Comprehensive Study Guide on Plasma Proteins

Blood Composition and Plasma Overview

• Blood accounts for approximately $8\%$ of the total body weight.

• Whole blood consists of three main components when centrifuged:

  • Plasma: Occupies $55\%$ of the total volume. It is a clear, straw-colored fluid portion in which blood cells are suspended.

  • Buffy Coat: Occupies less than $1\%$ of the total volume and contains White Blood Cells (Leukocytes) and Platelets.

  • Erythrocytes (Red Blood Cells): Occupy $45\%$ of the total volume.

• The formed elements of blood include:

  • Erythrocytes: $4.2$ to $6.2$ million per cubic mm.

  • Platelets: $250$ to $400$ thousand per cubic mm.

  • White Blood Cells: $5$ to $10$ thousand per cubic mm. These consist of:

    • Neutrophils ($60\% - 70\%$)

    • Lymphocytes ($20\% - 25\%$)

    • Monocytes ($3\% - 8\%$)

    • Eosinophils ($2\% - 4\%$)

    • Basophils ($0.5\% - 1\%$)

Chemical Composition of Plasma

• Plasma is composed of water and solids:

  • Water: Estimates range between $91\%$ and $93\%$.

  • Solids: $7\%$ to $8\%$ of the plasma volume.

• Inorganic Substances:

  • Sodium, Calcium, Potassium, Magnesium, Bicarbonate, Chloride, Phosphate, Iodide, Iron, and Copper.

• Organic Substances:

  • Plasma Proteins: Albumin, Globulin, and Fibrinogen.

  • Amino Acids: Both essential and non-essential.

  • Carbohydrates: Mainly 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 (NPN) Substances: Ammonia, Creatine, Creatinine, Xanthine, Hypoxanthine, Urea, and Uric acid.

  • Antibodies.

• Gases: Oxygen ($O_2$), Carbon dioxide ($CO_2$), and Nitrogen ($N_2$).

• Other Solutes ($2\% \text{ by weight}$): Includes Nutrients, Waste products, and Regulatory substances.

Properties and Normal Values of Plasma Proteins

• Total Proteins: The average value is $7.3\,g/dL$, with a normal range between $6.4\,g/dL$ and $8.3\,g/dL$.

• Concentration of Specific Proteins:

  • Serum Albumin: $4.7\,g/dL$ (the most abundant protein, constituting about $58\%$ to $60\%$ of total proteins).

  • Serum Globulin: $2.3\,g/dL$ (comprising roughly $35\%$ to $38\%$ of total proteins).

  • Fibrinogen: $0.3\,g/dL$ (constituting approximately $4\%$ of total proteins).

• Molecular Weights:

  • Albumin: $69,000$

  • Globulin: $1,56,000$

  • Fibrinogen: $4,00,000$ (the largest of the triplet).

• Synthesis:

  • Almost all plasma proteins (including albumin and fibrinogen) are synthesized in the Liver.

  • Immunoglobulins (Gamma globulins) are exceptions and are synthesized by plasma cells.

• Specific Gravity: The specific gravity of plasma proteins is $1.026$.

Major Functions of Plasma Proteins

• Oncotic Pressure (Colloid Osmotic Pressure):

  • Plasma proteins, specifically Albumin, exert an osmotic pressure known as oncotic pressure, which is approximately $25\,mm\,Hg$.

  • This pressure is critical for maintaining fluid distribution between the plasma and interstitial fluid.

• Coagulation of Blood:

  • Fibrinogen is essential for blood clotting.

  • Prothrombin (Factor II) and other clotting factors (V, VII, VIII, IX, X, XI, XII, and XIII) are also proteins involved in hemostasis.

  • Vitamin K-dependent factors (Factors II, VII, IX, and X) are synthesized in the liver.

• Defense Mechanism:

  • Gamma globulins serve as antibodies (immunoglobulins) and are vital for the body's immune defense.

• Transport Mechanism:

  • Proteins act as carrier molecules for various substances.

  • Albumin: Transports Bilirubin, fatty acids, hormones (thyroxine, cortisol), calcium, steroids, and drugs (e.g., sulfonamides, warfarin).

  • Alpha (\alpha) and Beta (\beta) Globulins: Transport metals, lipids, and fat-soluble vitamins.

  • Transferrin: Transports Iron ($Fe$).

• Buffering Action:

  • Plasma proteins (primarily Albumin) help regulate acid-base balance by accepting hydrogen ions.

  • They account for about $15\%$ of the total buffering capacity of the blood.

• Viscosity of Blood:

  • Plasma proteins provide the viscosity necessary to maintain blood pressure. Albumin provides more viscosity than other plasma proteins.

• Erythrocyte Sedimentation Rate (ESR):

  • Globulin and fibrinogen are Prosedimentation factors that promote Rouleaux formation, where Red Blood Cells stack together. This increases the ESR, which is used as a diagnostic and prognostic tool.

• Protein Reserve:

  • During starvation or inadequate protein intake, tissue macrophages split plasma proteins into amino acids to form cellular protein molecules as a last source of energy.

Classification and Roles of Globulins

• $\alpha_1$-Globulins: Include transport proteins like thyroxine-binding globulin and transcortin, and protease inhibitors such as antitrypsin.

• $\alpha_2$-Globulins: Includes Haptoglobin (which binds free hemoglobin), Ceruloplasmin (for copper transport), and Macroglobulin (a protease inhibitor).

• $\beta$-Globulins: Consists of Transferrin (for iron transport) and complement proteins used in innate immunity.

• $\gamma$-Globulins (Immunoglobulins): Provide humoral immunity and include five classes: $IgG$, $IgA$, $IgM$, $IgE$, and $IgD$.

Clinical Significance and Pathologies

• Hypoproteinemia (Decreased Proteins):

  • Leads to decreased plasma osmotic pressure, causing water retention and edema (swelling) of body tissues.

  • Causes: Dietary deficiency, malabsorption syndrome, liver diseases, renal diseases, extensive burns, hereditary albuminemia, and congenital afibrinogenemia.

  • Scenario: A $6$-year-old child with swelling around eyes and feet but normal blood pressure is likely suffering from Hypoalbuminemia. Lowered albumin causes fluid to leak into tissues (edema/ascites).

• Hyperproteinemia (Increased Proteins):

  • Causes: Acute inflammatory conditions (which increase acute-phase proteins), acute tissue destruction (such as Myocardial Infarction), chronic inflammation, and malignancies (which raise C-reactive protein).

• Specific Clinical Conditions:

  • Hypoalbuminemia: Can cause edema and ascites; seen in liver disease, nephrotic syndrome, and malnutrition.

  • Hypergammaglobulinemia: Overproduction of immunoglobulins; seen in Multiple myeloma, immune deficiency, and chronic infections.

  • $\alpha$-Globulin Deficiency: Linked to emphysema (specifically $\alpha_1$-antitrypsin deficiency).

  • $\beta$-Globulin Deficiency: Leads to increased risk of infections and anemia.

  • Reduced Fibrinogen: Results in a bleeding tendency due to impaired clot formation.