Liver Function Test Dr - PowerPoint Presentation

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Liver Function Test

Dr. Shaimaa Munther

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Basic Anatomy

• liver unequally dividedinto 2 lobes• it has a dual blood supply

– Portal vein

– Hepatic artery

It has an excretory system for bile excretion

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Gross anatomy of the liver

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Blood supply to the liver

There are two main blood vessels supplying the liver.

a) Hepatic artery a branch of the aorta :

Carrying oxygenated blood that contribute to about 20% of the blood supply

Provides most of the O

2

requierments

.

b) Hepatic portal vein carrying blood(deoxygenated) from the gut that:

Drains the GI tract.

Transports the most recently absorbed material from the intestine to the liver .

Note :

Blood leave the liver through hepatic vein

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• Liver is an essential organ for life that has diverse functions

– Carbohydrate metabolism– Lipid and lipoprotein metabolism– Protein metabolism– Bilirubin metabolism– Excretion (non-essential substances)

–

Detoxification

(drugs,

toxins

,

alcohol

,

etc

)

– Storage (glycogen, iron, vitamins, lipids, etc)

Liver Functions

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Liver Function Tests (LFTs)

Noninvasive methods for screening of liver dysfunction

Help in identifying general types of disorder

Assess severity and allow prediction of outcome for disease and treatment follow up

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Liver function tests (LFT) are helpful to detect the abnormalities and extent of liver damage.

LFT assays are frequently more sensitive than clinical signs and symptoms.

Typically the LFT comprises of:

1- Test for the synthetic function of the liver

( total protein, albumin &

prothrombin

time)

2- Tests for the integrity of liver cells

( AST, ALT , ALP, GGT& LDH)

3- Tests for the excretory function of the liver

(

bilirubin

total, direct & indirect)

Test to assess liver function

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Common serum liver chemistry tests

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Test for the synthetic function of the liver

( total protein, albumin & prothrombin time)

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Not a very useful measure, non-specific; only provides information on:

General nutritional statusSevere organ disease (specially protein losing diseases)Fractionated values of greater use

Total protein

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Serum Albumin

The most abundant protein synthesized by the liver

Normal serum levels: 3.5 – 5 g/

dL

Synthesis depends on the extent of functioning liver cell mass

because of its longer half-life, (20 days), its levels decrease in all chronic liver diseases

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Prothrombin

Time (PT)

Prothrombin

: synthesized by the liver,& its a marker of liver function

Half-life: 6 hrs.

PT is prolonged only when liver loses more than 80% of its reserve capacity

Vitamin K deficiency also causes prolonged PT

Dosage of vitamin K does not affect PT in liver disease

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Tests for the integrity of liver cells

( AST, ALT , ALP, GGT& LDH)

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Used for assessment of

Hepatocellular & Hepatobiliary diseases :1- AST: Liver (

hepatocellular

) disease (>3xULN)

Acute myocardial infarction (AMI)Skeletal muscle disease

2- ALT:

Liver (

hepatocellular

) disease (>3xULN)

3- Alkaline

phosphatase

(ALP)

Hepatobiliary enzymes >3 times ULN4- Gamma-glutamyltransferase (GGT)

Hepatobiliary enzymes >3 times ULNLiver Enzymes

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Tests for the excretory function of the liver

( bilirubin total, direct & indirect)

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Hemoglobin

Heme + Globin Bilirubin+ Iron

• Iron reused

•

Globin reused

Bilirubin

Metabolism

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Bilirubin

Metabolism

1-

Unconjugated

bilirubin

– Not water soluble

– Toxic to cells

– Bound to albumin making it soluble in plasma

– Transported through plasma to liver

for conjugation

–

Bilirubin

-albumin complex too large to pass

glomerular

filtering membrane

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Bilirubin

Metabolism2- Albumin dissociates from

unconjugated

bilirubin• Then the enzyme:

glucuronyl

transferase

form conjugated

bilirubin

in the liver

• Conjugated bilirubin

– Water soluble– Less toxic to cells– Can pass glomerular filtering membran

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Bilirubin

Metabolism3- Conjugated bilirubin

– Excreted into bile

– Not found in plasma unless

• Liver cell injury

• Obstruction

Then will be found in urine

Note:

– Only this form of

bilirubin

will be found in urine

4- Conjugated

bilirubin

– Excreted into bile

– In intestine, bacteria convertbilirubin to urobilinogen – Majority of urobilinogen remains in intestine and further reduced to sterocobilin giving feces characteristic color– Approx 20% UBG reabsorbed via portal vein and small amount found inurine

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1- Total

Bilirubin: measures both forms of bilirubin (unconjugated and conjugated)

2- Direct

Bilirubin

: measures only conjugated form

3- Indirect

bilirubin

Calculated by :

Total – direct = (indirect)

Unconjugated

represent indirect

bilirubinConjugated represent direct

bilirubin

Laboratory Analysis of Bilirubin

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• Total bilirubin: 0.2 – 1.0 mg/dl

• Conjugated bilirubin: 0.0 - 0.2 mg/dl• Unconjugated bilirubin: 0.2 – 0.8 mg/dl• Critical: >15.0 mg/dl

• Urine

bilirubin

: negative

Expected Values: Adults

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Some example of liver dysfunction

Jaundice

Hepatocellular

disease

Cholestasis

(obstruction of bile flow)

Cirrhosis

Hepatitis

Liver cancer

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• Increased plasma

bilirubin results in condition called jaundice (yellow pigmented skin & sclera)• Jaundice categorized as:– Pre-hepatic (Hemolytic Jaundice)– Hepatic ( Hepatocellular

Jaundice)

– Post-hepatic (Obstructive Jaundice )

Jaundice

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occurs when the problem causing the jaundice occurs prior to liver metabolism.

In This type of jaundice unconjugated bilirubin is increased only & it caused by :1- Acute and chronic hemolytic anemias, e.g sickle cell anemia &

thalassemia

2- Blood transfusion reaction3-Malaria

4- Drugs competing for

glucuronide

Pre-hepatic (Hemolytic Jaundice)

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Hemolytic jaundice

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Hepatic jaundice occurs when the primary problem causing the jaundice resides in the liver (intrinsic liver defect or disease). It caused by :

1- Disorders of bilirubin metabolism and transport defects, e.g. :Crigler-Najjar syndromeDubin- Johnson syndromeGilbert disease

Neonatal physiologic jaundice of the newborn

2- Diseases resulting in

hepatocellular injury or destruction, e.g.:

Cirrhosis

Tumors

Infection

Toxins

In hepatic jaundice either

unconjugated

bilirubin or conjugated bilirubin

or the both will be increased Hepatic jaundice

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Crigler-Najjar

syndrome, and physiologic jaundice of the newborn are hepatic causes of jaundice that result in elevations in unconjugated bilirubin. Conditions such as Dubin-Johnson and Rotor syndrome are hepatic causes of jaundice that result in elevations in conjugated

bilirubin

.

Gilbert syndrome,, is a benign hereditary disorder that characterized by intermittent

unconjugated

hyperbilirubinemia

in the absence of

hemolysis

and underlying liver disease due to a defective conjugation system

Hepatic jaundice

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Inherited Hyperbilirubinemias

Gilbert Syndrome

Reduction in the activity of UDP-

glucoronyl

transferase

Crigler-Najjar

syndrome

Defective UDPG-

transferase

Dublin-Johnson disease

Post-conjugation failure

Liver

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Posthepatic

jaundice is results from biliary obstructive diseaseIn This type of jaundice, conjugated bilirubin is increased only & it caused by :1-Physical obstructions (gallstones or tumors)2-

Cholestasis

3-

Biliary

atresia

Post-hepatic (Obstructive Jaundice )

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Many factors contribute to physiologic jaundice of Newborn :

• Increased bilirubin load due to shortened RBC lifespan• Relative lack of conjugating enzyme• Decreased binding to albumin leading to increased liver uptakePhysiologic jaundice has an increased potential risk of kernicterus

:

– Neurologic syndrome due to bilirubin

neurotoxicity– Lethargy with seizures

Physiologic jaundice prevented by phototherapy, exchange transfusion

Physiologic Jaundice of Newborn

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Cirrhosis

Scar tissue replaces normal healthy liver tissueAs time moves forward, function deteriorates and signs appearFatigue, nausea, weight loss, jaundice, etc

Common causes

Chronic alcoholism

Hepatitis

Results:

Increased:

unconjugated

and conjugated

bilirubin

, ALP, GGT,AST, ALT

Decreased: cholesterol, albumin

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Cirrhosis of the liver (Liver cirrhosis)

 Of 

Cirrhosis Impeding

Blood flow

Destruction by:

Alcoholism

Poisons

(carbon tetrachloride)

Virus

(infectious hepatitis)

Parenchymal cells around the blood vessels.

X

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Cancers of the liver are classified as primary or metastatic.

Primary liver cancer is cancer that begins in the liver cells.Metastatic cancer occurs when tumors from other parts of the body spread (metastasize) to the liverCancers of the liver may also be classified as benign(hepatocellular adenoma) or malignant hepatocellular carcinoma (HCC),

hepatocarcinoma

, and

hepatoma Whether primary or

metastasic

, any malignant tumor in the liver is a serious finding and carries a poor prognosis, with survival times measured in months.

Tumors

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Alcoholic Injury

StagesAlcoholic Fatty LiverMildest form

Elevations of AST, ALT, GGT

Complete recovery possible if drug removed

Alcoholic hepatitis

Moderate elevations of AST, ALT, GGT

Bilirubin

, ALP also elevated

Albumin decreased

PT prolonged

Alcoholic cirrhosis

Elevated AST, ALT, GGT, ALP, total

bilirubin

Albumin decreasedPT prolonged

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Hepatitis

Inflammation of the liverViral, bacterial, radiation, drugs, chemicals and others can cause inflammationViral infections account for the majority of cases in the clinical lab

Includes subtypes A, B,C, D, and E

Clinical Symptoms

Jaundice, dark urine, fatigue, nausea, abdominal pain

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Hepatitis Viruses

Virus

Incubation

Period

Mode of transmission

Vaccine

Chronic Infection

Hepatitis A

2-6 weeks

Fecal-oral

Yes

NO

Hepatitis B

8-26 weeks

Parenteral, sexualYesYesHepatitis C2-15 weeksParenteral, sexual

No

Yes

Hepatitis D

21-90 days

Parenteral

, sexual

Yes

Yes

Hepatitis E

3-6 weeks

Fecal-oral

No

?

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