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Gastric Acid Secretion Flashcards

1
Q

What does fundus + body secrete?

A

pepsinogen, mucus, acid

gland here contain parietal cells (oxyntic cells) secrete HCl + intrinsic factor

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2
Q

Describe anatomy of stomach

A

-Pyloric area has mucus secreting cells
-Antrum thick muscular structure + secreted mucus, pepsinogen, gastrin
-Body contains chief cells secreting pepsinogen +
parietal cells(oxyntic cells) release intrinsic factor for vit B12 absorption.
-Angle of his angle of fundus

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3
Q

Contents of gastric juice (in fasting state)?

A
  • Cations: Na+, K+, Mg2+, H+ (pH 3)
  • Anions: Cl- , HPO4 2-, SO4 2-
  • Pepsins (zynogin inactive) HCl activate it
  • Lipase
  • Mucus
  • Intrinsic factor

Gastric juice adds 2.5L/day to intestinal contents

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4
Q

Features of upper portion of stomach?

A
  • Thin-walled (fundus + body)
  • Secretes mucus, HCl, pepsinogen (exocrine secretions of stomach)
  • Body has epithelial cells with tubular glands
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5
Q

Features of lower portion of stomach?

A
  • Antrum : ↓HCl secretion, but ↑gastrin secretion
  • Pylorus : wall of glands lined with parietal cells which release HCl + intrinsic factor
  • Gastrin
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6
Q

Role of gastrin?

A

increases acid secretion but needs to bind to its receptor

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7
Q

Role of enterochromaffin-like cells (ECL)?

A

secrete paracrine agents eg histamine acting via H2 receptors

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8
Q

Features of gastric mucosa?

A
  • Stomach call contains gastric mucosa contains gastric pits
  • Pit base are gastric glands whose chief cells create gastric juice - mucous fluid containing digestive enzymes, parietal cells which secrete HCl + intrinsic factor
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9
Q

Describe how gastric acid made in stomach lumen?

A
  • CO2 diffuses in
  • CO2 + H2O -> carbonic acid
  • carbonic acid dissociates -> bicarbonate + proton
  • bicarbonate exchanged for Cl- in blood
  • decreases acidity of venous blood from stomach
  • excess Cl- diffuses into stomach via chloride channels as H+ pumped into stomach lumen via K+/H+ ATPase
  • pumps H+ into stomach lumen
  • H+ and Cl- out of parietal cell –> stomach lumen
  • forms HCl (2L of HCl/day at 150mM)
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10
Q

What drives formation of gastric acid?

A

Histamine - H2 via CAMP
Ach- M3 via Gq
Gastrin - CCK receptors

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11
Q

Role of fundal glands?

A

secrete into pits (pepsinogen inactive enzyme that’s needs activated to pepsin)

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12
Q

Role of histamine?

A

mediates acid secretion, pepsinogen promotes protein breakdown

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13
Q

Why’s blood draining from stomach more alkaline than blood serving it (alkaline tide)?

A
  • [HCO3-] increases
  • HCO3- leaves basal cell membrane into capillary blood
  • so blood draining from stomach is more alkaline
  • Cl- shift : HCO3- exchanged for Cl-
  • ATP binds to K+/H+ ATPase to counter transport of K+ in and H+ out into gastric gland
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14
Q

Why does cell make components of HCl separately?

A

HCl damaging

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15
Q

Factors responsible for HCl secretion?

A

histamine, ACh, gastrin
secretin neutralises
somatostatin blocks HCl secretion

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16
Q

Features of trefoil peptides?

A

Trefoil factor 1is a protein found in humans encoded by the TFF1 gene (pS2gene)

  • Stable secretory proteins expressed in GI mucosa
  • Protect mucosa from insults, stabilise mucus layer, effect healing of epithelium
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17
Q

Role of pepsin?

A

liberate fat of food by dissolving fibrous framework round its globules, prepares it for digestion by lipases in duodenum

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18
Q

What are non-parietal secretions?

A

contain resting juice = plasma; but alkaline, pH 7.4; ↑HCO3-

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19
Q

Role of mucus?

A

thick sticky, ↑HCO3-, forms water-insoluble gel on epithelial surface to protect stomach epithelial cells from the H+

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20
Q

Role of intrinsic factor?

A

prevents pernicious anaemia via absorption of vit B12

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21
Q

Role of HCl?

A
  • Kills bacteria
  • Acid denaturation of digested food
  • Activates pepsinogen -> pepsin (for protein digestion)
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22
Q

Role of HCl?

A
  • Kills bacteria
  • Acid denaturation of digested food
  • Activates pepsinogen -> pepsin (for protein digestion)
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23
Q

Features of rennin (chymosin)?

A
  • Proteolytic enzyme synthesised by chief cells
  • rennin produced in large amounts after birth
  • production decreases + replaced by pepsin
  • coagulation + curdling of milk
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24
Q

Phases vital within enteric nervous system?

A

1 Cephalic phase
2 Gastric phase
3 Intestinal phases

Things that influence gastic secretion!
So all this is pushing HCl secretion, so what is turning it off? Some of the
enterogastrins (duodenal hormones are important in this, because we need to
modulate release, so we don’t damage our gut)

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25
Q

Phases vital within enteric nervous system?

A

1 Cephalic phase
2 Gastric phase
3 Intestinal phases

Things that influence gastic secretion!
So all this is pushing HCl secretion, so what is turning it off? Some of the

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26
Q

How do neuronal pathways + enetrogasterones regulate HCl secretion?

A
  • Directly = acting on parietal cells to increase acid secretion
  • Indirectly = influencing secretion of gastrin + histamine to increase acid secretion
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27
Q

Role of enterogastrins?

A

duodenal hormones modulate release, so we don’t damage our gut

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28
Q

Describe cephalic phase

A
  • smelling, seeing (tasting or chewing) food
  • Ach release stimulates histamine release from ECL cells
  • Ach acts directly on parietal cells to increase HCl secretion
  • G-cells activated to release gastrin acting on ECL cells
  • release histamine
  • stimulates parietal cells to release HCl
  • D cells release somatostatin
  • inhibits ECL + G cells to curtail hypersecretion of HCl
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29
Q

Role of D cells?

A

HCl stimulating somatosatin releasing cells (D-cells). These
release somatostatin.
Somatostatin inhibits ECL and G cells to curtail hypersecretion of acid.

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30
Q

Role of D cells?

A

=HCl stimulating somatosatin releasing cells

release somatostatin to inhibit ECL + G cells to curtail hypersecretion of acid

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31
Q

Describe gastric phase

A
  • distension of stomach from food
  • stimulates neurones
  • protein (peptide conc goes up) stimulates acid release
  • lower pH
  • distention also stimulates enteric nervous system
  • release more Ach to : stimulate HCl release from parietal cells (acts on ECL + G-cells)
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32
Q

Effect of proteins of luminal acidity

A
  • peptides in food are buffer of acid
  • increase [H+ ] to prevent stimulation of D cells
  • prevent somatostatin release
  • more acid secretion occurs
  • peptides also directly stimulate Gcells to release gastrin
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33
Q

Summary of proteins

A

-Acidity of stomach lumen increases before meal
-More proteins increases peptides in stomach (increases
gastrin secretion)
-Effects of protein on luminal acididity (protein acts as buffer)
-H+ and proteins decreases [H+] so remove inhibitory
powers of HCl on gastrin secretion - aid acid secretion
-Meal of proteins elicits feedback inhibitory + stimulatory signals - increase acid secretion via stimulation of gastrin secretion

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34
Q

Summary of during cephalic + gastric phase

A

-increased para stimulation :
↑ histamine secretion
↑ gastrin secretion
act directly on the parietal cells to increase acid secretion- inhibit gastrin secretion, so no hypersecretion
-Luminal distension stimulate gastrin secretion - removes inhibitory effect of somatostatin
(patient with GORD ate lots of protein –> worse)

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35
Q

Describe intestinal phase

A

-high acidity of duodenal contents
-reflex inhibits acid secretion (cause increased acidity inhibits digestive enzymes, bicarbonate, bile salts)
-distension of duodenum
-hypertonic solution, AA, FA, monosaccharides inhibit
acid secretion
-enterogastrones reduce acid secretion
-inhibition of acid secretion depends on composition of chyme (hyperosmolar, containing AA) + volume of chyme

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36
Q

Role of intestinal phase?

A

balance secretory activity of stomach, digestive + absorptive capacities of small intestine

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37
Q

What’s osmolality?

A

=measures of how much substance has dissolved in another substance
-↑osmolarity = greater conc of substance dissolved

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38
Q

What’s GLP-1?

A

intestinal incretin, intact vagal innervation needed for it to work

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39
Q

What’s GIP?

A

gastrin-inhibitory peptide or glucose dependent-insulinotropic peptide; worked on denervated stomach, so unknown role

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40
Q

Effect of chyme in duodenum?

A

intestinal phase stimuli activate negative feedback mechanisms to reduce acid secretion + prevent chyme from becoming too acidic

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41
Q

How’s acid secretion inhibited during intestinal phase?

A

-Short neuronal reflex (within enteric system)
-Long neuronal (vagal) reflexes + enterogastrones eg secretin, CCK inhibit acid secretion by the parietal
cells or gastrin secretion by G cells - inhibited by somatostatin (stomach, intestine, delta cells of pancreas, hypothalamus, brainstem, hippocampus)

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42
Q

Features of long neural reflexes?

A
  • Increase sympathetic (inhibitory) discharge
  • Decrease para discharge: stimulatory of intestinal phase which decreases acid secretion so chyme not too acidic
  • Decrease contractions (NO + VIP involved)
  • Use neurons that link CNS to gut
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43
Q

Feature of short neural reflex?

A

Operate as enteric nervous system

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44
Q

Effect of histamine, ACh, gastrin binding to their receptors on parietal cells?

A

↑↑HCl secretion

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45
Q

Direct pathway?

A

Ach, gastrin, histamine stimulate parietal cell triggering H+ secretion into lumen

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46
Q

Indirect pathway?

A

Ach, gastrin stimulate ECL (Enterochromaffin-like cells) which stimulate histamine secretion then histamine acts on parietal cell

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47
Q

Describe what happens when parietal cell is stimulated

A
  • H-K pumps extrude H+into the lumen of gastric gland in exchange for K+
  • K+recycles back into lumen via K+channels
  • carbonic anhydrase (CA) provides H+ extruded by H-K pump
  • exits via basolateral anion exchanger (AE2)
  • Cl−enters across basolateral membrane via AE2
  • Na/K/Cl cotransporter NKCC1 + electrogenic SLC26A7
  • Cl−exits via apical CFTR (+ ClC) channels
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48
Q

Describe receptors + signal-transduction pathways in parietal cell

A

-stimulation of acid secretion by ACh, gastrin, histamine
-mediated by series of intracellular signal-transduction
-all 3 bind to specific G receptors on parietal membrane
-ACh bind to M3 coupled to Gαq
-gastrin bind to CCK2 coupled to Gαq
-activation of PLC
-activation of PKC
-release of Ca2+
-histamine bind to H2receptor, coupled to Gαs
-adenylyl cyclase (AC) → cAMP -> PKA
-inhibitors : somatostatin + prostaglandins (eg PGE2) bind to separate receptors coupled to Gαi on ER
-AChbinds to M3on parietal basolateral membrane
-coupled to Gαq
-activates PLC
-converts PIP2-> IP3 + DAG :
*IP3causes internal stores to release Ca2+, acts via calmodulin-dependent protein kinase
*DAG activates PKC
*M3receptor also activates Ca2+channel
-gastrinbinds to specific parietal receptor : gastrin-cholecystokinin type 2 (CCK2) receptor
-2 related CCK receptors : CCK1+ CCK2 (AA seq are ~50% identical + both are G protein)
-CCK2receptor’s affinity for gastrin + CCK equally
-CCK1receptor’s affinity for CCK is 3x > gastrin
-clarifies parallel, opposite effects of gastrin + CCK
-CCK2receptor couples to Gαq
-activates same PLC pathway as does ACh –> increase in [Ca2+]i+ activation of PKC
-histaminereceptor on parietal cell = H2receptor Gαs
-histamine activation of receptor complex stimulates adenylyl cyclase -> cAMP -> PKA
-phosphorylation of certain parietal-cell proteins eg H-K pump
PGE2 negatively regulates HCl secretion. What does that mean?

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49
Q

Role of somatostain?

A

inhibits histamine, gastrin, Ach-mediated acid secretion

50
Q

Describe Gαq pathway of Ach

A
  • AChbinds to M3on parietal basolateral membrane
  • coupled to Gαq
  • activates PLC
  • converts PIP2-> IP3 + DAG :
  • IP3causes internal stores to release Ca2+, acts via calmodulin-dependent protein kinase
  • DAG activates PKC
  • M3receptor also activates Ca2+channel
51
Q

Describe Gαs pathway of histamine

A
  • histaminereceptor on parietal cell = H2receptor Gαs
  • histamine activation of receptor complex stimulates adenylyl cyclase -> cAMP -> PKA
  • phosphorylation of certain parietal-cell proteins eg H-K pump
52
Q

Features of cholecystokinin B receptor (CCKBR)?

A
  • CCK2 protein encoded by CCKBR gene
  • Gene encodes a GPCR for gastrin + CCK regulatory peptides of brain, GIT
  • Protein is type B gastrin receptor
  • Found in CNS + GIT
  • Misspliced transcript variant including an intron observed in cells from colorectal + pancreatic tumours
53
Q

What causes [HCl] to reach 150mM?

A 
Rate of secretion
Amount of buffering provided by the resting juice
Composition of ingested food
Gastric motility
Rate of gastric emptying
Amount of diffusion back into mucosa
54
Q

Effect of lack of HCl?

A

failure of protein digestion (achlorhydria or hypochlorhydria = production of gastric acid in stomach is absent or low)

55
Q

Symptoms of HCl def?

A
  • Undigested food in stool
  • Flatulence + bloating
  • White spots on fingernail
  • Drowsiness after meals
  • Lack of intrinsic factor (vit B12 def →pernicious anemia)
  • Increases the chances of H. pylori infection
56
Q

Treatment of HCl def?

A
  • Bitter herbs stimulate HCl secretion
  • Dandelion, devil’s claw, yarrow, wormwood teas useful
  • Lemon juice + vinegar stimulate HCl secretion
  • Vit B1 stimulates HCl secretion by stomach
57
Q

How can acid secretion become elevated?

HCl secretion stimulants

A 
Histamine
Acetylcholine
Gastrin
Caffeine*
Alcohol*
NSAIDs*
Nicotine*
Helicobacter pylori
Zollinger-Ellison syndrome
Hyperparathyroidism (8-30%)
Stress 
Bile salts
Genetic
*Avoid drugs if peptic ulcer
58
Q

Why do patients with hyperparathyroidism at risk for peptic ulcer disease?

A

elevations in extracellular calcium potentiate cholinergic-mediated gastric gland acid secretion –> hyperparathyroid-related ulcer disease

59
Q

Features of primary hyperparathyroidism?

A
  • enlargement of one or more parathyroid glands
  • overproduction of hormone
  • hypercalcemia
  • health problems
  • Surgery = treatment for primary hyperparathyroidism
60
Q

Describe secretion of pepsin

A
  • secreted by chief cells as pepsinogen (inactive, a zymogen)
  • activated if high [H+]
  • pepsinogen -> pepsin in stomach lumen pH6 -> pH 1.5 - 2.5
  • shape altered by high acidity
  • exposes its active site (autocatalytic feedback process)
  • inactivated when food in small intestine (HCO3- + peptides neutralise H+)
61
Q

How’s pepsin stored?

A

inactive pepsinogen in chief cells of gastric mucosa

62
Q

Role of PGE2 (prostaglandin E2)?

A
  • Negatively regulates HCl secretion
  • Increases mucus secretion
  • Increases bicarb secretion
  • Promotes BF
  • Inhibit action of acid secreting stimulating molecules
63
Q

Diff between acid vs pepsinogen secretion?

A

Parallels between acid secretion + pepsinogen secretion, so stimulators/inhibitors of acid secretion during cephalic + intestinal phases exert same effect on pepsinogen secretion

64
Q

Describe stimulation of pepsinogen

A
  • input to chief cells from nerve plexuses (so can be stimulated by Ach)
  • histamine also stimulate chief cells
  • helicobacter affect cells regulating acid secretion, decreases G + D cells
  • D cells inhibit secretion
  • G cells increase it
65
Q

Effect of H.pylori on acid secretion?

A

H.pylori affects both D + G cells so increases acid secretion

66
Q

Role of pepsin secretion?

A
  • initiates digestion of proteins
  • degrades proteins -> peptides
  • but pepsin not required for food digestion since other enzymes : trypsin, chymotrypsin etc. which can digest proteins
67
Q

Required substance secreted by parietal cells?

A

Intrinsic factor for vit B12

68
Q

How NSAIDs (eg aspirin) affect gastric acid secretion disorders?

A

-topical irritation of gut
-impair the barrier properties of mucosa
-suppress gastric prostaglandin synthesis
-↓gastric mucosal BF
-interfere with repair of superficial injury
-inhibit platelet aggregation
-acid in stomach promotes NSAID-mediated gastric disorder by :
-impairs restitution process
-inactivates FGF which interferes with haemostasis process
Way forward = discover + develop stomach-sparing NSAIDS

69
Q

Role of GIT?

A

digestion, absorption of nutrients, salts, water, elimination of undigested waste

70
Q

Effect of malformation of GIT?

A

↓ nutrient status

71
Q

Describe peptic ulcer formation?

A
  • breakage of mucosal barrier
  • imbalance between protective + damaging factors
  • exposure of tissues to erosive effects of HCl + pepsin
72
Q

How much of population affected by ulcers + sites affected?

A

10% of population affected by ulcers

Sites affected: oesophagus, stomach, duodenum

73
Q

Factors responsible for gastric acid secretion?

A 
Histamine
Ach
Gastrin
Alcohol, smoking, caffeine,
NSAIDs
Zollinger-Ellison syndrome
Hyperparathyroidism
Food
H. pylori
Stress
Bile acids are irritants
Genetic
74
Q

Factors predisposing to peptic ulceration?

A
  • Gastric + duodenal infection with H. pylori risk factor :
  • H. pylori - acquired in childhood (in 10-15% UK population)
  • Environmental + host factors determine distribution + colonisation of H. pylori in stomach
  • If duodenal ulcer present, 80% H. pylori infection
  • Smoking, genetic factors, stress promote acid/pepsin secretion –> impairs mucosal defence –> peptic ulcers
  • NSAIDs impair mucosal defence mechanisms by removing :
  • PGE2 (gastro-protective effects, increase mucus + bicarb secretion)
  • thromboxane A2 (involved in healing)
75
Q

Role of HCl + pepsin serve?

A
  • Kill aerobic microorganisms
  • ↓Infection of gastric mucosa
  • Role in pepsinogen activation
  • Stimulate release of bile + pancreatic juice
76
Q

Factors that prevent infection of gastric mucosa?

A 
Mucus production 
Peristalsis and fluid movement
Seamless epithelium with tight junctions
Fast cell turnover
IgA secretion at mucosal surfaces
Peyer’s patches
77
Q

What are Peyer’s patches?

A

=aggregated lymphoid nodules

  • Small masses of lymphatic tissue found throughout ileum
  • Monitor intestinal bacteria populations + preventing growth of pathogenic bacteria in intestines
78
Q

Conc of gastric juices?

A

150mM HCl + pepsin in stomach

79
Q

Protective factors that prevent autodigestion of stomach?

A
  • Secretion of alkaline mucus + HCO3-
  • Protein content of food
  • Presence of tight junction between epithelial cells lining stomach + fibrin coat
  • Replacement of damaged cells within gastric pits
  • Prostaglandins (E + I) inhibit acid secretion + enhance BF
80
Q

What secretes mucus?

A

neck + surface mucous cells in body, fundus, similar cells in stomach form water-insoluble gel that coats mucosa

81
Q

Features of H. Pylori (Campylobacter pyloridis)?

A
  • Gram negative
  • Spiral shaped (can be coccoid) aerobic bacterium
  • Penetrates gastric mucosa (survive under harsh condition of stomach)
  • Highly pathogenic, with many virulence factors
  • Flagella enables ‘corkscrew’ motility towards gut epithelium
  • Commonest cause of peptic ulcer – ↑peptic ulcer risk by 10 to 20%
82
Q

Virulence factors of H. pylori?

A
  • Motility: moves close to epithelium (pH 7)
  • Produces urease (converts urea to ammonia, which buffers gastric acid + produces CO2)
  • Cytotoxin-associated antigen (CagA) – inserts pathogenicity islands + confers ulcer-forming potential
  • Vacuolating toxin A (VacA) – alters trafficking of intracellular protein in gastric cells
  • Large number of outer membrane proteins: Adhesins (BabA), phospholipases, porins, iron transporters, flagellum-associated proteins
83
Q

Define virulence factors

A

molecules produced by H. pylori (malaria, viruses, fungi) that add to their effectiveness + enables : colonisation of a niche in host by attachment to cells

84
Q

Effects of virulence factors of H. pylori infection?

A
  • Dysregulates gastrin secretion
  • Decreases D + G cells
  • Non-functioning neutrophils + macrophages
  • Activation of NF-ᴋB ↑inflammatory gene activation
  • CagA elicits strong serological response - vital in pathogenesis by inserting pathogenicity islands
85
Q

What’s the lamina propria?

A

Thin layer of loose areolar connective tissue beneath epithelium
Together with epithelium + basement membrane = mucosa

86
Q

Describe how H. Pylori causes mucosal damage?

A

-H. pylori bores through mucosa
-attaches to epithelium using some virulence factors
-releases ureases
-urea -> ammonia
-neutralises acidity
-bacteria survives
-epithelium is red due to bleeding + inflammation from
HCl, pepsin exposure + toxins
-inflammatory cells turn up - damaging effects

87
Q

Role of urease?

A
  • breaks urea -> CO2 + ammonia
  • CO2 blown off but ammonia stays to surround bug
  • raising pH so bug survive
88
Q

Role of mucinase?

A
  • breaks thick mucin layer that normally overlies gastric epithelium
  • allowing H. pylori through
  • onto surface of epithelial cells.
89
Q

What’s mucus composed of?

A

mucins + inorganic salts suspended in water

90
Q

What’s mucin?

A

family of proteins that are heavily glycosylated

91
Q

Why corkscrew motility?

A
  • H. pylori curved
  • has flagellae
  • corkscrews itself down via mucin to reach epithelial layer
  • more effective than straight rod trying to push its way through.
92
Q

Effect of CagA?

A
  • Disrupt cell junctions
  • Affect cell proliferation + differentiation
  • Induces inflammation
  • If CagA positive strains –> more severe gastritis, increased risk of developing ulcers, carcinoma
93
Q

Effect of VacA?

A
  • Making vacuoles
  • Inducing apoptosis
  • Disrupting cell pathways
  • Inducing inflammation
  • Modulating immune system (allows H. pylori to live in macrophages, inhibits T-cell production by decreasing IL-2 production)
  • If vacA positive strains –> increased risk of severe gastritis, ulcers, carcinoma
94
Q

Summary of aetiology of peptic ulcer

A

-↑Gastric secretions (HCl + pepsin) → mucosal breakdown
-Aggravators of peptic ulcer:
Regurgitated bile acids
NSAIDS
Genetics
Smoking, alcohol, spicy foods
Chronic gastritis
H. pylori infection
-Ureases + proteases interfere with epithelial protection

95
Q

Where are peptic ulcers common in?

A
  • Duodenal cap: 1st part of duodenal cap
  • Stomach – junction of antrum + body
  • Distal oesophagus - in Barrett’s oesophagus
  • Meckel’s diverticulum (abnormal pouch in the intestine that’s present from birth)
  • After gastroenterostomy (to treat gastric outlet obstruction) - weight loss, recurrent pains, ulcers
96
Q

Diagnostic tests of peptic ulcers?

A
  • Endoscopy (oesophagogastroduodenoscopy, EGD)
  • Histological examination + staining of EGD biopsy
  • Test for H. pylori
  • Stool antigen test (also test for virulence factors egCagA, VacA)
  • Evaluate urease activity
  • Urea breath test (measure C14 isotope in CO2 after given urea tablet containing C14 - indicate H.pylori if high levels)
97
Q

Symptoms of peptic ulcer?

A
  • Anaemia
  • Black, tarry stools
  • Chest discomfort, weight loss
  • Vomiting
98
Q

What’s peptic ulcer disease (PUD)?

A

=peptic ulcer/stomach ulcer

-Break in stomach lining, 1st part of small intestine, lower oesophagus.

99
Q

Features of gastric ulcer?

A

=ulcer in stomach

  • Duodenal ulcer = ulcer in 1st part of intestines
  • Common symptoms : waking at night with upper abdominal pain or upper abdominal pain that improves with eating
  • Pain is burning sensation or dull ache, belching, vomiting, weight loss, poor appetite
  • 1/3 people exhibit no symptoms.
  • Complications = bleeding (15%), perforation in extreme cases
100
Q

Causes of peptic ulcer?

A
  • Hyperacidity; reflux of duodenal contents (oesophagus, stomach, duodenum)
  • H. pylori risk factor for gastric cancer
  • NSAIDs, genetic factors, male
101
Q

Outcome of peptic ulcer?

A

Complete healing, replacement of tissue, some scarring

102
Q

Features of chronic peptic ulcer?

A
  • Occurs in upper GIT (pepsin + HCl)
  • Asymptomatic in >80%
  • Low incidence in young; common in over 50s
  • 90% incidence in developing countries
  • Inflammation plays role in disease process
103
Q

Features of acute peptic ulcer

A
  • Less frequent
  • Develops from areas of corrosive gastritis (oesophagus, stomach, proximal duodenum), severe stress or shock (burns, trauma)
  • Acute hypoxia of surface epithelium (ischaemia of gastric mucosa)
  • Severe bleeding
  • Heal with no scarring
  • Chronic peptic ulcer
104
Q

Complications of peptic ulcer?

A
  • Haemorrhage (GI bleeding)
  • Perforation (peritonitis), penetration (liver, pancreas affected), leakage of luminal contents
  • Narrowing of pyloric canal –> pyloric stenosis in stomach or oesophageal stricture
  • Malignant change becomes 3-6 times likely with H. pylori infection
105
Q

eg of H2 receptor antagonists?

A

cimetidine, ranitidine, famotidine, nizartidine

106
Q

Clinical uses H2 receptor antagonists?

A

Peptic ulcer

Reflex oesophagitis

107
Q

Describe mechanism of action of H2 receptor antagonists

A
  • Inhibit histamine action at H2 receptors on parietal cells
  • Reduce gastric acid secretion (+ reduces pepsin secretion)
  • Inhibit histamine-, ACh- and gastrin-stimulated acid secretion so block acid secretion mediated by these
  • Decrease basal + food-stimulated acid secretion by 90%
108
Q

Clinical trials on H2 receptor antagonists?

A
  • Promote healing of duodenal ulcers

- But if stop treatment –> relapse

109
Q

Unwanted effects of H2 receptor antagonists?

A

Diarrhoea, muscle cramps, transient rashes, hypergastrinaemia

110
Q

Unwanted effects of Cimetidine?

A

H2 receptor antagonist

  • Cimetidine → gynaecomastia in men (↓sexual function)
  • Cimetidine inhibits P450 enzymes → ↓metabolism of drugs metabolised by P450 enzymes eg anticoagulants, tricyclic antidepressants (imipramine, dosulepin, amytriptyline)
  • If taken withanticoagulants/anti-depressants –> bleeding so alter dosages
111
Q

Features of hypergastrinemia?

A
  • PPI therapy –> diminished acid secretion, diminished antral D-cell release of somatostatin, consequent increased G-cell release of gastrin + hypergastrinemia
  • Causes oxyntic cell hyperplasia, increased parietal cell mass, glandular dilatations, stimulation of enterochromaffin-like (ECL) cells to release chromogranin + histamine, raising their conc in serum
112
Q

Diff between Ranitidine vs Cimetidine?

A

Ranitidine produces 50% response at lower dosage so has lower IC50 - more potent then Cimetidine

113
Q

eg of proton pump inhibitors?

A

omeprazole, lanzoprazole, pantoprazole, rabeprazole

Drugs of choice, especially if hyper-secretion occurs, e.g. Zollinger-Ellison syndrome

114
Q

Clinical uses of proton pump inhibitors?

A
  • Peptic ulcer, reflux oesophagitis; as component therapy for H. pylori
  • Hypersecretion of acid eg Zollinger-Ellison syndrome
115
Q

Describe mechanism of proton pump inhibitors

A

-weak bases so inactive at neutral pH
-when pH lowers they irreversibly inhibit H+/K+ATPase
pump
-decreases basal + food-stimulated gastric acid secretion
-doesn’t matter where stimulation is coming from, as pump blocked
-long lasting effects so low or high dosage irrelevant

116
Q

Unwanted effects of proton pump inhibitors?

A

Headache, diarrhoea, mental confusion, rashes, somnolence, impotence, gynaecomastia; dizziness

117
Q

Drugs that protect gastric mucosa?

A

Prostaglandins (PGE2 and PGI2) are gastroprotective

118
Q

What’s misoprostol?

A

stable analogue of PGE1 - gastroprotective, protects gastric mucosa

119
Q

Describe mechanism of misoprostol

A
  • inhibits basal- + food-stimulated gastric acid secretion
  • inhibits histamine- + caffeine-induced gastric acid secretion
  • increases mucosal BF
  • increase secretion of HCO3- + mucus
120
Q

Effects of prostaglandin E1 (PGE1)?

A
  • Biosynthesized from dihomo-gamma-linoleic acid (an omega-6-fatty acid
  • Synthetic variant alprostadil - for treatment of erectile dysfunction) due to vasodilatory properties
  • Misoprostol = synthetic PGE1 prevents gastric ulcers – must be taken continuously, induces labour/abortion

GI (15 decks)

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