Pemeriksaan Fungsi Hati

Dr. Verdiansah, SpPK, MMRS

 Liver
1. 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 hati
1. Tes mengetahui gangguan fungsi
“Uptake” : bilirubin
konjugasi : bilirubin
ekskresi : bilirubin, asam empedu
sintesis : albumin
faktor koagulasi
kolinesterase
2. Tes integritas sel : AST, ALT, LDH
3. Tes kolestasis : Bilirubin, ALP, γ GT, 5’NT
4. Tes etiologi
– Marker hepatitis
– Tumor marker : CEA, AFP
BILIRUBIN
 Conjugated bilirubin :
- Unconjugated 1. Water soluble
bilirubin : 2. Less toxic to cells
Not water soluble 3. Can pass glomerular
Toxic to cells filtering membrane

–Bound to Not found in plasma

albumin making it unless
soluble in plasma •Liver cell injury
•Obstruction
–Transported
through plasma to Then will be found in
liver for excretion urine
•Bilirubin dipstick: (+)
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)
Gangguan metabolisme bilirubin

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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
 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

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Protein disintesis di
hati
Sintesis
membutuhkan vit.K

Dipengaruhi oleh :
- peny.hepatoselular (ggn sintesis)
- peny. Obstruktif (ggn absorpsi 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
 LOKASI ENZIM DALAM HEPATOSIT
Hepatocyte with cell organelles
AST,ALT,LDH (schematic representation)
and localization of the
diagnostically most important
enzymes etc

1. Stellate Kupffer cell

2. Space of Disse
ALP 3. Granular endopl. retic:ChE
GGT 4. Smooth endopl. retic
5. Mitochondrion: GlDH,AST
6. Bile canaliculi:ALP,LAP,G-GT
7. Nucleus
8. Lysosomes :hydrolases
9. Cytoplasm:LDH,ALAT,AST Iron

AST
ChE

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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 ↑

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 Alanine transaminase (ALT)

ALT

ALT or sGPT (serum glutamate pyruvate transaminase)

GPT (ALT) catalyses the transfer of amino-groups from alanine to 2-
oxoglutarate and thus the formation of glutamate and pyruvate.
 organ GOT GPT organ GOT GPT

heart 156000 7100 pancrease 28000 2000

liver 142000 44000 spleen 14000 1200

skeletal 99000 4800 lung 10000 700

kidney 91000 19000 serum 20 16

ALT is an enzyme produced in hepatocytes and is highly

concentrated in the liver.
Aspartate aminotransferase (AST)

AST

AST or sGOT (serum glutamate oxaloacetate

transaminase)
Aspartate aminotransferase (AST)
organ GOT GPT organ GOT GPT

heart 156000 7100 pancrease 28000 2000

liver 142000 44000 spleen 14000 1200

skeletal 99000 4800 lung 10000 700

kidney 91000 19000 serum 20 16

Both these enzyme are found in most tissues , but the relative
amounts vary . heart muscles are richer in AST, whereas liver
contains both but more of ALT.
 AST also reflects damage to the hepatic
cells and is less specific for liver disease. It can
also be released with heart, muscle and brain
disorders.

 Therefore, this test may be ordered to help

diagnose various heart, muscle or brain disorders,
such as a myocardial infarct (heart attack).
 Elevated levels of AST may indicate :

 acute hemolytic anemia,

 acute pancreatitis or inflammation of the pancreas.
 acute renal failure or loss of kidney function.
 cirrhosis of the liver.
 Hepatitis
 heart attack
 primary muscle disease
 recent surgery
 severe burns
 muscle injury
Medications causing elevation of
aminotransferases

Acetaminophen
Amoxicillin-clavulanic acid
HMGCoA reductase inhbtrs Herbs and toxins
INH •Herbs/alt. medicines
NSAIDS •Illicit drugs
Phenytoin •Toxins
Valproate
Many others
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

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 ALP (Alkaline Phosphatase)
• Dapat ditemukan:
• Liver
• Tulang
• Ginjal
• Intestine
• Placenta

• ALP liver:
• Half life 3 hari
• Permukaan kanalikuli → disfungsi bilier, ↑ 10x N
 Ratios between ALT and AST are useful to physicians
in assessing the etiology of liver enzyme abnormalities.

sALT/sAST (De Ritis) ratio, normally is less than 1,

about 0.7~0.9.

In infectious hepatitis and other inflammatory

conditions affecting the liver, ALT is characteristically as
high as or higher than AST, and the ALT/AST (De Ritis)
ratio becomes greater than unity, >1.5.
 LDH
• Terdapat di hampir semua sel
• LD isoenzim menunjukkan spesifisitas jaringan

LD-1 (HHHH) Cardiac muscle, kidney,

LD-2 (HHHM) erythrocyte
Infark (± 72 jam)
Peny. Hemolitik
Sampel lisis

LD-4 (HMMM) Liver, skeletal muscle

LD-5 (MMMM) Peny. Liver
Skeletal 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)
 INTERPRETASI TFH

• Markers of Hepatocellular damage

(Transaminases) :
- AST
- ALT
• Markers of Cholestasis:
• ALP
• Gamma GT
• 5’ nucleotidase / 5’NT

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• 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/ ALP Albumin PT
ALT

Hemolysis unconj ↑ N N N N
/ Gilberts

Acute Both Elevate N/<3 N Usually N

elevate ALT > times N
hep.
Bilirubin AST
cellular ds
uria+

Chronic Both Elevate N/ <3 Decrease prolonged

elevate <300u/l times N
hep.
Bilirubin
cellular. ds uria+
Disorder Bilirubin AST/ ALP Albumin PT
ALT
Alcohol Both elevate >2 sugg N / <3 ↓ prolonged
bilirubinuria + >3 diag times N
hepatitis
cirrhosis

Obs. Both elevate N to mod Elevate >4 N unless N/

jaundice Bilirubinuria+ elevate times N chronic Prolonged

Infiltrative N N / slight Elevate >4 N N

disease elevate times
GGT,5’N
Terima kasih