7/2/2015Basics of Significance Testing1 Chapter 15 Tests of Significance: The Basics.
Significance of Globulins
Transcript of Significance of Globulins
Significance of globulins
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Plasma proteins
albumin Globulins fibrinogen
Alpha 1Alpha 2 Beta1Beta2
Gamma
Globulins can be separated by half saturation and by
electrophoresis.
Site of synthesis:α and β in liver
γ in plasma cells or B-cells of lymphoid tissue
α globulins
• They are glycoproteins• Further subclassified as
α1and α2
• Depending on their electrophoretic mobility
α1 globulins
• α1-acid glycoprotein• Also called orosomucoid• Considered to be a reliable
indicator of acute inflammation• Functions:• Binds to progesterone as a
transport protein for this hormone
• Carry needed carbohydrate to the site of tissue repair
Clinical importance
• Increase:• In acute inflammation, liver
cirrhosis and malignant conditions
• Decrease:• Hypoproteinemia, hepatic
diseases, malnutrition and nephrotic syndrome
α1 fetoprotein
• Also known as α1 fetoglobulin
• Present in high concentration in fetal blood during pregnancy
• The normal value is 1 mg/dl• Clinical importance• Tumour marker of hepato
cellular carcinoma
α1globulin inhibitor
Are the inhibitors of coagulationAlso inhibit digestive enzymes like
trypsin and chymotrypsin
α1 antitrypsin• Also known as α antiprotease • The protein is highly polymorphic,multiple
forms can be separated by electrophoresis• Synthesised in the liver and it is the
principle inhibitor of human plasma• It is a protease inhibitor.• It inhibits all serine proteases• E.g trypsin,
chymotripsin,plasmin,thrombin
• A very low or absence of α1globulin band in electrophoresis suggests α1antitrypsin deficiency
Phenotype:the homozygous phenotype Z
Z suffers from severe deficiency α1antitrysin and is susceptible to lung disease
and cirrhosis of liver
• Increase:• In response to inflammation. It is
considered as one of the “acute phase reactant”
• In trauma, burns, infarction, malignancy, liver disease.
inflammatory cells and red blood cells
• Chronic hepato cellular diseases and bilary obstruction
• In pregancy and also during contraception medication
• Neonates have serum concentration much higher than adults
• Decrease• Protein losing disorders:• Nephrotic syndrome and diffuse
hypoproteinemia• Emphysema of lungs• Juvenile cirrhosis of liver
Clinical significance
• Role in emphysema of lungs • About 5% of emphysema• Occurs mainly with ZZ phenotype• Normally α1 antitrypsin protects the
lungs from bacterial infection by binding with “active elastase”.
• When α1 antitrypsin is deficient the complex with elastase is not formed
• Active elastase brings about proteolysis of lung and tissue damage
elastase
• Absence of AAT
• Active elastase
• Lung tissue damage
• emphysema
• Presence of AAT
• Inactive elastase
• No lung tissue damage
• Role in smoking• Smoking oxidises the methionine of α1
antitrypsin • Inactivates the protein• It cannot bind with active elastase • Proteolysis of lungs and tissue damage
occurs• Accelerating development of emphysema
• Role in cirrhosis• Zz phenotype accumulate in the cisternae
or endoplasmic reticulum of hepatocyte• Results in cirrhosis of liver
• Role as tumour marker• As an inhibitor of fibrinolysis
α2 globulins
CeruloplasminIt is a copper containing α2
globulinIt is a glycoprotein having 8 sites
for copper bindingNormal level in plasma is 25-
50mg/dlIt has enzyme activities
Functions of ceruloplasmin
• Contains 90% of total serum copper
• Acts as ferroxidase and helps in oxidation of Fe2+ to Fe3+ which can be incorporated into transferrin
Clinical significance
• Increase• In pregnancy, inflammatory
diseases, malignancy, oral oestrogen therapy and contraceptive pills
• Dercrease• In wilson disease and in menke’s
disease
Haptoglobin
• Formed by two types of polypeptide chains
• Two α chains ( possibly 3) and only one form of β chain.
• Synthesised in liver by hepatocytes
Function
• Binds with free Hb and minimises urinary loss of Hb
• Combining power of Hp with free Hb varies with different phenotypes
• After binding Hp-Hb complex circulates in blood which cannot pass through glomerular filtrate.
Clinical significance
• Concentration is increased in inflammatory diseases
• Mismatched blood transfusion• To evaluate the rheumatic
diseases
β-globulin
• β lipoprotein• Transferrin• True carrier of Fe• Site of synthesis is the liver• Functions• Transport Fe from the intestine
to site of synthesis of Hb• Unsaturated transferrin has a
bacteriostatic function
C reactive protein
• It precipitates with group C polysaccharide of pneumococci in the presence of Calcium ions
• Clinical significance• Binds to heme and bears some
chemical and antigenic relation to liver catalysis
• Bind to T lymphocyte and activate complement
• A role in the formation of heme • Non-specific indicator of inflammation• It remains increased in solid tumours
hemopexin• Synthesised by the parenchymal cell
of liver• Functions• Binds and removes circulating heme
from breakdown of Hb• Clinical significance• Inceases during pregnancy, diabetes
mellitus,• Duchenne muscular dystrophy and
melanomas• Decreases in hemolytic disorders, at
birth in new borns,
β2 microglobulins
• Increased in renal diseases and it is a reflection of impairment of function of glomerular membrane or renal tubules
• Tumour marker
• Urinary β2 M in Wilson disease, chronic nephritis, poisoning
• β2 M in serum in chronic nephritis, malignant tumors, abnormal pregnancy, chronic rheumatism
IgD
IgM IgA
IgG
IgE
γ globulins
reference
• Internet• Shinday• harper
Thank you