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School of Medicine @UoLmedicine
http://pcwww.liv.ac.uk/~bjcampbl/Indigestion%202.htm
Cellular & Molecular Physiology, Institute of Translational Medicine
Prof. Barry Campbell
How the gut protects itself…. ‘practising safe digestion’.
Year 1 MBChB –
Gastrointestinal system
Learning Outcomes:
➢ Describe the defensive role of the mucosal barrier in response to attack/digestion and the consequences for the gut when protection fails
➢ Describe the mucus-bicarbonate barrier
➢ Explain the role of prostaglandins in the GI tract
➢ Define how the gastrointestinal epithelium responds when insult leads to injury
➢ Explain the processes restitution and cell migration in response to gut injury
➢ Describe how immune competent tissue monitors intestinal bacteria populations and prevents growth of pathogenic bacteria in the intestine
➢ Define the mechanisms to sense and remove damaged cells (e.g. apoptosis (programmed cell death) and epithelial shedding )
➢ Define the vomiting reflex
Attack and defence in the gut
Acid and pepsin
Ingested drugs (alcohol, aspirin)
Refluxed bile
Smoking
Micro-organisms (e.g. H.pylori)
Ischemia (oxidative stress)
Food allergens
Mucus-HCO3
Cell membrane
Cell migration and renewal
Mucosal blood flow
Prostaglandins
Immune system
Acid inhibition
Programmed cell death
Damaging Protective
Attack and defence in the stomach
HCO3-
Tight junctions
between cells
slow H+
diffusion
Blood supply
carries H+ away, helps
antioxidant function
Mucus-HCO3-
barrier slows H+
diffusion
Acid & pepsin
MUCUS
Mucosal blood flow
Mucosal prostaglandins
Cell migration
and regeneration
pH 2
pH 7
H+
Cell surface
phospholipids
EXOCRINE
PANCREAS
stomach
chyme
VAGUS NERVE
SECRETIN
CCK
Ach
VIP
+
+
HCO3-
Enzymes
The exocrine pancreas produces bicarbonate to
neutralise acidic stomach chyme
DUODENUM
Stretch
receptor
acid Fats &
protein
Duct
cells acinar
cells
Sir William Maddock
Bayliss
Starling introduced the term
'hormone' in the Croonian
Lectures to the Royal College of
Physicians, 20-29th June 1905.
Ernest Henry
Starling
MUCUS
MUCOSA
H+
CGRP/NO releasing
efferent fibres
Afferent nerve fibre
HYPERAEMIA
Arteriole
Increased blood flow in response to
penetrating acid
Restitution - rapid repair mechanisms
Approx. 30 min
Damage
loss
Cell
migration =
restitution
Epithelium
thinner,
but
restored
Key players in repair: Gastrin Regenerating protein (Reg)
Prostaglandins Growth factors Trefoil peptides
Noble PJ et al., Am J Physiol Gastrointest Liver Physiol. 2003; 284(1):G75-84.
Gastrin stimulates migration
1h post addition of gastrin
The gut immune system: Peyer’s patches
FAE VE
LF
Microfold (M cells)
The gut immune system: Peyer’s patches
Immunoglobulin A
(IgA)
innervation
M cell
Cytokinescirculation
IEL
B cellT cell
Antibody
production
macrophageT cell
mast
cell
Antigens of
infectious agents
apical
basolateral
transported
intact
6-10
crypts/villus
CRYPT
250 cells
VILLUS
3500 cells
300 cells/crypt/day
1400 cells/villus/day
150 proliferative cells
32 clonogenic cells
<16 stem cellspaneth cells
Control Irradiated
Life and death of an enterocyte
Damaged cells undergo programmed cell death (apoptosis)
x40 objective.
Duckworth & Watson 2011
Methods Mol. Biol. 2011; 763, 105-114 Carrie Duckworth © 2011
• Cells take ~10 min to shed
Maintenance of tight junctions during cell shedding
The vomiting reflex
Efferent fibres:phrenic & vagus
nerve
Afferent fibres:pain, bloating,
inflammation,
irritants, toxins....
Vomit
Contraction of
duodenum,
pylorus and
antrum
Vomiting centremedulla oblongata
Diaphragm fixed
for inspiration
LOS, UOS &
pharynx relaxed
Intercostal muscles
contracted…
High abdominal
muscular pressure
