BUKOVINIAN STATE MEDICAL UNIVERCITY

Department of Pediatrics and Medical Genetics

DISEASES OF THE
HEPATOBILIARY SYSTEM IN
CHILDREN
 Functions of the liver
 The liver regulates most chemical levels in the blood and excretes a
product called bile. This helps carry away waste products from the liver.
 All the blood leaving the stomach and intestines passes through the liver.
 The liver processes this blood and breaks down, balances, and creates the
nutrients and also metabolizes drugs into forms that are easier to use for
the rest of the body or that are nontoxic.
 More than 500 vital functions have been identified with the liver.
 Some of the more well-known functions include the following:
 Production of bile
 Production of certain proteins for blood plasma
 Production of cholesterol and special proteins to help carry fats through
the body
 Conversion of excess glucose into glycogen for storage
 Regulation of blood levels of amino acids, which form the building
blocks of proteins
 Functions of the liver
 Processing of hemoglobin for use of its iron content (the
liver stores iron)
 Conversion of poisonous ammonia to urea (excreted in
the urine)
 Clearing the blood of drugs and other poisonous
substances
 Regulating blood clotting
 Resisting infections by making immune factors and
removing bacteria from the bloodstream
 Clearance of bilirubin, also from red blood cells.
 Functional disorders of the gallbladder and
sphincter of Oddi

 Functional disorders of the biliary tract

(FRBT) are functional disorders of the
gallbladder (MR) and (or) tone of the sphincter
apparatus due to inconsistent, untimely,
insufficient or excessive reduction of the gall
bladder and (or) sphincter apparatus.
 The disease is polyethiological, genetically
determined.
• The bile duct ends below by
piercing the medial wall of the
second part of the duodenum
about halfway down its length.

• It is usually joined by the main

pancreatic duct, and together they
open into a small ampulla in the
duodenal wall.

• The ampulla opens into the lumen of

the duodenum by means of a small
papilla, the major duodenal
papilla.
The terminal parts of both ducts and the
ampulla are surrounded by circular
muscle, known as the sphincter of the
hepatopancreatic ampulla
(sphincter of Oddi).
 FUNCTION OF THE GALLBLADDER

When digestion is not taking place, the sphincter of Oddi remains

closed and bile accumulates in the gallbladder. The gallbladder:
• concentrates bile;
• stores bile;
• selectively absorbs bile
salts,
• keeps the bile acid;
• excretes cholesterol;
• secretes mucus.
 Functional disorders of the biliary tract
- functional dysmotility of gallbladder and (or) the tone
of the sphincter apparatus because of inconsistent,
untimely, insufficient or excessive contraction of the
gallbladder and (or) sphincter apparatus.

The chain of pathological changes:

malformation ↓
functional disorder ↓
cholecystocholangitis, ↓
cholelithiasis.
 The pathophysiological formation of functional
disorders of the biliary tract in children is due to
a violation of the neuro-humoral mechanisms of
regulation of the contractile function of the
gallbladder and the tone of the sphincter of Oddi,
Liutkens, and Mirizzi.
 The motor activity of the biliary tract is regulated
by the parasympathetic and sympathetic parts of
the autonomic nervous system, gastrointestinal
hormones (cholecystokinin, secretin, gastrin,
glucagon), thyroidinum, oxytocin, corticosteroid
and sex hormones.
 Diagnostics:
Biochemical serum blood (cholesterol, alkaline phosphatase,
GGTP, total bilirubin and fractions, AST, ALT, amylase and
lipase).
Microscopic and biochemical research of bile.
Coprogram.

Instrumental: dynamic ultrasound cholecystography –

study of functional status of the gallbladder and sphincter Oddi
Endoscopy, cholecystography, fractional duodenal intubation,
Bacteriological examination of bile.
 Classification of functional disorders of the gallbladder and
sphincter of Oddi (Rome III consensus)

by origin by functional state:

•primary 1. Hypofunction or hyperfunction of gallbladder.
•secondary 2. Spasm or failure of the sphincter of Oddi.

by location clinical forms

1.functional disorder 1. hyperkinetic-hypertonic
of the gallbladder 2. hyperkinetic-hypotonic
2.functional disorder 3. hypokinetic-hypotonic
of sphincter of Oddi 4. hypokinetic-hypertonic
 Major clinical syndromes

• Pain (sharp
( or aching, in right upper quadrant)
• Dyspeptic (bitter
( belching, nausea, vomiting,
flatulence, constipation, diarrhea)
• Nonspecific toxicity
(fatigue, weakness)
DIAGNOSTIC CRITERIA OF FUNCTIONAL DISORDERS OF
THE GALLBLADDER:

- biliary pain is combined with normal levels of liver enzymes,

conjugated bilirubin, amylase / lipase
- at hypokinetic type of dysfunction - possible biochemical
cholestasis syndrome - increased serum cholesterol,
alkaline phosphatase,
GGTP,
total bilirubin (direct fractions);

- gallbladder dysfunction on the results of ultrasound.

 HYPOTONIC-HYPOKINETIC DISFUNCTION:

- almost constant pain, pain increased periodically by use of fatty foods,

after exercise;
- the pain is dull, aching, compressive, may be discomfort in the right upper
quadrant;
- tenderness in the right upper quadrant, positive bladder’s symptoms, liver
increased in size;
- expressed dyspeptic syndrome (loss of appetite, nausea, constipation);
- ultrasound: increased in size gallbladder,
reducing its diameter after stimulating
breakfast less than 33%.
 HYPERTONIC-HYPERKINETIC DISFUNCTION:

- pain occurs on the background of negative emotions, physical overload,

after eating cold foods or beverages;
- short-term acute, paroxysmal pain in the right upper quadrant, cutting
character;
- between pain attacks feeling is not violated;
- tenderness in the right upper quadrant, bladder symptoms mild positive,
liver rarely increased in size;
- dyspeptic syndrome: the tendency to diarrhea;
- ultrasound: a decrease in the size of the gallbladder,
especially its diameter, after stimulation
more than 65%.
Ultrasound examination
with stimulating breakfast
(2 row eggs)
On the 30-60 min
Contraction function of
gallbladder is evaluated
N=50% of the beginning diameter
Hypokinetic - less than 33%
Hyperkinetic – more than 66%
 DUODENAL INTUBATION
The first phase (holedohus-phase).
Common bile duct and pancreatic duct are relaxed;
From common bile duct follows a small number of light bile.
The duration of 14-16 minutes.

The second phase.

Common bile duct and pancreatic duct
are closed since the introduction of the
stimulus to the appearance of colored
bile secretion.
Duration 3-5 minutes.
The presence of bile indicates a failure of the sphincter of Oddi,
extended fase - inhibition of the production of bile.
The third phase – “A” bile portion
(the disclosure of the common bile duct
and pancreatic duct to the appearance of
dark bile from the gall bladder).
Duration 3-4 minutes.
Provided bright 5-6 ml of bile

The fourth phase – “B” portion - bile from the gallbladder

brownish-olive color, stands for 20-30 minutes in an
amount of 30-50 ml. (sphincter relaxation and emptying of the
gallbladder).
The duration of 20- 30 minutes.

Fifth phase – “C” portion

(bile from the liver ducts),
10-15 minutes
amount of 10-15 ml.
 TREATMENT
Hypokinetic type
1. Diet;
2. Bile preparations:
- Choleretic (drugs that stimulate the synthesis of bile): - alohol,
mineral water, holosas, halstena, Gepabene, ursofalk;
- Cholekinetics (drugs that stimulate motility of the gallbladder):
25% magnesium sulfate, sorbitol, xylitol;
3. Rinse with mineral water, xylitol, sorbitol
4. Physiotherapy
5. Therapeutic physical exercises.
 TREATMENT
Hyperkinetic type
1. Diet meals (5-7 times a day)
2. Sedative medications - herbal, homeopathic remedies;
3. Antispasmodic drugs: platifillin, papaverine, no-spa, meteospazmil;
4. Choleretic (drugs that stimulate the synthesis of bile, including those
containing bile extract):
true (stimulating bile acid synthesis) - ursodeoxycholic acid in
suspension: 5-10 mg / kg per day in 2 divided doses (one dimensional
spoon is 250 mg UDCA) and
hydrocholeretic (stimulating the synthesis of bile water
component) - Mineral water for 3 - 5 ml / kg, 2 - 3 weeks.
5. Physiotherapy: heat treatments (mineral wax, paraffin baths,
electrophoresis of antispasmodics in the right hypochondrium,
ultrasound);
6. Therapeutic physical exercises.
 CHRONIC CHOLECYSTOCHOLANGITIS

gall bladder disease, which is based on inflammatory changes in

the gallbladder wall of different etiologies.

Complaints:
- pain in the right upper quadrant, sometimes in the epigastrium,
umbilicus (usually after physical or emotional stress, intercurrent
diseases), possible irradiation in the right shoulder;
- nausea, vomiting bile, bitterness in the mouth, belching,
violations chair (tendency to diarrhea or constipation)
- chronic nonspecific signs of intoxication.
 Ker symptom
Oppenheim symptom
(pain on insufficientl yon palpation
in Ker-point - projection of the (pain on palpation of
gallbladder, which is located at the spinous processes of the
intersection of the lateral edge of thoracic vertebrae)
the rectus abdominis muscle and
the right costal arch)

De Musset's-George symptom
Ortner-Grekov symptom (frenikus)

(pain when tapped by (pain in the right upper quadrant

hand on the edge of the when pressed between the legs of
right costal arch) the right sternoclavicular-mastoid
muscle)
 DIAGNOSTICS;
1. Clinical blood test: significant neutrophilic leukocytosis, a tendency
to accelerate ESR;
2. Biochemical test:
cholestasis syndrome (high cholesterol, GGTP, alkaline phosphatase,
a tendency to increase total bilirubin due to direct fraction)
cytolytic syndrome - increased AST, ALT (acute stage, the stage of
incomplete clinical remission)
non-specific intoxication - positive "C" - reactive protein (acute
stage); amylase / lipase serum in the normal range.
3. Microscopic examination of bile:
indicators of inflammation (increased content of epithelial cells,
leukocytes in the portions B and C, crystals components of bile -
indirect signs of exacerbation or incomplete clinical remission);
4. Bacteriological study of bile
5. Ultrasound - compaction and thickening of the walls of the
gallbladder (>2 mm), "sludge" in the gall bladder, the presence of
inflammation of the liver parenchyma.
 TREATMENT
1. Diet;
2. In acute stage: spasmolytic therapy:
drotaverine (1-1.5 mg / kg) mebeverine (children from 12 years) 200
mg
3. Antibiotic therapy:
• medicines that are present in the bile in high concentrations,
penicillin, macrolide, cephalosporin group (age doses);
• medicines that accumulate in the bile in sufficient concentrations to
effect treatment, furazolidone (age dose).
The course of antibiotic therapy 7 - 10 days.
4. Choleretics
5. Cholekinetics
 CHOLELITHIASIS (GALLSTONES)
Gallstones are abnormal, inorganic masses formed in the gallbladder and, less
commonly, in the common bile or hepatic ducts

Types of gallstones:
• Pure cholesterol
• Pure pigment
• Mixed

Under normal conditions,

a delicate balance occurs among the levels
of bile acids, cholesterol, and phospholipids.
A disparity in this balance, especially with the supersaturation of cholesterol,
predisposes patients to the formation of lithogenic bile and the subsequent
development of cholesterol-type gallstones.
Pigmented gallstones are composed of calcium bilirubinate
and appear in 2 major forms: black and brown.

Females are more likely to develop gallstones than males,

with a ratio of 2:1.
Nonshadowing echogenic homogenerous mass shifting
position slowly
•Gallstone with shadowing:
high-level intraluminal
echoes+ acoustic shadowing
 TREATMENT

1. Diet;
2. In acute stage: spasmolytic therapy
3. Choleretics - ursodeoxycholic acid (UDCA) in suspension:
5-10 mg / kg per day in 2 divided doses
4. Surgical method
 Jaundice
 A yellowish straining of the skin, sclerae and
deeper tissues with bile pigments which are
increased in plasma

Pre-hepatic Post-hepatic
Haemolytic Cholestatic

Hepatocellular
 Pre-hepatic Hepatic Post-hepatic

Urine No Bilirubin ↑Bilirubin ↑Bilirubin

↑Urobilinogen ↑Urobilinogen ↓ Urobilinogen

Faeces Dark Pale Pale

Blood ↑Bilirubin – ↑Bilirubin – ↑Bilirubin -

unconjugated mixed conjugated
conjugated &
unconjugated
↑AST, ALT
CHRONIC HEPATITIS - inflammatory-dystrophic
lesions of the liver, which lasts more than 6 months and
appears cytolytic,
pain,
dyspeptic,
intoxication,
cholestatic syndromes
with symptoms of functional and
hepatovascular failure.
 ETIOLOGY:

•Viruses – A, B, C, D, F, G, TTV,
•Toxic
•Medication
•Cryptogenic
•Metabolic
 VIRAL HEPATITIES MARKERS
Hepatitis Marker Characteristic Clinical picture
Ig M Antibodies Acute infection
Anti-HAV
A
Ig G Antibodies Past infection
Anti-HAV Store in blood during lifetime
Ig M Antibodies Replication of virus
Anti-HDV
Ig G Antibodies Past infection or possible infection
D Anti-HAV
HD Ag Ag of virus Presence of HDV in organism
HDV-RNA Presence of virus and replication

Anti-HCV Ab G Past infection or possible infection

Anti-HCV Ab to nuclear Acute infection

core IgM proteins HCV
C Anti-HCV Ab to nuclear Past infection or infection by HCV
core IgG proteins HCV
HCV RNA Presence and replication of virus
 HBsAg Superficial Ag Marker of HBV
HBeAg Nuclear “e”-Ag Indicates replication of virus in
hepatocytes,
blood high infectivity
HBcAg Nuclear “core”-Ag Marks viral replication in hepatocytes,
Is detected only in liver biopsies on
morphological examination
In the blood in a free form is not
detectable
Anti-НВс Total Ab to HBcAg For retrospective diagnosis
B In case of negative HBsAg
(total)
(НВсАb)
НВсАb IgM Antibodies to nuclear Acute infection
Ag

HBeAb Antibodies to “e”-Ag Beginning of reconvalescence

HBsAb Antibodies to Past infection
superficial Ag Postvaccinal Ab
HBV-DNA Marker of HBV and replication
 Pathogenesis:

Infection

                               
Persistence of virus (replication) in the liver cells:
(Lack of interferon synthesis in hepatocytes)

                             
The destruction of the liver parenchyma,
inflammation and immunological changes;
microcirculation disturbances,
the development of cholestasis
                               

Fibrosis.
The activity of chronic hepatitis :
a)minimum (increase of ALT levels up to 3 times)

b)mild (ALT higher than normal in 4-10 times);

c)severe (ALT levels more than 10 times).

Stages of chronic hepatitis:

0- no fibrosis;
1 - low-periportal fibrosis;
2 - mild fibrosis with porto-portal septum;
3 - spread fibrosis with porto-central septum;
4 - cirrhosis.
 Syndromes
-pain
-dyspeptic
-intoxication
-hepatomegaly
-cholestatic (increase of bilirubin)
-cytolysis (increase of ALT, AST)
-mesenchymal-inflammatory (leykocytosis, increase ESR,
C-reactive proteine )
-hepatocellular insufficiency (decrease of proteins,
holesterine)
-hemorrhagic (anaemia, decrease of coagulation factors)
 Criteria's of diagnosis

blood transfusions, surgery history

the presence of hepatitis B markers in serum:
in replicative phase - HBsAg, HBeAg, HBV-DNA,
anti HBsIgM; tissue marker- HBsAg;
in integrative phase - HBsAg, anti HBeIgG anti-
HBsIgG in serum; HBsAg- in the liver tissue.
Patients with chronic hepatitis C are at risk for
extrahepatic complications. HCV may form immune
complexes with anti-HCV (IgG). The deposition of
immune complexes may cause small-vessel damage.
Complications of include rash, vasculitis, and
glomerulonephritis.
 TREATMENT
Antiviral therapy has a number of major goals. These include

1) to decrease viral replication or eradicate virus,

2) to prevent progression of disease,

3) to decrease the incidence of cirrhosis,

4) to decrease the incidence of HCC,

5) to decrease symptoms such as fatigue and joint pain,

6) to treat extrahepatic complications of HCV infection

 TREATMENT
Etiotropic therapy (aimed at inhibiting the replication of
viruses and their elimination) –
Interferon(α) and inhibitors of viral DNA-polimerase
(lamivudine 3 mg/kg).
Hepatoprotektors
Sorbents
Antiocsidants
Probiotics
Candidates for interferon therapy must have a clinical
diagnosis of chronic HBV infection, with an elevated
level of ALT. They must have evidence of active HBV
replication, as marked by a positive HBeAg or a
positive HBV DNA finding.
 lamivudine:
It inhibits DNA polymerase and can suppress
HBV replication.

Plasma-derived and recombinant HBV vaccines use

HBsAg to stimulate production of anti-HBs.
 Cirrhosis
A chronic disease of the liver marked by
pathological formation of widespread fibrosis
(scarring) and degenerative changes. Symptoms
result from loss of liver cell function, increased
resistance to blood flow through liver, leading to
ammonia toxicity
Clinical signs
 Hepatic Encephalopathy

 symptomocomplex of central nervous system

dysfunction arising from liver failure, against
the background of acute viral, drug hepatitis,
Wilson Konovalov's disease, Badda-Chiari
syndrome, liver cirrhosis, spontaneous
bacterial peritonitis, ascites; taking diuretics,
sedatives, opiates, alcohol, food protein;
paraabdominocentesis.
Symptoms of severe hepatic encephalopathy
are:
confusion
drowsiness or lethargy
anxiety
seizures
severe personality changes
fatigue
confused speech
shaky hands
slow movements
 Stages of liver encephalopathy
 Minimal (latent) – consciousness, intellectual status, behavior not
changed, change of psychometric tests.
 Stage I (mild) – drowsiness, sleep rhythm disturbance, behavior,
mood; reduced attention, concentration; memory impairment; positive
standardized psychomotor tests (line test and number test); finely
swept tremor; change of handwriting.
 Stage II (moderate) – lethargy or apathy; inadequate behavior;
disorientation; asterixis; ataxia.
 Stage III (severe) – somnolence, disorientation; aggression; deep
amnesia; asterixis, increased reflexes.
 Stage IV – coma; lack of consciousness and reaction to pain;
intellectual status is not determined; areflexia.
 EMERGENCY TREATMENT
 1. Identification and elimination of provoking factors (alcohol, bleeding, hypovolemia).
2. Restriction of animal protein intake to 40 g/day (meat, fish, eggs, cheese are
completely excluded). Then gradually increase the protein content by an average of 10
g over three days.
3. Rifaximin (drug of choice) 400 mg 3 times/day for 7-14 days or ciprofloxacin 100 ml
(200 mg) twice daily; in the development of peritonitis – ciprofloxacin 100 ml (200 mg)
twice/day + cefotaxime 1000 mg dissolved in 4 ml of water for injection 2-3 times/day
slowly for 3-5 minutes + metronidazole 100 ml 50 (500 mg) 3 times/day – in the
presence of infectious diseases, as the cause of encephalopathy, in order to reduce the
ammonia flora.
4. B vitamins: thiamine bromide (B1) 40 mg or cocarboxylase 200 mg; pyridoxine (B6)
50-100 mg; cyanocobalamin (B12) 200 mg/day; lipoic acid (4 ml of 0.5% solution);
piracetam (4-6 g); nicotinamide (PP) 100-200 mg; ascorbic acid (C) 1000 mg in of 5-
10% glucose solution (for every 10 g of glucose for intravenous infusions enter 1 unit
of short-acting insulin) for the purpose of detoxification.
 5. Sodium bicarbonate 200-600 ml 4% solution – for metabolic acidosis.
6. Potassium chloride 10-20 ml 7.5% solution for 200 ml 5% glucose solution or gelatinol
250-500 ml for metabolic alkalosis.
7. Hepasol A 500 ml once/day for 7 days, or
8. Ornithine aspartate 20-40 g/day for 20 ml of 0.9% NaCl solution slowly, after improvement
of condition – 2-3 times/day; heparamer 20 g (40 ml) with 500 ml of 0.9% NaCl solution at a
rate of 4-6 drops/min. 7 days, followed by ingestion of 18 g/day (pellets 6 g (2 packs) 3
times/day) – improve the metabolism of ammonia in the liver.
9. Lactulose at an initial dose of 90 mg/day with an increase to mild diarrhea every hour
orally (via gastric tube with preaspiration of gastric contents), for improvement of the
condition – 4 times/day; or through a nasogastric tube 1000 ml of 10% solution of mannitol
for 60-90 min.
10. Enema should be high, which cleans the colon to the cecum. This is achieved by changing
the position of the patient's body: the introduction of the solution begin in the position of the
patient on the left side, then continue in the position on the back with the trunk raised and end
in the position on the right side. Lactulose – enemas (300 ml of syrup in 700 ml of water
twice a day).
 11. Fresh frozen plasma of 400-800 ml intravenously in the presence of bleeding in order
to correct hemostasis.
12. Proteolysis inhibitor aprotinin 1 000 000 AU/day in 250 ml of 0.9% NaCl, dropwise
for 1 hour; an inhibitor of fibrinolysis – aminocaprone acid 4-5 g 51 per 250 ml of 0.9%
NaCl; etamzilate sodium 2 ml of 12.5% solution in the presence of hemoragic syndrome.
13. Heparin 5000-10 000 AU/4 timesday subcutaneous and transfusion of fresh single-
blood heparinized blood – in the presence of disseminated intravascular coagulation
syndrome. 14. Omeprazole 20 mg with 200 ml 5% glucose solution twice daily – to
prevent "stress" damage to the gastroduodenal mucosa.
N.B.! Exclusion of methionine, choline, barbiturates, morphine, phenothiazines, salicylic
acid. Ineffective: unithiol, galascorbin, lipoic acid, a-glutamine. The effectiveness of
therapy is evaluated by the level of consciousness and adequacy of the patient's behavior,
the dynamics of biochemical parameters of blood (bilirubin, albumin, prothrombin index,
urea, creatinine, ALT), as well as the absence of acute cardiovascular, renal insufficiency.
Thank you for
attention