Jaundice

DEFINITION
Yellow skin pigmentation caused by elevation in serum bilirubin
level (also termed icterus); often more easily discernible in
sclerae. Scleral icterus become clinically evident at a serum
bilirubin level of 3 mg/dL ; yellow skin discoloration also occurs
with elevated serum carotene levels but without pigmentation of
the sclerae.

BILIRUBIN METABOLISM

Bilirubin is the major breakdown product of hemoglobin released

from senescent erythrocytes. Initially it is bound to albumin,
transported into the liver, conjugated to a water-soluble form
(glucuronide) by glucuronosyl transferase, excreted into the bile,
and converted to urobilinogen in the colon. Urobilinogen is mostly
excreted in the stool; a small portion is reabsorbed and excreted
by the kidney. Bilirubin can be filtered by the kidney only in its
conjugated form (measured as the direct fraction); thus
increased direct serum bilirubin level is associated with
bilirubinuria. Increased bilirubin production and excretion (even
without hyperbilirubinemia, as in hemolysis) produce elevated
urinary urobilinogen levels.

Mechanisms of hyperbilirubinemia:

Hyperbilirubinemia may involve predominantly unconjugated or

conjugated bilirubin.

Unconjugated hyperbilirubinemia is most often caused by 1

of the following:

Increased production
Decreased hepatic uptake
Decreased conjugation
Conjugated hyperbilirubinemia is most often caused by 1 of
the following:
 Dysfunction of hepatocytes (hepatocellular dysfunction)
Slowing of bile egress from the liver (intrahepatic
cholestasis)
Obstruction of extrahepatic bile flow (extrahepatic
cholestasis)

Etiology :

Hemolytic Jaundice :

Mainly the etiology of hemolytic anemia which classified as :

Corpuscular Causes :

1.Membrane defect :

. Hereditary spherocytosis .

2. Hemoglobin defect :

. Thalassemias .

. Sickle cell anemia .

3.Enzyme defect :

.G6PD deficiency .

Extr-Corpuscular causes :
 1.Immune hemolytic anemia :

- Allo-immune : incompatible blood transfusion .

- Auto-immune : autoimmune hemolytic anemia .

2.Infection :

- Malaria

3. Physical :

- Micro Angiopathic Hemolytic Anemia : DIC , HUS(hemolytic

uremic syndrome)

4. Chemicals :

- Drugs : Amphotericin B

-Toxins : Lead , Copper , Renal Failure .

5.Hypersplenism .

Obstructive Jaundice (cholestatic jaundice )

Extrahepatic obstruction :

1.in the lumen :

- stones in the common bile duct or common hepatic duct .

2. in the wall :

-Strictures : postoperative .

-Tumors : cholangiocarcinoma .
 3.presseur from outside :

-cancer head of pancreas .

-cancer ampulla of vater .

- enlarged lymph nodes .

Intrahepatic obstruction :

1. Primary biliary cirrhosis .

2. Pregnancy Jaundice .

3. Cholestatic type of viral hepatitis .

4. Chronic hemolytic anemia .

5. Cancer liver HCC or secondaries .

Hepatoclleular Jaundice :

1. Acute fulminant liver failure .

2. Chronic liver failure .

3. Familial hyperbilirubinemia :

- Gliberts disease .

- Crigler Najjar syndrome

- Breast milk Jaundice .

Clinical approach :

History: History of present illness:

should include onset and duration of jaundice. Hyperbilirubinemia

can cause urine to darken before jaundice is visible. Therefore,
the onset of dark urine indicates onset of hyperbilirubinemia more
accurately than onset of jaundice. Important associated
symptoms include fever, prodromal symptoms (eg, fever, malaise,
myalgias) before jaundice, urine and stool color, pruritus,
steatorrhea, and abdominal pain (including location, severity,
duration, and radiation). Important symptoms suggesting severe
disease include nausea and vomiting, weight loss, and possible
symptoms of coagulopathy (eg, easy bruising or bleeding, tarry or
bloody stools).

Review of systems:

should seek symptoms of possible causes, including weight loss

and abdominal pain (cancer); joint pain and swelling (autoimmune
or viral hepatitis, hemochromatosis, primary sclerosing
cholangitis, sarcoidosis); and missed menses (pregnancy).

Past medical history

should identify known causative disorders, such as hepatobiliary

disease (eg, gallstones, hepatitis, cirrhosis); disorders that can
cause hemolysis (eg, hemoglobinopathy, G6PD deficiency); and
disorders associated with liver or biliary disease, including
inflammatory bowel disease, infiltrative disorders (eg,
amyloidosis, lymphoma, sarcoidosis, TB), and HIV infection or
AIDS.

Drug history should include questions about use of drugs or

exposure to toxins known to affect the liver and about
vaccination against hepatitis.

Surgical history should include questions about previous surgery

on the biliary tract (a potential cause of strictures).

Social history should include questions about risk factors for,

amount and duration of alcohol use, injection drug use, and
sexual history.

Family history should include questions about recurrent, mild

jaundice in family members and diagnosed hereditary liver
disorders. The patient's history of recreational drug and alcohol
use should be corroborated by friends or family members when
possible.

Physical examination:

Vital signs are reviewed for fever and signs of systemic toxicity
(eg, hypotension, tachycardia).

General appearance is noted, particularly for cachexia and

lethargy.

Head and neck examination includes inspection of the sclerae and

tongue for icterus and the eyes for Kayser-Fleischer rings. Mild
jaundice is best seen by examining the sclerae in natural light; it
is usually detectable when serum bilirubin reaches 2 to 2.5
mg/dL . Breath odor should be noted (eg, for fetor hepaticus).

The abdomen is inspected for collateral vasculature, ascites, and

surgical scars. The liver is palpated for hepatomegaly, masses,
nodularity, and tenderness. The spleen is palpated for
splenomegaly. The abdomen is examined for umbilical hernia,
shifting dullness, fluid wave, masses, and tenderness. The rectum
is examined for gross or occult blood.

Men are checked for testicular atrophy and gynecomastia.

The skin is examined for jaundice, palmar erythema, needle

tracks, vascular spiders, excoriations, xanthomas (consistent with
primary biliary cirrhosis), paucity of axillary and pubic hair,
hyperpigmentation, ecchymoses, petechiae, and purpura.

Red flags: The following findings are of particular concern:

Marked abdominal pain and tenderness

Altered mental status
GI bleeding (occult or gross)
Ecchymoses, petechiae, or purpura
Testing:

The following are done:

Blood tests (bilirubin, aminotransferase, alkaline

phosphatase)
Usually imaging
Sometimes biopsy or laparoscopy
Hepatocellular dysfunction: Marked aminotransferase
elevation (> 500 U/L) and moderate alkaline phosphatase
elevation (< 3 times normal)
Cholestasis: Moderate aminotransferase elevation (< 200
U/L) and marked alkaline phosphatase elevation (> 3 times
normal)
Hyperbilirubinemia without hepatobiliary dysfunction: Mild
hyperbilirubinemia (eg, < 3.5 mg/dL [<59 mol/L]) with
normal aminotransferase and alkaline phosphatase levels
Signs of hepatic insufficiency (eg, encephalopathy, ascites,
ecchymoses) or GI bleeding: Coagulation profile (PT/PTT)
Hepatitis risk factors or a hepatocellular mechanism
suggested by blood test results: Hepatitis viral and
autoimmune serologic tests
Fever, abdominal pain, and tenderness: CBC and, if
patients appear ill, blood cultures
Suspicion of hemolysis can be confirmed by a peripheral blood
smear.

Imaging is done if pain suggests extrahepatic obstruction or

cholangitis or if blood test results suggest cholestasis.

Abdominal ultrasonography usually is done first; usually, it is

highly accurate in detecting extrahepatic obstruction. CT and
MRI are alternatives.

Ultrasonography is usually more accurate for gallstones, and CT

is more accurate for pancreatic lesions. All these tests can
detect abnormalities in the biliary tree and focal liver lesions but
are less accurate in detecting diffuse hepatocellular disorders
(eg, hepatitis, cirrhosis).

If ultrasonography shows extrahepatic cholestasis, other tests

may be necessary to determine the cause; usually, magnetic
resonance cholangiopancreatography (MRCP) or ERCP is used.
ERCP is more invasive but allows treatment of some obstructive
lesions (eg, stone removal, stenting of strictures).
 Treatment :

Medical treatment :

Treatment varies based on the medical condition responsible for causing jaundice, and
the associated symptoms and complications. Treatments may include the following:

supportive care,

IV fluids in cases of dehydration,

medications for nausea/vomiting and pain,

antibiotics,

antiviral medications,

blood transfusions,

steroids,

chemotherapy/radiation therapy.

Surgical treatment :
Surgical treatment may be necessary in certain cases of cancer, congenital malformations,
conditions that obstruct the bile ducts,gallstones, and abnormalities of the spleen. Sometimes,
a liver transplant may be the only cure in cases of liver cirrhosis and liver cell failure .

References :
1. Approach to patient with liver
disease ( The Merk Manual )
2. Hepatology: Textbook and Atlas
By Erwin Kuntz, Hans-Dieter
Kuntz .
3. JAUNDICE AND EVALUATION OF

LIVER FUNCTION
4. Jaundice , Bhupinder Anand, MD
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