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7/27/2019 Gastrointestinal Physiology review
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GI Physiology Review
Brett Brownlee
[email protected] hours: Tuesdays 6-8
mailto:[email protected]:[email protected]:[email protected]:[email protected]7/27/2019 Gastrointestinal Physiology review
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Feedback Systems
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Regulated vs. Unregulated Processes
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Innervation of the GI Tract
Parasympathetic (vagus) - increases motility
and relaxes sphincters
Sympathetic- decreases motility and contracts
sphincters
Enteric- Myenteric and Submucosal plexuses
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Saliva
Components
Salivary amylase, lingual lipase, bicarbonate, mucins,
salts (hypotonic)
Effect of ANS
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Swallowing
Anatomically 4 tubes
are converging
Reflex- move cohesive
bolus created to back
of mouth
Once swallow- no
more control
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Esophageal Peristalsis
UES opens reflexively and allows material to
enter esophagus
Reflexive opening of the LES to allow material
into stomach
Propagated contraction of esophageal muscle
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Esophageal Peristalsis
Afferents and Efferents
Controlled by Swallowing Center in
Medulla
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Sphincters
Normal Pressure
UES - 80 mmHg
LES - 30 mmHg
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What if something gets stuck?
Secondary Peristalsis
Stuck food sensed by
stretch receptors in
the mucosa
Enteric reflex (No ANS
reqd)
Repeats every fewminutes
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Know Your Cases!
Achalasia
Diffuse Esophageal Spasm
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Anatomy and Function of the Stomach
StorageBreaks up foodDigests proteinBacterialcidalVirucidalKills parasites
Dissolves boneIncreases bioavailability of calcium & iron
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Gastric Filling
Receptive Relaxation
Part of swallowing reflex- vagus mediated
Reflex Relaxation
Gastric stretch receptors, Vagovagal reflex
Stress Relaxation
Property of smooth muscle
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Gastric Juice
Secretion SecretoryCell GastricLocation
HCl Parietal Fundus &Body
Pepsinogen Chief Body & AntrumGastrin G-cell AntrumIntrinsicFactor Parietal Fundus &BodyMucous Mucous Neck All
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Secretions
Endocrine Secretions
Gastrin
Histamine from ECL cells
Exocrine Secretions
HCl
Pepsinogen
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HCl Secretion
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Dietary pH buffers
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Regulation of HCl secretion
At a neutral pH
G cells secrete gastrin
Gastrin stimulates ECL
cells to secrete histamine Histamine stimulates
parietal cells to secreteHCl
Gastrin also stimulatesparietal cells to secreteHCl
GastricG-cell
Parietalcell
Gastrin
ECL
HistamineNeutral pH
Acid
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Regulation of HCl secretion
At a acidic pH (2-3)
G cells inhibited
Decreases secretion of HCl
by parietal cells
GastricG-cell
Parietalcell
Gastrin
ECL
HistamineNeutral pH
Acid
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Regulation of
Gastric Acid
Secretion
Cephalic phase of
Gastric Acid Secretion
Gastric phase of
Gastric Acid Secretion
gastric
G-cell
gastricD-cell
parietalcell
Protein
aminoacids
HStretch
Vagus
InhibitStimulate
Somatostatin
Gastrin
+Positive
Feedback
Negative
Feedback
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Gastric Protective Mechanisms
Epithelium/Tight Junction
Mucus secretion
Bicarbonate secretion
Rapid cell turnover Blood flow
Prostaglandins
Negative feedback
control of acid secretion
Blood Flow
PG PGPG
PG
PG
PG
PG
PG
PG
PGPGP
GPG
PG
PG
PG
P
G
PG
PG
PGPG
Stomach Wall
NSAID
X
XX
ChemotherapyX
Pepsin
Mucous
H
HCO3
+
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Pepsinogen Activation
Below pH 5 autocatalysis
Catalytic domain is no longer inhibited
Autolytic activation
Cleavage of 44 AA from N term
Activate other pepsinogen molecules
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Visible Mucous
Mucous and HCO3 line
the gastric mucosa
Protect mucosa from
pepsin and HCl
Think of as a chain
linked fence
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Know Your Cases!
Achalasia
Diffuse Esophageal Spasm
GERD PUD
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GERD Treatment
Life style changes Elevate head in bed
Avoid eating before bed
Diet avoid EtOH, chocolate, mint, fats
Surgical hiatal hernia repair
Life style changes Elevate head in bed
Avoid eating before bed
Diet avoid EtOH, chocolate, mint, fats
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Drugs To Treat GERD
H2 blockers- cimetidine
Takes 30 min to become effective
PPI- omeprazole- side effects
Takes 2-3 days to become effective
100% inhibition
Side effects- hip fractures
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PUD
Ulcer- hole in epithelium Gastric / Duodenal
Etiology Hypersecretion of Acid
gastrin secreting tumor of pancreas (Zollinger-Ellison)
H. pylori
Chemo
Ischemia
Gastric dumping duodenal ulcer
Stress
Alcohol
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Treatment of PUD
Prevention- replace NSAIDs with COX-2
inhibitors (celebrex)
Healing
neutralize gastric contents PPI
Eliminate H. pyloriantibiotic
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Vomiting
Control Center Brain Stem
2 steps
Retching
Move chyme from duodenum and stomach into lower
esophagus
Vomiting Move chyme from lower esophagus out
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Retching
Reverse peristalsis in jejunum and duodenum
Inhibition of gastric peristalsis
Relaxation of LES
Contraction of longitudinal esophageal body wallmuscle
Spasmodic, repeated insipiratory efforts againstclosed glottis
Contraction of abdominal muscle Contraction of diaphragm
Contraction of intercostals
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Vomiting
Contraction of Pylorus
Contraction of abdominal muscles
Relaxation of diaphragm Relaxation of UES
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Chronic Vomiting
Metabolic alkalosis
loss of hydrogen ion
elevated bicarbonate
Hypochloremia
direct loss of chloride ions
Dehydration
stimulates aldosterone secretion
retention of sodium and water by kidneys
excretion of potassium and hydrogen ions by kidneys
Hypokalemia secondary to sodium and water retention by kidney
Hypercapnia
response to metabolic alkalosis
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Worse On Empty or Full Stomach
Hypokalemia
cardiac arrythmias
muscular weakness
myalgia muscle cramps
Hypercapnia
tachypnea
dyspnoea muscle twitching
Dental erosion
acid desolves
hydroxyapatite
loss of dental enamel
Esophageal erosion
Mallory-Weiss tear
small tears of esophageal
mucosa
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Interstitial Cell of Cajal
Located between longitudinal and circularsmooth muscle layers
GI pacemaker
Spontaneous, oscillating changes inmembrane potentials
Occurs at different rates 3/min in the stomach, 12/min in the proximal
small intestine, 5/min in the ileum
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Controlling Composition of Duodenal
Chyme
DuodenalMotility
PancreaticSecretion
Bile
SecretionGastricEmptying
WaterSecretion
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Tonicity
Tonicity of chyme is
changed by passive
diffusion of water
Mucosal cells measure the
tonicity
Release enterogastrone to
slow gastric emptying
Hypertonicity
DecreasedEmptying
DecreasedSecretion
MucosalCell
Enterogastrone
Regulation of Duodenal Tonicity
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Proteins and AAs
Presence slows rate
of gastric emptying
Mucosal Cells release:
Gastrin
CCK
ProteinsAA
GASTRIN, CCK & GIP
IncreasedMixing
DecreasedEmptying
Increased
Secretion
MucosalCell
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Fats and FFAs
Presence of fats and
FFAs slows gastric
emptying
Mucosal Cell releases
CCK
FATSFFA
CCK & GIP
DecreasedEmptying
Decreased
Secretion
MucosalCell
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Duodenal pH Regulation
Acidity is measured induodenum
Short reflex slow
rate of emptying Endocrine (secretin)-
slow rate of emptyingand increase bicarbproduction inpancreas
H+
Short Reflex
Acidic Chyme
Decreased Rate ofGastric Emptying
Decreased Rate ofGastric Emptying
secretin
HCO3
Pancreas
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Primary Pancreatic
Exocrine Secretagogues
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Dumping Syndrome
Rapid gastric emptying - Causes
Decreased pH of duodenal chyme Decreased fat and protein solubility
Decreased bile acid solubility Decreased enzyme activity (lipase)
Increased rate of water secretion
Decreased enzyme:substrate ratio
Decreased emulsification of fat Osmotic and secretory diarrhea
Undigested and unabsorbed food
Bacterial free fatty acids
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Carbohydrate Digestion
Know the disaccharides
Sucrose
Lactose
Maltose
Pancreatic and Salivary Amylase
Disaccharidases
Monosaccharides are absorbed
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Carbohydrate Absorption
Monosaccharides are absorbed
Know the GLUT transporters
Luminal membrane
SGLT-1 indirect active transport of glucose
GLUT-5 fructosefacilitated diffusion
Basal Membrane GLUT-2 facilitated diffusion
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Digestion of Proteins
Pancreatic proteases secreted as zymogens Secretion is stimulated by CCK
Trypsinogen activated by
enteropeptidase/enterokinase(found in thebrush border)
Trypsin then activates the other proteases
Absorption of dipeptides, tripeptides and freeAAs via facilitated diffusion
In enterocyte dipeptides and tripeptidesbroken down by intracellular peptidases
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Fat Absorption
Bile Salts act like detergent, emulsify fat
Increase surface area
Micelles increase rate of diffusion across
unstirred layer
Colipase binds bile salts
Lipase binds colipase and cleave TAGFFA
and monoacylglycerol
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unstirred layer
absorptiveepithelium
fat drop
FFA
micelle
FFA
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Fat Absorption
FFA and MAG enter cell- head to the ER
Re-esterify and repackage into a chylomicron
Apolipoprotein binds receptor and is
exocytosed
Enter lacteal (lymphatic vessel)
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Reabsorption of Bile Acids & Salts
Indirect active transport of bile salts using Nagradient
In terminal ileum
Return to the liver via portal circulation
This recirculation is called the Enterohepatic
Circulation
The release of bile occurs when the smooth
mm of the gall bladder contracts (CCK)
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Absorption of Ca
Absorbed by facilitated diffusion (channels)
Huge concentration gradient
Expression of channels regulated by Vit D
Ca must be bound CaBP found in
enterocytes
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Absorption of Iron
Absorbed in duodenum and jejunum
Iron reductase converts ferric iron to ferrous
iron
Ferrous iron converted to ferric iron
intracellularly by ferroxidase
Ferric iron bound by ferritin and mobilferrin
Transported into blood, bound by transferrin
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Absorption
of
Iron
Ferroportin 1
FerritinFe
+++Fe+++Fe+++Fe
+++
Fe+++
Fe+++
Fe+++
Fe+++ Fe+++
Fe+++
Fe+++
Fe+++
Fe+++
Fe++
Fe+++
Fe+++
Fe+++
Fe+++
Fe+++
Fe+++
Heme
Heme
HephaestinTF
Ferroxidase
Lumen ofDuodenum& Jejunum
Mobilferrin
Ironreductase
Cap
illary
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Capillary
arterial
venous
B12
B12
B12 B12
B12B12
B12B12B12
B12
TCII
IF
IF
IFIF
IFreceptor
lysosome
endosome
intrinsicfactor
secretoryvesicle
transcobalamin II
Absorption of Vitamin B12
Standing Osmotic Gradient Mechanism
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Cl
-
Bulk Flowof H O2
Capilla
ry Na+
H O2
H O2
Lumenof
Colon
For Water Reabsorption
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Chronic administration of which of the following types
of drugs would lead to a sustained increase in serumgastrin levels?
a. H2
receptor antagonist
b. Proton pump inhibitor
c. Anticholinergic
d. Antacid
e. Beta blocker
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Withdrawal from chronic administration of an
antisecretory compound is followed by rebound gastric
acid hypersecretion. Which drug could account for theobserved result?
a. A H1
receptor antagonist
b. A proton pump inhibitor
c. A cholinergic receptor antagonistd. An antacid
e. A CCKB
receptor antagonist
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The paracrine secretion responsible for
inhibiting gastric acid secretion is
a. Histamineb. Enterogastrone
c. Somatostatin
d. Pepsin
e. Enterooxyntin
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Secondary esophageal peristalsis
a. Is preceded by an oral-pharyngeal phase of
swallowing
b. Involves activation of medullary swallowing
centers
c. Is accompanied by lower esophageal sphincter
relaxation
d. Occurs in both the skeletal and smooth muscle
portions of the esophagus
e. Is abolished by vagotomy
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Vitamin B
12
is absorbed primarily in the
a. Stomach
b. Duodenum
c. Jejunum
d. Ileum
e. Colon
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Absorption of fat-soluble vitamins requiresa. Intrinsic factor
b. Chymotrypsin
c. Pancreatic lipase
d. Pancreatic amylasee. Secretin
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In contrast to secondary esophageal peristalsis, primary
esophageal peristalsis is characterized by which of the
following statements?
a. It does not involve relaxation of the lower esophageal
sphincter
b. It involves only contraction of esophageal smooth
muscle
c. It is not influenced by the intrinsic nervous system
d. It has an oropharyngeal phase
e. It involves only contraction of esophageal skeletal
muscle
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Which one of the following statements about gastric
emptying is correct?
a. Solids empty more rapidly than liquids
b. Vagotomy accelerates the emptying of solids
c. Indigestible food empties during the digestive
period
d. Acidification of the antrum decreases gastric
emptying
e. Vagotomy decreases accommodation of the
proximal stomach
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The principal paracrine secretion involved in the
inhibitory feedback regulation of gastric acid secretion
is
a. Gastrin
b. Somatostatin
c. Histamine
d. Enterogastrone
e. Acetylcholine
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Which one of the following statements best describes water
and electrolyte absorption in the gastrointestinal tract?
a. Most water and electrolytes derive from the oral intake offluids
b. The small and large intestines have similar absorptive
capacities
c. Net secretion of potassium occurs from the ileumd. Osmotic equilibration of chyme occurs in the duodenum
e. Cholera toxin inhibits sodium-coupled nutrient transport
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Acidification of the duodenum will
a. Decrease pancreatic secretion of bicarbonate
b. Increase secretion of gastric acid
c. Decrease gastric emptying
d. Increase contraction of the gallbladdere. Increase contraction of the sphincter of Oddi
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The rate of gastric emptying increases with
an increase in
a. Intragastric volume
b. Intraduodenal volume
c. Fat content of duodenum
d. Osmolality of duodenum
e. Acidity of duodenum
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Basal acid output is increased by
a. Acidification of the antrumb. Administration of an H
2receptor antagonist
c. Vagotomy
d. Alkalinization of the antrum
e. Acidification of the duodenum
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After secretion of trypsinogen into the
duodenum, the enzyme is converted into its
active form, trypsin, by
a. Enteropeptidase
b. Procarboxypeptidase
c. Pancreatic lipase
d. Previously secreted trypsin
e. An alkaline pH
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Dietary fat, after being processed, is extruded
from the mucosal cells of the gastrointestinal tract
into the lymphatic ducts in the form of
a. Monoglycerides
b. Diglyceridesc. Triglycerides
d. Chylomicrons
e. Free fatty acids
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Contraction of the gallbladder is correctly
described by which of the following statements?
a. It is inhibited by a fat-rich meal
b. It is inhibited by the presence of amino acids in
the duodenum
c. It is stimulated by atropined. It occurs in response to cholecystokinin
e. It occurs simultaneously with the contraction of
the sphincter of Oddi
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Which of the following sugars is absorbedfrom the small intestine by facilitated
diffusion?
a. Glucoseb. Galactose
c. Fructose
d. Sucrose
e. Lactose
The major factor that protects the duodenal mucosa
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The major factor that protects the duodenal mucosa
from damage by gastric acid is
a. Pancreatic bicarbonate secretionb. The endogenous mucosal barrier of the duodenum
c. Duodenal bicarbonate secretion
d. Hepatic bicarbonate secretion
e. Bicarbonate contained in bile
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A medical student presents to the emergency room
with a two-day history of severe vomiting and
orthostatic hypotension. What kind of metabolicabnormalities would you expect?
a. Hypokalemia, hypochloremia, and metabolic acidosis
b. Hyperkalemia, hyperchloremia, and metabolic alkalosisc. Normal serum electrolytes and metabolic acidosis
d. Normal serum electrolytes and metabolic alkalosis
e. Hypokalemic, hypochloremic, metabolic alkalosis