Gastrointestinal Week 1 Flashcards
What is the general histology of the GI tract?
Mucosa:
- > Epithelium - is non-keratinised stratified squamous in the pharynx, anus and oesophagus and is simple columnar in the stomach and intestines
- > Lamina propria - connective tissue layer containing blood and lymphatic vessels
- > Muscularis mucosa - thin smooth muscle layer, produces rugae to increase SA
Submucosa:
-> submucosal plexus, connective tissue and glands
Muscularis propria/externa:
- > 3 muscles layers (inner circular, oblique and outer longitudinal)
- > myenteric plexus is inbetween circular and longitudinal layers of muscle
Serosa/adventitia:
-> connective tissue
Describe the anatomy of the stomach:
- 15-20cm long
- volume is 50ml -> 4L
- outer longitudinal, middle circular and inner oblique muscle layers
- has greater and lesser curvatures
- parts: fundus, cardia, body, pyloric antrum, pyloric canal and pyloric sphincter
- angular notch provides boundary between body and pyloric antrum
- lesser omentum = peritoneum extending from lesser curvature of stomach to the liver (contains hepatoduodenal and hepatogastric ligaments)
- greater omentum = peritoneum from the greater omentum that hangs down over the intestines
- lined with simple columnar epithelium
- there are columns of secretory cells that extend down into the lamina propria called gastric glands, which open into gastric pits
- drained by gastric, hepatic and pancreaticosplenic lymph nodes
Name 6 cell types in the stomach and their function:
- Mucous neck cell:
- > secrete mucous and bicarbonate tonically/when mucosa irritated and provide physical barrier between lumen and epithelium as well as preventing epithelial damage by buffering gastric acid. - Parietal cell:
- > Make HCl to activate pepsin and kill bacteria
- > Make intrinsic factor which complexes with vit B12 to allow its absorption - Enterochromaffin-like cell (ECL cell):
- > make histamine when stimulated by ACh/gastrin to stimulate HCl secretion - Chief cell: stimulated by acid and ACh
- > makes pepsinogen for protein digestion
- > makes gastric lipase for fat digestion - D cell:
- > releases somatostatin when there is XS acid present to reduce G cell activity and stop gastric acid secretion - G cell:
- > releases gastrin when triggered by ACh, peptides and amino acids to stimulate gastric acid secretion
Describe the arterial supply of the stomach:
- coeliac trunk has 3 branches
- > left gastric artery
- > splenic artery
- > common hepatic artery
- on lesser curvature of stomach there is a left and right gastric artery which anastomose (and corresponding veins)
- on greater curvature there is a left and right gastroepiploic artery (and corresponding veins) which anastomose
What is the innervation of the stomach?
Parasympathetic from vagus nerve
Sympathetic from coeliac ganglion beside the coeliac trunk, fibres from coeliac ganglion come from T5-9 and continue on to form the coeliac plexus
Describe gastric movements and their regulation:
- co-ordinated contractions of three muscle layers provides contraction in all orientations
- when fasting the stomach has weak contractile activity as BER occurs (smooth muscle cells undergo continuous repolarisation/depolarisation at rate of 3/min)
- when food is present, force of contractions increases but BER remains at ~3/min
- presence of food causes distension of stretch receptors in the stomach increasing BER and peristalsis
- contractions travel in waves towards pylorus and antral contents are mixed intensely
- with each peristaltic wave the pyloric sphincter opens a few mm allowing some stomach contents into duodenum (limited food passage)
- when the antrum contracts, as not all food is passed out into duodenum, retropulsion occurs which is extremely important for mixing the stomach contents even further
What three mechanisms are used to reduce gastrin production by G cells?
- circular muscle at the pyloric sphincter is 50-100x stronger than in other stomach areas, and remains constricted until all food has been mixed with chyme becoming almost fluid consistency
- ENTEROGASTRIC REFLEX: when chyme of pH 3-4 is detected in the duodenum, the D cells release somatostatin to reduce G cell activity (G cells release gastrin) and less gastric acid is produced
- when ACID is detected in the duodenum, S cells (in SI) release secretin to inhibit G cell action
- when FAT is detected in the duodenum, CCK (cholecystokinin) and GIP (gastric inhibitory polypeptide) are released to delay gastric emptying so fats are not delivered to the duodenum faster than they can be emulsified
- effects of CCK:
- > reduced gastric motility
- > increased GB contraction
- > increased pancreatic enzyme release
Where is CCK produced?
I cells of the small intestine
How is stomach acid produced?
- In the parietal cell, H2O + CO2 H2CO3 (carbonic acid) H+ and HCO3-
- H/K ATPases in the luminal membrane pump H ions out into the lumen of the stomach, and also transport K in but this diffuses out again
- As H+ is secreted out into the lumen, HCO3- is secreted to the opposite side of the parietal cell in exchange for Cl-
- The H+ and Cl- combine forming HCl = acid
How is stomach acid production controlled?
- 4 chemical messengers can bind to parietal cells:
1. Gastrin - stimulate H/K ATPase action
2. ACh - stimulate H/K ATPase action
3. Histamine - stimulate H/K ATPase action
4. Somatostatin - INHIBIT ACID PRODUCTION
What 4 factors provide defence to stomach mucosa?
Prostaglandins, mucus, mucosal blood flow and bicarbonate
What 4 factors can cause damage to stomach mucosa?
H.pylori, stomach acid, NSAIDS and pepsin
What is the pathophysiology of peptic ulcer disease?
- Peptic ulcer = break in mucosal lining of stomach/duodenum with a diameter 5mm+ that breaches the submucosa
- Peptic ulcer disease has a strong association with H.pylori infection
- H.pylori is a gram negative bacteria which resides in gastric lining deep in gastric glands
- peptic ulcers are caused by an imbalance between defence factors and damaging factors
- there are two types of peptic ulcer:
- > gastric ulcer (on stomach lining)
- > duodenal ulcer (on duodenal ulcer)
Outline how H. pylori cause peptic ulcers:
- produce the enzyme urease which converts urea into ammonium bicarbonate
- the bacteria reside in gastric glands in the pyloric antrum near D cells
- when the bacteria produce ammonia the D cells are clouded by it and cannot detect the true pH/acidic environment of the stomach
- This means the D cells have impaired somatostatin secretion and so not secrete it so G cell activity is not inhibited
- HCl production is therefore not stopped and XS gastric acid produced
- XS acid causes inflammation, mucosal damage and the tight junctions between epithelial cells can be damaged
Outline how NSAIDs cause peptic ulcers:
- block the COX pathway and inhibit the COX-1 enzyme
- COX pathway must be functioning for prostaglandin production
- prostaglandins are needed to increase and help with mucous production in the stomach
- use of NSAID’s reduces mucous production and so mucosal inflammation and damage can occur
- 50% patients taking regular NSAID’s will develop gastric mucosal damage
Name and describe 4 ways to diagnose a peptic ulcer:
- C.urea breath test
- > drink OJ to close pyloric sphincter
- > blow through straw into glass tube to obtain baseline sample
- > consume drink enriched with C-urea
- > is H.pylori bacteria are present they will break down the urea producing CO2 (14) which will increase the volume of exhaled CO2
- > measure volume of CO2 exhaled again and look for isotype C14 - Serological tests - detect IgG antibodies
- Stool antigen test - use monoclonal antibodies to detect the H.pylori antigen
- Upper GI endoscopy - to look for ulcer and also take biopsy to carry out H. pylori urease test on
- > you should order an endoscopy IMMEDIATELY is a patient is over 55yrs and has ‘alarm symptoms’
How is are peptic ulcers treated?
If due to H.pylori infection use triple therapy of PPI + 2 antibiotics
- other drugs used to protect the mucosa or provide symptomatic relief can also be used
- can use drugs for symptomatic relief e.g. alginates…
- can use H2 receptor antagonists
How do proton pump inhibitors work and give an example:
e.g. omeprazole, pantoprazole
- made with special coating to protect against stomach acid and should be taken 30mins before a meal so that they are inhibiting the proton pumps when they are most active
- diffuse into acidic microvesicles in parietal cells where acid is made
- once in the parietal cell the inhibitor drug is pronated so that is cannot leave again
- the inhibitor drug becomes concentrated at the site of the H/K ATPases
- the drug irreversibly denatures the H/K ATPase pumps so that HCl can no longer be produced
- for more stomach acid to be produced new H/K ATPases must be formed and so these drugs inhibit acid production for 24-48hrs and are more powerful and effective than H2 receptor antagonists
How do H2 receptor antagonists work and named example?
E.g. cimetidine
- bind to the histamine receptor on parietal cells preventing histamine from binding and causing an effect
- ECL cells are situated next to parietal cells and release histamine which binds to parietal cells and triggers HCl production
- they reduce gastric acid secretion by 60%
- long term tolerance can develop and their acid-inhibiting efficacy is decreased
What is a bad side effect of PPI inhibitors?
As they inhibit HCl production by parietal cells, they also inhibit intrinsic factor production. This can lead to vit B12 deficiency -> deficiency in RBC production -> pernicious anaemia
What is achalasia?
Failure of the lower oesophageal sphincter to relax in response to swallowing, food cannot enter stomach.
What is the physiology of swallowing?
3 phases:
1) Oral
- mastication occurs and then the tongue drives food into the pharynx
2) Pharyngeal
- tongue then drives food bolus into the oesophagus
3) Oesophageal
- food enters oesophagus upon relaxation of the upper oesophageal sphincter
- breathing temporarily halted and recommences on expiration
- food bolus propelled by peristalsis
- at lower oesophagus, LOS relaxes to allow food bolus to enter the stomach
- LOS then contracts to prevent reflux
Processes controlled by swallowing centre in the reticular formation of the brainstem
What is the pH of the stomach in:
a) fasted state
b) following a meal
a) pH 1-2
b) pH 3-4
What are the three phases of gastric secretion?
Cephalic
Gastric
Intestinal
