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Gastrointestinal

Physiology - Overview
& Neuroendocrine
Control
Jerome W. Breslin, PhD
Department of Molecular Pharmacology and
Physiology
USF Morsani College of Medicine
Friday, March 17, 2017
8:00-8:50 AM
1
Learning Objectives (1 of 2)
GI-Intro. Understand the basic functions of the gastrointestinal
system and the design features that subserve these.

GI 1*. Identify the sources and typical amounts of fluid and


nutrients entering and leaving the GI tract daily.

GI 2. For the major classes of nutrients (carbohydrates, proteins,


fats), differentiate the processes of ingestion, digestion,
absorption, secretion, and excretion; include the location in the GI
tract where each process occurs.

GI 3. Describe the functions of splanchnic blood flow in sustaining


intestinal viability and as a source/sink for material transported
across the GI tract epithelium.

GI 4. Describe how the single layer of epithelial cells that lines


most of the GI tract is renewed, and describe the mechanisms
whereby these cells are both a barrier and selective portal for
secretion and absorption.
*The numbers indicate APS/ADCP medical physiology learning objectives.
Link: http://www.the-aps.org/mm/Education/Publications/Education-Reports/Higher-Ed/MedPhysObj/
2
Learning Objectives (2 of
2)
GI 7. Describe the major anatomical characteristics of the
enteric nervous system and the major cellular divisions of the
enteric ganglia (sensory nerves, interneurons, and motor
neurons). Given either a cross section or whole mount of the
bowel wall, identify the anatomical positions and major
characteristics of themyenteric and submucosal plexi.

GI 8. Know how afferent and efferent extrinsic nerves


(sympathetic and parasympathetic) interact with the enteric
nervous system and regulate the functions of the GI tract.

GI 11. Compare and contrast the regulation of gut function by


nerves, hormones, and paracellular regulators.

GI 14. Define the incretin concept, and as an example,


describe the glucose-dependent release and action of an
incretin from the gut.

3
Raw
Materials

Life
4
Single Cell Organisms

Diffusion of water and ions,

Phagocytosis/Endocytosis of larger
particles, digestion & absorption in 5
Single Cell Organisms

6
Multicellular Organisms
Shape is important!

If the shape is not hollow: Greater Ratio of


Volume to Exterior Surface Area than in a
Single Cell 7
Simple Multicellular Organisms
Shape is
important!

Hydra
Cavity or Lumen
(Image from
Wikipedia)

for optimal
digestion and
absorption

Organization into shapes that


maximize surface area for
8
GI Function
Food Digest

Water Absorb

Salts Distribute

9
Vander
Physiology, Fig
15-1
1 Barrett, Fig. 1-1
0
GI System Processes:

Motility
Including Ingestion &
Excretion
Secretion
Digestion
Absorption

1
GI System Processes - Locations

(Splanchnic Circulation)

from Vander
1 Physiology Fig 15-2
Overview of what we will cover in detail...

Vander Old Fig 15-3 - upper half (now Table


15-1)
1
...as we go on with the lectures.

Old Fig 15-3 - lower half 1


Splanchnic Blood Flow

Objective GI3 1
By the end of the week you should be able to
match each function below to the organs in Old
Fig. 15-3

1
Question:
Which part of the GI tract is the major site of
nutrient absorption?

A. Mouth

B. Stomach

C. Pancreas

D. Small Intestine

E. Large Intestine

Objective GI-2 1
Daily Water and Solid Balance

2000 ml
+
400-800 g solid food
(can vary
significantly)

About 2000 mL enters


colon per day in this
example. Most of it is
absorbed.

Feces e.g. 100 ml + 50 g


solid

Objective GI1
Berne & Levy, Fig. 29-16 1
Recommended Daily Intake for
Active, 25-y.o. M/F, Average Height &
Weight
70 kg male 61 kg female

Dietary Reference Intake Calculator for Healthcare Professionals:


https://fnic.nal.usda.gov/dietary-guidance/dietary-reference-intakes/dietary
-reference-intake-calculator-healthcare
Objective GI1 - Accessed1 Feb. 1, 2016
Digestion and
Absorption
of carbohydrates, proteins, and lipids

Site Digestion Absorption

Mouth/Esophagus C, (L) none

Stomach C, P, L none

Small Intestine C, P, L C, P, L

Large Intestine (bacterial) none


Water, vitamins, minerals - not digested, just absorbed

Objective GI2 2
GI/Gut Wall

Objective GI4 2 Vander, Fig 15-5


GI/Gut Wall
Single Layer of Epithelium - Barrier & Secretory/Absorptive
Surface

Cells constantly replaced (~3 day life span for each cell)

Stem cells anchored in specific positions of GI wall.

Most cells migrate toward lumen of gut, some migrate


into crypts.

Rapid division and differentiation.

Proper blood flow to the GI tract crucial to maintain


(reconstitute) the epithelial cells.

Splanchnic Circulation

Variable circulation (functional hyperemia) important for


secretions and absorption.

Objective GI4 2
Folds in the small intestine increase
surface area for exchange:

Fold of Kerckring

Fig. 14-56 from Wilson et al, Histology Image Review


Folds of Kerckring = Plicae
circulares
Objectives GI-Intro & GI-4 2
Villi & Crypts

Vander, Fig. 15-6

Objectives GI-Intro & GI-4 2 Ganong, Fig. 26-27


Vander, Fig. 15-7: Microvilli on luminal
surface of intestinal epithelial cells

Objectives GI-Intro & GI-4 2


Degree by which different anatomical Objective GI-Intro 2
6

features increase surface area in the small


intestine: Increase in Surface Area
Structure (Relative to cylinder)
Surface Area (cm2)

Area of
simple 1 ~5,300
2.5 cm Dia. x 675 cm
cylinder L

Folds of
3 ~15,900
Kerckring

Folds + Villi 30 ~159,000

Folds + Villi + ~3,200,0


600
Microvilli 00
Barrier Function of GI Wall:

Epithelial Cell Tight Junctions


Mucus Production
Reconstitution of Epithelial Cells
Immune cells in GI wall, Peyers
patches

Objective GI-4 2
Question
Which of the following would be expected to
directly contribute the most amount of water
to the small intestine on a daily basis?

A. Ingestion (Eating and Drinking)

B. Secretion of Saliva

C. Gastric Secretion

D. Pancreatic and Liver Secretion

E. Intestinal Secretion

Objective GI-1 2
Question
Which of these structures alone accounts for
the greatest increase in small intestine surface
area?

A. Cylindrical Shape

B. Folds of Kercking

C. Villi

D. Microvilli

Objectives GI-Intro & GI-4 2


Multiple
Control
Mechanism
s
Specific Signals

Redundant Signals

3 Objective GI8
Major Neurohumoral
Regulators Immune/Jux
Endocrine Neurocrine Paracrine
tacrine
Acetylcholin
Gastrin Histamine Histamine
e
Cholecystokini Vasoactive Inestinal Prostaglandin
Cytokines
n (CCK) Polypeptide (VIP) s
Reactive
Somatostati
Secretin Substance P Oxygen
n Species
Motilin Nitric Oxide 5-Hydroxytryptamine Adenosine
Glucose-
Dependent Cholecystokini
Insulinotropic n (CCK)
Peptide (GIP)
5-Hydroxytryptamine

Somatostati
n
3
Calcitonin-Gene Objective GI8
Lets look at the neural and muscular layers:

Objective GI7 3 Vander, Fig 15-6


Intrinsic Innervation: Enteric Nervous
System

Barrett
Fig. 1-8
Objective GI7 3
from Barrett, Gastrointestinal Physiology
Objective GI8 3
Neural Control of the GI
System

Barrett, Fig. 2-1 3 Objective GI8


Extrinsic Innervation
Parasympathetic Sympathetic
(major) (minor)

Preganglionic Postganglionic
(paravertebral
Innvervate cell bodies ganglia)
in myenteric plexus
Innvervate
Mostly vagus nerve nerves and some
(second half of colon glands and blood
pelvic nerve) vessels
ACh; Excitatory NE; inhibitory

Objective GI8 3
Enteric & Central NS
Interface (Schematic)

PC=Program Circuit Barrett, Fig. 2-6


IC=Integration Circuit 3 Objective GI8
Question

For parasympathetic neurons innervating the


GI tract, where are the ganglia located?

A. Paravertebral

B. Myenteric plexus

C. Submucosal plexus

Objective GI7 3
Endocrine Control

Barrett, Figs. 2-3 & 2-4


3
Stimuli for GI
Hormones

from Barrett, Gastrointestinal Physiology

(Overview - these will be covered in subsequent lectures - come back to this slide for a
summary)
4
Candidate Hormones
Glucagon-Like-Peptide-1
Intestinal L-cells release in response to luminal
sugars.
Inhibits gastric secretion and emptying.
Pancreatic Polypeptide
Released from pancreatic islets in response to a
meal.
Role unclear - may inhibit pancreatic secretion.
Peptide YY
Released by enteroendocrine cells of distal small
intestine and colon in response to fat in the
ileum.
Inhibitory effects on GI motility, gastric secretion,
and Cl- secretion of intestinal epithelium.
Ileal Brake

4
Paracrine and Immune
Mediators

from Barrett, Gastrointestinal Physiology

Objective GI11 4
Putting it all
together:

Integration of
Many Signals

Optimal Response
Based on Specific
Conditions

Objective GI11 4
Question
Which of the following is both a neurocrine and
endocrine signal?

A. Acetylcholine

B. Cholecystokinin (CCK)

C. 5-Hydroxytryptamine

D. Histamine

E. Peptide YY

Objective GI11 4
Control of Food Intake

Barrett, Fig. 2-7


Objectives GI-11, 14 4
Incretins
Definition: Hormones that amplify glucose-
stimulated release of insulin from the pancreas.

Feed-Forward Signal

Example: Glucose-dependent insulinotropic


peptide (GIP)

Released by K cells of the intestine in response


to all nutrient groups.

Coincidentally, GIP also inhibits gastric


secretions and emptying (a.k.a. gastric
inhibitory peptide - also GIP) - Feedback
Signal

4
Objective GI14 6
Learning Objectives (1 of
2)
GI-Intro. Understand the basic functions of the gastrointestinal
system and the design features that subserve these.

GI 1*. Identify the sources and typical amounts of fluid and


nutrients entering and leaving the GI tract daily.

GI 2. For the major classes of nutrients (carbohydrates, proteins,


fats), differentiate the processes of ingestion, digestion,
absorption, secretion, and excretion; include the location in the GI
tract where each process occurs.

GI 3. Describe the functions of splanchnic blood flow in sustaining


intestinal viability and as a source/sink for material transported
across the GI tract epithelium.

GI 4. Describe how the single layer of epithelial cells that lines


most of the GI tract is renewed, and describe the mechanisms
whereby these cells are both a barrier and selective portal for
secretion and absorption.
4
Learning Objectives (2 of
2)
GI 7. Describe the major anatomical characteristics of the
enteric nervous system and the major cellular divisions of the
enteric ganglia (sensory nerves, interneurons, and motor
neurons). Given either a cross section or whole mount of the
bowel wall, identify the anatomical positions and major
characteristics of themyenteric and submucosal plexi.

GI 8. Know how afferent and efferent extrinsic nerves


(sympathetic and parasympathetic) interact with the enteric
nervous system and regulate the functions of the GI tract.

GI 11. Compare and contrast the regulation of gut function by


nerves, hormones, and paracellular regulators.

GI 14. Define the word incretin concept, and as an example,


describe the glucose-dependent release and action of an
incretin from the gut.

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