PLASMA PROTEINS

Introduction

• Plasma is the fluid portion of blood (55% of blood volume)
• Normal plasma volume: ~5% of body weight (~3500 mL in a 70 kg man)
• Total plasma protein concentration: 6-8 g/100 mL of blood

Classification of Plasma Proteins

I. Major Fraction

II. Minor Fraction

• Prothrombin: 0.04 g/dL
• Nucleoproteins
• Enzymes

Individual Proteins

1. Albumin

• Molecular weight: 69,000
• Site of synthesis: Liver
• Rate of synthesis: 200-400 mg/kg body weight/day
• Contributes ~80% of the total osmotic pressure of blood (due to highest concentration and lowest molecular weight)

2. Globulin

• Molecular weight: 90,000-1,50,000
• Subdivisions:
  • α-globulin: α₁ and α₂
  • β-globulin: β₁ and β₂
  • γ-globulin
• Site of synthesis:
  • α and β fractions: Liver, spleen, bone marrow
  • γ-globulin: Plasma cells derived from B lymphocytes and lymphoid tissue

3. Fibrinogen

• Molecular weight: 3,40,000
• Site of synthesis: Liver
• Helps in coagulation of blood

Protein Complexes in Blood

• Glycoproteins: e.g., Haptoglobin (combines with hemoglobin)
• Lipoproteins: LDL, HDL, VLDL
• Metalloproteins: Transferrin (transports iron), Ceruloplasmin (combines with copper)

Methods of Separation of Plasma Proteins

1. Precipitation method - salt used: ammonium sulfate or sodium sulfate
2. Ultracentrifugation
3. Fractional precipitation
4. Electrophoresis:
   • Tiselius method
   • Paper electrophoresis
   • Agar or cellulose acetate electrophoresis
   • Immunoelectrophoresis

In electrophoresis, migration rate depends on surface charge, molecular weight, and shape. Different fractions form different bands (see Fig. 12.1). Relative amounts: γ=11%, Fibrinogen=7%, β=14%, α=13%, Albumin=55%

Functions of Plasma Proteins

Albumin-Globulin (A:G) Ratio

• Normal value: 1.7-2
• Reversal of A:G ratio seen in:
  • Chronic liver diseases (decreased albumin synthesis)
  • Chronic renal diseases (albuminuria)
  • Autoimmune diseases (increased γ-globulin)
  • Old age (decreased albumin synthesis)

Variations in Plasma Protein Levels

Hypoproteinemia (Decreased plasma proteins)

• Hemorrhage and burns
• Pregnancy (hemodilution)
• Malnutrition, starvation, malabsorption
• Chronic liver diseases
• Renal diseases (e.g., nephrotic syndrome - protein loss in urine)

Hyperproteinemia (Increased plasma proteins)

• Dehydration (hemoconcentration)
• Acute inflammatory conditions and malignancies (increased acute phase proteins: CRP, haptoglobin, fibrinogen, globulins)

Hypoalbuminemia

• Hemodilution, Burns, Liver and renal diseases, Malnutrition

Agammaglobulinemia

• Congenital, total absence of γ-globulin
• Decreased immunity → recurrent infections

Hypergammaglobulinemia

• Multiple myeloma, SLE, Acute/chronic infections, Lymphatic leukemia

Hyperfibrinogenemia

• Pregnancy, Menstruation, Malaria, Malignancy

Plasmapheresis

• Procedure for collecting plasma from donors without depleting blood cells
• Process: Whole blood withdrawn → plasma separated by centrifugation → cells returned to donor
• Used in severe autoimmune disorders (e.g., myasthenia gravis, Guillain-Barre syndrome)
• In myasthenia gravis: removes excess IgG and AChR antibodies
• Dose: 40-50 mL/kg plasma exchange daily for 4-5 days
• Whipple's experiment demonstrated importance of plasma proteins using protein-depleted animals in Ringer-Locke fluid

Quick Revision - Key Values