Ecay---Gastro 1

Front 1

Program Circuits

Back 1

Afferent sensory nerves
synapse with interneurons and efferent motor nerves to form local reflex arcs (program
circuits)

Front 2

motor efferents synapse with

Back 2

The motor efferents of the ENS synapse with smooth muscle cells in the wall
of the gut (the muscularis mucosae and longitudinal and circular muscle layers) and
also with endocrine cells, exocrine cells, and some transporting epithelial cells.

Front 3

Sympathetic fibers of gi

Back 3

originate from prevertebral ganglia, release norepinephrine,
and synapse with intramural plexuses, blood vessels, and some smooth muscle cells.
About 50% of sympathetic fibers are afferents carrying sensory information to the CNS.

Front 4

Parasympathetic fibers

Back 4

are carried by the vagus and pelvic nerves.

Front 5

Parasympathetic fibers of gi

Back 5

They are
usually, but not always, cholinergic fibers. Some are peptidergic (substance P or
vasoactive intestinal peptide). They affect motility, exocrine enzyme secretion, and
endocrine hormone release.

Front 6

Parasymps

Back 6

Parasympathetics synapse mainly with ganglionic cells of
the intramural plexuses (myenteric and submucosal).

Front 7

Vagus nerve in gi

Back 7

The vagus nerve is 75% afferents.
These afferents mediate important vagovagal reflexes.

Front 8

Myenteric plexus

Back 8

contains inhibitory (vasoactive intestinal peptide (VIP) and
nitric oxide (NO)) and excitatory (acetylcholine and substance P) motor neurons.

Front 9

mysenteric plexus

Back 9

Most
project to smooth muscle cells in the circular and longitudinal muscle layers.

Front 10

mysenteric plexus

Back 10

The
myenteric plexus controls peristaltic and segmental contractions of the GI track. It also
sends projections to the submucosal plexus and to mucosal epithelial cells.

Front 11

Submucosal plexus

Back 11

primarily controls glandular, endocrine, and epithelial cell
secretions. Also projects to the myenteric plexus and to smooth muscle layers.

Front 12

Submucosal Plexus

Back 12

Stimulatory secretomotor neurons release acetylcholine or VIP onto endocrine and
exocrine gland cells or transporting epithelial cells.

Front 13

Parasympathetics

Back 13

Generally excitatory and release
acetylcholine to increase ENS activity. Increase GI motility and secretions. Reduce
sphincter tone (relaxes sphincter muscles). Indirectly cause vasodilation.

Front 14

Symps

Back 14

Generally inhibitory and release norepinephrine to decrease
ENS activity. Reduce GI motility and secretions. Increase sphincter tone. Directly cause vasoconstriction

Front 15

Local enteric reflexes:

Back 15

control local motility, peristalsis and segmental
contraction patterns of GI smooth muscle (program circuits)

Front 16

Gi reflex

Back 16

GI tract to prevertebral sympathetic ganglia back to GI tract: control motility in
response to severe distention or pain in the GI tract or pain/irritations in other organs.

Front 17

vasovagal reflex

Back 17

GI tract to spinal cord/brain stem back to GI tract via the vagus and pelvic
nerves: important reflexes that control motility and secretory activity

Front 18

Major mechanisms controlling GI blood circulation:

Back 18

Sympathetic vasoconstriction and metabolic vasodilation

Front 19

Minor mechanisms controlling GI blood circulation:

Back 19

Gastrin, CCK, glucose and fatty acids increase GI blood flow

Front 20

GALT has

Back 20

consists
of both organized aggregates of lymphoid tissue (Peyer’s patches) and diffuse
populations of immune cells. These include lymphocytes that lie adjacent to mucosal
epithelial cells and lymphocytes and mast cells in the lamina propria.

Front 21

Galt has two functions

Back 21

next

Front 22

1.

Back 22

protect against potential microbial pathogens (bacteria, protozoans and
viruses),

Front 23

2.

Back 23

permit immunogenic tolerance to both the potentially immunogenic dietary
substances and bacteria that normally reside in the lumen of the large
intestine.

Front 24

not immune defense

Back 24

These mechanisms include gastric acid
secretion, mucin secretion, peristalsis and the epithelial permeability barrier. Persons
with impaired small intestinal peristalsis (referred to as either “blind loop syndrome” or
“stagnant bowel syndrome”) have higher than normal levels of aerobic bacteria in the
lumen of their small intestine. As a consequence they are more susceptible to diarrhea
or steatorrhea (increased fecal fat excretion).

Front 25

autocrines

Back 25

Epidermal Growth Factor
Transforming Growth Factor α & ß
Insulin-like growth factor

Front 26

Secretin/GIP Family

Back 26

Secretin
*GIP (glucose-dependent insulinotrophic peptide or gastric inhibitory peptide)
VIP (vasoactive intestinal peptide)
Enteroglucagon (glucagon-like peptide or GLP-1)

Front 27

Structurally unrelated GI peptides

Back 27

Pancreatic Polypeptide (PP)
Substance P
Epidermal Growth Factor
*Motilin
Others - Gastrin releasing peptide (GRP or human bombesin),
guanylin, neurotensin, enkephalins, ghrelin, peptide YY.

Front 28

Gastrin and cck

Back 28

are structurally similar

Front 29

A protein-rich meal is a more
potent stimulator of gastrin release
than a carbohydrate-rich meal.

Back 29

gastrin

Front 30

gastrin released

Back 30

at higher pH

Front 31

GASTRINS EVERYWHERE

Back 31

Most of the gastrin in blood is a 17 amino acid polypeptide. This form is referred
to as “little gastrin” because a 34 amino acid form (G34) is also found in blood. Other
forms of gastin (G14 and G8) are also present in blood.

Front 32

ANtral G cells

Back 32

Antral G cells make primarily
G17.

Front 33

Duodenal G cells

Back 33

Duodenal G cells make G34. G17 and G34 are equipotent but G34 has a longer
half-life in plasma.

Front 34

Whats needed for activation

Back 34

The carboxy terminal four amino acids of gastrin are required for
strong gastin biological activity. The tyrosine residue six positions from the carboxy
terminus is sulfated in about 50% of gastrin molecules. Sulfation does not alter the
biological activity of gastrin.

Front 35

CCK and gastrin similar

Back 35

CCK is present in blood as a 33 amino acid peptide. The carboxy terminal 5
amino acid are identical to gastrin. The tyrosine at position 7 from the carboxy terminus
must be sulfated for CCK activity. If it is not, the molecule has gastrin-like effects.

Front 36

CCK and Gastrin bind to the CCK-A and CCK-B receptors.

Back 36

The CCK-A receptor has
100-fold greater affinity for CCK over gastrin. The CCK-B receptor has nearly equal
affinity for gastrin and CCK. The CCK-A receptor has very low affinity for the unsulfated
form of CCK.

Front 37

How is gastrin released

Back 37

Gastrin release from antral stomach G cells is stimulated by protein-containing
meals and gastric distension. Chemical stimulation of release occurs in response to
peptides and amino acids. Neural stimulation in response to distension or stretching of
the stomach wall is due to both long (vagovagal) and local (enteric) cholinergic reflexes.

Front 38

Gastrin does WHAT

Back 38

Gastrin stimulates gastric acid secretion by parietal cells and histamine release
by enterochromaffin-like (ECL) cells. Gastrin also stimulates GI mucosal proliferation
(gastrin is a GI trophic hormone).
Figure 7 A protein-rich meal is a more
potent stimulator of gastrin release
than a carbohydrate-rich meal.

Front 39

@Wht does CCK do

Back 39

CCK
is released from I cells in the
duodenum. CCK release is stimulated
by hydrolyzed proteins (peptides,
amino acids) and fatty acids > 8
carbons long. CCK’s main activities
are stimulation of gall bladder
contraction and pancreatic enzyme
secretion.

Front 40

Ingestion of a protein- and
fat-rich meal stimulates CCK release,
which coincides with gallbladder
contraction.

Back 40

cck

Front 41

Secretin does what

Back 41

Secretin release from S cells in the
mucosa of the duodenum is triggered
by acid (low pH). Secretin stimulates
pancreatic HCO3 and fluid secretion.
It is sometimes called “nature’s
antiacid”.

Front 42

gastrin and secretin

Back 42

Both responses are inhibited by cimetidine, a histamine (H2) receptor blocker
that inhibits gastric acid secretion.

Front 43

VIP does

Back 43

VIP stimulates pancreatic and intestinal
fluid secretion.

Front 44

VIP does

Back 44

VIP stimulates local mesenteric blood
flow.

Front 45

VIP does

Back 45

VIP relaxes GI smooth muscle,
especially at sphincters (lower
esophageal sphincter, pyloric sphincter,

Front 46

VIP concentraion

Back 46

Note that the local
concentration of VIP is highest at the
lower esophageal sphincter and the
pylorus consistent with its role as a
relaxer of smooth muscle.

Front 47

grehlin is important becasue

Back 47

Ghrelin is a peptide hormone produced by the stomach. It exhibits potent growth
hormone releasing activity and stimulatory effects on food intake and digestive function
while reducing energy expenditure. Plasma ghrelin levels are elevated during fasting
and decline after a meal. Ghrelin is the first and only feeding/hunger regulating hormone
produced outside the central nervous system.

Front 48

Endocrine

Back 48

classic hormones - there are five: gastrin, cholecystokinin (CCK),
secretin, glucose-dependent insulinotrophic peptide (GIP), and motilin.

Front 49

paracrine

Back 49

released by one cell to influence the behavior of
neighboring cell or cells. Examples are somatostatin, serotonin, histamine, adenosine,
prostaglandins, and cytokines.

Front 50

neurocrines

Back 50

released by neurons at synapses (acetylcholine, vasoactive
intestinal peptide (VIP), gastrin releasing peptide (GRP), nitric oxide, serotonin,
epinephrine, enkephalins).

Front 51

Glucose-dependent insulinotropic peptide (GIP)

Back 51

released by cells of the
duodenum and jejunum in response to fatty acids, amino acids, and oral glucose. GIP
stimulates insulin release by pancreatic ß-cells and may inhibit gastric acid secretion.

Front 52

Motilin

Back 52

released by cells of the duodenal mucosa during fasting or
interdigestive periods. Causes contraction of intestinal smooth muscle and regulates GI
motility during interdigestive periods, preparing the GI tract for the next meal.

Front 53

Somatostatin

Back 53

released by cells throughout the GI tract. In the stomach it is
released in response to acid in the lumen. Release is inhibited by vagal stimulation.
Somatostatin inhibits release of most GI hormones and inhibits gastric acid secretion.
Useful in the treatment of GI hormone-secreting tumors (see Clinical Case 1).

Front 54

Guanylin

Back 54

produced by mucosal endocrine cells from pylorus to rectum.
Stimulates intestinal Cl and fluid secretion. The guanylin receptor also responds to the
heat-stable enterotoxin of certain diarrhea-causing strains of E. coli. May be involved in
salt and water homeostasis.

Front 55

Histamine

Back 55

secreted by mast cells and ECL cells throughout the GI tract.
Increases gastric acid secretion and intestinal fluid secretion.

Front 56

GRP

Back 56

Gastrin releasing peptide (GRP) - (human bombesin) released by vagal
stimulation to the antral stomach. GRP stimulates gastrin secretion.

Front 57

Enkephalins/Opiods

Back 57

secreted by nerves in the mucosa and smooth muscle,
stimulates contraction of smooth muscle especially sphincters, inhibits intestinal fluid
secretion. Useful in the treatment of diarrhea.

Front 58

GI BLOOD FLOW

Back 58

Blood from GI organs (stomach, intestines and pancreas) drain via the hepatic
portal vein to the liver. Blood flow to the mucosa is greater than to the rest of intestinal
wall and responds to changes in metabolic activity. Even when fasting, the GI tract
receives 25% of cardiac output despite comprising only 5% of body mass. Blood flow to
the small intestines can double after a meal. Flow in individual vessels can increase five
fold, lasting up to 3 hours. Intestinal circulation is capable of extensive autoregulation.
Sympathetic innervation causes vasoconstriction, which can shunt blood to muscles
during heavy exercise or to other vital organs during circulatory shock.

Front 59

Last graphs of physiology lec 1

Back 59

are fucking scary.

Front 60

How does Gi smooth muscle function

Back 60

GI smooth muscle is a
unitary smooth muscle. Cells are
coupled by gap junctions (nexus).
Membrane depolarizations move
from one cell to another and large
groups of cells contract
simultaneously in response to
stimulation of just a few cells.

Front 61

Nerve endings at smooth
muscle cells are not synapses as in
skeletal muscle. Beaded enlargements
or varicosities are the sites of
neurotransmitter release. There may be
as many as 20,000 varicosities per
neuron. Thus, one neuron can innervate
many target cells.

Back 61

smooth muscle of Gi innervation

Front 62

Smooth muscle contraction

Back 62

Biochemical steps in
the contraction of smooth
muscle. Increased cytoplasmic
Ca2+ activates myosin light
chain kinase, which
phosphorylates myosin.
Myosin-P then binds to actin,
resulting in contraction. As
Ca2+ levels decline, the kinase
is inactivated, and a
phosphatase removes the
phosphate from myosin-P,
leading to relaxation.

Front 63

Smooth muslce

Back 63

Action potentials in smooth muscle
are more prolonged than skeletal
muscle, resulting in a slow increase in
force - not a twitch

Front 64

theantral stomach,
small intestine, large intestine

Back 64

are phasic contractors

Front 65

sphincters have

Back 65

tonic contractions

Front 66

GI smooth muscle displays tone or tonus that is constant partial contraction, the membrane potential is not stable and the osscillations are called

Back 66

The
oscillating membrane potentials are known as slow waves or the basic electric
rhythm (BER) of GI smooth muscle.

Front 67

BER sets the pace for

Back 67

contractions and are inherent

Front 68

AMPLITUDE OF BER

Back 68

but NOT FREQUENCY CAN BE ALTERED BY HORMONES ETC>>>

Front 69

smooth muscle of the gi also responds to

Back 69

stretch

Front 70

BER begins in the interstitial cells

Back 70

of CAJAL and spreads to the smooth muscle through electric gaps.

Front 71

ca in depolarixation k out ====

Back 71

repolarization

Front 72

Action potential results

Back 72

when a slow wave exceeds the depolarization threshold. ACTION potentials give a much stronger contraction than the mere slow waves.

Front 73

BER is just the rhyhthm

Back 73

of membrane oscillations, only amplitude is changed

Front 74

nerve inputs to smooth muscle do not by themselves initiate contraction

Back 74

nerves instead modify the inherent contractile activity of the smooth muscle.

Front 75

norepinephrine ihibts contractions

Back 75

by a and b mechanisms. a has Ca2+ efflux and b results from elevated cAMP and inhibted MCLK and activated phosphotases

Front 76

Acetycholine works by

Back 76

an IP3 mechanism for increasing Ca++ influx into the cell from internal storage. also influx from external stores

Front 77

excitatory agents include

Back 77

Acetylcholine, serotonin, opioid peptides, and substance P that increase Ca++

Front 78

INhibitory agents include

Back 78

VIP
ß-adrenergics
glucagon
nitric oxide (NO), that increase cAMP or cGMP

Front 79

CCK and GRP (bombesin)

Back 79

increase release of acetylcholine and substance P

Front 80

Somatostatin
neuropeptide Y
and a-adrenergics

Back 80

inhibt the release of acetycholine and substance P.

Front 81

Opioid peptides

Back 81

inhibt adenyly cyclase and decrease cGMP probably stims contraction

Front 82

reticular formation of the brain stem

Back 82

is the swallowing center

Front 83

esophagus

Back 83

Most of the esophagus is within the
thoracic cavity and below atmospheric pressure. Sphincters on either end prevent air
and gastric contents from entering the body of the esophagus. Between swallows both
sphincters are closed and the body of esophagus is flaccid.

Front 84

innervation of esophagus

Back 84

is at the vagus nerve

Front 85

Esophageal peristalsis

Back 85

from swallowing and distention

Front 86

stress activation and lower esophageal sphincter

Back 86

Lower esophageal sphincter (LES) smooth muscle responds to
stretch by contracting to oppose stretch. Does not require nerves. Resting tone of LES
may be entirely myogenic. Relaxation of LES during swallowing is neurally mediated.
Decreased activity of acetylcholine fibers, and an increase in VIP fibers.

Front 87

wierd lower sphincter contraction

Back 87

The lower esophageal sphincter (LES) is innervated by both vagal excitatory
fibers (VEF) and vagal inhibitory fibers (VIF). Relaxation of the LES is associated with
an increased frequency of action potentials in VIF and decreased frequency of action
potentials in VEF. Reciprocal changes occur when the sphincter regains its resting tone.

Front 88

Gastric smooth muscle is divided into

Back 88

orad and caudal for motility orad is more proximal to mouth

Front 89

orad relaxes

Back 89

The orad stomach relaxes at
about same time as the LES. After
passage of a bolus of food, pressure
in the orad region returns to the
preswallow level.

Front 90

The stomach is receptive to relaxation

Back 90

The stomach can accommodate large volumes without a
large change in pressure. Receptive relaxation is a vagovagal reflex elicited by
stretching of the stomach. Removal of vagal inputs (vagotomy), makes the stomach less
distensible. VIP may be important neurotransmitter for receptive relaxation.

Front 91

contractions of the ORAD

Back 91

CCK makes the orad area more distensible. Musculature in this area is thin and
contractions are weak. There are very small or no slow waves in this area of the
stomach. Food is layered and unmixed. As stomach empties, the orad region contracts
to normal size. Resting tone of the orad region is intrinsic to the orad smooth muscle.

Front 92

increasing contractions of the stomach

Back 92

Following a meal, peristaltic
contractions begin at mid stomach.
Velocity and force increase as
contractions move toward the
pylorus.

Front 93

retrograde contractions

Back 93

Contractions last 2-20 sec at
a rate of 3-5 contractions/min. Near
the pylorus, wall contractions
overtake contents and most is forced
retrograde (retropulsion; see next
Figure). This serves to mix and grind
stomach contents.

Front 94

WHere are contractions initiated in the stomach

Back 94

Contractions are
initiated by the intrinsic electrical
activity of smooth muscle cells (and
Interstitial Cells of Cajal) at the
pacemaker region.

Front 95

pyloric sphincter closes at food moves through

Back 95

to cause retrograde ejaculation of food for mixing and digesting

Front 96

Filling of stomach

Back 96

stimulates antral contractions
and inhibits pyloric contractions and is a local enteric reflex

Front 97

peptides and amino acids in the stomach and gastrin

Back 97

Peptides and amino gastrin stimulates antral contractions
acids in stomach

Front 98

acids in the duodenum are mediated by secretin and vasovagal reflex and

Back 98

slow antral contractions and
stimulates pyloric contractions

Front 99

Fats in duodenum

Back 99

CCK and stimulates both antral and pyloric contractions

Front 100

Fats in the duodenum mediate cck

Back 100

this stimulates both antral and
pyloric contractions and inhibts emptying

Front 101

Hyperosmolarity

Back 101

shit inhibts emptying

Front 102

peptides and amino acids

Back 102

inhibt emptying throuhg by stimulating pyloric and antral contractions...like cck...vasovagal refelx

Front 103

acid in duodenum

Back 103

stops antric contractions to inhibit food clearance

Front 104

if esophageal contents are not cleared by the primary then a secondary

Back 104

one activted by stretch will clear the esophagus

Front 105

LES lower sph.

Back 105

is totally myogenic and dependent on the muscle.VIP and/or nitric oxide is released from myenteric plexus motor neurons in
response to increased activity of vagal inhibitory fibers. At the same time, the orad
portion of the stomach relaxes (receptive relaxation).

Front 106

Achalasia

Back 106

dysphagia from LES not relaxing

Front 107

cck inreases receptive relaxtion

Back 107

of the orad stomach

Front 108

emptying

Back 108

Carbohydrates
are cleared faster than proteins, which are emptied faster than fats.

Front 109

review

Back 109

questions