Transcript CARDIAC ENZYMES

JANET LIM-DY, M.D., F,P.S.P. D.T.M.H.
EVALUATION OF
LIVER FUNCTION
TESTS
Overview
3 Systems involved in understanding
liver function tests:
•Proteins synthesis
•Coagulation factors
synthesis
Hepatocyte
Biliary Tract: bili metabolism
RES: Immune sys. , Heme &
globin metabolites
KREBS
CYCLE
GLUCONEOGENESIS
FA SYNTHESIS & BREAKDOWN
LIPOPROTEIN METABOLISM
AA & NUCLEIC ACID METABOLISM
GLYCOLYSIS
HMP-SHUNT
2 GENERAL METABOLIC PATHWAYS:
1. AA-CHO PATHWAY
involves ALT & AST
2. UREA CYCLE
NH4 urea
Enzyme OCT unique to liver
LIVER FUNCTION TESTS
hepatic
structure,
cell integrity,
 function
LIVER FUNCTION TESTS
Reasons for requesting LFT:
1. For Diagnosis
2. For Differentiation
Is Hepatic damage due to primary
hepatocyte damage or biliary system
obstruction?
3.
Prognosis / Monitoring
TESTS FOR DISCLOSING
HEPATIC DYSFUNCTION
Liver Enzymes
Aminotransferases (ALT and AST)
Lactate Dehydrogenase (LDH)
Alkaline Phosphatase (Alk Phos)
 Glutamyl transferase (GGT)
TESTS FOR DISCLOSING
HEPATIC DYSFUNCTION
Total Protein
Albumin
Gamma Globulins
Alpha Globulins
Clotting Factors
ProthrombinTime
HEPATOBILIARY DYSFUNCTION
 Serum Bilirubin ( total & direct)
PATIENT PREPARATION &
SPECIMEN COLLECTION
No special preparation required
Serum : Preferred Specimen
Heparinized Plasma : Acceptable
Liver Enzymes: Transaminases

2 major aminotransferases
– Aspartate transferase
 ALT(SGPT) – Alanine transferase
 AST(SGOT)

Catalyze reversibly the transfer of an amino gr.of either
AST or ALT to alpha-ketoglutarate to yield glutamate
plus the corresponding ketoacid of the starting a.a.
Liver Enzymes: Transaminases
Reaction catalyzed by ALT
COOH
|
CH2
|
CH2 +
|
C=O
|
COOH
CH3
+ |
H C- NH3
|
B6
COOH
-ketoglutarate L-alanine
COOH
|
CH2
|
COOH
|
C=O
|
CH2
+ COOH
|
pyruvate
C- NH3
|
COOH
L-glutamate
Transaminases
AST
AST
ALT
Distribution:
ALT: liver (1o location)
kidney & muscle (lesser
quantity)
more liver-specific
cytoplasmic enzyme
AST : in many body tissues,
ex heart,liver,muscle,RBC
brain,lung ,pancreas &
kidney.
cytoplasmic & mitochon
drial enzyme
Elevation of ALT activity
persist longer
Reference value


ALT :
Males
Females
AST :
Males
Females
10-40 U/L
7-35 U/L
15-40 U/L
13-35 U/L
Transaminases In
Hepatobiliary Diseases
Hepatocellular injury
AST
Mild:
AST
PM damaged
ALT
Cytoplasmic AST & ALT
released into serum
ALT
More severe:
Mitochondrial
membrane
damaged
Mitochondrial AST
released into serum:
AST
80%
Disproportionate
elevation---(De Ritis quotient)
AST/ALT (DeRitis) ratio: to
discriminate alcoholic hepatitis vs
other liver diseases ;
Sometimes help determine whether
the liver is damaged or another
organ has been damage
How to calculate AST/ALT ratio?
ex. AST= 52, ALT =67
52/67 = .75
AST / ALT > 2 ( 3:1 to 4:1) = ALD
AST/ALT <1,most likely assoc. with
other cause eg. Viral hep
Transaminases
acute hepatitis : ALT is more increased than AST
(20 -100 x the upper limit)
AST is 10x the upper limit
5-10x the upper limit in liver Ca
Cirrhosis : ALT is more increased than AST, but as
fibrosis progresses, ALTdec. In end stage = both enzymes
are dec.
Acute Fulminant hepatic failure,;AST : ALT > 1
AST value > 1000 = severe liver necrosis, AMI
TRANSAMINASES
REMEMBER: Levels are often compared
with results of other LFTs to help determine
which form of liver d’s is present
In most type of liver d’s ,ALT level > AST
AST/ALT ratio is low
AST : use for monitoring tx of potentially
hepatotoxic drugs
> 3x ULN  stop tx
Transaminases In
Asymptomatic Patients
Possible Causes of Chronic Elevation:
1. Alcohol or medication use
2. ChronicViral Hepatitis
3. Non-alcoholic fatty liver disease
4. Overweight (inc.ALT)
LIVER ENZYMES :
LACTATE DEHYDROGENASE
Cytoplasmic enzyme
Non specific for liver
Distribution of
isoenzymesLD1
LD2
LD4
LD5
LD4
LD5
LD1,LD2
Cardiac muscle,
kidney,rbc
LD1,LD
LD2
TRANS
Liver, skeletal
muscle
LD
LD4,LD5
N value(TLD) =150 IU/l
LIVER ENZYMES :
LD in Hepatitis
Is slightly inc. but only
transient ( low activity and
short half life
Large increment of total
LD= 500 -1000 iu/l
TRANS
CPK
LD
or+ elevated Alk.PO in
the absence of other
abn. Liver function tests
(AST,ALT)
LIVER ENZYMES :
LD in Other Liver Diseases
Total LD +
alkaline Phosphatase:
= space occupying lesions (e.g.)
 metastatic carcinoma
1o hepatocellular carcinoma
Hemangioma (rarely)
Source of LD (LD5) : ?
hepatocytes
tumor
both
ALKALINE PHOSPHATASE
Distribution:
liver *
Bulk *
Bone *
kidney
intestine
ALP
ALP
placenta
ALP
Each of w/c
contain distinct
isoenzymes
ALP
ALP
ALKALINE PHOSPHATASE
Canalicular membrane
Func.: facilitate transfer of metabolites
across cell membranes ;lipid transport,
& calcification process in bone
synthesis
Liver:
exists predominantly in
biliary tract
a marker for biliary
dysfunction
R.V.=20-105 U/L (adults)
ALKALINE PHOSPHATASE
Clinical Application
Obstruction of BT from:
Stones in duct
Infections
SOL
ALP (> 10 x ULN)
Reason for Increase:
Synthesis +
excretion of ALP
ALKALINE PHOSPHATASE
hepatocellular disease (due to
inflam/necrosis of the ductular
lining cells)
Obst.Cholestasis (2x
ULN,paralleling the rise of bili. )
Partial obst. Inc. ALP & normal
bili (dissociated jaundice)
CPC,liver-mod.elevated
SOL of liver
Clinical application
Conditions in Which the Serum ALP is
Hepatobiliary
Ds
Bone Ds
Other Conditions
Obstructive
jaundice
Osteitis deformans
Healing fractures
Biliary cirhosis
Rickets
Normal growth
Intrahep
cholestasis
Osteomalacia
Pregnancy
SOL(granuloma,abs Hyperthyroidism
Note: dec. ALP is
cess
,metastatic ca)
seen in malnutrition
Viral hepatitis
Metastatic bone ds
Cirrhosis
Osteogenic Sa
hypophosphotasia
 GLUTAMYL TRANSFERASE
(GGT)
Tissue distribution:
Kidney
Pancreas
Liver
Prostrate
GGT
Ref.values:
3-35 U/L
GGT
GGT
3-30 U/L
GGT
 GLUTAMYL TRANSFERASE
(GGT)
> 10x ULN in chronic cholestasis due to primary
biliary cirrhosis or sclerosing cholangitis.
> Inc. in 60-70% ---alcohol abuse;
> most sensitive enzyme to determine liver
damage from alcohol abuse
> inc. in obst. disorders, SOL in the liver than w/
liver inj.
> obese ;
> high conc.of therapeutic drugs
(acetaminophen,carbamazepine, Dilantine)
Regulates the transport of a.a. across cell
membranes by catalyzing the transfer of a
glutamyl gr.from glutathione
 GLUTAMYL TRANSFERASE
(GGT)
Increased Activity:
Application:
Detecting Alcoholic Liver Ds
Liver metastasis in
anicteric patient
Chronic obstruction of bile
duct
PROTEINS IN LIVER FUNCTION
Total serum protein
Composed of :
Albumin
Globulins (1,2, , immuno globulins)
A/G ratio is 2:1 ; a reversal ratio favors
renal / liver prob & chronic infect.
Ref. Range: 6-7.8 g/dL
(60% is albumin, 3.5-5 g/dL)
PROTEINS IN LIVER FUNCTION
ALBUMIN
Functions:
Major osmotically active component of
vascular system
Transport protein( e.g. for bilirubin &
thyroid hormone)
Synthesized by liver at 120 mg/kg/day
Hepatitis : total protein and albumin are
w/in their normal range
 Fulminant hep : abnormally
 Cirrhosis : low


Albumin together with PT are better
indices of severity and prognosis of liver
disease
Other Causes of dec. TP and ALB.
Renal disease
 Protein losing enteropathy
 Malnutrition
 Chronic inflammatory diseases
 Severe burn
An inc. in protein –Dehydration

BILIRUBIN METABOLISM
Senescent rbc’s
RES
Heme
Globin
RES
Iron
+
Albumin
Recycled into new rbc’s
Liver
Bilirubin uridine diphosphate
Glucoronyl transferase
Amino acid
pool
Protoporhyrin
Heme oxygenase
Biliverdin
Bilirubin reductase
Unconjugated + Albumin
bilirubin
2%-5% renal
excretion
Bilirubin glucoronide
Bile
Small intestine
Alkal;ine pH + β-glucoronidase
Unconjugated bilirubin
Intestinal bacteria
Urobilinogen
Urobilin (fecal pigment)
20%
reabosrobed
DISORDERS OF BILE PIGMENT METABOLISM
Reference values:
T serum bilirubin (A): 0.1 - 1 mg/dL (1.7 to
17 umol/L)
Congugated Bilirubin (Direct):
0.3 mg/dL(5 umol/L)
Unconjugated Bilirubin (Indirect):
T Bilirubin – Conjugated Bilirubin
BILIRUBIN
Serum / plasma , fasting state;shld.be tested
ASAP
Interference factors:
Hemolysis- false dec
lipemic – false inc
light – false dec.
DISORDERS OF BILE
PIGMENT METABOLISM
JAUNDICE/ICTERUS
Bilirubin
deposition in sclera
and in skin
> 2.5 mg/dL (43 umol/L)
DISORDERS OF BILE PIGMENT METAB
(HYPERBILIRUBINEMIA)
Unconjugated
Excess Bilirubin Prodxn Impaired Bili Conjugation
 Physiologic jaundice of NB
Hemolytic Anemia
Resorption of blood from  Breast milk jaundice
internal hge
 Genetic Def. Of bili UGT
Ineffective erythropoiesis (Criggler-Najar)
(e.g.pernicious An,
thalassemia
Hepatic uptake


Drug interference
Some cases of Gilbert
syndrome
 Gilbert
syndrome
 Diffuse Hepatocelular Ds
DISORDERS OF BILE PIGMENT METAB
(HYPERBILIRUBINEMIA)
Conjugated
Dec. hepatic excretion of Bili Glucuronides
Deficiency in canalicular membrane
transporters
(Dubin-Johnson syndrome, Rotor
syndrome)
In extrahepatic obst.,total bili rarely exceeds 25
ug/dl
Ammonia
Derived mainly from a.a. & nucleic acid
metabolism
 Metabolized only in the liver
 Px preparation: fasting,plasma, arterial
 good venipuncture technique,no fist
clenching
 R.V. 19- 16 ug/dl

Alpha-feto protein








An onco-fetal protein
Marker of differentiation
Synthesized by fetal yolk sac, hepatocytes
Detectable during 4th wks. of pregnancy
Increased in :
HCC , benign liver ds ( cirrhosis )
Testicular Tumors (embryonal &yolk sac)
Maybe inc. in breast,bronchial and colorectal Ca
Ref.value : < 20ng/ml
> 400 ng/dl =HCC
Inc. neural tube defect
6 Fundamental Patterns of Liver Function Tests
AST
ALT LD
ALP
TP ALB
BIL
NH4
1
H
H
H
H
N
N
H
N
2
N
N
N
N-sl L
H
L
H
H
3
N
N
N
H
N
N
N-H
N
4
N or
H
N or H
H
H
N
N
NH
N
5
sl
N
N
6
Very
L
L
N- N
SlH
H
H
CONDITION
H
H
sl H sl H Nsl H
H
H
H
The end
Good clinical history
Complete P.E.