Download - Dr.ehab plasma protein
Total blood volume is about 4.5 to 5 liters in adult human being
i.The defibrinated plasma is called serum,
which lacks coagulation factors including
prothrombin and fibrinogen.
ii.Total protein content of normal plasma is 6 to
8 g/100 ml.
iii.The plasma proteins consist of albumin (3.5
to 5 g/dl), globulins (2.5-3.5 g/dl) and fibrinogen
(200-400 mg/dl). The albumin:
globulin ratio is usually between 1.2:1 to 1.5:1.
iv.Almost all plasma proteins, except
immunoglobulins are synthesized in liver.
ELECTROPHORESIS
The term electrophoresis refers to the movement of
charged particles through an electrolyte when
subjected to an electric field.
Serum electrophoretic patterns
1.Chronic infections: The gamma globulins are increased, but the
increase is smooth and widebased.
2.Multiple myeloma: In para-proteinemias, a sharp spike is noted and
is termed as M-band. This is due to monoclonal origin of
immunoglobulins in multiple myeloma
3.Nephrotic syndrome: All proteins except very big molecules are
lost through urine, and so alpha-2 fraction (containing macroglobulin)
will be very prominent.
ALBUMIN
The name is derived from the white
precipitate formed when egg is boiled
Functions of Albumin
1. Colloid Osmotic Pressure of Plasma
Proteins cannot easily escape out of blood vessels,
and therefore, proteins exert the effective osmotic
pressure'. It is about 25 mm Hg The maintenance of blood volume is dependent on this
effective osmotic pressure.
Transport Function
Albumin is the carrier of various hydrophobic
substances in the blood.
i Bilirubin and nonesterified fatty acids are
specifically transported by albumin.
ii. Drugs (sulpha, aspirin, salicylates,
dicoumarol, phenytoin).
iii. Hormones: Steroid hormones, thyroxine.
iv. Metals: Calcium, copper and heavy metals
are nonspecifically carried by albumin.
NutritionalFunction
All tissue cells can take up albumin by
pinocytosis.
It is then broken down to amino acid level.
Albumin may be considered as the
transport form of essential amino acids
from liver to other tissues.
Blood Brain Barrier Albumin-fatty acid complex cannot cross
blood brain barrier and hence fatty acids
cannot be taken up by brain.
The bilirubin from albumin may be
competitively replaced by aspirin and such
other drugs.
In newborns, bilirubin is already high.
There is a probability that free bilirubin is
deposited in brain leading to kernicterus
and mental retardation.
Edema
Hypoalbuminemia will result in tissue edema
i. Manutrition, where albumin synthesis is depressed
(generalised edema) ii. Nephrotic syndrome, where albumin is lost
through urine (facial edema). Presence of albumin in
urine is called albuminuria.
Large quantities (many grams per day) of albumin is
lost in urine in nephrotic syndrome.
Small quantities are lost in urine in acute nephritis,
and other inflammatory conditions of urinary tract.
Detection of albumin in urine is done by heat and
acetic acid test.
iii. Cirrhosis of liver (mainly ascites). Albumin
synthesis is decreased.
iv. Chronic congestive cardiac failure: Venous
congestion will cause increased hydrostatic
pressure and decreased return of water into
capillaries and so pitting edema of feet may result.
Albumin-Globulin Ratio
In hypoalbuminemia, there will be increase
in globulins which are synthesised by the
reticuloendothelial system.
Albumin-globulin ratio (A/G ratio) is thus
altered or even reversed. This again leads
to edema.
TRANSPORT PROTEINS
Blood is a watery medium; so lipids and lipid
soluble substances will not easily mix in the
blood. Hence, such molecules are carried by
specific carrier proteins
Albumin
Pre-albumin or Transthyretin
Thyroxine binding globulin (TBG)
Retinol binding protein (RBP)
Transcortin or cortisol binding globulin
(CBG)
Transferrin
ACUTE PHASE PROTEINS
The level of certain proteins in blood may
increase 50 to 1000 folds in various
inflammatory and neoplastic conditions.
Such proteins are acute phase proteins.
Important acute phase proteins are described
C-Reactive Protein (CRP)
Ceruloplasmin
Wilson's Disease
STRUCTURE OF IMMUNOGLOBULINS
Immunoglobulin is abbreviated as Ig. The terms
gamma globulin and immunoglobulin are not
synonymous. Gamma globulin is the term
describing its mobility in electrical field. Most of
the immunoglobulin's have the gamma mobility;
but some may move along with beta or even with
alpha globulins. Immunoglobulin is a functional
term, while gamma globulin is a physical term. In
1962, Rodney Porter and Gerald Edelman
independently proposed the structure for
immunoglobulin molecule, for which both of them
were awarded Nobel prize in 1972.
Heavy and Light Chains The structure of IgG molecule. It is made up of 2
heavy (H) chains and 2 light (L) chains,
combined through disulfide bridges. In the case
of IgG, H chains are composed of 440 amino
adds and L chains made up of 214 amino acids.
Depending on the heavy chain make up, the
immunoglobulin's are
differentiated into 5 major
1. Immunoglobulin G (lgG) is made up of
heavy chain g (gamma)
2. IgM has m (mu) heavy chain
3. IgA has a (alpha) heavy chain
4. IgD contains (delta)
5. IgE heavy chain is called e (epsilon).
The light chains are either K (kappa) or l (lambda) in all the classes. For
example, IgG may consist of either g2 k2 g2 l2
Variable and Constant Regions Both the heavy and light chains contain
relatively variable (V) and constant (C) regions with regard to their amino
acid composition. VL and CL are the general terms for these regions on
the light chain; while VH and CH specify variable and constant regions on
the heavy chain
At the amino terminal end, about 100 amino acids in light chains and in
heavy chains constitute the variable region. Here the amino acid sequence
can vary in Hand L chains, so that the body could synthesise enormous
varieties of different proteins.
Different Classes of
Immunoglobulins 1. Immunoglobulin G (lgG) a. IgG contains two heavy chains and two light chains; heavy chains being
of gamma. Due to its sedimentation coefficient, it is sometimes referred to
as 78 Ig.
b. It is the antibody seen in secondary immune response.
c. It can pass from vascular compartment to interstitial space. It can cross
placental barrier, and protects the new born child from infections.
2. Immunoglobulin M (lgM) IgM are macroglobulins or 19S immunoglobulins.
Five subunits, each having 4 peptide chains (total
10 heavy chains and 10 light chains) are joined
together by a J-chain polypeptide
It can combine with 5 antigens simultaneously,
and so IgM is very effective for agglutinating
bacteria.
Being a large molecule, it cannot come out of
vascular space.
IgM are the predominant class of antibodies in
primary response.
3. Immunoglobulin A (lgA) a.IgA usually are dimers (total 4 heavy
chains and 4 light chains). The J chain
connects the dimers.
b.They are the secretory antibodies seen in
seromucous secretions of gastrointestinal
tract, nasopharyngeal tract, urogenital tract,
tears, saliva, sweat, etc. The dimers are
stabilised against proteolytic enzymes by
the secretory piece.
4. Immunoglobulin E (lgE) They mediate allergy, hypersensitivity and
anaphylaxis.
They have the property to fix on mast cells
and basophils. When certain antigens
such as penicillin are injected a few times,
IgE class antibodies are produced which
anchor on mast cells.
When the same antigen is injected next
time, the antigen fixes on cell surface
antibodies, causing mast cell
degranulation, and release of histamine
and slow reacting substance.
PARAPROTEINEMIAS 1. Multiple Myeloma (Plasmacytoma)
i. When Ig-secreting cells are transformed into malignant cells, one
clone alone is enormously proliferated. Thus, Ig molecules of the
very same type are produced in large quantities.
ii. This is seen in electrophoresis as the myeloma band or
monoclonal band or M band with a sharp narrow spike (Fig. 13.1).
iii. Multiple myeloma is characterized by paraproteinemia, anemia,
lytic bone lesions and proteinuria.
iv. Bone marrow examination reveals large number of malignant
plasma cells. Bone pain and tenderness are the common
presenting complaints. Spontaneous pathological fracture of weight
bearing bones, rib and vertebrae may occur.
2. Bence Jones Proteinuria Henry Bence
Jones described it in 1848.
i. This disorder is seen in 20% of patients with
multiple myeloma.
ii. Monoclonal light chains are excreted in
urine.
iii. The Bence Jones proteins have the special
property of precipitation when heated
between 45°C and 60°C; but redissolving at
higher than 80°C and lower than 45°C.
3. Hypergammaglobulinemia This
disorder can occur in:
i. Chronic infections, where antibody
production is high. Examples are
leprosy, tuberculosis, malaria and
subacute bacterial endocarditis
ii. Aberrant immune reactions such as rheumatoid
arthritis, collagen disorders, glomerulonephritis,
and such autoimmu ne disorders where
cryoglobulins may also be present.
iii. Paraproteinemias such as in multiple myeloma
Ceruloplasmin contains copper; it is
decreased in Wilson's hepato lenticular
degeneration. Blood fibrinogen level is
200-400 mg/dl. Hemophilia is due the
deficiency of anti-hemophilic globulin
(AHG) or factor VIII. Immunoglobulins
are classified into 5 classes; IgG, M, A,
0 and E. IgM is seen in primary
antibody response. IgA is secretory
antibodies. IgE is associated with
allergy and anaphylaxis.