PLASMA PROTEINS AND THEIR NORMAL VALUES

IMPORTANT AND MAJOR PROTEINS PRESENT IN PLASMA

1. Serum albumin
2. Serum globulin
3. Fibrinogen

NORMAL VALUES OF PLASMA PROTEINS

Molecular weight of fibrinogen is greater than that of the other two proteins.

ALBUMIN/GLOBULIN RATIO

• Ratio between plasma level of albumin and globulin is called albumin/globulin (A/G) ratio.
• It is an important indicator of some liver and kidney diseases.
• Normal A/G ratio = 2:1.

ORIGIN OF PLASMA PROTEINS

IN EMBRYO

• In embryonic stage, plasma proteins are synthesized by the mesenchyme cells.
• Albumin is synthesized first.
• Other proteins are synthesized later.

IN ADULTS

• In adults, plasma proteins are synthesized mainly from reticuloendothelial cells of liver.
• Plasma proteins are also synthesized from:
• Spleen
• Bone marrow
• General tissue cells
• B lymphocytes

PROPERTIES OF PLASMA PROTEINS

1. MOLECULAR WEIGHT

• Molecular weight of plasma proteins is given in the table of normal values.
• Molecular weight of fibrinogen is greater than that of the other two proteins.

2. ONCOTIC PRESSURE

• Plasma proteins exert oncotic or osmotic pressure in the blood.
• Normally, it is about 25 mm Hg.
• Albumin plays a major role in exerting oncotic pressure.

3. SPECIFIC GRAVITY

• Specific gravity of plasma proteins → 1.026.

4. BUFFER ACTION

• Acceptance of hydrogen ions is called buffer action.
• Plasma proteins have 1/6 of total buffering action of the blood.

FUNCTIONS OF PLASMA PROTEINS

1. ROLE IN COAGULATION OF BLOOD

• Fibrinogen is essential for coagulation of blood.

2. ROLE IN DEFENSE MECHANISM OF BODY

• Gamma globulins play an important role in defense mechanism of the body by acting as antibodies.
• Gamma globulins are also called immunoglobulins.

3. ROLE IN TRANSPORT MECHANISM

• Plasma proteins are essential for transport of various substances in the blood.
• Albumin, alpha globulin and beta globulin are responsible for transport of:
• Hormones
• Enzymes
• Etc.
• Alpha and beta globulins transport metals in the blood.

4. ROLE IN MAINTENANCE OF ONCOTIC PRESSURE IN BLOOD

• At capillary level, most substances are exchanged between blood and tissues.
• Because of their large size, plasma proteins cannot pass through the capillary membrane easily and remain in the blood.
• In blood, proteins exert:
  • Oncotic pressure
  • Colloidal osmotic pressure
• Albumin generates about 70% of oncotic pressure.
• Oncotic pressure exerted by plasma proteins → about 25 mm Hg.
• Since the concentration of albumin is more than other plasma proteins, it exerts maximum pressure.
• Albumin contributes about 70–80% of osmotic pressure.
• Globulin is the next.
• Fibrinogen exerts the least pressure.

5. ROLE IN REGULATION OF ACID-BASE BALANCE

• Plasma proteins, particularly albumin, play an important role in regulating acid-base balance in the blood.
• This is because of their buffering action.

6. ROLE IN VISCOSITY OF BLOOD

• Plasma proteins provide viscosity to the blood.
• This is important to maintain blood pressure.
• Albumin provides maximum viscosity than the other plasma proteins.

7. ROLE IN ERYTHROCYTE SEDIMENTATION RATE (ESR)

• Globulin and fibrinogen accelerate the tendency of rouleaux formation by red blood cells.
• Rouleaux formation is responsible for ESR.
• ESR is an important diagnostic and prognostic tool.

8. ROLE IN SUSPENSION STABILITY OF RED BLOOD CELLS

• During circulation, red blood cells remain suspended uniformly in the blood.
• This property of red blood cells is called suspension stability.
• Globulin and fibrinogen help in suspension stability of red blood cells.

9. ROLE IN PRODUCTION OF TREPHONE SUBSTANCES

• Trephone substances are necessary for nourishment of tissue cells in culture.
• Trephone substances are produced by leukocytes from plasma proteins.

10. ROLE AS RESERVE PROTEINS

• During:
  • Fasting
  • Inadequate food intake
  • Inadequate protein intake
• Plasma proteins are utilized by body tissues as the last source of energy.
• Plasma proteins are split into amino acids by the tissue macrophages.
• Amino acids are taken back by blood and distributed throughout the body to form cellular protein molecules.
• Because of this, plasma proteins are called reserve proteins.

PLASMAPHERESIS AND THERAPEUTIC PLASMA EXCHANGE

PLASMAPHERESIS

• Plasmapheresis is an experimental procedure done in animals to demonstrate the importance of plasma proteins.
• Earlier, this was called Whipple’s experiment as it was established by George Hoyt Whipple.

PROCEDURE

1. Plasmapheresis is demonstrated in dogs.
2. Blood is removed completely from the body of a dog.
3. Red blood cells are separated from plasma.
4. Red blood cells are washed in saline.
5. Red blood cells are reinfused into the body of the same dog along with physiological solution called Locke’s solution.
6. Due to sudden lack of proteins, the animal undergoes a state of shock.
7. If the animal is fed with a diet containing sufficiently high quantity of proteins:
   • Normal level of plasma proteins is restored within 7 days.
   • The animal survives.
   • New plasma proteins are also synthesized by the liver of the dog.
8. If the experiment is done in animals after removal of liver:
   • Even if the diet contains adequate quantity of protein, plasma proteins are not produced.
   • Shock persists in the animal.
   • It leads to death.

PLASMAPHERESIS DEMONSTRATES

1. Importance of plasma proteins for survival.
2. Synthesis of plasma proteins by liver.

THERAPEUTIC PLASMA EXCHANGE

IN AUTOIMMUNE DISEASE

• Immune system attacks the body’s own tissues through antibodies.
• Antibodies are proteins in nature.
• They circulate in the bloodstream before attacking the target tissues.
• Therapeutic plasma exchange is used to remove these antibodies from blood.

PROCEDURE

1. Venous blood is removed from the patient.
2. Blood cells are separated from plasma by a cell separator equipment called apheresis machine.
3. The equipment works on the principle of a centrifuge.
4. An anticoagulant is used to prevent clotting of blood when it is removed from the body.
5. After separation:
   • Plasma is discarded.
   • Blood cells are returned to the bloodstream of the patient by mixing with:
     • A substitute fluid (saline)
     • Sterilized human albumin protein

USES OF THERAPEUTIC PLASMA EXCHANGE

• Plasma exchange is used to remove antibodies from blood.
• It cannot prevent the production of antibodies by the immune system of the body.
• Therefore, it can provide only a temporary benefit of protecting the tissues from antibodies.
• Patients must go for repeated sessions of this treatment.

APPLIED PHYSIOLOGY: VARIATIONS IN PLASMA PROTEIN LEVEL

• Level of plasma proteins varies independently of one another.
• However, in several conditions, the quantity of albumin and globulin changes in opposite direction.
• Elevation of all fractions of plasma proteins is called hyperproteinemia.
• Decrease in all fractions of plasma proteins is called hypoproteinemia.

1. TOTAL PROTEINS

HYPERPROTEINEMIA — CONDITIONS WHEN INCREASED

1. Dehydration
2. Hemolysis
3. Acute infections like acute hepatitis and acute nephritis
4. Respiratory distress syndrome
5. Excess of glucocorticoids
6. Leukemia
7. Rheumatoid arthritis
8. Alcoholism

HYPOPROTEINEMIA — CONDITIONS WHEN DECREASED

1. Diarrhea
2. Hemorrhage
3. Burns
4. Pregnancy
5. Malnutrition
6. Prolonged starvation
7. Cirrhosis of liver
8. Chronic infections like chronic hepatitis or chronic nephritis

2. ALBUMIN

HYPERALBUMINEMIA — CONDITIONS WHEN INCREASED

1. Dehydration
2. Excess of glucocorticoids
3. Congestive cardiac failure

HYPOALBUMINEMIA — CONDITIONS WHEN DECREASED

1. Malnutrition
2. Cirrhosis of liver
3. Burns
4. Hypothyroidism
5. Nephrosis
6. Excessive intake of water

3. GLOBULIN

HYPERGLOBULINEMIA — CONDITIONS WHEN INCREASED

1. Cirrhosis of liver
2. Chronic infections
3. Nephrosis
4. Rheumatoid arthritis

HYPOGLOBULINEMIA — CONDITIONS WHEN DECREASED

1. Emphysema
2. Acute hemolytic anemia
3. Glomerulonephritis
4. Hypogammaglobulinemia

4. FIBRINOGEN

HYPERFIBRINOGENEMIA — CONDITIONS WHEN INCREASED

1. Acute infections
2. Rheumatoid arthritis
3. Glomerulonephritis
4. Myocardial infarction
5. Stroke
6. Trauma

HYPOFIBRINOGENEMIA — CONDITIONS WHEN DECREASED

1. Liver dysfunction
2. Use of anabolic steroids
3. Use of phenobarbital

5. A/G RATIO

CONDITIONS WHEN INCREASED

1. Hypothyroidism
2. Excess of glucocorticoids
3. Hypogammaglobulinemia
4. Intake of high carbohydrate or protein diet

CONDITIONS WHEN DECREASED

1. Liver dysfunction
2. Nephrosis