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CHAPTER I
INTRODUCTION
1.1 Background
Central to human digestive health are both the production of bile by
hepatocytes and cholangiocytes in the liver and the excretion of bile through the
biliary tree. By volume, conjugated bilirubin is a relatively small component of bile,
the yellowish-green liquid that also contains cholesterol, phospholipids, organic
anions, metabolized drugs, xenobiotics, and bile acids. In most cases, the elevation of
serum-conjugated bilirubin is a biochemical manifestation of cholestasis, which is the
pathologic reduction in bile formation or flow.1
Complex mechanisms exist for the transport of bile components from serum
into hepatocytes across the basolateral cell surface, for the trafficking of bile
components through the hepatocyte, and finally for movement of these bile
components across the apical cell surface into the bile canaliculus, which is the
smallest branch of the biliary tree. From the bile canaliculus, bile then flows into the
extrahepatic biliary tree, including the common bile duct, before entering the
duodenum at the ampulla of Vater. Isolated gene defects in proteins responsible for
trafficking bile components can lead to cholestatic diseases.1
Cholestasis is condition which secretion and excretion of bile from the liver to
duodenum is disrupted. So, substance which is excreted with bile is restrained in
liver. The parameter of cholestasis is serum conjugated bilirubin >1 mg/dl if total
bilirubin < 5mg/dl, or conjugated bilirubin >20% of total bilirubin when total
bilirubin >5mg/dl.2
Cholestasis can be due to infectious, genetic, metabolic, or undefined
abnormalities giving rise to mechanical obstruction of bile flow or to functional
conditions that cause cholestasis may also lead to better outcomes because better
support of the infant may avoid complications of liver disease.4
Despite these data showing that early diagnosis is potentially life saving,
referral for evaluation of cholestatic jaundice frequently occurs after 45 to 60 days of
age (12). In recognition of this, and noting that no evidence-based guideline for its
evaluation currently exists, the Cholestasis Guideline Committee was formed by the
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
(NASPGHAN) to develop a clinical practice guideline for the diagnostic evaluation
of cholestasis in infants.4
1.2 Objective
This paper is completed in order to fulfill one of the requirements in the
Senior Clinical Assistance program in Department of Child Health of Haji Adam
Malik General Hospital, University of North Sumatera. In addition, this paper passes
the knowledge of cholestasis and its management
CHAPTER II
THEORY
2.1 Definition
Cholestasis is defined as a decrease in bile flow due to impaired secretion by
hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts.
Therefore, the clinical definition of cholestasis is any condition in which substances
normally excreted into bile are retained. The serum concentrations of conjugated
bilirubin and bile salts are the most commonly measured.5
Conjugated hyperbilirubinemia is defined biochemically as a conjugated
bilirubin level of 2 mg/dL and >20% of the total bilirubin.1
2.2 Epidemiology
Sex
No clear difference in the incidence of cholestasis between males and females
is observed. Incidence is equal in most genetic diseases leading to cholestasis.
However, several conditions have a female dominance, including biliary atresia,
drug-induced cholestasis, and of course, cholestasis of pregnancy.5
Age
Cholestasis is observed in people of every age group. However, newborns and
infants are more susceptible and more likely to develop cholestasis as a consequence
of immaturity of the liver.5
Young gestational age, low birth body weight, more sepsis episodes, and long
duration of parenteral nutrition are risk factors associated with Parenteral nutritionassociated cholestasis.5
2.3 Etiology1
Congenital infection
Cytomegalovirus
Toxoplasmosis
Rubella
Herpes simplex virus
Syphilis
HIV
Acquired infection
Urinary tract infection
Sepsis
Metabolic
Alpha-1 antitrypsin deficiency
Cystic fibrosis
Galactosemia
Tyrosinemia
Defects in bile acid synthesis
Inborn errors of carbohydrate, fat, protein metabolism
Obstructive
Biliary atresia
Choledochal cyst
Inspissated bile syndrome
Spontaneous perforation of bile duct
Cholestatic syndromes
Alagille syndrome
Progressive familial intrahepatic cholestasis
Endocrinopathy
Hypothyroidism
Hypopituitarism
Drug or toxin induced
Parenteral nutrition
Drugs
Systemic disorder
Shock
Congenital heart disease/heart failure
2.4. Symptoms and Signs
The typical findings in an infant who has cholestasis are protracted jaundice,
scleral icterus, acholic stools, dark yellow urine, and hepatomegaly. Some infants
may have coagulopathy secondary to vitamin K malabsorption and deficiency and
present with bleeding or bruising. Coagulopathy may also be caused by liver failure,
indicating either severe metabolic derangement of the liver (as in respiratory chain
deficiency disorders) or cirrhosis and end-stage liver disease (as in neonatal
hemochromatosis). Splenomegaly can be observed in infants who have cirrhosis and
portal hypertension, storage diseases, and hemolytic disorders. Neurologic
abnormalities including irritability, lethargy, poor feeding, hypotonia, or seizures can
indicate sepsis, intracranial hemorrhage, metabolic (including Zellweger syndrome)
and
mitochondrial
disorders,
or
severe
liver
dysfunction
resulting
in
2.5. Diagnose
2.5.1 History
- Pregnancy and labor history (TORCH infection)
- Birth weight and gestational age
- History of administration vitamin K
- History of similar complaints in family
- History of current complaints : onset of jaundice, urine and fecess color, history of
therapy, parenteral nutrition, bleeding, history of feeding, diarrhea or emesis
- black urine
- acholic feces
- growth disorders 2
2.5.2. Physical examination
- jaundice
- acholic feces
- bleeding signs (vitamin K deficiency)
- hepatomegaly or hepatosplenomegaly
- abdominal mass, ascites
- growth failure
- other signs about specific disease or syndrome : dysmorphic signs (Trisomy,
Alagille syndrome); murmur (Alagille syndrome, extrahepatic billiary atresia
(EHBA)); baby is sick, vital signs abnormal (sepsis, HLH, congenital infection);
micropenis (panhipopituitarism); cataract (rubella, galactosemia); situs inversus
(EHBA); retinas problem (TORCH infection, Alagille syndrome); abdominal mass
(choledocus duct cyst); hemangioma cutaneus (hepar hemangioma); white hair
(Hemophagocytic lymphohistiocytosis/HLH).2
10
Cholestasis
ALT/AST
ALP/GGT
Bilirubin
Intrahepatic
+++
++
Extrahepatic
++++
+++
Recommendations
1. A detailed history and physical examination are essential
11
12
Kasai portoenterostomy
For biliary atresia, which is a condition of extrahepatic biliary duct having
obstruction. This condition need Kasai PE. Kasais procedure if done early can give
good survival for 20 years, which is 60,5%. But, the flow of bile will be hard to be
returned if the operation done after 8 weeks old.2
Liver transplantation
Liver Transplantation, the standard therapy for decompensated cirrhosis due to any
cause. Any baby, who has had Kasais PE and the bilirubin remains >6 mg/dL, three
months after surgery, should be referred to a transplant center. Babies with BA who
present with decompensated cirrhosis (low albumin, prolonged INR, ascites) are not
likely to improve with a Kasai PE and should be referred for liver transplantation.
Living related liver transplantation (the vast majority of liver transplants in India are
living related), performed at experienced centers, is associated with favorable
outcomes, with 5- and 10-year survival rates of 98% and 90%, respectively.8
13
CHAPTER III
CASE REPORT
3.1 Case
FA, a 8 months boy, with 5.2 kg of BW and 62 cm of BH, is a patient of
infection unit in Pediatric Department in Central Public Hospital Haji Adam Malik
Medan on October 31st 2015 at 19.30. His chief complaint was yellow all over body.
History of disease:
FA, a boy, 8 months old, came to Haji Adam Malik Hospital on October 31st 2015
with yellow all over body as the chief complaint. The patient have been experienced
since 1 week ago and got worst two days back. Discontinuous high fever (+) since 6
days ago with the temperature of 39C and reduced by taking anti pyretic drugs. The
patient has acholic stools since four days ago. The convulsion history (-), Diarrhea(-),
Cough(-), Sneezing(-), Dysphagia(-), Defecation (+) acholic stools, Urination (+)
Normal
History of previous illness:
The patient was already treated under Gastroanterohepatology at 5 months old.
Patient was done laparotomy due to infection ec hernia incarcerata. Then when the
patient was 6.5 months laparotomy was done in left side.
History of medication:
Sanmol, nystatin drops
History of family:
14
General status:
Body weight: 5.2 kg, Body length: 62 cm,
Z scores in Height for age boys: Z < -3
Z scores in Weight for age boys: Z < -3
Z scores in weight for height boys : -3 < Z< -2
Present status:
Level of consciousness: GCS 15 (E4 V5 M6)
Body temperature: 37.4C
BP: 160/100 mmHg
15
Nose
Neck
Thorax
Differential diagnosis
:-
Working diagnosis
Laboratory finding
Result
8.10
3.07
24.80
Unit
g%
106/mm3
103/mm3
Referral
12.0-14.4
4.40-4.48
4.5-13.5
16
Thrombocyte
Hematocrite
Eosinophil
Basophil
Neutrophil
Lymphocyte
Monocyte
Neutrophil absolute
Lymphocyte absolute
Monocyte absolute
Eosinophyl absolute
Basophyl absolute
MCV
MCH
MCHC
RDW
Morphology:
265
25.80
5.50
0.800
36.50
48.80
8.40
4.40
5.90
1.01
0.67
0.10
80.80
26.40
32.70
23.00
103/mm3
%
%
%
%
%
%
103/L
103/L
103/L
103/L
103/L
fL
Pg
g%
%
150-450
37-41
1-6
0-1
37-80
20-40
2-8
2.4-7.3
1.7-5.1
0.2-0.6
0.10-0.30
0-0.1
81-95
25-29
29-31
11.6-14.8
Clinical Chemistry
Test
Result
Unit
Referral
117.00
mg/dL
< 200
Natrium
137
mEq/L
135-155
Kalium
Chloride
Liver Function Test
4.4
105
mEq/L
mEq/L
3.6-5.5
96-106
Bilirubin Total
Bilirubin Direk
9.43
30.0
mg/dL
mg/dL
<1
0 - 0.2
Carbohydrate Metabolism
Blood Glucose
Electrolite
17
442
U/L
<462
AST/SGOT
185
U/L
<38
ALT/SGPT
167
U/L
<41
FOLLOW UP
November,1st 2nd 2015
S
O
Neck
Thorax
Abdomen
18
Extremities
Management
IV Inj cefepime Hcl 250mg/12jam
Urdafalk 2x30mg
Theobron syr 3x cth
IVFD D5% Nacl 0,225% 20gtt/i micro
Planning
Urine and Feaces test
Urine & feaces test Result
Normal
November, 3rd 4th 2015
S
Yellow all over the body(+), Fever (-)
O Sensorium : CM, Temp: 37,2 36,1o C BB: 5.2Kg
Head
Neck
Thorax
Abdomen
19
Neck
Thorax
Abdomen
20
S
O
Neck
Thorax
Abdomen
Management
IVFD D5% Nacl 0,225% 20gtt/menit mikro
Inj cefepime Hcl 250mg/12jam
Urdafalk 2x30mg
Theobron syr 3x cth
November, 9th-10th 2015
BB : 5.2kg
Neck
Thorax
21
Cholestasis + Bronkopneumonia
Management
Amoxicilin Syrup 3xcth I
Urdafalk 3x20mg
Theobron syr 3x cth
BB : 5.2kg
Neck
Thorax
Abdomen
Cholestasis + Bronkopneumonia
Management
Amoxicilin Syrup 3xcth I
22
Urdafalk 3x20mg
November, 13th 2015
BB : 5.2kg
Neck
Thorax
Abdomen
Cholestasis + Bronkopneumonia
Management
Amoxicilin Syrup 3xcth I
Urdafalk 3x20mg
Theobron syr 3x cth
Planning
Patient was discharged with regular check up
Inj vitamin K 1mg/IM/1 times a month
Urdafalk 3x20mg
CHAPTER 4
DISCUSSION
23
24
SUMMARY
FA, a boy, 8 months old, came to Haji Adam Malik Hospital on October 31st 2015
with yellow all over body as the chief complaint. The patient have been experienced
since 1 week ago and got worst two days back. Discontinuous high fever (+) since 6
days ago with the temperature of 39C and reduced by taking anti pyretic drugs. The
patient has acholic stools since four days ago. Patient treated with IVFD D5% Nacl
0,225% 20gtt/i micro, Inj cefepime Hcl 250mg/12jam, Urdafalk 2x30mg, Theobron
syr 3x cth.
25
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Pediatrics in Review July 2012, VOLUME 33 / ISSUE 7. Available at
http://pedsinreview.aappublications.org/content/33/7/291#T1
2. Tanto Chris, Liwang Frans, Hanifati Sona, Pradipta Eka Adip, Kapita Selekta
Kedokteran, 2014. Volume 1.
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2007.
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Olson, Alan D. MD; Brewer, Fred MD; Colletti, Richard B. MD; Heyman,
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-
pp
115-128.
Available
at.
http://journals.lww.com/jpgn/Fulltext/2004/08000/Guideline_for_the_Evaluation_
of_Cholestatic.
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http://emedicine.medscape.com/article/927624-overview#a5
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Edition.
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at
26
http://www.msdmanuals.com/professional/pediatrics/perinatal-problems/neonatalcholestasis
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Vidyut Bahtia, Ashish Bavdekar, John Matthai, Yogesh Waikar, and Anupam
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