Gastrointestinal System Lectures

PHPY 303.3
Lectures #3&4

Instructor: Dr. Francisco Cayabyab

Department of Surgery

Office: Rm. GD30.5 D-Wing,

Health Science Building

Tel: 966-8191

Email: frank.cayabyab@usask.ca
 Regulation of
Gastric Functions
Identify the mechanisms of gastric
regulation
Neurocrine
Endocrine
Paracrine
 STOMACH
4. Secrete gastrin-acid secretion
Functions:
1. Store food ingested
during meal
2. Regulate release of
chyme into duodenum
3. Secrete HCl and
enzymes to begin
protein digestion
4. Secrete Ghrelin
control of feeding
5. Churn and Mix food
with digestive
secretions
 Gastric Motility
Receptive relaxation of orad region
of stomach and weak mixing in body
and fundus (reservoir function)
Constant pressure vs. volume
relationship
How food moved?
Tonic contractions of fundus and
body (little mixing)
Both gastrin and CCK
contractions, which gastric
distensibility
Phasic contractions of the
proximal and distal antrum (the
antral pump), retropulsion
Max. frequency 3
contractions/min
Example Video of Gastric and Small Intestinal Motility

Motility Video #2
Extrinsic Branches of the Autonomic Nervous System
Parasympathetic Sympathetic

(Excitatory) (Inhibitory)

A: Preganglionic parasympathetic innervation by the vagus (cranial nerve 10)

and pelvic nerves of the sacral spinal cord. Dashed line - input for striated
muscle
B: Postganglionic sympathetic innervation from the coeliac ganglion (CG),
superior mesenteric ganglion (SMG) and inferior mesenteric ganglion (IMG)
 Vago-Vagal Reflexes in Receptive
Relaxation of Stomach
Overall process
NO/VIP relaxations induced by Vago-vagal reflexes
vago-vagal reflexes and ENS (mechanoreceptors), ACh
acts by causing release of
inhibitory mediators
(NO/VIP)
Intrinsic reflexes
(ascending) within wall of
stomachrelax
Signals triggered by
nutrients in duodenal
lumen, duodenal or colonic
distension, or presence of
fat/glucose in ileum (ileal
brake) cause relaxation of
gastric fundus (decreased
tone)
All retard gastric emptying
CCK-A receptors on vagal sensory afferents
 Gastric Emptying and Gastric Contents
B

Fig. 41-14

Receptive relaxation, a vago-vagal reflex, responsible for increased

volume with constant pressure
Vagotomy decreases receptive relaxation and accomodation, but ENS
exerts major control
Vagotomy tends to DECREASE or DELAY gastric emptying of solids
Emptying depends on nature of gastric contents
Hormonal Regulation of Gastric Emptying

acid secretion

antral contractions Gastrin pyloric smooth

pyloric sphincter contractions muscle contractions,
gastric juice secretion,
mixing by antral muscle
contractions

Both hormones pyloric

smooth muscle contractions both gastric emptying and
rate of HCl secretion
Four established GI hormones + unidentified enterogastrone inhibit gastric emptying; allows pancreatic
and bile secretions to act on proteins, fats and carbohydrates presented to duodenum
 Enterogastrones
Hormones released from duodenal mucosa by
acid, fatty acid, or hyperosmotic solutions
Inhibit acid secretion as well as gastric emptying
Gastric inhibitory peptide (GIP) released by fatty acids,
acts at parietal cell to inhibit acid secretion
Secretin inhibits gastric acid secretion
Cholecystokinin (CCK), a physiologically significant
inhibitor of gastric emptying, also inhibits gastrin release
Acid initiates nervous reflex from receptors found in
duodenal mucosa, decreases acid secretion
Pathophysiology and Clinical Correlations

Gastroparesis, gastric emptying impaired

Symptoms: early satiety, nausea, vomiting,
bloating
Causes: systemic disease, e.g., long-standing
diabetes mellitus (neuropathy, damage to ICCs);
injury to vagus nerve (need extrinsic input to
stomach for full expression of gastric emptying);
medications (anticholinergics, opiates); gastric
cancer and peptic ulcer disease
Treatment/management: eat small meals, liquids
better tolerated than solid meals
Oxyntic gland: Gastric Secretions
mucus (2 L/day)
enzymes
HCL
Ghrelin (Hormone)
Mucus
Pyloric gland:
gastrin (hormone)

HCL,
Intrinsic Factor
(prevents pernicious
anemia)

Pepsinogen,
Gastric Lipase

Histamine
(ECL cells)
 Interdigestive Phase

Q: Factors to explain low Why acid secretion rate so low?

pH during fasting state?
 Control of Gastric Acid Secretion (Fasting)
C
D
A Since no food in stomach, See also
B, C, and D pathways are Page 897,
not activated; hence, see Fig. 41.8
_ Medical
B very low acid secretion rate!
Physiology

ACID SECRETION
Antrum
A- Luminal H+ directly stimulates D cells to secrete ---
somatostatin, which inhibits gastrin release from G cells
B- vagal stimulation (via ACh) inhibits somatostatin
release from D cells +++
C- Peptides/amino acids directly stimulate G cells to
release gastrin +++
D- Vagus stimulation of G cells via GRP stimulates gastrin
release +++
Control of Gastric Acid Secretion (Fed State)

A See also
Page 897,
Fig. 41.8
_ D Medical
Physiology

C
B
Fundus ACID SECRETION
A- vagal stimulation (via ACh) directly stimulates
parietal cells +++
B- vagal stimulation directly stimulates histamine +++
release from ECL cells
C- The hormone gastrin stimulates release of +++
histamine from ECL
D- Gastrin directly stimulates parietal cell +++
 Morphological Changes in Parietal
Cells During Acid Secretion

Nonsecreting Secreting

Resting parietal cell (nonsecreting) with elaborate system

of intracellular membranes and abundant mitochondria
Actively secreting parietal cell with amplified apical
membrane from fusion of tubulovesicles and secretory
canaliculi
Apical membranes invaginate and interdigitate
 Parietal Cell Receptors and Pumps
Involved During Acid Secretion

Amplification of apical surface area accompanied by an

increased density of H+,K+ ATPase molecules
Note acetylcholine (via m3 muscarinic receptor) and gastrin (via
CCK-B receptor) signal via increased cytosolic calcium,
whereas histamine signals via increased cAMP (H2 receptor)
 Mucosal Barrier
1. Apical membrane impermeable to H+
2. Tight junction between cells

HCl 3.
4.
Layer of mucus
Damaged cells replaced every 3 days

K+
Hypokalemia

K+

Na+
Na/K ATPase
HCO3-
(Alkaline tide in blood supply of stomach during max. acid secretion)
 Pathophysiology and Clinical Correlation
Gastrinoma (Zollinger-Ellison Syndrome)
Extragastric endocrine tumor whose cells undergo
unregulated secretion of large amounts of gastrin
E.g., non-beta cell tumors of pancreas or duodenal tumors
High rates of gastric acid secretion at rest and in response
to a meal
Tumor cells dont respond to normal negative feedback
mechanisms that reduce gastrin release at low luminal pH

Question: Pts with gastrinoma present with what

types of symptoms?
Peptic and duodenal ulcers, diarrhea, steatorrhea (fatty
stool), hypokalemia
Question: What pharmacotherapy would be useful to
alleviate the symptoms of gastrinomas?
E.g., H2 antagonists (ranitidine, cimetidine) and PPIs
(omeprazole)
 Breakdown of mucosal barrier peptic ulcer

From:
Helicobacter pylori
Chemical exposure (NSAIDs)
Stressful situations (increase
gastric secretions)

Combination therapy: antibiotics + proton pump inhibitors reduce H pylori infection

and acid secretion
Cephalic Phase
~30% of total acid secretion
, thought
of food Stimulated vagus nerve
ACh release stimulates
H+ release
ACh stimulates histamine
release
in antrum
parasympathetic & ENS
neurons release GRP, which
releases gastrin
Vagus (via ACh) inhibits
somatostatin release, which
increases acid secretion
Gastric Phase Major source of gastric
secretion (~50% total)
Vagal influences +
mechanoreceptors and
chemoreceptors act with
ENS to produce maximal
secretion of acid
Mucosal distension sends
signals to the vagal
nucleus. Vagal efferent
signals sent back to G
cells and parietal cells
Gastrin release inhibited
when antral pH<3, and
completely inhibited when
pH<2; BUT proteins are
pH buffers (so, pH 5)
Gastric Phase
Proteins effective pH
buffers, so effective pH
may rise up to 5 while
acid secretory rates
remain high
Prevents somatostatin
release from D cells
(promotes acid secretion)
Intestinal Phase 5-10% of gastric acid
secretion
Duodenal G cell and
unknown intestinal
endocrine cell stimulate
parietal acid secretion
Luminal absorption of
amino acids in intestine
stimulates acid secretion
? (undefined mechanism)
In humans, duodenal
mucosa hormone named
entero-oxyntin acid
secretion without
increasing serum gastrin
Lipids & acid, vagovagal
inhibits gastrin release
Gastric Digestion and Absorption
Digestion
Proteins from the action of pepsin
Fat from the action of gastric lipase
Carbohydrate digestion from salivary amylase (for a time)

Absorption
Few short chain fatty acids
Some drugs (weak acids - aspirin) and alcohol