Gastric Secretions Flashcards
Which 5 substances are secreted in the saliva?
Amylase Lysozymes Bicarbonate Growth factors Haptocorrin transcobalamin-1
How do the saliva secretions help vitamin B12 to be absorbed?
B12 binds to Haptocorrin proteins produced in the salivary glands
What is the role of haptocorrin transcobalamin-1?
It is a chaperone that binds to and chaperones cobalamin (vitamin B12)
What substances are included in the gastric secretions?
Mucus Acid (HCl) Pepsinogen Chymosin (rennin) Lipase Intrinsic factor
Where are intrinsic factors secreted from and what do they do?
Secreted from parietal cells
Glycoprotein - binds vitamin B12 in intestine for absorption
Summarise vitamin B12 absorption in the GI tract.
- Bind to Haptocorrin proteins produced in the salivary glands
- Must be complexed with stomach derived intrinsic pathway
- Absorbed in the terminal ileum
- Transported in portal circulation and transferred to transcobalamin II (TC-II/B12)
What are the four types of gastric epithelial cells and what are their functions?
Surface mucus cell (secrete mucus, trefoil peptides (associated with mucus), bicarbonate
Mucus neck cell (stem cell compartment)
Parietal cell (secrete acid, intrinsic factor)
ECL cell (secrete histamine)
Chief cell (pepsinogen, chymosin, lipase)
Where is the proton pump in the parietal cell? How does it work?
- The proton pump is located on the apical membrane of the parietal cell
- Driven by the energy released by ATP
- Electroneutral- K+ goes the other way
- Crystal structure determined in 2018
Where are the parietal cells located? What do they do upon stimulation?
- Parietal cells located at base of gastric pits
- Insert H+-ATPase Pump into membrane on stimulation
What is the first stage in the normal absorptive process for proteins?
- 1- ‘luminal phase’ Begins in the stomach with the action of pepsin. In the stomach, chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the gastric pits.
What is the function of the surface mucus cell?
Secrete mucus, trefoil peptides (associated with mucus), bicarbonate
Why is mucus so important in acid control? What can this be disrupted by?
- Without mucus the acid would interact with the cells directly
o Pain/injury - Mucus cells secrete mucus and bicarbonate to prevent the local low pH from damaging stomach lining
- Mucus layer therefore crucial as
o Physical barrier; gel layer
o Chemical barrier; bicarbonate - This can be disrupted by Stress/chemicals/alcohol/NSAIDS
What happens in Zollinger-Ellison syndrome in relation to gastrin?
- Zollinger-Ellison syndrome (ZES):
- Ectopic secretion of gastrin by a neuroendocrine tumor (gastrinoma derived from G cells)
- Tumours secrete excess gastrin
- Leads to gastric acid hypersecretion
- Results in severe gastroesophageal peptic ulcer disease
- Usually present in the duodenum
What is the physiologic and pathologic role of gastrin?
- Under physiologic conditions gastrin is released from antrum G cells in response to food, decreased acid, and gastric distension.
- Gastrin circulates in the peripheral blood and binds to parietal and ECL cells of the body.
- The ECL cells release histamine, which activates the H2 receptors on parietal cells and HCl (H+) is released.
What are the important anatomical features to prevent gastric reflux?
o A viable lower oesophageal sphincter which normally seals off the stomach from the oesophagus.
o The angle at which the oesophagus enters the stomach.
o The presence of the terminal portion of the oesophagus inside the abdominal cavity.
o Contraction of the crural diaphragm exerts a ‘pinchcock‘ action at the terminal oesophagus.
What is GORD? How prevalent is it? What is it caused by?
- GORD (or GERD) = a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications
- 10-20% of population- someone you know has this
- Caused by:
o Excessive reflux of normal gastric juice (increased frequency of Transient Lower Oesophageal Sphincter Relaxations)
o Weakened lower oesophageal sphincter
o Hiatal hernia
o Hypersensitivity of oesophageal pain sensing nerves
o Can be caused by bile and non-acid components of gastric juice
What are the medical options for treating GORD?
- Not excessive HCl secretion!
- All mitigated by PPIs
- TLOSRs reduced by neurological drugs – e.g. baclofen
What are examples of proton pump inhibitors (PPIs)?
Dexlansoprazole Esomeprazole Lansoprazole Omeoprazole Immediate-release omeprazole, with sodium bicarbonate Pantoprazole Rabeprazole Worth $10bn/year
What are some of the different treatment options for reducing effect of acid in GORD?
Antacids (neutralises)
PPIs (inhibits)
H2RAs (blocks)
NSAIDs (blocks)
Which GORD treatment has been recalled and why?
Ranitidine
- The recall is a precautionary measure due to possible contamination of the active substance in Zantac, ranitidine, with an impurity called NDMA (N-nitrosodimethylamine) which has been identified as a risk factor in the development of certain cancers.
What are the 2 active ingredients in Gaviscon? How does it work?
Sodium alginate* & Potassium hydrogen carbonate
o * Formation of protective raft over acid pocket
Why can NSAIDs have a negative effect on GORD? How can this be addressed?
- NSAIDS can have negative effect on managing acid in the stomach, so PPIs may be needed to be taken by the patient as well
What are the surgical options for GORD patients?
- Fundoplication: standard surgical treatment for GORD.
o Tightens and reinforces the LOS.
o The upper part of the stomach is wrapped around the outside of the lower oesophagus to strengthen the sphincter. - 2 types:
o Laparoscopic Nissen fundoplication
o LINX® magnetic anti-reflux device
What are the self-help options for GORD?
- Eat smaller and more frequent meals, rather than 3 large meals a day –
- Avoid anything that triggers symptoms – common triggers include coffee, chocolate, tomatoes, alcohol, and fatty or spicy food.
- Raise the head of the bed
- Relaxation – stress can make heartburn and GORD worse (learning relaxation techniques may help)
- Maintain a healthy weight
- Stop smoking – smoke can irritate the digestive system and may make symptoms worse.
What is helicobacter pylori? Why is it significant? What pathology can it contribute to, and which other factors are also involved? How does it cause this pathology?
- > 50% of world population infected with this bacteria
- Can survive in the duodenum and stomach
- Major cause of peptic ulcer (up to 20%), combined with: stress, smoking, alcohol, NSAIDs
- 4 stages:
o Tunnel through mucus layer
o Secrete ammonia to neutralise pH
o Recruit more H pylori
o Mucosal damage
What is present at a low level in gastric juices?
Urea
How can helicobacter pylori be diagnosed? Who discovered it?
o Urea breath test: urea C13 is given to patient and H. Pylori converts urea C13 to ammonia (NH3) + C13O2
o CLO test (Campylobacter-like organism test): biopsy placed in media with urea and pH indicator conversion of urea to ammonia raises pH ( if H. pylori present), which changes the colour of pH indicator.
o Blood antibody test: antibodies to H. Pylori
o Stool antigen test (H. Pylori proteins)
- Nobel prize 2005- Warren and Marshall
- Bacteria kept over the Easter weekend allowed
o Identification of the slow growing organism
- Marshall drank broth, got gastritis, treated himself with antibiotics
What are the treatment options for peptic ulcer disease?
- Vagotomy (surgery): truncal/highly selective (no longer performed)
o Reduces ACh secretion from enteric neurones
o Reduce acid secretion - Histamine (H2) antagonists: cimetidine, ranitidine, famotidine
o Block H2 receptors on parietal cell
o Reduce acid secretion - Proton pump inhibitors: omeprazole
o Prevent H+/K+ ATPase on parietal cell
o Reduce acid secretion - Antibiotics: e.g. Amoxycillin + Clarithomycin
o Kill H Pylori bacteria
o Eradicate infection - Triple therapy (2 antibiotics and 1 proton pump inhibitor) used for treatment of H pylori
