Upper GI Flashcards
What factors are involved in gastric emptying?
Particle size (retained until <2mm) Fat content (high = slower emptying) Calorie content
Where are the parietal cells located? Function?
Upper 2/3 gastric mucosa. Produce HCl
Where are the chief cells located? Function?
Upper 2/3 gastric mucosa.
Secrete pepsinogen which initiates proteolysis
Which cells involved in digestion are located in the antrum of the stomach and what do they secrete? And function.
- D cells = somatostatin. Suppresses acid production by inhibiting gastrin and histamine release
- Mucous secreting cells
- HCO3-
- G cells = gastrin.
Stimulates acid production directly and indirectly via histamine.
What are the 3 phases of acid secretion?
- Cephalic phase: sight/smell/thought of food stimulates the vagus to produce ACh
- Gastric phase:
Distension stimulates secretory cells and gastrin release. - Intestinal phase:
Passage of food into the intestine stimulates GI hormone release
How is HCL produced?
By the parietal cells.
K+ and Cl- diffuse into the canaliculi within the cell. The H+/K+ ATPase pump, pumps K+ back into the main cell in exchange for H+ which enters the canaliculi. The pump is stimulated by a rise in cAMP and Ca2+
On the basal cell surface:
1. Gastrin stimulates CCKBB receptors (increases Ca2+) and histamine release
2. Histamine from ECL cells stimulates H2 receptors
3. ACh from the vagus stimulates M3 receptors. ACh also stimulates histamine release
What are the causes of high gastrin?
- prolonged acid suppression by PPI/H2 blockers
- H.pylori
- atrophic gastritis from pernicious anaemia
- SB resection
- Zollinger- Ellison syndrome
- Vagotomy
- Hypercalcaemia
- Hyperlipidaemia (artefact)
- renal failure
What do the intestinal I cells secrete? Effects?
CCK
- reduces gastric emptying
- increases enzyme fluid secretion from pancreas
- contraction of gallbladder/sphincter of oddi relaxation
What do the intestinal S cells secrete? Effects?
Secretin:
- Increases secretion of HCO3- from the pancreas
Where is VIP secreted from and what does it do?
Small intestine and pancreas.
Inhibits acid secretion
What do the D cells secrete?
Somatostatin: decreases acid and pepsin secretion by inhibiting gastrin and histamine release
What do the L cells secrete? Where are they? what is the effect?
Ileal L cells: GLP: regulates insulin release, inhibits gastric emptying, promotes satiety, slows intestinal transit.
What do the K cells secrete?
GIP (gastric inhibitory peptide): inhibits H+ and regulates insulin release.
What is the mechanism of action of PPIs?
Inhibit the H+/K+/ATPase pump
What are the indications for long term use of PPIs?
Barrett’s oesophagus
Erosive oesophagitis with strictures
Zollinger-Ellison syndrome
Scleroderma oesophagus
High risk patients on NSAIDs: Over 60, hx of PUD.
Or aspirin + concomitant use of NSAIDS, anticoagulant, SSRI, steroids
What are the potential risks/SEs of PPIs and what was an important recent study?
- HypoMg, Ca, low B12
- Infection: pneumonia, C.diff, gastroenteritis
- Cancer
- osteoporosis
- dementia
- interstitial nephritis
Important study: 2019 COMPASS trial: large RCT looking at LT safety of PPI: found only a slightly increased risk of GI infection
What is zollinger ellison syndrome, where is it found, how do you dx it and what should you consider?
Gastrin secreting tumour - 90% found in the gastrinoma triangle. Gastrin levels > 10000, a Gallium 68 DOTATATE CT-PET is very sensitive. Gold standard is a secretin provocation test.
1/3 of patients have MEN1 (AD, chromosome 11, PPP)
What effect does smoking have on chronic pancreatitis?
Smoking cessation reduces the risk of pancreatic cancer in chronic pancreatitis
What types of inherited pancreatitis are there?
- Hereditary pancreatitis
- SPINK1 mutation inherited pancreatitis
- CFTR mutation inherited pancreatitis
Hereditary pancreatitis:
- What is the mode of inheritance,
- what is the mutation?
- What are diagnostic features?
- AD, 80% penetrance
- Trypsinogen PRSS1 mutation (ch 7)
- INcreased risk of cancer, small pancreas on CT, normal amylase/lipase as not much pancreas left.
What is autoimmune pancreatitis and how is it classified?
Type 1 disease in which the pancreas is involved as part of an IgG4 systemic disease
Type 2 disease: idiopathic duct centric disease without systemic involvement
How may autoimmune pancreatitis present, how is it diagnosed and what is the treatment?
Acute, recurrent pancreatitis. May have a pancreatic mass. Pancreatic and biliary duct strictures. May be associated with retroperitoneal fibrosis.
Diagnosed on biopsy, elevated IgG4 is supportive.
Treatment: steroids. Rituximab is 2nd line.
What the different types of fluid collections associated with pancreatitis? How are they classified and how should they be managed?
< 4 weeks: acute fluid collection or acute necrotic collection
> 4 weeks: pseudocyst (no debris but does have an encapsulated wall. Or walled off necrosis.
Evidence to suggest conservative management associated with fewer complications than early surgical intervention.
If acute: wait
If pseudocyst: drain
If walled off necrosis: debride
Evidence shows that endoscopic trans gastric drainage using a metal stent has lower mortality/complications than necrosectomy.
What is ABCB4 disease?
Newly recognised cause of recurrent pancreatitis, intraheptic cholestasis of pregnancy, progressive familial intraheptic cholestasis, low phospholipid associated cholelithiasis.
Codes for multi drug resistance protein 3 (MDR3)
Which pancreatic cysts are benign and which can be premalignant?
Benign: pseudocysts and serous cystadenoma
Premalignant: MCN (mucinous cystic neoplasm), IPMN (intraductal papillary mucinous neoplasm), neuroendocrine tumour.
IPMN branches off the pancreatic duct.
MCN has ovarian like stroma histology
What are the RFs for pancreatic Ca?
Smoking
Chronic pancreatitis, CF
Genetic: BRCA1, 2, Lynch syndrome, FAMMM (Familial atypical multiple mole melanoma), hereditary pancreatitis, Peutz-Jeghers syndrome,
FHx
What are the RFs for Barrett’s oesophagus?
Male, older, smoking, reflux symptoms > 5 years, central obesity, caucasian.
What is the estimated cancer risk for Barrett’s, low grade dysplasia and high grade dysplasia?
Barrett’s: 0.2%/year
low grade dysplasia: 0.7%/year
High grade dysplasia: 7%/year
How is Barrett’s oesophagus managed?
Start on lifelong PPI (poor evidence)
If no dysplasia, endoscopy every 3-5 years
If low grade dysplasia, endoscopy + biopsy every 6 months
If high grade dysplasia, endoscopy + biopsy every 3 months +/- endoscopic ablative therapies/resection
What is the main pathophysiological mechanism of reflux?
transient relaxations of the lower oesophageal sphincter
What are the causes of low resting LES?
gastric distension, alcohol, caffeine, fat, CCK, smoking
What is the relationship between symptoms of reflux and severity of endoscopic appearance?
there is no correlation
Summarise the pathogenesis of coeliac disease
- Gluten specific CD4+ T cell pro-inflammatory response.
- CD8+ intraepithelial lymphocytes target and destroy ‘stressed’ epithelium
- CD4+ T cells help B cells produce abs to gliadin, gluten peptides and transglutaminase
What are the RFs associated with coeliac disease?
- Infection with rotavirus/pseudomonas
- female
- first degree relative
- type 1 DM
- geography
- seasonality
- high gluten intake
- HLADQ2
What are the extra intestinal manifestations of coeliac disease?
- weak tooth enamel
- osteoporosis
- AI: type 1 DM, pernicious anaemia, Addison’s, thyroid disease, alopecia
- Haematological: neutropenia, anaemia, hyposplenism, thrombocytopenia, lymphoproliferative disorders
- Neurological: peripheral neuropathy, migraines, depression
- Infertility
- GI: mouth ulcers, NAFLD, LFT abnormalities, autoimmune hepatitis, pancreatic insufficiency
How do you diagnose coeliac disease?
- Serology: either tTG-IgA abs + total IgA level
or tTG-IgA + DGP-IgG - Duodenal Biopsy (should still be on gluten): villous atrophy, crypt hyperplasia, raised intraepithelial lymphocytes
- HLADQ2/8 testing has very good negative predictive value
What possible causes are there for villous atrophy?
- coeliac
- tropical sprue/small bowel overgrowth, giardia, H.pylori
- Drugs: olmesartan, mycophenolate, NSAIDS
- CVID, Crohn’s disease, cow’s milk protein intolerance, autoimmune enteropathy
What are RFs for GORD?
+ve: age, hiatus hernia, obesity, pregnancy, asthma, scleroderma, smoking,
-ve: H.pylori
