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.