PEMERIKSAAN LABORATORIUMFAAL HATI*

*ANATOMI HEPAR

*Pemeriksaan Laboratoriumuntuk penyakit hati, bertujuan :

1. Skrining2. Diagnosis3. Monitoring4. Prognosis

Faal Hati :1. Fungsi ekskresi : bilirubin, bile acids2. 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 HATIPenyakit hatikadar 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 dilakukanuntuk skrining>>>

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*AMINOTRANSFERASEAST / SGOT ensim mitokondrial & sitoplasmik distribusi : jantung, hati, otot skeletal, ginjalALT / SGPTensim membran hepatosit & sitoplasmikdistribusi : hati, ginjal

ALKALINE PHOSPHATASE (ALP)terlibat pada transpor metabolit melewati membran seldistribusi : plasenta, ginjal, tulang, hati>>> :Penyakit hati : Cholestasis : menstimulasi hepatosit mensintesa ALPGaram empedu : meningkatkan pelepasan ALPnon hati :hamil, anak-anak, penyakit tulang, tumor yg memproduksi ALPdibedakan dg pemeriksaan GGT

*GGT (GAMMA-GLUTAMYL TRANSFERASE)ensim yg terikat pd membran hepatosit>>>> :- obat : carbamazepine, cimetidin, furosemid, heparinisotretinoin, methotrexate, oral contraceptives,phenobarbital, phenitoin, valproic acid- alkohol

*JAUNDIS / IKTERIKTanda fisik berupa warna kekuningan pada kulit & skleraAkibat deposisi pigmen empedu

Bilirubin serum > 2-3 mg/dl

Penyebab :Penyakit Hati bukan penyakit hati :- Hemolisis- gangguan metabolisme bilirubinBilirubin yg diperiksa : bilirubin total bilirubin direk : conjugated bilirubin & bilirubin bilirubin indirek (unconjugated) = total - direk

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*KLASIFIKASI HIPERBILIRUBINEMIA INDIREK/UNCONJUGATEDProduksi 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 ?

*KLASIFIKASI HIPERBILIRUBINEMIA CONJUGATEDPenurunan sekresi ke kanalikuli : - Penyakit hepatoseluler :HepatitisCholestasis (intahepatik) - Dubin-Johnson & Rotor syndromes - Obat (estradiol)

Penurunan drainase :- Obstruksi ekstrahepatik:batustrikturcarcinomaatresia- Sclerosing cholangitis- Obstruksi intrahepatik :obatprimary biliary cirrhosisgranulomabile duct paucitytumor

*ALBUMINProtein 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

*TES FUNGSI HATI

TESFUNGSIBilirubinDiagnosa jaundis, berkorelasi dg keparahanALPDiagnosa kolestasis & space occupying lesionsFraksi bilirubinDiagnosa gangguan metabolisme & jaundice of the new bornAST (SGOT)Tes yg sensitif untuk penyakit hepatoseluler,SGOT > SGPT pada penyakit alkohol & penyakit hati kronik beratALT (SGPT)Tes yg sensitif & lebih spesifik untuk penyakit hepatoselulerAlbuminIndikator kronisitas & keparahanProthrombin time (PT)Indikator keparahan & kolestasis

*HEPATITIS AKUTAktivitas transaminase >>>, meski belum tampak ikterik

tingkat kerusakan sel rendah perluasan kerusakan sel besar

Kenaikan SGPT > SGOTRasio De Ritis SGOT / SGPT < 1

Minggu Itransaminase > sampai SGPT 1200 u/l SGOT 700 u/lMinggu II & IIIbila tidak ada komplikasi transaminaseturun kembali

bila ada kolestasis : GGT, ALP >>>

*PENYEBAB HEPATITIS AKUT

Hepatitis toksik- toksin- obat : Acetaminophen, NSAID, valproic acid, isoniazid

Hepatitis virusHepatitis A, B, C, D, E, GCytomegalovirus, Ebstein Barr virusHerpes simplex virus

*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

*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 BThe 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.

*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

*MONTHS012345678Anti-HBcAnti-HBsAnti-HBeHBsAgHBeAgRELATIVE CONCENTRATIONThe 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.Diagnosis

*Diagnosis

Presence of HBsAg

Presence of Anti-HBs

Presence of Anti-HBc

Interpretation

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Acute Infection

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Acute or Chronic infection can differentiate by testing for IgM anti-HBc

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Previous HBV infection

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Could be results of vaccination.

Validate by retesting anti-HBs and anti-HBc reactivity

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Liver toxicity is due to some other agent other than HBV

*04812162024283236HBsAgTotal anti-HBcanti-HBsIgM anti-HBc52100TiterWeeks after ExposureSymptomsHBeAganti-HBeInfection with Recovery

*0481216202428323652TiterWeeks after ExposureHBs AgTotal anti-HBcIgM anti-HBcanti-HBeHBeAgAcute (6 months)Chronic (Years)Progression to Chronic InfectionYears

*Pada pasien dg kronik HBsAgPeriksa :

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

*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. Post Hepatic Syndrome

*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.Hepatocellular Carcinoma

*HEPATITIS VIRUS Chypervariableregioncapsidenvelopeproteinprotease/helicaseRNA-dependentRNA polymerasec225coreE1E2NS2NS333cNS4c-100NS53S t r u c t u r e

*SymptomsTime after ExposureTiteranti-HCVALTNormal01234561234YearsMonthsSerological Course-HCV

*HEPATITIS KRONIKInflamasi kronik dari hati yang menetap sekurangnya6 bulan

Pola ensim :

Parameter Hepatitis kronikSirosis SGOT75 (90) U/L49 (64) U/LSGPT59 (118) U/L22 (45) U/LGLDH5,8 (10,8) U/L1,5 (3,5) U/LGGT256 U/L102 U/LCHE1843 U/L1085 U/LRasio De RitisSGOT/SGPTSekitar 0,8 Sekitas 2,3

*Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

Periksa :

AMONIA >>>

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