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

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)

10 10

2

3

1

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

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

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

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

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,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

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

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