Atan Baas Sinuhaji

Sub Division of Pediatrics Gastroentero-Hepatology

Department of Childhealth,School of Medicine

University of Sumatera Utara / Adam Malik Hospital

Medan

JAUNDICE

YELLOW APPEARANCE OF THE SKIN & MUCOUS MEMBRANES

BILIRUBIN

BODY FLUIDS TISSUE

CHILDREN & ADULTS : > 2-3 mg %

NEONATES : > 5 mg %

YELLOWNESS OF THE SKIN/PALMS

JAUNDICE ≠ CAROTENEMIA

BILIRUBIN

UNCONJUGATED

FREE

ALBUMIN

FAT

BILIRUBIN

CONJUGATED

FREE

ALBUMIN

(DELTA)

WATER

∆-BILIRUBIN

HALF LIFE ± 22 DAYS

PROLONGING JAUNDICE

BIOCHEMICAL LIVER TEST ARE IMPROVING

Hb

RES

TRANSPORT ALBUMIN

LIVER UPTAKE

CONJUGATION

GLUCORONYL

TRANSFERASE

GLUCURONIC

ACID

LIGANDIN

SECRETION

ACID

ADULTS

GUT

INFANTS

BILIRUBIN METABOLISM

B. Glucuro-

nidase

Bilinogen

Bacteria

Urine Stools

Urobilin Stercobilin

DECONJUGATION

STOOLS

UNCONJUGATED HYPERBILIRUBINEMIA

1. INCREASED PRODUCTION

- Hemolysis

- Hematoma

- Drugs: Vit. K

G6 PD def

Infection

Antagonism

Conc. : Premature

2. DEFECT OF

TRANSPORTALBUMIN

Conc. : Premature

Capacity : Acidosis

Competitive : Sulfa,

Free Fatty Acid

3. DECREASED

UPTAKE

LIGANDIN : GILBERTS SYNDR.

(Y – Z PROTEIN

= GLUTHATHIONE – S – TRANSFERASE)

4. DEFECT OF

CONJUGATION

- GLUCORONYL

TRANSFERASE

Conc. : Crigler Najjar Synd.

Block : Chloramphenicol

Activity : Infection, dehydration

- GLUCURONIC ACID - GLUCURONIC ACID

5. ENTEROHEPATIC CIRCULATION : - OBSTRUCTION

- ANTIBIOTICS

- BREAST MILK JAUNDICE

Jaundice

HUMAN MILK

Breast milkBreast milk Breast FeedingBreast Feeding

AbnormalityAbnormality IntakeIntake

CONSEQUENCES OF UNCONJUGATEDHYPERBILIRUBINEMIA

1. KERN ICTERUS = BILIRUBIN ENCEPHALOPATHY

2. CHOLESTASIS2. CHOLESTASIS

3. UNDERLYNG - HEMOLYTIC- CHOLESTASIS

CONJUGATED HYPERBILIRUBINEMIA

CHOLESTASISNON CHOLESTASIS

HEPATOCYTE

- ROTOR SYNDROME- DUBIN JOHNSON SYND.

DUCTS =OBSTRUCTIVE

HEPATOCYTE

INTRAHEPATIC

EXTRAHEPATIC

Hepatocyte

canaliculi

terminal bileduct

intralobular bileduct

interlobular bileduct

septal bileduct

Intrahepatic

left hepatic

duct

right hepatic

duct

Common hepatic duct

Choledochal duct

duodenum

Pancreatic duct

Cystic ductExtrahepatic

BILIARY TRACT

CHOLESTASIS

STAGNATION/INTERFERENCE OF BILE FLOW

CONSEQUENCES

DEFECT OF

CANALICULAR

BILE SECRETION

ACCUMULATION RETENTION

IN

THE BLOOD

BILE

Bile Salt ← bile acid ← cholesterol

Bilirubin ← Hb

electrolytes

phospholipid

protein

cholesterol

HEPATOCYTE CHOLESTASIS

1. CHOLEPOEIESIS

INTERFERENCES OF:INTERFERENCES OF:

1. CHOLEPOEIESIS

2. SECRETION

3. CANALICULAR CONTRACTION

OBSTRUCTIVE CHOLESTASIS

= DUCTS

1. Ducts → EHBA (Extrahepatic Biliary Atresia)1. Ducts → EHBA (Extrahepatic Biliary Atresia)

2. Inpissated bile

3. Intrabilier pressure ↑↑4. Interferences of bile delivery

INFECTION NON INFECTION

INFLAMMATION

EMBRYOGENESIS CHOLANGIOPATHIA

INFANTILE OBSTR.

BILE DUCT ABNORMALITY

1. ATRESIA → EHBA

2. HYPOPLASIA

3. PAUCITY

4. CYSTS

5. FIBROSIS

CYST

A tissue enclosed space that is abnormal in location or size

CONTAIN STRUCTURE

Air Liquid or solids(partially or wholly)

STRUCTURE

NORMAL ABNORMAL

DILATED

BILIARY TRACT

WITH A DISCRETE WALL

RATIO BILE DUCT / PORTAL TRIADE < 0,9

BILE DUCT PAUCITY

SYNDROMIC NON SYNDROMIC

ALAGILLE SYNDROME PRIMARY

-α-1 antitrysin deficiency

-Byler disease

-etc

SECONDARY

-Graft vs host disease

-etc

OBSTRUCTION

PROXIMAL PRESS. ACCUMULATION

OF CHEMICAL

AGENT

INFECTION

SECRETION DAMAGE OF

HEPATOCYTE

ISCHEMIC OF

DUCTS WALL“CHOLANGITIS”

SUPERSATURATION “HEPATITIS”

OBSTRUCTION

CONSEQUENCES OF OBSTRUCTIVE

CHOLESTASIS

CHOLESTASIS

HEPATOCYTE DUCTS

“HEPATITIS” “CHOLANGITIS”

+

“HEPATITIS”“HEPATITIS”

DIAGNOSIS CHOLESTASIS

- BILIRUBIN CONJ. > 2 mg %

- BILIRUBIN CONJ. > 20% TOTAL BILIRUBIN

- SERUM ASAM EMPEDU > 10 µµµµgr / L a 2 X N

OROR

WITHWITH

- SERUM ASAM EMPEDU > 10 µµµµgr / L a 2 X N

USBA

(URINARY SULFATED BILE ACID) > 55 µµµµmol/grcreatinine

S I N U S O I D

PARACELLULAR

SPACE OF DISSE

Central Vein

Portal Vein

HEPATIC ARTERY

HEPATOCYTE

DUCT

BOWEL

entero hepatic

circulation

BILE ACID

CIRCULATION

BILE ACID

HEPATOCYTE

BILE ACID

ENTEROHEPATIC CIRC ±±±± 95%

CHOLESTASIS

BILE ↓↓↓↓↓↓↓↓

FAT MALABSORPTION

* STEATORRHOEA* PCM* DEF. VIT. A →→→→ HEMERALOPIA

D →→→→ RICKETS

ENTEROHEP. CIRC. ↓↓↓↓↓↓↓↓

INPISSITED BILE

D →→→→ RICKETSE →→→→ NEUROMUSC. DEGK →→→→ INTRACRANIAL

BLEEDING

RETENTION CHOLESTEROL →→→→ XANTHOMAS

BILE ACID →→→→ BILIARY CIRRHOSIS

TRACE ELEMEN →→→→ CUPRUM

CONJ. BILIRUBIN →→→→ ICTERUS

CHOLESTASIS

NEONATES CHILDREN

- EHBA- INTRAHEPATIC CHOLESTASIS

- VIRAL HEPATITIS- MECHANICAL OBSTR.

- INTRAHEPATICCHOLESTASIS

INTRAHEPATIC CHOLESTASIS

1. IDIOPATHIC NEONATAL HEPATITIS

( IDIOPATHIC NEONATAL GIANT CELL HEPATITIS )

2. INFECTION HEPATITIS IN A NEONATE

3. INTRAHEPATIC BILE DUCT PAUCITY

EHBA

OPERATIVE

CORRECTABLE UNCORRECTABLECORRECTABLE UNCORRECTABLE

PARTIAL ATRESIA TOTAL ATRESIA

KASAI OPERATION

KASAI OPERATION

To bypass the obstructed extrahepatic bile ducts and

to restore the biliary flow

Fails to clear jaundice and/or complications

associated with biliary cirrhosis appear

LIVER TRANSPLANTATION

KASAI OPERATION

INCREASED AGE AT SURGERY HAD A PROGRESSIVE

AND SUSTAINED DELETERIOUS EFFECT

Serinet MO.Pediatrics 2009;123 :1280-6

KASAI I

KASAI II (double Roux-en-Y)

SAWAGUCHI

SURUGA I

Sonde

SURUGA II

KASAI I with an INTESTINAL VALVE

HEPATITIS

= INFLAMMATION OF HEPATOCYTE

ALT (ALANINE AMINOTRANSFERASE)ALT (ALANINE AMINOTRANSFERASE)= SGPT (SERUM GLUTAMATE PYRUVATE TRANSAMINASE)

≥≥≥≥ 2 x N

HEPATITIS

INFECTION

VIRAL

BACTERIA

PARASITES

HEPATOTROPIC

NON HEPATOTROPIC

NONINFECTION

•DRUGS ����DRUG INDUCED HEPATITIS

•TOXIN

•METABOLIC

•INFARCT

•Ag-Ab

HEPATOTROPIC VIRAL

A HEP. INFEKSIOSA

B HEP. B

C HEP. CC HEP. C

D HEP. DELTA

E HEP. E

F ??

G HEP.G

STADIUM

PRODROMAL

ICTERUS= FEVER(-)

RECOVERY

VIRAL HEPATITIS

RECOVERY

PROGRESSIVE

ACUTE FULMINANT HEPATIC FAILURE

CHRONIC HEP. (SGPT ↑↑↑↑ >= 6 MONTHS )

HEPATITISCHRONIC

CARRIER

HEPATIC CIRRHOSIS

VIRAL HEPATITIS

SYMPTOMATIC ASYMPTOMATIC

ICTERIC ANICTERIC SUBCLINICALINAPPARENT INFECTION

‘FLU LIKE’ BIOCHEMISTRYSEROLOGY

eg. IgM ANTI HAV (+)

HEPATITIS. A

TREATMENT : 1.BED-REST2.WATER & ELECTROLYTES :

PREVENTION OF PREVENTION OF DEHYDRATION

3.DIET : FAT IS NOT LIMITATED

HEPATIC CIRRHOSIS

- FIBROSIS(+)

- NODULE (+)

LIVER DYSFUNCTION

HEPATIC FAILURE= HEPATIC ENCEPHALOPATHY

PORTALHYPERTENSION

HYPERSPLENISM

HYPERSPLENISME

INCREASED SPLENIC FUNTION

SEQUESTRATION OR DESTRUCTION OF CIRCULATING CELL

1. PERIPHERAL BLOOD CYTOPENIA

2. INCREASED BONE MARROW ACTIVITY

3. SPLENOMEGALY

HEPATIC CIRRHOSIS

NODULAR

47

MICRO MACRO MIXED

< 3 mm > 3 mm – 5 cm

HEPATIS CIRRHOSIS

BIOCHEMICAL CLINICAL

48

Active Inactive Compensated Decompensated

CAUSES OF BLEEDING IN CIRRHOSIS

1. VIT. K DEFICIENCY

2. DEFECT OF SYNTHESIS CLOTTING FACTORS

3. RUPTURE OF ESOPHAGEAL VARICES3. RUPTURE OF ESOPHAGEAL VARICES

4. GASTROPATHY

5. ABNORMAL TROMBOCYTES

6. COAGULATION INHIBITOR

7. DIC (DISSEMINATED INTRAVASCULAR COAGULATION)

MAJOR SEQUELAE OF CIRRHOSIS �mnemonic

1.Hepatic encephalopathy

2.Esophageal varices

3.Portal hyperension

HEPATIC

3.Portal hyperension

4.Ascites

5.Thrombosis of portal vein

6.Infection ( spontaneous bacterial peritonitis )

7.Carcinoma ( hepatocellular )

PORTAL HYPERTENSION

= PORTA VENOUS PRESSURE ≥≥≥≥ 12 mmHg HIGHER THAN THE PRESSURE IN THE INFERIOR VENA CAVA

VARICES

ASCITES SPLENOMEGALY

COLLATERAL VEINS

SUP. MESENTERIC V. SPLENIC V.

PORTAL V.

PANCREATICODUODENAL V.

CAPUT MEDUCAE

CORONARY V. ESOPH. VARICES

UMBILICAL V.

RIGHT PORTAL V. LEFT PORTAL V.

HEPATIC VEIN

INFERIOR VENA CAVA

HEART

DIAGRAM OF PORTAL VENOUS

PORTAL HYPERTENSION

INTRAHEPATIC

PRE HEP

HYPERTENSION

EXTRAHEPATIC

(50-70%)

THROMBOSIS V.UMBILICALIS

POST HEP.

BUDD CHIARY SYNDR.

INTRAHEPATIC

POST SINUSOIDAL

SINUSOIDAL

TERMINAL

HEPATIC

VENULE

VENO OCCLUSIVE DISEASE

HEPATICCIRRHOSIS

INTRAHEPATIC

PRE SINUSOIDAL

TERMINAL

PORTAL

VENULE

SCHISTOSOMIASIS

BLEEDING IN PORTAL HYPERTENSION

INTRAHEPATIC EXTRAHEPATIC FREQUENCY > >>>

SEVERITY >>> >

LIFE EXPECTANCE > >>>

ASCITES >>> >

THE OTHER SIGNS

- JAUNDICE + -

- PALMAR ERYTHEMA + -

- VASCULAR SPIDER+ -

- LIVER DYSFUNCTION + -