Evaluation of Liver - PowerPoint Presentation

Slide1

Evaluation of Liver Function

Dr.

Baghbanian

M.

Gastroenterologist

Shaheed

Sadoughi

hospital / 2012Slide2

liver tests

(

1) detect the presence of liver

disease

(2)

distinguish

different types of liver

disorders

(3)

extent of liver damage

(

4) follow the response to

treatmentSlide3

Liver tests

Can

be normal in

serious

liver

disease

Can be abnormal in non hepatic diseases

Rarely

suggest a specific

diagnosis

They

suggest a general category of liver disease, such as

hepatocellula

r

or

cholestatic

Slide4

liver carries out thousands of biochemical functions

most

cannot be easily measured by blood tests.

Laboratory

tests measure only a limited number of these functions

.Slide5

Aminotransferases /Alkaline

phosphatase

do not measure liver function at all.

Rather, they detect:

liver cell damage

interference with bile flow.

Thus, no one test FOR assess the liver's total functional capacity.Slide6

Liver test

Bilirubin

aminotransferases

alkaline

phosphatase

albumin

prothrombin

time tests. Slide7

USE MULTIPLE TEST for detection of liver disease

probability of liver disease is high When :

more than one of these tests are abnormal

tests persistently abnormal on serial determinations

probability of liver disease is

lowWhen

:

all test results are normalSlide8

Tests Based on Detoxification and Excretory Functions

Serum

Bilirubin

Blood Ammonia

Serum EnzymesSlide9

Serum Bilirubin

breakdown product of the

porphyrin

of

heme

-containing

proteins

two

fractions:

Conjugated = direct

water soluble

excreted by the kidney.

Unconjugated

=

indirect

insoluble

in water

bound to albumin in the blood. Slide10

Normal Serum Bilirubin

Total = 1 -

1.5

mg/

dL

.

Direct <15

% of the

total → considered indirect

upper

limit of normal for conjugated

=

0.3 mg/

dL

.Slide11

Isolated unconjugated

hyperbilirubinemia

is

rarely due to liver

disease

Causes:

hemolytic

disorders

genetic conditions such as

:

Crigler-Najjar

Gilbert's syndromesSlide12

bilirubin elevated but <15% direct

should prompt a workup for

hemolysis

In the

absence of

hemolysis

, an isolated,

unconjugated

hyperbilirubinemia

in an otherwise healthy patient can be attributed to

Gilbert's

syndrome, and

no further evaluation is required.Slide13

conjugated hyperbilirubinemia

always implies liver or

biliary

tract disease.

In

most liver diseases, both conjugated and

unconjugated

fractions of the

bilirubin

tend to be

elevatedSlide14

rate-limiting step in bilirubin metabolism

transport

of conjugated

bilirubin

into the bile

canaliculi

not conjugation Slide15

Fractionation of the bilirubin

rarely helpful in determining the

cause

of jaundice

Except :

purely

unconjugated

hyperbilirubinemia

,.Slide16

Degree of elevation of bilirubin

not

as a prognostic

marker

But is important

in

:

viral

hepatitis:

higher

bilirubin

→ greater

hepatocellular

damage.

alcoholic hepatitis:

Total

serum

bilirubin

correlates with poor

outcomes

component

of the Model for

End stage

Liver Disease (

MELD

)

drug-induced liver disease:

elevated

total serum

bilirubin

indicates

more severe injury.Slide17

Urine Bilirubin

Unconjugated

bilirubin

binds to albumin in the serum and is not filtered by the kidney.

any

bilirubin

in

urine is conjugated

bilirubin

;

the

presence of

bilirubinuria

implies the presence of liver disease

.

In

patients recovering from jaundice, the urine

bilirubin

clears prior to the serum

bilirubin

.Slide18

Blood Ammonia

is produced

during

normal protein metabolism

intestinal

bacteriain

the colon.

liver plays

: detoxification

of ammonia by converting it to

urea→ excreted

by the

kidneys

Striated muscle

→detoxification of ammonia(combination with

glutamic

acid ) Slide19

Elevated ammonia levels

Has very

poor correlation

with:

presence or severity of

acute encephalopathy

hepatic function

.Slide20

Elevated ammonia levels

occasionally useful for

occult liver disease

in mental changes.

correlate with outcome in

fulminant

hepatic failure.

in severe portal hypertension and

shunting

around the liver

even in normal or near-normal hepatic function.Slide21

Serum Enzymes

The

liver contains

thousands

of

enzymes

These

enzymes have

no known function

probably

cleared by

r

eticuloendothelial

cells

liver cells damage → entrance of Enzymes into serumSlide22

3 type of LIVER enzyme tests

enzymes whose elevation reflects

damage to

hepatocytes

2) enzymes whose elevation reflects

cholestasis

3) enzyme tests that do

not fit

either pattern.Slide23

Enzymes that Reflect Damage to Hepatocytes

include:

aspartate

aminotransferase

(AST) =

serum

glutamic

oxaloacetic

transaminase

(SGPT)

alanine

aminotransferase

(ALT) =

serum

glutamic

pyruvic

transaminase

(SGPT)

sensitive

indicators of liver cell injury

most

helpful in recognizing acute

hepatocellular

diseases

(hepatitis) Slide24

AST is found in

Liver

cardiac muscle

skeletal muscle

kidneys

brain

pancreas

lungs

leukocytes, and erythrocytesSlide25

ALT is found primarily in the liver and is more specific for liver injury.

The

aminotransferases

are normally present in the serum in low concentrations.Slide26

Aminotransferases

damage

to the liver cell → enzymes release into blood

Liver cell necrosis is not required

poor correlation with degree of liver cell damage

not prognostic in acute

hepatocellular

disorders.Slide27

Levels of aminotransferases

normal : 10-40

U/L.

<300

U/L are nonspecific and may be found in any type of liver disorder.

Minimal

ALT elevations

in asymptomatic blood donors rarely indicate severe liver disease;

fatty liver

is

the most

cause.Slide28

Aminotransferases >1000 U/L

Extensive

hepatocellular

injury such:

viral

hepatitis

ischemic

liver injury (prolonged hypotension or acute heart failure)

toxin- or drug-induced

liver injury.Slide29

The pattern of the aminotransferase

acute

hepatocellular

disorders: ALT ≥ AST.

chronic

viral hepatitis

: ALT ≥ AST

cirrhosis : AST ≥ ALT

Slide30

Alcoholic liver disease

AST/ALT >2:1 is suggestive

AST/ALT >3:1 is highly suggestive

The AST is rarely >300 U/L

ALT is often normal.

A low level of ALT in the serum is due to an alcohol-induced

deficiency of

pyridoxal

phosphate.Slide31

Aproach to asymptomatic elevation of serum

aminotransferaseSlide32

Obstructive jaundice

Aminotransferases

not

greatly elevated

Exception:

passage of a

gallstone

into the common bile duct → acute

biliary

obstruction

→

aminotransferases

1000–2000

→ decrease quickly → liver-function

tests rapidly evolve

typical

of

cholestasis

.Slide33

Aproach to isolated elevation of bilirubinSlide34

Enzymes that Reflect Cholestasis

Are usually elevated in

cholestasis

Alkaline

phosphatase

5

'-

nucleotidase

Gama

glutamyl

transpeptidase

(GGT

) Slide35

Gama glutamyl

transpeptidase

(GGT)

GGT is more diffuse in liver

→

is

less specific

for

cholestasis

than alkaline

phosphatase

or 5'-nucleotidase.

GGT

in

occult alcohol use?

lack of specificity

/ questionable.Slide36

Serum alkaline phosphatase

found

in

:

Liver

Bone

Placenta

Small intestineSlide37

ALKP non pathologically elevated

Age > 60

Blood types O and B after fatty meal (influx of

intestinal

ALKP into the blood.)

Children and adolescents undergoing rapid bone growth, (

bone)

Late in

normal pregnancies

(influx of

placental

)Slide38

Elevation of liver-derived alkaline phosphatase

N

ot specific

for

cholestasis

< 3 fold

occur in :

any

type of liver disease

.

>4 fold

occur in:

cholestatic

liver

disorders

infiltrative

liver diseases such as

cancer

and

amyloidosisSlide39

If an elevated ALKP is only finding

First

aproach

: ALKP

electrophoresis

.

S

econd

approach

:

inactivation

by

heat

heat-stable : placenta

or a tumor is the

source.

heat –unstable: intestinal, liver

, and

bone

measurement of serum 5'-nucleotidase or GGTSlide40

In the absence of jaundice or elevated aminotransferases, an elevated ALKP of liver origin

Often

:

early

cholestasis

less often

:

hepatic infiltration by

tumor

or

granulomata

.Slide41

isolated elevations of the alkaline phosphatase

Hodgkin's disease

diabetes

hyperthyroidism

congestive heart failure

amyloidosis

inflammatory bowel disease.Slide42

Level of ALKP IS

NOT helpful in distinguishing

between

intrahepatic

and

extrahepatic

cholestasis

obstructive

jaundice due to cancer, common duct stone,

sclerosing

cholangitis

, or bile duct stricture. Slide43

Alkaline phosphatase

increased in :

intrahepatic

cholestasis

due to drug-induced hepatitis

primary

biliary

cirrhosis

rejection of transplanted livers

rarely, alcohol-induced

steatohepatitis

.Slide44

Serum alkaline phosphatase

Greatly elevated in

hepatobiliary

disorders in

AIDS

AIDS

cholangiopathy

due to cytomegalovirus or

cryptosporidial

infection

tuberculosis with hepatic involvementSlide45

Aproach to isolated elevation of ALKPSlide46

Serum Albumin

S

ynthesized

exclusively by

hepatocytes

.

L

ong

half-life: 18–20

days

Not a good indicator of

acute

or

mild

hepatic dysfunction (slow turnover

)Slide47

Hypoalbuminemia

C

ommon in

chronic liver disorders

such as cirrhosis than in acute liver disease

R

eflects

severe liver damage

and decreased albumin synthesis.

is not specific for liver

disease

and

occur in:

protein malnutrition

protein-losing

enteropathies

nephrotic

syndrome

chronic infections that inhibit albumin synthesis. Slide48

Serum Globulins

Immunoglobulins

produced by

B lymphocytes

Globulins are increased in chronic hepatitis and cirrhosis. Slide49

increased Serum Globulins

In cirrhosis: due to the increased synthesis of

antibodies

against intestinal bacteria.

Cause : cirrhotic liver fails to clear bacterial antigens that normally reach through the hepatic circulation.Slide50

Specific globulins are helpful in recognition of certain liver diseases

Diffuse polyclonal

IgG

↑ in

autoimmune hepatitis

IgM

↑in

primary

biliary

cirrhosis

IgA

↑

in

alcoholic liver disease.Slide51

Coagulation Factors

Are made

exclusively in

hepatocytes

.

Exception:

factor VIII

,

(

which is produced by vascular endothelial cells

) Slide52

Coagulation Factors

Half-lives are shorter

than albumin

6 h for factor VII to 5 days for fibrinogen.

Single best acute measure

of hepatic synthetic function FOR diagnosis and assessing the prognosis of acute

parenchymal

liver disease.Slide53

Coagulation Factors

Prothrombin

time

: measures factors II, V, VII, and X.

(25710)

Depends on vitamin K: synthesis of factors II, VII, IX, and X

(29710)Slide54

Prothrombin time

May be elevated in :

hepatitis

cirrhosis

vitamin K deficiency

obstructive jaundice

fat

malabsorption

Slide55

prothrombin time >5 s above control

If not corrected by

parenteral

vitamin K

is a poor prognostic sign in acute viral hepatitis and other acute and chronic liver diseases. Slide56

MELD (model of end stage liver disease)

Allocate for liver transplantation.

Has 3 component:

INR,

Total serum

bilirubin

CreatinineSlide57

Percutaneous Liver Biopsy

Is a safe procedure

Easily performed at the bedside

With local anesthesia and ultrasound guidance. Slide58

Percutaneous Liver Biopsy Indication

Hepatocellular

disease of uncertain cause

Prolonged hepatitis (chronic active hepatitis)

(3) Unexplained

hepatomegaly

(4) Unexplained

splenomegaly

(5) Hepatic filling defects IN imaging

(6) Fever of unknown origin

(7) Staging of malignant lymphomaSlide59

Liver biopsy

is most accurate in disorders causing diffuse changes IN liver

Sampling error in focal infiltrative disorders such as hepatic metastases.

Should not be the initial procedure in

cholestasis

. Slide60

Liver biopsy Contraindications

Significant

ascites

Prolonged INR

Under these circumstances, the biopsy can be performed via the

transjugular

approachSlide61

Ultrasonography

First diagnostic test in

cholestasis

:

dilated

intrahepatic

extrahepatic

biliary

tree

gallstones.

space-occupying lesions IN

liver, →distinguish between cystic and solid masses, and helps direct

percutaneous

biopsies. Slide62

Ultrasound with Doppler

Detect the patency of the :

portal vein

hepatic artery

hepatic veins

First test in patients suspected Budd-

Chiari

syndrome.Slide63

Abnormal in...

Liver Test

Cirrhosis, severe hepatocellular injury

Albumin

Cholestasis, hepatocellular enzyme induction, canalicular injury, children during bone growth, bone disease, pregnancy (placenta origin)

Alkaline phosphatase

Hepatocellular injury (ethanol, drug-induced hepatitis, hepatitis B and C, ischemic injury, chronic liver disease, NAFLD, chronic viral hepatitis, alcoholism, nonspecific viral injury, and cholestatic or replacement disease); acute biliary obstruction; rarely in hyperthyroidism, celiac disease, skeletal muscle disease

Aminotransferases (AST, ALT)

Any acute or chronic liver disease; congenital disorders of bilirubin metabolism.

Bilirubin

Cholestasis

5′ nucleotidase

Cholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism, myotonic dystrophy

GGT

Impaired synthesis of vitamin K-dependent coagulation factors

INR

Ischemic injury, Epstein-Barr virus infection, hemolysis, solid tumor

Lactate dehydrogenase

Alcohol consumption, gout

Uric acidSlide64

Aproach to cholestatic

liver enzyme elevationsSlide65