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Pediatric GERD

Content
Physiology of Gastric Acid secretion
An introduction to GERD
Management of GERD

Physiology of Gastric Acid Secretion


Stomach is divided into four areas:
Cardia, Fundus, Body and Pylorus.
It has two valve-like sphincters
1. LES Lower esophageal sphincter
2. Pyloric sphincter
. These sphincters regulate the entry
and exit of food from the stomach.

. Acid secreted in stomach causes


hydrolysis, sterilizes the meal content
& activates pepsinogen to pepsin
. Acid secretion:
Basal
Stimulated
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Regulation of acid secretion


Parietal cells in the gastric glands secrete
hydrochloric acid, which is needed for
digestion.
The parietal cells have 3 kinds of
receptors on their surface. These
include:
1. Histamine (H2) receptor
2. Gastrin (G) receptor
3. Muscarinic (M3) receptor

Stimulation by any one of these receptors


causes stimulation of HCl secretion from the
parietal cells.

ACh

Gastrin

Histamine

_ Adenyl

M3

cyclase

ATP

Ca++
+

H2

`
+

cAMP

Gastrin
receptor

Ca++
+

Protein Kinase
(Activated)

K+

+ H+
Proton pump

Gastric acid

Parietal cell
Lumen of stomach
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Acid Peptic Disease (APD)


Acid peptic disorders include a number of
conditions whose patho-physiology is believed to
be the result of damage from acid and pepsin
activity in the gastric secretions.

Gastric Ulcer
Duodenal Ulcer
GERD
Hyper acidity etc.
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Acid Peptic Disease (APD)


FACTORS
THAT
PROTEC
T
AGAINST
ACIDITY

Mucus
bicarbonate
layer
Blood flow
cell renewal
Prostaglandi
ns
Tight

IMBALAN
CE

Acid
Pepsin
Bile
acids
NSAIDs
H.
pylori
Alcohol
Pancre
FACTORS
atic
THAT
enzyme
INCREAS
E ACID
s
SECRETI
ON

GER & GERD in Children


Gastroesophageal reflux (GER), defined as
passage of gastric contents into the esophagus, is
normal physiological process that occurs
throughout the day in healthy infants, children
and adults. The terms:
Regurgitation is defined as passage of refluxed gastric
contents into the oral pharynx.
Vomiting is defined as expulsion of the refluxed gastric
contents from the mouth.
Gastroesophageal reflux disease (GERD) occurs
when gastric contents reflux into the esophagus or
oropharynx and produce symptoms.
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GER & GERD in Children


Most infants occasionally spit up throughout the
day ,when regurgitation causes other problems or is
associated with other symptoms, it may be due to
Gastroesophageal Reflux Disease (GERD), which can
also occur in older children.
The difference between GER and GERD is a matter of
severity and associated consequences to the patient.
GER differs from vomiting in that it is generally not
associated with a violent ejection.

Epidemiology of GERD

GER / regurgitation is very common in infancy including in


India.

Atleast one bout of


regurgitation.1:
50% babies between 0 -3
months,
67% at 4 6 months,
21% at 7-9 months of age
5% at 10-12 months only

Significant regurgitation:
20% at 0-3 months,
23% at 4-6 months,
3% at 7-9 months
2% by 12 months.

UJJAL PODDAR, Diagnosis and management of GERD, Indian Pediatrics, Volume 50-January 16, 2013.

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Pathology of GERD
The pathogenesis of GERD is multi-factorial and
complex, involving:

The frequency of reflux


Gastric acidity
Gastric emptying
Esophageal clearing mechanism
The esophageal mucosal barrier
Visceral hypersensitivity / allergy e.g. cows milk ((IgG anti-
lactoglobulin)
Airway responsiveness as seen in Asthma

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Causes of GERD
Increased pressure on the abdomen (over eating, obesity, straining
with stool due to constipation, etc.).
Decreased gastric emptying and reduced acid clearance from
esophagus.
Supine position
Medications: diazepam, theophylline, methylxanthines (decrease
sphincter tone)
Poor dietary habits: like overeating, eating late at night.
Food allergies, certain foods like greasy highly acidic..
Some beverages may also be implicated in facilitating such
pathological reflux.
Neurodevelopmental disabilities: like cerebral palsy, Down
syndrome etc..
Tracheo-esophageal fistula
Laryngomalacia
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Symptoms of GERD
The symptoms of GER are most often directly
related to the consequences of emesis (eg, poor
weight gain) or result from exposure of the
esophageal epithelium to the gastric contents.
One must remember that the typical symptoms
(eg, heartburn, vomiting, regurgitation) in adults
cannot be readily assessed in infants and
children.
Pediatric patients with gastroesophageal reflux
typically cry and report sleep disturbance and
decreased appetite.

Gastroesophageal reflux in infants and


young children

Vomiting
Weight loss or poor growth (failure to thrive)
Typical or atypical crying and/or irritability
Poor appetite
Chronic cough, Apnea and/or bradycardia
Wheezing, Stridor, Sore throat
Hoarseness and/or laryngitis
Recurrent pneumonia
Apparent life-threatening event (ALTE)
Sandifer syndrome - Ie, posturing with
opisthotonus or torticollis
Abdominal and/or chest pain

Diagnostic Approaches
History and Physical Examination
Barium Contrast Radiography
Esophageal pH Monitoring
Multichannel Intraluminal Impedance
Endoscopy and Biopsy
Scintigraphy
Empiric Therapy
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GER and Asthma


Many studies and numerous reviews have attempted to
define the relationship between gastroesophageal reflux
disease (GERD) and asthma in children. However, the nature
of the relationship is uncertain.
The sample-sizeweighted average prevalence of GERD in
patients with asthma from 19 studies was 22.8%.
The average prevalence of GERD in patients with asthma
seems to be lower in children (22.8%); studies of adults
have revealed an average prevalence of 59.2%.
The prevalence of GERD in children with asthma varied
widely (from 19.3% to 80.0%).

pesh Thakkar et al. PEDIATRICS Volume 125, Number 4, April 2010.


ww.pediatrics.org/cgi/doi/10.1542/peds.2009-2382.

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GERD and Asthma


Does GERD cause Asthma ? Does asthma cause
GERD?
Asthma

GERD

Asthma + GERD

Coexistence seems to be more frequent


than would be expected for a chance
occurrence.

Does Asthma Trigger GERD?


Proposed Mechanisms
Asthma
Medicatio
ns

Coughing

Increase
Intraabdomin
al Pressure
Increasing
Pressure
Gradient
Across The LES

GER
D

Lower LES
Pressure

Does GERD Trigger Asthma?


Reflux Theory

Direct contact
between gastric
refluxate and lung
tissues
Inflammation of the
airway
Bronchial
smooth
muscle
reactivity

Am J Med 2001; 111: 37S

Does GERD Trigger Asthma?

Reflex Theory
Esophagus and bronchial tree
have identical embryological
derivation
Share common innervation
(via vagus nerve) and
common reflexes
Stimulation of receptors in
distal esophagus by reflux
Leads to vagal reflux
Producing bronchial
constriction and/or cough
Moser et al, Gastroenterology 1991; 101: 1512
Tuchman et al, Gastroenterology 1984; 87: 872

GER and Asthma


Medical therapy does not consistently improve
pulmonary function, asthma symptoms
or
need of asthma medication
Approach to GER related asthma should be
individualized
Selected subgroup of asthmatics benefit from
anti reflux therapy
Cochrane Systematic Review

Management

Empiric
Therap
y

Diagnostic
Workup

Treatment Options

Lifestyle Changes

Feeding Changes in Infants


Positioning Therapy for Infants

Pharmacological Therapies

Acid

Suppressants
Histamine-2 receptor antagonists (H2RAs)
Proton Pump Inhibitors (PPI)
Antacids

Prokinetic

Agents
Surfce agents

Surgical Treatment

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Rome III
criteria
Must include all of the following
in otherwise
Healthy infants 3 weeks to 12
months of age:
1. Regurgitation 2 or more times
per day for 3 or more weeks
2. No retching, hematemesis,
aspiratioin, apnea, failure to
thrive, feeding or swallowing
difficulties, or abnormal
posturing

Paul E. et al. Childhood Functional Gastrointestinal Disorders.


Gastroenterology. 2006;130:1519-26

Management Approach

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Lifestyle Modification
For infants:

Elevating the head of the baby's crib


Holding the baby upright for 30 minutes after a feeding
Thickening bottle feedings with cereal
Changing feeding schedules

For older children:


Elevating the head of the child's bed
Keeping the child upright for at least two hours after
eating
Serving several small meals throughout the day, rather
than three large meals
Limiting foods and beverages that seem to worsen the
reflux
Encouraging your child to get regular exercise
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Goals of Treatment

Eliminate symptoms
Heal esophagitis
Manage or prevent complications
Maintain remission

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Drug Treatment.1
Antacids:

Basic compounds which neutralizes gastric acid


Used in symptomatic management of acid disorders
Do not reduce volume of HCl secreted
Most commonly used antacids are Aluminium &
Magnesium salts
Most common side effect of magnesium salts is
diarrhea and with aluminum salts is constipation
Inconvenient in children
Chronic antacid therapy is not recommended. 1
1. Digestion 2004;69 Suppl 1:3-8
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Drug Treatment.2
Proton Pump Inhibitors (PPI):
Acts by blocking enzyme system i.e.
H+K+ATPase, which is found at acid secretory
surface of parietal cells that mediates final
transport of H+ ions in exchange of K+ into
gastric lumen.
These drugs inhibit H+K+ATPase which activate
proton pump.
E.g are Omeprazole, lansoprazole and
pentoprazole
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Proton Pump Inhibitors (PPI):


For activation, PPIs require acid in the parietal cell
canaliculus, and they are most effective when the
parietal cell is stimulated by a meal following a fast.
A steady state of acid suppression is not achieved
for several days. There are limited data on the
pharmacology of PPIs in infants and children 1.
So, difficult to adjust dose schedule with fasting and
food intake in pediatric age group for maximum
activation.
1. J Pediatr Gastroenterol Nutr, Vol. 32, Suppl. 2, 2001

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PPI in children ???


PPIs are not effective in reducing GERD symptoms in
infants. Placebo-controlled trials in older children are
lacking.Although PPIs seem to be well tolerated during
short-term use, evidence supporting the safety of PPIs is
lacking
PEDIATRICSVol. 127No. 5May 1, 2011

Some of the PPIs are approved for use only after the
age of 1 year.

Journal of Pediatric Gastroenterology & Nutrition : Nov/Dec 2002 - Vol 35 - Issue

Drug Treatment.3
H2RA (H2 Receptor Antagonist):
These block H2 receptors on parietal cells,
and antagonize normal stimulatory effect of
histamine on acid secretion e.g. Ranitidine,
Famotidine
Inhibit acid production by reversibly
competing with histamine for binding to H2
receptors on the basolateral membrane of
parietal cells.
Inhibit basal and stimulated acid secretion,
which accounts for their efficacy in
suppressing nocturnal acid secretion.

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H2RA (H2 Receptor Antagonist):


These are considered one of the best option for the
treatment of GERD and APD in children because of
their excellent safety profile.
The duration was reduced by 90% for gastric pH
<41.
Suppress acid production > 90% within 45 minutes2.
Nelson Textbook of Pediatrics mentioning H2RA
have been recommended as first line therapy
because of their excellent overall safety profile.

1. J Pediatr Gastroenterol Nutr, Vol. 32, Suppl. 2, 2001


2. J Pediatr Gastroenterol Nutr, Vol.19, No.3, 1994.

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Why Ranitidine in Children


Ranitidine 5 mg/kg per dose orally has been shown to
increase gastric pH for 9 to 10 hours in infants, very
useful for infants who need persistent acid
suppression1.
First line of therapy for GERD in pediatrics as
mentioned by Nelson Text book of Pediatrics
Efficacy in suppressing nocturnal acid secretion
No activation required in parietal cell: Ease of
administration in pediatric patients; better response
Safety established from 1 month onwards. No other
molecule (antacid or PPI) for this age group.
USFDA and DCGI approved
Fast onset of action with sustainable duration of action

1.Pediatr Gastroenterol Nutr, Vol. 32, Suppl. 2, 2001

Warning Signals Suggestive of a


Non-GER Diagnosis
Recurrent
vomiting
History and
physical exam

Are there warning


signals?

Bilious or forceful vomiting


Hematemesis or
hematochezia
Vomiting and diarrhea
Abdominal tenderness or
distention
Onset of vomiting after 6
months of life
Fever, lethargy,
hepatosplenomegaly
Macrocephaly,
microcephaly,
seizures

Adapted from Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1

Warning Signals in the


vomiting infant
Bilious vomiting
GI bleeding :
hematemesis,
hematochezia
Forceful vomiting
Onset of vomiting after 6
months of life
Failure to thrive
Diarrhea
Constipation
Fever
Lethargy

Hepatosplenomegaly
Bulging fontanelle
Macro/microcephaly
Seizures
Abdominal
tenderness, distention
Genetic disorder
(eg:Trisomy21)
Other chronic
disorders(eg:HIV)

Signs of Complicated GERD


Recurrent
vomiting
History and
physical exam

Are there
warning signals?

Poor weight gain


Excessive crying or
irritability
Feeding problems
Respiratory problems,
including:
wheezing
stridor
recurrent pneumonia

Are there signs


of complicated
GERD?

Adapted from Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1

Management of an infant with uncomplicated GER


(the happy spitter)

Colin D. Rudolph et al. Pediatric GE Reflux Clinical Practice Guidelines. JPGN, 2001;32:S1-S31

Management of an infant with vomiting and poor weight gain

Colin D. Rudolph et al. Pediatric GE Reflux Clinical Practice Guidelines. JPGN, 2001;32:S1-S31

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