Transcript Gastrointestinal Physiology, Lecture 3: The Gastric Phase of Digestion

Gastrointestinal Physiology, Lecture 3:
The Gastric Phase of Digestion
IDP/DPT GI Section 2011
Jerome W. Breslin, PhD
LSUHSC-NO Dept. of Physiology
Downtown Campus, MEB 7208
(504) 568-2669
[email protected]
Required Reading
Kim Barrett, Gastrointestinal Physiology:
Chapter 3
Chapter 8
Three Phases of Gastric Secretion
Slide number
Cephalic Phase
1. The taste or smell of food, tactile
sensations of food in the mouth, or
even thoughts of food stimulate the
medulla oblongata (green arrow).
Taste or smell of food
Tactile sensation in mouth
2. Parasympathetic action potentials
are carried by the vagus nerves to
the stomach (pink arrow).
Medulla oblongata
3. Preganglionic parasympathetic
1
vagus nerve fibers stimulate
postganglionic neurons in the enteric
plexus of the stomach.
4. Postganglionic neurons stimulate
secretion by parietal and chief cells
and stimulate gastrin secretion by
endocrine cells.
5
Vagus nerves
2
Secretions
stimulated
3
Gastrin
4
Circulation
5. Gastrin is carried through the
circulation back to the stomach
(purple arrow), where it stimulates
secretion by parietal and chief cells.
Stomach
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GI Physiology Lecture 3 Outline:
Gastric Phase of Digestion: Overview
Gastric Motility - Part 1
LES Relaxation
Receptive Relaxation
Mixing and Grinding
Gastric Secretions and Their Regulation:
HCl, HCO3-, mucus, pepsin, gastrin
Gastric Motility - Part 2
Gastric Emptying and its Regulation
Vomiting
Figure 15-16
Body (Corpus)
Reservoir Function
Antrum: Mixing
Function
The abundant smooth muscle in the
stomach is responsible for gastric motility.
Gastric Phase
Receptive Relaxation
Entry of Meal
Increased Gastric Secretions
Motility: Mixing and Grinding
Digestion of protein, CHO, fat
Gastric Emptying
Figure 15-15
1. Peristalsis of
bolus to the
stomach
2. Opening of
LES
3. Receptive
relaxation in
stomach
The coordinated sequence of contraction and relaxation in the upper
esophageal sphincter, the esophagus, and the lower esophageal sphincter
is necessary to deliver swallowed food to the stomach.
LES Relaxation:
Neurogenic process, although the
relative importance of neural inputs is not
clear, and the specific neurotransmitter is
unknown.
Vagal stimulation causes LES relaxation.
Swallowing causes LES relaxation, as
well as receptive relaxation of the
stomach to facilitate entry of the bolus.
Gastric Motor Function during
the Gastric Phase:
Receptive Relaxation. Fundus and Body
relax to accommodate the volume of the meal.
Mixing and Grinding. Antral peristalsis to
grind the meal into small particles and mix with
secretions.
Gastric Emptying. Coordination of antropyloro-duodenal motor activity for regulation of
gastric emptying. In addition, gastric reservoir
function participates by regulating fundus tone.
Receptive Relaxation
Swallowing causes relaxation of
gastric smooth muscle.
Mediated by vagus nerve.
Receptive relaxation increases
compliance, so that luminal pressure
changes very little between the empty
state (50 mL volume) and filled state
(1500 mL volume).
Receptive
Relaxation
Intrinsic and vago-vagal
reflexes mediate receptive
relaxation.
Duodenal distension also
results in relaxation of the
gastric fundus.
Barrett, Fig. 8-4
Mixing and Grinding
Pacemaker Region induces peristaltic contraction from the
body to the antrum, which closes the pyloric sphincter.
Pacemaker Cells (ICC) induce slow waves (BER) ~ 3
times per minute.
Force of Contraction, Regulation:
Increased by gastric distension, via short reflexes and
gastrin.
Inhibited by 1) duodenal distension, 2) appearance of
fat, protein, acid or hypertonic chyme in the duodenum
3) increased sympathetic tone.
Figure 15-22
Waves of smooth muscle contraction mix and propel the
ingested contents of the gastric lumen, but only a small amount of
the material enters the small intestine (duodenum) as a result of
each wave cycle.
Motor behavior of the antral pump is
initiated by the dominant pacemaker
in the mid-corpus.
PACEMAKER
POTENTIALS DETERMINE
CONTRACTILE
PARAMETERS:
1. MAXIMAL FREQUENCY
2. PROPAGATION
VELOCITY
3. PROPAGATION
DIRECTION
Barrett, Fig 8-2
BER established by the gastric pacemaker. Note
that a contractile stimulus is needed to reach the
threshold for gastric contractions to occur.
THRESHOLD
Barrett, Fig. 8-3
Gastric Secretions
Oxyntic Gland Area - proximal 80% of the
stomach (body and fundus) - secretes HCl
and pepsinogen into stomach lumen.
Pyloric Gland Area - distal 20% of the
stomach (antrum) - secretes pepsinogen
into the lumen, as well as the hormone
gastrin to the bloodstream.
Gastric Mucosa Surface - secretes mucus
and HCO3 for protection from the acidic
environment.
Composition Of Gastric Juice
Component
Source
Function
Pepsinogen
Chief Cells
Inactive Protease
Pepsinogen
Protease
(activated by HCl)
HCl
Parietal Cells
Acid Environment
Activation of Pepsin
Mucus
Mucous Cells
Goblet Cells
Viscous, Alkaline
Protective Layer
Parietal Cells
Vitamin B12
Absorption
Pepsin
Intrinsic Factor
HCl Secretion during the Cephalic, Gastric, and
Intestinal Phases of Digestion:
Figure 15-16
1. Cardia
Three Regions of
Stomach with
Specialized
Functions
2. Body &
Fundus
Specialized cells
in the stomach
synthesize and
secrete mucous
fluid, enzyme
precursors,
hydrochloric acid,
and hormones.
3. Antrum & Pylorus
The abundant smooth muscle in the
stomach is responsible for gastric motility.
Stomach Wall:
Gastric Gland
Mucous cells secrete mucous,
HCO3-, & trefoil peptides.
Chief cells secrete pepsinogen &
gastric lipase.
Parietal cells synthesize and
secrete hydrochloric acid &
intrinsic factor.
ECL Cells secrete histamine.
Enteroendocrine cells (specifically
G cells) secrete gastrin.
25
Parietal Cells secrete
HCl
Resting Parietal Cell
Stimulated Parietal Cell Secreting HCl
Barrett, Figs 3-2 and 3-3 or Berne & Levy Fig. 32-10
Upon stimulation, the intracellular canniculi fuse to the apical membrane,
and the tubulovesicles fuse to the canniculi, increasing the apical
(luminal) membrane surface area 5-10 times.
The tubulovesiclar membrane is a storage site
for the H+/K+ ATPase. Fusion of tubulovesicles
to the apical membrane increases availability of
the H+/K+ ATPase for H+ secretion.
•
Barrett, Fig. 3-6
Regulation of HCl and pepsin
secretion
Potentiation
A phenomenon in which the effect produced when
two (or more) agents act to together is greater than
the sum of their effects when they act separately.
Acid Secretion in the Stomach - potentiation
among the three stimuli: histamine, ACh, gastrin,
such that histamine H2 receptor blockade
drastically reduces acid secretion.
Figure 15-19
X
H2 Blockers (Pepcid, Zantac, Axid)
X
Atropine (not
practical)
One inhibitory and
three stimulatory
signals that alter
acid secretion by
parietal cells
in the stomach.
H/K-ATPase Inhibitors (Prilosec, Prevacid, Nexium)
X
X
Antacids (e.g. Tums, Maalox, PeptoBismol)
Figure 15-18
F
O
O
D
Acid production by the parietal cells in the stomach
depends on the generation of carbonic acid; subsequent
movement of hydrogen ions into the gastric lumen results
from primary active transport.
Note: Some of the bicarbonate secreted into the blood goes to surface epithelium, where it
is taken up and then secreted in the mucus layer to protect cells.
Surface epithelium secretes a mucus
layer containing bicarbonate for
protection from gastric acid.
•
Berne & Levy,
Fig. 32-13
Figure 15-21
The acidity in the gastric lumen converts the protease
precursor pepsinogen to pepsin; subsequent conversions
occur quickly as a result of pepsin’s protease activity.
Gastric Phase: Both Vago-vagal reflexes and
gastrin increase HCl and pepsinogen
release.
Dorsal
Vagal
Complex
Response:
HCl Secretion
Pepsinogen Secretion
Gastrin
(hormone)
Vago-vagal
Reflex
Pepsinogen
pH < 5
G Cells
Pepsin
Oligopeptides
Proteins
Distension sensed
by mechanoreceptor
Response:
HCl Secretion
Pepsinogen Secretion
Gastrin Secretion
Note: The ENS is also stimulated by distension.
Enteroendocrine Cells and Pathways
Regulating Acid Secretion:
Acid in Antrum
stimulates
somatostatin
release from D
cells
Cellular Mechanism of HCl Secretion:
38
Regulation of Pepsinogen Secretion:
Vagus Nerve (can be activated by
distension of stomach)
ACh
+
Circulation
+
Secretin
Secretin
Gastrin
G Cell
+
D Cell
SS Peptides
S Cell
+
H+
Parietal Cell
+
H+
ENS
+ ACh+
Proteins
Pepsin
+
Pepsinogen
H+
(SS = Somatostatin)
Peptides
Gastric acid output at rest and
during maximal stimulation:
Representative Ranges
Condition
Basal Acid
Maximal Acid
Output (mEq/h) Output (mEq/h)
Normal
1-5
6 - 40
Gastric Ulcer
0-3
1 - 20
0
0 - 10
Duodenal Ulcer
2 - 10
15 - 60
Gastrin-Secreting Tumor
(Zollinger-Ellison Syndrome)
10 - 30
30 - 80
Pernicious Anemia (Loss of
Parietal Cells)
Output = Hourly volume of gastric juice x [H+]
Ulcers
The cause is usually mucosal breakdown due to an
infection with H. pylori.
Other possible causes: Chronic use of NSAIDs,
gastrinoma.
Gastric Ulcer - Cause is usually breakdown of
mucosa
lower basal pH due to leakage of acid from
stomach
Duodenal Ulcer - Cause may have to do with more
acid present in duodenum than normal (not clear,
though) - increased parietal cell mass.
Doubled HCl and pepsinogen secretion.
Gastric Emptying
• Gastric Distension increases emptying (rate is
proportional to size of meal)
• Gastric Emptying Inhibited By:
– Entry of chyme into duodenum
–Fat, protein digests in duodenum
–Acidity (pH < 3.5) in duodenum
–Hypo/hyper-osmotic chyme in duodenum
–Distention of the Duodenum
–Solids more inhibitory than liquids.
Figure 15-24
(CCK, Secretin)
Delivery of acid and nutrients into the small intestine initiates
signaling that slows gastric motility and secretion which allows
adequate time for digestion and absorption in the duodenum.
Between meals: MMCs
Vomiting
VARIOUS CAUSES:
antibiotics, Analgesics
narcotics, cancer chemotherapy,
mechanical obstruction, radiation
injury, gastroparesis, functional
bowel disorders, intraperitoneal
inflammation, increased
intracranial pressure, Emotional
responses, psychiatric
conditions, tumors, bayrinthine
disorders, pregnancy, uremica,
diabetic ketoacidosis, viral or
bacterial gastroenteritis
Summary: Digestion of a Meal in the
Stomach
Entry
•
•
•
•
•
•
•
•
•
Bolus
Large Particles
Triglycerides
Protein
Starch
Monosaccharides
Disaccharides
Salivary Secretions
Water and Ions
Departure
• Small Particles (<2 mm)
• Emulsion
• Triglyceride + small amount of
2-monosaccharides and free
fatty acids.
• Protein + small amount of
peptides and amino acids.
• Starch + 20% oligosaccharides
• Monosaccharides
• Disaccharides
• Water, ions, low pH