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Gastric physiology Flashcards

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1
Q

Functions of the stomach

A
  • Store and mix food
  • Dissolve & continue digestion
  • Regulate emptying into the duodenum
  • Kill microbes
  • Secrete protease
  • Secrete intrinsic factor
  • Activate proteases
  • Lubrication
  • Mucosal protection
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2
Q

Key cell types of the stomach

A
  • Mucous cells: produce mucous, at entrance to gland
  • Parietal cells: produce gastric acid and intrinsic factor
  • Chief cells: produce pepsinogen
  • Enterochromaffin-like (ECL) cell: releases histamine
  • G cells: release gastrin
  • D cells: release somatostatin
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3
Q

How are the tubule glands of the stomach formed

A

The epithelial layer lining the stomach invaginates into the mucosa, forming many tubular glands

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4
Q

Glands in the thin walled upper portions of the body of the stomach secrete

A

mucous, hydrochloric acid (parietal cells) and the enzyme precursor pepsinogen (chief cells)

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5
Q

The lower portion of the stomach, the antrum has a much thicker layer of smooth muscle and is responsible for what

what do the glands here do

A

mixing and griffin the stomach contents - the glands in this region of the stomach secrete little acid but contain the endocrine cells that secrete the hormone gastrin (G cells)

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6
Q

What cells secrete gastric acid and how much

A

Occurs from parietal cells

•Hydrochloric acid: very strong, pH 2, [H+] > 150mM, approximately 2 litres/day

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7
Q

what happens to H2O in the parietal cells

A

H2O in the parietal cell breaks down into OH- and H+

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8
Q

GASTRIC ACID SECRETION 1

what is the origin of H+ IONS

A

CO2

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9
Q

GASTRIC ACID SECRETION 2

CO2 & H2O from respiration are converted into what

via what enzyme

A

bicarbonate (H2CO3) via the enzyme carbonic anhydrase

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10
Q

GASTRIC ACID SECRETION 3

what happens to the bicarbonate converted by carbonic anhydrase

and why

A

As seen in the respiratory notes, H2CO3 rapidly disassociates into HCO3- and H+

The H+ ions produced can then react with the OH- ions from the breakdown of H2O to regenerate H2O

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11
Q

GASTRIC ACID SECRETION 4

The H+ ions from the break down of H2O are then pumped into where via what

A

The H+ ions from the break down of H2O are then pumped into the stomach lumen via H+/K+ ATPase pumps in the luminal membrane of parietal cells,

they pump 1 K+ ion into the parietal cell for every 1 H+ ion they pump out into the stomach (so as to ensure there is no change in polarity of the cell) - these pumps require ATP to function

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12
Q

GASTRIC ACID SECRETION 5

What happens to the K+ ions pumped into the stomach lumen by the H+/K+ ATPase pumps

A

The K+ ions pumped in can then diffuse back out into the stomach via K+ channels on the plasma membrane of parietal cells

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13
Q

GASTRIC ACID SECRETION 6

what happens to the The HCO3- from the breakdown of H2CO3

A

The HCO3- from the breakdown of H2CO3 is secreted into the capillary for the exchange of Cl- ions

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14
Q

GASTRIC ACID SECRETION 7

What then happens to the Cl- ions

A

Cl- ions can then enter the stomach by diffusing through Cl- channels in the plasma membrane of the parietal cell

Then in the stomach, the H+ ions and Cl- ions can react to form HCl

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15
Q

GASTRIC ACID SECRETION 8

Removal of the end products of this reaction cause what

A

Removal of the end products of this reaction enhance the forward rate of reaction - in this way production and secretion of H+ are coupled

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16
Q

GASTRIC ACID SECRETION 9

Increased acid secretion stimulated by the factors mentioned below, cause what

A

results from the migration of H+/K+ - ATPase protein in the membranes membranes of intracellular vesicles in the parietal cell to the plasma membrane by fusion of these vesicles with the membrane thereby increasing the number of pump protein in the plasma membrane meaning more H+ can be pumped in = more acid

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17
Q

What causes gastric acid secretion to turn on (3)

A

Cephalic phase
Gastric phase
protein in the stomach

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18
Q

What is the cephalic phase
how is it initiated
and by what

A

during a meal
Parasympathetic nervous system
Initiated by the sight, smell, taste of food and chewing

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19
Q

What happens during the cephalic phase that causes gastric acid secretion

A
  • Acetyl choline is released
  • ACh acts indirectly on parietal cells, triggering the release of GASTRIN (from G cells in the pyloric antrum of stomach) & HISTAMINE (from enterochromaffin-like (ECL) cells)
  • Both gastrin & histamine increase the number of H+/K+-ATPase pumps on the plasma membrane of the parietal cell
  • Net effect = increased acid production
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20
Q

What is the gastric phase and what triggers it

A

once food has reached stomach

•Initiated by; gastric distension from the volume of ingested material & the presence of peptides and amino acids (released by the digestion of luminal proteins)

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21
Q

What does ACh cause

A

ACh acts indirectly on parietal cells, triggering the release of GASTRIN (from G cells in the pyloric antrum of stomach) & HISTAMINE (from enterochromaffin-like (ECL) cells)

  • Both gastrin & histamine increase the number of H+/K+-ATPase pumps on the plasma membrane of the parietal cell
  • Net effect = increased acid production
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22
Q

What happens during gastric phase that causes gastric acid secretion

A
  • Gastrin is released which acts directly on parietal cells
  • Gastrin also triggers the release of histamine which also acts directly on the parietal cells
  • Both gastrin & histamine increase the number of H+/K+-ATPase pumps on the plasma membrane of the parietal cell
  • Net effect = increased acid production

•NOTE: it can be deduced that histamine is really important since it mediates the effects of gastrin and acetylcholine - thus can be a good therapeutic target for e.g. acid overproduction etc.

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23
Q

How does protein in the stomach cause gastric acid secretion

A
  • Direct stimulus for gastrin release (as seen above)
  • Proteins of foods in the lumen, act as a buffer thereby reducing the amount of H+ ions = increase in pH : resulting in the decreased secretion of somatostatin (see below) which results in more parietal cell activity resulting in more acid production
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24
Q

What causes gastric secretion to switch off

A

gastric phase

Intestinal phase

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25
How does the gastric phase turn off gastric secretion
Low luminal pH (high [H+]) directly inhibits gastrin secretion thereby indirectly inhibiting histamine release •Low pH also stimulates SOMATOSTATIN release which inhibits parietal cell activity
26
Where is the intestinal phase and what triggers it
in the duodenum: •Initiated by; duodenal distension, low pH, hypertonic solutions, the presence of amino acids & fatty acids
27
How does the intestinal phase cause gastric secretion to stop
Initiated by; duodenal distension, low pH, hypertonic solutions, the presence of amino acids & fatty acids * These all trigger the release of a locally produced chemical messengers called enterogastrones such as SECRETIN (inhibits gastrin release & promotessomatostatin release) & CHOLECYSTOKININ (CKK)•They also trigger short & long neural pathways which reduce ACh release * Net effect = reduced acid secretion
28
so in summary what regulates gastric acid secretion
Regulation of gastric acid secretion is controlled by the brain, stomach & duodenum
29
What is involved in gastric acid secretion
* 1 parasympathetic neurotransmitter - ACh (+) * 1 hormone - gastrin (+) * 2 paracrine (produced in stomach) - histamine (+) & somatostatin (-) * 2 key enterogastrones - secretin (-) & CCK (-)
30
What Neurotransmitter is used in gastric acid secretion
1 parasympathetic neurotransmitter - ACh (+)
31
What hormone is used in gastric secretion
1 hormone - gastrin (+)
32
What paracrine is used in gastric secretion
2 paracrine (produced in stomach) - histamine (+) & somatostatin (-)
33
What enterogastrones are used in gastric secretion
2 key enterogastrones - secretin (-) & CCK (-)
34
What is a peptic ulcer
An ulcer is a breach in a mucosal surface
35
Cause sof peptic ulcers
- Helicobacter pylori infection - most common: - Drugs - NSAIDS e.g. aspirin and ibuprofen - Chemical irritants: alcohol, bile salts (secreted into duodenum but can reflux into stomach and wash way protective mucous lining) - Gastrinoma - rare
36
What is helicobacter pylori and how does it cause peptic ulcers
Lives in gastric mucus •Secretes urease, splitting urea into CO2 and ammonia •Ammonia + H+ = ammonium •Ammonium is toxic to gastric mucosa resulting in less mucous produced •Secreted proteases, phospholipase & vacuolating cytotoxin A can then begin attacking the gastric epithelium further reducing mucous production •Results in an inflammatory response and less mucosal defence
37
What is the treatment for H pylori caused ulcer
Treatment: eradicate organism using triple therapy;proton pump inhibitor (inhibits pump pumping H+ ions into stomach lumen thereby increasing gastric pH making conditions inhospitable for helicobacter pylori) & antibiotics (clarithromycin, amoxicillin, tetracycline & metronidazole)
38
What drugs cause peptic ulcers and how
Drugs - NSAIDS e.g. aspirin and ibuprofen: •NSAIDS - non-steroidal anti-inflammatory drugs * Mucous secretion is stimulated by prostaglandins (in inflamed tissue, prostaglandin triggers inflammatory response thus inhibition = less inflammation) * Cyclo-oxygenase 1 is needed for prostaglandin synthesis * NSAIDS inhibitcylclo-oxygenase 1 * Thus reduced mucosal defence
39
How to treat NSAID caused peptic ulcer
use prostaglandin analogues (mimic effect of prostaglandins) e.g. misoprostol and reduce acid secretion
40
How can chemical irritants cause peptic ulcers
alcohol, bile salts (secreted into duodenum but can reflux into stomach and wash way protective mucous lining) Duodenal-gastric reflux causes bile to enter stomach, alkaline bile strips away gastric mucous layer of stomach resulting in reduced mucosal defence
41
What is a gastrinoma and how does it cause peptic ulcer
rare tumours of parietal cells = excessive gastrin release = increase in gastric acid = increased attack on gastric mucosa = ulcer
42
How do proton pump inhibitors reduce gastric acid secretion
inhibit pumps pumping H+ into stomach lumen, they only block pumpsNOT the activators e.g. gastrin, examples include; omeprazole, lansoprazole & esomeprazole (all have varied side effects)
43
How do H2 receptor agonists prevent gastric acid secretion
block receptors for histamine thereby reducing acid secretion, examples include; cimetidine & ranitidine
44
What are the protective mechanisms the mucosa have to protect against gastric acid
* Alkaline mucus on luminal surface * Tight junctions between epithelial cells * Replacement of damaged cells - stem cells at the base of pits to produce new cells * Feedback loops
45
what produced pepsinogen
chief cells
46
how is pepsin stored and secreted and why
Pepsin is secreted as an inactive zymogen (pepsinogen) - it is stored this way to prevent it digesting the chief cells and the rest of the body
47
how is pepsinogen mediated
Pepsinogen is mediated by input from the enteric nervous system via neurotransmitter ACh (parasympathetic)
48
what is the pepsinogens secretion like
Secretion parallels HCl secretion
49
what happens when pepsinogen is released into the stomach lumen
When pepsinogen is released into the stomach lumen the low pH (generated by HCL) of the stomach activates a rapid autocatalytic process in which pepsin is produce from pepsinogen
50
what happens when some pepsin is produced
Once some pepsin is prodcued, it can be used to produce more since it can aid in the cleavage of pepsinogen - positive feedback
51
what pH is the most effect for the activated of pepsin from pepsinogen
pH < 2
52
what inactivated pepsin
HCO3- released in the duodenumirreversibly inactivates pepsin
53
what happens to protein digestion if the stomach is removed
Not essential - protein digestion can occur if the stomach is removed, HOWEVER if removed then no vitamin B-12 absorption can occur in the small intestine since the stomachparietal cells produce intrinsic factor - essential for vitamin B-12absorption in the small intestine
54
whats the role of pepsin in protein digestion
Accelerates protein digestion
55
how much of protein digestion does pepsin account for
Normally accounts for 20% of total protein digestion
56
how does pepsin help digest protein
Breaks down collagen in meat thereby helping shred meat resulting in smaller pieces with greater surface area for digestion
57
whats the empty volume of the stomach
Empty stomach has volume of around 50ml
58
how much can full stomach take
When eating it can accommodate roughly 1.5L with little increase in luminal pressure
59
how can the stomach accommodate 1.5L of food
It does this by the smooth muscles in the body & fundus receptive relaxation
60
how does the parasympathetic nervous system mediate receptive relaxation
-Mediated by parasympathetic nervous system acting on the enteric nerve plexuses with coordination provided by afferent input from the stomach via the vagus nerveand by the swallowing centre in the brain
61
What causes receptive relaxation in the stomach
- Nitric oxide and serotonin released by the enteric nerves mediate relaxation - Acetyl choline activates parietal & chief cells & initiates receptive relaxation
62
What does the stomach do when food arrives and how
As in the oesophagus the stomach produces peristaltic waves in response to the arriving food Each wave begins in the body of the stomach producing a ripple as it proceeds towards the antrum
63
What is wrong with the intimal contraction of the stomach
The initial contraction in the body is too weak to produce much mixing of luminal contents with acid and pepsin There are more powerful contractions in the antrum which enables better mixing of the luminal contents
64
what happens to the pyloric sphincter when the peristaltic waves reach it
The pyloric sphincter closes as peristalticwaves reach it
65
what is the pyloric sphincter
a ring of smooth muscle and connective tissue between the atrium and duodenum
66
what does the peristaltic wave cause
This contraction, every time a wave reaches it means little chyme (smooth, somewhat orange coloured liquid = the end result of stomach digestion and peristalsis) enters the duodenum -It also means that the antralcontents are forced back towards the body meaning there is more mixing and thus digestion
67
What determines the frequency of pacemaker cells
The frequency of peristaltic waves are determined by pacemaker cells (INTERSTITIAL CELLS OF CAJAL) in the muscular propria (longitudinal smooth muscle layer) and is constant (3 every minute)
68
What do pacemaker cells undergo
slowdepolarisation-repolarisation cycles
69
how is depolarisation transmitted to the smooth muscle cells of the stomach
The depolarisation waves are transmitted through gap junctions to adjacent smooth muscle cells
70
Do the smooth muscle cells of the stomach cause contractions when the stomach is empty
These cells do not cause significant contraction in the empty stomach
71
What causes the strength of the peristaltic waves to vary
* Excitatory neurotransmitters and hormonesfurther depolarise membranes * Action potentials are generated when the threshold is reached * The interstitial cells of cajal are activeall the time, but the action potential threshold for muscle contraction can be altered by the entericnervous system
72
What is the strength of the contractions increased by
* Gastrin | * Gastric distension (mediated by mechanoreceptors)
73
What is the strength of the contractions decreased by
* Duodenal distension * Increase in duodenal fat * Increase in duodenal osmolarity * Decrease in duodenal pH * Increase in sympathetic nervous system stimulation * Decrease in parasympathetic nervous system stimulation
74
capacity of stomach is more than duodenum what happens if it becomes overfilled
The capacity of the stomach is greater than that of the duodenum, the overfilling of the duodenum by a hypertonic solution results in dumping syndrome; vomiting, bloating, cramps, diarrhoea, dizziness, fatigue, weakness, sweating & electrolyte imbalances
75
what happens to duodenal pH when food enter
pH falls
76
what regulates gastric emptying
regulated by the same things that regulates parietal & chief cells
77
what is gastroparesis
delayed gastric emptying
78
causes of gastroparesis
- Idiopathic (cause unknown) - Autonomic neuropathies e.g. diabetes mellitus - Abdominal surgery - Parkinsons disease - Multiple sclerosis - Scleroderma (connective tissue disorder) - Amyloidosis - Female gender (more common in women)
79
what can gastroparesis cause
Gastroparesis can cause matter in the stomach to rot and smell and become a similar appearance to faeces
80
`symptoms of gastroparesis
Early satiety (feeling full early) - Vomiting undigested food - GORD (gastro-oesophageal reflux disease - can be caused by; PREGNANCY, HIATUS HERNIA (when stomach goes above oesophagus), OBESITY & SMOKING) - NOTE: a sedentary lifestyle does not increase the risk of acid reflux-Abdominal pain/bloating-Anorexia (loss of appetite)
81
what drugs cause gastroparesis
- H2 receptor antagonists - Proton pump inhibitors - Opiod analgesics - Diphenhydramine (Benadryl) - Beta-adrenergic receptor agonists - Calcium channel blockers - Levodopa (Parkinson's drug)
82
What is the most abundant substance in chyme
water
83
Around 8000ml of ingested & secreted water enters the small intestine each day what happens to most of it and where does it go
Around 8000ml of ingested & secreted water enters the small intestine each day but only around 1500mL passes on into the large intestine since 80% of water reabsorption occurs in the small intestine
84
what part of the small intestine absorbs most of the water
jejunum
85
only a small amount of water is absorbed in the stomach, why is this
Small amounts of water are reabsorbed in the stomach, but the stomach has a much smallersurface area available for diffusion and lacks the solute-absorbing mechanisms that create the osmotic-gradient necessary for absorbing water
86
how much of overall water is excreted in stools
Around 98% of the fluid load is reabsorbed, with only around 200ml (2%) being excreted in stools
87
when does net water diffusion occur in the small intestine
The epithelial membranes of the small intestine are very permeable to water, and net water diffusion occur across the epithelium whenever a water concentration difference is established by the active absorption of solutes
88
what is the most abundantly absorbed solute in the small intestine
Na+ accounts for most of the actively transported solutes because it constitutes the most abundant solute in chyme - it is actively transported from the lumen in the cell membranes of the ileum & jejunum Luminal membrane transport is variably coupledglucose, amino acids or other substances
89
Why is Na+ actively transported from the lumen causing water to follow in the colon
The contents are iso-osmotic (concentration in lumen of colon = that of blood) in the colon so Na+ is actively pumped from the lumen and water follows
90
how is potassium reabsorbed in the colon
In general K+ reabsorption is by passive diffusion, the net movement begin determined by the potential difference between the lumen and intestinal capillaries. Note: Diarrhoea can result in severe hypokalaemia (loss of K+)
91
How is Cl- reabsorbed in the colon
Cl- is actively reabsorbed in exchange for bicarbonate - resulting in the intestinal contents becoming more alkaline

GI (7 decks)

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