PLASMA PROTEINS

  • Plasma proteins are key proteins found in blood plasma, essential for maintaining homeostasis, immune defense, and the transport of substances.
  • Mostly synthesized in the liver, with the exception of immunoglobulins (Igs), which are produced by plasma cells.

BLOOD

  • Total volume in adults: 4.5-5 L
  • Key Functions:
    • Respiration
    • Excretion
    • Acid-base maintenance
    • Water balance
    • Transport of metabolites, hormones, and drugs
    • Body defense
    • Coagulation

PLASMA

  • Liquid portion of blood: Comprises 55-60% of total blood volume.
  • Contains suspended cell components including RBCs, WBCs, and platelets.
  • When blood containing anticoagulant is centrifuged:
    • Plasma separates as the supernatant.
    • Cells remain at the bottom.
  • PCV/Hematocrit: Approximately 45%.

SERUM

  • Serum forms when blood clots and the liquid is separated.
  • Lacks fibrinogen and other clotting factors.
  • Difference between plasma and serum: Presence or absence of fibrinogen.

PLASMA PROTEINS - COMPLEX MIXTURE

  • Total concentration ranges from 6-8 g/dl.
  • Albumin:Globulin ratio: Typically between 1.2:1 and 1.5:1.
  • Most plasma proteins (excluding Igs) are synthesized in the liver, generally on membrane-bound polyribosomes, and the majority are glycoproteins.

PLASMA PROTEINS - SEPARATION

  • Separation methods include:
    • Salting out process: Divides proteins into albumin, globulin, and fibrinogen groups.
    • Electrophoresis: Utilizes paper or agar gel with veronal buffer (pH 8.6).
    • Distinct Bands in Electrophoresis:
    • Albumin
    • α1
    • α2
    • β
    • γ globulins.
    • Concentration of each fraction can be measured using a densitometer.

ELECTROPHORESIS OF PLASMA PROTEINS

  • Mechanism: Movement of charged particles through an electrolyte under an electric field.
  • Concentration of protein fractions includes:
    • Albumin: 55-65%
    • Alpha-1 globulin: 2-4%
    • Alpha-2 globulin: 6-12%
    • Beta globulin: 8-12%
    • Gamma globulin: 12-22%.
  • Mobility in Electric Field:
    • Albumin has maximum mobility; gamma globulin has minimum.
    • Gamma globulins contain antibodies/immunoglobulins.
    • Alpha-1 fraction predominantly consists of alpha-1-antitrypsin; Alpha-2 is mainly alpha-2-macroglobulin; Beta fraction contains LDL.

ABNORMAL ELECTROPHORETIC PATTERNS

  • Multiple Myeloma: Sharp M band appears in the γ-globulin fraction.
  • Nephrotic Syndrome: Decreased albumin with prominent α-globulins.
  • Primary Immune Deficiency: Diminished γ-globulin band.
  • Alpha-Antitrypsin Deficiency: Missing α-globulin band.
  • Fibrinogen Presence: Prominent band in γ region during plasma electrophoresis; can be confused with M band.
  • Acute Infections: Increased α- and α-globulins.
  • Chronic Infections: Increased γ-globulins.
  • Liver Cirrhosis: Thin albumin band and wide β fraction; fusion of β and γ fractions possible.
  • Chronic Lymphatic Leukemia: Reduced γ-globulin.

ALBUMIN

  • Introduction: Major plasma protein (60%), concentration: 3.5-5 g/dl, molecular weight: 69,000.
  • Synthesis: Exclusively synthesized by the liver. Decreased synthesis in liver disease implies liver function.
  • Half-life: Approximately 20 days.
  • Functions:
    • Osmotic Pressure: Contributes 75-80% of plasma osmotic pressure, maintaining blood volume and fluid distribution.
    • Transport: Binds fatty acids, bilirubin, steroid hormones, calcium, and copper.
    • Nutritive Role: Source of amino acids for protein synthesis during nutritional deprivation.
    • Buffering: Provides buffering capacity but less significant than bicarbonate.

CLINICAL SIGNIFICANCE OF ALBUMIN

  • Preventing Blood-Brain Barrier Passage: Binds certain compounds preventing their passage e.g., albumin-bilirubin complex.
  • Hypoalbuminemia: Associated with malnutrition, nephrotic syndrome, and liver cirrhosis leading to edema.
  • Albumin in Urine: Secreted during nephrotic syndrome and urinary tract inflammation; microalbuminuria indicates future renal disease risk.
  • Therapeutic Use: Helpful in treating burns and hemorrhages.

POLYMORPHISM OF PLASMA PROTEINS

  • Proteins exhibiting different phenotypes within the population; only one form appears in individuals.
  • Examples: Haptoglobin, transferrin, ceruloplasmin, α1-antitrypsin, and Igs.

TRANSPORT OF LIPIDS IN BLOOD

  • Challenge of Lipid Solubility: Blood is aqueous; hence, lipids require carrier proteins for transport in blood.

GLOBULINS

  • Comprised of multiple proteins, separated into four bands during electrophoresis.
  • Generally larger than albumin.

GLOBULINS - ALPHA1-ANTITRYPSIN

  • Major α-globulin (~200 mg/dl), a glycoprotein, inhibits activity of proteases (e.g., trypsin).

GLOBULINS - CLINICAL SIGNIFICANCE

  • Antitrypsin Deficiency: Linked to emphysema, liver disease, and lung tissue damage due to elastase activity.

HAPTOGLOBIN

  • Glycoprotein that binds free hemoglobin after hemolysis, preventing kidney loss.
  • Increased level in inflammatory conditions; decreased in hemolytic anemia.

CERULOPLASMIN

  • Copper-binding alpha-globulin; provides oxidase activity.
  • Binds to nearly 90% of plasma copper; implicated in Wilson’s disease.

TRANSFERRIN

  • Transport protein for iron in circulation, associated with beta-globulin fraction.

C-REACTIVE PROTEIN (CRP)

  • Major acute-phase protein involved in the immune response; produced in the liver to mediate inflammation.
  • Elevated levels post-surgery can indicate infection.

IMMUNOGLOBULINS

  • Specialized proteins primarily found in the gamma globulin fraction; responsible for immune response.
  • Five Classes: IgM, IgG, Secretory IgA, IgE, IgD with varying binding sites and functions.

MULTIPLE MYELOMA

  • A plasma cell cancer leading to overproduction of abnormal immunoglobulins.
  • Characterized by the sharp M band in electrophoresis.

BLOOD CLOTTING

  • The hemostatic process stops blood loss after injury through clot formation.
  • Anticoagulants: Inhibit clotting (e.g., oxalate, heparin).
    • Fibrinolysis: Process of dissolving blood clots, involving plasmin and tissue plasminogen activator (TPA).

HEMOPHILIA A/B

  • Clotting disorders due to deficiencies in specific clotting factors, leading to prolonged bleeding.
  • Common manifestations include joint and gastrointestinal bleeding due to the inability to form stable blood clots.