Professor niazy abu farzakh

jaundice

Jaundice is a clinical term (sign) but it reflects biochemical abnormality

hyperbilirubenemia is found in pt's blood that has jaundice.
Normal bilirubin = (3-17 mol/L)(0.1-1.3mg), jaundice usually detectable when
plasma bilirubin exceeds 3 times more than normal upper limit of blilirubin ,i.e
when the serum belirubin is greater than 3 mg/dl.
Bilirubin accumulates in mucous membrane, skin & sclera producing yellow to green
discoloration.
Important to know that discoloration (due to jaundice) occurs in both skin & sclera,
while some diseases cause discoloration in sclera without skin (Ex: alcoholic, black,
Negros, chronic obstructive airway diseases) or skin without sclera (Ex:
hypercarotenaemia).

Bilirubin formation and excretion

Yellowish antioxidant that is the result of destruction of erythrocytes by
macrophages.
Bilirubin is waste products for RBCs, and because there are large amounts of RBCs in
blood and body always renews RBCs (RBCs life span 120 days) so destruction of RBCs
will give between (250-300mg) of bilirubin daily .this destruction occurs in
reticuloendothelial system.
** Bilirubin results from catabolism of heme moiety of hemoglobin and other
hemoproteins:
Globin is a protein, heme is iron & protoporphyrin.
Metabolism of protoporphyrin produces bilirubin.

Reticuloendothelial system takes old RBCs and destroy them
pure bilirubin
results from this process and released in blood
binding to albumin
taken by
liver, kidney & lung (mainly by liver).
Bilirubin is up taken from plasma by hepatocyte in liver, hepatocyte made three
processes for bilirubin:
1- Uptake.
2- Conjugation with glucuronic acid (gluc =glucose)
converted to bilirubin
diglucuronide "conjugated bilirubin" which is water soluble (this reaction is
catalyzed by the enzyme UDP-glucuronide transferase).
3- Excreted in bile via specific carriers on the hepatocyte membrane, it is the most
difficult process (the rate limiting step).

Biliary system : bilirubin excreted by hepatocyte in bile canaliculi
goes to bile

duct
common bile duct
second part duodenum (small intestine)

reaches large intestine , metabolized by colonic bacteria to form stercobilinogen

changing the green color of bilirubin to brown
excreted in the stool .(bilirubin is

responsible of the color of stool).
Small amount of this bilirubin(stercobilinogen) is absorbed from the bowel into the
circulation and excreted in urine as urobilinogen ,less than 2%
2mg/24 hours.(in
davidson's:4mg/day)
So Bilirubin released by reticuloendothelial system in circulation is in nonconjugated
pattern with undetectableamont of Monoconjugated, Diconjugated & conjugated
bilirubin but practically it is almost all nonconjugated in circulation.

Ven den Bergh test

Two types of reaction to detect bilirubin:
1- Direct reaction: Alcoholic reagent (sulfanilic acid) is added to the solution, lf the
bilirubin is conjugated the color changes immediately.
2- Indirect reaction: If the solution contains nonconjugated bilirubin, then we add
another reagent (methanol) which leads to breaking down of the intramolecular
hydrogen bonds of unconjugated bilirubin reacting with sulfanilic acid leads to color
change.
So:
Indirect reflex>>non conjugated bilirubin>> indirect hyperbilirubinaemiea.
Direct reflex>> conjugated bilirubin>> Direct hyperbilirubinaemiea.

Serum bilirubin
Serum bilirubin is:
1- Mainly unconjugated fraction, gives indirect ven den reaction
2- Little amount of monoconjugated & diconjugated fraction, gives direct ven den
reaction
3- Bilirubin-Alb fraction (delta bilirubin or biliprotein): conjugated bilirubin released
from hepatocyte into circulation due to obstruction of biliary system, gives direct
reaction:
-

bilirubin covalently bound with albumin.(strong bond)

Occur in obstructive jaundice and irreversible.

# By chromatography we can separate the four fractions of bilirubin.

Classification of jaundice
Jaundice is classified according to bilirubin:
1- Increase production of bilirubin: the amount of the bilirubin synthesized is
more than the capacity of liver to take ,liver can work 5 times more than his
normal capacity work (in Davidson's>>six times greater than normal), so
hemolytic jaundice -which result in elevated production of bilirubin occurs
after liver do its maximum work.
2- Decrease excretion.
Another classification:
1- Unconjugated hyperbilirubinemia (before the conjugated of bilirubin):
when the indirect -reacting fraction exceeds 1 mg /dl (as written in the
slides ).
2Due to:
Hemolysis
Increased bilirubin production in reticuloendothelial
system.
Liver disease
Decreased hepatic bilirubin clearance.
Congenital.
3- Conjugated hyperbilirubinemia (after the conjugated of bilirubin): occurs
in hepatocyte if the direct-reacting fraction of serum bilirubin exceeds
20% of total serum bilirubin.
Due to:
Intrahepatic disorder (no flow of bilirubin inside the liver):
hepatocellular disorder, cholestatic disease, congenital disorders.
Extrahepatic disorders (disease in major biliary system): Stricture,
stone, tumor.
Congenital.
For practical purposes, jaundice occurs commonly bcz of five conditions:
1- Hemolysis.
2- Hepatitis.
3- Liver cirrhosis.
4- Biliary disease (obstruction).
5- Congenital disease.

Approach to patient with jaundice

These five conditions subdivided into many categories so we want at least to know
from which categories the pt is having the jaundice:
1- Age and sex.
2- Duration of jaundice.(jaundice for long time(20 years) may be malignancy
result in obstruction)
3- Abdominal pains, color of stool & urine, and itching
these three
characters important to differentiate obstructive jaundice. (It is not necessary
to find all these characters together to diagnose obstructive jaundice, may be
just one of them is present).
Abdominal pains: # Obstruction in biliary system as any other obstruction in
hollow organ lead to colic pain called biliary colic (pain which comes gradually
10-15 min then continues dull aching pain for at least 30 min (rest platue)
then goes away in another 15 min. So it is not practically colic; it is dull aching
pain which comes slowly and goes slowly).see figure blow

Pain

15

45

60

Time (mins)
# another type of pain is in acute hepatitis -not chronic- due to distention and
inflammation of liver which leads to distention in the capsule of liver and
makes a sort of discomfort or dull ache in RUQ.
Color of stool & urine:
In urine: Urobilinogen secreted in urine is colorless, but on standing
ureobilinogen transforms to uroebilin which is yellow in color.
When conjugated bilirubin exceeds specific amount in circulation, kidney
starts releasing it away with urine, Presence of bilirubin in urine gives it a tea
color (it is not ureobilinogen which colorless changed its color after
urination).
In stool: Also fresh stool changes to dark brown after exposure to air.
In patient who had obstruction there is no bilirubin in stool, so stool color will
be pale.

Itching: occurs in obstructive jaundice due to bile salt not to bilirubin (so it is
not
Because congenital disease), itching all over the body.
4- Ask about history of contact with jaundiced patients (hepatitis).
5- History of drug and alcoholic intake: every one with jaundice must asked
about drugs (like: NASID, antibiotic, chemotherapeutic reagents, paracetamol
"fulminant liver") and alcohol.
6- Exposure to toxins.
7- History of blood transfusion.
8- History of jaundice and hemolytic diseases in family.
9- History of operations especially abdominal operations (blood transfusion,
adhesionsobstructions, strictures, operation for malignancy in or out liver).

Physical examination:
1- jaundice in sclera and skin.(color of patient in hemolysis is yellow lemon
color, in obstructive jaundice is greenish color)
2- Pallor (hemolytic anemia+hepatitis).
3- signs of chronic liver disease (liver cirrhosis):gynocomastia ,feminization
,palmer ereythemia ,spider naevi , koilonychias ,parotid enlargement
,dupuytren's contracture(alcoholic pt) ,shrinkage liver span.
4- itching marks
5- abdominal examination:
A- Abdominal masses
b- Liver span
c- Splenomegaly
d- Ascites
6- Look for lymph nodes.
7- Signs of hepatic encephalopathy: flapping tremor.

Student asked: why there is parotid enlargement?

Dr: because in chronic alcoholic liver disease pt
there is not flow of saliva.

Common finding in liver

cirrhosis: ascites, umbilical
hernia, caput medusa.

Investigations for jaundiced patient:

1- Serum bilirubin: direct & total
2- CBC & ESR: anemia
3- Retics: sometimes patient will come to you (somewhat later on) where
his HG is in borderline and you cannot say "anemia", retics will give you
a clue.
4- AST & ALT : indicate hepatitis(liver disease)
5- Alkaline phosphotase : indicates biliary disease
6- Serum albumin : chronic liver disease , liver cirrhosis
7- Prothrombin time : chronic liver disease , liver cirrhosis
8- Urine for urobilinogen and bilirubin : not necessary but to conferred
your diagnosis .(urobilinogen in liver disease &hemolysis , bilirubin in
obstructive jaundice)
9- Abdominal ultra sound: every patient has direct
hyperbilirubinemia>20% of his bilirubin should do US , look for dilatation
in biliary system(obstructive disease)

Classification of jaundice according to etiology:

1-

Increased production:

Increased total bilirubin and indirect fraction.

CBC: low Hb, reticulocytosis.
Increased LDH and AST; due to hemolysis.
Normal ALT and Alkaline Phosphatase.
Normal PT and Albumin.
Normal US liver, gall stones may be present; patient with
hemolysis more liable for gallbladder stone pigmentation.
** Jaundice due to increased bilirubin production:
A- Hemolysis.
B- Infective erythropoiesis : Thalassemias, pernicious anemia due
to vitamin B12 deficiency.
C- Hematoma formation: elevated RBCs
RBCs
destruction
elevated bilirubin.

2- liver disease(hepatocellular disease):

Increased bilirubin in both direct and indirect fractions.

Elevated ALT & AST.
Mild elevation in alkaline phosphatase.
Low albumin.

Prolonged prothrombin time (PT).

US: shoes normal biliary system.

**Causes of hepatocellular jaundice:

A- All type of hepatitis.
B- All types of cirrhosis.

3- Cholestatic jaundice:
How to diagnose Cholestatic jaundice (jaundice due to obstruction in
biliary system)?

Elevated bilirubin with direct fraction more than 20%.

Elevated Alkaline phosphatase and gamma GT.
PT may be prolonged, corrected with vit K (important clue).
US should be done in anyone with elevated direct bilirubin
US will show two types either:
@- dilated biliary system: stricture, stone, neoplasm.
Or
@-non dilated biliary system: any liver condition inside liver
leading to the slow flow of the bile.

US will help you to decide if there is obstruction or not, but it is not always
conformity test ,you should do conformity test which sometimes also helps in
treatment :@- ERCP(endoscopic retrograde cholangiopancreatography ) or PTC(
Percutaneous Transhepatic Cholangiography).
In ECRP: enter the scope until it reaches ampulla
canulates ampulla
to see
pancreatic or/and biliary system.
PTC: this is indicated when there is dilatation in biliary system; radiologist punctures
needle in one of biliary canculai and inject dye.

Stone in US

Pancreatic duct bcz it is crossing the

vertebra column .

ECRP picture differentiate it by:

scope + common bile. duct.

Complication of ECRP: (v.important)

1234-

Pancreatitis(the most common)

Infection
Hemorrhage
Perforation

4- Congenital hyperbilirubinemia:
Rise in direct or indirect fractions:
# Indirect hyperbilirubinemia: very common type called Gilbert's disease.
Gilbert's disease: everything normal except indirect bilirubin
, normal (CBC, ALT, AST, ALK phosp, retic, & biopsy) .
# Direct hyperbilirubinemia: Rotors disease, Dubin Johnsons disease.
Every thing normal except direct bilirubin.
Elevated Direct bilirubin+ normal ALK phosp= Rotor's or Dubin
Roter's disease
not liver pigmented.
Dubin Johnsons disease
liver pigmented.

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Done by : saffanah alal-dolat.

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