CL-4 Plasma proteins

Plasma and its Components

Dr. K. M. Huria Parveen

• MBBS, MD (Clinical Biochemistry)

Learning Objectives

• Describe the components of plasma protein.

• Explain the role and functions of plasma protein.

Composition of Blood

• Blood: A fluid connective tissue with two components:

  • Plasma: 55%

  • Formed Elements: 45%

    • Red Blood Cells (Erythrocytes)

    • White Blood Cells (Leukocytes)

    • Platelets (Thrombocytes)

Plasma

• A clear, straw-colored fluid portion of the blood.

• Normal plasma volume: about 5% of body weight.

• Serum: The fluid remaining after blood clots, lacking fibrinogen and clotting factors II, V, and VIII.

Composition of Plasma

• Water: 91%

• Plasma Proteins: 7%

  • Albumin, globulins, fibrinogen, others.

• Other Organic Molecules: 1%

  • Glucose, neutral fats, phospholipids, cholesterol, amino acids, creatine, creatinine, urea, uric acid, hormones, enzymes, antibodies.

• Inorganic Substances: 1%

  • Sodium, potassium, calcium, magnesium, chloride, iodide, iron, phosphates, copper.

Plasma Proteins

• Major solute constituents of plasma.

• Normal concentration: 6-8 g/dl.

• Includes enzymes, hormones, and hormone-binding proteins.

• Biosynthesis Locations:

  • Liver (most), lymphocytes (immunoglobulins), enterocytes (e.g., apoprotein B-48).

Types of Plasma Proteins

1. Albumin: 4.5-5 g/dl

2. Globulin: 2.0-3.0 g/dl

   • α globulins, β-globulins, γ-globulins

3. Fibrinogen: 0.2-0.45 g/dl

Albumin

• Major constituent of plasma proteins.

• Comprises 75-80% of plasma colloid oncotic pressure and 50% of overall protein content.

• Formed in the liver, half-life ~20 days, molecular weight: 66,000.

• Functions:

  • Controls colloid osmotic pressure.

  • Transports bilirubin, fatty acids, metals, ions, hormones, and exogenous drugs.

Effects of Albumin Deficiency

• In kidney diseases, albumin may appear in urine (albuminuria).

• Leads to decreased plasma protein concentration.

• Results in decreased colloid osmotic pressure of plasma, causing edema.

Causes of Albumin Deficiency

• Liver diseases (e.g., cirrhosis): Decrease in albumin/globulins ratio.

• Protein malnutrition.

• Excessive renal excretion (renal disease).

• Genetic mutations (analbuminemia).

Hypoalbuminemia

• Causes:

  • Decreased albumin synthesis (liver cirrhosis, malnutrition).

  • Increased loss of albumin (nephrotic syndrome, severe burns).

• Effects:

  • Edema due to low oncotic pressure.

  • Reduced transport of drugs & substances in plasma.

  • Reduced protein-bound calcium levels.

Hyperalbuminemia

• No known clinical conditions cause increased albumin production; primarily due to dehydration.

Globulin

• Formed in liver, cells of reticuloendothelial system, and plasma cells.

• Molecular weight: 90,000-156,000.

• Categories:

  • α (α1, α2)

  • β (β1, β2)

  • γ (γ1, γ2)

• Includes glycoproteins, lipoproteins, transferrin, ceruloplasmin, immunoglobulins.

α1-Antitrypsin

• Main globulin of α1 fraction (90%) synthesized in liver, functions as an inhibitor of serine proteases.

• Deficiency leads to proteolytic lung damage (e.g., emphysema).

Types of α-Antitrypsin

• Over 30 types known; most common is M type.

• Genetic deficiencies result in accumulation in hepatocytes and deficiency in plasma.

Clinical Consequences of α-Antitrypsin Deficiency

• Neonatal jaundice, childhood liver cirrhosis.

• Pulmonary emphysema in young adults.

• Diagnosed via lack of α-globulin band in electrophoresis.

α-Fetoprotein (AFP)

• Synthesized in developing embryos by liver cells.

• Levels decrease during gestation, reaching adult levels at birth; specifics of function remain unclear.

• Elevated levels: linked to neural tube defects; decreased levels: increased risk of Down's syndrome.

• A tumor marker for hepatoma and testicular cancer.

Transferrin

• A β-globulin binding free iron in serum.

• Decreased levels in liver disease, chronic infections, nephrosis.

• Increased levels during iron deficiency anemia due to increased synthesis.

Ferritin

• Intracellular protein for iron storage; only a small portion exists in plasma.

• Elevated in primary hemochromatosis, damaging organs due to increased iron absorption.

Ceruloplasmin

• Plasma concentration: 300 mg/l.

• Functions include transporting 90% of copper; deficiency leads to Wilson’s disease.

Haptoglobin (Hp)

• An α2 globulin that binds free hemoglobin for delivery to reticuloendothelial cells.

• Prevents loss of free hemoglobin through the glomerulus, which could lead to kidney damage.

• Levels increase with inflammation, infection, injury, and malignancies.

β-Microglobulin

• A component of human leukocyte antigen (HLA), filtered by kidneys but mostly reabsorbed.

• Elevated levels indicate impaired kidney function or overproduction in disease; may serve as a tumor marker for leukemias and lymphomas.

C-Reactive Protein (CRP)

• An acute-phase protein synthesized by the liver; involved in phagocytosis.

• Increased levels in inflammatory conditions like rheumatoid arthritis and marker for ischemic heart disease.

Hypergammaglobulinemia

• Result of B cell stimulation, resulting in polyclonal or monoclonal proliferation.

• Clinical conditions include chronic infections, autoimmune diseases, chronic liver diseases.

Immunoglobulins

• Antibodies produced by B cells in response to antigen stimulation, react specifically with antigens.

Fibrinogen

• Formed in the liver with molecular weight of 340,000.

• Crucial in blood coagulation, contributing to plasma viscosity.

Properties of Plasma Proteins

1. Large molecular weights (50,000 - 300,000 Daltons) mainly glycoproteins.

2. Charged residues often located on the surface.

3. Unable to cross capillary membranes, exerting oncotic pressure.

4. Contribute significantly to blood viscosity.

5. Soluble in water, can be separated by ultracentrifugation.

6. Amphoteric nature allows them to act as buffers.

7. Bind metallic ions and steroids.

Functions of Plasma Proteins

1. Oncotic Pressure: Maintain blood volume and prevent fluid loss from capillaries (normal ~25 mmHg).

2. Viscosity Contribution: Shapes determine overall blood viscosity; fibrinogen more influential than albumin.

3. Immunity: Antibodies as plasma proteins (gamma globulins).

4. Transport: Carrier molecules for hormones and drugs (e.g., albumin, transferrin).

5. Coagulation: Dependent on fibrinogen and prothrombin concentration.

6. Buffering: Helps maintain acid-base balance.

7. Reservoir Function: Forms bonds with hormones, drugs, and metals.

8. Synthetic Function: Substrates for the synthesis of protein hormones.

Measurement of Plasma Proteins

A) Quantitative Measurement: Through chemical or immunological reactions. B) Semiquantitative Measurement: Via electrophoresis separating proteins by charge; five bands observed.

Normal Pattern of Plasma Protein Electrophoresis

• Bands include:

  • α1-antitrypsin, TBG, transcortin, haptoglobin, ceruloplasmin, α2-macroglobulin, transferrin, β-lipoprotein, albumin.

Thank You!

Plasma and its Components - Dr. K. M. Huria Parveen

Learning Objectives

• Describe the components of plasma protein.

• Explain the role and functions of plasma protein.

Composition of Blood

• Blood: a fluid connective tissue divided into two components:

  • Plasma: 55%

  • Formed Elements: 45%

    • Red Blood Cells (Erythrocytes)

    • White Blood Cells (Leukocytes)

    • Platelets (Thrombocytes)

Plasma

• A clear, straw-colored fluid portion of blood.

• Normal plasma volume: about 5% of body weight.

• Serum: fluid remaining after blood clots, lacking fibrinogen and clotting factors II, V, and VIII.

Composition of Plasma

• Water: 91%

• Plasma Proteins: 7% (Albumin, globulins, fibrinogen, others)

• Other Organic Molecules: 1% (Glucose, neutral fats, phospholipids, cholesterol, amino acids, creatine, creatinine, urea, uric acid, hormones, enzymes, antibodies)

• Inorganic Substances: 1% (Sodium, potassium, calcium, magnesium, chloride, iodide, iron, phosphates, copper)

Plasma Proteins

• Major solute constituents of plasma with a normal concentration of 6-8 g/dl.

• Include enzymes, hormones, and hormone-binding proteins.

• Biosynthesis Locations: liver (most), lymphocytes (immunoglobulins), enterocytes (e.g., apoprotein B-48).

Types of Plasma Proteins

• Albumin: 4.5-5 g/dl

• Globulin: 2.0-3.0 g/dl (α globulins, β-globulins, γ-globulins)

• Fibrinogen: 0.2-0.45 g/dl

Albumin

• Major constituent of plasma proteins, comprising 75-80% of plasma colloid oncotic pressure and 50% of overall protein content.

• Formed in the liver, half-life ~20 days, molecular weight: 66,000.

Functions of Albumin

• Controls colloid osmotic pressure.

• Transports bilirubin, fatty acids, metals, ions, hormones, and exogenous drugs.

Effects of Albumin Deficiency

• In kidney diseases, albumin may appear in urine (albuminuria).

• Leads to decreased plasma protein concentration and decreased colloid osmotic pressure causing edema.

Causes of Albumin Deficiency

• Liver diseases (e.g., cirrhosis)

• Protein malnutrition

• Renal excretion (renal disease)

• Genetic mutations (analbuminemia)

Hypoalbuminemia

• Causes: Decreased synthesis or increased loss

• Effects: Edema, reduced transport of drugs, reduced protein-bound calcium levels

Hyperalbuminemia

• Generally associated with dehydration, no known clinical conditions cause increased production.

Globulin

• Formed in the liver and plasma cells; molecular weight: 90,000-156,000.

Categories of Globulin

• α (α1, α2)

• β (β1, β2)

• γ (γ1, γ2)

Specific Proteins:

• α1-Antitrypsin: Inhibitor of serine proteases, deficiency leads to lung damage.

• Transferrin: Binds free iron; decreased in liver disease, increased in iron deficiency anemia.

• Ferritin: Iron storage protein; elevated levels in hemochromatosis.

• Ceruloplasmin: Transports copper; deficiency leads to Wilson’s disease.

• Haptoglobin (Hp): Binds free hemoglobin, increases with inflammation.

• β-Microglobulin: Indicator of kidney function, potential tumor marker.

• C-Reactive Protein (CRP): Acute-phase protein; increased in inflammatory conditions.

• Immunoglobulins: Antibodies produced by B cells.

Fibrinogen

• Molecular weight: 340,000; crucial for blood coagulation.

Properties of Plasma Proteins

• Large molecular weights (50,000 - 300,000 Daltons) and soluble in water.

• Contribute to oncotic pressure and blood viscosity, unable to cross capillary membranes.

• Amphoteric nature enables buffering.

Functions of Plasma Proteins

• Maintain blood volume and prevent fluid loss.

• Shape determines blood viscosity; fibrinogen more influential than albumin.

• Act as carriers for hormones and drugs.

Measurement of Plasma Proteins

• Quantitative Measurement: Chemical/immunological reactions.

• Semi-quantitative Measurement: Electrophoresis separates proteins; five bands observed.

Normal Pattern of Plasma Protein Electrophoresis

• Bands observed: α1-antitrypsin, TBG, transcortin, haptoglobin, ceruloplasmin, α2-macroglobulin, transferrin, β-lipoprotein, albumin.