Pemeriksaan Fungsi Hati

dr.Diah Puspita Rini, SpPK

Liver1. Biochemycal hepatocyte system:

- protein & lipoprotein synthesis

- aerob/anaerob metabolism glucose

- glycogen synthesis & breakdown

- iron & vitamin storage, drug metabolism

- synthesis & clearance of hormone

2. Hepatobiliary system: - bilirubin metabolism

3. Reticuloendothelial system:- Kupffer cells

FUNCTIONS OF THE LIVER

• Regulating blood glucose level by making glycogen, which is stored in hepatocytes.

• Synthesizing blood glucose from amino acids of lactate through gluconeogenesis.

• Converting ammonia produced from gluconeogenetic by-products and bacteria to urea

• Synthesizing plasma proteins such as albumin, globulins, clotting factors, and lipoproteins.

• Breaking down fatty acids into ketone bodies• Storing vitamins and trace metals• Affecting drug metabolism and detoxification• Secreting bile

Manfaat Tes Fungsi Hati

1. Deteksi penyebab - gangguan fungsi hati - penyakit hati 2. Derajat gangguan fungsi/penyakit hati 3. Evaluasi : Perjalanan Penyakit

Hasil terapi Prognosis

Keterbatasan TFH

1. Fungsi metabolik hati beragam

2. Kapasitas cadangan fungsi hati besar

3. Korelasi dg derajat kerusakan hati tidak linier

4. Sensitivitas thd kerusakan jar hati tidak sama

5. Spesifisitas tidak sama

→ tdk ada tes tunggal yg dpt mendeteksi seluruh penyakit hati

Macam Tes Fungsi hati1. Tes mengetahui gangguan fungsi

“Uptake” : bilirubin konjugasi : bilirubin ekskresi : bilirubin, asam empedu sintesis : albumin faktor koagulasi

kolinesterase2. Tes integritas sel : AST, ALT, LDH3. Tes kolestasis : Bilirubin, ALP, γ GT, 5’NT4. Tes etiologi

– Marker hepatitis – Tumor marker : CEA, AFP

BILIRUBIN

Conjugated bilirubin :1. Water soluble 2. Less toxic to cells 3. Can pass glomerular

filtering membrane

Not found in plasma unless

•Liver cell injury •Obstruction

Then will be found in urine

•Bilirubin dipstick: (+)

- Unconjugated bilirubin :Not water soluble Toxic to cells

–Bound to albumin making it soluble in plasma

–Transported through plasma to liver for excretion

Gangguan Metabolisme Bilirubin

• Icterus/Jaundice: keadaan yang disebabkan peningkatan bilirubin plasma – Pre hepatik: anemia hemolitik– Hepatik: kerusakan hepatoselular– Post hepatik: batu empedu, tumor pankreas

• Klinis : bila bilirubin total > 2.5mg/dl ICTERUS (JAUNDICE) bila bilirubin unconjugated > 15 mg/dl KERN ICTERUS (terutama pada bayi)

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Gangguan metabolisme bilirubin

Peningkatan Unconjugated Bilirubin

1.Peningkatan produksi: Hemolisis

2.Gangguan uptake : sindroma Gilbert’s

3. Gangguan konjugasi :

- Neonatal jaundice

enzim glukuronil-transferase belum aktif

- penyakit hati yang berat (hepatitis, sepsis)

- beberapa macam obat :

*kloramfenikol

*pregnanediol breast-milk jaundice

- defisiensi glukuronil transferase herediter

sindroma Criggler Najjar

Peningkatan Conjugated Bilirubin

• Kolestasis intra dan ekstra hepatik• Hepatitis, sirosis hepatis• Atresia bilier• Kelainan kongenital, ggn ekskresi:

- Sindroma ROTOR- Sindroma DUBIN-JOHNSON

Ciri Klinis Hemolitik Hepatoseluler Obstruktif

Warna kulit Kuning pucat Kuning muda-tua kuning

Warna urine normal Gelap Gelap

Warna feses Normal/gelap Pucat (sterkobilin ↓) Warna ≈ dempul

Pruritus - - Menetap

Bilirubin indirek ↑ ↑ ↑

Bilirubin direk N ↑ ↑

Bilirubin urine - ↑ ↑

Urobilinogen urine ↑ Sedikit meningkat ↓

Analisis Laboratorium Bilirubin

Nilai yang akurat tergantung dari pengambilan dan penanganan spesimen yang benar

Sampel tidak hemolisis (hasil akan rendah palsu karena adanya interference)

Tidak lipemia (lebih utama sampel dalam keadaan puasa)

Light sensitive (cahaya merusak bilirubin)

• BilirubinTotal : diukur dari kedua macam bilirubin (unconjugated and conjugated)

• Bilirubin Direct : hanya mengukur conjugated bilirubin

• Parameter dihitung :

Total – direct = unconjugated (indirect)

Expected Values: Adults

•Total bilirubin: 0.2 – 1.0 mg/dl

•Conjugated bilirubin: 0.0 - 0.2 mg/dl

•Unconjugated bilirubin: 0.2 – 0.8 mg/dl

•Urine bilirubin: negative

Expected Values: Infants

Total bilirubin Premature Full Term

24 hours 1 – 6 mg/dl 2 – 6 mg/dl

48 hours 6 – 8 mg/dl 6 – 7 mg/dl

3-5 days 10 – 12 mg/dl 4 – 6 mg/dl

FUNGSI SINTESIS HATI

• Sintesis – Total protein – Albumin– Protein koagulasi /faktor koagulasi

• Banyak disintesis di hati• Membutuhkan vitamin K untuk sintesisnya

– Cholinesterase

Perubahan Fraksi Protein Pada Penyakit Hati

ALBUMIN ↓· Kapasitas cadangan sintesis protein besar, bila Albumin

berarti KERUSAKAN HEPATOSIT LUAS/BERAT· Waktu Paruh albumin : cukup lama ( 20 hr )

bila albumin → kerusakan hepatosit berlangsung lama

GLOBULIN ↑

terutama globulin- respon terhadap inflamasi

- kompensasi

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FAKTOR KOAGULASI PLASMA

disintesis oleh hepatosit - kecuali faktor III,IV,VIII penyakit hati diffus gangguan sintesis faktor koagulasi. sintesis faktor II, VII, IX & X (prothrombin complex) perlu vit K. test : PPT

Dipengaruhi oleh :- peny.hepatoselular (ggn sintesis)- peny. Obstruktif (ggn absorpsi vit.K)

Protein disintesis di hati

Sintesis membutuhkan vit.K

CHOLINESTERASE (CHE)

- Penyakit hati kronis, sirosis, hepatitis akut fulminan.

- Malnutrisi.

- Keracunan insektisida (organofosfat)

AKTIVITAS , SINTESIS NORMAL

Pada hepatitis akut CHE prognosis buruk.

ENZIM• Protein intraseluler yang dikeluarkan ke

dalam sirkulasi krn adanya kematian /injury sel

• Cardiac enzymes (CK, CK-MB, LD, AST) → IMA• Pancreatic enzymes (amylase, lipase) → pankreatitis• Muscle enzymes (CK, LD, AST) → muscular dystrophy• Bone (ALP) → peny. degeneratif tulang• Liver enzymes (AST, ALT, ALP, GGT)→ peny. liver

• Fungsi: katalisator

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Hepatocyte with cell organelles(schematic representation)and localization of thediagnostically most importantenzymes etc

1. Stellate Kupffer cell2. Space of Disse3. Granular endopl. retic:ChE4. Smooth endopl. retic5. Mitochondrion: GlDH,AST6. Bile canaliculi:ALP,LAP,G-GT7. Nucleus8. Lysosomes :hydrolases9. Cytoplasm:LDH,ALAT,AST Iron

LOKASI ENZIM DALAM HEPATOSIT

ChEAST

ALP

GGT

AST,ALT,LDH

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TRANSAMINASE SERUM

SGOT : Serum Glutamic Oxaloacetic Transaminase/AST : ASpartate amino Transferase

→ liver, heart skeletal muscle, kidneys, brain, RBCs half-life 17hrs In liver 20% activity is cytosolic and 80% mitochondrial

SGPT : Serum Glutamic Pyruvic Transaminase/ALT : ALanine amino Transferase

- more specific to liver, very low concentrations in kidney and skeletal muscles.

In liver totally cytosolic

Half-life 47hrs

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AST dan ALT• Dalam sitoplasma hepatosit:

- kadar AST 1,5 – 2 x ALT• Pada hepatitis akut:

– AST > ALT– 24-48 jam: kerusakan berlanjut → ALT > AST krn

waktu paruh yg lebih panjang

• Kerusakan hati ringan: ALT ↑• Kerusakan hati berat/nekrosis : AST ↑

Medications causing elevation of aminotransferases

Acetaminophen

Amoxicillin-clavulanic acid

HMGCoA reductase inhbtrs

INH

NSAIDS

Phenytoin

Valproate

Many others

Herbs and toxins

• Herbs/alt. medicines

• Illicit drugs

• Toxins

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RASIO AST/ALT ( de RITIS )

Biasa dipakai bila ada kenaikan transaminase

tidak terlalu tinggi < 1 KERUSAKAN HATI AKUT > 1 KERUSAKAN HATI MENAHUN /

SIROSIS

• DASAR :ALT KERUSAKAN MEMBRAN.AST KERUSAKAN ORGANEL +

KERUSAKAN MEMBRAN

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RASIO AST/ALT ( rasio de RITIS )

Biasanya tidak banyak berarti, kecuali bila:

- rasio > 2 : 1 → alkoholic liver disease

- sirosis / hipertensi portal + rasio > 3:

primary billiary cirrhosis

- ALT > AST :

- viral hepatitis

- chronic active hepatitis

- cholestasis

ALP (Alkaline Phosphatase)

• Dapat ditemukan:• Liver• Tulang• Ginjal • Intestine• Placenta

• ALP liver:• Half life 3 hari• Permukaan kanalikuli → disfungsi bilier, ↑ 10x N

LDH• Terdapat di hampir semua sel• LD isoenzim menunjukkan spesifisitas

jaringan

LD-1 (HHHH) LD-2 (HHHM)

Cardiac muscle, kidney, erythrocyte

LD-4 (HMMM) LD-5 (MMMM)

Liver, skeletal muscle

Infark (± 72 jam)Peny. HemolitikSampel lisis

Peny. LiverSkeletal muscle disease

Gamma-GT• hepatocytes and biliary epithelial cells, pancreas,

renal tubules and intestine• Very sensitive but Non-specific• Raised in ANY liver discease hepatocellular or

cholestatic• Usefulness limited• Confirm hepatic source for a raised ALP• Alcohol• Isolated increase does not require any further

evaluation, suggest watch and repeat only if other LFT’s become abnormal then investigate

Causes of raised serum gammaglutamyl transferase (GGT)

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INTERPRETASI TFH

• Markers of Hepatocellular damage(Transaminases) :

- AST

- ALT• Markers of Cholestasis:

• ALP• Gamma GT• 5’ nucleotidase / 5’NT

• Bilirubin, Albumin dan Prothrombin time (INR)– Useful indicators of liver synthetic function

– In primary care when associated with liver disease abnormalities should raise concern

– Thrombocytopaenia is a sensitive indicator of liver fibrosis

Disorder Bilirubin AST/ ALT

ALP Albumin PT

Hemolysis/ Gilberts

unconj ↑ N N N N

Acute hep. cellular ds

Both elevateBilirubin

uria+

ElevateALT > AST

N / < 3 times N

N Usually N

Chronic hep.cellular. ds

Both elevateBilirubin

uria+

Elevate<300u/l

N/ <3 times N

Decrease prolonged

Disorder Bilirubin AST/ ALT

ALP Albumin PT

Alcohol hepatitis cirrhosis

Both elevate bilirubinuria +

>2 sugg >3 diag

N / <3 times N

↓ prolonged

Obs. jaundice

Both elevate Bilirubinuria+

N to mod elevate

Elevate >4 times N

N unless chronic

N / Prolonged

Infiltrative disease

N N / slight elevate

Elevate >4 times GGT,5’N

N N

S I R O S I S H A T I Definisi:Penyakit hati yang kronik dan progresif mengakibatkan destruksi dan degenerasi sel parenkim yang extensif

Terdiri dari 4 tipe: Alcoholic (Laennec’s) cirrhosis

→ Associated with alcohol abuse Postnecrotic cirrhosis

→ Complication of toxic or viral hepatitis Biliary cirrhosis

→ Associated with chronic biliary obstruction and infection

Cardiac cirrhosis → Results from longstanding severe right-sided heart failure

Manifestations of Liver Cirrhosis

Fig. 42-5

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S I R O S I S H A T I

COMPENSATED PHASE :- Gangguan fungsi minimal

ACTIVE PHASE :- Nekrosis progresif ( ALT )- Fibrosis kolestasis ( ALP , BILI )

DECOMPENSATED PHASE : - Gangguan fungsi berat

+ hipo albumin + hiperbilirubinemia GAGAL HATI

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=00_ykzmsy33SDM&tbnid=7_FLEgOAWG_-DM:&ved=0CAUQjRw&url=http://depts.washington.edu/hepstudy/definitions/&ei=CUmeUbr2FYWQrgf41IBA&bvm=bv.46865395,d.bmk&psig=AFQjCNFv7of3QZF8MZQzY9kdMxrt9O-PIg&ust=1369414274626046

SOAL KASUS• Laki-laki 48 th datang dengan keluhan nyeri perut

kanan atas dan febris naik turun selama 3 bulan. Nafsu makan dan BB↓. Dia menderita hepatitis 10 thn y.l.

Pemeriksaan fisik: sklera ikterik, hepatomegali 2 cm bac, splenomegali (+)

• Hasil Lab: Hb 9 g /dL

WBC 8000/uL

PLT 90.000/uL

ALT 120 U/L (normal < 45)

AST 200 U/L (normal < 45)

Bilirubin total 10 mg/dl (normal 0,3-1 mg/dl)

Bilirubin direk 7,8 mg/dl (normal 0-0,3 mg/dl)

HBsAg (+), HBeAg (+), anti-HBc IgM (+)

a. Apa diagnosis pasien ini?

b. Ikterus tipe apa yang dialami oleh pasien sehingga terjadi peningkatan bilirubin?

Need a break??

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