BY2202
Lecture 19
Gut Function and Regulation 1
Dr. Neil Docherty
Teaching Objec-ves •  Describe the role of key secretory events and their triggers
occurring during transit of food from the mouth to the
duodenum
•  Understand basics of gastric motility
•  Refer to the causes of gastritis
•  Refer to exocrine pancreatic insufficiency in cystic fibrosis
Pre-processing of the Bolus in the Mouth
1, Sensory analysis of material before swallowing
2. Mechanical processing (teeth, tongue, palate)
3. Lubrication (mucus, and salivary gland secretions)
4. Sterilisation (lysozyme)
4. Neutralisation (bicarbonate)
4. Beginning of digestion (amylase, lipase)
PAROTID-amylase
EBNER’S-lipase
SUBMANDIBULAR
-mucus, amylase
SUBLINGUAL
-mucus
-1-1.5 litres per day
-99.4% water, 0.6% salts, mucus, other proteins
Swallowing Reflex
-The Oropharyngeal Stage
Tongue moves bolus to back of mouth
and pharynx
Brain stem arc activation of swallowing
muscles
net effect
Uvula-(connective tissue at end of
soft palate) prevents nasal flux
Larynx elevated and vocal folds closed
Over glottis. Epiglottis covers glottis
-prevents tracheal flux
The Oesophagus and Oesophageal Phase
Muscular tube 25cm long 2 cm wide
Takes the food to the stomach
Sphincters at either end
Transverse
section
The Stomach
-Large reservoir capacity
-HCl, pepsinogen
and intrinsic factor
All areas secrete
-mucous
-bicarbonate
-Hormone production
-Major site of muscular contraction
Gastric Glands and Their Secretions
DEF: Entero-endocrine cells
Specialised cells in epithelial lining of intestine
Which release short peptide hormones
Parietal Cell Rearrangements During HCl Secre4on canaliculi
Fusion of canaliculi
and tubulovesicles
with plasma membrane
Tubulovesicles
(inc.
H+/K+ ATPase)
cAMP/Ca2+
ACh
Histamine Gastrin
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
HCl
N.B. Low pH causes autoactivation
Of pepsinogen from Chief cells
Na+/ K+
ATPase
H+ + HCO3Cl-
3Na+
Cl-/HCO3exchanger
START HERE!-Secretory stimuli induce
apical plasma membrane localization!!!
HCO3-
Gastric HCl Secre4on Overview •  Parietal cell in fundic mucosa •  Basolateral s4mula4on with ACh,gastrin and histamine •  S4mula4on causes profound morphological changes •  Cytoskeletal rearrangement, increase in apical surface area densely covered in H+/K+ ATPase •  Carbonic Anhydrase II generated H+ secre4on matches Cl-­‐ secre4on 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
Gastric Motility
Physical Functions of Stomach
Reservoir
Homogeniser
Control of delivery
Small particle formation
emulsification
SMOOTH MUSCULE RELATED FUNCTIONS
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
Contraction and Mixing and Grinding
Fed pattern motility
Distal stomach
Rapid phasic contractions
Gastric Emptying
Following feeding
Pyloric Sphincter
RELAX-OPEN
CONTRACT-CLOSED
Only small triturated particles <2mm can pass
Effect of Composition on Gastric Emptying
Lag phase prolonged further
by fatty meals
Gastric Acid and Gastritis
-Erosive gastritis
-Gastric Ulcer
H Pylori
Tobacco
Alcohol
NSAIDs stress
Motility defects
-Impaired mucosal protection
-Inflammation
-Ulceration
The Duodenal Cluster Unit
The duodenum receives exocrine pancreatic and biliary secretions
Pancreatic Secretions
-bicarbonate, proteolytic, amylolytic and lipolytic enzymes and co-factors
Biliary Secretions
-bile acids, cholesterol, lecithin
-conjugated billirubin(N.B. EXCRETION)
Basics of Pancreatic Secretion
ACINUS
Pro-enzymes
INTERCALATED DUCT
H 2O
HCO3-
ALKALINE ENZYME
MIX
Regulated Exocytosis of Pro-enzymes
Pancreatic Acinar Cells
Cellular Physiology of Ductular Bicarbonate Secre-on Ductular Epithelium
HCO3-
D
U
C
T
L
U
M
E
N
Na+/ HCO3-
Na+
Na+
2K+
H2O + CO2
ClHCO3
Na+/ K+
ATPase
-
Cl-
Cl-/HCO3exchange
CFTR
Carbonic
anhydrase II
HCO3
H
+
3Na+
Na+/ H+
H+
Na+
phosphorylation PKA
K+
K+ channel
K+
cAMP
H 2O
Trans-epithelial osmotic gradient
SECRETIN (hormone released from
Entero-endocrine S cells in duodenum)
DILUTE ALKALINE SECRETION
Cys-c Fibrosis: A Consequence of Failure of CFTR Func-on Pancreas in Cystic Fibrosis
-CFTR (7q31.2) mutations are the cause of cystic fibrosis,
so named because of the pancreatic pathology
-Most frequent mutation due to loss of CFTR F508 and misfolding
-Pancreatic ductular secretions become thick and obstruct ductules
-Intra-pancreatic enzyme activation and fibrotic scarring
-Exocrine Pancreatic Insufficiency=Maldigestion and malabsorption
Learning Objec-ves •  Appreciate anatomical and functional correlates in GI tract in
terms of digestion and absorption
•  Understand the role of key secretory events and their triggers
occurring during transit of food from the mouth to the
duodenum
•  Explain the basics of gastric motility
•  Demonstrate a fundamental understanding of the causes of
gastritis and exocrine pancreatic insufficiency in cystic fibrosis