laboratory evaluation of liver...
TRANSCRIPT
1. Diagnostic m eth ods of liver dis eas e s2. Typical ch ange s of enzym e activitie s in m ajor type s of liver dis eas e s3. Alcoh ol induced liver dis eas e s4. A com parison of different viral h epatitis type s5. H epatitis A6. Serological ch ange s in h epatitis B: s e roconvers ion7. Serological ch ange s in h epatitis B: no s e roconvers ion8. Norm al bilirubin m etabolism9 . Norm al and elevated bilirubin levels10. Clas s ification of unconjugated and conjugated h yperbilirubinem ias11. H em olytic jaundice12. O bstructive jaundice13. H epatocellular jaundice14. Serum and urine bilirubin, and urine UBG levels in acute viral h epatitis15. Th e differential diagnos is of jaundice
Laboratory evaluation of liver d isease s
Diagnostic m eth ods of liver d isease s
• Ph ys ical exam inationTh e color of th e s k in, urine and fece s , oth e r clinical sym ptom s
• Enzym e diagnosticsM easuring th e activity of enzym e s getting into th e plasm a in parench ym al necros is (ASAT, ALAT) and in biliary obstruction (ALP, GGT)
• Evaluation of th e conjugation-excretion functionSerum bilirubin fractions , urine bilirubin, urine UBG, fecal UBG, fasting s e rum bile acids
• Evaluation of th e s ynth etic function of th e liverAlbum in, m any clotting factors , som e globulins , ps eudoch oline steras e , proth rom bin tim e
• M icrobiological/im m unological te stsH BSAg etc.
• Plasm a levels of oth er m aterialsNH 4
+ , Fe, Cu, ch olesterol, LP-X, AFP, CEA
• Im aging m eth odsultrasound, rtg, ERCP, PTC, CT, MRI
• Liver biopsy
1
Typical ch anges of enzym e activitie s in m ajor types of liver d isease s
Acute viralh epatitis (A)
Acute alcoh olich epatitis
Biliary obstruction
jaundice biliary colic
[w e e k s] [w e e k s] [days]
Enzy
me
activ
ity in
pla
sma
[U/l]
ALAT ASAT GGT ALP
1 2 3 4 5 6 1 2 3 4 5 60 1 2 3 4 5 600
200
400
600
800
1000
1200
2
Fatty liverAcute
alcoh olich epatitis
Cirrh os is
recurrence
revers ible irrevers ible
s everity of th e dis eas e
Alcoh ol induced liver d isease s 3
Com parison of different h epatitis types
VirusIncubation tim e (m ean)
O ns et
Typical route of infection
Ch ronic h epatitis
Prevention
Typical clinical cours e
H BV1– 6 m onth s
(2– 3)slow or acute
parenteral, s exual
rare (1– 10%)
none
som etim e s s evere
H AV2– 6
w e e k s (4)
acute
fecal-oral
never
IG, vaccine
m ild
IG, vaccine
H CVh alf– 6
m onth s (2)
slow
parenteral
very com m on
(cca. 50%)
average
H DV1– 6 m onth s
(2– 3)
slow or acute
parenteral, s exual
com m on
som etim e s s evere
H BV vaccine
none
never
m ild
fecal-oral (th rough w ater)
acute
2– 8 w e e k s (6)
H EV
Th e oth er h epatotropic virus e s (F, G) identified don't s e em to be clinically im portant.
4
H epatitis A
H AV in fece s
anti-H AV total
anti-H AV IgM
clinical sym ptom s
ALATbilirubin
tim e s ince th e infection[days]
ALA
T [U
/l]H
AV a
ntig
en in
fece
s [cp
m]
anti-HAV
[relative conc.]
bilirubin [µmol/l]
2000
1000
1000800600400200
010 20 30 40 50 60 70 80 9 0 100
80604020
5
Serological ch anges in h epatitis B:norm al seroconversion
tim e
sym ptom s
H BSAganti-H BS
H BeAg
anti-H Be
anti-H Bc-total
anti-H Bc-IgM
core -w indow
incubationno sym ptom s(4– 12 w e e k s)
acuteinfection
(2– 12 w e e k s)
recentacute infection(2– 26 w e e k s)
dis eas e -fre estate
(years)
[rela
tive
conc
entra
tion]
6
H BSAg
H BeAg
anti-H Bc-totalanti-H Bc-IgM
tim e
incubationno sym ptom s(4– 12 w e e k s)
acuteinfection
(6 m onth s)
ch ronicinfection(years)
[rela
tive
conc
entra
tion]
Serological ch anges in h epatitis B:no seroconversion
7
Norm al bilirubin m etabolism
Kidney
liver cell
GI tract
fece s
blood ve s s el
urine : UBG norm .
enteroh epatic circulation
RBC
RES
h em eglobin
ironncB
H b
ncB ncB cB
albu-m in cB
UBG
stercobilin urobilin
UBG
UBG
8
Norm al and elevated bilirubin levels
h yperbilirubinaem ianorm alindirect
norm
alhy
perb
iliru
bina
emiaicte
rus
subi
cter
us
direct
50
17
direct Bi < 5 µm ol/l direct directtotal Bi < 17 µm ol/l total total< 0,2 ≥ 0,4
seru
m b
iliru
bin
leve
l (to
tal)
[µm
ol/l]
9
h em olys is , increas ed ineffective eryth ropoie s is
Clas s ification of unconjugated és conjugated h yperbilirubinem ias
Pre h epatic:(increas ed bilirubin production)
I.
II. H epatic:im paired bilirubin uptak e
Gilbert-dis eas e com petition
a)
b) im paired conjugation
Gilbert-dis eas eCrigler-Najjar sy. I, IIph ys iological jaundice of new borns
no s ign of h em olys is
no s ign of h epatic le s ion
c)
d)
im paired excretion
Dubin-Joh nson sy.Rotor sy.ch olestas is in pregnancybenign recurrent ch olestas is
s igns of m ild obstructive jaundice
s igns of m ild
obstruction
s igns of h epatic le s ion
III.
com bined abnorm .(h epatocellular inflam m ation)
h epatitis : viraloth er m icrobe s , toxic dam age s , cirrh os is
Posth epatic:(biliary obstruction)a) intrah epaticb) exrah epatic
s igns of obstruction
s igns of m ild h epatic le s ion
prim ary biliary cirrh os isdrug induced, bile stone , tum or
10
H em olytic jaundice
Kidney
liver cell
GI tract
fece s : pleioch rom ic
blood ve s s el
urine : UBG ↑
enteroh epatic circulation
RBC
RES
ncB ncB cB
albu-m in cB
UBG
stercobilin urobilin
UBG
UBG
11
O bstructive jaundice
Kidney
liver cell
GI tract
fece s : ach olic
blood ve s s el
urine : UBG negativebilirubin (conjugated) pos itive
RBC
RES
ncB ncB cB
albu-m in
cB
cB
cB
12
H epatocellular jaundice
Kidney
liver cell
GI tract
fece s : ligh t colored
blood ve s s el
urine : UBG ↑bilirubin (conjugated) pos itive
RBC
RES
ncB ncB cB
albu-m in cB
UBG
stercobilin urobilin
UBG
UBG
cB
cB
13
s e rum bilirubin
urine bilirubin
urine UBG[rela
tive
units
]
[w e e k s]1 2 3 4 5 6 7 8
Serum and urine b ilirubin, and urine UBG levels in acute viral h epatitis
14
Th e d ifferential diagnosis of jaundice
Serum
Urine
Stool
Serum
O th er
Pre h epatic(h em olys is)
H epatic(h epatitis)
Posth epatic(obstruction)
unconjugated bilirubin
conjugated bilirubinconjugated bilirubin
UBGUBGLDH
ASAT, ALATALP, GGT
FeCh olesterol
↑
N, ↑–
↑↑↑↑
LDH 1 ↑NN↑
N
↑
↑+
↑↓
LDH 5 ↑↑↑↑↑
N, ↓
↑
↑↑+
↓ –↓ –N
↑↑↑N
↑
h aptoglobin: ↓reticulocyte : ↑
INR: ↑After vitam in K:
no ch ange
INR: ↑After vitam in K:
N
N: norm al value, or th e ch ange is not typical– : cannot be detected+ : can be detected
15