Heller: Lecture 1 Overview of the Gastro-Intestinal System
Ruth Olson
The physiological homeostatic role of the GI system
is to provide a large surface area for nutrient, salt,
and water transfer between the internal
environment and the outside world.
1.
2.
3.
4.
liver first before the heart!!! The liver is incredibly
important, esp. biochemically.
Gross structure and function of the GI system
Microscopic anatomy of the gut
GI smooth muscle function
GI exocrine secretions
I. Gross Structures of the Gastro-Intestinal Track
and Accessory Glands
II. GI Microscopic Anatomy - General characteristics
The GI wall has modulations for dif. activities in dif.
places. The mucosa is characterized by a epithelial
cell layer. They interface with outside envt. The
mucosa contains endo, exo (into gut) and mucus
(exo secretion) cells. Ducts from various accessory
glands come through the wall of the gut. There is
some wimpy muscle here as well. Submucosa:
blood, lymphatics, submucosal and myenteric
nerve plexi. The muscle layers have muscle
organized in circular and lungitudal fashion
(squishing and sloshing.)
Abnormal behavior of accessory glands cause
problems.
•GI Tract - Basic Processes
Digestion, Absorption, Secretion and Motility.
We have four processes we’ll talk about ( we’ll
ignore ingestion, this is left for endo and behavioral
science.) Once we put food and H2O into the gut,
we have to digest large, complex molecules.
Digestion is aided by the secretion of digestive
enzymes (these aren’t secreted in esophagus, which
is simply a conduit.) Once things, are digested, they
are absorbed (most is absorbed by the middle of the
jejunum.) The mobile process ensures things flow
through at the correct speed. Excretion is a
byproduct, you excrete what you don’t digest or
absorb. Absorbed molecules go into blood  to the
The villi stick into gut, secrete and absorb, they’re
richly endowned with capillaries and lymphatics.
Heller: Lecture 1 Overview of the Gastro-Intestinal System
Ruth Olson
There is HUGE surface area for absorbption.
Invaginations at bottom are crypts (lots of important
things going on.) Without microvilli, intestine is no
good.
• Epithelial cell proliferation and turnover in the
intestine
- stem cells in the Crypts of Lieberkuhns divide,
differentiate and migrate to the tips of the villi with
complete turnover every 3-6 days. They are dividing
ALL the time. Chemotherapeutics have SEVERE GI
consequences because these cells are so mitotically
active.
•Caveolae may increase surface area 50-70%.
Function not well understood (we don’t understand
how filaments interact to cause movement.) No
troponin (Ca2+ is doing something different.)
•Membrane blebs have Ca2+ sequestering abilities.
GI Smooth Muscle: Excitation-contraction coupling
initiated by increases in intracellular calcium ion
concentration.
Myosin and actin interact (somehow) to cause
contraction. These cells can decrease by half their
original length (SM 15% of its length only.) Myosin
is phosphorylated by myosin light chain kinase,
which is activated by calcodulin:Ca2+ (which way or
may not be freely floating in the cytoplasm.)
Smooth muscle relaxation: dephosphorylation of
myosin (triggered by myosin light chain
phosphatase.)
Maintains tension without splitting ATP (like rigor.)
This is called latch state. We see this at the
sphincters [upper esophageal (prevents air entry
into stomache), lower esophageal (prevents regurg),
pyloric (keeps content in stomache), illealsecal
(allows content into intestine, anal (makes you
socially acceptable)].
•III. GI Smooth Muscle
- long, slender cells separated into branching
bundles covered by connective tissue
- “gap junctions” or “nexuses” are low-resistance
electrical coupling between cells (cytoplasmic
ridges.) Wave of depol spreads.
- tissue responds as a “single functional unit”
- rare discrete nerve-muscle junctions
-neurotransmitters released from intermittent
swellings along the nerve axon. NTs influence cells in
a variety of ways.
GI Smooth Muscle
•Large surface area-to-volume require low ionic
permeability to maintain membrane potential
•Actin and myosin present
•Intermediate filaments form an internal
cytoskeleton with dense bodies and dense bands.
Structural.
•Scarce sarcoplasmic reticulum (normally mops up
all the calcium.
GI Smooth Muscle Membrane Potential:
The Transmembrane Potential at a given instant in
time:
- is determined by the electro-chemical gradients for
permeant ions
- is estimated by applying the Nernst Equation to the
MOST permeant ion:
- is more accurately estimated by taking into
consideration the relative permeability of the
membrane to all permeant ions and applying the
Goldman Field Equation:
GI Smooth Muscle Membrane Potential:
- Resting membrane potentials are lower (less
polarized) than in most nerve and striated muscle
fibers.
- Transmembrane potential is strongly influenced by
the electrogenic sodium/potassium pump (3 Na+ out
for 2 K+ in) which hyperpolarizes the membrane. This
tidies up the gradients so it’s about -60 mV. If you
poison this pump, the membrane will depol.
Commmon cardiac drug (digitalis) works by
Heller: Lecture 1 Overview of the Gastro-Intestinal System
Ruth Olson
poisoning this pump everywhere, so there are GI
effects (diarrhea due to inc gut motility.)
•3. GI smooth muscle has a remarkable ability to
shorten (e.g., to 50% of resting length.
•4. Neural activity can increase or decrease
contractile activity by influencing the amplitude of
the slow electrical waves.
**** In general, parasympathetic stimulation
increases activity and sympathetic stimulation
decreases activity.
GI Smooth Muscle - Excitation-Contraction Coupling
Slow wave electrical activity (3-12/min, 5-15 mV)
initiated by interstitial cells of Cajal
•Slow waves due to oscillations in ion permeability
or membrane Na+/K + ATPase. The speed of the
waves are dif in dif parts of gut.
•Amplitude, but not frequency, of slow waves can be
altered by neural and hormonal signals
•GI Smooth Muscle - Contractile characteristics:
5. GI smooth muscle has a length-tension
relationship (like striated muscle) but with a much
broader maximum.
•Action potentials can occur on the crests of the
slow waves and involve an initial increase in PCa and
a delayed increase in PK
•Muscle contraction accompanies action potential
occurrence.
•GI Smooth Muscle - Contractile characteristics:
•1. Contraction times vary between rapid “phasic”
(seconds) and long “tonic” types (minutes to hours).
•2. Basal resting tension of “tone” is a highly
efficient level of contraction that is maintained
without elevation in intracellular Ca++ and without
much energy expenditure. (found at sphincters)
IV. GI Secretory Processes
•GI Exocrine Secretions - A. enzymes and protein
products into the lumen of the gut. - B. electrolyte
movements
Heller: Lecture 1 Overview of the Gastro-Intestinal System
Ruth Olson
Common processes found in GI epithelial cells:
- Na/K ATPase on abluminal membrane
- Carbonic anhydrase forming H+ and HCO3- Na/H exchangers and HCO3-/Cl- exchangers
on either side
These cells are polar (do one thing on one side and
another thing on the other.) Carbonic anhydrase is
involved in A/B balance.
Almost everywhere in gut there is a HCo3exchanger.
C. Water movement: Water moves through and
between cells according to osmotic gradients and
“conductivity” of the specific epithelia.
GI Exocrine Secretions - D. Mucus
- Mucus is a highly viscous, hydroscopic gel secreted
by specialized epithelial cells throughout the gut.
(Mucus is the noun, mucous is the adjective)
- Monomers are combined into tetramers by
disulfide links between protein subunits
- Glycosylation (sugar coated) protects the protein
core from digestion (by pepsin in the stomach)
- Trefoil peptides influence the viscosity and integrity
of the mucus gel
GI Exocrine Secretions D - Functions of Mucus
•Lubrication
–Protection (physical, chemical, antiseptic). E.g.,
Gastro-mucosal barrier