Download PK LFT_dr_Diah - FK UWKS 2012 C

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, γ GT, 5’NT
4. Tes etiologi
– Marker hepatitis
– Tumor marker : CEA, AFP
BILIRUBIN
- Unconjugated
bilirubin :
Not water soluble
Toxic to cells
–Bound to
albumin making it
soluble in plasma
–Transported
through plasma to
liver for excretion
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: (+)
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
3
2
1
10 10
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
19 19
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
(schematic representation)
and localization of the
diagnostically most important
enzymes etc
AST,ALT,LDH
ALP
GGT
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
AST
ChE
23 23
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
24
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 ↑
25 25
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
>1
 KERUSAKAN HATI AKUT
 KERUSAKAN HATI MENAHUN /
SIROSIS
• DASAR :
ALT  KERUSAKAN MEMBRAN.
AST  KERUSAKAN ORGANEL +
KERUSAKAN MEMBRAN
27 27
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
28 28
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
Infark (± 72 jam)
Peny. Hemolitik
Sampel lisis
LD-4 (HMMM)
LD-5 (MMMM)
Liver, skeletal muscle
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
(Transaminases) :
- AST
- ALT
• Markers of Cholestasis:
• ALP
• Gamma GT
• 5’ nucleotidase / 5’NT
damage
34 34
• 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
↓
prolonged
Alcohol
hepatitis
cirrhosis
Both elevate >2 sugg
bilirubinuria + >3 diag
N / <3
times N
Obs.
jaundice
Both elevate N to mod
Bilirubinuria+ elevate
Elevate >4
times N
N unless
chronic
N/
Prolonged
Elevate >4
times
GGT,5’N
N
N
Infiltrative
disease
N
N / slight
elevate
SIROSIS HATI
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
SIROSIS HATI
COMPENSATED PHASE :
- Gangguan fungsi minimal
ACTIVE PHASE :
- Nekrosis progresif
( ALT  )
- Fibrosis  kolestasis
( ALP , BILI  )
DECOMPENSATED PHASE :
- Gangguan fungsi berat
+ hipo albumin + hiperbilirubinemia
GAGAL HATI
40 40
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??
44