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Laboratory Diagnosis

of the
LIVER & BILIARY TRACT
dr. Dumais A.A. Mandagie

I.

- Liver Function
- Liver Function Tests
II. - Bilirubin Metabolism
- Pathophysiology of Jaundice
III. - Laboratory Diagnosis of Liver and
Biliary Tract Disorders
IV. - Hepatitis Viruses
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Fungsi hati; tes


Metabolisme bilirubin: bagaimana bilirubin terbentuk
Diagnosis lab
Virus-virus radang hati
Fungsi Hati Tes Fungsi Hati
- Metabolisme Bilirubin
- Patofisiologi dari Penyakit kuning
- Laboratorium Diagnosis Hati dan
Gangguan Saluran empedu
- Hepatitis Virus

The Liver
Center of several metabolic processes
Blood supply from systemic circulation &
portal system
Tissue is comprised by :
parenchymal cells (60%)
Kupffer cells (RES) (30%)
vascular
bile canaliculi
supporting tissue
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Liver adalaH pusat metablisme dalam tubuh


Liver juga ini 2 sistemik : sirkulasi dan portal
sistem
Histologis:
Hepatosit
Retikuli E system Kuffter sel
Vaskular : pembuluh
Canalikuli
jaringan penunjang
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Important Role of the Liver in the


Metabolism of :
Carbohydrate
Protein
Lipid
Vitamin
Mineral
Hormone
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Funsi hati yang terpenting metabolisme


Karbohidrat
Protein
Lipid
Vitamin
Mineral
Hormon

LIVER FUNCTIONS :
Synthesis Functions :
(albumin, globulin, coagulation factors,
lipoproteins, primary bile acids)
Storage Functions :
(vitamin, minerals, glycogen and several
drugs)
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Fungsi hati
Sintesa
Albumin : sagt penting :
Globulin selain hati (protein pertahanan (-) daya
pertahana tubuh hilang
Faktor koagulasi : I XIII

Funsi penyimpanan
Vit, mineral, glikogen (glukosa) : sumber tenaga,
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Excretory Functions :
(bilirubin, bile acids, cholesterol and several
drugs)
Detoxification Functions :
(ammonia, steroid hormones, bilirubin, drugs)
Filtration Functions :
(absorbed toxins from intestines by Kupffer cells)
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Fungsi eksresi
(bilirubin, asam empedu, kolesterol dan
beberapa obat-obatan)

Penghilangan racun
(amonia, hormon steroid, bilirubin, obat-obatan)

Fungsi Filtrasi:
(racun diserap dari usus oleh sel-sel Kupfer)

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The Aims to Request Liver Function


Tests :
As screening tests
To assist establishing diagnosis, diferential
diagnosis
To assist making prognosis
To follow up the disease course &
therapeutic result
To help differentiating jaundice
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Tujuan meminta tes hati


Membantu diagnosa, DD
Membuat prognosis: meramal penyakitnya
nanti bagaimana
Mengikuti jalannya penyakit
mengikuti hasil yang diberikan
Membeda2kan berbagai ikterus

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Charactreristic :
In general most (but not all) of the liver function
tests are :
Not sensitive (large reserve capacity (80-90%) &
rapid regeneration
Not specific (extrahepatic factors)
Influence by extension of the process

Weakness or limitations
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Ciri-ciri pemeriksaan diagnosis liver


Tidak sensitif
Tidak spesifik (faktor ekstra hepatik
menggangu) Hati terganggu hanya RES
yang terganggu
Proses yang menggangu hati sendiri
bukan eluruh hati

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Attitude:
Appropriate LFT Panel :
select & combine a few
but established tests of
several functions

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sikap
Bagaimana anda bisa memilih /
mennetukan tes2 berbagai fungsi yang
sudah mapan dipake,

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Synthesis Functions Tests :


1. Serum Albumin concentration
2. Serum Protein Electrophoresis
3. Serum CHE (Cholinestrase) Enzyme
activity
4. Plasma Coagulation Factors, Prothrombin
Time and Its Response after vitamin K
injection

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Fungsi sintesis
Serum albumin: letaknya dibagian tubuh (darah)
Serum elektroforesis protein :
Elektroforesis : migrasi partikel koloid dibawah pengaruh medan listrik/ cara
pemisahan protein serum dgn cara memisahkan dgn bidang listrik

Aktifitas CHE enzim aktif


Faktor koagulasi plasma
Protombin time (PT)
Sebelum dan sesudah memasukkan vit K
Hubungan dgn vit K : pembekuan darah/ protrombin tak akan dibuat jika vit. K tdak
ada
Saluran empedu berhub dg vit K : vit K sifat larut lemak diusus supaya dapat
diabsorsi ,
Jika hati baik empedu keyok, maka langsung ke tubuh , maka protrombin yang
memanjang akan memendek
Empedu buntu, protrombin tidak ada -- maka mempengaruhi fibrinogen menjadi fibrin

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Serum Albumin Concentration :


Hepatic Synthesis Function Decreased :
Hypoalbuminemia
# more prominent in chronic process
# less sensitive
# influence by extrahepatic factors
# less specific
# less differentiating capacity
# good for prognosis
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Konsentrasi serum albumin


Fungsi hati tidak mampu membuat albumin : HipO
Albuminemia disebabkan dibuat sedikit atau dibuat
normal tpi terbuang:
Gangguan buang air kecil
lebih menonjol dalam proses kronis
kurang sensitif
dipengaruhi oleh faktor extrahepatic
kurang spesifik
kurang membedakan kapasitas
baik untuk prognosis

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Serum Protein Electrophoresis :


Protein in serum is fractionated
# Albumin
# Globulins :
# Alpha-1 Globulin
# Alpha-2 Globulin
# Beta Globulin
# Gamma Globulin
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Multiple Mieloma
Globulin sanagt tinggi

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Serum Cholinesterase (ChE) Enzyme Activity :


Activity Decreased
# Hepatocellular destruction
# Organophosphate intoxication

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Pemeriksaan enzim akif ChE


Hati keyo
2 keadaan rusaknya hati
Sel hati rusak
Penggunaan obat anti serangga

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Plasma Coagulation Factors :


Prothrombin Time (PT) and its response
after vitamin K injection :
# PT Increased in hepatocellular dysfunction &
cholestasis
# PT with vitamin K injection :
# in cholestasis PT corrected
# in hepatocellular damage PT not correcred
# Good for prognosis
# As pre-biopsy screening test
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PT Peningkatan disfungsi hepatoseluler & ch


olestasis
PT dengan suntikan vitamin K:
di kolestasis -->PT dikoreksi dalam
kerusakan hepatoseluler PT tidak correcred

Baik untuk prognosis


Sebagai tes skrining pra-biopsi
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Excretory Functions Tests :


1. Blood (Serum) Bilirubin (Total, Direct &
Indirect Bilirubins, Urinary Bilirubin,
Urobilinogen & Urobilin, Fecal
Urobilinogen, Urobilin & Stercobilin)
2. Serum Bile Acids (BA).
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Tes Fungsi eksresi


Bilirubin dan turunannya
Asam empedu
UDP ; urobilinogen diposphat

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BILE ACIDS (BA) :


BA are synthesized from cholesterol :
# In the Liver :
BA + AA (Amino Acids : glycine & taurine)
conjugated bile salt emulsify fat & activate
pancreatic lipase
# In the Ileum :
BA reabsorbed enterohepatic cycle a
small part enter systemic circulation (fasting
blood level < 6 umol/L

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DalamHatiini:
BA + AA (Asam amino: glisin & taurin) terkonjugasi garame
mpedu emulsi lemak & mengaktifkan lipase pankreas
Dalamileum:
BA diserap siklus enterohepatik sebagian kecil
memasukisirkulasi sistemik (puasa tingkat darah <6 umol / L

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BILE ACIDS (BA) :


Sensitive & Specific
Increased for hepato-biliary disorders
But
Could not differentiate hepato-cellular
damage from cholestasis
Peningkatan untuk gangguan hepatoempedu
Tapi
Tidak dapat membedakan kerusakan
hepato-selular dari cholestasis

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Detoxifying Functions Tests :


1. Blood (Serum) Ammonia Level
2. Hippuric Acid Test
Darah (serum) Tingkat Amonia
Asam Hippuric Test

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Blood Ammonia Level :


Intestinal Ammonia Urea (by the liver cells :
Urea Cycle) Excreted by kidney
Intestinal Increased due to :
Gastrointestinal hemorrhage
Dietary protein
Influenced by medication and infections

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Amonia level
Amonia usus Urea (oleh selsel hati: Urea Siklus) diekskresikan oleh
ginjal
Peningkatan usus karena:
Perdarahan gastrointestinal
Dietary protein
Dipengaruhi oleh obat dan infeksi
Jika hati teganggu, gagal hati amonia tinggi dan
ia akan koma =koma hepaticum
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Increased Blood Ammonia Level :


# Porto-Caval Shunt
# Hepatic Failure
# Hyperammonemia :
# Hepatic Encephalopathy Hepatic Coma
Porto-kava Shunt
Kegagalan hati
Hiperamonemia:
Ensefalopati hati Coma hati

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Tests For Liver Cells Integrity


Hepatocellular Enzymes Activity :
1. Increased Cytoplasmic Enzymes (ALT, AST, LDH5)
2. Increased Mitochondrial Enzymes (AST, GlDH)

Peningkatan sitoplasma Enzim (ALT, AST, LDH5)


Peningkatan Enzim mitokondria (AST, GlDH)

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Integritas tes sel hati


Ganguan enzim citoplasma
(ALT =SPOT)
Gangguan Mitokondria enzim
(AST= SPGT), GIDH

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Tests For Liver Cells Integrity


Very Sensitive :
1. More permeable or mildly destroyed cell wall
Cytoplasmic enzymes activity increased
2. Necrosis of cells Mitochondrila enzymes also increased

Lebih permeabel atau sedikit hancur dinding


sel sitoplasma aktivitas enzim meningkat
Nekrosis sel Mitochondrila enzim juga meningkat

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Tests for Cholestasis


1. Especially in extrashepatic blockage Cholestatic enzymes (GGT,
ALP & 5Nucleotidase) Increased
2. In hepatocellular destruction only mildly increased

Terutama dalam enzim penyumbatan extrashepatic Cholestatic(GGT, ALP & 5'Nucleotidase)


Meningkatnya
Dalam kehancuran hepatoseluler hanya sedikit meningkat

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Tes cholestasis
3 enzim jika meningkat nyata = org
kuning, terjadi hambatamn aliran empedu
intra hepatik

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Tests for Etiologic Factors


1. Autoantibodies (ANA, AMA, SMA)
2. Alphafetoprotein (AFP)
3. Hepatitis Viral Seromarkers

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Auto
Ana = antibodi
AMA=
SMA= antibodi otot polos

Alpha = khusus kanker hati


Hepatitis Viral =auto imun

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Alphafetoprotein (AFP)=mencari
tahu kanker hati jika >500
Normal : <15 ng/mL
1. Increased in : Acute Hepatitis, Chronic Hepatitis,
Convalescence phase of Hepatitis
2. Highly Increased in Hepatoma

Peningkatan: Hepatitis akut, hepatitis kronis, pemulihan tahapHepatitis


Sangat Peningkatan hepatoma

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Alphafetoprotein (AFP)
mencari tahu kanker hati jika >500

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Hepatitis Viral Seromarkers


HAV : Anti-HAV (Total, IgG, IgM)
HBV : HBsAg, HBeAg, Anti-HBs,
Anti-Hbe, Anti-HBc (IgG, IgM),
HBV-DNA
HCV : Anti-HCV (Total, IgM), HCV-RNA
HDV : HDAg, Anti-HDV (IgG, IgM)
HEV : Anti-HEV (Total, IgG, IgM)
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