Pediatric GERD

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Content• Physiology of Gastric Acid secretion

• An introduction to GERD

• Management of GERD

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Physiology of Gastric Acid Secretion • Stomach is divided into four areas: Cardia,

Fundus, Body and Pylorus.

• It has two valve-like sphincters1. LES –Lower esophageal sphincter2. 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

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) receptor2. Gastrin (G) receptor3. Muscarinic (M3) receptor

• Stimulation by any one of these receptors causes stimulation of HCl secretion from the parietal cells.

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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+

+

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)

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IMBALANCE

FACTORS THAT

PROTECT AGAINST ACIDITY

FACTORS THAT

INCREASE ACID

SECRETION

AcidPepsin Bile acidsNSAIDsH. pylori AlcoholPancreatic

enzymesMucusbicarbonate layerBlood flowcell renewalProstaglandinsTight junction b/w

epithelium

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.

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Epidemiology of GERD

101. 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.

Pathology of GERDThe 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

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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 Therapy15

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%).

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

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?

Does Asthma Trigger GERD? Proposed Mechanisms

Coughing

Increase Intraabdominal

Pressure

Increasing Pressure Gradient Across

The LES

Asthma Medications

Lower LESPressureGERD

Does GERD Trigger Asthma?

Am J Med 2001; 111: 37S

Reflux TheoryDirect contact between

gastric refluxate and lung tissues

Inflammation of the airway

Bronchial smooth muscle

reactivity

Does GERD Trigger Asthma?

Moser et al, Gastroenterology 1991; 101: 1512Tuchman et al, Gastroenterology 1984; 87: 872

Reflex TheoryEsophagus 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

• 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

Management

EmpiricTherapy

DiagnosticWorkup

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

Rome III criteria

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

Must include all of the following in otherwiseHealthy infants 3 weeks to 12 months of age:1. Regurgitation 2 or more times per

day for 3 or more weeks2. No retching, hematemesis,

aspiratioin, apnea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing

Management Approach

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Lifestyle ModificationFor 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…….1Antacids:

– 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

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

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 children1.

• So, difficult to adjust dose schedule with fasting and food intake in pediatric age group for maximum activation.

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

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

PEDIATRICS Vol. 127 No. 5 May 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”.

331. J Pediatr Gastroenterol Nutr, Vol. 32, Suppl. 2, 20012. J Pediatr Gastroenterol Nutr, Vol.19, No.3, 1994.

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

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 andphysical exam

Are there warning signals?

• 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

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 andphysical exam

Are therewarning signals?

Are there signsof complicated

GERD?

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”)

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

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THANK YOU

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