Update on GERD in Pediatrics, Clinical features, diagnosis, treatment

1. Pediatric GERD
1

2. Content
• Physiology of Gastric Acid secretion
• An introduction to GERD
• Management of GERD
2

3. 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
3

4. 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.
4

5. ACh
Histamine Gastrin
Adenyl
cyclase
_
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
`
+
Ca++
Proton pump
K+ H+
Gastric acid
Parietal cell
Lumen of stomach
H2M3
++
+
Gastrin
receptor+
+
5

6. 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…….
6

7. Acid Peptic Disease (APD)
7
IMBALANCE
FACTORS
THAT
PROTECT
AGAINST
ACIDITY
FACTORS
THAT
INCREASE
ACID
SECRETION
Acid
Pepsin
Bile acids
NSAIDs
H. pylori
Alcohol
Pancreatic
enzymesMucus
bicarbonate layer
Blood flow
cell renewal
Prostaglandins
Tight junction b/w
epithelium

8. 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.
8

9. 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.
9

10. Epidemiology of GERD
10
1. UJJAL PODDAR, Diagnosis and management of GERD, Indian Pediatrics, Volume 50-January 16, 2013.
Significant regurgitation: 1
20% at 0-3 months,
23% at 4-6 months,
3% at 7-9 months
2% by 12 months.
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
– GER / regurgitation is very common in infancy including in India.

11. 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. cow’s milk ((IgG anti-β lactoglobulin)
– Airway responsiveness as seen in Asthma
11

12. 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
12

13. 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.

14. 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

15. Diagnostic Approaches
• History and Physical Examination
• Barium Contrast Radiography
• Esophageal pH Monitoring
• Multichannel Intraluminal Impedance
• Endoscopy and Biopsy
• Scintigraphy
• Empiric Therapy
15

16. 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-size–weighted 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%).
16
Kalpesh Thakkar et al. PEDIATRICS Volume 125, Number 4, April 2010.
www.pediatrics.org/cgi/doi/10.1542/peds.2009-2382.

17. GERD and Asthma
Coexistence seems to be more frequent than
would be expected for a chance occurrence.
Asthma GERD
Asthma + GERD
Does GERD cause Asthma ? Does asthma cause GERD?

18. Does Asthma Trigger GERD?
Proposed Mechanisms
Coughing
Increase
Intraabdominal
Pressure
Increasing Pressure
Gradient Across
The LES
Asthma
Medications
Lower LES
PressureGERD

19. Does GERD Trigger Asthma?
Am J Med 2001; 111: 37S
Reflux Theory
Direct contact between
gastric refluxate and
lung tissues
Inflammation of the
airway
Bronchial
smooth muscle
reactivity

20. Does GERD Trigger Asthma?
Moser et al, Gastroenterology 1991; 101: 1512
Tuchman et al, Gastroenterology 1984; 87: 872
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

21. • 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
GER and Asthma

22. Management
Empiric
Therapy
Diagnostic
Workup

23. Treatment Options
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 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

24. Rome III criteria
Paul E. et al. Childhood Functional Gastrointestinal Disorders. Gastroenterology.
2006;130:1519-26
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

25. Management Approach
25

26. 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
26

27. Goals of Treatment
– Eliminate symptoms
– Heal esophagitis
– Manage or prevent complications
– Maintain remission
27

28. 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
28
1. Digestion 2004;69 Suppl 1:3-8

29. 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
29

30. 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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31. 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”.
31
1. J Pediatr Gastroenterol Nutr, Vol. 32, Suppl. 2, 2001
2. J Pediatr Gastroenterol Nutr, Vol.19, No.3, 1994.

32. 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

33. Warning Signals Suggestive of a
Non-GER Diagnosis
Adapted from Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
• 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
Recurrent vomiting
History and
physical exam
Are there warning
signals?

34. • 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)
Warning Signals in the vomiting infant

35. Signs of Complicated GERD
Adapted from Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
• Poor weight gain
• Excessive crying or irritability
• Feeding problems
• Respiratory problems, including:
– wheezing
– stridor
– recurrent pneumonia
Recurrent vomiting
History and
physical exam
Are there
warning signals?
Are there signs
of complicated
GERD?

36. Colin D. Rudolph et al. Pediatric GE Reflux Clinical Practice Guidelines. JPGN, 2001;32:S1-S31
Management of an infant with uncomplicated GER
(the “happy spitter”)

37. 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

38. 38