JAUNDICE & LIVER FUNCTION TESTS

By

DR KHALED SALEH ALGERIRI International Medicine School – MSU

February 2016

Functions: Liver is the largest Organ of the body

weighing about 1.5kg. Liver is called kitchen of our body.Carbohydrate Metabolism

In fed state glycogen synthesis and excess glucose is converted to fatty acid and then TAGS which get incorporated to VLDL and transported to adipose tissue.

In Fasting state glucose concentration is maintained by glycogenolysis and gluconeogenesis

LIVER

Protein Metabolism:

Synthesis of albumin and various plasma proteins except immunoglobulins.

Most of the coagulation factors like fibrinogen, Prothrombin(II), V, VII, IX , X , XI, XII, XIII.

Out of these II , VII ,IX, X cannot be synthesized with out vitamin –K.

Transport proteins – eg: Transferrin

Lipid Metabolism: Synthesis of lipoproteins, Phospholipids ,

Cholesterol.

Fatty acid Metabolism – βOxidation , Ketone body formation,

Bile acid synthesis.

Excretion and Detoxification:Conjugation and Excretion of bilirubinCholesterol is excreted in the bile as bile acids and

cholesterol.

Steroid hormones are metabolized and inactivated by conjugation with glucuronic acid and sulphate and are excreted in Urine.

Drugs are metabolised and inactivated by CYT P450 of endoplasmic reticulum and excreted through bile / urine

Enzymes:

ALT(SGPT) – Marker enzyme for liver diseases

AST(SGOT) Alkaline phospatase (ALP) Gama glutamyl transferase (GGT) 5’ – Nucleotidase

LIVER FUNCTION TESTS

Special tests: Bile acid levels

Blood ammonia

α1- antitrypsin

α1-Fetoprotein

Hepatitis markers

Immunoglobulins

Ceruloplasmin

Ferritin

LIVER FUNCTION TESTS

What role do LFTs in clinical management ?

Detecting the presence of liver disease

Indicating the broad diagnostic category of the liver disease

Monitoring treatment

1. Serum Bilirubin :• A bilirubin test measures the amount of bilirubin in a blood sample. Bilirubin is

a brownish yellow substance found in bile. It is produced when the liver breaks down old red blood cells. Bilirubin is then removed from the body through the stool (feces) and gives stool its normal color.

Elevations in serum and urine bilirubin levels are normally associated with Jaundice.

• Primary site of synthesis:-

SPLEEN: The Graveyard

of Red Blood Cells• Secondary site of synthesis:-

LIVER & BONE MARROW

Liver Function Tests

RBCs Breakdown

Hemoglobin Produces & Breakdown

Heme

Biliverdin

Bilirubin

Heme Oxygenase

BiliverdinReductase

Bilirubin Metabolism

• Bilirubin circulates in the bloodstream in two forms:• Indirect (or unconjugated) bilirubin. This form of bilirubin does not dissolve

in water (it is insoluble). Indirect bilirubin travels through the bloodstream to the liver, where it is changed into a soluble form (direct or conjugated).

• Direct (or conjugated) bilirubin. Direct bilirubin dissolves in water (it is soluble) and is made by the liver from indirect bilirubin.

Normal range Bilirubin type Bilirubin levelTotal bilirubin 0.0-1.4 mg/dL or 1.7-20.5 mcmol/LDirect bilirubin 0.0-0.3 mg/dL or 1.7-5.1 mcmol/L

Indirect bilirubin 0.2-1.2 mg/dL or 3.4-20.5 mcmol/L

Bilirubin in Urine:Normally bilirubin is absent in urine.Conjugated bilirubin being water soluble is excreted in urine in obstructive jaundice.Urine urobilinogen - normally trace amounts is present.In obstructive jundice no urobilinogen is present in urine.

2-TOTAL PLASMA PROTEIN

A total serum protein test measures the total amount of protein in the blood. It also measures the amounts of two major groups of proteins in the blood: albumin and globulin.• Albumin is made mainly in the liver. It helps keep the blood from leaking out

of blood vessels. Albumin also helps carry some medicines and other substances through the blood and is important for tissue growth and healing.

• Globulin is made up of different proteins called alpha, beta, and gamma types. Some globulins are made by the liver, while others are made by the immune system. Certain globulins bind with hemoglobin. Other globulins transport metals, such as iron, in the blood and help fight infection. Serum globulin can be separated into several subgroups by serum protein electrophoresis.

Albumin is tested to:• Check how well the liver and kidneys are working.• Find out if your diet contains enough protein.• Help determine the cause of swelling of the ankles (edema) or abdomen (ascites)

or of fluid collection in the lungs that may cause shortness of breath (pulmonary edema).

• Globulin is tested to:• Determine your chances of developing an infection.• See if you have a blood disease, such as multiple myeloma or macroglobulinemia.

Normal range of Total plasma proteins Total protein: 6.4-8.3 grg/dL or 64-83 (g/L)

Albumin: 3.5-5.0 g/dL or 35-50 g/L Alpha-1 globulin: 0.1-0.3 g/dL or 1-3 g/L Alpha-2 globulin: 0.6-1.0 g/dL or 6-10 g/L Beta globulin: 0.7-1.1 g/dL or 7-11 g/L

High albumin levels may be caused by: Severe dehydration.High globulin levels may be caused by:Diseases of the blood, such as multiple myeloma, Hodgkin's lymphoma, leukemia, macroglobulinemia, or An autoimmune disease, such as rheumatoid arthritis, hepatitis, Kidney diseases, Liver disease.and Tuberculosis.

• Low albumin levels may be caused by:• A poor diet (malnutrition).• Kidney disease. Liver disease.• An autoimmune disease, such as lupus or rheumatoid arthritis.• Gastrointestinal malabsorption syndromes, such as sprue or

Crohn's disease.• Hodgkin's lymphoma.• Uncontrolled diabetes.• Hyperthyroidism.• Heart failure.

(Inhibits elastase)

20 to 40mg/dl

< 25 μg/L

3-Prothrombin time Normal 11 to 12 seconds

PT is prolonged in severe parenchymal liver disease due to decreased synthesis of prothrombin.

Elevated PT may be reflection of decreased synthetic activity of liverVitamin K is required for synthesis of prothrombin.

vitamin K deficiency can also lead to prolonged PT.

Note:If PT returns to normal after vitamin K injection it indicates that hepatocyte function is good.

4-Transaminases:

ALT(SGPT) 7 to 56 IU/LAST(SGOT) 10 to 40 IU/LALT is primarily localized to the liver. It is the marker enzyme of the liver.ALT is present in the cytosol of hepatocytes. AST is present in a wide variety of tissues like heart, liver, skeletal muscle, kidney, brain.AST is present both in the cytosol and mitochondria of the hepatocytes.

Liver contains both enzymes but more of ALT

Estimation is very useful in assessing severity and prognosis of liver parenchymal disease especially infective hepatitis.

Also very useful as screening test in outbreak of infective hepatitis.

Diseases That Cause Abnormal (Elevation)Aminotransferase Levels

• Acute viral hepatitis, such as hepatitis A or B• Chronic viral hepatitis, such hepatitis B or C• Cirrhosis of the liver (scarring of the liver due to long standing

inflammation of the liver) • Liver damage from alcohol abuse or alcoholic fatty liver• Hemochromatosis (a genetic condition causing long standing liver

damage due to iron build up in the liver)• Diminished blood flow to the liver (from shock or heart failure) 

Medications That Cause Abnormal Aminotransferase LevelsSome pain medications, or example, diclofenac (Voltaren) and naproxen Cholesterol-lowering medications, statins, for example, atorvastatin (Lipitor) and simvastatin .Some antibiotics, for example, sulfonamides and macrodantin;.Some tuberculosis medications, for example, isoniazid .Some anti-fungal medications,

5-Alkaline Phosphatase( ALP) - Adult 25 -100 IU/L Children Less than 350 U/L

A group of enzymes that catalyze the hydrolysis of a large number of organic phosphate esters..• Found in:

• Liver• Bone• intestine• First trimester placenta• Kidney

.

A test for alkaline phosphatase (ALP) is done to:

Check for liver disease or damage to the liver. Symptoms of liver disease can include jaundice, belly pain, nausea, and vomiting. An ALP test may also be used to check the liver when medicines that can damage the liver are taken.

Check bone problems (sometimes found on X-rays), such as rickets, bone tumors, Paget's disease, or too much of the hormone that controls bone growth (parathyroid hormone).

The ALP level can be used to check how well treatment for Paget's disease or a vitamin D deficiency is working.

High values Very high levels of ALP can be caused by liver problems, such as

hepatitis, blockage of the bile ducts (obstructive jaundice), gallstones, cirrhosis, liver cancer, or cancer that has spread (metastasized) to the liver from another part of the body.

High ALP levels can be caused by bone diseases, such as Paget's disease, osteomalacia, rickets, bone tumors, or tumors that have spread from another part of the body to the bone, or by overactive parathyroid glands (hyperparathyroidism).

Normal healing of a bone fracture can also raise ALP levels. Heart failure, heart attack, mononucleosis, or kidney cancer can raise

ALP levels. Women in the third trimester of pregnancy have high ALP levels

because the placenta makes ALP.

Low valuesConditions that lead to malnutrition (such as celiac disease) or are caused by a lack of nutrients in the diet (such as scurvy) can cause low ALP levels.

What Affects the TestTaking medicines that may damage the liver, such as some antibiotics, birth control pills, long-term aspirin use, and oral diabetes medicines.

Going through menopause. Postmenopausal women may have higher ALP levels than women who still have menstrual cycles.

The age:Children normally have much higher ALP levels than adults because rapid bone growth is normal in children and bones make ALP.

Drinking a lot of alcohol

6-Gamma glutamyl transferase (GGT)Gamma glutamyl transferase (GGT), or gamma glutamyl transpeptidase, may be measured in the blood to check the difference between bone ALP and liver ALP.

High levels of GGT are present when the liver is damaged but not present with bone disease. A high level of GGT may be caused by alcohol use or may mean that blocked bile ducts are causing inflammation.

The level of GGT may be high with the use of certain medicines, such as phenytoin and phenobarbital.

In some medical centers, a test that measures a substance called 5-nucleotidase is done instead of the GGT test because it is better at finding liver disease.

7- 5'-nucleotidase The normal value is 2 to 17 IU/L

High levels may indicate: Cholestasis (when bile, which is made by the liver to help digest fats, is blocked from flowing out of the liver

Destruction of liver cells Hepatitis (liver inflammation) Liver ischemia (loss of blood and oxygen to the liver) Liver tumor

8- Lactate dehydrogenaseNormal value range is 105 - 333 IU/L Why It's DoneThe LDH test is generally used to screen for tissue damage. This damage

may be acute (as in the case of a traumatic injury) or chronic (due to a long-term condition such as liver disease or certain types of anemia). It also may be used to monitor progressive conditions, such as muscular dystrophy and HIV.

Different LDH isoenzymes are found in different body tissues. The areas of highest concentration for each type of isoenzyme are:

LDH-1: heart and red blood cells LDH-2: white blood cells LDH-3: lungs LDH-4: kidneys, placenta, and pancreas LDH-5: liver and skeletal muscle

Lactate dehydrogenaseHigh value indicatesBlood flow deficiency (ischemia) 1-Heart attack 2- Hemolytic anemia3-Infectious mononucleosis 4- Liver disease (for example, hepatitis)5-Low blood pressure 6- Muscle injury7-Muscle weakness and loss of muscle tissue (muscular dystrophy)8-New abnormal tissue formation (usually cancer)9-Pancreatitis 10-Stroke

If the LDH level is raised, your doctor may order an LDH isoenzymes test to determine the location of any tissue damage.

High levels of LDH indicate some form of tissue damage. High levels of more than one isoenzyme may indicate more than one cause of tissue damage. For example, a patient with pneumonia could also have a heart attack. High levels of all five LDH isoenzymes could indicate multiple organ failure.

Low LDH Level indicates

LDH deficiency affects how the body breaks down sugar for use as energy in cells, particularly muscle cells. It’s very rare for a person to have low LDH levels.

9-Blood AmmoniaAn ammonia test measures the amount of ammonia in the

blood. Most ammonia in the body forms when protein is broken down by bacteria in the intestines . The liver normally converts ammonia into urea, which is then eliminated in urine.

Ammonia levels in the blood rise when the liver is not able to convert ammonia to urea. This may be caused by cirrhosis or severe hepatitis.

For this test, a blood sample may be taken from either a vein or an artery.

Normal range Adults: 9.5-49 mg/dL 7-35 mmol/L)

Children: 40-80 mg/dL 28-57 mmol/LNewborns: 90-150 mg/dL 64-107 mmol/L

High level indicates Liver disease, such as cirrhosis or hepatitis. Reye syndrome. Heart failure. Kidney failure. Severe bleeding from the stomach or intestines.

10- Blood FerritinA ferritin blood test checks the amount of ferritin in the blood. Ferritin is a protein in the body that binds to iron; most of the iron stored in the body is bound to ferritin. Ferritin is found in the liver ,spleen ,skeletal muscles, and bone marrow. Only a small amount of ferritin is found in the blood. The amount of ferritin in the blood shows how much iron is stored in your body.

Men: 18-270 (ng/mL) or 18-270 (mg/L)

Women: 18-160 ng/mL or 18-160 mg/LChildren: 7-140 ng/mL or 7-140 mg/LBabies 1 to 5 months: 50-200 ng/mL or 50-200 mg/LNewborns: 25-200 ng/mL or 25-200 mg/L

High values

Very high ferritin levels (greater than 1,000 ng/mL) can mean a large buildup of iron in the body (hemochromatosis).

Some diseases, including alcoholism, thalassemia, and some types of anemia that cause red blood cells to be destroyed, can also cause hemochromatosis. Also, if you have many blood transfusions, this can sometimes cause the body to store too much iron (acquired hemochromatosis).

High ferritin levels may also be caused by Hodgkin's disease, leukemia, infection, inflammatory conditions (such as arthritis), or a diet that is too high in iron.

Too much iron in body organs, such as the pancreas or heart, can affect how the organ works.

Low values

Low ferritin levels often mean an iron deficiency is present. This can be caused by long-term (chronic) blood loss from heavy menstrual bleeding, pregnancy, not enough iron in the diet, or bleeding inside the intestinal tract (from ulcers, colon polyps camera.gif, colon cancer, hemorrhoids camera.gif, or other conditions). In rare cases, too much iron may be lost through the skin (because of a disease such as psoriasis camera.gif) or in the urine.