FAAL HATI.ppt

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PEMERIKSAAN LABORATORIUM

FAAL HATI

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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

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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 (γ-glutamyltransferase) CHE ( cholinesterase)

G-LDH (LDH) (Lactic-dehydrogenase)

Pemeriksaan kombinasi beberapa ensim : dapat dilakukan untuk skrining

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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

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Penyakit hati :

Cholestasis : menstimulasi hepatosit mensintesa ALP Garam empedu : meningkatkan pelepasan ALP

non hati :

hamil, anak-anak, penyakit tulang, tumor yg memproduksi ALP

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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

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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 & δ bilirubin  bilirubin indirek (unconjugated) = total - direk

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KLASIFIKASI HIPERBILIRUBINEMIA INDIREK /UNCONJUGATED

Produksi dari heme >>> : Penurunan pengangkutan ke hati :

- hemolisis - congestive heart failure

- eritropoisis inefektif - portacaval shunt

Penurunan Uptake membran : Penurunan penyimpanan di sel : - 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 ?

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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

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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 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)

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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

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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,

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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

• The infectious virion,

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

• Contains all the HBV

surface proteins as well as the HBV core protein, HBV genome and HBV's DNA polymerase. Core Protein (HBc) DNA DNA Polymerase Surface Protein (HBs)

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mRNA mRNA Assemble y Assemble y

NUCLEUS

• 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. Life Cycle

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21 MONTH S 0 1 2 3 4 5 6 7 8

Anti-HBc

Anti-HBs

Anti-HBe

HBsAg

HBeA

g

RE LA TIVE CONC EN TR ATION

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

of HBsAg Presence ofAnti-HBs Presence ofAnti-HBc Interpretation

   Acute Infection

 or  

Acute or Chronic infection can

differentiate by

testing for IgM anti-HBc    Previous HBV_infection    Could be results of vaccination. Validate by retesting HBs and anti-HBc reactivity

  

Liver toxicity is due to some other agent other than HBV

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23 0 4 8 ₁₂ ₁₆ ₂₀ 24 28 32 ₃₆ HBsAg Total anti-HBc anti-HBs IgM anti-HBc 52 100 T iter

Weeks after Exposure

Symptoms

HBeAg anti-HBe

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0 4 8 ₁₂ ₁₆ ₂₀ ₂₄ ₂₈ ₃₂ ₃₆ ₅₂

T

iter

Weeks after Exposure

HBs Ag Total anti-HBc IgM anti-HBc anti-HBe HBeAg Acute (6 months) Chronic (Years)

Progression to Chronic Infection

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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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 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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27  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

hypervariable region capsid envelop e protein protease/helica se RNA-dependent RNA polymerase c22 5’ cor e E1 E2 NS2 NS3 33c NS4 c-100 NS5 3’ S t r u c t u r e

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29 Symptoms Time after Exposure T iter anti-HCV ALT Normal 0 1 2 3 4 5 6 1 2 3 4 Years Months Serological Course-HCV

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HEPATITIS KRONIK

Inflamasi kronik dari hati yang menetap sekurangnya 6 bulan

Pola ensim :

Parameter Hepatitis kronik Sirosis

SGOT 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

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Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

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