CLINICAL LABORATORY DIAGNOSTICS OF LIVER PATHOLOGY Slide 2
portal vein hepatic artery bile duct sinusoids bile canaliculi
central vein LIVER STRUCTURE Slide 3 LIVER FUNCTIONS
MetabolicMetabolic -Carbohydrate metabolism -Lipid metabolism
-Protein metabolism -Vitamin metabolism -Mineral metabolism
ExcretoryExcretory -Biosynthesis of urea -Synthesis of bile
DetoxicationDetoxication Slide 4 Metabolism of carbohydrates in
liver 1. Conversion of glucose-6- phosphate 2. Synthesis and
decomposition of glycogen 3. Gluconeogenesis 4. Conversion of
mannose, fructose and galactose to glucose Slide 5 Lipid metabolism
in liver Synthesis and decomposition of triacylglycerolsSynthesis
and decomposition of triacylglycerols Synthesis and oxidation of
fatty acidsSynthesis and oxidation of fatty acids Synthesis and
decomposition of phospholipidsSynthesis and decomposition of
phospholipids Synthesis and transformation of cholesterolSynthesis
and transformation of cholesterol KetogenesisKetogenesis Slide 6
Protein metabolism in liver Deamination, transamination and
decarboxilation of amino acidsDeamination, transamination and
decarboxilation of amino acids Synthesis of albumins of blood
plasmaSynthesis of albumins of blood plasma Synthesis of majority
of blood plasma globulinsSynthesis of majority of blood plasma
globulins Synthesis of blood clotting factorsSynthesis of blood
clotting factors Slide 7 Vitamin metabolism in liver Formation of
active form of vitamin DFormation of active form of vitamin D
Formation of vitamin A from carotinsFormation of vitamin A from
carotins Depo of cyanocobalamine and folic acidDepo of
cyanocobalamine and folic acid Depo of vitamin EDepo of vitamin E
Phosphorilation of vitamins B, formation of coenzyme
formsPhosphorilation of vitamins B, formation of coenzyme forms
Slide 8 Detoxification in liver Substances detoxification in liver:
-Xenobiotics -Products of protein decay in the intestine -The
terminal products of metabolism Slide 9 Slide 10 NORMAL METABOLISM
OF BILE PIGMENTS CELLS OF RES Indirect bilirubin NADP + NADPH 2
Biliverdin reductase Biliverdin Iron Globin Verdoglobin NADP +
Hemoxi- genase NADPH 2 Hemoglobin ERYTHROCYTES KIDNEYSKIDNEYS
Stercobilinogen URINE Stercobilin Indirect bilirubin 1,7- 20,5
mkmol/l albumin Indirect bilirubin UDP-glucoronil- transferase
Direct bilirubin 0.8- 4.3 mkmol/l BLOODBLOOD LIVERLIVER Bilirubin
mono- glucoronid, 20 % Bilirubin di-glucoronid, 80 % Dipyrols
-glucoro- nidase Glucoronic acid Direct bilirubin BILEBILE
INTESTINEINTESTINE Mesobilirubin Mesobilirubin (urobilinogen)
Stercobilinogen Stercobilin STOOL Slide 11 The decomposition of
hemoglobin in tissues, bile pigments formation. After a life span
of about 120 days the erythrocytes die. The dead erythrocytes are
taken up by the phagocytes of the reticuloendothelial system of the
body. About 7 gram of Hb is released daily from these phagocytosed
erythrocytes. The Hb molecule is broken down into 3 parts: Slide 12
(i) The protein (globin) part is utilized partly as such or along
with other body proteins. (ii) The iron is stored in the
reticuloendothelial cells and is reused for the synthesis of Hb and
other iron containing substances of the body. (iii) The porphyrin
part is converted to bile pigment, i.e. bilirubin which is excreted
in bile. Slide 13 Heme in the presence of the enzyme, heme
oxygenase, loses one molecule of CO and one atom of iron in Fe 3+
form producing biliverdin. Biliverdin which is green in color is
the first bile pigment to be produced; it is reduced to the
yellow-colored bilirubin, the main bile pigment, by the enzyme
biliverdin reductase Slide 14 Bilirubin is a very toxic compound.
For example, it is known to inhibit RNA and protein synthesis and
carbohydrate metabolism in brain. Bilirubin formed in
reticuloendothelial cells then is associated with plasma protein
albumin to protect cells from the toxic effects. As this bilirubin
is in complex with plasma proteins, therefore it cannot pass into
the glomerular filtrate in the kidney; thus it does not appear in
urine, even when its level in the blood plasma is very high.
However, being lipid soluble, it readily gets deposited in
lipid-rich tissues specially the brain. Slide 15 This bilirubin is
called indirect bilirubin or free bilirubin or unconjugated
bilirubin. Slide 16 The detoxication of indirect bilirubin takes
place in the membranes of endoplasmatic reticulum of hepatocytes.
Here bilirubin interact with UDP-glucuronic acid and is converted
to the water soluble form - bilirubin mono- and diglucoronids.
Another name of bilirubin mono- and diglucoronids is conjugated
bilirubin or direct bilirubin or bound bilirubin. This reaction is
catalized by UDP- glucoroniltransferase. Slide 17 Conjugated
bilirubin is water soluble and is excreted by hepatocytes to the
bile. Conjugated (bound) bilirubin undergoes degradation in the
intestine through the action of intestinal microorganisms.
Bilirubin is reduced and, mesobilirubin is formed. Then
mesobilirubin is reduced again and mesobilinogen is formed. The
reduction of mesobilinogen results in the formation of
stercobilinogen (in a colon). Stercobilinogen is oxidized and the
chief pigment (brown color) of feces stercobilin is formed. Slide
18 A part of mesobilinogen is reabsorbed by the mucous of intestine
and via the vessels of vena porta system enter liver. In
hepatocytes mesobilinogen is splitted to pyrol compounds which are
excreted from the organism with bile. If the liver has undergone
degeneration mesobilinogen enter the blood and is excreted by the
kidneys. This mesobilinogen in urine is called urobilin, or true
urobilin. Thus, true urobilin can be detected in urine only in
liver parenchyma disease. Slide 19 Another bile pigment that can be
reabsorbed in intestine is stercobolinogen. Stercobolinogen is
partially reabsorbed in the lower part of colon into the
haemorroidal veins. From the blood stercobolinogen pass via the
kidneys into the urine where it is oxidized to stercobilin. Another
name of urine stercobilin is false urobilin. Slide 20 The total
bilirubin content in the blood serum is 1,7-20,5 micromol/l,
indirect (unconjugated) bilirubin content is 1,7-17,1 micromol/l
and direct (conjugated) bilirubin content is 0,86-4,3 micromol/l.
Slide 21 Differentiation between unconjugated and conjugated
bilirubin. Direct and indirect bilirubin. Diazoreagent which is a
mixture of sulfanilic acid, HCI and NaN0 2 is added to the serum.
The conjugated bilirubin gives a reddish violet color with it and
the maximum color intensity is obtained within 30 seconds; this is
called direct test. Slide 22 The unconjugated bilirubin does not
give the direct test; however, it gives indirect test in which
alcohol or caffeine is also added which sets free the bilirubin
frum its complex with plasma proteins. Due to this difference in
the type of diazo reaction given by these two forms of bilirubin,
the term direct and indirect forms of bilirubin are also used Slide
23 Jaundice or icterus is the orange-yellow discoloration of body
tissues which is best seen in the skin and conjunctivae; it is
caused by the presence of an excess of bilirubin in the blood
plasma and tissue fluids. Depending upon the cause of an increased
plasma bilirubin level, jaundice can be classified as (i)
pre-hepatic, (ii) hepatic and (iii) post-hepatic Slide 24
Pre-hepafic jaundice This type of jaundice is due to a raised
plasma level of unconjugated bilirubin. It is due to an excessive
breakdown of red cells which leads to an increased production of
uncongugated bilirubin; it is also called haemolytic jaundice. As
the liver is not able to excrete into the bile all the bilirubin
reaching it, the plasma bilirubin level rises and jaundice results.
Slide 25 Hemolytic jaundice is characterized by Increase mainly of
unconjugated bilirubin in the blood serum. Increased excretion of
urobilinogen with urine. Dark brown colour of feces due to high
content of stercobilinogen. Slide 26 METABOLISM OF BILE PIGMENTS IN
HEMOLYTIC JAUNDICE CELLS OF RES Indirect bilirubin albumin Indirect
bilirubin Biliverdin reductase UDP-glucoronil- transferase Direct
bilirubin NADP + NADPH 2 Biliverdin Iron Globin Verdoglobin NADP +
NADPH 2 Hemoglobin Hemoxi- genase BLOODBLOOD LIVERLIVER Bilirubin
mono- glucoronid, 20 % Bilirubin diglucoronid, 80 % -glucoro-
nidase Glucoronic acid Direct bilirubin BILEBILE ERYTHROCYTES
KIDNEYSKIDNEYS INTESTINEINTESTINE STOOL Stool hypercholic URINE
Urine dark Mesobilirubin Mesobilinogen (urobilinogen)
Stercobilinogen Stercobilin Stercobilinogen Stercobilin Urobilin
Slide 27 Hepatic jaundice.This is typically seen in viral
hepatitis. Several viruses are responsible for viral hepatitis and
include hepatitis A, B, C and D viruses. The liver cells are
damaged: inflammation produces obstruction of bile canaliculi due
to swelling around them. This cholestasis causes the bile to
regurgitate into the blood through bile canaliculi. The blood
contains abnormally raised amount both of conjugated and
unconjugated bilirubin and bile salts which are excreted in the
urine. Slide 28 Hepatic jaundice is characterized by 1.Increased
levels of conjugated and unconjugated bilirubin in serum. 2.Dark
coloured urine due to the excessive excretion of bilirubin and
urobilinogen. 3.Pale, clay coloured stools due to the absence of
stercobilinogen. 4.Increased activities of alanine and aspartate
transaminases. Slide 29 METABOLISM OF BILE PIGMENTS IN HEPATIC
JAUNDICE CELLS OF RES Indirect bilirubin albumin Indirect bilirubin
Biliverdin reductase UDP-glucoronil- transferase Direct bilirubin
NADP + NADPH 2 Biliverdin Iron Globin Verdoglobin NADP + NADPH 2
Hemoglobin Hemoxi- genase BLOODBLOOD LIVERLIVER Bilirubin mono-
glucoronid, 20 % Bilirubin diglucoronid, 80 % -glucoro- nidase
Glucoronic acid Direct bilirubin BILEBILE ERYTHROCYTES
KIDNEYSKIDNEYS Urobilinogen INTESTINEINTESTINE STOOL Stool
hypocholic URINE Urine dark Stercobi- linogen Stercobilin Bilirubin
Urobilin Mesobilirubin Mesobilinogen (urobilinogen) Stercobilinogen
Stercobilin Slide 30 Post hepatic jaundice. This results when there
is extrahepatic cholestasis due to an obstruction in the biliary
passages outside the liver. In this way, the bile cannot reach the
small intestine and therefore the biliary passages outside as well
as inside the liver are distended with bile. This leads to damage
to the liver and bile regurgitates into the blood. Slide 31 Liver
function tests will vary according to the degree of obstruction,
i.e complete or incomplete. If the obstruction is complete, the
stools become pale or clay-colored and the urine does not have any
stercobilin. The absorption of fat and fat soluble vitamins also
suffers due to a lack of bile salts. Excess of bile salts in the
plasma produces severe pruritus (itching). Slide 32 Obstructive
(post hepatic ) jaundice is characterized by 1.Increased
concentration mainly of conjugated bilirubin in serum. 2.Dark
coloured urine due to elevated excretion of bilirubin and clay
coloured feces due to absence of stercobilinogen. Slide 33
METABOLISM OF BILE PIGMENTS IN OBSTRUCTIVE JAUNDICE CELLS OF RES
Indirect bilirubin albumin Indirect bilirubin Biliverdin reductase
UDP-glucoronil- transferase Direct bilirubin NADP + NADPH 2
Biliverdin Iron Globin Verdoglobin NADP + NADPH 2 Hemoglobin
Hemoxi- genase BLOODBLOOD LIVERLIVER Bilirubin mono- glucoronid, 20
% Bilirubin diglucoronid, 80 % Bile acids -glucoro- nidase
Glucoronic acid Direct bilirubin BILEBILE ERYTHROCYTES
KIDNEYSKIDNEYS Direct bilirubin INTESTINEINTESTINE STOOL Stool
acholic, steatorhea URINE Direct bilirubin Bile acids Urine dark,
foaming Slide 34 FATTY LIVER Slide 35 Spider naevus in liver
cirrhosis in the ventral side of the left shoulder Slide 36 Palmar
erythema Slide 37 Mild jaundice Slide 38 Jaundiced patient
