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Pemeriksaan Fungsi

Hati
dr.Diah Puspita Rini, SpPK
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, GT, 5NT
4. 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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3
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Gangguan metabolisme bilirubin
Peningkatan Unconjugated Bilirubin
1.Peningkatan produksi: Hemolisis
2.Gangguan uptake : sindroma Gilberts
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 the
diagnostically most important
enzymes etc


1. Stellate Kupffer cell
2. Space of Disse
3. Granular endopl. retic:ChE
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





LOKASI ENZIM DALAM HEPATOSIT
ChE
AST
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. Hemolitik
Sampel lisis
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
LFTs 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 / 5NT

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
elevate
Bilirubin
uria+
Elevate
ALT >
AST
N / < 3
times N
N Usually N
Chronic
hep.
cellular. ds
Both
elevate
Bilirubin
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,5N
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 (Laennecs) 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

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