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Block 1 > Gastric Motility and Secretions and Drugs > Flashcards

Gastric Motility and Secretions and Drugs Flashcards

1
Q

What are the 5 functions of the stomach?

A

To store food

To minimise ingestion of bacteria

To dissolve and partially digest the macromolecules in food

To regulate the rate at which the contents of the stomach empty into the small intestine

To secrete intrinsic factor

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2
Q

What is the one indispensable function of the stomach?

A

To secrete intrinsic factor

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3
Q

Gastric motility allows the stomach to:

A

Serve as a reservoir for large volumes of food

Fragment food and mix it with gastric secretions

Empty gastric contents into the duodenum at a controlled rate

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4
Q

Name the 3 divisions of the stomach

A

Fundus

Body

Antrum

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5
Q

What are the four layers of the stomach, from the lumen outwards?

A

Mucosa

Submucosa

Muscularis

Serosa

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6
Q

In which layer of the stomach do the enteric neurons lie?

A

Submucosa

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7
Q

Name the three layers of the mucosa, from the lumen outwards

A

Epithelium
Lamina propria
Muscularis mucosae

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8
Q

When the stomach is empty, which 2 layers are folded and what are they called?

A

The mucosa and submucosa are folded into rugae

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9
Q

Name the 2 plexus found in the enteric nervous system.

A

Myenteric plexus

Submucosal plexus

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10
Q

Where does the enteric nervous system get input from?

A

Autonomic nervous system:

Parasympathetic

  • vagus nerves
  • pelvic nerves (sacral spinal cord)

Sympathetic postganglionic fibres

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11
Q

In which layer of the stomach/GI tract is the submucosal plexus found in?

A

Submucosa

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12
Q

In which layer of the stomach/GI tract is the myenteric plexus found?

A

Muscularis

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13
Q

Outline the 3 stages of receptive relaxation of the stomach

A

It is mediated by the vagus nerve (CN X)

CN X coordinates with the enteric nerve plexuses

Enteric neurons release (NO) and serotonin, which relax the smooth muscle of the stomach

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14
Q

What 2 chemicals do the enteric neurons release to mediate receptive relaxation?

A

Nitric oxide (NO)

Serotonin

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15
Q

Describe the peristaltic wave movements in the stomach

A

Begin in the body and move towards the antrum

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16
Q

What is retropulsion?

A

When strong peristaltic movements force food towards the antrum of the stomach, closing the pyloric sphincter. This then forces food backwards towards the body of the stomach

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17
Q

Define peristalsis

A

Waves of alternating contractions and relaxations of smooth muscle layers

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18
Q

Define segmentation

A

Cycles of contraction that mix contents but do not push them in any one direction.

Aims to mix gastric contents with secretions

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19
Q

What 2 types of electrical activity start contractions in the GI tract?

A

Slow waves

Action potentials

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20
Q

What is the basic electrical rhythm of the GI tract?

A

When smooth muscle cells undergo spontaneous cycles of depolarisation and repolarisation (spontaneous movement of Na+)

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21
Q

What is the rate of gastric slow waves?

A

3 per minute

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22
Q

Where is the rhythm of gastric slow waves generated?

A

In the pacemaker zone in the body of the stomach

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23
Q

What are slow waves?

A

Fluctuations in membrane potential spreading to adjacent sections of muscle

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24
Q

Describe the relationship between slow waves and action potentials

A

They do not elicit contractions, but coordinate them by controlling the appearance of action potentials.

They set the rate of contractions by controlling action potentials

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25
Q

Action potentials elicit ___

A

Muscle contraction

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26
Q

What determines the strength of a muscle contraction?

A

The number of action potentials appearing at the peak of a slow wave

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27
Q

Why is it important to regulate gastric emptying?

A

It allows for optimal digestion and absorption of ingested material

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28
Q

What is the pyloric sphincter?

A

A ring of smooth muscle and connective tissue between the gastric antrum and the duodenum

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29
Q

What are the 2 functions of the pyloric sphincter?

A

Allows regulated gastric emptying at a rate consistent with the ability for the duodenum to process it

To prevent regurgitation of duodenal contents into the stomach

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30
Q

What do sympathetic nerves do to the pyloric sphincter?

A

Increase constriction of it

fight or flight, ANS

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31
Q

What do vagal (parasympathetic) nerves do to the pyloric sphincter?

A

Can be excitatory or inhibitory

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32
Q

What hormones act on the pyloric sphincter?

A

Gastrin

Cholecystokinin (CCK)

Gastric inhibitory peptide (GIP)

Secretin

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33
Q

What do hormones do to the pyloric sphincter?

A

Constrict it

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34
Q

What 3 things decrease the rate of gastric emptying?

A

High fat

Low pH

Hypertonic solution

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35
Q

What can the duodenum and jejunum detect in chime?

Where are these receptors found?

Why is this useful?

A

Acidity

Osmotic pressure

Fats

Amino acids

Peptides

Mucosae of the duodenum and jejunum

The receptors cause the release of intestinal hormones, which inhibt antral contractions and/or elicit constricting the pyloric sphincter, decreasing the rate of gastric emptying

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36
Q

What are the four main components of gastric secretion?

A

Hydrochloric acid (HCl)

Mucus

Enzymes

Intrinsic factor

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37
Q

Where is gastric juice secreted from?

A

Gastric glands of the gastric mucosa

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38
Q

What 2 types of enzyme does the stomach secrete?

A

Pepsinogens

Gastric lipase

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39
Q

Name the 5 major cell types found in the mucosa of the stomach in gastric glands

A

Surface mucus cell

Mucous neck cell

Parietal cell

Chief cell

G cell

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40
Q

What does the parietal cell secrete

A

HCl

Intrinsic factor

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41
Q

Which type of cell secretes HCl and intrinsic factor?

A

Parietal cell

42
Q

What do chief cells secrete?

A

Pepsinogen

43
Q

What type of cell secretes pepsinogen?

A

Chief cells

44
Q

What do G cells secrete?

A

Gastrin

45
Q

What type of cell secretes gastrin?

A

G cell

46
Q

Where are parietal cells (HCl, IF) found?

A

Proximal 80% of the stomach

47
Q

What does the body of the stomach secrete?

A

Mucus

Pepsinogen

HCl

48
Q

What does the antrum of the stomach secrete?

A

Mucus

Pepsinogen

Gastrin

49
Q

Where are G cells found?

A

In the antrum of the stomach

50
Q

Where are gastric hormones secreted from?

A

Gastric glands

51
Q

What is the purpose of gastric hormones?

A

To control the secretion of gastric juice

52
Q

What are the 3 gastric hormones?

A

Gastrin

Histamine

Somatostatin

53
Q

Which of the 3 gastric hormones has a paracrine effect?

A

Histamine

54
Q

Name the 3 gastric effects of gastrin

A

Stimulates secretion of acid, pepsinogen, mucus, HCO3-

Stimulation of gastric motility

Inhibition of gastric emptying

55
Q

Name the 3 GI wide effects of gastrin

A

Stimulation of pancreatic enzyme and HCO3- secretion

Stimulation of insulin release

Stimulation of intestinal motility

56
Q

Which cells secrete histamine?

A

Enterochromaffin-like (ECL) cells

57
Q

Name the 2 gastric effects of histamine

A

Stimulation of acid secretion

Increased local blood flow to support the increase in metabolism

58
Q

Which cells secrete somatostatin?

A

D cells

59
Q

Where are D cells found?

A

Antrum and body of the stomach

60
Q

What are the 2 gastric effects of somatostatin?

A

Inhibition of gastrin release

Inhibition of acid secretion

61
Q

What is the average gastric luminal pH?

A

pH 1-2

62
Q

How much HCl does the stomach secrete per day?

A

2-3 litres

63
Q

Describe the shape and structure of a parietal cell

A

Truncated pyramidal shape, apex towards lumen

Invaginations of the luminal membrane (canaliculi), membranes lined with ion pumps

High mitochondrial content

64
Q

Why is a parietal cell’s structure related to it’s function

A

High mitochondrial content = lots of ATP for ion pumps to push acid into stomach

Large surface area to secrete HCl

65
Q

What are the 4 stages of acid secretion by the parietal cell?

A
  1. H+ and HCO3- are produced from CO2 and H2O
  2. H+ is pumped into lumen by H+/K+ ATPase pump
  3. HCO3- moves out of basolateral membrane in antiport with Cl-
  4. Cl- passively diffuses into the lumen via Cl- channel
66
Q

Which enzyme converts CO2 and H2O into H2CO3 (carbonic acid)?

A

Carbonic anhydrase

67
Q

What 3 things stimulate acid secretion?

A

Gastrin

Acetylcholine

Histamine

68
Q

What 3 things inhibit acid secretion?

A

Somatostatin

Prostaglandins E2 and I2

Intestinal hormones

69
Q

DIAGRAM:

Draw out the relationship between an ECL cell, parietal cell, with muscarinic, gastrin, and H2 receptors

A

Slide 44 of gastric motility lecture

70
Q

What 5 receptors does a parietal cell have on its surface and what hormones act on those receptors?

A

Muscarinic receptor - ACh

H2 receptor - Histamine

Gastrin receptor - Gastrine

Somatostatin receptor - somatostain (inhibitory)

PGE2 receptor - prostaglandin E2

71
Q

What is the name given to the H+/K+ ATPase pump on the parietal cell?

A

Proton pump

72
Q

Which 2 cells does ACh act on?

A

ECL cell (increase histamine –> parietal cell)

Parietal cell (direct acid stimulation)

73
Q

Give 3 functions of somatostatin

A

Inhibit gastrin (stops stimulation of ECL and parietal cell)

Inhibit the action of the parietal cell (slow production of HCl)

Inhibit the action of the ECL cell (inhibit histamine production –> less stimulation of parietal cell to produce HVl)

74
Q

Give 3 symptoms and 3 complications of reflux oesophagitis

A

Heartburn
Regurgitation
Haematemesis

Oesophageal ulceration
Peptic stricture
Barrett’s oesophagus

75
Q

What are prostaglandins?

A

A group of lipids derived from arachidonic acid

76
Q

Mucus is a mixture of..

A

Glycoproteins and glycopolysaccharides

77
Q

What is the gastric mucosal barrier?

A

Mucus and alkaline secretions entrapped within it

78
Q

What converts pepsinogen to pepsin?

A

A low pH environment

79
Q

Pepsin is used to accelerate…

A

Protein digestion

80
Q

What is the oxyntic gland area?

A

The proximal 80% of the stomach that secretes HCl (parietal cells found here)

81
Q

What is the pyloric gland area?

A

The antrum of the stomach that produces gastrin (G cells) near the pyloric sphincter

82
Q

Which cell does PGE2 have its affect on?

A

Parietal cell - inhibits acid secretion

83
Q

Local irritation of the mucosa stimulates….

What effect does this have?

A

The production of prostaglandins (PGs)

Increase production of mucus and HCO3-
Inhibit acid secretion

The stimulation of acid secretion also promotes mucus and HCO3- secretion

84
Q

Intrinsic factor is a..

A

Glycoprotein

85
Q

Which cells in the stomach secrete HCO3-?

A

Gastric surface epithelial cells

86
Q

What 3 types of drugs are used to treat disorders of acid secretion?

A

Antacids and alginates

Histamine H2 receptor antagonists

Proton pump inhibitors

87
Q

Describe how NSAIDs impair the renewal of the gastric mucosal barrier

A

NSAIDs inhibit the enzyme COX - COX converts arachidonic acid into prostaglandins

Prostaglandins inhibit acid production from parietal cells and stimulate gastric mucus production

If prostaglandins are inhibited, they impair the renewal of the gastric mucosal barrier –> less mucus production, more acid production

88
Q

Give the names of 2 antacids

What is their MoA?

A

Aluminium hydroxide and magnesium hydroxide

Calcium carbonate and magnesium carbonate

They are a bases which buffer gastric acid, raising the gastric pH

89
Q

Give the name of an alginate.

What is its MoA?

A

Sodium alginate, sodium bicarbonate, calcium carbonate

Anionic polysaccharides that form a viscous gel upon binding with water

Increases viscosity of the stomach contents and protects the oesophageal mucosa from acid reflux.

The gel floats on the surface of the stomach contents

90
Q

Give the name of 2 histamine H2-receptor antagonists

What is their MoA?

A

Ranitidine
Cimetidine

Competitively inhibit histamine actions at H2-receptors

91
Q

What does cimetidine inhibit?

A

P450 enzymes

92
Q

Give the name of 2 proton pump inhibitors

What is their MoA?

A

Omeprazole
Lansoprazole

Irreversibly inhibit the H+/K+ ATPase pump.

Inactive at neutral pH

Accumulate in secretory canaliculi of parietal cells

93
Q

Why does increasing the dose of a PPI disproportionally increase the plasma concentrations of the drug?

A

Given orally as enteric-coated capsules

Increasing the dose leads to a less acidic environment, which means more of the enteric coating survives through the stomach

More is then available

94
Q

What is reflux oesophagitis?

A

Inflammation of the lower oesophagus produces by persistent episodes of reflux

95
Q

What is the prescribed drug of choice for reflux oesophagitis?

A

PPIs

96
Q

Where are the majority of peptic ulcers found?

A

Duodenum

97
Q

Which artery is at risk of damage in a duodenal peptic ulcer?

A

Gastroduodenal artery

98
Q

How can GI-adverse affects be reduced in NSAID prescriptions?

A

Alternative drug

Lowest dose, shortest duration

Avoid concomitant NSAIDs

Frequent review

Co-prescription of PPIs in increased risk patients

99
Q

Helicobacter pylori is gram…..

A

Negative

100
Q

Which bacteria is responsible for 80% of peptic ulcers?

A

H. pylori

Gram-negative bacterial infection

101
Q

How does H. pylori produce peptic ulcers?

A

Produces and secretes urease, which breaks urea into CO2 and NH3 (imonia)

NH3 neutralises gastric acid

H pylori then penetrates mucus barrier, facilitating acid penetration to the epithelial cells causing damage = ulcer

102
Q

What is achlorhydria/hypochlorhydria?

What is it caused by?

What are the consequences?

A

Absence/deficiency of hydrochloric acid in gastric juice

Iatrogenic (drugs)
Atrophy of gastric mucosa (age)

Impaired ability to digest and absorb iron + B vitamins
Increased vulnerability of GI tract to infection

Block 1 (13 decks)

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