PEMERIKSAAN LABORATORIUMFAAL HATIOleh : 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]

*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 synthesisLipogenesis, 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 is a glycoprotein hormone that regulates the production of platelets by the bone marrow

*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.

*OTHER FUNCTIONS

The liver stores a multitude of substancesglucose (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 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).

*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 the extent of known liver damage, and

(4) follow the response to treatment.

*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>>>

*TES SKRINING PENYAKIT HATI

PENYAKITPEMERIKSAANCuriga hepatitis virusSGPT, SGPTCuriga kelainan hati krn alkoholGGTCuriga perlemakan hatiSGPT, CHECuriga hepatitis kronikSGOT, CHECuriga jaundis obstruktifSGPT, GLDH, ALPCuriga tumor hatiSGOT, GLDH, GGT

*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

*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 PEMBEKUAN DARAHHati mensintesa Faktor pembekuan darah :I, II, V, VII, IX, X

F. II , VII, X diaktifkan oleh ensim yg tergantung Vit. K

Dekompensasi hati menyebabkan pemanjanganSemua tes pembekuan darah :

aPTTactivated partial thromboplastin time( Pembekuan darah jalur intrinsik)

PPTplasma prothrombin time( Pembekuan darah jalur ekstrinsik)

*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

*ALGORITME PENGGUNAAN HASIL TES FUNGSI HATISGOT > 3x URLSGOT < 3x URLALP < 2x URLALP > 3x URLPenyakit hepatoseluler Penyakit kolestatikAlbuminalbuminalbuminalbuminNormalturunnormalturun

HepatitisHepatitis KolestasisKolestasisAkutkronik akutkronikUSG atau Percutaneous cholangiographyKolestasis KolestasisIntrahepatikekstrahepatik

*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

*

FAKTORABCDEGTYPERNADNARNAPARTIALRNARNAINCUBATION15-50 days30-15015-16030-15020-40?TRANSMISSION:FECAL-ORALyesnominnoyesNoHOUSEHOLDyesminminyesyesNoVERTICALnoyesminyesnoYesBLOODrareyesyesyes?YesSEXUALnoyesminyes? YesDIAGNOSISAnti HAV,IgMHBsAg, PCR, Anti HBc IgMAnti HCV, PCRAnti HDVAnti HEVAnti HGVCARRIER STATENoyesyesyesyesYesCHRONIC Hpttsno10%80%yesnoNoLIVER CaNo yesyesnonoNoPREVENTIONVACCINEyesyesnoYes*noNoIgyesyesnoYes*noNoINTERFERON?50%20-45%yes?yes

*(*) vaksinasi & imunisasi pasif HB V melindungi juga untuk infeksi HDV

*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

(

(

(

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 anti-HBs and anti-HBc reactivity

(

(

(

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 >>>

Kontrol managemen diet

*PENYEBAB HEPATITIS KRONIK & STRATEGI DIAGNOSISPCR :polymerase chain reaction; ANA ; antinuclear antibody;ASTHMA : anti smooth muscle antibody; LKM1 : anti Liver kidney Microsomal antibody-1; AT : antytripsisn

PENYEBABDIAGNOSISHepatitis BRiwayat, HBsAg, anti HBs, anti HBc, HBV-DNAHepatitis CAnti HCV, HCV RNA dg PCRAutoimmune type 1ANA, ASTHMAAutoimmune type 2SLA, Anti LKM1Wilsons diseaseCeruloplasminObat Riwayat -1 antitrypsin deficiency-1 AT phenotypeidiopatikBopsi hati, petanda-petanda negatif

*HEPATOCELLULAR CARCINOMA (HCC)Penyebab kematian terbanyak oleh kanker

Terbanyak didahului oleh sirosis

Gejala klinik :sirosis kemudian berkembang adanya right upper quadrant painfever, malaise, anorexia, anemia,jaundismasa di right upper quadrant ascites

Laboratorium :ALP >>>AFP (-feto protein) >>>