Protection of the digestive system…practising safe digestion...
Prof. Barry Campbell
GI Physiology
e-mail: [email protected]
http://pcwww.liv.ac.uk/~bjcampbl
Key concepts in Digestion...
GORD module
Contribution to the following milestone set out for CLC1:
FoP2.1(1) identify and describe the common/ serious, extrinsic and
intrinsic factors that can affect the normal biological processes in
individual organs or organ systems, which could affect the level of oral
and general health risk, treatment complications and/or outcomes
Objectives: - To develop an understanding of:
1. the defensive role of the mucosal barrier and the consequences for the
gut when protection fails
2. how the gastrointestinal epithelium responds when insult leads to injury
3. how the gut detects and removes infectious agents
4. the mechanisms to sense and remove any damaged/mutated cells
5. the mechanisms and regulation of vomiting
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
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 stem 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