1. JAUNDICE & LIVER FUNCTION
TESTS
By
DR KHALED SALEH ALGERIRI
International Medicine School – MSU
February 2016
2. 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
3. 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
4. Lipid Metabolism:
Synthesis of lipoproteins, Phospholipids ,
Cholesterol.
Fatty acid Metabolism – βOxidation , Ketone body
formation,
Bile acid synthesis.
5. Excretion and Detoxification:
Conjugation and Excretion of bilirubin
Cholesterol 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
7. Special tests:
Bile acid levels
Blood ammonia
α1- antitrypsin
α1-Fetoprotein
Hepatitis markers
Immunoglobulins
Ceruloplasmin
Ferritin
LIVER FUNCTION TESTS
8. What role do LFTs in clinical management ?
Detecting the presence of liver disease
Indicating the broad diagnostic category of the liver disease
Monitoring treatment
9. 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
11. • 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.
12. Normal range
Bilirubin type Bilirubin level
Total bilirubin 0.0-1.4 mg/dL or 1.7-20.5 mcmol/L
Direct 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
13. 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.
14. 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.
15. 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.
16. 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.
17. • 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.
19. 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 liver
Vitamin 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.
20. 4-Transaminases:
ALT(SGPT) 7 to 56 IU/L
AST(SGOT) 10 to 40 IU/L
ALT 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.
21. 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.
22. 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)
23. Medications That Cause Abnormal Aminotransferase
Levels
Some 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,
24. 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
.
25. 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.
26. 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.
27. Low values
Conditions 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.
28. What Affects the Test
Taking 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
29. 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.
30. 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
31. 8- Lactate dehydrogenase
Normal value range is 105 - 333 IU/L
Why It's Done
The 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
32. Lactate dehydrogenase
High value indicates
Blood flow deficiency (ischemia)
1-Heart attack 2- Hemolytic anemia
3-Infectious mononucleosis 4- Liver disease (for example, hepatitis)
5-Low blood pressure 6- Muscle injury
7-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.
33. 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.
34. 9-Blood Ammonia
An 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/L
Newborns: 90-150 mg/dL 64-107 mmol/L
35. High level indicates
Liver disease, such as cirrhosis or hepatitis.
Reye syndrome.
Heart failure.
Kidney failure.
Severe bleeding from the stomach or intestines.
36. 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/L
Children: 7-140 ng/mL or 7-140 mg/L
Babies 1 to 5 months: 50-200 ng/mL or 50-200 mg/L
Newborns: 25-200 ng/mL or 25-200 mg/L
37. 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