crohn’s, Sjogren’s syndrome
What is the most common cause of GORD?
transient lower oesophagel relaxations cause of reflux if resting LES is normal mechanism responsible for belching increased prevalence in obesity vagally mediated (not by pharynx)
What are causes of a low resting LES tone?
Gastric distension Alcohol Caffeine Fat CCK Smoking
What are features of Grade A reflux oesophagitis?
One or more mucosal break, no longer than 5mm, that doesn’t extend between folds
What are features of Grade B reflux oesophagitis?
One or more mucosal break, more than 5mm long, that does not extend between folds
What are features of Grade C reflux oesophagitis?
One or more mucosal breaks that extends between two or more mucosal folds, but which involves less than 75% of the circumference
What are features of Grade D reflux oesophagitis?
One or more mucosal breaks that involves at least 75% of the mucosal circumference
What is the relationship between severity of reflux symptoms and grade of oesophagitis?
Similar between grades of oesophagitis
What is the relationship between GORD and H. pylori?
questionable
H pylori causes gastric disease
Hp may be protective in patients with atrophic gastritis and low acid production
What are complications of GORD?
Oesophagus - metaplasia, malignancy, ulceration, strictures
Extra-oesophageal - refluxate can exacerbate pharyngeal, laryngeal, pulmonary structures
What is the relationship between cough and GORD?
43-75% of patients with GERD related cough have no reflux symptoms
GORD related cough may respond to PPI
up to 40% of cases of chronic cough are caused by GORD
What is the possible MoA of chronic cough in GORD?
Possibly vagally mediated cough, stiumlation by refluxate to cough centre
What are surgical treatments for GORD?
Nissen fundoplication gold standard - 90% symptomatic improvement at 5 years
Dysphagia 6%
10-65% still on PPI
Must exclude achalasia (LES
What is the definition of barrett’s oesophagus?
Metaplasia of squamous epithelium to columnar epithelium in the lower oesophagus in response to low pH refluxate
What is the relationship between reflux and BE?
Barrett’s is associated with prolonged reflux episodes and increased frequency of reflux episodes.
Prevalence increases with duration of reflux symptoms.
Significant predominance in white males, who are fat
What is the role of HALO in BE?
eradicates metaplasia and low and high grade dysplasia in barrett’s oesophagus
What are current guidelines for barrett’s surveillance?
Nil dysplasia - q3-5yr surveillance endoscopy with Bx
Low-grade dysplasia - Bx - surveillance endoscopy with Bx every six months - 1yr
High grade dysplasia - surveillance endoscopy with Bx every 3 months - or proceed to resection or ablation
What is the relationship between BE and adenocarcinoma risk?
between 40-125x increased risk of oesophageal adenocarcinoma
What is the most common cause of oesophageal SCC?
smoking
