Human Form & Function 2
Gastric Secretion & Motility
Dr. Neil Docherty
My Teaching Objec/ves •  Describe the physiological basis of gastric motility and
secretion and explain how they contribute to digestion
•  Identify the synergies that exist between maximal gastric
secretion and motility
•  Highlight the importance of the pyloric sphincter and the
mucus gel barrier and how damage to them is
associated with disease
The Stomach
•  Infolded muscular bag lined by glandular epithelium
involved in sterilization, preliminary digestion/capture
and storage of nutrient
Key Phenomena:
1)  Filling and Mixing (Motility based Phenomena)
Involves-relaxation/contraction of smooth muscle
Controlled by-mechanosensitive induction of neural circuitry
and endocrine messengers
2) Digestion (Secretion Based Phenomena)
Involves the release of glandular secretions
Controlled by-chemosensitive and mechanosensitive
induction of neural circuitry and endocrine messengers
The Stomach
FUNDUS-BODY-ANTRUM
-Large reservoir capacity
-HCl, pepsinogen
and intrinsic factor
All areas secrete
-mucous
-bicarbonate
-Hormone production
-Major site of muscular contraction
Major Gastric Secretory Products
PRODUCT
HCl
Intrinsic Factor
SOURCE
FUNCTION
Parietal cell
Hydrolysis, sterilisation
"
Vitamin B12 absorption
Pepsinogen
Chief cell
Protein digestion
Mucus
Mucous cell
Gastric protection
Trefoil Factors
"
"
Bicarbonate
Parietal cell
"
Histamine
ECL cells
Gastrin
G cells
"
Gastrin releasing peptide
Nerves
"
Acetylcholine
Nerves
"
Somatostatin
D cells
"
Regulation of secretion
Gastric Glands and Their Secretions
Entero-endocrine cells
Specialised cells in epithelial
lining of intestine which release
short peptide hormones
Parietal Cell Rearrangements
During HCl Secretion
canaliculi
Fusion of canaliculi
and tubulovesicles
with plasma membrane
Tubulovesicles
(inc.
H+/K+ ATPase)
cAMP/Ca2+
ACh
Histamine Gastrin
Parietal Cell Rearrangements
During HCl Secretion Why all the mitochondria??
-Think active transport
H+/K+ ATPase
T.E.M.x9600
Cellular Physiology of Acid Secre/on -­‐Ion Fluxes in HCl secre/on K+ channel
L
U
M
E
N
2K+
K+
K+
H+
Cl-
H2O + CO2
Carbonic
anhydrase II
H+/K+
ATPase
Cl- channel
Na+/ K+
ATPase
H+ + HCO3Cl-
3Na+
Cl-/HCO3exchanger
HCO3-
START HERE!-Secretory stimuli induce
apical plasma membrane localization!!!
HCl
N.B. Low pH causes autoactivation
Of pepsinogen from Chief cells
Clinical Correlate
-Proton Pump Inhibitors
H2 antagonists
Gastric HCl Secre/on Overview •  Parietal cell in fundic mucosa
•  Basolateral stimulation with ACh,gastrin and histamine
•  Stimulation causes profound morphological changes
•  Cytoskeletal rearrangement, increase in apical surface
area densely covered in H+/K+ ATPase
•  Carbonic Anhydrase II generated H+ secretion matches
Cl- secretion into lumen
Protection of Gastric Mucosa
Secondary Gastroprotective Effects of
Basolateral HCO3- Secretion
Bloodstream
Transport towards luminal mucosa in gastric
microvasculature
Apical secretion by surface
Mucosa=GASTROPROTECTION
Negative Feedback Control
Duodenal
Mucosa
Antral G cells fat
GIP
Bloodstream
D cells
Somatostatin
(-ve reg.)
ECL
histamine
cells
Gastrin
Chief
cells
Parietal
cells
peptides
Pepsin
+VE
-VE
Acid Secretion
Pepsinogen
Secretion Summary
•
•
•
•
•
•
•
Positive
Mechanical Stretch
Gastrin
Histamine
ACh
GRP
Pepsin derived, peptideinduced, gastrin release
•  Alcoholic Drinks
•  Coffee
•  Negative
•  pH sensitive D cell
somatostatin release
•  Presence of fat in
duodenum causes gastric
inhibitory peptide (GIP)
release
The Three Phases of Gastric Secretion
•
•
•
Cephalic
Gastric
Intestinal
Cephalic phase
• Higher centres, (sight,smell, taste, anticipation)
• Vagal efferents
• Stimulation of secretory and motor responses
• Direct (Ach-G-cell-Gastrin)
• Indirect 1) (ACh-ENS-GRP-G-cells-Gastrin)
2) (ACh-ECL cells-Histamine-G-cells
Gastrin)
Gastric phase
•  Quan/ta/vely most important •  Short and long reflexes (mechanical, vago-­‐vagal) •  Amplifica<on of secre<on •  Recep<ve relaxa<on •  Increased gastric blood flow •  Sustained secre<on possible due to buffering capacity of luminal protein on bulk content pH Intestinal phase
•  D cell mediated somatostatin release
•  Duodenal mucosa GIP release
Leads to
•  Reduction in secretory activity
•  Residual secretory activity serves to sterilize stomach
ahead of next meal
Gastric Motility
Physical Functions of Stomach
Reservoir
Homogeniser
Control of delivery
Small particle formation
emulsification
SMOOTH MUSCLE RELATED FUNCTIONS
Basal Electrical Rhythm
Slow wavedepolarisation of smooth muscle
Pacemaker potential (greater curvature origin)
determines:
FREQUENCY, VELOCITY and DIRECTION
Only result in contraction when superimposed with
stimuli sufficient to generate an action potential
3 cycles/min
e.g ACh release from vago-vagal
response to baroreceptor stimulation
Relaxation of Stomach Upon Feeding
DEF: Relaxation of stomach to increase volume
RESERVOIR FUNCTION
Two reflexes
1
Receptive
Swallowing
2
Accomodative
Following gastric
mechanoreceptor stimulation
Adaptive Relaxation
Involves the same mediators as
gastric secretion and input from
Arrival of bolus in duodenum
Contraction and Mixing and Grinding
Fed pattern motility
Distal stomach
Rapid phasic contractions
Gastric Emptying
Following feeding
Pyloric Sphincter
duodenal feedback
OPEN
CLOSED
Only small triturated particles <2mm can pass
Effect of Composition on Gastric Emptying
Lag phase prolonged further
by fatty meals due to endocrine
derived negative feedback on pyloric
sphincter opening induced by
Hormone release in the duodenum
Gastric Motility During Fasting
Migratory Motor Complexes
100
mins
Phase 1: 40-60% of cycle=quiescence
Phase 2: =low grade contraction
Phase 3: 5-10% of cycle=intense contractions
pylorus fully open
Phase 3
antral
contractions
In dog
ONSET OF FEEDING
In response
to fasting
induced
motilin
release from
duodenum
Gastroparesis
Collection of disorders
Delayed gastric emptying
Satiety, nauseas vomiting
Systemic disease related neuromuscular dysfunction
(diabetes mellitus-vagal nerve dysfunction)
Vagal nerve injury during surgery
Small liquid based meals low in fat recommended Why????
Your Learning from Today Should focus on being able to;
•  Describe the physiology basis of gastric motility and
secretion and explain how they contribute to digestion
•  Link gastric secretion and motility in terms of activators
•  Appreciate and describe the importance of the pyloric
sphincter and the mucus gel barrier and how damage to
them is associated with disease