gastrointestinal physiology review

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]


2/75

Feedback Systems


3/75

Regulated vs. Unregulated Processes


4/75

Innervation of the GI Tract

Parasympathetic (vagus) - increases motility

and relaxes sphincters

Sympathetic- decreases motility and contracts

sphincters

Enteric- Myenteric and Submucosal plexuses


5/75

Saliva

Components

Salivary amylase, lingual lipase, bicarbonate, mucins,

salts (hypotonic)

Effect of ANS


6/75

Swallowing

Anatomically 4 tubes

are converging

Reflex- move cohesive

bolus created to back

of mouth

Once swallow- no

more control


7/75

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


8/75

Esophageal Peristalsis

Afferents and Efferents

Controlled by Swallowing Center in

Medulla


9/75

Sphincters

Normal Pressure

UES - 80 mmHg

LES - 30 mmHg


10/75

What if something gets stuck?

Secondary Peristalsis

Stuck food sensed by

stretch receptors in

the mucosa

Enteric reflex (No ANS

reqd)

Repeats every fewminutes


11/75

Know Your Cases!

Achalasia

Diffuse Esophageal Spasm


12/75

Anatomy and Function of the Stomach

StorageBreaks up foodDigests proteinBacterialcidalVirucidalKills parasites

Dissolves boneIncreases bioavailability of calcium & iron


13/75

Gastric Filling

Receptive Relaxation

Part of swallowing reflex- vagus mediated

Reflex Relaxation

Gastric stretch receptors, Vagovagal reflex

Stress Relaxation

Property of smooth muscle


14/75

Gastric Juice

Secretion SecretoryCell GastricLocation

HCl Parietal Fundus &Body

Pepsinogen Chief Body & AntrumGastrin G-cell AntrumIntrinsicFactor Parietal Fundus &BodyMucous Mucous Neck All


15/75

Secretions

Endocrine Secretions

Gastrin

Histamine from ECL cells

Exocrine Secretions

HCl

Pepsinogen


16/75

HCl Secretion


17/75

Dietary pH buffers


18/75

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


19/75

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


20/75

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


21/75

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

+


22/75

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


23/75

Visible Mucous

Mucous and HCO3 line

the gastric mucosa

Protect mucosa from

pepsin and HCl

Think of as a chain

linked fence


24/75

Know Your Cases!

Achalasia

Diffuse Esophageal Spasm

GERD PUD


25/75

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


26/75

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


27/75

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


28/75

Treatment of PUD

Prevention- replace NSAIDs with COX-2

inhibitors (celebrex)

Healing

neutralize gastric contents PPI

Eliminate H. pyloriantibiotic


29/75

Vomiting

Control Center Brain Stem

2 steps

Retching

Move chyme from duodenum and stomach into lower

esophagus

Vomiting Move chyme from lower esophagus out


30/75

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


31/75

Vomiting

Contraction of Pylorus

Contraction of abdominal muscles

Relaxation of diaphragm Relaxation of UES


32/75

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


33/75

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


34/75

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


35/75


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37/75

Controlling Composition of Duodenal

Chyme

DuodenalMotility

PancreaticSecretion

Bile

SecretionGastricEmptying

WaterSecretion


38/75

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


39/75

Proteins and AAs

Presence slows rate

of gastric emptying

Mucosal Cells release:

Gastrin

CCK

ProteinsAA

GASTRIN, CCK & GIP

IncreasedMixing

DecreasedEmptying

Increased

Secretion

MucosalCell


40/75

Fats and FFAs

Presence of fats and

FFAs slows gastric

emptying

Mucosal Cell releases

CCK

FATSFFA

CCK & GIP

DecreasedEmptying

Decreased

Secretion

MucosalCell


41/75

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


42/75

Primary Pancreatic

Exocrine Secretagogues


43/75


44/75

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


45/75

Carbohydrate Digestion

Know the disaccharides

Sucrose

Lactose

Maltose

Pancreatic and Salivary Amylase

Disaccharidases

Monosaccharides are absorbed


46/75

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


47/75

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


48/75

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


49/75

unstirred layer

absorptiveepithelium

fat drop

FFA

micelle

FFA


50/75

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)


51/75

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)


52/75

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


53/75

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


54/75

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


55/75

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


56/75

Cl

-

Bulk Flowof H O2

Capilla

ry Na+

H O2

H O2

Lumenof

Colon

For Water Reabsorption


57/75

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


58/75

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


59/75

The paracrine secretion responsible for

inhibiting gastric acid secretion is

a. Histamineb. Enterogastrone

c. Somatostatin

d. Pepsin

e. Enterooxyntin


60/75

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


61/75

Vitamin B

12

is absorbed primarily in the

a. Stomach

b. Duodenum

c. Jejunum

d. Ileum

e. Colon


62/75

Absorption of fat-soluble vitamins requiresa. Intrinsic factor

b. Chymotrypsin

c. Pancreatic lipase

d. Pancreatic amylasee. Secretin


63/75

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


64/75

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


65/75

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


66/75

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


67/75

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


68/75

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


69/75

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


70/75

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


71/75

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


72/75

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


73/75

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


74/75

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


75/75

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

gastrointestinal physiology review

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