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Synthetic Function
Plasma proteins (albumin, globulins),
cholesterol, triglycerides and lipoproteins
Detoxification and excretion
Ammonia to urea (urea cycle), bilirubin,
cholesterol, drug metabolites
Storage Function
Vitamins A, D, E, K and B
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Production of bile salts
Helps in digestion
Hepatocellular disease
Cholestasis (obstruction of bile flow)
Cirrhosis
Hepatitis
Jaundice
Liver cancer
Steatosis (fatty liver)
Genetic Disorders
Hemochromatosis (iron storage)
Greek word yellow
Irreversible scarring process
Classify according to 1. size of nodules
2.
etiology
One of the 10 leading causes of death
Dec. synthetic ability, portal
hypertension, esophageal varices
- A, B, C, D, E, CMV, EBV
Hepatitis A- also known as infectious
hepatitis and short incubation hepatitis
Transmitted by contaminated food or
water
Production of anti-HAV
Hepatitis B
Serum hepatitis or long incubation
hepatitis
ROT: parenteral, perinatal, sexual
Manifests in all body fluids
Core of the antigen is synthesized in the
nuclei of hepatocytes
HBsAg, HBcAg, HBeAg
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Hepatitis C
Parenteral, sexual, via blood transfusion
Hepatitis D/ delta Hepatitis
Satellite virus infection; cause disease
only in HBV infected patients (due to
base pair homology)
Hepatitis E
Feco-oral route; pregnant women
Jaundice
Jaune- yellow
Icterus; yellowish discoloration of the
skin mucous membranes and sclerae
Prehepatic, hepatic, posthepatic
Hyperbilirubinemia
Infants-kernicterus
Gilberts syndrome
Crigler-Najjar syndrome
Liver cancer
Hepatocellular
carcinoma/hepatocarcinoma/hepatoma
Related to previous infection with Hepatitis
Reyes syndrome
Disease of unknown cause; primarily in
children
Hepatic destruction following recovery
from a viral infection; neurologic
abnormalities
Noninvasive methods for screening of
liver dysfunction
Help in identifying general type of
disorder
Assess severity and allow prediction of
outcome
Disease and treatment follow up
Broadly classified as
1. Tests to detect hepatic injury:
mild or severe; acute or chronic
Nature of liver injury (hepatocellular or
cholestasis)
2. Tests to assess hepatic function
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Group I: Markers of liver dysfunction
Serum bilirubin: total and conjugated
Urine: bile salts and urobilinogen
Total protein, serum albumin and
albumin/globulin ratio
Prothrombin Time
Group II: Markers of hepatocellular injury
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Group III: Markers of cholestasis
I. Alkaline phosphatase (ALP)
II. - glutamyl transferase (GGT)
Normal LFT values do not always indicate
absence of liver disease
Liver has very large reserve capacity
Asymptomatic people may have
abnormal LFT results
Diagnosis should be based on clinical
examination
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Clinical Lab tests
Synthetic function Excretory function Integrity of liver cells
Bilirubin, ALP
Proteins
TP, Alb, A/G ratio
Liver enzymes
AST, ALT, GGT, ALP
Bilirubin is derived from the breakdown of hemoglobin when
aged RBC are phagocytized by the RES
Heme source in body:
80% from hemoglobin
20% other hemo-protein: cytochrome, myoglobin,
catalase
yellow pigment present in bile, urine and feces .
Heme four pyrrols rings connected together to form
(porphyrin).
Bilirubin consists of an open chain of four pyrrols-like
rings
Spleen
Plasma
Protein and a.a
pool
Iron pool
Liver
globin
iron
Heme
Hemoglobin
uncojugated
Bilirubin
Binds with
albumin
Conjugation
process
transferrin Heme
oxygenase
Stored as ferritin
Biliverdin
Biliverdin
reductase
albumin-Bilirubin
ligandin
Bilirubin diglucuronide
ER
hepatocyte
Uridyldiphosphat
e Glucuronyl
Transferase(UDPG
T)
albumin
ligandin-Bilirubin
bile (gall bladder)
direct
conjugated
post-hepatic
2 UDP-glucuronate
2 UDP
Y & Z
protein
Water
soluble
Bilirubin diglucuronide
Enterohepati
c
urobilinogen
cycle
Stercobilinogen
Bacterial enzymes
mesobilirubin
Bacterial enzyme 2 glucuronate
Bacterial enzyme
Urobilinogen
liver
Urobilin
kidneys
Stercobilin feces
kidneys
intestines
mesobilirubinoge
n
oxidatio
n
reabsorbe
d
urine
urobilin
200-300mg of bilirubin/day
Systemic circulation
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However 10% of the
secreted bile is reabsorbed by
the small intestine. This bile is
then resecreted by the liver
into the small intestine. This
process is known as
enterohepatic circulation
Direct bilirubin: is conjugated (water soluble bilirubin) in
aqueous solution it reacts rapidly with reagent (direct reacting).
Indirect bilirubin: is unconjugated (water insoluble bilirubin)
because it is less soluble in it reacts more slowly with reagent
(reaction carried out in methanol).
- in this case both conjugated and unconjugated bilirubin are
measured given total bilirubin. Unconjugated will calculated
by subtracting direct from total and so called indirect.
Total bilirubin = D+ ID
Knowing the level of each type of bilirubin has diagnostic
important.
It is a medical term describes the elevation of bilirubin in
blood result in yellow color of skin and sclera.
Defect in conjugation or excretion of bilirubin
Other symptoms include nausea, vomiting, dark-colored
urine and fatigue.
According to the cause of jaundice
it is classified to three main types:
Pre-hepatic jaundice
Hepatic jaundice
Post-hepatic (most common type)
Post-hepatic jaundice Hepatic jaundice Pre-hepatic jaundice
Due to obstruction of bile
duct which prevents
passage of bilirubin into
intestine.
D.Bil will back to liver
and then to circulation
elevating its level in blood
and urine.
Occur in:
Biliary stricture
Cancer of the pancreas or
gallbladder
Gallstones
Due to liver cell damage
(cancer, cirrhosis or hepatitis)
Impaired cellular uptake
Defective Conjugation of
bilirubin (ID.Bil. ).
Blilirubin that is conjugated is
not efficiently secreted into
bile but leaks to blood (D.Bil.
)
Occur in :
Cirrhosis (scarring of the liver)
Hepatitis
Gilbert's disease
Criger-Najar syndrome
Due to increase in RBCs
breakdown due to
hemolytic anemia.
Unconjugated
hyperbilirubinemia
The rate of RBCs lysis and
bilirubin production more
than ability of liver to
convert it to the conjugated
form
Occur in:
Erythroblastosis fetalis
Hemolytic anemia
Transfusion reaction
Rarely exceed 5 mg/dL
Causes
D.Bil (High) D.Bil, ID.Bil, T.Bil all (High) ID.Bil > D.Bil Type of Bil.
ALP ( High) ALT, AST (High)
K
+
( High)
Hematology:
CBC (low Hb)
Conformatio
nal test
haemolytic
jaundice
hepato-cellular
jaundice
obstructive
jaundice
GILBERT SYNDROME
Benign autosomal
recessive disorder
Genetic mutation of
gene UGT1A1
Impaired cellular
uptake of bilirubin
Less than 3mg/100mL
unconj
CRIGLER-NAJJAR
SYNDROME
Deficiency of the
enzyme UDPGT
Type I
Complete absence of
enzyme
Rare, fatal
Type II
severe deficiency of
enzyme
some conj bili is formed
Dubin-Johnson
syndrome
Rare autosomal
recessive disorder
Conj
hyperbilirubinemia
from defective
excretion by the liver
cell
Delta bilirubin- conj.
bilirubin bound to
albumin
Rotors syndrome
reduction in
concentration of
intracellular binding
proteins
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A fasting serum specimen is preferred.
Samples should be stored in the dark and measured
within 2-3 hours after collection.
Hemolyzed specimens- decrease in bilirubin
Lipemia- can cause interference
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Urine samples
Bilirubin + DSA
Formation of red or blue pigment
Same reaction with
Ehrlichs
Added alcohol as an
accelerator
1937 - Malloy and Evelyn
50% methanol as
accelerator
1938 Jendrassik and
Grof
Plasma + sodium acetate + diazotized sulfalinic
acid-purple
Caffeine sodium benzoate
azobilirubin
Sodium acetate- buffers pH
Caffeine-sodium benzoate- accelerates coupling of bilirubin to
DSA
Blue
azobilirubi
n read at
600nm
Alkaline tartrate
Principle:
Urobilinogen + P-
dimethylaminobenzaldehyde RED
(Ehrlichs reagent)
Addition of ascorbic acid- reducing agent
Sample- fresh 2-hour urine
Normal Results
It is normal to have some bilirubin in your blood.
Normal levels are:
Direct (also called conjugated) bilirubin: 0 to 0.5 mg/dL
Total bilirubin: 0.3 to 1.9 mg/dL
Note: mg/dL= milligrams per deciliter
Normal value ranges may vary slightly among different
laboratories.
Bilirubin form Normal value
Total (elderly, adult, child)
(newborn)
Critical value (adult)
(newborn)
0.2 to 1.0 mg/dL
1.0 to 12.0 mg/dL
>12 mg/dL
>15 mg/dL
Pre-hepatic, unconjugated, indirect 0.2 to 0.8 mg/dL
Post-hepatic, conjugated, direct 0.0 to 0.2 mg/dL
Fecal urobilinogen 40 to 280 mg/day
Urine 0.1 to 1.0 Ehrlich units
Conjugated bilirubin - water soluble -
direct reaction with dyes
Unconjugated bilirubin - water insoluble -
alcohol is needed for dye (indirect) reaction
