Download Liver - KSU Faculty Member websites

Dr. Abdulrahman Al-Ajlan
 Liver
is the largest internal organ
in the body. It consists of two
main lobes divided into right and
left by the hepatic vein that
together weigh from 1400 to
1600g in the normal adult.
2



The liver is complex organ, located in the
upper right corner of the abdomen. The
liver received approximately 15 ml of blood
per minute from two major vessels:
* The hepatic artery supplies 25% of the
total blood flow and provides most of the
oxygen requirement.
* The portal vein drains most of the
gastrointestinal tract (GI). It supplies 75% of
the blood flow and transports the most
recently absorbed material from the
intestines to the liver.
3
4
5






The liver is a vital organ, which has many
vital roles.
The liver plays a major role in protein,
carbohydrate and lipid homeostasis.
The liver stores glycogen, vitamins and iron.
It contains an extensive reticuloendothelial
system for the synthesis and breakdown of
blood cells.
Liver cells metabolize, detoxify and excrete
both endogenous and exogenous
compounds.
(Metabolism and execration of drugs and toxins)
6



A request for LFTs will provide results for
Bilirubin, the aminotransferases and
alkaline phosphatase in serum specimen.
Bilirubin: Bilirubin is composed of four
pyrrole rings joined by methyl bridges and
it’s the principal pigment in bile, which is
derived from breakdown of Hb.
About 80 % of the Bilirubin formed daily
comes from the degradation of Hb, whereas
the remainder comes from the destruction
of heme containing proteins (myglobin,
cytochromes , catalase).
7
Hemoglobin
Iron
Protein (globin)
(Reused for synthesis of
Hb, myoglobin , enzyme
, stored in liver , bone
marrow)
Is reused
Porphyrrin
(Is not recycle)
Bilirubin (Slightly soluble in plasma
and is transported to the liver binding to
albumin)
8
Blood
Bilirubin –
albumin complex
Albumin
In the liver
Bilirubin diglucuronide
Bilirubin
monoglucuronide
9



It is a yellow discoloration of the skin or
sclera, this is due increase of bilirubin con in
the blood upper the normal average.Free
bilirubin will accumulate in the body fat, while
the conjugated bilirubin accumulate in elastic
tissues such as the eyeballs, the mucous
membrane of the mouth, nose and the skin of
the abdomen and chest.
Jaundice is not detectable until the con of
bilirubin is greater than about 40µmol/L.
Normal concentration of Bilirubin in plasma is
less than 22µmol/L.
Jaundice may be due to diseases of the blood,
of the liver or the bile ducts or pancreas.
10

1- Haemolysis. Due of
◦ a)-The life span of RBC is less than the
normal 120 days.
◦ b)-Abnormal spherical shape of RBC
(hereditary spherocytosis).
◦ c) -Deficiency of glu-6-P dehydrogenase.
The cells are destroyed when exposed to
oxidant drugs.
◦ e) - Sickle cell anemia.
◦ All these factors increase Hb breakdown
produces bilirubin which overloads the
conjugating mechanism.
11
2-Failure of conjugating mechanism
within the hepatocytes.
 A- Gilbert s disease
 There is impairment in the ability of
the liver cells to take up free bilirubin
from the blood. The bilirubin levels in
serum slightly high. The patient is
slightly jaundiced, but all other liver
function tests are normal {enzyme,
etc}

12



B- Najjar syndrome (deficiency of
glucuronyl transferase)
The deficiency of this enzyme in infants
leads to high level of free bilirubin, and
there is no conjugated bilirubin. The infants
become jaundiced shortly after birth.
In infant, free bilirubin is able to enter the
brain (only in infants because the immature
central nervous system). It is toxic to nerve
cells; these children usually die within first
year of live due brain damage.
13



C-Physiological jaundice (jaundice in
newborns)
Newborn infants (premature babies), often
accumulate bilirubin because the activity of
hepatic bilirubin glucuronyl transferase is
low at birth and reaches about levels in
about two weak, bilirubin enter the brain
and causes damage of brain cells.
The new born with elevated level of
bilirubin are treated with blue fluorescent
light, which converts bilirubin to more polar
(water soluble).
14


3- Obstruction in the biliary system.
Bile is excreted from the liver cells into bile
duct through canaliculi (tiny vessels or little
channeles). Bile duct carries bile to the
small intestine. Obstruction at any point will
cause bile to back up. Some of the
conjugated bilirubin is reabsorbed into the
blood and jaundice results. The bile duct
obstruction may be due to gallstones or a
tumor.
15
1-Partially block of the bile duct by
gallstones.
 Diagnosis:
 Alkaline phosphatase may be high,
although serum bilirubin within the
reference range.

16
2- Fully block of the bile duct.
 Diagnosis;
 If the blockage is complete, both
bilirubin and alkaline phosphatase are
raised.
 The degree of obstruction reflected by
the levels of alkaline phosphate.

17
Intrahepatic biliary
obstruction:
 The bile canaliculi become
blocked due cirrhosis, liver
cancer or infection.
 Diagnosis;
 It is lead to increase con of
conjugated bilirubin in serum.
B.
18
4- Diseases of the liver.
 Any disease that damages or destroys
a large number of liver cells lead to
decrease the capacity of the liver to
covert free bilirubin to bilirubin
glucuronide and jaundice will results.

Glutamic Oxalacetic Transaminase
(sGOT) or Aspartate Aminotransferase
(AST)
 Glutamic Pyruvic Transaminase (GPT)
or Alanine Transaminase (ALT).
 Alkaline Phosphatase (ALP)
 Gama Glutamyl Transpeptidase (GGT)
or γGT


20




Bile:
It is consists of a watery mixture of organic
and inorganic compounds.
phosphatidylcholine and bile salts are the
most important organic components of bile.
Bile can either pass directly from the liver
into the duodenum throw the common bile
duct or be stored in the gallbladder when
not needed immediately for digestion
Bile is composed of bile acids or salts bile
pigment (biluribin esters) cholesterol and
substances extracted from the blood
21




Total bile production averages about three liters
per day although only one liter is extracted
The bile acids cholic acid and chenodeoxycholic
cholesterol
The bile acids are conjugated with the amine acids
glycine or taurine forming bile salts (conjugated
bile acids) are excreted into the bile canaliculi
During fasting and between meals ,a major of the
bile acids pool is concentrated up ,to fold in the
gallbladder ,bile acids reach the intestines when
the gallbladder contracts after each meal ,about
500 to 600 ml of bile enter the duodenum each
day .it is involved with the digestion and
absorption of lipids
22

Bile acids:



The bile acids contain 24 carbons with two
or three hydroxyl groups and a side chain
that terminates in a carboxyl group
The most common bile acids are cholic
chenodeoxycholic acid .bile and acids are
synthesized in the liver by multi step pathway
from cholesterol
23

The molecule have both a polar and a non
polar face and can act as emulsifying agent in
intestine helping to prepare dietary triacylglycerol and other complex lipids for
degradation by pancreatic digestive enzyme


Bile salt:


Chenodeoxycholic acid +taurine

24


The main functional constituent of the bile are
the salts which are involved in fat digestion and
absorption from the small intestine. Fat of the
bile salts in the intestine. They may be
reconjugated and dehydroxylated (at postion7)
by intestinal bacteria. 95% of bile salts are
absorbed in the ileum and return to the liver
where they may be reconjugated with glycine or
taurine, however they are not rehydroxylated
.those that laclc the 7α -hydroxylproup are
called secondary bile salts
The liver recycles 95% of the bile salts each day
.5% are lost in the feces
25

Transaminase enzymesTransaminase
that transfer of an amino group from
one amino acid to an α-keto acid.
Transaminase reactions are readily
reversible and can used in the
syntheses or the degradation of amino
acids.
26






Example, glutamic oxalacetic transaminase
(GOT)
aspartate aminotransferase (AST).
Or aminotransferase
Example of transamintaion reaction are :
Oxaloacetic +glutamate
Aspartate + α –ketoglutarate
Enzyme: Aspartate aminotransaminase
(AST) witch is also known as glutamate
oxaloacetate transaminase (GOT)
27


GOT or AST:
It is found in highest concentration in the
liver and heart muscle and also skeletetal
muscle it is clinical usefulness is largely
restrict to the diagnosis of disease of the
liver and heart the case of liver disease,
large amount of GOT may be released into
the blood very high levels are observed in a
cute disease while lesser elevation are seen
in chronic liver disease
28






In case of infection hepatitis the level of GOT increase
in the first stage of the illness and very high level
during the height of the disease the level of GOT
remains very high throughout the period of illness
The level of GOT increase to 100 times the upper
adult reference limit in the following cases
-Acute vival or toxic hepatitis
-Circulatory failure with “shock” and hypoxia
-Myocardial infraction
In some cases such as cirrhosis cholestatic jaundice
and skeletal muscle disease after trauma or surgery
such as cardiac surgery the level GOT moderate
increase
29



Some chemical such us chlorine containing
organic compounds are toxic to the liver
Carbon tetra chloride is a hepatotoxin
chloroform less toxic
All these chemicals may causes damage to
the liver
30






Infectious mononucleosis:
It is a virus disease and it is quite common
among young adults
The most characteristic feature of the disease
is (sore throat)
With enlarged lymph nodes in the neck and
fever and jaundice Diagnosis.
GOT levels are elevated in 80% of the patient
.the degree of elevation is less than in
infectious or toxic hepatitis
31





Glutamic pyruvic transaminase GPT
Alanine +glutamate
alanine +αketoglutamate
This enzyme transfer the amino group of
alanine into α–ketoglutarate to form Glutamic
acids
ALT is present in highest concentration in the
liver and to a lesser extent in kidney skeletal
muscle and heart .the level of ALT in serum
occurs only in disease of the liver
GPT is measured conjugated with GOT to
determine the source of GOT is the liver or the
heart
32


In case of infection hepatitis large amount
of infectious hepatitis large amount of ALT
and AST are released into blood circulation
especially in sever acute hepatitis
GPT (ALT) level is usually equal to or slightly
highest than GOT (AST) level
33






Some of the liver disease which produces ALT (GPT)
is
1/ obstructive jaundice
When the out flow of bile from the liver into the
duodenum is blocked the level of GOT and GPT are
moderately increased
The level of GOT in this case are if about the same
level after a myocardial infract (coronary or heart
attack) so an associated rise in GPT (ALT) may help to
differentiate these two conditions
Cirrhosis and other liver disease
In case of cirrhosis, the level of the ALT may be
normal or up twice the upper adult reference limit .so
it is elevated to a lesser extent than GOT.
34






In some cases the ration of GOT / GPT is
used to diagnosing the nature of the liver
disease :
In acute hepatitis the ratio is 1 or less
Cirrhosis the ratio is usually about 2-5
In case of myocardial infraction GPT (ALT) is
not elevated ordinarily Abnormal
ALT level would confirm the hypothesis that
an elevated GOT is due to cardiac disease.
Slightly elevation of ALT may occur if the
infraction of ALT may occur if the infraction
destroys a very large volume of heart
muscle
35




Alkaline phosphatase (ALP)
ALP is present in most of tissues but is used
most often in the clinical diagnosis of bone
and liver disease
ALP synthesis by cells lining the bile canaliculi
In liver disease the activity of ALP increase
due to the result of increased synthesis of the
enzyme by cells lining the bile canaliculi
36




Alkaline phosphatase (ALP)
ALP is present in most of tissues but is used
most often in the clinical diagnosis of bone
and liver disease
ALP synthesis by cells lining the bile canaliculi
In liver disease the activity of ALP increase
due to the result of increased synthesis of the
enzyme by cells lining the bile canaliculi
37



There are a very large number of enzyme
which catalyze the hydrolysis of most organic
phosphate monoesters
Inhibition with l-phenylalanine is also of
some use in isoenzyme
Investigation intestinal and placenta alkaline
phosphatase are strongly inhibited by this
amino acids while bone and liver alkaline
phosphatase are not .
38


Since bone is a source of the enzyme bony
metastases and other diseases associated
with increased osteoblastic activity may
produce high levels of ALP in the absence of
liver disease
The enzyme is found in placenta and
pregnant women also have elevated levels
especially in the third trimester of pregnancy.
39







Gama – glutamyl transfpeptidase (GGT) or gamma GT
Function of GGT
It is an enzyme which catalyze the transfer of the
gamma glutamyl group from one peptide to another
or to amino acid .also the specific function of this
enzyme relates to the transport of aminoacids
through cell membranes (recent hypothesis)
Gamma GT occurs mainly in the cells of liver, kidney
pancreas and prostate
Plasma GGT activity is highest in men that in women
GGt is measured in serum
Causes of raised plasma GGT activity
40








Indication of enzyme synthesis without damage
by drugs or alcohol anticonvulsants or phenytion.
Disease of the liver such as:
Those associated with obstruction of the bile
flow
Obstruction of the bile flow may be due to
disease of the duct it self or of the liver cell or of
adjacent organs
These include inflammation of the walls of bile
duct (cholangitis)
Inflammation of the gall bladder (cholecystitis )
Precipitation of bile within the smallest duct
(cholestasis) in case of vival hepatitis.
In case of gall stones witch is blocked in large
duct (due to precipitated by cholesterol or
bilirubin)
41







Tumors with or outside liver, which compress and
block the duct (such as spread of cancer from other
organs to the liver or tumor of the biliary duct
themselves or cancer of the pancreas
The highest level have been seen in cancer of the bile
duct at the point where it enters the wall of the small
intestine this disease lead to elevation of both GGT
and alkaline phosphatase
Hepatocellular damage such us that due to infectious
hepatitis (measurement of plasma transaminase
activity is a more sensitive indicator of such
conditions)
Very high plasma GGT activities out of proportion to
those of the transaminase may be due to:
1/ induction by anticonvulsant drugs or by chronic
alcohol intake
2/ alcoholic hepatitis
3/ cholestatic liver diseases
42







Tumors with or outside liver, which compress and
block the duct (such as spread of cancer from other
organs to the liver or tumor of the biliary duct
themselves or cancer of the pancreas
The highest level have been seen in cancer of the bile
duct at the point where it enters the wall of the small
intestine this disease lead to elevation of both GGT and
alkaline phosphatase
Hepatocellular damage such us that due to infectious
hepatitis (measurement of plasma transaminase activity
is a more sensitive indicator of such conditions)
Very high plasma GGT activities out of proportion to
those of the transaminase may be due to:
1/ induction by anticonvulsant drugs or by chronic
alcohol intake
2/ alcoholic hepatitis
3/ cholestatic liver diseases
43



It required pyridoxal phosphate, a member of
the vitamin B6 groups, as coenzyme, the
letter acting as the carrier of the –NH group.
Transaminase are widely distributed in the
body. Only L-amino acids can undergo
transamination.
Lysine, praline, hydrosy prolone an threonine
can not undergo transamination
44