Case Discussion Gastroenterohepatology I

Extrahepatic Cholestasis in
9-Month-Old Boy

Hariogie Putradi

Moderator: dr. Anik Widijanti, Sp. PK (K)

DATA BASE

Boy, 9 month old.

Admitted on August 7th, 2018.

Chief complain: Patient suffered from diarrhea.

History of present illness:

- Patient suffered from diarrhea since 2 days ago. The
frequency of diarrhea about 8-9 times per day,
white color stool (+), mucus (+), blood (-).
DATA BASE
˗ He has also vomiting since 1 day before admission,
frequency > 5x/day, containing food. Vomiting
occured every after meal.
˗ Icteric on his eye and body since the age of 3 days.
˗ He had also low grade fever since 1 day ago.
˗ Dark colored urine (+).

• History of past illness:

- He had been diagnosed with cholestasis since 26 Juni
2018 (he had history of icteric on his body and
abdominal enlargement +).
• History of family disease: (-)
DATA BASE
Pregnancy history:
• ANC every month at midwife, vitamin (+), DM (-), HT (-).

Antenatal history:
• SCTP e.c. nuchal cord, 2800 grams, complete
vaccination.
• History of icteric at the age of 3 days,
got phototherapy, and then resolved.
The icteric appear again at the age of 1 week.

Social history:
• Mother: housewife, Father: private employee.
• First child.
PHYSICAL EXAMINATION
General Moderately ill, GCS: 4-5-6
status BW: 7,3 kg Height: 66 cm
(AC: 10 cm, HC: 41 cm)
Malnutrition - Marasmus
Vital sign BP: - mmHg HR: 143 bpm
RR: 30 bpm Tax: 36,2°C

Head & Anemic conjunctiva -/-,

Neck Icteric sclera +/+,
Sunken eyes +/+,
Sunken fontanelle +.

5
 PHYSICAL EXAMINATION
Thorax Pulmo:
symetrical, vesicular sound +/+,
Rh-/-, Wh -/-

Cardiac:
ictus at 5th ICS left MCL, single S1/S2, murmur
(-), gallop (-)

Abdomen Flat, BS (+)↑, Hepatomegaly (+) 1/2-1/2,

Splenomegaly (+), traube space: dullness,
shifting dullness (-)
Extremities Anemic -/-, edema -/-, warm acral.
6
LABORATORY RESULT
MRS
HEMATOLOGY 21-07-18 07-08- - 12-08- - 14-08- Reference
PRC
18 18 18
1 pack
Hemoglobin 8,80 10,20 8,2 8,00 10,5– 12,9 g/dl

Erythrocyte 3,55 4,57 3,73 3,69 3,6 – 5,2.106/µl

Hematocrit 28,40 34,50 27,80 26,60 35 – 43 %

MCV 80,00 75,50 74,50 72,10 74 – 106 fl

MCH 24,80 22,30 22,00 21,70 21 – 33 pg

MCHC 31,00 29,60 29,50 30,10 28 – 32 g/dL

RDW 23,20 21,70 22,60 23,80 11,5 – 16,0 %

Leukocyte 13,71 14,21 6,44 7,48 6 – 17,5 x 103/µl

Thrombocyte 351 318 117 105 217 – 497 x

103/µl

Diff. count 2/0/0/ 0/0/0/ 2/0/0/ 4/0/0/ 1-5/<1/<8/17-

60/20-70/1-11
48/39/11 69/25/6 49/40/9 39/48/9
 MRS
BLOOD 21-07- 07-08- - 12-08- 13-08- Reference
CHEMISTRY 18 18 18 18
AST/ SGOT 571 681 - - < 89 U/L
ALT/ SGPT 362 418 - - < 57 U/L
Albumin 3,22 3,56 2,71 - 3,8-5,4 g/dL
Ureum 27,40 - - - 11 - 36 mg/dL

Creatinine 0,08 - - - < 0,42 mg/dL

RBS - 102 - - 50-180 mg/dL

Total bilirubin 29,20 - - 19,2 < 1,0 mg/dL

Direct 22,75 - - 16,23 < 0,25 mg/dL

bilirubin
Indirect 6,45 - - 2,97 < 0,75 mg/dL
bilirubin
 MRS
Serum 07-08- 08-08- 12-08- 13-08- Reference
Electrolyte 18 18 18 18
Natrium 157 161 144 140 131 - 140
mmol/L
Kalium 4,56 4,42 3,73 3,47 3,5 – 6,1
mmol/L
Chloride 128 137 116 111 97 – 106
mmol/L
Calsium 9,8 9,8 8,1 8,2 9,0 – 11,0
mg/dL
Phosphorus - 4,1 1,8 1,9 3,5 – 6,6
mg/dL
Procalcitonin - - 0,54 - <0,5 ng/mL
URINALYSIS Result Reference
(23-07-18)

Clarity Cloudy -
Color Orange -
pH 7,0 4,5-8.0
SG 1,010 1,002-1,006
Glucosa negative negative
Protein negative negative
Keton negative negative
Bilirubin +3 negative
Urobilinogen negative negative
Nitrit negative negative
Leukocyte negative negative
Blood negative negative
URINALYSIS Result Reference
10 x
Epithel + ≤3
Cylinder negative LPF
40 x
Erythrocyte 0-1 ≤3
Eumorphic - %
Dismorphic - %
Leukocyte 0-2 ≤5
Crystal bilirubin crystal + HPF
Bacteria negative ≤ 93 x 103/mL
Others - -
STOOL ANALYSIS Result Reference
(07/08/18) MRS
Color White -
Consistency Mushy -
Element negative -
Epithelium + HPF negative - (+1)
Leukocyte negative HPF ≤5
Erythrocyte negative HPF negative
Parasite negative negative
• Worm egg negative HPF negative
•Worm egg negative negative
identification
• Larva negative HPF negative
•Larva identification negative negative
STOOL ANALYSIS Result Reference
• Trophozoite negative HPF negative
•Trophozoite negative negative
identification
• Cyst negative HPF negative
•Cyst identification negative negative
Food remnants negative
Muscle fiber negative HPF < 10
Plant fiber negative HPF -/+
Amylum negative HPF -/+
Fat globules negative HPF Steatorrhea>60
Others Bacteria +
Stool Analysis
Abdominal USG (25-6-2018)

Conclusion :
• Biliary atresia
• Chronic liver disease (cirrhosis)
• Splenomegali
• Ascites
DATA INTERPRETATION

• Boy, 9 m.o.
• Laboratory results showing :
• normocytic normochromic anemia, elevated RDW.
• elevated SGOT (7,6x), SGPT (7,3x), elevated bilirubin
D>I, hypoalbuminemia, hypernatremia,
hyperchloremia.
• white mushy stool.
• USG : Biliary atresia, Chronic liver disease (cirrhosis),
Splenomegali, Ascites.
DATA INTERPRETATION
• Based on medical history, physical examination,
laboratory data and others examinations showed
normocytic normochromic anemia, extrahepatic
cholestatic jaundice e.c. biliary atresia, elevated
transaminase e.c. liver cirrhosis, and
hypernatremia/hyperchloremia d.t. gastroenteritis with
moderate dehydration
• Suggestion: Peripheral blood smear, Reticulocyte count,
Total protein, Globulin, ALP, GGT, Coagulation tests,
Ureum, Creatinine, Urinalysis, Urine electrolyte.
• Monitoring: CBC, SGOT, SGPT, Bilirubin T/D/I, Albumin,
Serum electrolyte.
 Discussion

Establishment of Diagnosis

Elevated Transaminase

Hypernatremia
19
 1. Cholestatic Jaundice

• Cholestasis2 : is a reduced bile flow and abnormal

accumulation of conjugated bilirubin.
• Jaundice1 : increasing bilirubin in the blood
becomes visible within the sclera, skin, and
mucous membranes.
• Cholestatic jaundice2 is jaundice caused by an
elevated serum conjugated bilirubin.

1. Beckingham, 2001. Abc Of Liver, Pancreas And Gall Bladder

2. Urganci et al., 2012. Infants with Cholestasis: Diagnosis, Management and
Outcome. 20
 1. Cholestatic Jaundice…

• Indicator of cholestasis :

Direct reacting serum bilirubin levels >17 μmol/L

(>1.0 mg/dL).
Direct reacting bilirubin >20% of the total serum
bilirubin concentration, if total bilirubin is >85
μmol/L (5.0 mg/dL).

Urganci et al., 2012. Infants with Cholestasis: Diagnosis, Management and Outcome.
21
 1. Cholestatic Jaundice…
Cholestasis in newborns and infants can caused by :
Extrahepatic (Obstructive disorder) : biliary atresia (35%),
gall stone, tumor, cholangitis  infected cholestasis,
pancreatitis.
Intrahepatic/hepatocellular diseases/neonatal hepatitis
(30%) :
Liver disease/disorder (viral hepatitis : CMV, Hepatitis B,
Toxoplasma, bacterial infection, drugs)
Metabolic
Other causes : sepsis (endotoxin), genetic or idiopathic
Poisoning
Other common causes are α1-antitrypsin deficiency (17%),
Alagille syndrome (6%), and choledochal cysts (3%).
Urganci et al., 2012. Infants with Cholestasis: Diagnosis, Management and Outcome.22
BILIARY ATRESIA

• Biliary atresia is a progressive, fibro-obliterative

disorder of the intra and extrahepatic bile ducts in
infancy.

Epidemiology :
• Biliary Atresia is more common among females, and
non white individuals.
• Full-term infants with low birth weight (<2500 g)
are at a higher risk of developing Biliary Atresia than
infants born at term with normal birth weights.

Ghazy RM, Adawy NM, Khedr MA, Tahoun MM. 2018. Biliary atresia recent insight.
Egyptian Pediatric Association Gazette 66: 1-8.
BILIARY ATRESIA
Classification of biliary atresia according to the
location of involvement (yellow areas).

Ghazy RM, Adawy NM, Khedr MA, Tahoun MM. 2018. Biliary atresia recent insight.
Egyptian Pediatric Association Gazette 66: 1-8.
BILIARY ATRESIA

Etiology :

• Genetic factors → mutation of Jagged [Jag 1] gene

• Immunological injury → MN inflammatory infiltrates
within damaged IHBDs and the biliary epithelium
• Viral infection → hepatitis B, CMV
• Environmental factors → drugs used during gestation,
agricultural/ industrial toxin

Ghazy RM, Adawy NM, Khedr MA, Tahoun MM. 2018. Biliary atresia recent insight.
Egyptian Pediatric Association Gazette 66: 1-8.
BILIARY ATRESIA
Clinical presentation :

• usually present early in the neonatal period

and are associated with persistent jaundice,
hepatosplenomegaly, pale stool, and dark
urine.

Ghazy RM, Adawy NM, Khedr MA, Tahoun MM. 2018. Biliary atresia recent insight.
Egyptian Pediatric Association Gazette 66: 1-8.
Intrahepatic Cholestasis Extrahepatic bile
disorder duct occlusion

Consequency of cholestasis :
Retention of bile components  bilirubin leads to
jaundice (kernicterus in neonatus)
Cholesterol deposition in skin folds and tendon and in
the cell membrane of the liver, kidney, erythrocytes
Pruritus (caused by retained bile salt)
Absence of bile in the intestine  pale stool and
malabsorption
Infection of accumulation bile (cholestasis 
cholangitis)
Case :
 A Boy 9 m.o
 Icteric, pale stool, dark urine Cholestatic
 Hepatosplenomegaly Jaundice
 Hiperbilirubinemia D>I
 Increased SGOT 7,6 x URL,
SGPT 7,3 x URL Extrahepatic
 FL : white mushy stool
Abd. USG : Biliary atresia, Biliary
Chronic liver disease
(cirrhosis),
Atresia
Splenomegali, Ascites.
Suggestion :
-Urinalysis, Total protein, Globulin, ALP, GGT,
Coagulation Tests.
- Monitoring SGOT-SGPT, Bilirubin T/D/I and
 2. ELEVATED TRANSAMINASE

Liver Cirrhosis in Biliary Atresia

• During the course of the disease, children may
present with complications from the disease itself,
such as the consequences of chronic cholestasis
(steatorrhea, malnutrition, fat soluble vitamin
deficiency, delayed neuropsychomotor
development, jaundice, pruritus, portal hypertension
and secondary biliary cirrhosis), as well as those
related to portoenterostomy (ascending cholangitis).

Elisa de Carvalho, Cláudia Alexandra Pontes Ivantes, Jorge A. Bezerra Extrahepatic

biliary atresia: current concepts and future directions
J Pediatr (Rio J). 2007;83(2):105-120
 2. ELEVATED TRANSAMINASE
Liver Cirrhosis in Biliary Atresia

Elisa de Carvalho, Cláudia Alexandra Pontes Ivantes, Jorge A. Bezerra Extrahepatic

biliary atresia: current concepts and future directions
J Pediatr (Rio J). 2007;83(2):105-120
 2. ELEVATED TRANSAMINASE
Liver Cirrhosis in Biliary Atresia

Elisa de Carvalho, Cláudia Alexandra Pontes Ivantes, Jorge A. Bezerra Extrahepatic

biliary atresia: current concepts and future directions
J Pediatr (Rio J). 2007;83(2):105-120
 2. ELEVATED TRANSAMINASE

Liver Cirrhosis in Biliary Atresia

• The majority of affected children will
eventually develop end-stage liver
disease and require liver transplantation.
• Early diagnosis of BA is critical as a
surgical Kasai portoenterostomy (KPE)
may restore bile flow if performed prior to
age 3 months and help prevent rapid
progression of liver injury and
development of cirrhosis.
Shikha S. Sundaram, Cara L Mack, Amy G Feldman, Ronald J Sokoi
Biliary Atresia: Indications and Timing of Liver Transplantation and Optimization of
Pre-Transplant Care. Liver Transpl. 2017 Jan; 23(1): 96-109
 2. ELEVATED TRANSAMINASE
• de Ritis Ratio>1 → Liver
Cirrhosis, Chronic liver disease, Liver malignancy

This patient :
• de Ritis ratio 1,63
• Hepatosplenomegaly
Liver
• Hyperbilirubinemia D>I
• Hypoalbuminemia
Cirrhosis
• Abd.USG: Biliary atresia, Chronic
liver disease (cirrhosis), Splenomegali,
Ascites.

Suggestion : Total protein, Globulin, ALP, GGT,

Coagulation Tests.
Monitoring SGOT/ SGPT, Bilirubin T/D/I, Albumin.
 3. HYPERNATREMIA

• Definition :
–increase of plasma Natrium level (> 150 mmol/L)
–hyperosmolarity
• Symptoms :
–neurological sign e.c intracellular dehydration 
tremor, ataxia, iritable, confuse, coma
• Hypernatremia can be caused by :
–Water loss or failure of water loss replacement
(Hypovolemia)
–Increase of Natrium in water excess condition
(Hypervolemia)
–Euvolemia
35
HYPERNATREMIA

36
37
Hypertonic (Hypernatraemic) Dehydration

• Some children with diarrhoea, especially young infants,

develop hypernatraemic dehydration.
• It usually results from the ingestion during diarrhoea of
fluids that are hypertonic (owing to their content of
sodium, sugar, or other osmotically active solutes) and not
efficiently absorbed, and an insufficient intake of water or
other low-solute drinks  create an osmotic gradient 
causes a flow of water from the ECF into the small intestine,
 decrease in the ECF volume and an increase in sodium
concentration within the ECF.

Readings on diarrhoea. Student Manual.

World Health Organization. Geneva.
Hypertonic (Hypernatraemic) Dehydration

The principal features of hypernatraemic dehydration

are:
• There is a deficit of water and sodium, but the deficit of
water is greater;
• serum sodium concentration is elevated (>l50 mmol/l);
• serum osmolality is elevated (>295 mOsmol/l);
• thirst is severe and out of proportion to the apparent
degree of dehydration; the child is very irritable;
• seizures may occur, especially when the serum sodium
concentration exceeds 165 mmol/l.
Readings on diarrhoea. Student Manual.
World Health Organization. Geneva.
 Hypernatremia in this Patient
This Patient : • Patient got RD5
• Diarrhea → 2 days, 8-9x/day, white infusion.
color stool (+), mucus (+), blood (-) • Sample taken not
• Vomiting → 1 day, > 5x/day, from i.v. line.
containing food, every after meal
• Malnutrition-marasmus
• Sunken eyes +/+, Sunken fontanelle +. Hypernatremia
Hyperchloremia
d.t. Gastroenteritis
with moderate
dehydration
Suggestion :
Ureum, Creatinine, Urinalysis, Urine Electrolyte,
40
Monitoring Serum Electrolyte
 Liver Cirrhosis and Anemia

• Liver is the major storage site for iron, vit B12 and
folic acid.
• The liver is involved in or is responsible for various
hematological abnormalities due to its unique
portal circulation and its synthetic (clotting factor,
thrombopoietin) and immune functions.

Prevalence of Anaemia in Decompensated Chronic Liver Disease

E. Halleys Kumar and A. Radhakrishnan
World Journal of Medical Sciences 10 (1): 56-60, 2014
 Liver Cirrhosis and Anemia

• Liver cirrhosis is characterized by the accumulation

of extracellular matrix, resulting from its increased
production and degradation and leading to
distorted reconstruction of the liver parenchyma
that accompanies liver function impairment during
most chronic liver disease.
• Liver cirrhosis can lead to hematological
abnormalities.

Prevalence of Anaemia in Decompensated Chronic Liver Disease

E. Halleys Kumar and A. Radhakrishnan
World Journal of Medical Sciences 10 (1): 56-60, 2014
 Liver Cirrhosis and Anemia

• Kumar, 2014  normocytic normochromic anemia

is more prevalent than other type of anemias,
about 30 males (50 percent) and 15 females ( 57.7
percent) in chronic liver disease patient.
• According to sheilasherlock and oxford text book of
hepatology, most common anemia seen in cirrhotic
patients is normochromic and normocytic anemia.

Prevalence of Anaemia in Decompensated Chronic Liver Disease

E. Halleys Kumar and A. Radhakrishnan
World Journal of Medical Sciences 10 (1): 56-60, 2014
 Liver Cirrhosis and Anemia
• Red blood cell distribution width (RDW) reflects
the heterogeneity of circulating red blood cell size.
• It has been widely applied for the differential
diagnosis of anemia for decades.
• In recent years, RDW has been reported to be
increased in cardiopulmonary vascular diseases
(coronary artery disease, myocardial infarction,
pulmonary hypertension), chronic kidney disease, and
systemic lupus erythematosus, as well as liver
diseases.
Red Blood Cell Distribution Width Levels Correlate With Liver Fibrosis and Inflammation
A Noninvasive Serum Marker Panel to Predict the Severity of Fibrosis and Inflammation in
Patients With Hepatitis B, Wen-Shen Xu, MM, Xiao-Ming Qiu, BS, Qi-shui Ou, PhD, Can Liu,
MM, Jin-Piao Lin, PhD, Hui-Juan Chen, MS, Sheng Lin, BS, Wen-Hua Wang, BS, MM, Shou-
Rong Lin, MM, and Jing Chen, MM, Medicine (Baltimore).2015 Mar; 94(10): e612.
 Liver Cirrhosis and Anemia

• It has been claimed that elevated RDW values

positively correlate with MELD scores in
different disease statuses of hepatitis B virus
(HBV) infection.
• In addition, RDW increased with worsening of
Child–Pugh grade in hepatic cirrhosis.

Red Blood Cell Distribution Width Levels Correlate With Liver Fibrosis and Inflammation
A Noninvasive Serum Marker Panel to Predict the Severity of Fibrosis and Inflammation in
Patients With Hepatitis B, Wen-Shen Xu, MM, Xiao-Ming Qiu, BS, Qi-shui Ou, PhD, Can Liu,
MM, Jin-Piao Lin, PhD, Hui-Juan Chen, MS, Sheng Lin, BS, Wen-Hua Wang, BS, MM, Shou-
Rong Lin, MM, and Jing Chen, MM, Medicine (Baltimore).2015 Mar; 94(10): e612.
 Anemia in this Patient
This Patient :
 Normocytic Normochromic Anemia
with elevation of RDW
d.t. liver cirrhosis

Suggestion :
Peripheral blood smear, Reticulocyte count,
Monitoring CBC

46
CONCLUSION
 It has been discussed a 9 month old boy with
normocytic normochromic anemia,
extrahepatic cholestasis jaundice ec. biliary
atresia, elevated transaminase and
hypernatremia/ hyperchloremia.
 Elevated transaminase in this patient may be
caused by liver cirrhosis.
 Hypernatremia in this patient may be caused
by dehydration.
 Normocytic normochromic anemia d.t. liver
cirrhosis
CONCLUSION

 Suggestion: Peripheral blood smear, Reticulocyte

count, Total Protein, Globulin, ALP, GGT,
Coagulation Tests, Ureum, Creatinine, Urinalysis,
Urine Electrolyte.

 Monitoring: CBC, SGOT, SGPT, Bilirubin T/D/I,

Albumin, Serum Electrolyte.
THANK YOU