JAUNDICE

DR MUHAMMAD FIAZ
 Jaundice
• The word jaundice comes from the French word
jaune,which means “yellow
• Jaundice, or icterus, is used to describe the
yellow discoloration of the skin, eyes, and
mucous membranes most often resulting from the
retention of bilirubin.
• Although the upper limit of normal for total
bilirubin is 1.0–1.5 mg/dL.
• jaundice is usually not noticeable to the naked eye
(known as overt jaundice) until bilirubin levels
reach 3.0 mg/dL.erm icterus is
Yellow discolorization
Some underlying conditions that may cause jaundice are:

 Acute inflammation of the liver

 Inflammation of the bile duct
 Obstruction of the bile duct
 Hemolytic anemia
 Gilbert's syndrome
 Cholestasis
 CLASSIFICATION OF JUANDICE
 Jaundice is most commonly classified based
on the site of the disorder:
1. Prehepatic
2. Hepatic
3. Posthepatic jaundice.
 This classification is important because
knowing the
 Pre-hepatic jaundice
 when the problem causing the jaundice occurs prior
to liver metabolism.
 Commonly caused by an increased amount of
bilirubin being presented to the liver such as that
seen In acute and chronic hemolytic anemias.
 Hemolytic Anemia causes an increased amount of
RBCs destruction and release of increased amounts
of bilirubin presented to the liver for processing.
 The liver responds by functioning at maximum
capacity; therefore, people with from prehepatic
jaundice rarely have bilirubin levels that exceed 5
mg/dL
 Pre-hepatic jaundice
 This type of jaundice may also be referred to as
unconjugated hyperbilirubinemia.
 This fraction of bilirubin (unconjugated
bilirubin) is
Water Insoluble
Bound to albumin
Not filtered by the kidneys and therefore
Not be seen in the urine
At 120 Days…. in RBC’s
 Bilirubin production
65% to 80% comes from Hb breakdown
 Maximum amount taken up by liver so,
Normal plasma concentration
- ∼0.5 mg/dL or lower
The skin or eyes may begin to appear yellow

- 1.5 to 3 mg/dL.
 Hepatic jaundice
 when the primary problem causing the jaundice
resides in the liver (intrinsic liver defect or
disease).
 This intrinsic liver defect can be due to disorders
of bilirubin metabolism and transport defects
Crigler-Najjar syndrome
Dubin Johnson syndrome
Gilbert disease
Neonatal physiologic jaundice of the newborn
 Due to diseases resulting in hepatocellular injury
or destruction.
 Hepatic jaundice
Gilbert syndrome
 Benign hereditary disorder -affects 5% of the U.S.
population.
 It is characterized by unconjugated hyperbilirubinemia in
the absence of hemolysis and underlying liver disease due to
a defective conjugation system.
 The molecular basis of Gilbert syndrome is related to the
UGT (uridine Diphosphoglucose glucuronyltransferase)
responsible for encoding enzymes that catalyze the
conjugation of bilirubin.
• The UGT1A1 promoter contains the sequence (TA) 6 TAA.
• The insertion of an extra TA in the sequence, as seen in
Gilbert syndrome, reduces the expression of the UGT1A1
 Hepatic jaundice
• Crigler-Najjar syndrome
• Described by Crigler and Najjar in 1952 as a syndrome of
chronic non hemolytic unconjugated hyperbilirubinemia.
• CriglerNajjar syndrome is an inherited disorder of
bilirubin metabolism resulting from a molecular defect
within the gene involved with bilirubin con jugation.
• Crigler-Najjar syndrome may be divided into
– Type 1, where there is a complete absence of
enzymatic bilirubin conjugation
– Type II, where there is a mutation causing a severe
deficiency of the enzyme responsible for bilirubin
conjugation.
 Hepatic jaundice
• Dubin-Johnson syndrome
 A rare inherited disorder caused by a deficiency of the
canalicular multidrug resistance/multispecific organic
anionic transporter protein (MDR2/cMOAT).
 Liver’s ability to uptake and conjugate bilirubin is
functional; however, the removal of conjugated bilirubin
from the liver cell and the excretion into the bile are
defective.
 This results in accumulation of conjugated and
unconjugated bilirubin leading to hyperbilirubinemia.
 Dubin-Johnson is a condition that is obstructive in nature,
so much of the conjugated bilirubin circulates bound to
albumin.
 Hepatic jaundice
Dubin-Johnson syndrome
 This type of bilirubin (conjugated bilirubin bound
to albumin) is referred to as delta bilirubin.
 A distinguishing feature of Dubin-Johnson
syndrome is the appearance of dark-stained
granules (thought to be pigmented lysosomes) on
a liver biopsy sample.
 Usually the total bilirubin concentration remains
 between 2–5 mg/dL with more than 50% due to
the conjugated fraction
 Hepatic jaundice
• Neonatal physiologic jaundice of the newborn
• A result of a deficiency of glucuronyl transferase, one of
the last liver functions to be activated in prenatal life since
bilirubin processing is handled by the mother of the fetus.
• In premature births, infants may be born with out
glucuronyl transferase, the enzyme responsible for
bilirubin conjugation.
• This results in the rapid buildup of unconjugated
bilirubin.
• When this type of bilirubin builds up in the neonate, it
cannot be processed and it is deposited in the nuclei of
brain and nerve cells, causing kernicterus., results in cell
damage and death in the newborn (Bilirubin -20mg/dl)
 Post-hepatic jaundice
• Results from biliary obstructive disease, usually from
physical obstructions (gallstones or tumors), that
prevent the flow of conjugated bilirubin into the bile
canaliculi.
• Bilirubin not properly excreted from the liver.
• Stool loses its source of normal pigmentation and
becomes clay-colored.
• The laboratory findings for bilirubin and its
metabolites
• in the above-mentioned types of jaundice are
summarized in table 24.1.
Clay stool
Obstructive jaundice conjugated
bilirubin imparts a
dark yellow color
to the urine.
Measurement of
free and
conjugated
bilirubin in serum
serves as a
sensitive test for
detecting liver
disease.
 Pathophysiology
Accumulation of bilirubin in extracellular fluid
- yellow-green pigment
- degradation product of heme (iron-
binding portion of hemoglobin)
 RBCs after 120 days

Fragile

Membranes of RBC rupture

Phagocytized by Reticulo endothelial system

Tissue macrophages
» Kupffer cells
» Spleen
 Hemoglobin split

Heme Globin Amino acid

pool-
reuse
• Happens Inside the macrophage
Free Iron

Transported in
blood by transferrin

Reused
Formation
of
biliveridin
Formation
of
bilirubin
 Straight chain of 4 pyrrole nuclei
HEME OXYGENASE

Biliverdin
BILIVERDIN REDUCTASE

Free Bilirubin (released by Macrophages into plasma)

Combination with plasma Albumin

Blood u.b

Liver Interstitial fluids

 Glucaryl
tansferase
• Conjugated bilirubin more soluble and can be
excreted into bile
Formation
of
uroblinin
Thank you
Hepatitis
Dr FiAZ
 Hepatitis
 Hepatitis is an injury to liver characterised by
presence of inflammatory cells in the liver tissue.
 It can be self limiting,or It can progress to
scarring of the liver.
 Hepatitis viruses cause most cases of liver
damage worldwide

40
 Types of Hepatitis
viruses
A B C D E

Source of feces /blood /blood /blood feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention -pre/post -pre/post blood donor -pre/post ensure safe

exposure exposure ;screening exposure drinking
immunization immunization risk behavior ;immunization water
modification risk behavior
modification 41
 Hepatitis A
 Hepatitis A (HAV), also known as infectious hepatitis
or short-incubation hepatitis, is the most common
form of viral hepatitis worldwide.
 HAV is excreted in bile and shed in the feces, which
can contain up to 10 9 infectious virions per gram
 The fecaloral route is the primary means of HAV
transmission.
 Patients with HAV infection present with symptoms
of fever, malaise, anorexia, nausea, abdominal
discomfort, dark urine, and jaundice. Symptoms are
generally self-limited and resolve within 3 weeks.
 Hepatitis A
 Clinical markers for the diagnosis and the progression
 of HAV infection are measured through the presence of
serologic antibodies.
 Immunoglobulin M (IgM) antibodies to HAV (IgM anti-
HAV) are detectable at or prior to the onset of clinical
illness and decline in 3–6 months,
 IgG antibodies to HAV (IgG antiHAV) appear soon after
IgM, persist for years after infection, and confer lifelong
immunity.
 IgM anti-HAV has been used as the primary marker of
acute infection.
• The presence of elevated titers of IgG anti-HAV in
the absence of IgM indicates a past infection.
 Hepatitis B
 Known as serum hepatitis or long-incubation
hepatitis,
 Hepatitis B virus (HBV) can cause both acute and
chronic hepatitis
 HBV is comparatively stable in the environment and
remains viable for longer than 7 days on
environmental surfaces at room temperature.
 It is detected in virtually all body fluids, including
blood, feces, urine, saliva, semen, tears, and breast
milk;
 The three major routes of transmission are parenteral,
perinatal, and sexual.
 Serologic Markers of HBV Infection
 HBV is a 42-nm DNA virus classified in the
Hepadnaviridae family.
 The liver is the primary site of HBV replication.
 Following an HBV infection, the core of the antigen
is synthesized in the nuclei of hepatocytes and then
passed into the cytoplasm of the liver cell, where it is
surrounded by the protein coat.
 An antigen present in the core of the virus (HBcAg)
and a surface antigen present on the surface protein
(HBsAg) have been identified by serologic studies.
Another antigen, called the e antigen (HBeAg), also
has been identified.
 Hepatitis B Surface Antigen
 Previously known as the Australia antigen and hepatitis
associated antigen (HAA),
 HBsAg is the antigen for which routine testing is performed on
all donated units of blood.
 HBsAg is a useful serologic marker in patients beforethe onset
of clinical symptoms because it is present during the prodrome
of acute hepatitis B.
 The HBsAg is not infectious; however, its presence in the serum
may indicate the presence of the hepatitis virus.
 Therefore, persons who chronically carry HBsAg in their serum
must be considered potentially infectious because the presence
of the intact virus cannot be excluded.
 Therefore, persons who chronically carry HBsAg in their serum
must be considered potentially infectious because the presence
of the intact virus cannot be excluded.
 Hepatitis B Surface Antigen
 HbSAg is the only serologic marker detected during the
first 3–5 weeks after infection in newly infected patients.
 The average time from exposure to detection of HBsAg is
30 days (range, 6–60 days).
 The presence of anti-HBs antibody in patients is
frequently observed in the general population, suggestive
of past infection.
 Patients who have developed the antibody to the Hepatitis
B surface antigen are not susceptible to future.
 reinfection with HBV.
6
 Hepatitis B Core Antigen
 HBcAg has not been demonstrated to be present in
the
 plasma of hepatitis victims or blood donors.
 This antigen is present only in the nuclei of
hepatocytes during an acute infection with HBV.
 The antibody to the core antigen, anti-HBc, usually
develops earlier in the course of infection than the
antibody to the surface antigen.
 A test for the IgM antibody to HBcAg was recently
 Developed as a serologic marker for clinical use.
 The presence of this IgM antibody is specific for
acute hepatitis B infection.
 Hepatitis B e Antigen
 The e antigen, an antigen closely associated with the
core of the viral particle, is detected in the serum of
persons with acute or chronic HBV infection.
 The presence of the e antigen appears to correlate well
with both the number of infectious virus particles and
the degree of infectivity of HBsAg-positive sera.
 The presence of HBeAg in HBsAg carriers is an
unfavorable prognostic sign and predicts a severe
course and chronic liver disease.
 Conversely, the presence of anti-HBe antibody in
carriers indicates a low infectivity of the serum .
 The e antigen is detected in serum only when surface
antigen is present