Uji Fungsi Hati 1 ppt kuliah fkh braawijaya
- 1. Uji Fungsi Hati (Liver Profile) Drh. Dyah Ayu Oktavianie, M.Biotech
- 2. 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
- 3. 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
- 4. 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
- 5. Keterbatasan Tes Fungsi Hati 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
- 6. 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
- 7. BILIRUBIN
- 8. 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
- 9. 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)
- 11. 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
- 12. Peningkatan Conjugated Bilirubin • Kolestasis intra dan ekstra hepatik • Hepatitis, sirosis hepatis • Atresia bilier • Kelainan kongenital, gangguan ekskresi
- 13. 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 ↓
- 14. 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)
- 15. • BilirubinTotal : diukur dari kedua macam bilirubin (unconjugated and conjugated) • Bilirubin Direct : hanya mengukur conjugated bilirubin • Parameter dihitung : Total – direct = unconjugated (indirect)
- 16. Expected Values: Adults (human) •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 (human) 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
- 17. FUNGSI SINTESIS HATI • Sintesis – Total protein – Albumin – Protein koagulasi /faktor koagulasi • Banyak disintesis di hati • Membutuhkan vitamin K untuk sintesisnya – Cholinesterase
- 18. 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
- 19. 19 19 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
- 20. Dipengaruhi oleh : - peny.hepatoselular (ggn sintesis) - peny. Obstruktif (ggn absorpsi vit.K) Protein disintesis di hati Sintesis membutuhkan vit.K
- 21. CHOLINESTERASE (CHE) - Penyakit hati kronis, sirosis, hepatitis akut fulminan. - Malnutrisi. - Keracunan insektisida (organofosfat) AKTIVITAS , SINTESIS NORMAL Pada hepatitis akut CHE prognosis buruk.
- 22. 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
- 23. 23 23 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
- 24. 24 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
- 25. 25 25 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 ↑
- 26. 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
- 27. 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
- 28. 28 28 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
- 29. ALP (Alkaline Phosphatase) • Dapat ditemukan: • Liver • Tulang • Ginjal • Intestine • Placenta • ALP liver: • Half life 3 hari • Permukaan kanalikuli → disfungsi bilier, ↑ 10x N
- 31. 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
- 32. Gamma-GT • hepatocytes and biliary epithelial cells, pancreas, renal tubules and intestine • Very sensitive but Non-specific • Raised in ANY liver disease 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
- 33. Causes of raised serum gammaglutamyl transferase (GGT)
- 34. 34 34 INTERPRETASI TFH • Markers of Hepatocellular damage (Transaminases) : - AST - ALT • Markers of Cholestasis: • ALP • Gamma GT • 5’ nucleotidase / 5’NT
- 35. • 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
- 36. 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
- 37. 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
- 38. 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
- 39. Manifestations of Liver Cirrhosis Fig. 42-5
- 40. 40 40 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
- 43. CONTOH KASUS • Bilirubin total 0,8 mg/dl dan direk 0,3 mg/dl, • SGOT 80 IU, SGPT : 120 IU, Elektroforesis • protein dalam batas normal, HBsAg negative, • anti HCV negativ; kolesterol total 360 mg/dl • Trigliserida 600 mg/dl; LDL 210 mg/dl ; HDL 45 mg/dl. • Pembahasan : diagnosis penderita tersebut adalah