Dr.

MABEL SIHOMBING SpPD-KGEH

Dr.ILHAMD SpPD
DPERTEMEN ILMU PENYAKIT DALAM
What? RS.HAM/FK-USU MEDAN
Who?
PERUBAHAN WARNA ( KULIT,SKLERA MATA ATAU
JARINGAN LAIN ) MENJADI KUNING DISEBABKAN
PENINGKATAN KONSENTRASI BILIRUBIN DALAM
SIRKULASI DARAH.
BILIRUBIN TERBENTUK DISEBABKAN OLEH
PEMECAHAN CINCIN HEM PADA METABOLISME SEL
DARAH MERAH.
KATA “IKTERUS/JAUNDICE” BERASAL DARI PERANCIS
“JAUNE” BERARTI KUNING.
IKTERUS/JAUNDICEKADAR BILIRUBIN >3 MG/DL
 Bilirubin Metabolism
- Bilirubin  breakdown of mature RBCs in the RES.

- 15% of bilirubin comes from the catabolism of other

haem-containing proteins, such as myoglobin.

- 250 – 300 mg of bilirubin are produced daily.

- Biliverdin is formed from the haem and this is reduced to

form bilirubin.
- The bilirubin produced is unconjugated and is transported to
the liver attached to albumen.
Bilirubin Metabolism
RES (SPLEN,LIVER,BONE MARRAOW)
* Increased bil. production (e.g. haemolysis), or
resorption of haematoma.
Inability of the hepatocytes to take up
bilirubin from the blood e.g. Gilbert & Crigler-
Najjar syndromes.
By (for example) biliary calculi causes backup
and reabsorption of conjugated bilirubin.
Blood levels of conjugated bilirubin increase.
Fisiologi produksi dan transportasi bilirubin
 Jaundice can occur in four different
ways:
1- Increased bilirubin load as in haemolysis.
2- Disturbance in the hepatic uptake & transport
of bilirubin within the hepatocytes
3- Defects in conjugation.
4- Defects in the excretion of conjugated
bilirubin across the canalicular cell
membrane or an obstruction of the large
biliary channels.
Pathophysiologic
classification of Jaundice

 Hemolytic Jaundice

 Hepatic Jaundice

 Obstructive
Jaundice(Cholestasis)

 Congenital Jaundice
Jaundice classification
 predominantly unconjugated
hyperbilirubinaemia

 predominantly conjugated
hyperbilirubinaemia
Causes:
1. Increased bilirubin
production
Lead to increases in
2. Reduced bilirubin uptake
free (unconj.) bilirubin
by hepatic cells
3. Disrupted intracellular
conjugation
4. Disrupted secretion of
bilirubin into bile
canaliculi Result in rise in conj.
5. Intra/extra-hepatic bile bilirubin levels
duct obstruction
Causes of Jaundice
Pre-hepatic unconjugated hyperbilirubinaemia

 Haemolysis
 Congenital defects:
 Gilbert’s syndrome (uptake/conjugation
defect)
 Crigler-Najar (conjugation defect)
Isolated elevation of serum Bilirubin

Unconjugated Hyperbilirubinaemia
* Increase bil. production (e.g. haemolysis,
resorptionof haematoma)
* Decrease hepatocellular uptake (e.g.
rifampcin)
* Decrease conjugation (Gilbert S, Crig. Nagar S)
Conjugated Hyperbilirubinemia
* Dubin-Junson syndrome
* Roter syndrome
Causes of Jaundice
Hepatocellular
Acute Chronic

 Viral hepatitis A, B, C..  Viral hepatitis B, C

 Other viruses: EBV,  Chronic AI hepatitis
CMV  End-stage liver disease
 Drugs (of any cause)
 Dose-dependant e.g.  Alcoholic
paracetamol  Hepatitis B, C
 Idiosyncratic
 Autoimmune
 Toxins  Haemochromatosis
 Autoimmune hepatitis  Wilson’s disease
 Alcoholic hepatitis
 Tumours
 Causes of Jaundice

Cholestatic
Extra-hepatic Intra-hepatic

 Gallstones  Drugs
 Carcinoma of head of  Primary biliary
pancreas cirrhosis
 Benign stricture  Cholestatic phase of
 Congenital
viral hepatitis
 Traumatic
 Alcoholic hepatitis
 iatrogenic
 Primary or secondary
 Carcinoma of ampulla cancer
of Vater or bile ducts
 Sclerosing Cholangitis  Lymphoma
 pancreatitis  Pregnancy
Clinical symptoms and signs
 History:
- The onset of Jaundice in viral hepatitis is
associated with a prodrome of ANV, malaise &
myalgia.
- The onset of cholestasis is insidious, it is
associated with pruritus.
- A history of fever with rigors, Rt upper abd. pain
or a past history of biliary surgery suggest
cholangitis.
- Dark urine & pale stool exclude the possibility of
haemolytic jaundice.(related autoimun).
- A history of multiple sex partners, travel, ethanol
intake, drugs, bl. transfusion, needlestick
exposure & tattooing is also important.
- Recent surgery with subsequent jaundice after one
week may suggest halothane toxicity.
- Previous biliary surgery with subsequent jaundice may
suggest stricture, residual stones or hepatitis.
- A family history of jaundice or liver disease suggests
the possibility of hereditary hyperbilirubinaemia or
genetic disorder such as Wilson disease.
- Painless jaundice in older person with epigastric mass &
weight loss = biliary obstruction from malignancy
The clinical assessment & basic biochemical
parameters lead to three broad subgroups of
patients:
1- Isolated elevation of s. bilirubin: when AST,
ALT & ALP levels are normal.
2- Hepatocellular jaundice: when the AST & ALT
levels are elevated out of proportion to the ALP
levels.
3- Cholestatic jaundice: when the ALP level is
elevated out of proportion to the AST & ALT
levels.
Examination
 Pale yellow vs. deep yellow
 Signs of cirrhosis,Sp.Nevy,Caput
Medusa,Gynecomasty,ascites,Palmar Erytema,.
 Liver – tender, enlarged, firm, shrunken,
irregular
 Gallbladder – tender (Murphy’s sign), palpable
 splenomegaly
 Stigmata of Chronic Liver Disease

Palmar eryth. Spider nevi Parotid enlag Gynecomastia

Muscle atrop. Astraxis WHITE NAIL EXTR. edema

Spooning
Laboratory Tests
 Serum bilirubin level  CBC
(total and direct)  PT
 Liver aminotransferase  Other labs pertinent to
levels,Albumin history
 Alk. Phos  Coombs test
 U/A for bilirubin and  Hgb electrophoresis
urobilogen  Viral hepatitis panel
 U/S Gallbladder
Investigations
Pre-hepatic Hepatic Post-hepatic

Urine No Bilirubin ? Bilirubin Bilirubin

 Urobilinogen  Urobilinogen  Urobilinogen

Faeces Dark Pale Pale

Blood FBC - Reticulocyte Bilirubin – mixed Bilirubin (up to

count conjugated & 1000μmol/L) –
Coombs’ test unconjugated conjugated
Bilirubin (up to  ALP, γGT  ALP, γGT
100μmol/L) – AST, ALT  PT – correctable
unconjugated  PT – not with Vit K
ALP Normal correctable with Vit
PT Normal K
RADIOLOGI
CHEST RONTGEN

ULTRASONOGRAPY :
EUS:ENDOS-ULTRASONO
ENDOSKOPY: GASTROSKOPY,ERCP
CT-ABDOMEN/MRI/MRCT
BIOPSI
Imaging Procedures:

Radiological imaging is important for the

diagnosis of a focal liver mass or biliary
disease. However, imaging plays little role in
the evaluation of diffuse hepatocellular e.g.
hepatitis
Ultrasonography (US):
It is a valuable but operator-dependent
investigation.
It has sensitivity of 55-91% & specificity of 82-
95% for biliary obstruction.
Although US may not detect stones in the
extrahepatic bile duct, which may be
obscured by overlying gas, it reliably
establishes the presence of a dilated bile
ducts
Ultrasonography (US): Cont
Beside it can differentiate intrahepatic from
extrahepatic cholestasis, US can also detect
the associated abnormalities such as portal
hypertension, focal lesions & fatty liver.
USG ACUTE HEPATITIS

ENLARGE LIVER
NORMAL

HEPATIC PARENCHYMAL
ECHODENSITY DECREASED.

PORTAL TRIADE PROMINENCE

Gall Bladder Carcinoma

Doppler: internal vascularity within the material

Stone and non shadowing echogenic
material

Doppler wave form

analysis
documents arterial flow
within the mass wich histologically
Confirmed to represent
gallbladder carcinoma
Computerized Tomography (CT):
CT has a sensitivity of 63-96% & a specificity of 93-
100% to detect biliary obstruction.

Non-calcified cholestrol gall stones can be easily

missed on CT because they may be isodense with
bile.
Endoscopic retrograde
cholangiopancreaticography (ERCP):

ERCP not only permits direct visualization of

the biliary tree but also allows therapeutic
intervention e.g. removal of CBD stones or
biliary stenting. It is the gold standard test for
the evaluation of extrahepatic biliary disease
causing jaundice.
Benign distal CBD stricture
Magnetic resonance
cholaniopancreaticography: MRCP
MRCP is superior to US & CT in detecting
biliary obstruction. It has a sensitivity
of 82-100% & a specificity of 92-98% to
detect biliary obstruction.
Liver Biopsy:
It has relatively low risk, it is needed in only a
minority of cases with hepatic dysfunction.

Major indications include chronic

hepatitis, cirrhosis, unexplained liver
enzyme abnormalities,
hepatosplenomegaly of unknown
aetiology, suspected infiltrative
disorder, suspected granulomatous
disease.
Liver Biopsy: Cont
Relative contraindications include a tendency
for clinical bleeding, INR>1.5 or PT >3 sec
above the control, severe thrombocytopenia
& marked ascites.

The risk of fatal haemorrhage in patients

undergoing LB is 0.4% if they have a
malignancy & 0.04% if they have non-
malignant disease.
Management
 ANEMIA HEMOLITIC  HEMATOLOGY
DIVISION TREATMENT

 GENETICAL DISORDER GEN THERAPY

AND SYMPTOMATIC THERAPY

 HEPATIC CELLULER ICTERIC

ANTIVIRAL THERAPY
Management (cont)
 Symptom relief
 Pain, itch
 Fluid resuscitation
 Correction of coagulopathy
 Treat secondary complications
 Sepsis, bleeding, anaemia
 Treat underlying cause
 Medical or surgical
 ENDOSCOPY TREATMENT AND
Surgical Management
 Relieve obstruction
 Definitive or temporising, Curative or palliative

 ERCP / PTC
 Remove stones
 Stent or dilate stricture

 Surgery
 Cholecystectomy with bile duct exploration

 Resection of obstructing tumour

 Whipple’s procedure

 Bypass of irresectable lesion

ERCP and stent insertion for obstructing cholangiocarcinoma
Thank You