D.D OF JAUNDICE
BY
DR. Hayam Hebah
Associate Professor of Internal Medicine
AL Maarefa College
DEFINITION
Jaundice is a yellowish staining of the skin,
sclera, and mucous membranes by ↑ bilirubin.
 Clinically detected typically once the serum
bilirubin level rises above 3 mg /dl.
 Can be caused by a wide variety of benign or
life-threatening disorders.
 Pseudojaundice - a harmless form of
jaundice in which the yellowing of the skin
results from an excess of beta-carotene, not
from an excess of bilirubin; usually from eating
lots of carrots, pumpkin, or melon.
 N= 0.2-1 mg/dL (3.4-17.1 µmol/L),
 direct bil. ≤ 0.2 mg/dL (3.4 µmol/L)
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Pathophysiology
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Hepatic form of
jaundice includes
Dubin Johnson
syndrome and
Rotor
syndrome.
Bilirubin handling in Kidney
Conjugated
Bilirubin
• Bound (20 days)
• Bilirubin in urine
is conjugated
• Not filtered
Unconjugated or secreted
• Nil in urine
Bilirubin
Urobilinogen • Normally traces
in urine
• ↑ in Cholestaiss
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DD OF UNCONJUGATED
HYPERBILIRUBINEMIA(Prehepatic jaundice)
Increased bilirubin production : -Hemolysis
-Dyserythropoiesis
-Hematoma
 Impaired hepatic bilirubin uptake : -Congestive heart failure
- Portosystemic shunts
-Drugs - Rifamycin, rifampin,
probenecid
 Impaired bilirubin conjugation :-Crigler-Najjar syndrome types I and
II
- Gilbert syndrome (decreased uptake
and/or conjugation)
-Neonatal physiologic jaundice
-Breast milk jaundice
-Hypothyroidism/hyperthyroidism
-Ethinyl estradiol
-Liver diseases - Chronic hepatitis,
cirrhosis, and Wilson disease
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Gilbert Syndrome
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AD, low glucuronyl transferase enzyme, low
uptake of bilirubin,
diagnosed by a history and physical examination
and confirmed by standard blood tests. Repeated
investigations and invasive procedures are not
usually justified for establishing a diagnosis.
Hyperbilirubinemia( mild) is the only biochemical
serum abnormality in Gilbert syndrome. Serum
bilirubin concentrations range from 1-5 mg/dL.
2 provocative tests, energy deprivation and
nicotinic acid administration, have been used to
diagnose the condition. SO FASTING IS
associated with ↑ jaundice.
Does not need ttt
Hepatocellular jaundice
Parenchymal liver disease , enables liver to
transport bilirubin to bile.
 Both conjugated and unconjugated
bilirubin increase
 Occur in acute or chronic liver disease.
 Associated with ↑ transaminases(AST ,
ALT) ,
 GGT, ALP may also ↑
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POSTHEPATIC(OBSTRUCTIVE )
(CHOLESTATIC) JAUNDICE
Mechanism of jaundice:
1. Failure of hepatocytes to initiate bile
flow
2. Obstruction of bile ducts or portal
tracts.
3. Obstruction of bile flow in the
extrahepatic bile ducts between the
porta hepatis and ampulla of Vater.
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Causes of cholestatic jaundice
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Intrahepatic
Primary biliary cirrhosis
Primary sclerosing
cholangitis
Alcohol
Drugs as OCP,
hepatic infiltration
(lymphoma,
granuloma,amyloid,metasta
ses)
cystic fibrosis
severe bacterial infections
Pregnancy
Chronic rt heart failure
Inherited cholestatic liver
disease
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Extrahepatic
Carcinoma
Ampullary
Pancreatic
Bile duct
(cholangiocarcinoma)
Liver metastasis
Choledocholithiasis
Parasitic infection
Traumatic biliary strictures
Chronic pancreatitis.
Suggestive clinical features of
cholestatic jaundice
Static or increasing jaundice
 Fluctuating jaundice
 Abdominal pain
 Cholangitis
 Abdominal scar
 Irregular hepatomegaly
 Palpable GB
 Abdominal mass
 Occult blood in stools.
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Key diagnostic points in history in
patients with jaundice
History of itching preceding the
jaundice(obstructive d.t bile acids)
 Abdominal pain( stones)
 Weight loss (CLD or malignancies)
 Urine and stool colors
 Fever ± rigors (cholangitis)
 Drug history
 Alcohol intake
 Iv drug abuse or blood transfusion
 Travel history
 Autoimmune diseases or IBD
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history
Potential toxins (eg, drugs), environmental
chemicals (eg, solvents), or wild mushrooms
must be carefully excluded(toxic hepatitis).
 Risk factors for viral hepatitis should be
elicited : Transfusion ,IV drug use ,multiple
sexual partners ,exposure to a person who is
infected.
 Colicky abdominal pain or fever suggests
gallstone disease.
 Weight loss or constitutional systems
suggests malignancy or chronic infection.
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Recent anesthesia with halothane suggests
halothane hepatitis.
 A history of intense pruritus suggests
cholestatic disease .
 A family history of jaundice suggests inborn
errors of bilirubin metabolism.
 In patients with severe intercurrent illnesses,
consider sepsis, hepatic ischemia, and
opportunistic infections.
 Severe right heart failure or tricuspid
insufficiency with hepatomegaly suggests
hepatic congestion.
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Patients on parenteral nutrition may experience
cholestasis that sometimes improves with the
addition of lipid infusions.
Patients with AIDS may experience biliary
obstruction from opportunistic infections (e g,
AIDS cholangiopathy).
Patients with chronic liver disease may
experience transient elevation of their bilirubin
levels following blood transfusion, which results
due to a more rapid turnover of the infused
cells.
In patients younger than 20-25 years, a history of
a recent flulike syndrome treated with aspirin
raises the possibility of Reye syndrome.
Pregnancy suggests benign recurrent cholestasis
or, in late pregnancy, acute fatty liver of
pregnancy.
Examination:
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Depending on the underlying illness, stigmata
of chronic liver disease may or may not be
present.
Palpation of the abdomen may reveal the
following:
A mass (eg, a distended gallbladder,
abdominal tumors)
Tenderness over the liver (eg, as in cases of
hepatitis or hepatic distention resulting from
congestion or infiltrative disease)
Tenderness over the gallbladder fossa (as
occurs in cases of biliary disease or
infection)
 Unexplained darkening of the skin,
diabetes, or heart failure suggests
hemochromatosis.
 Kaiser-Fleisher rings suggests Wilson
disease.
 Cutaneous or neurologic findings of
chronic alcoholism may be helpful
diagnostic findings.
 In addition to color of sclera it self .
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Differential Diagnosis of Conjugated
Hyperbilirubinemia
I. Acute or Chronic Hepatocellular
Dysfunction
 A. Infection
 Viral hepatitis A-E
 Cytomegalovirus (CMV) hepatitis
 Epstein-Barr virus hepatitis
 Sepsis
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 B. Inflammation Without
 Toxic
Infection
liver injury
 Drug toxicity (eg, acetaminophen)
 Halothane hepatitis
 Alcoholic hepatitis
 Iron overload (hemochromatosis)
 Copper overload (Wilson disease)
 Autoimmune hepatitis
C. Metabolic Dysfunction
 Ischemia ("shock liver")
 Acute fatty liver of pregnancy
 Alpha-1 antitrypsin deficiency
 Preeclampsia
 Reye syndrome
 Total parenteral nutrition
 D. Inborn Errors of Metabolism
 Dubin-Johnson syndrome
 Rotor syndrome
 Benign recurrent cholestasis
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II. Diseases That Prevent Flow
of Bile into the Intestine
A. Damage to Intrahepatic Bile
Ducts or Portal Tracts
 Primary biliary cirrhosis
 Graft versus host disease
 Sclerosing cholangitis.
 Veno-occlusive disease
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B. Damage to or Obstruction of
Larger Bile Ducts
Choledocholithiasis
Sclerosing cholangitis
AIDS cholangiopathy
Hepatic arterial chemotherapy
Postsurgical strictures
Bile duct cancers
Developmental disorders of the bile ducts (eg,
Caroli)
 Extrinsic compression of the bile duct
 Tumors
 Acute pancreatitis
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c. Diffuse Infiltrative Diseases
Granulomatous diseases
 Sarcoidosis
 Disseminated mycobacterial infections
 Lymphoma
 Wegener granulomatosis
 Amyloidosis
 Diffuse malignancy
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D. Diseases That Interfere with
Biliary Secretion of Bilirubin
Anabolic steroids (testosterone, norethandrolone)
 Antithyroid agents (methimazole)
 Azathioprine (Immunosuppressive drug)
 Chlorpromazine HCI (Largactil)
 Clofibrate, Erythromycin estolate
 Oral contraceptives (containing estrogens)
 Oral hypoglycemics (especially chlorpropamide)
ALGORITHMIC
APPROACH FOR
JAUNDICE
First Step : estimate serum bilirubin
if> 1 mg /dl so it is elevated.
 Second Step : is the hyperbilirubinemia
conjugated (>20%) or unconjugated or both?
 Third Step : If CSB is increased , do AST, ALT,
serum alkaline phosphatase & GGT.
 Fourth Step : If hepatocellular:
1. hepatitis markers, EBV, CMV
2. toxic hepatitis : drugs & alcohol
3. Malignancy: alpha fetoprotein
4. Cirrhosis: ALD-NAFLD
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↑ in Unconjugated Bilirubin
Hemolytic Jaundice - Uncommon
1. Hemolytic Disorders + Anemia
Inherited – Sphero, SS, G6PD, PK
Acquired – MAHA, PNH
2. Ineffective Erythropoesis –B12, Fe, F
3. Drugs – Rifampicin, Probenecid
4. Inherited –Crigler Najjar, Gilberts
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Other helpful tests:
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Complete blood cell (CBC) count to screen for hemolysis
Serologic screen for viral hepatitis, including hepatitis C virus
(HCV) antibody and hepatitis B surface antigen (HBsAg) or
antihepatitis B core antibody (anti-HBcAb)
Alkaline phosphatase (ALP): If elevated or if an obstruction is
suspected, images of the bile ducts should be obtained. Gammaglutamyl transpeptidase (GGTP) results may help differentiate a
hepatic source of the elevated ALP from bone or other causes.
Blood alcohol or acetaminophen levels upon admission (may be
useful in certain cases).
Antimitochondrial antibody (AMA)when considering primary
biliary cirrhosis
Antinuclear antibodies (ANAs), smooth-muscle antibodies, and
when considering autoimmune hepatitis
Iron and genetic studies when considering hemochromatosis
Copper and ceruloplasmin when considering Wilson disease
Alpha-1 antitrypsin fractionation and other studies when
considering hereditary liver diseases
AND ABDOMINAL U/S
AUTOIMMUNE HEPATITIS
More in females 2nd &3rd decades but may
occur in any age or sex.
Clinical presentation:
 acute or chronic hepatitis
 well-established cirrhosis
 rarely fulminant hepatic failure marked
bycoagulopathy and jaundice
 1/3 of patients present with symptoms of
acute hepatitis marked by fever, hepatic
tenderness, and jaundice.
 Chronic liver disease .
CONDITIONS ASSOCIATED WITH
AUTOIMMUNE HEPATITIS:
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Hashimoto thyroiditis
Thyrotoxicosis
Myxedema
Pleurisy
Coombs positive hemolytic anemia
Ulcerative colitis
SLE
Rheumatoid arthritis
Sjogren ‘s syndrome
Diabetes
Membranoproliferative GN
Celiac disease.
Common findings on physical examination
are as follows:
 Hepatomegaly (83%)
 Jaundice (69%)
 Splenomegaly (32%)
 Spider angiomata (58%)
 Ascites (20%)
 Encephalopathy (14%)
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Lab diagnosis:
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Elevated aminotransferase levels (1.5-50 times reference
values)
Elevated serum immunoglobulin G (IgG)
Mild to moderately elevated serum bilirubin and alkaline
phosphatase – In 80-90% of patients; a sharp increase in the
values during the course of autoimmune disease may reflect
the development of primary sclerosing cholangitis (PSC) or
the onset of hepatocellular carcinoma as a complication of
cirrhosis
Seropositive results for antinuclear antibodies (ANAs),
smooth-muscle antibodies (SMAs), or liver-kidney
microsomal type 1 (LKM-1) or anti–liver cytosol 1 (anti-LC1)
antibodies
Hypoalbuminemia and prolongation of prothrombin time –
Markers of severe hepatic synthetic dysfunction, which may
be observed in active disease or decompensated cirrhosis
 the
hematologic abnormalities may
include the following:
 Mild leukopenia
 Normochromic anemia
 Coombs-positive hemolytic anemia
 Thrombocytopenia
 Elevated erythrocyte sedimentation
rate
 Eosinophilia (uncommon)
Management:
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Corticosteroids, alone or in combination with azathioprine,
have been the mainstays of drug therapy for patients with
autoimmune .
Relapse occurs in 50% of patients within 6 months of
treatment withdrawal and in 80% of patients within 3 years
of treatment. Reinstitution of the original treatment regimen
usually induces another remission; however, relapse
commonly recurs after a second attempt at terminating
therapy. Patients who relapse twice require indefinite therapy
with either prednisone or azathioprine.
Liver transplantation
for patients in whom medical therapy has failed
or for those with decompensated cirrhosis caused by
autoimmune hepatitis.
FOR patients who present with fulminant hepatic failure
secondary to autoimmune hepatitis.
Primary Sclerosing Cholangitis
Narrowed abnormal
intra-heptic bile ducts.
Normal Extra hepatic BD
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