PEMERIKSAAN LABORATORIUM FAAL HATI

ANATOMI HEPAR

Pemeriksaan Laboratorium untuk penyakit hati, bertujuan :

1. Skrining 2. Diagnosis 3. Monitoring 4. 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

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 dilakukan untuk skrining

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 membran sel distribusi : plasenta, ginjal, tulang, hati >>> : Penyakit hati : Cholestasis : menstimulasi hepatosit mensintesa ALP Garam empedu : meningkatkan pelepasan ALP non hati : hamil, anak-anak, penyakit tulang, tumor yg memproduksi ALP dibedakan dg pemeriksaan GGT
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GGT (GAMMA-GLUTAMYL TRANSFERASE) ensim yg terikat pd membran hepatosit >>>> : - obat : carbamazepine, cimetidin, furosemid, heparin isotretinoin, methotrexate, oral contraceptives, phenobarbital, phenitoin, valproic acid - alkohol

JAUNDIS / IKTERIK
Tanda fisik berupa warna kekuningan pada kulit & sklera 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 & bilirubin bilirubin indirek (unconjugated) = total - direk

KLASIFIKASI HIPERBILIRUBINEMIA INDIREK /UNCONJUGATED Produksi dari heme >>> : - hemolisis - eritropoisis inefektif Penurunan Uptake membran : - inhibisi kompetitif (obat) - Gilbert syndrome - sepsis - fasting Penurunan pengangkutan ke hati : - congestive heart failure - portacaval shunt Penurunan penyimpanan di sel : - inhibisi kompetitif - febris

Penurunan biotransformasi (konjugasi) : - neonatal jaundice (fisiologik) - inhibisi (obat) - herediter (Crigler Najjar) - disfungsi hepatoseluler - Gilberst syndrome ?
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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
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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, protein losing entropathy) - albumin turn over >> (catabolic state, glucocrticoid) - penurunan protein intake (malnutrisi) - PENYAKIT HATI Pada Hepatitis kronik yg progresif menjadi cirrhosis Albumin << (petanda dekompensasi & prognosis)
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TES FUNGSI HATI

TES FUNGSI

Bilirubin ALP
Fraksi bilirubin AST (SGOT)

Diagnosa jaundis, berkorelasi dg keparahan Diagnosa kolestasis & space occupying lesions
Diagnosa gangguan metabolisme & jaundice of the new born Tes yg sensitif untuk penyakit hepatoseluler, SGOT > SGPT pada penyakit alkohol & penyakit hati kronik berat Tes yg sensitif & lebih spesifik untuk penyakit hepatoseluler Indikator kronisitas & keparahan Indikator keparahan & kolestasis

ALT (SGPT) Albumin Prothrombin time (PT)

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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 >>>

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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

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HEPATITIS A
Infectious disease caused by Hepatitis A virus transmitted by the fecal-oral route via contaminated food or drinking water the incubation period, is between two and six weeks and the average incubation period is 28 days Hepatitis A does not have a chronic stage, is not progressive, and does not cause permanent liver damage

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Virology
The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a protein shell.[8] There is only one serotype of the virus, but multiple genotypes exist

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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

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Life Cycle

Replication of the HBV genome occurs within the nucleus of an infected cell.
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.

mRNA

Assemble y Assemble y

NUCLEUS
mRNA

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Diagnosis

RELATIVE CONCENTRATION

The most sensitive and specific methods used are RIA and ELISA.

Anti-HBc

HBsAg
HBeA g

Anti-HBs

Anti-HBe
5 6 7 8 MONTH S

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.

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Diagnosis
Presence Presence of of HBsAg Anti-HBs or Presence of Anti-HBc 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

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Infection with Recovery

Symptoms HBeAg anti-HBe

Total anti-HBc
Titer

HBsAg

IgM anti-HBc

anti-HBs

12

16

20

24

28

32

36

52

100
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Weeks after Exposure

Progression to Chronic Infection

Acute (6 months) Chronic (Years) HBeAg anti-HBe

HBs Ag Titer

Total anti-HBc

IgM anti-HBc

12 16 Weeks after Exposure

20

24

28

32

36

52

Years

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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

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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.

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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.

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HEPATITIS VIRUS C
Structure

capsid envelop e protein c22 5 cor E1 e E2 NS2

protease/helica se 33c

RNAdependent c-100

RNA polymerase

3
NS3 NS4 NS5

hypervariable region
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Serological Course-HCV

Symptoms

antiHCV

Titer

ALT

Normal 0
Time after Exposure

3
Months

3
Years

4
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HEPATITIS KRONIK
Inflamasi kronik dari hati yang menetap sekurangnya 6 bulan Pola ensim :
Parameter SGOT SGPT GLDH GGT CHE Rasio De Ritis SGOT/SGPT Hepatitis kronik 75 (90) U/L 59 (118) U/L 5,8 (10,8) U/L 256 U/L 1843 U/L Sekitar 0,8 Sirosis 49 (64) U/L 22 (45) U/L 1,5 (3,5) U/L 102 U/L 1085 U/L Sekitas 2,3

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Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

Periksa : AMONIA >>>

Kontrol managemen diet

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