Digestive Disorders in

the Pediatric Age

Maria Victoria Matias-Villarica RN, MD, FPSECP
OLFU College of Medicine
Session Outline:
Hepatitis

Liver Abscess

Biliary Atresia

Cirrhosis

Cystic Fibrosis

Acute Pancreatits

Celiac Disease
Viral Hepatitis
Caused by 5 hepatotropic viruses (A,B,C,D,E)

Other causes: systemic infections, non-viral liver infections,

autoimmune, metabolic, drug-induced, anatomic,
hemodynamic and non-alcoholic fatty liver disease

Manifestations: CLINICAL ICTERUS mixed or conjugated

hyperbilirubinemia; enlarged, tender liver, splenomegaly,
lymphadenopathy; change in sensorium and hypereflexia
indicate encephalopathy and ALF
Pathogenesis
Direct cytopathic and immune-mediated injury

Necrosis centrilobular areas; acute mixed inflammatory

infiltrates; balloon degeneration and necrosis (parenchymal
cells; fatty change (HCV); diffuse Kupffer cell hyperplasia
(siunusoids); formation of GIANT CELLS (neonates)

Parenchymal collapse (fulminant hepatitis)

Liver morphology returns to normal 3 mos. of the acute

infection
Common Biochemical Profiles in the
Acute Infection
3 main functional liver biochemical profile:
A. ALT (alanine aminotransferase)and AST (aspartate
transaminase); rapidly falling + bilirubin levels and prolonged PT
poor outcome
- reflection of the cytopathic injury to the hepatocytes
B. Cholestasis - serum conj. bili. levels due to abnormal bile flow
at the canalicular and cellular level due to hepatocyte damage
and inflammatory mediators
C. Altered synthetic function most impt. marker of liver injury:
prolonged PT, high INR, low serum albumin, hypoglycemia, lactic
acidosis, poor clearance of drugs, altered sensorium (deep
tendon reflexes (hepatic encephalopathy)
Hepatitis A
Most prevalent

RNA virus (picornavirus)

Fecal- oral route; highly contagious; common source food-borne and

waterbourne outbreaks

IP: 3 weeks; duration of symptoms: 7-14 days

Fecal excretion of the virus resolves 2 weeks after onset of jaundice

Clinical manifestations: anicteric illness (asymptomatic); older children:

symptomatic (fever, anorexia, vomiting, malaise, jaundice)

Contagious 2 week before and 7 days after the onset of jaundice

Hepatitis A
Diagnosis: antibodies to HAV (anti-HAV IgM): detectable with
symptoms and lasts 4-6 mos; stool viral particles; viral PCR ;
neutralizing anti-HAV (IgG) seen 8 weeks from onset and
CONFERS long-term protection;

Complication: No long term sequelae

ALF (rare); cholestatic syndrome (pruritus, fat malabsorption)

Treatment: supportive treatment (Iv hydration, antipruritic meds

and fat-soluble vitamins)

If with ALF transplantation

Hepatitis A
Prevention: exclusion from school, child care; careful
handwashing; contact and standard precaution

Ig Pre-exposure: <3 mos. 0.02ml/kg ; 3- 5mos. 0.06ml/kg; >5mos.

0.06ml/kg at departure then every 5 mos. thereafter;
immunocompromised, older child, chronic liver disease should
receive both Ig and HAV vaccine;

Post-exposure: <2 weeks - <1yr: 0.02ml/kg; immunocompromised,

older child, chronic liver disease should receive both Ig and HAV
vaccine; Ig is optional to healthy 12mos-40 yrs since HAV vaccine
is preferred ; > 2weeks - none

Vaccine: > 1 yr. 2 doses (6-12months apart); protective Ab titer

persists for 10 yrs.
Hepatitis B
Hepadnaviridae

4 genes: S (surface), C (core), X and P (polymer)

Surface of the virus: HBsAg

Inner core of the virion: a.) HBcAg encodes the viral DNA
b.) HBeAg nonstructural, nonparticulate soluble Ag that
SERVES as a marker of active viral replication and correlates
with HAV DNA levels

Highest prevalence in subSaharan Africa, China, ME, Amazon

basin, Pacific Islands, Alsaka

Asymptomatic in many children

Hepatitis B
High concentration: blood, serum, serous exudates

Moderate concentrations: saliva, vaginal fluid, semen

Transmitted: blood exposure, sexual contact, intimate contact with

carriers; IV drug use, tattoos, acupuncture; children: perinatal
exposure to HBsAg/HBeAg (+) mother at the time of delivery
serologic markers appear 1-3 mos after birth

Not spread by breastfeeding, kissing, hugging or sharing water or

utensils; should not be excluded from school unless prone to biting

Breastfeeding not C/I

Chronic HBV infection HBsAg (+) > 6 mos is inversely related to age
of acquisition; related to chronic liver disease and hepatocellular
carcinoma
Hepatitis B
8 genotypes: A pandemic; B and C Asia; D Southern
Europe, E Africa; F US; G US and France; H Central
America

Pathogenesis: Acute hepatitis: non-cytopathogenic virus that

causes injury by immune-mediated response; infection of
hepatocytes leads to expression of viral Ags on the cell
surface (HBeAg and HBcAg) + class I MHC proteins target
for cytotoxic cell lysis; Chronic hepatitis: tolerance
phenomenon: perinatal transmission no activation of
cytotoxic lymphocytes; cirrhosis and hepatocellular Ca is
seen; 3 phases: immune-tolerant, immune-active and inactive
Hepatitis B
Clinical manifestations: asymptomatic; ALT just before
development of fatigue, anorexia and malaise seen 6-7
weeks after exposure; jaundice 8 weeks after exposure and
lasts for 4 weeks
Diagnosis: HBsAg 1st to appear; infection; if persists > 6mos,
chronic infection; anti-HBs marks serologic recovery and
protection and present in persons immunized with hep B
vaccine; HBeAg active acute or chronic hepatitis; antiHBe
marks improvement; anti-HBc IgM marker of acute infection
before but is replaced by anti-HBc IgG valuable serologic
marker of acute infection; HBV DNA acute infection and
chronic carriers and in HBeAg and typically falls once anti-
Hbe develops
Hepatitis B
Complications: ALF , esp. with co-infection with HDV; mortality to
ALF is >30% - transplantation
Treatment: supportive; reduce viral replication a. Interferon -
2b immunomodulator and antiviral effects; SC X 24 weeks; AE:
bone marrow suppression, retinal changes, autoimmune
disorders) b. Lamivudine oral nucleoside analog that prevents
viral enzyme reverse transcriptase X 52 weeks (to >6mos after
viral clearance emergence of mutant viral strain, YMDD); c.
Adefovir purine analog that inhibits viral replication in > 12 yrs.
old; d. Peginterferon-2 and several new
nucleotide/nucleoside analogs (Telbivudine, Tenofevir,
Entecavir) used in adults
Response is seen with patients with low HBV DNA titers, HbeAg
(+), > 2x ALT (active inflammation), immunoactive individuals
Hepatitis B
Prevention: HB Vaccine (Recombivax HB and Engerix-B) and HBIG
(temporary protection 3-6 mos)

AE: pain at injection site

HB vaccine: < 19 yrs. - 5/10ug and > 19 yrs. 10/20ug at 0,1,6 mos.;
immunocompromised 40/40ug

HBIG given within 12 hrs. after birth and post vaccination testing is done
9-18 mo later (importance!) ; within 24 hrs. after blood exposure; within 14
days after sexual exposure; dose: 0.5 uL NB and 0.06uL/kg for all

Universal vaccination - >95% sero(+) after 2nd dose; 3rd dose booster;
long term immunity; 4th dose immunocompromised and infants < 2kg; 1st
dose birth but can be delayed if mother is HBsAg (-); preterm and HBsAg
(-) mother delayed 1 month of age or until hospital discharge; middle
school entry
Hepatitis B
Prognosis: outcome after acute HBV infection is
favorable despite risk of ALF

HBV infections and complications are effectively

controlled and prevented with vaccination
Hepatitis C
Single stranded RNA virus (Flaviviridae family)
6 genotypes 1b most common genotype but LEAST
responsive to medications; genotype 2 and 3 responsive to
treatment
Most common cause of chronic liver disease in adults
Risk for transmission: blood transfusion; sexual contact;
perinatal transmission
Pathogenesis: cytotoxic and immune-mediated immunity
Clinical manifestations: 1-2mos- jaundice
Hepatitis C
Diagnosis: widely used: EIA (enzyme immunoassay) to detect
anti-HCV; antibodies to HCV (2 mos after exposure) or viral RNA
(PCR) (1-2 mos after exposure) NEITHER can predict the severity
of liver disease because anti-HCV is not a protective Ab and
does not confer immunity; it occurs simultaneously with the virus;
commonly used: PCR assay (HCV RNA) qualitative while
quantitative identify patients who are likely to respond to therapy
and monitors response to therapy
Screening for HCV hx of illegal drug use, receiving clooting
factors (before 1987) or blood products (before 1992),
hemodialysis, idiopathic liver disease and children born to HCV-
infected women
Complication: Chronic hepatitis; cirrhosis; HCC
Hepatitis C
Treatment: Peginterferon (SC, weekly) combined with oral
Ribavirin; IFN-2b (48weeks) ; should be stopped if still
detectable on viral PCR at 24th week of therapy

Goal: SVR (sustained viral response or absence of viremia 6

months after stopping the medication)

Newer therapy: Peginterferon and teleprevir (NS3 viral

protease inhibitor)

Yearly screening with a liver UTZ and serum fetoprotein for

HCC; referral to pediatric gastroenterologist
Hepatitis D
HDV; smallest known animal virus; defective because it cannot
produce infection without concurrent HBV infection (co-infection and
super-infection)

Transmission: intrafamilial or intimate contact

IP: 2-8 week

Pathogenesis: cytopathic; complication: ALF

Diagnosis: IgM antibody to HDV seen 2-4 weeks in co-infection and

10th week in super-infection; PCR assay for viral RNA research

Treatment: supportive

Prevention: no vaccine
Hepatitis E
HEV not isolated but is cloned; RNA virus (nonenveloped
sphere shape with spikes)

Non-A, non-B hepatitis; causes ALF

Fecal-oral transmission; peak age: 15yrs and 34 yrs.

Cytopathic virus

Diagnosis: Ab HEV; IgM and IgG assays

Prevention: HBE recombinant vaccine

Hepatitis G
Blood-borne disease

Transmitted by organ transplantation

Associated with HCV

Unknown IP
Approach to Acute and
Chronic Hepatitis
Prevention

Referral to pediatric gastroenterologist

Avoid alcohol consumption and obesity; care when taking

new medications and herbal medications
Liver Abscess
Pyogenic liver abscess

Bacteria entering the liver via the portal circulation (omphalitis,

portal vein pylephlebitis, intra-abdominal infection or abscess
secondary to appendicitis or IBD or primary bacteremia

Organisms: S. aureus, Strep. Species, E. coli, K. pneumoniae,

Salmonella and anaerobic organisms; E. histolytica or T. canis

Manifestations: nonspecific: fever, chills, night sweats, malaise,

fatigue, nausea, abdominal pain (RUQ), hepatomegaly;
jaundice is uncommon

Diagnosis: percutaneous UTZ or CT-guided needle aspiration;

cultures
Liver Abscess
Treatment: open-surgical drainage (less often)

Antibiotics: ampi/sulbactam, ticarcillin/clavulanic acid,

or piperacillin/tazobactam; 3rd generation
cephalosporin + metronidazole

Amoebic abscess: metronidazole or tinidazole +

paramomycin

IV X 2-3 weeks followed by oral therapy to complete 4-

6week course
Cirrhosis
End stage of chronic liver diseases, biliary atresia and chronic
hepatitis; infectious, autoimmune or toxic factors

Jaundice, poor growth, anorexia, muscle weakness and

lethargy; ascites, edema, GI bleeding, anemia and
abdominal pain; spider angiomas and prominent blood
vessels in the upper torso

Liver transplantation
Biliary Atresia
Extrahepatic biliary atresia (EHBA)
Progressive inflammatory process that causes both intra- and
extrahepatic bile duct fibrosis, resulting to obstructed bile
flow; unknown cause fetal/embryonic and postnatal
(immune-mediated mechanism)
F>M; prematures
Untreated leads to cirrhosis, liver failure and death in 1st 2
yrs of life
cholestasis accumulation of compounds that cannot be
excreted resulting to injury to the liver
Biliary Atresia
Clinical manifestation:

1. Jaundice earliest, most striking feature (sclerae)

2. Urine dark and stains diaper

3. Stools lighter or white

4. Hepatomegaly and abdominal distention

5. Splenomegaly later

6. Failure to thrive, poor weight gain

7. Pruritus

8. Irritability, difficult to comfort infant

Biliary Atresia
Surgical laparotomy and intraoperative cholangiogram
definitive diagnosis

Endoscopic retrograde cholangiopancreatography

(ERCP) 80% diagnostic accuracy

Percutaneous liver biopsy

CBC, electrolyte, bilirubin, liver enzymes

Abdominal UTZ
Biliary Atresia
Therapeutic management:

1. hepatic portoenterostomy (Kasai procedure)

a segment of the intestine is anastomosed to the
resected porta hepatis to attempt bile drainage;
not a cure

2. liver transplantation

3. medical management supportive (nutritional

support, fat-soluble vitamin supplementation); low
in sodium; Ursodeoxycholic acid for pruritus abd
hypercholesterolemia
Cystic fibrosis
Inherited multisystem disorder in children and adults

Most common life-limiting recessive genetic trait among white persons

dysfunction of the cystic fibrosis transmembrane conductance

regulator protein (CFTR)

Characterized by obstruction and infection of airways and by

maldigestion

Pancreatic insufficiency; severe chronic lung disease; responsible for

many cases of salt depletion, nasal polyposis, pansinusitis, rectal
prolapse, pancreatitis, cholelithiasis, insulin-dependent hyperglycemia

Manifest as failure to thrive, cirrhosis and other forms of hepatic

dysfunction
Cystic Fibrosis
Inherited as autosomal recessive trait

CF gene codes for CFTR that is expressed in epithelial cells

of the airway, GIT (pancreas and biliary system), sweat
glands and GUT

CFTR (member of ATP-binding casette superfamily) that

functions as cyclic AMP-stimulated protein kinase A (PKA)
regulation of Cl-conductance

CFTR polymorphisms 5 classes of mutations

Genotyping
Cystic Fibrosis
Pathogenesis:

a. failure to clear mucous secretions

b. paucity of water in mucous secretions

c. elevated salt content of sweat and other serous secretions

d. chronic respiratory infection

Membranes of CF epithelial cells are unable to secrete Cl

ions in response to cyclic AMP-mediated signals and
excessive Na are absorbed through membranes
Cystic Fibrosis
Hypothesis:1. inability to secrete salt and secondarily to
secrete water in the presence of excessive reabsorption of
salt and water insufficient water on airway surface to
hydrate secretions dessicated secretions become
more viscous and elastic (rubbery) harder to clear by
mucociliary mechanisms

2. altered microenvironment with low HCO3 and a more

acidic pH, altering mucus rheology and aggrevates poor
mucociliary clearance
Cystic Fibrosis
Pathology:

1. bronchiolitis, bronchiolar obliteration, bronchiolectasis,

bronchiectasis

2. paranasal sinuses

3. pancreas cystic; acini and ducts are filled with eosinophilic

material to disruption of acini and replacement with fibrous
tissue (2nd decade of life)

4. intestinal tract shows minimal change- inspissated

meconium

5. focal biliary cirrhosis

Cystic Fibrosis
Although both Na and Cl are affected, primary
defect is a result of abnormal Cl movement

Primary factor: mechanical obstruction caused

by increase viscosity of mucous gland secretion

Instead of a thin, free-flowing secretion, it

produce a thick, mucoprotein that acculmulates
and dilates them obstruction of small passages
in all organs (ducts and glands)
Cystic Fibrosis
Clinical manifestations:

1. respiratory tract cough- dry and hacking; repeated pneumonia

2. intestinal tract meconium ileus; ground glass appearance on

lower central abdomen; maldigestion from exocrine pancreatic
insufficiency; prolapse of the rectum

3. biliary tract evidence of liver dusfunction

4. pancreas pancreatic insufficiency; hyperglycemia and

glycosuria

5. GUT sexual development is often delayed but sexual function is

unimpaired

6. sweat glands hypochloremic alkalosis

Cystic Fibrosis
Diagnosis and assessment:
1. sweat testing difficult in 1st 2 week of life because of low
sweat rates but recommended any time after 1st 48 hr of life; >
60mEq/L of Cl in sweat
2. DNA testing tests for CFTR mutations
3. pancreatic function quantification of elastase-1 activity in
the fresh stool
4. chest xray patchy atelectasis, obstructive emphysema;
abnormal PFTs
5. sputum cultures S. aureus, P. aeruginosa, Burkholderia
cepacia
Cystic Fibrosis
Baseline assessment, initiation of treatment, clearing of
pulmonary involvement and education of patient and
parents

Multidisciplinary approach (MD, nurse, respiratory

therapist, dietician, social worker and psychologist)

Ff-up evaluations : every 1-3 mos, depending on age at

diagnosis

IV antibiotics may be required every 2-3mos.

Cystic Fibrosis
Pulmonary therapy:

1. Inhalational therapy aerosol deliver medication and

hydrate the lower respiratory tract (MDIs, spacer, compressor
use) Human Recombinant Dnase (2.5mg) > 12mos single
daily aerosol dose; improves pulmonary function,
exacerbations, promote a sense of well-being; N-
acetylcysteine should be avoided since it is toxic to the
epithelium; 7% hypertonic saline 2-4X daily improves
mucociliary clearance; aerosolized antibiotic (tobramycin,
TOBI) suppressive therapy for P. aeruginosa ( 1 month on, 1
month off)
Cystic Fibrosis
2. Airway clearance technique (ACT) Chest Physical Therapy (CPT) 1-
4x/day; coughing, huffing, forced expiration; routine aerobic exercises,
weight training slows the rate of pulmonary function decline

3. Antibiotic therapy mainstay of therapy to control progression of lung

infection

oral (> 2 weeks) Dicloxacillin, Linezolid, Cephalexin, Clindamycin,

Co0amixiclav, Amoxicillin, Ciprofloxacin, Azzithromycin

IV (14 days) Nafcillin, Vancomycin, Tobramycin, Amikacin, Piperacillin,

Meropenem, Ceftazidime, Aztreonam, Chloramphenicol

Aerosol (6 mos on alternate months) Tobramycin (BID), Colistin (2-

4x/day), Gentamicin
Cystic Fibrosis
4. Bronchodilator Therapy adrenergic agonist aerosol (improvement
of >15% in airflow rates; alternative agents: Cromolyn sodium and
ipratropium no evidence to support

5. Anti-inflammatory agents corticosteroids useful for tx of allergic

bronchopulmonary aspergillosis and severe reactive airway disease
(modest efficacy and prohibitive side effects in a 4-yr double blind
study); ibuprofen shown to slow down disease progression

6. endoscopy and lavage instillation of saline or mucolytic agent

through fibroptic bronchoscope

7. expectorants iodides and guaifenesin not effective

8. mutation-specific therapies denufosol and Moli1901 bypasses the

CFTR defect by regulating alternative ion channels
Cystic Fibrosis
Nutritional Therapy high caloric diet 130 kcal /kgBW

1. recombinant GH therapy (3X/week)

2. pancreatic enzyme replacement lipase capsules

20,000IU capsules (<2,500 lipase units/kg/meal to prevent
colonic strictures)

3. vitamin and mineral supplement A,D,E,K and zinc

Diatrizoate (Gastrografin) enemas for meconium ileus; stool

softeners (polyethylene glycol, docusate sodium)

Proton pump, fundoplication for GERD; cholinergic agonist is

C/I
Cystic Fibrosis
Prognosis:

- life-limiting disorder although survival has improved

dramatically

- median cumulative survival exceeding 35 yrs.

- achievement of an independent and productive adulthood

is a realistic goal
Acute Pancreatitis
Common pancreatic disorder in children

Causes: blunt abdominal injury, multisystem disease, biliary

stones or microlithiasis (sludging) and drug toxicity (valproic
acid, L-asparaginase, 6-mercaptopurine, azathioprine)

Ductal disruption or obstruction premature activation of

trypsinogen to trypsin within the acinar cell activation of
other pancreatic enzymes autodigestion, further enzyme
activation, release of active proteases phospholipase A2
activates lecithin to toxic lysolecithin release of cytokine
and proinflammatory mediators
Acute Pancreatitis
Mild: severe abdominal pain (RUQ, epigastric, steady pain),
persistent vomiting, fever

Severe: acutely ill, severe nausea, vomiting, abdominal pain;

shock, fever, jaundice, ascites, hypocalcemia, pleural
effusion; Cullen sign (bluish discoloration around umbilicus);
Grey Turner sign (bluish discoloration in the flanks

Diagnosis: serum lipase test of choice; more specific; serum

amylase; CT scan pancreatic enlargement, hypoechoic,
sonolucent, edematous pancreas, pancreatic masses and
abscesses (80%); MRI cholangiopancreatography (MRCP)
and ERCP for recurrent/nonresolving pancreatitis
Acute Pancreatitis
Treatment: medical management to relieve pain and
restore metabolic homeostasis
Fluid and electrolyte and mineral balance
NPO if vomiting
Recovery in 4-5 days
Severe pancreatitis: antibiotic prophylaxis, gastric acid
suppression, elemental alimentation by mouth, NGT or
nasojejunal tube within 2-3 days of onset
Prognosis: uncomplicated resolves within 4-5 days
Malabsorption Syndrome
Chronic diarrhea and malabsorption of nutrients

Failure to thrive complication

1. Digestive defects CF, biliary or liver disease, lactase

deficiency

2. Absorptive defects celiac disease or UC

3. Anatomic defects short bowel syndrome

Celiac Disease (CD)
Gluten-induced enteropathy, gluten-sensitive enteropathy
(GSE) and celiac sprue
Disease of the proximal small intestine characterized by
abnormal mucosa and permanent intolerance to gluten
CD is 2nd to CF in malabsorption cause in children
Pathophysiology: intolerance to gluten (wheat, barley, rye
and oats); unable to digest gliadin component of gluten,
resulting to accumulation of toxic substance that is
damaging to the mucosal cells
Gluten hydrolized vegetable protein on canned labels
Celiac Disease
Failure to thrive and diarrhea

Diagnosis: biopsy of the SI mucosal inflammation, crypt

hyperplasia, villous atrophy; serologic testing detect Abs to
connective tissue (endomysium and reticulin more specific
markers)) and to gliadin (IgG and IgA antibodies); enzyme
tissue transglutaminase (tTG) autoenzyme by antiendomysial
Ab

Therapeutic management: gluten-free diet; substitute: corn

and rice; vitamin, iron and caloric supplementation

Prognosis: chronic disease

Lymphoma most serious complication

End of Session