GERD September7 2nd

8/14/2019 GERD September7 2nd

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GENETICS


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BASICANATOMY

ACKNOWLEDGEMENTS

WHAT GERD

IS

GENETICS

INFLAMMATION

PHARMOCOGENOMICS

STRESS RESPONSE

CELL GROWTH

AND DEATH

SUMMARY


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Population based survey revealed that 44

% of the population reported monthly

heartburn and 19.8 % suffered fromheartburn or acid regurgitation at least

once a week.(Zuckschwerdt, W. 2001)

Clip Art derived from

Microsoft Office


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GERD is more common in whites

compared with other ethnic groups.However, the prevalence is increasing inAsians.(Fennerty, 2003)

It is also more common in women,however men & people over the age of 60

develop more complications.(Fennerty, 2003)


Microsoft Office


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BASIC ANATOMY

The upper GI or gastro-intestinaltract consists of the:

Mouth

PharynxEsophagus

Stomach

The small & large intestines formthe lower GI tract.

(Porth, 1998 )


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Once any food enters the mouth, it

moves into the pharynx, which

is the back of the throat.

(Porth,1998)


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Peristalsis continues in the

esophagus.The food is carried

from the esophagus

to the stomachwhere acid

production is formed.(Porth,1998)

Image with permission from MDA


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The esophagus is very

muscular and collapses

when empty.

It is 10 inches or 25cm inlength

(Porth, 1998)


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The esophagus is sometimesreferred to as the food tubeor the gullet. It extends from the

pharynx, which is the back of thethroat and goes through thediaphram to the stomach.


Microsoft OfficeImage with permission from Bristol-Meyers Squibb


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The esophagus producesbicarbonate and mucus.(Kahrilas, 2003)

The bicarbonate buffers the acid

and mucus forming a protective

barrier.(Kahrilas, 2003)


Microsoft Office


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This creates an environment in the

esophagus of a higher pH than that of

the stomach. The pH in the esophagusis normally about 7-8, whereas the pH

in the stomach is generally 2-4. (Kahrilas,2003)


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pH stands for potential of hydrogen.

Hydrogen is what causes materials to

become acidic. 7 is considered neutral;

anything under 7 is considered acidic. (Porth,1998)


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There are specialized cells deep in the

stomach lining that affect the rate of acid

production. The primary cells whichcontribute to acid production are known

as parietal cells. (Kahrilas, 2003)


Microsoft Office


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The binding of these 3 receptors in the

parietal cells initiates the process of

acid production. (Kahrilas,2003)

PARIETAL

CELLS

Acetylcholine Gastrin Histamine


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The primary function of the

activated pumps are to :

Exchange hydrogen ions from the parietalcells to potassium using energy derived

from splitting ATP.(Kahrilas, 2003)

Each gastric parietal cell contains

about 1 million acid pumps.


Microsoft Office


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The stomach produces an average of 2

liters of HCL a day, which in

combination with the protein-splittingenzyme pepsin, breaks down chemicals in

food. (Kahrilas 2003)


Microsoft Office


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The gullet is another name for

the esophagus.


Microsoft Office


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The esophagus is divided into:

Upper

It has a sphincter to

prevent air fromentering the esophagusduring respirations.The sphinctergenerally only opensfor food to pass.

Lower

It has a sphincter thatopens while food is

being passed into thestomach. It is knownas the LES, loweresophageal sphincter.

( Porth, 1998)


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The esophagus is divided into:

Upper

It has a sphincter to

prevent air fromentering the esophagusduring respirations.The sphinctergenerally only opensfor food to pass.

Lower

It has a sphincter thatopens while food is

being passed into thestomach. It is knownas the LES, loweresophageal sphincter.

( Porth, 1998)


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Click on

Trueor False

The gullet is part of the

stomach.


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the esophagus.


Microsoft Office


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the esophagus.


Microsoft Office


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Click on

True or False

The esophagus is in front

of the trachea.


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The esophagus

is behind (posterior)

the trachea.

Image with permission from

Bristol-Meyers Squibb.


Microsoft Office


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The esophagus

is behind (posterior)

the trachea


Bristol-Meyers Squib.Clip Art derived from

Microsoft Office


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Click on

Trueor FalseThe upper sphincter of the

esophagus is in the upper GI & the

lower sphincter is the lower GI.


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The entire esophagus is in the upper

GI. The upper GI tract consists of

the: mouth

pharynx

esophagus

stomachThe small & large intestines form the

lower GI tract. Clip Art derived fromMicrosoft Office


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The entire esophagus is in the upper GI.

The upper GI tract consists of the: mouth

pharynx

esophagus

stomach

The small & large intestines form the

lower GI tract.Clip Art derived from

Microsoft Office


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Click on

True or False

There are a million acid pumps in

each gastric parietal cell.


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There are 1 million acid pumps in

each gastric parietal cell.


Microsoft Office


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What GERD isIt is quite a complex process, my goal isto simplify it for you. First, lets break it

down to the words it is made up of:

gastro = stomach

esophogeal = food tube

reflux = back flow

disease = abnormal conditionof physiologic functioning.


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The Lower

Esophageal

Sphincter isThe primary

focus relating

to GERD.

Image with permission from Dr. Scott Tenner
http://www.gerd.com/maps/grossovw.map


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If the Lower Esophageal Sphincter (LES)

is not working properly creating a

dysfunctionthe acid from the stomach

can backflow into the esophagus.(Porth, 1998)


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Images withpermission from

Life Enhancement


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In addition to a dysfunction of the

lower esophageal sphincter (LES)

Another factor is:

Percentage of time the esophagus is

exposed to a low pH. Clearance of theacid depends on peristalsis & exposure to

the saliva.(Porth, 1998)


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In addition to a dysfunction of the

lower esophageal sphincter (LES)

Another factor is:

Percentage of time the esophagus is

exposed to a low pH. Clearance of theacid depends on peristalsis & exposure to

the saliva.(Porth, 1998)


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Healthy Living

This uncomfortablefeeling can

sometimes beconfused with otherconditions, even aheart attack.

People with this dysfunction, often experience an

uncomfortable feeling in the chest, neck,

and throat area due to acid exposure.


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Sometimes, just drinking water may

help relieve the symptoms, by

washing the irritating acids back

into the stomach.(Porth, 1998)


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This discomfort can be

precipitated by lifestyle, diet, and

even certain medications.(Kaynard,, Flora, 2001)


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Medications that relax the LES

Benzodiazepines

Theophylline

Narcotics containingcodeine.

Calium channelBlockers

Nitroglycerine

Anticholinergics

Potassium

supplements Iron supplements

NSAIDS

Fosamax

Erythromycin(CNN)


Microsoft Office

The 3 mechanisms d ring s allo ing


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The 3 mechanisms during swallowing

that keep acid out of the esophagus

include: Swallowed saliva which helps neutralize

stomach acid.

Sweeping muscles contractions that actto cleanse the lower esophagus of

stomach acid.

Protective contracture of the LES(Jackson Gastroenterology - 2005)


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The 3 mechanisms of the lower

esophageal sphincter (LES)

which prevent backflow are: Pressure in the LES is greater than that of

the stomach.

High levels of Acetylcholine, a

neurotransmitter increases constriction of

the LES.

Gastrin, a hormone also increasesconstriction of the LES.

(Porth 1998 )


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Some conditions that can interfere

with the 3 mechanisms of the Lower

Esophageal Sphincter (LES): OBESITY - excess weight puts extra pressure on the

stomach & diaphragm. (CNN.com)

Pregnancyresults in greater pressure on the stomach

& also has a higher level of progesterone. Thishormone relaxes many muscles, including the LES.(CNN.com)

ASTHMAit is unsure why, but, is believed that thecoughing leads to pressure changes on the diaphragm.

(CNN.com)

HIATAL HERNIAwhich is the following topic.


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In addition to the 3 swallowing

mechanisms & the 3 mechanisms of

the LESanatomical structures

certainly play a role in the

development of GERD.


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In individuals with hiatal hernia, the

opening of the esophageal hiatus is larger

than normal, and a portion of the upper

stomach slips up or passes (herniates)

through the hiatus and into the chest.(Kahrilas, 2003)

A hiatal hernia is an

anatomical abnormality


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In individuals with hiatal hernia, the

opening of the esophageal hiatus is larger

than normal, and a portion of the upper

stomach slips up or passes (herniates)

through the hiatus and into the chest.(Kahrilas, 2003)

A hiatal hernia is an

anatomical abnormality


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The diaphragm supports and puts

pressure on the sphincter to keep it closedwhen youre swallowing.

But a hiatal hernia raises the sphincterabove the diaphragm, reducing pressure

on the valve. This causes the sphincter

muscle to open at the wrong time.(MayoClinic.com)


Microsoft Office


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Do you think Genetics is a

factor?

There is evidence that genetics is a

factor in pediatric patients. This is

reported in the Journal of the American

Medical Association from the July issue

in 2000. (Spice, B., 2000)


Microsoft Office


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The specific gene has not been

identified as of yet, however research

has narrowed it to a portion ofchromosome 13

(Hu, Fen Ze MS; et al 2000)


Microsoft Office


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As far as adults, studies have been

performed on identical twins who

share the same genes & it has been

identified that there is a 43%

chance of genetic influence.

( MedicineNet.com)


Microsoft Office


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Click on

Trueor False

GERD can sometimes cause a discomfort

in the chest, confusing it

with a heart attack.


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Healthy Living

People with GERD

can experience an

uncomfortable

feeling in the neck,chest, & throat area.

This can be confused

with other diseases,

even a heart attack.


Microsoft Office


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Narcotics such as codeine relax the

LES, making it more likely for acidto reflux back into

the esophagus.


Microsoft Office


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LES, making it more likely for acidto reflux back into

the esophagus.


Microsoft Office


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LES, making it more likely for acid

to reflux back into

the esophagus.


Microsoft Office


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Click on

Trueor False

The diaphragm helps to open

the esophagus.


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pressure on the sphincter to keepit closed while swallowing.


Microsoft Office


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pressure on the sphincter to keep

it closed while swallowing.


Microsoft Office


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Saliva produces more acid,

creating a potential

for increased reflux.

Click on

Trueor False


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Swallowed saliva helps neutralize

acid. It is one of the 3 mechanismsthat keeps acid out of the esophagus.


Microsoft Office


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Swallowed saliva helps neutralize

acid. It is one of the 3 mechanisms

that keeps acid out of the esophagus.


Microsoft Office


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Inflammation is the bodys response, as

a protective measure against

infection and injury.

Repeated exposure to acid in theesophagus will cause inflammation

and injury to the mucosa.


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Inflammation as a result of GERD can

cause epithelial changes, marked by

polymorphonuclear or mixedpolymorphonuclear and round cell

infiltration.(Fennerty, 2003)


Microsoft Office


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There are 3 inflammatory

processes that can occur withesophagitis:

Erosive Esophagitis

Esophageal Strictures

Barretts Esophagus (Fennerty, 2003)


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Erosive Esophagitis

Erosions appear in esophageal

mucosa as eroded endothelium.(Fennerty, 2003)


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Contributing factors of

Erosive Esophagitis:

Hiatal Hernia

Decreased pressure in

the lower esophagealsphincter (LES)

Impaired ability of the

tissue to resist injury

Impaired esophageal

clearance

Increased volume ofacid(Fennerty, 2003)


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Strictures

A stricture is a narrowing If

esophagitis is left untreated, scarring

can occur resulting in a

stricture that is irreversible.(Fennerty, 2003)


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Contributing Factors of

Esophageal Strictures

Decreased pressure in the lower

esophageal sphincter (LES)

Hiatal Hernia

Ineffective peristalsis(Fennerty, 2003)


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Microsoft Office

People with strictures often feel like

there is something stuck in their throat.

Severe strictures result in difficultyswallowing (dysphagia).

(Fennerty,2003)


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Those with severe strictures usually have

less symptoms of heartburn, acid is

not able to reflux due to the narrowing

of the esophagus.(Fennerty, 2003)


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Those with strictures may also have weight

loss, due to a change in their diet to

accommodate the strictures.(Fennerty, 2003)


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Stress Response

Stress is a complex physiological

response to changes in

the environment.


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Prolonged stress has the

ability to decrease the immune system,

making the body susceptibleto inflammation and infection. (Porth, 1998)


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In an effort to cope with the

disruption in routine, caused by

stress, unhealthy lifestylesbecome evident.


Microsoft Office


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Pharmocogenomics

There are 3 categories

of medications that

can help alleviate or

prevent symptoms

from occurring.(Kaynard, Flora, 2001)

Antacids

H-2 receptor blockers

Proton pump

inhibitors


Microsoft Office


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In an effort to cope with the

disruption in routine, caused by

stress, unhealthy lifestylesbecome evident.


Microsoft Office


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Pharmocogenomics

There are 3 categories

of medications that

can help alleviate or

prevent symptoms

from occurring.(Kaynard, Flora, 2001)

Antacids

H-2 receptor blockers

Proton pump

inhibitors


Microsoft Office


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Antacids

Maalox

Mylanta

Tums

Rolaids

These medications help

to neutralize stomach

acid. They usually

provide quick relief,

however, will not heal

any inflammation.(CNN.Com)


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H-2 Receptor Blockers

Tagamet

Zantac

Pepcid AC

These medicationsreduce the acid

production. They do

not act as quickly asantacids, but providelonger relief. (CNN.Com)They start working in

about 30 minutes.


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Proton Pump Inhibitors Prevacid

Prilosec

Aciphex

Protonix

Nexium

These medications are

long acting and blockacid production.Because of this,they have the abilityto allow time fordamaged tissue toheal frominflammation.

(CNN.Com)


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Cell Growth and Death

As mentioned earlier, as a result of

inflammation:

cellular changes can occur.


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These cellular changes can be

a precursor to cancer. (Fennerty, 2003)


Microsoft Office


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Barretts Esophagus is the outcome


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Barrett s Esophagus is the outcome

of these cellular changes.

Cells in the lining of the esophagus are

actually replaced with abnormal cells

similar to those in the stomach.(Fennerty, 2003)


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This would be, metaplasia. Asthe cells replicate to multiply,

dysplasia is occurring. (Porth, 1998)


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Ulcers, although not a common symptom,can be found with Barretts Esophagus.

The ulcers can lead to Gastrointestinal

bleeding. (Fennerty, 2003)

Cli k


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Click on

Trueor False

Some people with strictures have

decreased symptoms of reflux.


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A stricture is a narrowing, as a

result, the acid is sometimes

unable to reflux.


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Cli k


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Click on

Trueor False

If esophagitis is left untreated,

scarring can occur resulting in a

stricture, which eventuallyheals itself.

Cli k


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Click on

Trueor False

GI bleeding is one of the symptoms

of Barretts Esophagus.


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GI bleeding can be a symptom

of an ulcer, which can be

present in someone with Barretts

Esophagus, although not common.


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Gi bleeding can be a symptom

of an ulcer, which can be

present in someone with Barretts

Esophagus, although not common.


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High Prevalence of Gastroesophageal


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Locke et al. Gastroenterology 1997;112:1148.

High Prevalence of Gastroesophageal

Reflux Symptoms

19.8%

59%

0%

10%

20%

30%

40%

50%

60%

Weekly Monthly

Frequency of heartburn and/or

regurgitation


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Important Reasons to Diagnose and Treat


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GERD

Negative impact on health-related quality of life1

Risk factor for esophageal adenocarcinoma2

1. Revicki et al. Am J Med 1998;104:252.

2. Lagergren et al. N Engl J Med 1999;340:825.


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Clinical Presentations of GERD


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Classic GERD

Extraesophageal/Atypical GERD Complicated GERD


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Extraesophageal Manifestations


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of GERD

Pulmonary

Asthma

Aspiration pneumonia

Chronic bronchitisPulmonary fibrosis

OtherChest pain

Dental erosion

ENT

Hoarseness

Laryngitis

PharyngitisChronic cough

Globus sensation

Dysphonia

SinusitisSubglottic stenosis

Laryngeal cancer

Potential Oral and Laryngopharyngeal SignsAssociated with GERD


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Associated with GERD

Edema and hyperemia of

larynx

Vocal cord erythema,

polyps, granulomas,

ulcers

Hyperemia and lymphoid

hyperplasia of posterior

pharynx

Interarytenyoid changes

Dental erosion

Subglottic stenosis

Laryngeal cancer

Vaezi MF, Hicks DM, Abelson TI, Richter JE. Clin Gastro Hep 2003;1:333-344.

Pathophysiology of Extraesophageal


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GERD


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When to Perform Diagnostic Tests


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When to Perform Diagnostic Tests

Uncertain diagnosis

Atypical symptoms

Symptoms associated with complications Inadequate response to therapy

Recurrent symptoms

Prior to anti-reflux surgery


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Diagnostic Tests for GERD

Barium swallow

Endoscopy Ambulatory pH monitoring

Esophageal manometry

Barium Swallow


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Useful first diagnostic test forpatients with dysphagia

Stricture (location, length)

Mass (location, length) Birds beak

Hiatal hernia (size, type)

Limitations

Detailed mucosal exam for erosiveesophagitis, Barretts esophagus

Endoscopy


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Indications for endoscopy

Alarm symptoms

Empiric therapy failure

Preoperative evaluation

Detection of Barretts

esophagus

Ambulatory 24 hr. pH Monitoring


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Physiologic study

Quantify reflux in

proximal/distalesophagus

% time pH < 4

DeMeester score

Symptom correlation

Ambulatory 24 hr. pH Monitoring


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Normal

GERD

Wireless, Catheter-Free Esophageal pH Monitoring


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Improved patient

comfort and acceptance

Continued normal work,activities and diet study

Longer reporting periods

possible (48 hours)Maintain constant probe

position relative to SCJ

Potential Advantages

Esophageal Manometry


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Assess LES pressure,

location and relaxation Assist placement of 24 hr.

pH catheter

Assess peristalsis

Prior to antireflux surgery

Limited role in GERD

Treatment Goals for GERD


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Treatment Goals for GERD

Eliminate symptoms

Heal esophagitis Manage or prevent complications

Maintain remission

Lifestyle Modifications areCornerstone of GERD Therapy


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Cornerstone of GERD Therapy

Elevate head of bed 4-6 inches

Avoid eating within 2-3 hours of bedtime

Lose weight if overweight

Stop smoking

Modify diet

Eat more frequent but smaller meals

Avoid fatty/fried food, peppermint, chocolate,alcohol, carbonated beverages, coffee and tea

OTC medications prn

Acid Suppression Therapy for GERD


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H2-Receptor Antagonists

(H2RAs)

Cimetidine (Tagamet)

Ranitidine (Zantac)

Famotidine (Pepcid)Nizatidine (Axid)

Proton Pump Inhibitors

(PPIs)

Omeprazole (Prilosec)

Lansoprazole (Prevacid)

Rabeprazole (Aciphex)

Pantoprazole (Protonix)Esomeprazole (Nexium )

Effectiveness of Medical Therapies for


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Effectiveness of Medical Therapies for

GERD

Treatment Response

Lifestyle modifications/antacids 20 %

H2-receptor antagonists 50 %

Single-dose PPI 80 %

Increased-dose PPI up to 100 %

Treatment Modifications forPersistent Symptoms


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y p

Improve compliance

Optimize pharmacokinetics

Adjust timing of medication to 1530 minutesbefore meals (as opposed to bedtime)

Allows for high blood level to interact with

parietal cell proton pump activated by the meal

Consider switching to a different PPI

GERD is a Chronic Relapsing Condition


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Esophagitis relapses quickly after cessation

of therapy

> 50 % relapse within 2 months

> 80 % relapse within 6 months

Effective maintenance therapy is imperative

Complications of GERD


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p

Erosive/ulcerative esophagitis

Esophageal (peptic) stricture

Barretts esophagus

Adenocarcinoma


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Peptic Stricture


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Barium Swallow Endoscopy


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Barretts Esophagus


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Esophageal Cancer


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Barium Swallow Endoscopy


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When to Discuss Anti-Reflux


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Surgery with Patients

Intractable GERDrare

Difficult to manage strictures

Severe bleeding from esophagitisNon-healing ulcers

GERD requiring long-term PPI-BID in a

healthy young patient Persistent regurgitation/aspiration symptoms

Not Barretts esophagus alone

Endoscopic GERD Therapy


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Endoscopic antireflux therapies

Radiofrequency energy delivered to the LES

Stretta procedure

Suture ligation of the cardia

Endoscopic plication

Submucosal implantation of inert material in

the region of the lower esophageal sphincter Enteryx

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GERD September7 2nd