2. 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 2
3. 3
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. ACh
Histamine Gastrin
_ Adenyl
cyclase
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
`
Ca++
Proton pump
K+
Gastric acid
Parietal cell
Lumen of stomach
H2
M3
+
+
+ H+
Gastrin
receptor
+
+
5
5. 5
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…….
7. 7
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. 8
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. 9
Epidemiology of GERD
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.
10. 10
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. 11
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. 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.
13. 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
14. Diagnostic Approaches
• History and Physical Examination
• Barium Contrast Radiography
• Esophageal pH Monitoring
• Multichannel Intraluminal Impedance
• Endoscopy and Biopsy
• Scintigraphy (A procedure that produces pictures (scans) of
structures inside the body, using radio active chemical)
15
15. 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.
16. GERD and Asthma
Asthma GERD
Asthma + GERD
Coexistence seems to be more frequent
than would be expected for a chance
occurrence.
Does GERD cause Asthma ? Does asthma cause GERD?
17. Does Asthma Trigger GERD?
Proposed Mechanisms
Coughing
Increase
Intraabdominal
Pressure
Increasing
Pressure
Gradient Across
The LES
Asthma
Medications
Lower LES
Pressure
GER
D
18. Does GERD Trigger Asthma?
Reflux Theory
Direct contact between
gastric refluxate and lung
tissues
Inflammation of the
airway
Bronchial smooth
muscle reactivity
22. 22
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
23. 23
Goals of Treatment
– Eliminate symptoms
– Heal esophagitis
– Manage or prevent
complications
– Maintain remission
24. 24
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
25. 25
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
26. 26
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.
27. 27
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”.
28. 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
29. 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?
30. • 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
31. 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?
