Kwame Nkrumah University of

Science & Technology, Kumasi, Ghana

LIVER FUNCTION/ DISORDERS &

INVESTIGATIONS

SN Darko
Dept of Molecular Medicine

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 Course Outline
▪ Functions of the Liver
▪ Bilirubin Metabolism
Structure of Bilirubin
▪ Jaundice/Icterus in Adults
Pre-hepatic Jaundice
Hepatocellular Jaundice
Intra-hepatic cholestasis
Post-hepatic Jaundice
▪ Inherited hyperbilirubinemia
▪ Neonatal Jaundice

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 References

▪ Clinical Biochemistry by Nessar Ahmed

▪ Lecture Notes on Chemical Pathology 2013;
University of Cape Town.
▪ Lecture Notes in clinical Chemistry by Whitby,
Smith and Percy-Robb
▪ Clinical Chemistry in Diagnosis and Treatment by
McGilvery.

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 Course Objectives
• Know the various functions of the liver
• Describe how bilirubin is metabolized and
excreted.
• Mention the characteristics of Jaundice
• Understanding the categories and basis of
Jaundice.
• Know some rare inherited conditions and their
association with hyperbilirubinemia
• Know some indicators to look out for in
dysfunctional bilirubin metabolism

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 Bilirubin Metabolism
• 80% of the daily output
of bilirubin from
breakdown of
erythrocytes
• 20% from red cell
precursors and haem
proteins e.g.
myoglobin, cytochrome
& peroxidase
• Breakdown commences
with removal of the iron
moiety

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 Bilirubin Metabolism
• Ligandin Y and Z =
intracellular binding and
transport of bilirubin
• UDP-glucuronyl
transferase
1=conjugation of
bilirubin + 2 glucuronic
acid
• Intestinal flora =
deconjugates bilirubin
diglucuronide (BG)
• => urobilinogen,
mesobilinogen and
stercobilinogen

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 Enterohepatic Circulation
• Urobilinogen is a
normal
constituent of the
urine
• The pigments
contribute to the
colour of the stool
• Normal adults do
not excrete
bilirubin in the
urine and stool

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What happens?

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 Jaundice/Icterus in Adults
• The reference range of
bilirubin in adults is up to
17.1 µmol/L

• Jaundice is characterized by the yellowish

colouration of the tissues due to retention of
pigments

• Experienced physicians discern when blood

[bilirubin] is about 35 µmol/L

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 Jaundice/Icterus in Adults
• It becomes overt (sclera,
skin) when levels are
about 55-70 µmol/L

• Is a symptom of an underlying disease

• It may be due to
✓ pre-hepatic
✓ hepato-cellular or
✓ post-hepatic causes

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 Pre-hepatic Jaundice
• It may be due to haemolytic or non-haemolytic
causes

• Haemolytic jaundice may be due to acquired

(malaria) or congenital (G6PD deficiency)
causes

• It may also be due to ineffective erythropoiesis

(pernicious anaemia) or right sided congestive
cardiac failure

• Non haemolytic jaundice is usually of congenital

origin e.g Criglar-Najjar and Gilberts’syndrome

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G6PD in Haemolytic Jaundice

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 Hepatocellular Jaundice
• Due to defects in conjugation of bilirubin or
defects in its hepatic uptake (flavispidic acid)

• Defects in conjugation may result from diffuse

hepatic injury which may occur in the following:
✓ acute,
✓ subacute,
✓ chronic and
✓ fulminant hepatitis

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Agents of Hep’cellular Jaundice

Antioxidant
function ↓
ATP production ↓

NAPQI =N-acetyl-para-benzo-quinone
imine

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 Intra-hepatic cholestasis
• This may occur in subacute or chronic
hepatitis
• Due to hepatotoxicity of some drugs such as
• 17 α-alkylated steroids e.g
methyltestosterone or norethisterone
• Phenothiazine e.g chlorpromazine
(Psychotic disorder)
• Hypersensitivity reactions e.g.
erythromycin, tetracycline

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 Post-hepatic Jaundice
• This is usually due to mechanical
obstruction of the biliary tree as a result
of:
• Gallstones
• Carcinoma of the head of the pancreas
• Scarring from infection

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 Inherited Hyperbilirubinemia
This may be classified into unconjugated and
conjugated types
• Congenital unconjugated
hyperbilirubinaemias are Gilberts and
Criggler-Najjar Syndromes

• Congenital conjugated hyperbilirubinaemias

are Dubin Johnson and Rotor Syndromes

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 Gilbert’s and Crigglar-Najjar
Syndromes
Alb=Albumin
UCB=Unconjugated
bilirubin
UDPGA=Uridine
diphosphate
glucuronic acid

Crigglar-Najjar I= Severe (kernicterus) Gilbert’s syndrome= may be associated ↓

Crigglar-Najjar II=Moderate in RBC life span. [Bilirubin] between 20
Presents at birth and 40 μmol/L. 2nd decade of life
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Dubin-Johnson and Rotor
Syndromes
Alb=Albumin
UCB=Unconjugated
bilirubin
UDPGA=Uridine
diphosphate
glucuronic acid
BG= Bilirubin
diglucuronide
MRP=Multidrug
resistant protein
OATP=Organic
anion transporter

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Summary of Inherited
Hyperbilirubinaemia

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 Neonatal Jaundice
• The reference range of bilirubin in neonates
is 8-67 µmol/l

• In the first week of a neonates life, there

may be a physiological hyperbilirubinaemia

• The serum [bilirubin] may rise to as high as

200 µmol/l and is usually prolonged in
preterm neonates

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 Causes of Neonatal Jaundice
• Haemolytic disease e.g blood group
incompatibility and G6PD deficiency

• Immaturity of the hepatic processes for

uptake and excretion of bilirubin

• Interference with hepatic transport

functions by drugs e.g progesterone or
steroids with progesterone-like activity

• Biliary atresia may lead to cholestatic

jaundice

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Differential Diagnosis of Jaundice

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 Investigative Biochemical
Parameters of Liver Disorder
• ↑ blood nitrogen
• ↑ bilirubin, Alkaline Phosphatase AST and
ALT
• ↓ blood urea, serum albumin and clotting
factors

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