Liver function test

By

Dr. Ali H. Sadiek
Prof. Of Internal Veterinary Medicine and Clinical Lab. Diagnosis Faculty of Vet. Medicine, Assiut University For the undergraduate student of 5th year Internal medicine

Liver 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 & prothrombin Filtration: bacteria, endotoxins, viruses, antigens, byproducts of coagulation Storage: fluids, vitamins, minerals

Liver diseases
1ry 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 RVF By spread from another organs e.g. Lung abscess, T.B. RVF, etc.

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 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 billiary disease
1- Jaundice 2- Nervous signs. 3- Edema. 4- Digestive Troubles (Diarrhea/constipation) 5- Photosensitization. 6- Hemorrhagic diathesis.

Signs of liver and billiary disease
7- 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 appearance

Fatty liver

Submandibular edema (Bottle Jaw)

Submandibular edema (Bottle Jaw)

Photosensitization

Photosensitization

Photosensitization

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

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.
• No single test is specific, not very sensitive (cirrhosis) or specific (nonhepatic factors). 2 categories - Tests that assess: 1. Synthetic Function tests. 2. Liver Damage tests. a. Hepatocellular disease b. Cholestastic disease

I- Synthetic function: Prothrombin: Pl. protein synthesized by the liver.
Prothrombin time Normal Liver disease, Vit. K deficiency 12-13 sec Prothrombin conc 100 % INR 1

I- Synthetic Function 1-Prothrombin
↑ 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-Albumin
Albumin Normal 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 abnormal transaminases suggests acute process viral hepatitis or choledocholithiasis)

Causes of Low Serum Albumin and Total Protein
• Malnutrition

• Liver disease • Nephrotic syndrome • Protein losing enteropathy.

II- Excretory function 1- Bilirubin
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 Bilirubin
Cattle Sheep Camel Horse Dogs

0-0.5 0-0.4 0-0.6 0-2.0 0-0.3

0-0.2 0-0.2 0-0.25 0-0.5 0-0.1

Mg/dl Mg/dl Mg/dl Mg/dl Mg/dl

Hyperbilirubinemia Physiological: • 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

III-Tests based on excretion of foreign dyes.

It is of little clinical significance, but it is a good indicator for liver function. BSP or Rosbengal or endothiazine injectd 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.

IV-Others Tests depend on the specific biochemical function of the liver

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

V- Tests depends on enzymatic activity 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 Choline esterase.

Enzymes of clinical importance in liver 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 damaged ALT = 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 Disease
Cholestasis = 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 bone Component of cells lining bile ducts ↑ ALP synthesis by liver in cholestasis ALP >3-5X: cholestatic disease doesn’t differentiate intra/extrahepatic t½ = 7d ↑ after several days

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

Causes of Elevated ALP
Pregnancy Pancreatic Cancer Sarcoid Amyloid Hyperthyroid Primary biliary cirrhosis Cholestasis Hypernephroma

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 sensitive Not specific: inducible in other diseases/drugs. Used to confirm liver source of ↑ ALP ↑’s with alcohol ingestion not 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 enzuyme
Clinical significance AST (sGOT) ALT ALP
Its increase explained within muscular and hepatic disorders within the package of clinical & lab. findings Injury of liver cells in human, cannine

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

Human, cannine Bone, intestinal mm, liver and placenta Non specific, good in hepatic cell necrosis

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

VI- Liver 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 LFT
Test Unit result Normal

T. protein Albumin Globulin Total Bilirubin Direct Bilirubin Indirect Bilrubin

mg/dl mg/dl mg/dl mg/dl mg/dl mg/dl

65-85 35-45 30-45 0-2.5 0-0.3 0-1.5

Report of LFT
Test AST ALT GGT ALP unit U/l U/l U/l U/l result Normal Up to 100 Up to 80 Up to 25 Up to 120 12-14

Prothrombin sec time

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