BY2202
Gut Development, Function and Regulation 1
Dr. Neil Docherty
Content Relative to BY2202 Learning Outcomes
Primary material covered directly in lectures. More structure and function than
development.
What is presented is not remote from what has been covered on muscle types,
nervous and endocrine signalling and gross anatomy. Study of the digestive system
as with all body systems is INTEGRATIVE ANATOMY (FORM) AND PHYSIOLOGY
(FUNCTION).
My Teaching Objectives
• To (briefly) remind you of the developmental origins of the
gastrointestinal tract in humans
• To outline the anatomical and functional correlates in GI tract
in terms of digestion and absorption of ingested nutrient and
excretion of waste.
• Highlight the respective roles of secretory and mechanical
events and their triggers occurring during transit of food from
the mouth to the duodenum
• Provide a disease related context to the material covered in
terms of the causes of gastritis and exocrine pancreatic
insufficiency in cystic fibrosis
Components of The Digestive System
Embryology describes gut development arising from
three regions;
-PHARYNGEAL GUT
Development of pharynx
and related glands
UPPER
FOREGUT
G.I. Tract
Oropharyngeal membrane to liver bud level
of duodenum (inc. liver and pancreas)
-MIDGUT
From liver bud as far as 2/3 of the length of
LOWER
the colon
G.I. Tract
-HINDGUT
the last 1/3 of the colon to the cloacal membrane
Once developed we think of the following subdivisions
The primary alimentary canal (Oral cavity, oesophagus,
stomach, small intestine (duodenum, jejnum, ileum), large
intestine (vermiform appendix, colon, rectum) and anus.
Also the digestive glandular organs including the pancreas and
liver
General Features of The G.I. Tract Wall
EPITHELIUM
VASCULAR AND LYMPHATIC
ENDOTHELIUM
LYMPHOID TISSUES
LEUKOCYTES
CONNECTIVE TISSUE
NERVE PLEXES
SMOOTH MUSCLE
The cartoon illustrates the structure of
the distal part of the foregut, the duodenum
With a number of specialised features
However general wall structure has
Significant commonality from oesophagus
to rectum.
Origin of The Gut Tissues
Gastrulation (week 3 of gestation)
ECTODERM
MESODERM
ENDODERM
•Lining
•Muscle, vessels, immune component
connective tissue
•Enteric Nerves
Sagittal Midline Sections of Embryo
(Day 17-28)
17d
22d
28d
24d
Foregut
Hingut
Growth in the head and tail region leads to cephalocaudal folding
Lateral Folding and Body Wall Closure
Lateral folding of the embryo proceeds to body wall closure
by end of week 4
Suspension of Parts of The Gut Tube
From Dorsal Mesenteries Persists
Through Development
Enveloping of regions of the gut tube leads to their designation as
INTRAPERITONEAL
Traffic of vessels and nerves to and from the gut occurs via the mesenteries
Specification of Endodermal Lining
of Digestive Track
(Week 4 and Week 5)
•Specification occurs during lateral body wall folding
•Defined by the activity of specific transcription factors
•Reciprocal inductive events occur between endoderm
and mesoderm
Remember this principle for Dr. Wride’s kidney development
lecture (metanephric mesenchyme and ureteric bud)
GI Tract Origin and Regions in Summary
End of fourth week of development
Foregut
Midgut
Hindgut
Alimentary canal
and accessory
glandular tissues and
organs
What the GI Tract Contributes to The Body
ROLE IN NUTRITION AND EXCRETION
(focus of these lectures)
-Mechanical and secretory promotion of
digestion
-Specialised pathways for the absorption of
macronutrients and micronutrients.
-Excretion of digestive waste and metabolic
waste products from around the body
ROLE IN DEFENCE
Gut associated lymphoid tissue protects
against harmful microorganisms and actively
promotes tolerance to commensal
microorganisms and dietary antigen.
-FLUID HOMEOSTASIS
Plays a role in whole body fluid & electrolyte
balance
Functional Anatomy of the GI Tract:
A Useful Analogy Regarding Nutritive
Function
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
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
Cellular Physiology of Acid Secretion
-Ion Fluxes in HCl secretion
K+ channel
L
U
M
E
N
2K+
K+
H2O + CO2
K+
H+
Cl-
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+
HCO3Cl-/HCO3exchanger
START HERE!-Secretory stimuli induce
apical plasma membrane localization!!!
Gastric HCl Secretion 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 Clsecretion 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
H2O
HCO3-
ALKALINE ENZYME
MIX
Regulated Exocytosis of Pro-enzymes
Pancreatic Acinar Cells
Cellular Physiology of
Ductular Bicarbonate Secretion
Ductular Epithelium
HCO3-
D
U
C
T
L
U
M
E
N
Na+/ HCO3-
Na+
Na+
2K+
Na+/ K+
ATPase
H2O + CO2
ClHCO3Cl-
Carbonic
anhydrase II
Cl-/HCO3exchange
CFTR
HCO3
H+
3Na+
Na+/ H+
H+
Na+
phosphorylation PKA
K+
K+ channel
K+
cAMP
H2O
Trans-epithelial osmotic gradient
SECRETIN (hormone released from
Entero-endocrine S cells in duodenum)
DILUTE ALKALINE SECRETION
Cystic Fibrosis:
A Consequence of Failure of CFTR Function
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
Your Learning Objectives from This Lecture
You should be able to do the following;
1) Outline the developmental origins of the gastrointestinal tract
in humans
2) Appreciate and explain the anatomical and functional
correlates in the G.I. tract in terms of digestion and absorption of
ingested nutrient and excretion of waste.
3) Describe the secretory and mechanical events occurring in
the stomach and duodenum and identify their origin in
signals derived from digestion products and hormonal triggers
4) Discuss and apply the material covered to the disease
setting with reference to gastritis and exocrine pancreatic
insufficiency in cystic fibrosis