Composition and Physiological Functions of Plasma Proteins

Blood Composition and Distribution

  • Blood constitutes approximately 8%8\% of the total body weight.
  • Total blood volume is divided into two primary components:
    • Plasma: Makes up 55%55\% of the total blood volume. It is a clear, straw-colored fluid portion of the blood in which blood cells are suspended.
    • Formed Elements: Make up 45%45\% of the total blood volume. This consists of erythrocytes (red blood cells), leukocytes (white blood cells), and platelets.
  • A centrifuge process separates blood into layers:
    • Plasma: The top layer (55%55\%
    • Buffy Coat: A thin middle layer (<1%<1\%
    • Erythrocytes: The bottom layer (45%45\%
  • Quantitative Breakdown of Formed Elements (per cubic mm):
    • Red Blood Cells (Erythrocytes): 4.2 to 6.2 million4.2\text{ to }6.2\text{ million}
    • White Blood Cells (Leukocytes): 5 to 10 thousand5\text{ to }10\text{ thousand}
    • Platelets: 250 to 400 thousand250\text{ to }400\text{ thousand}
  • Differential White Blood Cell Count:
    • Neutrophils: 60% to 70%60\%\text{ to }70\%
    • Lymphocytes: 20% to 25%20\%\text{ to }25\%
    • Monocytes: 3% to 8%3\%\text{ to }8\%
    • Eosinophils: 2% to 4%2\%\text{ to }4\%
    • Basophils: 0.5% to 1%0.5\%\text{ to }1\%

Detailed Composition of Plasma

  • Plasma is comprised of water and solids, containing organic and inorganic substances.
  • Water Content: Accounts for 91% to 93%91\%\text{ to }93\% of plasma weight.
  • Solids (Organic and Inorganic): Account for 7% to 9%7\%\text{ to }9\% of plasma weight.
    • Plasma Proteins (7% to 8%7\%\text{ to }8\%): Albumin, Globulin, and Fibrinogen.
    • Amino Acids: Includes both essential and non-essential amino acids.
    • Carbohydrates: Primarily Glucose.
    • Fats: Triglycerides, Cholesterol, and Phospholipids.
    • Internal Secretions: Hormones.
    • Enzymes: Amylase, Carbonic anhydrase, Acid phosphatase, Alkaline phosphatase, Lipase, Esterase, Protease, and Transaminase.
    • Non-protein Nitrogenous Substances: Ammonia, Creatine, Creatinine, Xanthine, Hypoxanthine, Urea, and Uric acid.
    • Antibodies: Crucial for immune defense.
  • Inorganic Substances: Sodium, Calcium, Potassium, Magnesium, Bicarbonate, Chloride, Phosphate, Iodide, Iron, and Copper.
  • Gases: Oxygen (O2O_2

Characteristics and Physical Properties of Plasma Proteins

  • Normal Values for Total Plasma Protein: Average is 7.3 g/dL7.3\,\text{g/dL}, with a normal range of 6.4 to 8.3 g/dL6.4\text{ to }8.3\,\text{g/dL}.
    • Serum Albumin: 4.7 g/dL4.7\,\text{g/dL} (The most abundant protein component at approximately 58% to 60%58\%\text{ to }60\%
    • Serum Globulin: 2.3 g/dL2.3\,\text{g/dL} (Approximately 35% to 38%35\%\text{ to }38\%
    • Fibrinogen: 0.3 g/dL0.3\,\text{g/dL} (Approximately 4%4\%
  • Synthesis Sites:
    • All plasma proteins are synthesized by the liver, with the exception of immunoglobulins.
    • Immunoglobulins are synthesized by plasma cells.
  • Molecular Weights (MWMW):
    • Albumin: 69,00069,000
    • Globulin: 156,000156,000
    • Fibrinogen: 400,000400,000 (Fibrinogen possesses the highest molecular weight among the major plasma proteins).
  • Specific Gravity: The specific gravity of plasma proteins is 1.0261.026.

Physiological Functions of Plasma Proteins

  • Oncotic (Colloid Osmotic) Pressure:
    • Plasma proteins are responsible for exerting oncotic pressure, which is approximately 25 mm Hg25\,\text{mm Hg}.
    • This pressure is critical for maintaining fluid distribution between the plasma and the interstitial fluid.
    • Albumin is the primary protein responsible for maintaining this pressure.
  • Transport Mechanism:
    • Plasma proteins serve as carrier molecules for lipids, hormones, minerals, and drugs.
    • Albumin: Transports bilirubin, fatty acids, thyroid hormones (thyroxine), steroids (cortisol), calcium, and drugs such as sulfonamides and warfarin.
    • Alpha (\alpha) and Beta (\beta) Globulins: Transport metals, lipids, and fat-soluble vitamins.
    • Specific Transport Proteins:
      • Transferrin: Transports Iron (FeFe
      • Haptoglobin: Binds free Hemoglobin (HbHb
      • Ceruloplasmin: Transports Copper.
      • Thyroxine-binding globulin and Transcortin: Transport specific hormones.
  • Regulation of Acid-Base Balance:
    • Plasma proteins act as buffers that resist changes in pH by accepting hydrogen ions.
    • They are responsible for 15%%15\%\% of the total buffering capacity of the blood, with albumin playing a particularly important role.
  • Blood Viscosity:
    • Plasma proteins provide viscosity to the blood, which is essential for maintaining blood pressure.
    • Albumin contributes more to viscosity than other plasma proteins.
  • Reserve Proteins:
    • In states of fasting, starvation, or inadequate protein intake, plasma proteins are utilized by body tissues as a final source of energy.
    • Tissue macrophages split plasma proteins into amino acids, which are then distributed to form cellular protein molecules.

Role in Erythrocyte Sedimentation Rate (ESR)

  • Rouleaux Formation: This occurs when red blood cells stack together like coins. Fibrinogen adsorbs onto the cell membrane and forms bridges to adjacent cells.
  • Prosedimentation Factors: Globulin, fibrinogen, and acute phase proteins promote rouleaux formation, which increases the ESR.
  • Increased ESR serves as an important diagnostic and prognostic tool in clinical settings.

Defense and Hemostatic Functions

  • Defense Mechanism:
    • γ\gamma-globulins (immunoglobulins) provide humoral immunity.
    • Major classes include IgGIgG, IgAIgA, IgMIgM, IgEIgE, and IgDIgD.
    • Complement proteins (part of β\beta-globulins) contribute to innate immunity.
  • Coagulation and Hemostasis:
    • Fibrinogen (Factor I) is the precursor to fibrin, essential for forming blood clots.
    • Clotting Factors: Prothrombin (Factor II), Fibrinogen, and Factors V, VII, VIII, IX, X, XI, XII, and XIII.
    • Vitamin K-Dependent Factors: Factors II, VII, IX, and X are synthesized in the liver and require Vitamin K.

Clinical Scenario: Hypoalbuminemia

  • Case Presentation: A 66-year-old child presents with swelling around the eyes (periorbital edema) and swollen feet (pedal edema). Blood pressure is normal, but laboratory tests reveal a very low serum albumin level.
  • Trigger Questions and Answers:
    • Why has this child developed swelling? The child has developed swelling because the low serum albumin level has led to a decrease in plasma oncotic pressure. This allows fluid to move out of the capillaries and into the interstitial tissues, resulting in edema.
    • What is the most likely cause of this child's swelling? Likely causes include liver disease (impaired protein synthesis), renal disease (such as nephrotic syndrome where protein is lost in urine), or malnutrition.
    • What are the major functions of plasma proteins? Key functions include maintaining oncotic pressure, transport of substances, blood clotting, immunity, and buffering.

Clinical Significance of Plasma Protein Deviations

  • Hypoproteinemia (Decreased Proteins):
    • Leads to decreased plasma osmotic pressure, causing water retention in tissues (edema).
    • Causes: Dietary deficiency, malabsorption syndrome, liver diseases, renal diseases, extensive burns, hereditary albuminemia, and congenital afibrinogenemia.
    • Specific Deficiencies:
      • Hypoalbuminemia: Results in edema and ascites (fluid in the abdominal cavity).
      • α1\alpha_1-Antitrypsin Deficiency: Linked to the development of emphysema.
      • β\beta-Globulin Deficiency: Leads to increased susceptibility to infections and anemia.
      • Reduced Fibrinogen: Results in a bleeding tendency due to impaired clot formation.
  • Hyperproteinemia (Increased Proteins):
    • Causes: Acute inflammatory conditions (increases acute-phase proteins), acute tissue destruction (e.g., Myocardial Infarction or MI), chronic inflammation, and malignancies.
    • Hypergammaglobulinemia: Overproduction of immunoglobulins, seen in conditions like Multiple myeloma, immune deficiency, and chronic infections.
    • C-reactive protein: Raised levels are indicative of chronic inflammation or malignancies.

Questions & Discussion

  • Question: What is the specific function of transferrin mentioned in the summary table?
  • Response: Transferrin is specialized for the transport of iron.
  • Question: Where are globulins synthesized?
  • Response: They are synthesized in both the liver and lymphoid tissues.
  • Question: What happens when α1\alpha_1-antitrypsin is deficient?
  • Response: α1\alpha_1-antitrypsin is a protease inhibitor; its deficiency leads to emphysema.