Faal Hati 3j1b6j

PEMERIKSAAN LABORATORIUM FAAL HATI

Oleh : dr.Aulia Syavitri D.

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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 synthesis Lipogenesis, the production of triglycerides (fats). 4

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 substances glucose (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 7

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 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

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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 11

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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 >>> : 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 14

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 & 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 >>> : - hemolisis - eritropoisis inefektif

Penurunan pengangkutan ke hati : - congestive heart failure - portacaval shunt

Penurunan Uptake membran : - inhibisi kompetitif (obat) - Gilbert syndrome - sepsis - fasting

Penurunan penyimpanan di sel : - inhibisi kompetitif - febris

Penurunan biotransformasi (konjugasi) : - neonatal jaundice (fisiologik) - inhibisi (obat) - herediter (Crigler Najjar) - disfungsi hepatoseluler - Gilberst syndrome ? 18

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 19

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) 20

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 > 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 DNA 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 27

Life Cycle

mRNA

Assemble y Assemble y

NUCLEUS

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

mRNA

• 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.

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Diagnosis

RELATIVE CONCENTRATION

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

Anti-HBc HBsAg

Anti-HBs

Anti-HBe

HBeA g 0

1

2

3

4

5

6

7

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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.

MONTH S

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Diagnosis Presence Presence of of HBsAg Anti-HBs  

Presence of Anti-HBc 



 or 





















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

Titer

Total anti-HBc

IgM anti-HBc

HBsAg

0

4

8

12

16

20

24

28

32

anti-HBs

36

52

100

Weeks after Exposure 31

Progression to Chronic Infection Chronic (Years)

Acute (6 months)

HBeAg

anti-HBe

Titer

HBs Ag

Total anti-HBc

IgM anti-HBc

0

4

8

12 16 Weeks after Exposure

20

24

28

32

36

52

Years 32

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

protease/helica se 33c

RNAdependent

RNA polymerase

c-100 3’

5’ cor E1 e

E2

NS2

NS3

NS4

NS5

hypervariable region 36

Serological Course-HCV

antiHCV

Titer

Symptoms

ALT

Normal 0 Time after Exposure

1

2

3 Months

4

5

6

1

2

3

4

Years

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HEPATITIS KRONIK Inflamasi kronik dari hati yang menetap sekurangnya 6 bulan Pola ensim : Parameter SGOT

Hepatitis kronik

Sirosis

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

Sekitar 0,8

Sekitas 2,3

Rasio De Ritis SGOT/SGPT

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Pada sirosis dg hipertensi portal & gastrointestinal hemorrhage

Periksa : AMONIA >>>

Kontrol managemen diet

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