Lecture 2 - Gastrointestinal regional variation
Gastrointestinal regional
variation
Mouth
Type of cell lining
Muscle tissues/layers
Glands
Stratified squamous
epithelium
Stratified squamous
epithelium
Skeletal muscle: inner longitudinal & outer
pharyngeal constrictors
Mucus glands found on the lower
pharynx
Esophagus
Stratified squamous
epithelium
Skeletal muscle and smooth muscle (in the
muscularis externa)
Stomach
Simple columnar epithelial
layer in the mucosa tunic
Small intestine
Simple columnar
Large intestine
Simple columnar
Anal canal
Stratified squamous
Pharynx


Muscularis mucosa – smooth muscle
Muscularis externa – circular and
longitudinal muscle
 Oblique muscle layer
Jejunum and ileum – supported by mesentery
Gastric pits and gastric glands
Glands – no enzyme secretion
Lecture 3 – gastrointestinal regulations
Stimulation
Type of
stimulation
Neural
Source
Function of source
Enhance function
Inhibit function
Interstitial cells of
Cajal – pacemakers
cells located on
muscularis externa
Stretch, acetylcholine,
PNS stimulate spikes to
occur on crest of slow
wave  AP generated
Norepinephrine,
SNS
Extrinsic activity:
conditioned stimuli
Neural
Sight, smell, thought
of food
Neurotransmitters (nts)
Neural
Circulating hormones:
extrinsic or intrinsic
Local factors: intrinsic
Hormonal
Neurotransmitters
from CNS or ENS
Endocrine
Pacemakers cells deliver info
form enteric neurons to
smooth muscle cells 
generate slow wave in the
stomach
Involve CNS to stimulate
salivary centers and vagal
nuclei in the medulla
Act on cells at the synapses
to regulate cell activity
Paracrine
Paracrine cells
Intrinsic activity:
mediated by local
enteric nervous system
plexuses
Sources of stimulation
CNS
Neuroregulation
Autonomic nervous system - SNS
CNS
Autonomic nervous system – PNS
AP release
neurotransmitters
Act on cells near the site of
paracrine release
Components and functions
 Preganglionic nerves: release Ach to bind w/ nicotinic receptors on
postganglionic nerves
 Postganglionic nerves: release norepinephrine (NE)


Preganglionic: comprised of vagus nerve and pelvic nerves; release Ach to
activate nicotinic receptors on enteric neurons
Postganglionic: release Ach which activate muscarinic receptors in gut;
may also release neuropeptides as neurotransmitters
ENS
GI nerve supply: myenteric plexus
Plexus regulates motility
ENS
GI nerve supply: submucosal plexus
Plexus controls secretion, blood flow and absorption
ENS
Neurotransmitters


Ach: stimulate contraction of smooth muscle, secretion of salivary gland,
stomach, pancrease
NE – inhibit contractions of smooth muscle, stimulate contraction of some
sphincters
Lecture 4 – Gastrointestinal motility
Factors affecting GI motility
Gastrin
Function
 Increase frequency and velocity of gastric slow wave
 Stimulate antrum motility (contraction)
 Raise LES pressure  contraction
 Increase emptying into duodenum
Increase/decrease emptying
Increase
Volume of chyme in the stomach
Increasing volume cause distention and stimulate
mechanoreceptors  enhanced motility via intrinsic nerve
Increase
Volume/chemical composition of chyme in
the duodenum


Cause neural response: enterogastric reflex 
inhibits gastric emptying and stimulate contraction of
pyloric sphincter
Hormonal response: stimulate release of
enterogastrone
Enterogastrones inhibits emptying
pH
Low pH
Decrease
Osmolality
Isotonic osmolality of chyme
Increase
Particle size
Large size
Decrease
Caloric load of content
High load
Decrease
Lecture 5 - Secretion Part 1
Control of extrinsic
salivary glands
Cl-/HCO3- symporter
Location
Process
Gain/Loss
On luminal/apical
membrane of acinar cell
Losing Cl- and HCO3- into
the lumen
Na+/H+ antiporter
Basolateral membrane on
ductal cells
CL-/HCO3- antiporter
Basolateral membrane on
ductal cells
Transport Cl- and HCO3out into the lumen of the
salivary gland
Na+ is reabsorb from
lumen and H+ is secreted
into lumen of salivary
gland
Cl- gets reabsorb and
HCO3- gets secreted
K+/H+ antiporter
Basolateral membrane of
ductal cells
H+ is reabsorbed and K+ is
secreted into the lumen
Balance H+ that was loss
from the Na+/H+ antiporter
Ach receptor
Acinar cell
Ach bind to activate 2nd
messenger system to
activate protein kinase to
activate release of
zymogen granules
Function
Losing H+
Gaining Na+
Balance Cl- that was lost
from acinar cells; increase
the loss of HCO3-
HCO3- in salivary gland
contribute to buffer against
acid for reflux and dental
caries
Anticholinergic drugs:
scopolamine, benztropine,
ipratropium will inhibit
Ach receptor and cause dry
mouth
Stomach mucosa
epithelial cells
Surface mucosal cells (all
over the stomach)
Secretion/components
Neck mucosal cells (all
over the stomach)
Parietal cells (at the
fundus)
Mucus
Parietal cells (at the
fundus)
HCl
Parietal cells
H+/K+ ATPase (protein
pump protein) on
luminal/apical membrane
HCO3-/CL- antiporter on
Basolateral membrane
Parietal cells
Parietal cells
Mucus (mucin) and HCO3-
Intrinsic factor
(glycoprotein)
Ach (M3 muscarinic)
receptor on basolateral
membrane
Function of
secretion/component
Maintain pH 7 on surface
epithelial cell; prevent gastric
mucosa from stomach acid
damage
Form protective flexible gel
against stomach acid
Form complex with Vit B12
so that Vit B12 can be absorb
in the ileum
Produce stomach pH of 1-3
 Activate pepsinogen
 Kill most bacteria
 Denature protein
 Destroy plant cell wall
 Break down animal
connective tissue (CT)
 Inactivate salivary
amylase
Transport H+ to stomach
lumen and bring in K+ into
the cell
HCO3- transported out to the
blood and Cl- is brought
inside
Ach bind to receptor which
cause an increase in IP3
increase Ca+ level 
increase protein kinase
activity  promote more
proton pump (H+/K+
ATPase) activity
Complications
H-pyloric can
producing urease to
hydrolyze urea to form
NH4+ and HCO3-;
NH4+ can damage
these surface cells 
gastric ulcers
Vit B12 is needed for
RBC production; w/out
its absorption RBC
cannot be produce 
pernicious anemia
Increasing amount of
H+ in lumen
Cl- diffuse across cell
to the lumen where it
can bind w/ H+  HCl
Increase in HCl
production
Treatment of the
complication
 H-pyloric tx: 2
antibiotics, bismuth
containing
compound
 Ulcer: H2-receptor
blocker or PPI
Parietal cells
Gastrin/CCK-B receptor on
basolateral membrane
Enterochromaffin-like
(ECL) mast cells (located
in the gastric mucosa at
the fundus)
Histamine (paracrine)
Chief cells (at the fundus)
Pepsinogen (precursor
enzyme)
Chief cells
Gastric lipase
Gastrin bind to receptor 
increase IP3  increase Ca+
 increase protein kinase 
promote more proton pump
(H+/K+ ATPase) activity
Histamine will bind to H2
receptor on basolateral
membrane of parietal cell 
increase 2nd messenger cAMP
 increase protein kinase 
increase HCl
Increase in HCl
production
Histamine is released
as a result of
inflammation;
histamine stimulate
more acid production
 not good for the
already damaged
stomach lining 
gastric ulcer
Tx of gastric ulcer
 PPI: permanent
inhibition of H+/K+
ATPase activity
 Anticholinergic:
block Ach from
binding to receptor
 H2-receptor blocker
Activated to become pepsin
in the presence of acid at pH
of 2. Pepsin starts protein
digestion.
Active at pH of 3. Activated
form will digest triglycerides
Pyloric enteroendocrine cells
G cells (at the antrum)
Secretion
Gastrin (hormone)
D cells (at the antrum)
Somatostatin
(hormone)
Function of secretion
 Stimulate acid release by parietal cell
 Stimulate pepsinogen release by chief cells
 Stimulate stomach mucosal growth
 Stimulate gastric contractions that mix and stir the gastric contents
 Stimulate ECL release of histamine



Inhibit gastric release from G cells
Inhibit histamine release from ECL cells
Bind to receptor on parietal cell and inhibit acid secretion
Lecture 6 - Secretion Part 2
Pancreatic cells
Acinar cell
Secretion
Enzyme
Acinar cell
Pancreatic amylase
Acinar cell
Acinar cell
Ductal cells
Function of secretion
Store enzyme in zymogen
granules until they are
released via exocytosis to
aid in digestion
For starch digestion
Site of release
Site of action
Duodenum
Small intestine
Tyypsine, chymotripsine
and carboxypeptidase
For protein digestion
Duodenum
Small intestine - duodenum
Pancreatic lipase (lipolytic
enzyme)
For fat digestion
Duodenum
Small intestine - duodenum


Water and
electrolyte
HCO3-
HCO3- will neutralize
excess stomach acid in the
duodenum
Duodenum
Duodenal
enteroendocrine
cells
Secretion
Stimulus for secretion
(enterogastrone)
CCK
Fatty chyme that is
(cholecystokinin) partially digested
Duodenal
enteroendocrine
cells
Secretin
Low pH of less than
4.5
Duodenal
enteroendocrine
cells
Cells of the
duodenum &
jejunum
GIP (gastric
inhibitory
peptide)
Motilin
Fatty acid, amino acid,
glucose
When fasting
Function of secretion
Site of action

Tell the pancrease to produce
more enzymes
 Dominant regulator of
inhibiting gastric emptying
 Stimulate gall bladder and
pancreatic functions
 Stimulate constriction of
pyloric sphincter
 Tell pancrease to produce
more HCO3 Stimulate liver to release more
HCO3- into the bile
 Inhibit gastric acid secretion
and emptying
 Stimulate release of water and
HCO3- into bile
 Stimulate secretion of insulin
 Inhibit gastric emptying and
gastric secretion of HCl
Stimulate motility (contraction) of the
stomach and small intestine to prevent
bacterial overgrowth





Gastrin/CCK receptor on acinar
cells in the pancrease  more
enzyme production
Bind to gallbladder  contraction
to release bile
Bind to Oddi’s sphincter  relax
the sphincter to allow bile into
duodenum so bile can emulsify fat
Ductal cells of the pancrease
Liver cells
Absorptive epithelia cells transporter
(on the villi of Sm. Intestine)
Location
Function
Na+/K+ ATPase
Brush border
Pump Na+ out of the cell and bring in K+ using ATP to set
up the gradient for Na+ wanting to come into the cell
SGLT 1 (sodium glucose galactose
cross) co-transporter
Luminal side of brush border cells
Transport these molecules against their concentration
gradient into the cell by using sodium’s energy
GLUT 5 (fructose)
Luminal side of brush border cells
Brings fructose into the cell
GLUT 2
Basolateral membrane of brush border cells
Helps all monosaccharide get out from the cell and into the
blood