jaundice - yellow discoloration of tissue a medical lecture by Dr.Azad UOD-COM

1. Jaundice

2. Jaundice, or icterus, is a yellowish discoloration of tissue
resulting from the deposition of bilirubin.
Tissue deposition of bilirubin occurs only in the presence of
serum hyperbilirubinemia and is a sign of either liver
disease or, less a hemolytic disorder.
Slight increases in serum bilirubin are best detected by
examining the sclerae, which have a particular affinity for
bilirubin due to their high elastin content.

3. Presence of scleral icterus indicates a serum
bilirubin exceeds 40 µmol/L (~2.5 mg/dL)).
The ability to detect scleral icterus is made more
difficult if the examining room has fluorescent
lighting.
A second place to examine is underneath the
tongue.
if the process is long-standing; the green color is
produced by oxidation of bilirubin to
biliverdin.

4. Production and Metabolism of Bilirubin
About 70–80% of (the 250–300 mg of bilirubin
produced each day) is derived from the breakdown
of hemoglobin in senescent red blood cells.
The remainder comes from prematurely destroyed
erythroid cells in bone marrow and from the turnover
of hemoproteins such as myoglobin and cytochromes
found in tissues throughout the body.
The formation of bilirubin occurs in reticuloendothelial
cells, primarily in the spleen and liver.

5. Bilirubin formed in the reticuloendothelial cells is
virtually insoluble in water. To be transported in
blood, is accomplished by its reversible, noncovalent
binding to albumin. Unconjugated bilirubin bound to
albumin is transported to the liver, where it taken up
by hepatocytes.
After entering the hepatocyte, unconjugated bilirubin is
bound to the protein, bilirubin is solubilized by
conjugation to glucuronic acid, and yields bilirubin
monoglucuronide and diglucuronide.

6. Cont.
The conjugated bilirubin diffuse from the endoplasmic
reticulum to the canalicular membrane.
The conjugated bilirubin excreted into bile drains into
the duodenum and passes unchanged through the
proximal small bowel.
When the conjugated bilirubin reaches the distal ileum
and colon, it is hydrolyzed to unconjugated bilirubin
by bacterial B-glucuronidases. The unconjugated
bilirubin is reduced by normal gut bacteria to form
stercobilinogens.

7. About 80–90% of these products are excreted in feces,
either unchanged or oxidized to orange derivatives
called stercobilins.
The remaining 10–20% of the urobilinogens are
passively absorbed, enter the portal venous blood,
and are reexcreted by the liver.
A small fraction (usually <3 mg/dL) escapes hepatic
uptake, filters across the renal glomerulus, and is
excreted in urine

9. Measurement of Serum Bilirubin
 The terms direct- and indirect-reacting bilirubin are
based on the original van den Bergh reaction.
 van den Bergh method, the normal serum bilirubin
concentration usually is 17 µmol/L (<1 mg/dL).
 Up to 30%, or 5.1 µmol/L(0.3 mg/dL), of the total
may be direct-reacting (conjugated) bilirubin.
 Total serum bilirubin concentrations are between 3.4
and 15.4 µmol/L (0.2 and 0.9 mg/dL) in 95% of a
normal population.

10. Measurement of Urine Bilirubin
 Unconjugated bilirubin is always bound to albumin in
the serum, is not filtered by the kidney, and is not
found in the urine.
 Conjugated bilirubin is filtered at the glomerulus and
the majority is reabsorbed by the proximal tubules; a
small fraction is excreted in the urine.
 Any bilirubin found in the urine is conjugated
bilirubin. The presence of bilirubinuria implies the
presence of liver disease.
 A urine dipstick test (Ictotest) gives the same
information as fractionation of the serum bilirubin.
This test is very accurate.

11.  Hyperbilirubinemia may result from :
(1) overproduction of bilirubin;
(2) impaired uptake, conjugation, or excretion of
bilirubin.
(3) regurgitation of unconjugated or conjugated
bilirubin from damaged hepatocytes or bile
ducts.
 The initial steps in evaluating the patient with
jaundice are to determine
(1) whether the hyperbilirubinemia is
predominantly conjugated or unconjugated in
nature, and
(2) whether other biochemical liver tests are
abnormal.

12. Isolated Elevation of Serum Bilirubin
 Unconjugated Hyperbilirubinemia:
The critical determination is whether the patient is suffering from
a hemolytic process resulting in an overproduction of bilirubin
(hemolytic disorders and ineffective erythropoiesis) or from
impaired hepatic uptake/conjugation of bilirubin (drug effect
or genetic disorders).
 in haemolytic disease the serum bilirubin rarely exceeds 86
µmol/L (5 mg/dL).

13.  Causes of Isolated Hyperbilirubinemia
I. Indirect hyperbilirubinemia
A. Hemolytic disorders:
1. Inherited
a. Spherocytosis, elliptocytosis ,Glucose-6-phosphate dehydrogenase and
pyruvate kinase deficiencies
b. Sickle cell anemia
2. Acquired
a. Microangiopathic hemolytic anemias
b. Paroxysmal nocturnal hemoglobinuria c. Spur cell anemia
d. Immune hemolysis
B. Ineffective erythropoiesis:
1. Cobalamin, folate, thalassemia, and severe iron deficiencies
C. Drugs: 1. Rifampicin, probenecid, ribavirin
D. Inherited conditions
1. Crigler-Najjar types I and II
2. Gilbert's syndrome
II. Direct hyperbilirubinemia
A. Inherited conditions
1. Dubin-Johnson syndrome
2. Rotor's syndrome

15. Approach to patient with jaundice
 History:
– age and sex
– duration of jaundice
– abdominal pains
– color of stool and urine
– Itching
– History of contact with jaundiced patients
– History of drug and alcohol intake
– Exposure to toxins
– history of blood transfusion
– history of jaundice and hemolytic diseases in family
– history of operations especially abdominal op

16. Physical examination
 Color and distribution of discoloration.
 Pallor
 Signs of chronic liver disease
 Scars of operations, tattoo markings
 Itching marks
 Abdominal Examination:
– Abdominal masses
– Liver span
– Splenomegaly
– Ascites
 palpable lymph nodes
 Signs of hepatic encephalopathy

17. signs of chronic liver disease
 spider nevi, palmar erythema
 warm extremities, large volume pulse
 gynecomastia, distribution of hair
 liver span and splenic enlargement
 abdominal distension, ascites
 Dupuytren’s contracture, parotid enlargement
 Signs of hepatic encephalopathy:
– Disturbed level of consciousness
– Behavioral disturbances
– Abnormal movements
– Fluctuating neurological signs

19. Close-up view of a spider angioma of the skin in a patient
with liver disease. Note the central, punctate filling vessel
and the "spider-like" vessels emanating from it

20. Laboratory Tests
 The initial tests total and direct serum bilirubin,
aminotransferases, alkaline phosphatase, albumin, and
prothrombin time tests.
 Enzyme tests [alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and alkaline phosphatase] are helpful
in differentiating between a hepatocellular process and a
cholestatic processes.
 Patients with a hepatocellular process generally have a
disproportionate rise in the aminotransferases compared to the
alkaline phosphatase.
 Patients with a cholestatic process have a disproportionate rise
in the alkaline phosphatase compared to the aminotransferases.
 The bilirubin can be prominently elevated in both
hepatocellular and cholestatic conditions and therefore is not
necessarily helpful in differentiating between the two

21. Pre-hepatic jaundice
 This is caused either by haemolysis or by congenital
hyperbilirubinaemia, and is characterised by an isolated raised
bilirubin level.
 In haemolysis, destruction of red blood cells or their marrow
precursors causes increased bilirubin production..
 Jaundice due to haemolysis is usually mild because a healthy
liver can excrete a bilirubin load six times greater than
normal.
 The most common form of non-haemolytic hyper-
bilirubinaemia is Gilbert’s syndrome, an inherited disorder of
bilirubin metabolism.

22. Hepatocellular jaundice
 Hepatocellular jaundice results from an inability
of the liver to transport bilirubin into the bile,
occurring as a consequence of parenchymal
disease.
 In hepatocellular jaundice the concentrations
of both unconjugated and conjugated bilirubin in
the blood increase.
Hepatocellular jaundice can be due to acute or
chronic injury .

23.  Characteristically, jaundice due to
parenchymal liver disease is associated with
increases in transaminases (AST, ALT), but
increases in other LFTs, including cholestatic
enzymes (GGT, ALP) may occur, and suggest
specific aetiologies .

24.  Hepatocellular Conditions that May Produce Jaundice
1-Viral hepatitis
Hepatitis A, B, C, D, and E
Epstein-Barr virus Cytomegalovirus Herpes simplex
2-Alcohol
3-Drug toxicity Predictable, dose-dependent, e.g.,
acetaminophen Unpredictable, idosyncratic, e.g., isoniazid
4-Environmental toxins: Vinyl chloride , Kava Kava , Wild
mushrooms—Amanita phalloides or A. verna.
5-Wilson's disease
6-Autoimmune hepatitis

25. Obstructive (cholestatic) jaundice
 Cholestatic jaundice may be caused by:
• failure of hepatocytes to initiate bile flow.
• obstruction of the bile ducts or portal tracts.
• obstruction of bile flow in the extrahepatic bile
ducts between the porta hepatis and the papilla
of Vater.

28.  If the gallbladder is palpable, the jaundice is
unlikely to be caused by biliary obstruction
due to gallstones, probably because a
chronically inflamed stone-containing
gallbladder cannot readily dilate.
 This is Courvoisier’s Law, and suggests that
jaundice is due to a malignant biliary
obstruction (pancreatic cancer).
 Cholangitis is characterised by ‘Charcot’s
triad’ of jaundice, right upper quadrant pain
and fever.

29.  Cholestatic jaundice is characterised by a
relatively greater elevation of ALP and GGT
than the aminotransferases.
 Ultrasound is indicated to determine
whether there is evidence of mechanical
obstruction and dilatation of the biliary
tree.

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