Physiology 17

Question 1

What is intrinsic factor?

Answer 1

• Glycoprotein
• Secreted by parietal cells into gastric lumen
• Essential for absorption of vit B12, binding it in the stomach and protecting it from destruction in the GI tract
• IF-B12 complex absorbed in the terminal ileum

Question 2

What is the most likely cause of anaemia post-gastrectomy?

Answer 2

IDA due to impaired absorption from loss of acidic environment

B12 deficiency due to lack of IF also relevant, but above is main driver

Question 3

What is pepsin?

Answer 3

• Collection of proteolytic enzymes facilitating protein digestion
• Stored as inactive precursor, pepsinogen in membrane-bound zymogen granules in chief cells
• Activated in acidic environ of stomach (maximal activity at pH <3
• Act by hydrolysing peptide bonds producing polypeptides and amino acids

Question 4

What factors stimulate release of pepsin?

Answer 4

• Vagal stimulation
• low gastric pH
• Gastrin
• β stimulation

Question 5

Where is gastric mucus produced?

Answer 5

• Gastric mucus neck cells

- Surface epithelial cells

Question 6

How thick is the gastric mucus layer?

Answer 6

200 um

Question 7

What factors stimulate gastric mucus production?

Answer 7

• Vagal stimulation
• Gastrin
• PGE2/PGI2 (synthesised within mucosa)

Question 8

What are the components of the gastric ‘mucosal barrier?’

Answer 8

• Alkaline mucus

- Tight junctions between epithelial cells

Question 9

Through what mechanism does H. pylori cause gastric ulcers?

Answer 9

H. pylori infection is associated with sustained gastrin release, which increases acid production and reduces the pH gradient between the gastric lumen and mucosa, causing ulceration.

Question 10

What are the physiological effects of gastrin?

Answer 10

• Increased gastric acid secretion
• Release of gastric enzymes and mucus
• Increases gut motility
• Regulates mucosal growth
• Unclear effect on gastric emptying and pyloric sphincter

Question 11

How does the secretion and composition of gastric juice vary in the fed state?

Answer 11

3 phases:

1. Cephalic (30%)
   - Anticipation of food
   - Mediated by efferent vagal stimulation
   - Causes increased gastric motility, juice secretion and release of gastrin and histamine
2. Gastric (60%)
   - Arrival of food into stomach
   - Initiated by gastric distension -> vagal reflex and stimulation of gastrin release due to antral peptide and amino acid detection
   - Self-limiting (~30 mins) due to inhibition of gastrin production when pH <2 and by release of somatostatin by D cells.
3. Intestinal (10%)
   - Arrival of chyme into duodemun
   - Initial increase in gastrin production due to duodenal stretch
   - Subsequent reduction in gastric secretion due to duodenal production of secretin (by S cells)

Question 12

What are the main functions of secretin with regard to digestion?

Answer 12

1. Reduction of duodenal pH through:
   - Stimulation of pancreatic secretion
   - Increasing somatostatin release
   - Inhibiting gastrin release
   - Directly downregulating parietal cell acid secretion
2. Triggering increased insulin release in response to increasing glycaemia

Question 13

Summarise the absorptive capacity of the stomach

Answer 13

Little absorption

Notable exceptions:

• Alcohol (due to lipid solubility)
• Aspirin (due to pKa 3.5 -> mostly unionised in stomach lumen)

Question 14

What are the main drivers of physiological gastric emptying?

Answer 14

• In general, rate of emptying is proportional to stomach volume
• This is due to vagal reflexes increasing antral pump activity in response to gastric distension
• Rate also affected by food particle size

Question 15

What is the difference in gastric transit time between clear fluid and solid food?

Answer 15

Clear fluid: 95% in 1 hour

Solid meal: 50% in 2 hours

Question 16

What methods can be used to measure gastric emptying?

Answer 16

• Paracetamol absorption (none absorbed in stomach)
• Ultrasound studies
• Applied potential tomography
• Scintigraphy

Question 17

What factors increase gastric emptying?

Answer 17

• Stomach distension
• Cholinergics / anticholinesterases
• Small particle size of gastric contents
• Prokinetic drugs

Question 18

What factors delay gastric emptying?

Answer 18

• Duodenal distension
• Antimuscarinics
• Duodenal chyme high in [H+], fat, protein or osmolality
• Sympathetic stimulation
• Opioids
• Alcohol

Question 19

Explain how the contents of duodenal chyme influence gastric emptying

Answer 19

Low pH - secretin release
High fat - CCK release
High protein - Gastrin release (though effect on emptying contested)
Hypertonia - osmoreceptor reflex

Question 20

Outline the phases of swallowing

Answer 20

1. Voluntary movement of food bolus to back of mouth by tongue
2. Sensory receptor reflex from tonsillar pillars initiate involuntary phase. This begins with lifting of the soft palate to occlude access to the nasal cavity and formation of a ‘sagittal slit’ through which food passes to the posterior pharynx
3. Vocal cords are adducted and larynx is drawn anteriorly and cephalad, widening the upper oesophagus. Epiglottis swings over closed glottis. Upper oesophageal sphincter relaxes.
4. Enlargement of upper oesophagus initiates peristaltic wave which is propagated down the oesophagus

Question 21

How is swallowing coordinated?

Answer 21

By swallowing centre in reticular substance of the medulla and lower pons. The swallowing centre inhibits the respiratory centre, preventing respiration during swallowing.

Question 22

How long does a co-ordinated swallowing sequence last?

Answer 22

1-2 seconds

Question 23

How is oesophageal barrier pressure defined?

Answer 23

OBP = LOSP - GP

LOSP - Lower oesophageal sphincter pressure
GP - Gastric pressure

Question 24

Describe the reflex arc involved in regulating LOS tone

Answer 24

-Spinal and vagal sensory afferents -> NTS -> vagal motor nucleus

Question 25

What are the substances involved in LOS relaxation?

Answer 25

NO ATP? VIP? CO?

Question 26

What anaesthetic factors affect oesophageal barrier pressure?

Answer 26

Reduce OBP: - LMA - Cricoid pressure in awake patient - Volatile anaesthesia - N2O - Thiopental No effect: - Propofol - Remi - NMBs (except vecuronium and pancuronium) Increase OBP: -Vec- / Pancuronium

Question 27

What is the overall incidence of PONV following elective surgery without prophylaxis?

Answer 27

33%

Question 28

Contrast vomiting and regurgitation

Answer 28

Vomiting: Active, forceful, coordinated expulsion of GI contents from the mouth Regurgitation: Passive, effortless flow of undigested stomach contents back into oesophagus

Question 29

Summarise the vomiting reflex

Answer 29

Two phases: Pre-ejection phase: - Gastric relaxation - Retrograde peristalsis - Airway protective reflexes immediately preceding ejection (deep inspiratory breath, elevation of larynx + hyoid, opening of upper oesophageal sphincter, closure of glottis, elevation of soft palate) Ejection phase: - Contraction of abdominal and diaphragmatic muscles - Retrograde oesophageal contraction - Crural relaxation - Dilatation of upper oesophageal sphincter

Question 30

What evidence is there to suggest that nausea and vomiting have at least partially separate mechanisms?

Answer 30

- Nausea is harder to treat than vomiting - Some situations (eg. raised ICP, radiotherapy, pregnancy) can cause vomiting without nausea - Vomiting is attenuated post-vagotomy but nausea can still occur - Sensation of nausea requires involvement of higher (conscious) centres in CNS

Question 31

List the main pathways for stimulation of nausea and vomiting

Answer 31

1. Toxins in GI lumen 2. Toxins in bloodstream 3. GI/visceral pathology 4. CNS stimuli 5. Vestibulocochlear disturbance

Question 32

What is the mechanism of N&V stimulation by toxins in the gut lumen?

Answer 32

Enterochromaffin (EC) cells in the gut mucosa release paracrine intermediates - 5-HT - Substance P - CCK 5-HT3 receptors in the gut are coupled to Na+ channels, causing vagal afferent activity 5-HT3 receptors also found in NTS and CTZ

Question 33

What is the mechanism of N&V stimulation by toxinaemia?

Answer 33

Mediated by CTZ (area postrema) CTZ expresses many receptors including 5-HT3, dopamine receptors and neurokinin-1 (substance P receptor)

Question 34

Where is the CTZ found?

Answer 34

- Circumventricular organ | - Midline brainstem structure found in the dorsal medulla, at the caudal border of the 4th ventricle

Question 35

What is the mechanism of N&V stimulation by GI or visceral pathology?

Answer 35

Not well understood, varied May include obstruction, cardiac vagal afferents stimulation and renal failure (azotaemia?)

Question 36

What is the mechanism of N&V stimulation by CNS stimuli?

Answer 36

- Not usually associated with nausea - Poorly understood - Include emotional stimuli eg. fear, anticipation and physical stimuli eg. brain trauma and raised ICP

Question 37

What is the mechanism of N&V stimulation by vestibulocochlear disturbance?

Answer 37

- Thought to modulate sensitivity of brainstem to emetogenic stimuli - Afferents to vomiting centre involve ACh and H1 receptors

Question 38

Classify the dopamine receptor subtypes and their actions

Answer 38

D1-5 D1-like (D1, D5) - Adenylate cyclase stimulation D2-like (D2, D3, D4) - Adenylate cyclase inhibition

Question 39

How are dopamine receptors implicated in N&V?

Answer 39

D2 receptors clearly linked with N&V | D3 receptors may evoke vomiting or facilitate vomiting induced by D2Rs

Question 40

Where is the vomiting centre found?

Answer 40

- No clearly defined area | - Consists of neural network in NTS

Question 41

List the risk factors for PONV

Answer 41

Patient-specific / anaesthetic / surgical Patient-specific: - Female sex - Non-smokers - History of PONV/motion sickness Anaesthetic: - Use of volatiles - N20 - Perioperative opioid use Surgical: - Prolonged surgery - Specific procedures (laparoscopy/laparotomy, ENT, neurosurgery, breast, strabismus, plastics)

Question 42

How are children affected by PONV?

Answer 42

<2 years - rare >3 years - incidence 40% No difference between sexes prior to puberty

Question 43

What are some important complications of PONV?

Answer 43

Surgical site: - Wound dehiscence - Anastomotic breakdown Poor analgesia, patient distress Aspiration Electrolyte disturbances

Question 44

Which induction agents are implicated in PONV?

Answer 44

All but propofol

Question 45

What receptor subtypes are involved in N&V

Answer 45

``` D2/3 H1 M3/5 5-HT3 NK1 ```