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Plasma Proteins

  1. Composition of plasma
    Water : 91.5%
    Solutes : 8.5%
  2. The solute fraction consists of Proteins
    The relative percentage of the plasma proteins are:
  • Albumin (55%)
  • Globulins (38%)
  • Fibrinogen (7%)
  1. Non-protein nitrogenous substances
  • Nitrogen, urea, uric acid, creatinine, ammonium salts

Regulatory substances

  • Enzymes and hormones


  • Na, K, Mg, Ca, Cl, HPO4 - , HCO3-

Amino acids, glucose

Total plasma proteins = 6.4 gm to 8.3 gm /dL (average = 7.4 gm /dL)


Albumin = 3.5 to 5.2 gm/dL

Globulins = 1.7 to 3.2 gm/dL

Fibrinogen = 0.2 to 0.4 gm/dL


The normal albumin : globulin ratio (A : G ratio) :  about 1.7

  1. Classification of plasma proteins :-

1.  Classical or Howe method
In this method, the plasma proteins are classified into 3 major groups :
albumin, globulins and fibrinogen; the globulin fraction is further subdivided into other components
2.  Some fractions of globulins are :
Lipoproteins, glycoproteins, interleukins, haptoglobulins, cortisol-binding globulin, ceruloplasmin, transferrin, immunoglobulins
3. Electrophoretic method
By this, the plasma proteins can be separated into 5 fractions viz.  albumin, alpha 1, alpha 2, beta and gamma fractions.

  1. Functions of plasma proteins

1.  Maintenance of colloidal osmotic pressure
The osmotic pressure exerted by the plasma protein colloids is also called as oncotic pressure. The plasma proteins are able to exert osmotic pressure because the capillary walls are relatively impermeable to plasma proteins.

Value of this oncotic pressure : about 25 mm Hg
2.  Maintenance of blood pH
The plasma proteins can combine with acids or bases to maintain the pH o f blood. The plasma proteins are also responsible for 15% of the buffering capacity of the blood. How? There is weak ionization of their carboxyl (COOH) and amino (NH2) groups; these are capable of combining with acids or bases and buffer them. At the normal plasma pH of 7.40, the proteins are mostly in the an­ionic form
3.  Blood clotting
Plasma proteins contain a large number of proteins called clotting factors (viz. fibrinogen, prothrombin). Fibrinogen is converted into fibrin during the process of blood coagulation.
4.  Carriers
Plasma proteins act as carriers of metals, hormones (e.g. thyroid, adrenocortical, gonadal etc.), lipids, fat-soluble vitamins and drugs. 

  1. Advantage of the protein binding
    1. Prevents filtration of the bound hormones through the glomeruli
    2. Acts as a reservoir of the hormones
      Albumin acts as a non-specific transport protein for a number of substances e.g. metals, ions, fatty acids, amino acids, steroids, vitamins, hormones, bilirubin, enzymes, and drugs.

5. Defence mechanism
Immunoglobulins (also called gamma-globulins) and complement system are the plasma proteins responsible for body defence mechanism.

  1. Production of plasma protiens
1. Plasma cells
Circulating antibodies in the gamma globulin fraction of the plasma proteins are manufactured in the plasma cells

2. Liver
Most of the other plasma proteins are syn­thesized in the liver.
Properties of the individual plasma proteins

Molecular weight = 70,000
Half-life = about 10 days
Synthesis : in liver
  1. Function
    It is responsible for the carriage in the plasma of most of the bilirubin and of non-ionized calcium
  2. Metabolism
    In normal adult humans,
    1. The plasma albumin level = 3.5-5.0 g/dL
    2. The total ex­changeable albumin pool = 4.0-5.0 g/kg body weight
    3. 38-45% of this albumin is intravascular
    4. Much of the extravascular albumin is in the skin.
    5. Between 6% and 10% of the exchangeable pool is degraded per day
    6. The de­graded albumin is replaced by hepatic synthesis of 200-400 mg/kg/d.
  3. Regulation
    Albu­min synthesis is carefully regulated. It is decreased during fasting and increased in conditions such as nephro­sis in which there is excessive albumin loss.
  4. Globulins
    Molecular weight = 90,000 to 1,56,000
  5. Components
    The globulins consist of alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 fractions; the gamma globulins consist of the antibodies
  6. Synthesis
    Gamma globulin : in plasma cells
    Other globulins : liver
  7. Fibrinogen
    Molecular weight = 5,00,000
    Synthesis : liver
    The plasma fibrinogen concentration is raised in almost all diseases in which raised ESR is found, particularly in acute infections and in pregnancy.

Applied aspects

1.  Causes of hypoproteinemia

  1. Prolonged starvation
  2. Malabsorption syndrome
  3. Liver disease (because hepatic protein synthesis is decreased)
  4. Nephrosis (because of increased loss of albumin in urine) Because of the decrease in the plasma oncotic pressure, edema tends to develop Afibrinogenemia

2.  Causes

  1. Congenital: This can occur as a rare congenital abnormality; here, there is congenital absence fibrinogen
  2. Severe liver disease
  3. In pregnancy, as a complication of detachment of placenta. 
    It is characterized by defective blood clotting.


The plasma volume in a 60-kg man will be approximately:

A. 3 L              
B. 4 L              
C. 5 L              
D. 1.5 L



Plasma volume = 5 % of body weight So, in a 60-kg man, it will be 5/100 x 60 = 3 L


All the following are true statements except.

A. Plasma clots on standing
B. Serum = whole blood minus clot
C. Serum does not contain fibrinogen, clotting factors II, V and VIII
D. Serum has a lower serotonin content than plasma


Plasma remains fluid only if an anticoagulant is added.
Composition of serum and plasma
Serum has the same composition as plasma except a
a. That serum does not have fibrinogen and clotting factors II, V, and VIII
b. It has a higher serotonin content than plasma; this is because of the breakdown of platelets during clotting.

More text through MCQs


All the following plasma proteins are produced mainly in the liver except.

A. Albumin
B. Fibrinogen
C. Haptoglobin
D. Immunoglobulins



Immunoglobulins are produced by the plasma cells. Most other plasma proteins are produced by the liver.



The Hb transport protein in the plasma is:

A. ceruloplasmin
B. haptoglobin
C-reactive proteins (CRP)
F. Transthyretin





This binds and transports porphyrins, especially heme. One molecule of hemopexin binds with one molecule of heme.


A.   Ceruloplasmin

This transports copper. One mole of ceruloplasmin binds 6 copper atoms


1.  CRP

  1. This is one of the acute phase proteins. It plays a role in tissue inflammation; it binds complement C1q. Its level increases in inflammation. Called CRP because it reacts with the C polysaccharide of pneumococcus. Reference Values Normal
  2. <1.0 mg/dL, or <l0 mg/L by rate nephelometry for CRP
  3. <0. 1 mg/dL or < 1 mg/L by immunoturbidimetric assay for hs-CRP
  4. Clinical Implications
  1. The traditional test for CRP has added significance over the elevated erythrocyte sedi­mentation rate (ESK), which may be influenced by altered physiologic states. CRP tends to increase before rises in antibody titers and ESR levels occur. CRP levels also tend to decrease sooner than ESR levels.
  2. The traditional test for CRP is elevated in rheumatic fever , RA , myocardial infarction , malignancy, bacterial and viral infections, and postoperatively (declines after fourth post­operative day).
  3. A single test for hs-CRP may not reflect an individual patient's basal hs-CRP level; there­fore, follow-up tests or serial measurements may be required in patients presenting with increased hs-CRP levels.
  4. CRP levels may predict future cardiovascular events , diabetes, & hypertension and can be used as a screening tool.
  5. One of the minor criteria of Modified Jones criteria

B.    Transferrin

This transports iron. One mole of transferring binds 2 iron atoms.


C.   Transthyretin

The other name for this is thyroid-binding prealbumin. It binds and carries thyroid hormones. The other thyroid hormone- binding protein is thyroid-binding globulin.



The following blood clotting factors are produced in the liver except:

A. factor 2

B. factor 3
C. factor 7
D. factor 9
E. factor 10


‘B’. factor 3




Which of the following plasma proteins is structurally similar to albumin?

A. Alpha-fetoprotein
B. protein C
C. apolipoprotein B

D. Alpha2-macroglobulin
E. antithrombin III
F. alpha 1-antiprotease


'A' Alpha-fetoprotein


All the above proteins are produced in the liver. The function of alpha-fetoprotein is not exactly known. Like albumin, it may function as an osmotic regulator and as a non-specific carrier protein (for hormones, amino acids etc). It is found normally in fetal blood; hence, the name.

Alpha2-macroglobulin binds and inhibits serum endoproteases.

Antithrombin III
is a protease inhibitor of the intrinsic clotting system. One molecule of antithrombin III binds one molecule of these proteases.

Protein C (also, anti-thrombin C) inhibit blood clotting.

Apolipoprotein B is a plasma lipid carrying protein.

Alpha1-antiprotease : this is a trypsin and general protease inhibitor.



The plasma or serum concentration of which of the following proteins is maximum?

A. Fibrinogen           
B. albumin               
C. haptoglobin         
D. C-reactive proteins



'B' albumin


The plasma levels of some plasma proteins are :

Plasma protein

Plasma/serum concentration (mg/dL)


3500 to 5000


200 to 450

Globulins (total)

1700 to 3200

Alpha 2 macroglobulin

150 to 420


40 to 180


50 to 100


15 to 60


3 to 6.5

Antithrombin III

15 to 30

Clotting factors 2, 7, 9 and 10


TBG (thyroid-binding globulin)


TBPA (thyroid-binding prealbumin) or transthyretin



D.   Hemoglobin

Molecular weight = 64450.


It is a globular protein. Each molecule of Hb has 4 subunits.

Each subunit has :

1. Pigment heme conjugated to a polypeptide.

Thus, there are 4 polypeptide chains in each Hb molecule; the polypeptide chains are collectively called ‘globin’.



This is an iron-containing porphyrin known as iron-protoporphyrin IX. The porphyrin nucleus consists essentially of 4 pyrrole rings joined together by 4 methine (=CH-) ‘bridges’; the porphyrins are thus tetrapyrroles. The iron in heme is in the ferrous (Fe2+ ) form.


1.  The iron in heme is attached to the

  1. N of each pyrrole ring
  2. N of the imidazole group of the associated globin

Synthesis of heme (Hb appears in the intermediate stage of erythropoiesis in the bone marrow).

Heme is synthesized from glycine and succinyl CoA as shown below :



  1. Succinyl CoA + glycine à alpha amino beta keto adipic acid
  2. Alpha amino beta adipic acid à delta levulinic acid + CO2
  3. Delta levulinic acid (2 molecules) à porphobilinogen
  4. Porphobilinogen (4 molecules) à protoporphyrin
  5. Protoporphyrin IX + Fe 2+  + globin à Hb

1.  A single Hb molecule has

  • 4 protoporphyrin IX molecules
  • 4 ferrous atoms
  • 4 polypeptide chains

1 gram of Hb has about 3.34 mg of ferrous ion.

1 gram of Hb, when fully saturated, carries 1.34 ml of oxygen.

Different states of Hb:
OxyHb (HbO2)
Oxygen binds loosely and reversibly with Hb; this Hb is called oxyHb. The oxygen attaches to the ferrous ion in the heme. 2-3 DPG and H+ compete with oxygen for binding to the deoxygenated Hb; thus, increase in 2-3 DPG and temperature shift the oxygen-Hb curve to the right. The affinity of CO to Hb is 210 times the affinity of oxygen for hemoglobin.

2.  DeoxyHb (Hb or HHb)

Hb to which oxygen is not attached is called deoxy Hb. It is also called reduced Hb.



High affinity of HbF with O2 due to: (AIIMS May 09)

A. Decrease binding with 2,3 DPG
B. Decrease concentration of Hb
C. Increase in the pH
D. Bohr effect




3.  Carbamino compound :

This is a compound of Hb with carbon dioxide


4.  Sulphaemoglobin :

This is a compound of Hb with hydrogen sulphide


This is a compound of Hb with CO; it is better called as carbonmonoxy Hb.

Oxidised Hb (HbOH) or Methaemoglobin :

In this form of Hb, the ferrous (Fe2+ ) ion gets oxidized to ferric ion (Fe 3+ )

When reduced or oxygenated Hb is treated with an oxidizing agent, the ferrous ion gets oxidized to ferric ion; this state of Hb is called as methaemoglobin. The disadvantage of this methaemoglobin is that it cannot unite reversibly with oxygen.

MetHb is represented like ‘HBOH’; because, here the ferric ion is attached to OH group

The iron in Hb in the normal state is in the ferrous form. Drugs and oxidizing agents convert the ferrous to ferric form, making it methaemoglobin. Methaemoglobin is dark coloured and when present in large quantities causes a dusky discolouration of skin resembling cyanosis.

Hb (Ferrous ion)   -à oxidized (ferric ion) à gives methaemoglobin


  Hb MetHb
Iron Ferrous form Ferric form
State of Hb Reduced form Oxidised form
Colour Red     Darker
Binding to oxygen reversible irreversible

6.  Note

Oxygenated Hb = HbO2; oxidized Hb = MetHb (HBOH)

Glycosylated or glycated Hb (HbAic)

When blood glucose enters the RBCs, the glucose gets attached to Hb at various positions ; this Hb is called glycated Hb. One of the glycosylated/glycated Hbs is HbAic. This glycated Hb has a glucose attached to the terminal valine in each beta chain.


The percentage of glycosylated Hb = 50 %. This percentage is directly proportional to blood glucose concentration. Since the half-life of RBC is 60 days, the level of glycated Hb (HbAic) reflects the mean blood glucose concentration over the preceding 6 to 8 weeks. So, its estimation is important in management of diabetes mellitus.

Different Types of Hb

In the different types of Hb, the heme portion is identical; physical and chemical differences are due to variations in the composition of the peptides of the globinfraction.

HBA (alpha2, beta 2) :

this is the normal and main form of adult Hb; it has 2 alpha and 2 beta chains. Each alpha chain has 141 amino acids; each beta chain has 146 amino acids.


HbA2 (alpha 2, delta 2)

This constitutes about 2.5% of the normal adult Hb. It has 2 alpha and 2 delta chains. Each delta chain has 146 amino acids (but 10 amino acids are different from those of beta chains)


HbF or foetal Hb(alpha 2, gamma 2)

This occurs in foetal RBCs; it usually disappears by 2-3 months after birth. Since 2-3 DPG has less affinity to bind to HbF, HbF has greater affinity for oxygen. So, at a given pO2, the percentage saturation of HbF with oxygen is more than that of HbA.



This increased affinity helps in uptake of oxygen from maternal to foetal circulation.

HbF is much more resistant to alkali than HbA.

1.  Fate of RBC/Hb

At the end of their life span, RBCs are destroyed in the reticuloendothelial system (nowadays called as tissue macrophage system) and Hb is released from the RBC.

In the tissue macrophage system, the globin and heme portion are split off. The heme is oxidized (by heme oxygenase) to biliverdin. In this process, CO is formed.

Most of the biliverdin is reduced (by biliverdin reductase) to bilirubin and is excreted in the bile. The iron released from the heme is reused for Hb synthesis.

1 gram of Hb gives 35 mg of bilirubin. About 250 to 375 mg of bilirubin is produced per day (mostly from Hb; also from ineffective erythropoiesis and from other heme proteins such as cytochrome P 450)

Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin.


Other heme containing compounds:


Heme is present in myoglobin also. It is found in the red (slow) muscles.Has very high affinity for O2 acts as O2 storing protein.  Binds 1 mole of O2 only. O2 dissociation curve is rectilinear parabole.


This is an oxygen-binding globin in the brain; its function may be to supply oxygen to neurons.

Cytochrome C

This is a respiratory chain enzyme; it contains heme.

  1.  More text through MCQs

HbF is
A. alpha 2, beta 2                     B. alpha 2, gamma 2
C. alpha 2, delta 2                    D. alpha 2, zeta 2             E. epsilon 2, zeta 2


Gamma chain has 146 amino acids (like beta chain, which also has 146 amino acids); however, 37 amino acids are different.

Epsilon 2, zeta 2 : Gower 1 Hb
Alpha 2, epsilon 2 : Gower 2 Hb

Gower 1 and Gower 2 Hb present in the young embryo; thus, epsilon and zeta chains are embryonic.

Alpha chain gene is present on chromosome 16; the gene for other chains (beta, gamma, delta, epsilon, zeta) are present on chromosome 11.
Espison, zeta : disappear at approximately 3 months of intrauterine life

  1. Gamma
    Maximum percentage (about 45%) occurs at about 3 months of intrauterine life; its percentage starts decreasing just before birth and gets decreased to very low level by about 3 months after birth; it almost completely disappears at 6 months after birth.
  2. Beta chain
    The graph for beta chain is almost a mirror image of gamma chain. It starts increasing just before birth; reaches very high level (about 45 %) at about 3 months after birth and almost 50% at 6 months (that is the maximum percentage possible because the other 50% is alpha chain)
  3. Alpha chain
    This reaches 50% at about 3 months of intrauterine life and remains so throughout life.
  4. Delta chain
    This starts appearing just before birth and becomes maximum (about 2%) at about 6 months after birth. 

MCQ round up

At 3 months of intrauterine life

  • Zeta, epsilon chains disappear
  • Alpha chain percentage becomes maximum (about 50%)
  • Gamma chain percentage becomes maximum (about 45%)

At 3 months after birth

-   Gamma decreases to very low level

-   Beta increases to very high level


At 6 months after birth

  • Gamma almost disappears
  • Beta becomes almost maximum

6.  Alpha chain

Becomes maximum at about 3 months of intra uterine life; thereafter, it remains so throughout.  

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