Liver function testBy

Dr. Ali H. SadiekProf. Of Internal Veterinary Medicine

and Clinical Lab. DiagnosisFaculty of Vet. Medicine, Assiut University

For the undergraduate student of 5th year Internal medicine

Liver function testLiver function test• Liver is the Largest solid organ in the

body.• It have a Large reserve capacity• It is Capable of regeneration

Function of the liver

Metabolism: fat, CHO, protein, drugs, hormones.

- Maintenance of normal blood sugar by providing the source as glycogen

- Synthesis of some of the pl. proteins & prothrombinFiltration: bacteria, endotoxins, viruses, antigens, byproducts of coagulationStorage: fluids, vitamins, minerals

Liver diseasesLiver diseases1ry liver diseases are uncommon in

domestic animals, with the exception of Fascioliasis, Fatty liver and poisoning.

2ndry liver diseases" Associating other diseases frequently seen in animals e.g RVFBy spread from another organs e.g.

Lung abscess, T.B. RVF, etc.

Liver diseases either:Liver diseases either:

1- Acute diseases (Obstructive or non)2- Chronic dis. (Obstructive or non)Liver diseases either:• Localised: T.B. Cysts, Abscess• Diffused: Hepatitis or hepatosis.• Inflammatory or Non Inflam.

Functional disorders resulting Functional disorders resulting from liver diseases are due to:from liver diseases are due to:

• Injury of hepatic cells and leakage of its secretion (↑ALT, AST, ADH).

• Shrinkage of functional mass of the Liver due to atrophy, fibrosis or cancer (↓levels of Albumin, prothrombin).

• Obstruction of bile ducts (↑Bilirubin, AlP, GG).

• Change in Vankupfer cell activities.

Signs of liver and Signs of liver and billiarybilliary diseasedisease

1- Jaundice2- Nervous signs.3- Edema.4- Digestive Troubles

(Diarrhea/constipation)5- Photosensitization.6- Hemorrhagic diathesis.

Signs of liver and Signs of liver and billiarybilliary diseasedisease7- Abd. Pain.8- Change of Liver size.9- Displacement of liver.10- Rupture of liver.11-Black liver in sheep.12- Anorexia, vomition, emaciation,

anemia

Normal appearanceNormal appearance

Fatty liverFatty liver

SubmandibularSubmandibular edema (Bottle Jaw)edema (Bottle Jaw)

SubmandibularSubmandibular edema (Bottle Jaw)edema (Bottle Jaw)

PhotosensitizationPhotosensitization

PhotosensitizationPhotosensitization

PhotosensitizationPhotosensitization

Diagnosis of liver diseaseDiagnosis of liver disease• Case history:• Signs:• X-ray.• Abdominal sonography• Liver function tests• Liver biopsy

Clinical significance of LFT.Clinical significance of LFT.• Conformation of liver diseases, its

severeity, taking in consideration hepatic huge compensatory power.

• Differentiation of types of Jaundice.• Therapeutic follow-up and evaluation of

prognosis.• Evaluation of the influence of other

systemic diseases on liver e.g renal, cardiac, malignancies, toxicities etc.

Classification of liver function tests.Classification of liver function tests.• No single test is specific, not very

sensitive (cirrhosis) or specific (non-hepatic factors).

2 categories - Tests that assess:1. Synthetic Function tests.2. Liver Damage tests.a. Hepatocellular diseaseb. Cholestastic disease

II-- Synthetic function: Synthetic function: ProthrombinProthrombin: : Pl. protein synthesized by the liver.Pl. protein synthesized by the liver.

Liver disease, Vit. K deficiency

1100 %12-13 secNormal

INRProthrombinconc

Prothrombintime

I- Synthetic Function 1-ProthrombinProthrombin

↑ prothrombin time, ↓Prothr. conc ↑ INR, ■ substantial impairment� not specific for liver disease� give Vitamin K:- responds �Vit. K deficiency- unresponsive �liver

I-Synthetic Function 2-AlbuminAlbumin

AlbuminNormal serum Albumin: 35-45 mg/dl.Albumin level decrease in:

- Chronic affections e.g Liver fascioliasis, Liver cirrhosis, fatty liver, Cancer

Normal level couples with abnormaltransaminases suggests acute process viral hepatitis or choledocholithiasis)

Causes of Low Serum Albuminand Total Protein

• Malnutrition• Liver disease• Nephrotic syndrome• Protein losing enteropathy.

IIII-- Excretory functionExcretory function11-- BilirubinBilirubin

Serum bilirubin• Direct bilirubin or conjugated• Indirect bilirubin or unconjugated (free) Urinary bile pigments• Urine bilirubin (mainly conjugated)

- Normally absent in urine- Its presence : Hepatitis, obstructed duct

• Urobilinogin (free birubin) :- Its presence means open bile duct- Its increase : hemolysis of RBCs

Normal serum Total & Direct Normal serum Total & Direct BilirubinBilirubin

Mg/dl0-0.10-0.3Dogs

Mg/dl0-0.50-2.0Horse

Mg/dl0-0.250-0.6Camel

Mg/dl0-0.20-0.4Sheep

Mg/dl0-0.20-0.5Cattle

HyperbilirubinemiaHyperbilirubinemiaPhysiological:• Lipid mobilization, Fasting horses• Inability of liver cells to metabolize

bilirubin.Pathological:• Excessive Hemolysis of RBCs

(increased free bilirubin)• Hepatitis (Increased direct & indirect

bilirubin)• Obstruction of bile duct: Excess direct

and mild indirect bilirubin

Elevated Direct Bilirubin

Normal level < 0.2 mg/dl• Biliary obstruction• Hepatocellular disease

IIIIII--Tests based on excretion of foreign Tests based on excretion of foreign dyes.dyes.

It is of little clinical significance, but it is a good indicator for liver function.BSP or Rosbengal or endothiazineinjectd iv in 5mg/kg bwt.Blood sample drawn every 5 min.Value of dye in each correlated negatively with liver capacity to get ride the dye.

IVIV--Others Tests depend on the specific Others Tests depend on the specific biochemical function of the liverbiochemical function of the liver

• Galactose Tolerance test.• Cholesterol level in blood.• Ammonia, urea, indole etc

VV-- Tests depends on enzymatic Tests depends on enzymatic activity of the liveractivity of the liver

• Increased levels indicate hepatic cell injury, its necrosis or increased permeability e.g. AST, ALT, LDH.• Increased ALP , GGT means bile

obst.• Decreased level means disturbance

of its production in liver e.g Cholineesterase.

Enzymes of clinical importance in Enzymes of clinical importance in liver diseasesliver diseases

1 – Aspartate aminotransferase (AST )2 – Alanine aminotransferase (ALT)3 – Gamma Glutamyle Transpeptidase (GGT)4- Arginase (Arg)5 – Sobitol dehydrogenase (SDH)6 – Lactate dehydrogenase (L.D.H)7 – Alkaline phosphatase (ALP)

Aminotransferases• Enzymes that leak when liver cells

damagedALT = more specific for liver disease in human AST:ALT ratio: >2:1 alcoholic liver disease

• ALT>AST pyridoxine (B6) deficiency:• Alcohol causes mitochondrial injury• AST: cytosol & mitochondria

Aminotransferases• levels don’t correlate with degree of damage• typical ranges

Cholestatic DiseaseCholestasis = lack of bile flow•� jaundice: pruritis, weight loss

Extrahepatic: obstruction in bile duct eg. strictures, stones, tumors

Intrahepatic : impairment bile formation in liver or obstruction of bile ducts within liver eg. viral/alcoholic hepatitis, drugs, biliary cirrhosis, sclerosing cholangitis

Cholestatic Disease• Alkaline Phosphatase (ALP)

>80% in liver and boneComponent of cells lining bile ducts↑ ALP synthesis by liver in cholestasisALP >3-5X: cholestatic diseasedoesn’t differentiate intra/extrahepatict½ = 7d �↑ after several days

Sources of Alkaline Phosphatase• Liver• Bone• Small intestines• Placenta/Pregnancy• Regan isoenzyme (lung

teratoma)

Causes of Elevated ALP

PregnancyPancreatic CancerSarcoidAmyloidHyperthyroid

Primary biliarycirrhosis CholestasisHypernephroma

Primary Biliary Cirrhosis

• Elevated ALP levels• Elevated bilirubin• Mildly elevated transaminases• + Antimitochondrial antibodies• + Antinuclear antibodies (ANA)

Cholestatic Disease

γ-Glutamyl Transpeptidase (GGT)Enzyme produced in bile ducts

�sensitiveNot specific: inducible in other

diseases/drugs.Used to confirm liver source of ↑ ALP↑’s with alcohol ingestionnot specific� use when AST:ALT >2:1

Elevated Lactate Dehydrogenase

(Normal 50-150)• Myocardial infaction• Pneumocystis Pneumonia (yeast

like fungus)• Hemolytic Anemia• Pancreatitis• Mononucleosis (Epstein Barr virus)

Clinical significance of hepatic Clinical significance of hepatic enzuymeenzuyme

Non specific, good in hepatic cell necrosis

within the package of clinical & lab. findings

Arginase

Bone, intestinal mm, liver and placenta

within the package of clinical & lab. Findings, especially for bile duct

ALP

Human, cannineInjury of liver cells in human, cannine

ALT

Skelatal, cardiac, hepatic, good tool in cows, horses

Its increase explained within muscular and hepatic disorders within the package of clinical & lab. findings

AST (s-

GOT)

SpecificityClinical significance

VIVI-- Liver biopsyLiver biopsy

• Technique.• Instrumentation.• Animal preparation.• Uses:• Fatty liver cirrhosis.

Stepwise approach• Confirm the abnormal liver test result

actually reflects liver disease.- rule out non-hepatic factors- confirm each abnormal test with another test

• eg. ↑ AST with ↑ ALT• ↑ ALP with ↑ GGT• ↑ albumin with ↑ INR

Report of LFTReport of LFT

0-1.5mg/dlIndirect Bilrubin

0-0.3mg/dlDirect Bilirubin

0-2.5mg/dlTotal Bilirubin

30-45mg/dlGlobulin35-45mg/dlAlbumin65-85mg/dlT. protein

NormalresultUnitTest

Report of LFTReport of LFT

12-14secProthrombintime

Up to 120U/lALP

Up to 25U/lGGT

Up to 80U/lALT

Up to 100U/lAST

NormalresultunitTest