GORD Flashcards

1
Q

outline 6 mechanisms of gastric protection

A
  1. pH gradient
    -mucus cells secrete bicarbonate + mucus in response to vagal stimulation + fundic distention
  2. Surfactant like substances
    -Prevents water soluble substances from reaching and damaging the gastric epithelium
  3. Non-protein sulfhydryls
    -Bind free radicals to prevent damage.
  4. Rapid cell turnover
    - Quick cell turn over (5-7 days)
  5. Mucosal blood flow of sub-epithelium
    - Supplies oxygen + nutrients to epithelium
    -disposes of hydrogen ions + noxious agents
  6. Prostaglandins
    - maintain blood flow
    -prevent vascular endothelial injury caused by ethanol
    - has direct cytoprotective effects.
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2
Q

what is a normal stomach acid pH?

A

1.5 to 3.5

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3
Q

Outline how acid is produced ?

A

HCL is produced by parietal cells.

*Intracellular CO2 + H2O -> H2CO3 (by carbonic anhydrase)
*H2CO3 spontaneously dissociates -> H+ + HCO3-
* H+ is transported to gastric lumen via H+/K+ ATPase pump on apical end.
*HCO3- is pumped into blood on basolateral end by anion exchanger- exchanged for Cl-
*Cl- then transported out the apical end into lumen to combine with H+ to form HCL

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4
Q

Name 3 PPI’s, outline MOA and 2 ways that make them better than antacids/alginates

A

Omeprazole, Esomeprazole, Pantoprazole

MOA:
-> Absorbed from small intestine into general circulation
-> Concentrates in secretory canaliculi of gastric parietal cells where it is activated.
->IRREVERSIBLY binds to the H+/K+ ATPase pump on the luminal end of parietal cell, via covalent bond on cysteine residue of pump.
-> prevents the release of H+ into gastric lumen.

  1. This is the final common step in acid production so H+ stopped regardless of means by which it was stimulated to be released.
  2. Irreversible bond means that the parietal cell must make a new pump from scratch before it can counteract the PPI affect.
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5
Q

4 adverse affects of PPI use and 1 drug interaction

A
  1. Hypomagnesemia
  2. Reduced Vit B12 absorption (due to raised pH)
  3. Increased fracture risk in hip, wrist, spine
  4. C-diff
  5. Community acquired pneumonia.

Drug interaction:
*Clopidogrel -> clopidogrel is activated by CYP2C19
-> PPI’s can inhibit CYP2C19 thereby reducing metabolism of clopidogrel; reducing its systemic effects.

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6
Q

Outline 3 direct and 2 indirect routes of increasing acid production

A

Direct:
(1) Ach -> M3 receptors (mediated by vagus)
(2) G cells -> Gastrin -> CCK receptor
-> Both receptors are Gq PCR
-> results in activation of IP3
-> increases intracellular Calcium
-> H+/K+ ATPase pump out H+

(2) Histamine
->Enterochromaffin cells release histamine ->H2 receptors.
-> Gs PCR
-> activation of adenylyl cyclase
-> activation of cAMP
-> H+/K+ ATPase activation

Indirect:

(1) Gastrin -> ECL cells -> Histamine
(2) Gastrin releasing peptide -> G cells -> Gastrin

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7
Q

3 routes of gastric acid reduction

A

(1) Prostaglandins E2 + I2
-> inhibit cAMP
-> stimulates mucus production
-> dilates mucosal blood vessels.

(2) Somatostatin
-D cells -> somatostatin -> SST2 receptor
-> inhibits cAMP
-> inhibits G cells + ECL cells.

(3) Chyme in duodenum
-> Triggers enterogastric reflex
-> sends inhibitory signals to reduce vagal stimulation of acid production

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8
Q

list the 3 phases of gastric acid secretion and the mediators involved in each phase

A

(1) Cephalic
-> Ach from vagus

(2) Gastric
-> Ach (vagus)
-> Gastrin (G cells)
-> Histamine (ECL cells)

(3) Intestinal
-> Cholecystokinin (I cells)
-> Secretin (S cells)
-> Gastric inhibitory peptide (K cells)
-> Somatostatin (D cells)

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9
Q

How does cholecystokinin, Secretin, Gastric inhibitory pepitide and somatostatin function in intestinal phase of gastric acid secretion

A

These function during the intestinal phase of acid secretion

(1) Cholecystokinin (I cells)
-> Released from I cells
-> stimulates release of bile + digestive enzymes from pancreas + gall bladder

(2) Secretin (S cells)
-> Released from S cells of duodenum
-> stimulates water + bicarb release from pancreas to neutralise contents of duodenum
-> stimulates somatostatin release which in turn reduces H+ release by inhibiting cAMP, gastrin and histamine release

(3) GIP (K cells)
-> Inhibits gastrin release

(4) Somatostatin (D cells)
-> inhibits G + ECL cells
-> inhibits cAMP

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10
Q

How do NSAIDs contribute to ulcer formation

Outline 3 ways to reduce ulcer risk with NSAIDS

A

Inhibition of COX-1 mainly.
-> Inhibits PGE2 and PGI2 formation
-> PGE2 functions to inhibit gastric acid secretion + stimulates mucosal secretion.
-> PGI2 reduces acid secretion and contributes to mucosal blood flow.

-> reduction in these will result in reduced mucosal protection, increased acid production and vasoconstriction leading to mucosal injury and ulcer formation.

Reduce risk by:
(1) Use COX-2 selective NSAID - will better maintain PGE2
(2) Replace lost PGE with PGE analogue such as Misoprostol
(3) Co-prescribe a PPI

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11
Q

What type of bacteria is H-pylori.
List 3 regions in the GI tract where it is most commonly found.
What percentage of people with gastric/duodenal ulcers have H-pylori?

A

Gram negative, spiral shaped bacillus

Found in:
Antrum
Cardia
Gastric-type mucosa of barretts esophagus

Gastric 80%
Duodenal 95%

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12
Q

What are the factors that permit colonisation with H.pylori? (SUM-ACE)

What is the toxin produced by h.pylori? What does it do to stomach lining?

A

(1) Spiral shape and flagellated
-> motile

(2) Urease activity
-> Can generate ammonium to buffer acid
-> Hydrogenase allows for it to use H2 produced in stomach as an energy source
-> Oxidase for neutralising ROS produced against it

(3) Micro-aerophilic
-> can survive in low O2 environments in mucosa

(4) Adhesins
-> attachment to epithelial cells

(5) Evasion of immune response
-> LPS somewhat resembles glycans of normal cells
-> mucosal layer more immunologically priviledged.

Toxin produced is CAG-A
-> Triggers release of pro-inflammatory cytokines
-> Can precipitate ulceration/cancer development by dysregulating cell-signalling, proliferation, apoptosis, adhesions and polarity.

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13
Q

What is the triple therapy course for Hpylori eradication?

A

Clarithromycin 500mg every 12 hours
Amoxicillin 1g every 12 hours
PPI every 12 hours

for two weeks.

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14
Q

How does the breath test work for H.pylori?

List 3 other diagnostic tests

A

C-urea is given orally
Hydrolysed by urease
Labelled CO2 is expired and detected.

  1. Oesophago-gastro-duodenoscopy with biopsy (antral biopsy)
  2. Antibody serology tests
  3. Fecal antigen test
  4. Gram culture + Staining (warthin-silver)
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15
Q

List 5 factors for peptic ulcer

A
  1. NSAIDS
  2. H-pylori
  3. First degree relative with PUD
  4. Smoking
  5. Alcohol
  6. Zollinger-ellison disease (gastrinoma)
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16
Q

To what dermatomes will stomach pain be referred?

A

T5-T9 dermatomes

Visceral afferents travel back within sympathetic fibres and synapse on second-order neurons of T5-T9 dermatomes

17
Q

What artery is most at risk by erosion of a duodenal ulcer? From what artery is it branching from?

A

Gastro-duodenal from the common hepatic artery

18
Q

Define barrett’s oesophagus and outline what epithelial change is seen.

A

Barrett’s oesophagus is a metaplastic change in the distal oesophagus due to prolonged exposure to gastric acid. It is visible of endoscopy and confirmed as intestinal-type columnar epithelium on biopsy.

Non-keratinized stratified squamous -> non-cilliated columnar with goblet cells.

19
Q

How is barrett’s oesophagus subclassified? What percentage of those with GORD will develop barrett’s?

A

Subclassified based on the distance the metaplasia extends beyond the squamo-columnar junction (Z line)

(1) Short segment
<3 cm beyond Z
0.07 % chance of malignant progression

(2) Long segment
>3cm beyond
0.25% chance of malignant progression

10% GORD -> Barretts

20
Q

What does Atypia mean? List 3 things that can cause it

A

Atypia refers to cells that are abnormal in terms of colour, shape, size when compared to normal healthy cells in the same location.

Causes:
(1) Infection
(2) inflammation
(3) Radiation
(4) Pre-cancerous diseases.

21
Q

What 2 types of cancers can arise in esophagus? Which one is most common overall and which one is assoc with barretts? What part of esophagus are they most commonly found?

A

Adenocarcinoma - barretts - distal third
Squamous cell carcinoma - most common - prox 2/3rd.

22
Q

Define dysplasia

A

Dysplasia refers to the abnormal growth and proliferation of cells in response to a stimulus. It is considered non-neoplastic and can regress once stimulus is removed. However, it can progress to neoplasia.

Outcomes:
Regression
Persistance
Progression to neoplasia

23
Q

Briefly describe the pattern of motility that moves food through the oesophagus.

A
  • Primary peristalsis moves food through the esophagus. It involves co-ordinated contraction of circular and longitudinal layers of the muscularis region.
  • Stretching of pharynx increases the afferent activity from the myenteric plexus. This results in contraction of the proximal esophagus through increased firing of efferent motor innervatiton -> Ach and substance P.
  • Relaxation distal to the bolus is achieved through reduced motor activity, increased nitric oxide and increased VIP.
  • Receptive relaxation of the lower esophageal sphincter and orad region of the somach is achieved through VIP from the vagus nerve.