PEMERIKSAAN

LABORATORIUM
FAAL HATI

Oleh : dr. Diah Hermayanti, SpPK

ANATOMI
HEPAR

This organ plays a major role in

metabolism and

has a number of functions in the body :

glycogen storage,
decomposition of red blood cells,
plasma protein synthesis,
hormone production, and
detoxification.
It produces bile, an alkaline compound (which
aids in digestion,
via the emulsification of lipids.
synthesis and breakdown of small and complex
molecules
(many of which are necessary for normal vital
functions.[2]
3

SYNTHESIS FUNCTION
amino acid synthesis
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)
protein metabolism, synthesis as well as
degradation
several roles in lipid metabolism:
Cholesterol synthesis
Lipogenesis, the production of triglycerides
(fats).

Cont.

produces coagulation factors I (fibrinogen), II (prothrombin)

V, VII,
IX, X and XI, as well as protein C, protein S and antithrombin
produces and excretes bile (a greenish liquid) required for
emulsifying fats.

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)

a major site of thrombopoietin production. (thrombopoietin

a glycoprotein
hormone that regulates the production o
platelets by the bone marrow
5

BREAKDOWN FUNCTION
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
(eg. methylation) and most medicinal products in a
process called drug metabolism. This sometimes
results in toxication, when the metabolite is more
toxic than its precursor. Preferably, the toxins are
conjugated to avail excretion in bile or urine.
The liver converts ammonia to urea.
6

OTHER FUNCTIONS
The liver stores a multitude of substances
glucose (in the form of glycogen),
vitamin A (12 years' supply),
vitamin D (14 months' supply),
vitamin B12,
iron, and copper.
The liver is responsible for immunological effects- the
reticuloendothelial system of the liver contains many
immunologically active cells, acting as a 'sieve' for
antigens carried to it via the portal system.
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, a kidney enzyme that is released when the
7
juxtaglomerular apparatus senses low blood pressur

LIVER FUNCTION TESTS (LFTs or

LFs)
which include liver enzymes, are groups of clinical
biochemistry laboratory blood assays designed to
give information about the state of a patient's
liver.
Some tests are associated with :
functionality (eg. albumin);
cellular integrity (eg. transaminase)
conditions linked to the biliary tract
(gamma-glutamyl transferase and alkaline
phosphatase).
8

Several biochemical tests are useful in

the evaluation and management of patients with
hepatic dysfunction.
These tests can be used to :
(1) detect the presence of liver disease,
(2) distinguish among different types of
liver disorders,
(3) gauge
damage, and

the

extent

of

known

liver

(4) follow the response to treatment.

Pemeriksaan Laboratorium
untuk penyakit hati, bertujuan :
1.
2.
3.
4.

Skrining
Diagnosis
Monitoring
Prognosis

Faal Hati :
1. Fungsi ekskresi : bilirubin, bile acids
2. Fungsi sintesa
: protein, albumin, Fx
Koagulasi
Cholinesterase (CHE)
3. Fungsi metabolik
Kerusakan Hati : ensim-ensim hati (SGOT, SGPT)
Obstruksi Hati : bilirubin, ALP, GGT
Keganasan Hati : AFT
10

ENSIM ENSIM HATI

Penyakit hati
kadar serum ensim sel hati:
- sitosolik
- mitokondrial
- membran

>>>

SGOT / AST (aspartate aminotransferase)

SGPT / ALT ( alanine aminotransferase)
ALP
(akaline phosphatase)
GGT
(-glutamyltransferase)
CHE
( cholinesterase)
G-LDH (LDH) (Lactic-dehydrogenase)

Pemeriksaan kombinasi beberapa ensim : dapat dilak

untuk skrining

11

TES SKRINING PENYAKIT HATI

PENYAKIT
Curiga hepatitis virus
Curiga kelainan hati
krn alkohol

PEMERIKSAAN
SGPT, SGPT
GGT

Curiga perlemakan hati

SGPT, CHE

Curiga hepatitis kronik

SGOT, CHE

Curiga jaundis
obstruktif

SGPT, GLDH,
ALP

Curiga tumor hati

SGOT, GLDH,
GGT

12

AMINOTRANSFERASE
AST / SGOT
ensim mitokondrial & sitoplasmik
distribusi : jantung, hati, otot skeletal, ginjal
ALT / SGPT
ensim membran hepatosit & sitoplasmik
distribusi : hati, ginjal

ALKALINE PHOSPHATASE (ALP)

terlibat pada transpor metabolit melewati membra
distribusi : plasenta, ginjal, tulang, hati
>>> :
Penyakit hati :
Cholestasis : menstimulasi hepatosit mensin
Garam empedu : meningkatkan pelepasan AL
non hati :
hamil, anak-anak, penyakit tulang,
tumor yg memproduksi ALP
dibedakan dg pemeriksaan GGT
13

GGT (GAMMA-GLUTAMYL TRANSFERASE)

ensim yg terikat pd membran hepatosit
>>>> :
- obat :
carbamazepine, cimetidin,
furosemid, heparin
isotretinoin, methotrexate, oral
contraceptives,
phenobarbital, phenitoin, valproic
acid
- alkohol

14

JAUNDIS / IKTERIK

Tanda fisik berupa warna kekuningan pada kulit & skle

Akibat deposisi pigmen empedu
Bilirubin serum > 2-3 mg/dl
Penyebab :
Penyakit Hati
bukan penyakit hati :
- Hemolisis
- gangguan metabolisme bilirubin
Bilirubin yg diperiksa :
bilirubin total
bilirubin direk : conjugated bilirubin & bilirub
bilirubin indirek (unconjugated) = total - direk

15

KLASIFIKASI HIPERBILIRUBINEMIA INDIREK

/UNCONJUGATED
Produksi dari heme >>> :
- hemolisis
- eritropoisis inefektif

Penurunan pengan
- congestive heart failure
- portacaval shunt

Penurunan Uptake membran : Penurunan penyimpanan

- inhibisi kompetitif
- inhibisi kompetitif
(obat)
- febris
- Gilbert syndrome
- sepsis
- fasting
Penurunan biotransformasi (konjugasi) :
- neonatal jaundice (fisiologik)
- inhibisi (obat)
- herediter (Crigler Najjar)
- disfungsi hepatoseluler
- Gilberst syndrome ?
16

KLASIFIKASI HIPERBILIRUBINEMIA CONJUGATED

Penurunan sekresi ke kanalikuli :
- Penyakit hepatoseluler :
Hepatitis
Cholestasis (intahepatik)
- Dubin-Johnson & Rotor syndromes
- Obat (estradiol)
Penurunan drainase :
- Obstruksi ekstrahepatik:
batu
striktur
carcinoma atresia
- Sclerosing cholangitis
- Obstruksi intrahepatik :
obat
primary biliary cirrhosis
granuloma bile duct paucity
tumor
17

ALBUMIN
Protein yg disintesa terbanyak oleh hepatosit
Kecepatan produksi dipengaruhi oleh :
- suplai asam amino
- tekanan onkotik plasma
- kadar sitokon inhibitor ( IL-6)
- jumlah sel hepatosit yg berfungsi baik

Penyebab penurunan kadar albumin plasma :

- protein loss (nephrotic syndrome, burns, prote
entropathy)
- albumin turn over >> (catabolic state, glucocrt
- penurunan protein intake (malnutrisi)
- PENYAKIT HATI

Pada Hepatitis kronik yg progresif menjadi cirrhosis A

(petanda dekompensasi & prognosis)
18

TES PEMBEKUAN DARAH

Hati mensintesa Faktor pembekuan darah :
I, II, V, VII, IX, X
F. II , VII, X diaktifkan oleh ensim yg tergantung Vit. K
Dekompensasi hati menyebabkan pemanjangan
Semua tes pembekuan darah :
aPTT

activated partial thromboplastin time

( Pembekuan darah jalur intrinsik)

PPT

plasma prothrombin time

( Pembekuan darah jalur ekstrinsik)

19

TES FUNGSI HATI

TES

FUNGSI

Bilirubin

Diagnosa jaundis, berkorelasi dg

keparahan

ALP

Diagnosa kolestasis & space occupying

lesions

Fraksi
bilirubin

Diagnosa gangguan metabolisme &

jaundice of the new born

AST (SGOT)

Tes yg sensitif untuk penyakit

hepatoseluler,
SGOT > SGPT pada penyakit alkohol &
penyakit hati kronik berat

ALT (SGPT)

Tes yg sensitif & lebih spesifik untuk

penyakit hepatoseluler

Albumin

Indikator kronisitas & keparahan

Prothrombin
time (PT)

Indikator keparahan & kolestasis

20

ALGORITME PENGGUNAAN HASIL TES FUNGSI HATI

SGOT > 3x URL
ALP < 2x URL

Penyakit hepatoseluler
Albumin
Normal

albumin
turun

Hepatitis
Akut

Hepatitis
kronik

SGOT < 3x URL

ALP > 3x URL

Penyakit kolestatik
albumin
normal
Kolestasis
akut

albumin
turun
Kolestasis
kronik

USG atau
Percutaneous cholangiography
Kolestasis
Intrahepatik

Kolestasis
ekstrahepatik
21

HEPATITIS AKUT
Aktivitas transaminase >>>, meski belum tampak ikterik

tingkat kerusakan sel rendah

perluasan kerusakan sel besar

Kenaikan SGPT > SGOT

Rasio De Ritis SGOT / SGPT < 1
Minggu I

transaminase > sampai SGPT 1200 u/l

SGOT 700 u/l
Minggu II & III bila tidak ada komplikasi transaminase
turun kembali
bila ada kolestasis : GGT, ALP >>>

22

PENYEBAB HEPATITIS AKUT

Hepatitis toksik
- toksin
- obat : Acetaminophen, NSAID,
valproic acid, isoniazid
Hepatitis virus
Hepatitis A, B, C, D, E, G
Cytomegalovirus,
Ebstein Barr virus
Herpes simplex virus

23

FAKTOR

RNA

DNA

RNA

PARTIAL

RNA

RNA

15-50
days

30-150

15-160

30-150

20-40

FECALORAL

yes

no

min

no

yes

No

HOUSEHOL
D

yes

min

min

yes

yes

No

VERTICAL

no

yes

min

yes

no

Yes

BLOOD

rare

yes

yes

yes

Yes

SEXUAL

no

yes

min

yes

Yes

Anti
HAV,IgM

HBsAg,
PCR, Anti
HBc IgM

Anti HCV,
PCR

Anti HDV

Anti HEV

Anti HGV

CARRIER
STATE

No

yes

yes

yes

yes

Yes

CHRONIC
Hptts

no

10%

80%

yes

no

No

LIVER Ca

No

yes

yes

no

no

No

VACCINE

yes

yes

no

Yes*

no

No

Ig

yes

yes

no

Yes*

no

No

50%

20-45%

yes

yes

TYPE
INCUBATIO
N
TRANSMISS
ION:

DIAGNOSIS

PREVENTIO
N

INTERFERO
N

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(*) vaksinasi & imunisasi pasif HB V melindungi juga

untuk infeksi HDV

25

HEPATITIS VIRUS B
Core Protein
(HBc)

The infectious virion,

otherwise known as the
Dane Particle, is about
42nm in diameter.
DNA

Contains all the HBV

surface proteins as well as
the HBV core protein, HBV
genome and HBV's DNA
polymerase.

Surface Protein
(HBs)
DNA Polymerase
26

Life Cycle

mRNA

Assemble
y
Assemble
y

NUCLEUS

Replication of the HBV

genome occurs within the
nucleus of an infected cell.

mRNA

RNA polymerase II
transcribes the circular
HBV DNA to mRNA.
Once produced, the
genomic RNA exits the
nucleus and enters the
cytoplasm where it is been
translated to generate the
HBV reverse polymerase,
core and e proteins.

27

Diagnosis

RELATIVE CONCENTRATION

The most sensitive and

specific methods used
are RIA and ELISA.

Anti-HBc
HBsAg

Anti-HBs
Anti-HBe

HBeA
g
0

Both assays make use

of specific antibodies
against various HBV
proteins and can detect
HBsAg as low as 0.5
ng/mL and anti-HBs
antibodies at a level of
1mU/mL.

MONTH
S

28

Diagnosis

Presence Presence of
of HBsAg Anti-HBs

Presence of
Anti-HBc

or

Interpretation
Acute Infection
Acute or Chronic
infection can
differentiate by
testing for IgM antiHBc
Previous HBV
infection
Could be results of
vaccination.
Validate by retesting
anti-HBs and antiHBc reactivity
Liver toxicity is due
to some other agent
other than HBV

29

Infection with Recovery

Symptoms
HBeAg

anti-HBe

Titer

Total anti-HBc

IgM
anti-HBc

HBsAg

12

16

20

24

28

32

anti-HBs

36

52

100

Weeks after Exposure

30

Progression to Chronic Infection

Chronic
(Years)
HBeAg

Acute (6
months)

anti-HBe

Titer

HBs Ag

Total anti-HBc

IgM anti-HBc

12
16
Weeks after Exposure

20

24

28

32

36

52

Years
31

Pada pasien dg kronik HBsAg

Periksa :
HBe Ag & Hbe Ab
(menentukan status infeksi)
HBV-DNA
HBe Ag (+) arti : virus aktif bereplikasi (infeksius)
HBV-DNA aktif diproduksi
HBe Ag (+) kemudian tjd serokonversi Hbe Ab (+)
arti : HBV-DNA tidak aktif diproduksi

32

Post Hepatic Syndrome

Common features are anxiety, fatigue, failure to regain weight,

anorexia, alcohol intolerance and right upper abdominal
discomfort. The edges of the liver may be tender

Serum transaminase levels may be up to three times that of

normal.

Hepatic histology reveals only mild, residual portal zone

cellularity and fibrosis, sometimes fatty changes in the liver
cells.

33

Hepatocellular Carcinoma

Hepatocellular carcinoma is the liver cancer.

This form of the disease may develop after a long time in

individuals suffering from chronic hepatitis B infection.

The events will trigger the development of this disease form are
unknown.

34

HEPATITIS VIRUS C
Structure

capsid envelop
e
protein
c22

protease/helica
se
33c

RNAdependent

RNA polymerase

c-100
3

5
cor E1
e

E2

NS2

NS3

NS4

NS5

hypervariable
region
35

Serological Course-HCV

antiHCV

Titer

Symptoms

ALT

Normal
0
Time after
Exposure

3
Months

Years
36

HEPATITIS KRONIK
Inflamasi kronik dari hati yang menetap sekurangnya
6 bulan
Pola ensim :
Parameter
SGOT

Hepatitis kronik

Sirosis

75 (90) U/L

49 (64) U/L

SGPT

59 (118) U/L

22 (45) U/L

GLDH

5,8 (10,8) U/L

1,5 (3,5) U/L

GGT

256 U/L

102 U/L

CHE

1843 U/L

1085 U/L

Rasio De Ritis
SGOT/SGPT

Sekitar 0,8

Sekitas 2,3

37

Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

Periksa :
AMONIA >>>
Kontrol managemen diet

38

PENYEBAB HEPATITIS KRONIK & STRATEGI DIAGNOSIS

PENYEBAB

DIAGNOSIS

Hepatitis B

Riwayat, HBsAg, anti HBs,

anti HBc, HBV-DNA

Hepatitis C

Anti HCV, HCV RNA dg PCR

Autoimmune type 1

ANA, ASTHMA

Autoimmune type 2

SLA, Anti LKM1

Wilsons disease

Ceruloplasmin

Obat

Riwayat

-1 antitrypsin
deficiency

-1 AT phenotype

idiopatik

Bopsi hati, petandaPCR :polymerase chain reaction; ANApetanda

; antinuclearnegatif
antibody;
ASTHMA : anti smooth muscle antibody; LKM1 : anti Liver kidney
Microsomal antibody-1; AT : antytripsisn

39

HEPATOCELLULAR CARCINOMA (HCC)

Penyebab kematian terbanyak oleh kanker
Terbanyak didahului oleh sirosis
Gejala klinik :
sirosis kemudian berkembang adanya
right upper quadrant pain
fever, malaise, anorexia, anemia,
jaundis
masa di right upper quadrant
ascites
Laboratorium :
ALP >>>
AFP (-feto protein) >>>
40