peptic ulcer disease

Question 1

peptic ulcers

Answer 1

• sore that develop in the lining of the stomach/lower oesophagus/small intestine
• ulcers can penetrate the entire wall resulting in leakage of luminal content into abdominal cavity
• more common in men than women

Question 2

peritonitis

Answer 2

• when ulcer perforation allows bacteria that live in your stomach to infect the lining of the abdomen (peritoneum)
• infection can spread into blood (sepsis) reaching other areas causing organ failure if untreated

Question 3

peptic ulceration symptoms

Answer 3

• epigastric pain (relieved by antacids)
• nocturnal pain (spasms in leg muscles when sleeping)
• vomiting

Question 4

causes of peptic ulcer disease

Answer 4

• H. pylori
• NSAIDs/steroids
• pepsin
• smoking/alcohol
• bile acids
• stress
• genetics

Question 5

mucosa

Answer 5

• lined with goblet cells that secrete alkaline mucus that forms a layer over luminal surface
• protein content and alkalinity of mucus neutralises
  H+ in the epithelium
• mucus forms a chemical barrier between acidic contents of lumen and cell surface

Question 6

defence mechanisms from body to combat ulceration

Answer 6

• mucus
• bicarbonate
• mucosal blood flow
• prostaglandins

Question 7

duodenal mucosa

Answer 7

• forms gel layer which is impermeable to acid and pepsin
• other cells secrete bicarbonate which aids in buffering acid that lies near the mucosa

Question 8

prostaglandins

Answer 8

• type E (PGE)
• increases the production of bicarbonate and the mucous layer

Question 9

H. pylori

Answer 9

• infects lower part of stomach (antrum) causing inflammation of the gastric mucosa which leads to duodenal/gastric ulcer
• resides within gastric mucosa
• high activity of the enzyme urease which enables it to colonise the stomach
• stimulates increased gastrin release thereby increased acid secretion causing direct damage to mucosa

Question 10

NSAIDs

Answer 10

• impair mucosal resistance but do not alter acid secretion
• patients with an ulcer caused by NSAID discontinue the NSAID and be given a H2 antagonist
• if patient cannot stop NSAID then PPI should be given to heal ulcer

Question 11

H. pylori mechanism of action

Answer 11

• using its flagella to burrow into mucus lining of stomach to reach epithelial cells where pH is neutral
• it adheres to the cells by producing adhesions that bind to lipids and carbohydrates in the membrane
• uses chemotaxis to avoid areas of low pH and neutralises the acid in its environment by producing large amounts of urease
• urease breaks down the urea present in the stomach to carbon dioxide and ammonia

Question 12

urea breath test

Answer 12

patients swallow capsule containing urea made from an isotope of carbon and CO2 exhaled by patients is measured for the isotope and if detected the patient is H. pylori positive

Question 13

stool antigen test (SAT)

Answer 13

enzyme immunoassay (EIA) designed to detect H. pylori in faecal specimens by measuring H. pylori antigen released from organisms lining the stomach wall as the antigen is only detected if H. pylori is present

Question 14

fundus

Answer 14

• thin walled upper portion of stomach
• secretes mucus, pepsinogen, HCl

Question 15

antrum

Answer 15

• lower part of the stomach
• thicker layer of smooth muscle responsible for mixing and grinding stomach contents
• contain endocrine cells that secrete hormone gastrin

Question 16

parietal cells

Answer 16

secrete acid and intrinsic factor

Question 17

chief cells

Answer 17

secrete pepsinogen

Question 18

gastric glands in antrum

Answer 18

• contain enterochromaffin-like cells which release paracrine agent histamine and endocrine cells called D cells which release the peptide somatostatin
• histamine binds to the H2 receptor on the parietal cell resulting in the activation of adenylyl cyclase which increases cAMP and activates protein kinase that stimulates acid secretion from the H+/K+ ATPase

Question 19

acid secretion in the stomach

Answer 19

• when parietal cells are activated by ACh/gastrin there is an increase in the intracellular Ca2+ which stimulates acid secretion from the H+/K+ ATPase (proton pump) on the canalicular surface

Question 20

chemistry of acid secretion

Answer 20

• carbonic anhydrase produces HCO3- and H+
• HCO3- is exchanged for Cl-
• Cl- diffuses into lumen
• H+ is pumped into lumen by H+/K+ ATPase

Question 21

gastric HCl

Answer 21

activates pepsinogen which breaks down peptide bonds in a process called proteolysis

Question 22

canaliculus

Answer 22

• found on gastric parietal cells
• a deep folding/channel which increases surface area for secretion

Question 23

H+/K+ ATPase (proton pump)

Answer 23

• located within cytoplasmic membrane of resting parietal cells
• translocated to the canalicular membrane and begins to pump cytoplasmic H+ into the canalicular space in exchange for extracellular K+ ions

Question 24

antacids

Answer 24

• weak alkalis
• partly neutralise free acids in stomach
• can stimulate mucosal repair mechanisms around ulcers by stimulating prostaglandin release
• used for symptomatic relief of peptic ulcer disease/GORD and non-ulcer dyspepsia

Question 25

antisecretory agents

Answer 25

- inhibit gastric acid secretion - more effective in treating peptic ulcer disease

Question 26

histamine receptor antagonists (H2)

Answer 26

- cimetidine, ranitidine, famotidine, nizatidine - competitive antagonists for histamine at H2 receptor on parietal cells - reduce acid secretion by parietal cells especially at night/fasting state - less effective at reducing food-stimulated acid secretion - treat duodenal ulcers faster than gastric ulcers

Question 27

H2 antagonists mechanism of action

Answer 27

- histamine release from enterochromaffin-like (ECL) cells by gastrin or vagal stimulation is blocked by the binding of H2 antagonists to parietal cell H2 receptor - inhibiting histamine from binding to H2 receptor thus decreasing gastric acid production

Question 28

adverse effects of H2 antagonists

Answer 28

- diarrhoea - headache/dizziness - confusion in elderly - erythema-multiforme - hepatitis (inflammation of liver) - gynaecomastia (man boobs) with cimetidine

Question 29

H2 antagonist interactions

Answer 29

- cimetidine inhibits CYP450 - cimetidine increases blood concentration of erythromycin - famotidine/ranitidine reduce plasma concentration of atazanavir

Question 30

proton pump inhibitors (PPIs)

Answer 30

- omeprazole, lansoprazole, pantoprazole, esomeprazole - irreversible inhibitors of the H+/K+ ATPase pump - bind covalently via disulphate bond - most effective when taken around meal times as they only bind to active pumps - acid production is inhibited 90% for 24 hrs by a single dose

Question 31

adverse effects of PPIs

Answer 31

- epigastric discomfort - nausea - vomiting - diarrhoea - headache - skin rashes - arthralgia/paraesthesia - gynaecomastia - gastric atrophy (thinning of inner lining of stomach)

Question 32

PPI interactions

Answer 32

- omeprazole has stimulatory/inhibitory effects on CYP450 enzyme system in liver - omeprazole also inhibits the hepatic metabolism of diazepam/phenytoin/warfarin - esomeprazole/omeprazole decreases antiplatelet effect of clopidogrel - pantoprazole may increase anticoagulant effect of warfarin

Question 33

patients with peptic ulcer disease and tested positive for H. pylori triple therapy:

Answer 33

- PPI - amoxicillin - clarithromycin or metronidazole patients with penicillin allergy: - PPI - clarithromycin - metronidazole

Question 34

misoprostol

Answer 34

- synthetic prostaglandin E analogue - inhibitory effect on acid secretion - enhances secretion of bicarbonate - can be used to heal ulcers but used prophylactically to prevent NSAID induced ulceration - avoid in pregnancy as induces abortion

Question 35

zollinger-ellison syndrome

Answer 35

- rare disorder that causes gastric/duodenal ulcers (usually multiple) as well as jejunum - due to gastrin secreting tumour in the pancreas/duodenum that stimulates acid secretion in stomach

Question 36

gastro-oesophageal reflux disease (GORD)

Answer 36

- lower oesophageal sphincter relaxes inappropriately at times other than during swallowing which allows an excessive reflux of gastric contents into oesophagus - symptoms: retrosternal burning (heartburn)

Question 37

barretts oesophagus

Answer 37

- commonly diagnosed in patients with long term GORD - replacement of normal stratified squamous epithelium lining of the oesophagus by columnar epithelium with goblet cells - can lead to oesophageal adenocarcinoma (cancer)