Protection of the digestive system…practising safe digestion...

Prof. Barry Campbell

GI Physiology

e-mail: bjcampbl@liv.ac.uk

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