PEMERIKSAAN LABORATORIUMFAAL HATI

Oleh : dr. Diah Hermayanti, SpPK

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ANATOMI HEPAR

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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]

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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).

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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

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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.

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OTHER FUNCTIONS

The liver stores a multitude of substancesglucose (in the form of glycogen), vitamin A (1–2 years' supply),

vitamin D (1–4 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

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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).

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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.

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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

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ENSIM – ENSIM HATI

Penyakit hatikadar 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 dilakukanuntuk skrining

>>>

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AMINOTRANSFERASEAST / SGOT ensim mitokondrial & sitoplasmik

distribusi : jantung, hati, otot skeletal, ginjalALT / SGPT

ensim 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 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

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JAUNDIS / IKTERIK

Tanda 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 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 :

HepatitisCholestasis (intahepatik)

- Dubin-Johnson & Rotor syndromes - Obat (estradiol)

Penurunan drainase :- Obstruksi ekstrahepatik:

batu strikturcarcinoma atresia

- Sclerosing cholangitis- Obstruksi intrahepatik :

obat primary biliary cirrhosisgranuloma bile duct paucitytumor

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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)

Indikator keparahan & kolestasis

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HEPATITIS AKUT

Aktivitas transaminase >>>, meski belum tampak ikterik

tingkat kerusakan sel rendah perluasan kerusakan sel besar

Kenaikan SGPT > SGOTRasio De Ritis SGOT / SGPT < 1

Minggu I transaminase > sampai SGPT 1200 u/l SGOT 700 u/l

Minggu II & III bila tidak ada komplikasi transaminaseturun kembali

bila ada kolestasis : GGT, ALP >>>

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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

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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

• 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

Assembley

Assembley

NU

CLE

US

• 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 CycleLife Cycle

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MONTHS

0 1 2 3 4 5 6 7 8

Anti-HBc

Anti-HBs

Anti-HBe

HBsAg

HBeAg

REL

ATI

VE C

ON

CEN

TRA

TIO

NThe 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.

DiagnosisDiagnosis

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DiagnosisDiagnosis

Presenceof HBsAg

Presence ofAnti-HBs

Presence ofAnti-HBc

Interpretation

Acute Infection

or

Acute or Chronicinfection candifferentiate bytesting for IgM anti-HBc

Previous HBVinfection

Could be results ofvaccination.Validate by retestinganti-HBs and anti-HBc reactivity

Liver toxicity is dueto some other agentother than HBV

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0 4 8 12 16 20 24 28 32 36

HBsAg

Total anti-HBc

anti-HBsIgM anti-HBc

52 100

Tit

er

Weeks after Exposure

Symptoms

HBeAg anti-HBe

Infection with RecoveryInfection with Recovery

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0 4 8 12 16 20 24 28 32 36 52

Tit

er

Weeks after Exposure

HBs Ag

Total anti-HBc

IgM anti-HBc

anti-HBeHBeAg

Acute (6 months)

Chronic (Years)

Progression to Chronic InfectionProgression to Chronic Infection

Years

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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

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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.

Post Hepatic SyndromePost Hepatic Syndrome

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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 CarcinomaHepatocellular Carcinoma

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HEPATITIS VIRUS C

hypervariableregion

capsid envelope

protein

protease/helicase

RNA-dependent

RNA polymerase

c22

5’

core

E1 E2 NS2 NS3

33c

NS4

c-100

NS5

3’

S t r u c t u r eS t r u c t u r e

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Symptoms

Time after Exposure

Titer

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

YearsMonths

Serological Course-HCVSerological Course-HCV

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HEPATITIS KRONIK

Inflamasi kronik dari hati yang menetap sekurangnya6 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 RitisSGOT/SGPT

Sekitar 0,8 Sekitas 2,3

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Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

Periksa :

AMONIA >>>

Kontrol managemen diet