D4 USB

2016

ANATOMY
An adult human liver normally weighs between 1.4

1.6kg (3.13.5lb)
It is located in the right upper quadrant of the
abdominal cavity, resting just below the diaphragm
The liver lies to the right of the stomach and overlies
the gallbladder

LIVER FUNCTION :
Synthesis
Breakdown
Other Function

SYNTHESIS
A large part of amino acid synthesis
The liver performs several roles in carbohydrate metabolism:

Gluconeogenesis (the synthesis of glucose from certain

amino acids, lactate or glycerol)
Glycogenolysis (the breakdown of glycogen into glucose)
Glycogenesis (the formation of glycogen from glucose)
(muscle tissues can also do this)
The liver is responsible for the mainstay of protein
metabolism, synthesis as well as degradation
The liver also performs several roles in lipid metabolism:
Cholesterol synthesis
Lipogenesis, the production of triglycerides (fats).
The liver produces coagulation factors I (fibrinogen), II
(prothrombin), V, VII, IX, X and XI, as well as protein C,
protein S and antithrombin

In the first trimester fetus, the liver is the main site

of red blood cell production. By the 32nd week of

gestation, the bone marrow has almost completely
taken over that task. The liver produces and
excretes bile (a greenish liquid) required for
emulsifying fats. Some of the bile drains directly into
the duodenum, and some is stored in the gallbladder
The liver also produces insulin-like growth factor 1
(IGF-1), a polypeptide protein hormone that plays an
important role in childhood growth and continues to
have anabolic effects in adults
The liver is a major site of thrombopoietin production
Thrombopoietin is a glycoprotein hormone that
regulates the production of platelets by the bone
marrow

BREAKDOWN
The breakdown of insulin and other hormones
The liver breaks down hemoglobin, creating

metabolites that are added to bile as pigment

(bilirubin and biliverdin)
The liver breaks down or modifies toxic
substances (e.g., methylation) and most
medicinal products in a process called drug
metabolism
The liver converts ammonia to urea

Penguraian
Penguraian insuline dan hormon lainnya.
Hati menguraikan hemoglobin, menyusun

metabolit. yang dimasukkan ke kantung

empedu sebagai pigmen (billirubin dan
biliverdin).
Hati menguraika pembentukan senyawa toxic
(ex: methylasi) dan sebagian besar produksi
obat dalam proses yang disebut metabolisme
obat.
Hati dapat mengkonversi amonia menjadi urea.

OTHER FUNCTION
The liver stores a multitude of substances,

including glucose (in the form of glycogen), vitamin

A, vitamin D, vitamin B12, iron, and copper
The liver produces albumin, the major osmolar
component of blood serum
The liver synthesizes angiotensinogen, a hormone
that is responsible for raising the blood pressure
when activated by renin, an enzyme that is
released when the kidney senses low blood
pressure

Fungsi Lainnya
Hati menyimpan banyak kandungan zat,

termasuk glukosa (dalam bentuk glikogen),

vitamin A, Vitamin D, Vitamin B12, Besi, dan Cu.
Hati memproduksi albumin, sebagian besar
komponen osmolar pada serum darah.
Hati mensintesis angiotensinogen, hormon yang
bertanggung jawab untuk meningkatkan
tekanan darah ketika diaktikan oleh renin,
sebuah enzim yang dilepaskan ketika ginjal
merasakan penurunan tekanan darah.

LIVER DISEASE
Hepatitis, inflammation of the liver, caused mainly by

various viruses but also by some poisons (e.g. alcohol),

autoimmunity (autoimmune hepatitis) or hereditary
conditions.
Non-alcoholic fatty liver disease, a spectrum in disease,
associated with obesity and characterized as an
abundance of fat in the liver; may lead to a hepatitis
Cirrhosis is the formation of fibrous tissue in the liver,
replacing dead liver cells. The death of the liver cells
can for example be caused by viral hepatitis,
alcoholism or contact with other liver-toxic chemicals.
Cancer of the liver (primary hepatocellular carcinoma
or cholangiocarcinoma and metastatic cancers, usually
from other parts of the gastrointestinal tract)

HEPATITIS
Hepatitis means inflammation of the liver. Many

illnesses and conditions can cause inflammation of

the liver, for example, drugs, alcohol, chemicals,
and autoimmune diseases
Many viruses, for example, the virus of
mononucleosis and the cytomegalovirus can
inflame the liver
There are several hepatitis viruses; they have been
named types A, B, C, D, E, F (not confirmed), and G
The most common hepatitis viruses are types A, B,
and C

VIRAL HEPATITIS A
THE VIRION: The virus

is small, 27nm in
diameter, of the
Picornaviridae
(pico=very small) rna
family
It was taught to be an
enterovirus
It is spherical with a
protein shell which
encapsidates a single
stranded RNA of over
7000 bases

CLINICAL FEATURE
The virus is acquired by ingestion. It multiplies in

the intestine and invades the blood, liver and

saliva before any clinical manifestation of the
disease appears. This period of incubation lasts
an average of 4 (2-6) weeks
In adults, the infection is more severe with
general symptoms malaise and jaundice
Jaundice lasts for 7-10 days and the whole illness
lasts about 4 weeks
Fulminant is very rare, 0.5% of cases. Survival
with good medical treatment may be 80%

LABORATORY DIAGNOSIS
Serum IgM antibody is present

during the acute phase and

disappears in 3 months. It may
last up to 2 years in a few
cases. The test is 100%
sensitive and very specific.
Serum IgG antibody develops
after the acute illness and
persists for life, representing
immunity
Serum transaminase rise with
the acute illness and return
normal with recovery. They
seldom are higher than 1000.
There is no correlation between
their level and prognosis

HEPATITIS B
Hepatitis B virus (HBV) is a member of the

Hepadnavirus family
The virus particle, (virion) consists of an
outer lipid envelope and an icosahedral
nucleocapsid core composed of protein
The nucleocapsid encloses the viral DNA
and a DNA polymerase that has reverse
transcriptase activity
The outer envelope contains embedded
proteins which are involved in viral
binding of, and entry into, susceptible
cells
The virus is one of the smallest enveloped
animal viruses with a virion diameter of
42nm, but pleomorphic forms exist,
including filamentous and spherical bodies
lacking a core
These particles are not infectious and are
composed of the lipid and protein that
forms part of the surface of the virion,
which is called the surface antigen
(HBsAg), and is produced in excess during
the life cycle of the virus.[

TRANSMISSION
Hepatitis B can spread by :
Sexual contact
The transfer of blood or serum through

shared needles in drug abusers

Accidental needle sticks with needles
contaminated with infected blood
Blood transfusions
Hemodialysis, and
By infected mothers to their newborns
The infection also can be spread by
tattooing, body piercing, and sharing
razors and toothbrushes (if there is
contamination with infected blood)

PENULARAN
Hepatitis B dapat ditularkan melalui:
Hubungan seksual
darah atau serum melalui jarum suntuk dalam
penyalahgunaan obat.
kecelakaan jarum suntik dengan jarum yang telah
terkontaminasi oleh infeksi darah.
Transfusi darah.
Hemodialysis, dan
Infeksi oleh ibu melalui keturunannya.
Infeksi dapat juga disebarkan melalui pembuatan tato,
tindik, dan penggunaan bersama pisau cukur dan sikat gigi.
(jika terdapat kontaminasi oleh darah yang terinfeksi).

PATHOGENESIS

LABORATORY DIAGNOSIS

LABORATORY DIAGNOSIS

HEPATITIS C

HEPATITIS C
The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped,

single-stranded, positive sense RNA virus

It is the only known member of the hepacivirus genus in the
family Flaviviridae
There are six major genotypes of the hepatitis C virus, which are
indicated numerically (e.g., genotype 1, genotype 2, etc.)
The genome consists of 5 and 3 untranslated regions (5UTR and
3XR) that have little sequence variation among all genotypes and
are important for translation of viral proteins and replication of the
virus
The HCV structural proteins comprise the core protein and the two
envelope glycoproteins E1 and E2
The nonstructural proteins, including proteases (NS2/3 and NS3),
helicase (an enzyme that unwinds double-stranded nucleic acid)
(NS3), and RNA-dependent RNA polymerase (NS5B), perform
various functions essential for the viral life cycle

Hepatitis C
Hepatitis C virus (HCV) berukuran kecil (diameter 50 nm), terbungkus,

tunggal, positiv sebagai RNA virus.

Virus ini hanya dikenal sebagai anggota dari genus hepacivirus dalam
family (flaviviridae).
Terdapat 6 genotipe virus hepatitis C, yang teridentifikasi (sebagai contoh:
genotipe 1, genotipe 2, dst.).
Genom terdiri dari 5 dan 3 yang tidak ditranslasikan dalam wilayah
(5UTR dan 3XR) yang memiliki sedikit variasi squencing untuk semua
genotipe dan penting untuk translasi oleh protein virus dan replikasi virus.
HCV memiliki protein struktural yang sesuai dengan inti protein dan dua
pembungkus glikoprotein E1 dan E2.
Protein non struktural, termasuk proteases (NS2/3 dan NS3), helicase
(sebuah enzim yang tidak melepaskan dobel strended asam nukleat).
(NS3), dan RNA- bergantung pada RNA polymerase (NS5B), menunjukkan
sejumlah fungsi pokok untuk siklus hidup virus.

TRANSMISSION
Vertical transmission refers to the transmission
of a communicable disease from an infected
mother to her child during the birth process.
Mother-to-child transmission of hepatitis C has
been well described, but occurs relatively
infrequently
Transmission occurs only among women who
are HCV RNA positive at the time of delivery;
the risk of transmission in this setting is
approximately 6 out of 100
Among women who are both HCV and HIV
positive at the time of delivery, the risk of
transmitting HCV is increased to approximately
25 out of 100.
The risk of vertical transmission of HCV does
not appear to be associated with method of
delivery or breastfeeding

VIRUS
Hepatitis C virus lewat jarum suntik atau

tranfusi darah yang terkontaminasi virus

barrier hepatosit replikasi virus replikasi
DNA

LIVER FUNCTION
TEST
Fungsi ekskresi : bilirubin, asam empedu
Fungsi sintesis : protein (albumin), lipid &

lipoprotein, urea, dan faktor pembekuan.

Fungsi metabolisme : amonia, karbohidrat

ALBUMIN
Albumin is a protein made specifically by the liver, and can

be measured cheaply and easily

It is the main constituent of total protein; the remaining
fraction is called globulin (including the immunoglobulins)
Albumin levels are decreased in chronic liver disease, such
as cirrhosis. It is also decreased in nephrotic syndrome,
where it is lost through the urine
Poor nutrition or states of protein catabolism may also lead
to hypoalbuminaemia
The half-life of albumin is approximately 20 days
Albumin is not considered to be an especially useful marker
of liver synthetic function; coagulation factors (see below)
are much more sensitive.

ALBUMIN
Albumin merupakan protein yang terbentuk spesial oleh hati, dan

dapat terukur dengan murah dan mudah.

Albumin memiliki unsur pokok dari keseluruhan protein;
mengandung fraksi yang disebut globulin (termasuk
immunoglobulin).
Jumlah albumin menurun pada saat penyakit hati kronis, seperti
cirrhosis. Ia juga akan menurun pada saat sindrom neprotik,
dimana akan hilang melalui urin.
Nutrisi yang buruk atau berhentinya proses katabolisme juga
menjadi penyebabhypoalbuminaemia.
Waktu paruh albumin adalah sekitar 20 hari.
Albumin tidak memiliki kegunaan khusus dalam fungsi sintetik
hati; faktor koagulasi (lihat di bawah) merupakan hal yang lebih
sensitif.

ALT/SGPT
Alanine transaminase (ALT), also called Serum

Glutamic Pyruvate Transaminase (SGPT) or

Alanine aminotransferase (ALAT) is an enzyme
present in hepatocytes (liver cells)
When a cell is damaged, it leaks this enzyme into
the blood, where it is measured.
ALT rises dramatically in acute liver damage, such
as viral hepatitis or paracetamol (acetaminophen)
overdose
Elevations are often measured in multiples of the
upper limit of normal

ALT/SGPT
ALT (Alanin Transminase), juga disebut sebagai

serum Glutamic Pyruvate Transminase (SGPT)

atau alanin amino transferase (ALAT) adalah
enzim yang terdapat di dalam hepatosit (sel hati).
Ketika sel ini rusak, sel akan merusak enzim ini
dalam darah, dimana ia terdapat didalamnya.
ALT meningkat secara cepat dalam kerusakan hati
yang parah, seperti virus hepatitis atau karena
over dosis paracetamol (acetaminophen).
Kenaikan ini akan meningkat dari batas atas
normal.

AST/SGOT
Aspartate transaminase (AST) also called Serum

Glutamic Oxaloacetic Transaminase (SGOT) or

aspartate aminotransferase (ASAT) is similar to ALT in
that it is another enzyme associated with liver
parenchymal cells
It is raised in acute liver damage, but is also present in
red blood cells, and cardiac and skeletal muscle and is
therefore not specific to the liver
The ratio of AST to ALT is sometimes useful in
differentiating between causes of liver damage
Elevated AST levels are not specific for liver damage,
and AST has also been used as a cardiac marker

AST/SGOT
Aspartat transaminase (AST) yang juga disebut Serum

Glutamik oksaloasetat Transaminase (SGOT) atau aspartate

aminotransferase (ASAT), mirip dengan ALT, yaitu enzim lain
yang teekumpul dengan sel-sel parenkim hati.
Serum ini akan meningkat ketika terjadi kerusakan hati akut.
Sel ini juga berada pada sel darah merah, dan otot jantung
dan rangka. Oleh karena itu tidak hanya spesifik untuk hati
saja.
Rasio AST untuk ALT terkadang berguna untuk membedakan
penyebab kerusakan hati.
Peningkatan kadar AST tidak spesifik untuk kerusakan hati,
dan AST juga digunakan sebagai penanda jantung.

ALKALI PHOSPHATASE
Alkaline phosphatase (ALP) is an enzyme in the

cells lining the biliary ducts of the liver

ALP levels in plasma will rise with large bile duct
obstruction, intrahepatic cholestasis or
infiltrative diseases of the liver
ALP is also present in bone and placental tissue,
so it is higher in growing children (as their bones
are being remodelled) and elderly patients with
Paget's disease

ALKALI PHOSPATASE
Alkali fosfatase (ALP) adalah enzim dalam sel-sel

yang melapisi saluran empedu pada hati.

kadar ALP dalam plasma akan meningkat sesuai
dengan besarnya obstruksi saluran empedu,
kolestasis intrahepatik atau penyakit infiltratif
hati.
ALP juga terdapat di dalam tulang dan jaringan
plasenta, sehingga enzim ini lebih banya pada
pertumbuhan anak-anak (selama tulang mereka
masih dalam tahap perkembangan) dan pasien
orang tua dengan penyakit Paget.

TES FUNGSI HATI

Enzim yang dilepaskan dari sel yang
sakit
AST/ GOT : mitokondria dan
sitoplasma
ALT/ GPT : sitoplasma
ALP : sinusoid & endotelium vena
sentral & perifer
GGT : saluran empedu dan epitel
kandung empedu

ENZIM-ENZIM HATI
ALKALI PHOSPHATASE/ ALP
Terdapat di hati (hepatobilier), tulang
(osteoblat), tubulus ginjal, epitel usus, dan
plasenta
Half life 3 7 hari
GAMMA GLUTAMYL TRANSFERASE/GGT
Terdapat di sel hati, saluran empedu,
ginjal, usus dan pankreas, prostat
Half life 3 4 hari
Meningkat pada alkoholik, obese, terapi
acetaminofen dosis tinggi

ENZIM-ENZIM HATI
LACTATE DEHYDROGENASE/ LDH
LD 1 & 2 terutama di otot jantung, ginjal dan
eritrosit
LD 4 & 5 terutama di hati dan otot skelet
Half life 8 12 jam
5-NUCLEO TIDASE/ 5-NT
Terdapat di selaput sinusoid dan saluran bilier
Menguatkan peningkatan ALP karena
gangguan hati

ENZIM-ENZIM HATI
CHE
CHE/ pseudo-CHE terdapat di serum,
jantung, bagian putih otak (white matter),
pankreas dan hati
Half life 8 10 hari
AcCHE/ true-CHE terdapat di sel darah
merah, paru-paru, limpa, sel saraf, sinaps
& motor end plate dan bagian abu-abu
dari otaK (grey matter)

BILIRUBIN
Erythrocytes (red blood cells) generated in the bone

marrow are disposed of in the spleen when they get

old or damaged
This releases hemoglobin, which is broken down to
heme as the globin parts are turned into amino
acids
The heme is then turned into unconjugated bilirubin
in the reticuloendothelial cells of the spleen
This unconjugated bilirubin is not soluble in water, it
is then bound to albumin and sent to the liver
In the liver it is conjugated with glucuronic acid by
the enzyme Glucuronosyltransferase, making it
soluble in water

Bilirubin
Eritrosit (sel darah merah) yang dihasilkan oleh sumsum

tulang belakang akan dibuang di limpa ketika mereka telah

menjadi tua atau rusak.
Ini akan melepaskan hemoglobin, yang dipecah ke heme
sebagai bagian globin yang berubah menjadi asam amino.
heme ini kemudian berubah menjadi bilirubin tak terkonjugasi
dalam sel retikuloendotelial limpa.
bilirubin tak terkonjugasi ini tidak larut dalam air, yang
kemudian terikat oleh albumin dan dikirim ke hati.
Dalam hati ia akan terkonjugasi dengan asam glukuronat oleh
enzim glusuronosiltransferase, sehingga membuatnya larut
dalam air.

BILIRUBIN
Much of it goes into the bile and thus out into the

small intestine
Some of the conjugated bilirubin remains in the
large intestine and is metabolised by colonic
bacteria to urobilinogen, which is further
metabolized to stercobilinogen, and finally oxidised
to stercobilin
This stercobilin gives feces its brown color
Some of the urobilinogen is reabsorbed and excreted
in the urine along with an oxidized form, urobilin

BILIRUBIN
Banyak dari bilirubin yang masuk ke empedu dan

keluar melalui usus kecil.

Beberapa bilirubin terkonjugasi akan tetap berada
dalam usus besar dan dimetabolisme oleh bakteri
kolon menjadi urobilinogen, yang selanjutnya
dimetabolisme untuk sterkobilinogen, dan akhirnya
dioksidasi menjadi sterkobilin.
sterkobilin ini yang memberikan warna coklat pada
kotoran.
Beberapa urobilinogen diserap dan diekskresikan ke
dalam urin bersama dengan bentuk yang teroksidasi,
yaitu urobilin.

RAPID TEST

MICROTITER PLATE ELISA

SANDWICH ELISA

KOMPETITIVE ELISA

INDIRECT ELISA

DNA PCR

REAL TIME PCR

RNA PCR

REVERSE
TRANSCRIPTASE PCR

REVERSE
TRANSCRIPTASE PCR

RADIOIMMUNOASSAY
(RIA)