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    7) Plasma Proteins

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    7) Plasma Proteins

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    6 views34 pages

    7) Plasma Proteins

    Uploaded by

    ubaidhashmi1326

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 34

    Plasma Proteins

    GIT Block

    1 Lecture

    Dr. Sumbul Fatma


    Overview:
    • Functions and characteristics of plasma proteins

    • Measurement of plasma proteins and diagnosis of


    diseases

    • Electrophoretic patterns of plasma proteins

    • Acute phase proteins


    Plasma Proteins (pps)

    — Plasma contains >300 different proteins


    — Many pathological conditions affect level
    of plasma proteins
    — Mostly synthesized in the liver
    — Some are produced in other sites
    — A normal adult contains ~70 g/L of pps
    Functions of plasma proteins

    • Transport (Albumin, prealbumin, globulins)

    • Maintain plasma oncotic pressure (Albumin)

    • Defense (Immunoglobulins and complement)

    • Clotting and fibrinolysis (Thrombin and


    plasmin)
    Measurement of Plasma Proteins
    A) Quantitative measurement of a specific protein:
    Chemical or immunological reactions

    B) Semiquantitative measurement by electrophoresis:

    — Proteins are separated by their electrical charge in


    electrophoresis
    — Five separate bands of proteins are observed
    — These bands change in disease
    Normal Pattern of Plasma Protein Electrophoresis
    Types of Plasma Proteins
    — Prealbumin
    — Albumin
    — α1-Globulins:
    — α1-Antitrypsin, α-fetoprotein
    — α2-Globulins:
    — Ceruloplasmin, haptoglobin
    — β-Globulins:
    — CRP, transferrin, β2-microglobulin
    — γ- Globulins
    Prealbumin (Transthyretin)
    — A transport protein for:
    — Thyroid hormones
    — Retinol (vitamin A)
    — Migrates faster than albumin in electrophoresis
    — Separated by immunoelectrophoresis
    — Lower levels found in:
    — liver disease, nephrotic syndrome, acute phase
    inflammatory response, malnutrition
    — Short half-life (2 days)
    Albumin
    — Most abundant plasma protein (~40 g/L) in normal
    adult

    — Synthesized in the liver as preproalbumin and


    secreted as albumin

    — Half-life in plasma: 20 days

    — Decreases rapidly in injury, infection and surgery


    Functions
    • Maintains oncotic pressure:
    – The osmotic pressure exerted by plasma
    proteins that pulls water into the
    circulatory system
    – Maintains fluid distribution in and
    outside cells and plasma volume

    • 80% of plasma oncotic pressure is


    maintained by albumin
    Functions
    • A non-specific carrier of
    – hormones, calcium, free fatty acids, drugs, etc.

    • Tissue cells can take up albumin by


    pinocytosis where it is hydrolyzed to
    amino acids

    • Useful in treatment of liver diseases,


    hemorrhage, shock and burns
    Hypoalbuminemia
    • Causes
    – Decreased albumin synthesis (liver
    cirrhosis, malnutrition)
    – Increased losses of albumin
    • Increased catabolism in infections
    • Excessive excretion by the kidneys (nephrotic
    syndrome)
    • Excessive loss in bowel (bleeding)
    • Severe burns (plasma loss in the absence of skin
    barrier)
    Hypoalbuminemia
    Effects
    • Edema due to low oncotic pressure
    – Albumin level drops in liver disease causing low
    oncotic pressure
    – Fluid moves into the interstitial spaces causing
    edema
    • Reduced transport of drugs and other substances
    in plasma
    • Reduced protein-bound calcium
    – Total plasma calcium level drops
    – Ionized calcium level may remain normal
    Hyperalbuminemia

    • No clinical conditions are known that


    cause the liver to produce large
    amounts of albumin
    • The only cause of hyperalbuminemia is
    dehydration
    α1-Antitrypsin
    — Synthesized by the liver and macrophages
    — An acute-phase protein that inhibits proteases
    — Proteases are produced endogenously and from
    leukocytes and bacteria
    — Digestive enzymes (trypsin, chymotrypsin)
    — Other proteases (elastase, thrombin)
    — Infection leads to protease release from
    bacteria and from leukocytes
    Types of α1-Antitrypsin

    — Over 30 types are known


    — The most common is M type
    — Genetic deficiency of α1-Antitrypsin
    — Synthesis of the defective α1-Antitrypsin occurs
    in the liver but it cannot secrete the protein
    — α1-Antitrypsin accumulates in hepatocytes and
    is deficient in plasma
    Clinical Consequences of α1-Antitrypsin
    Deficiency
    — Neonatal jaundice with evidence of cholestasis
    — Childhood liver cirrhosis
    — Pulmonary emphysema in young adults

    Laboratory Diagnosis
    — Lack of α1-globulin band in protein electrophoresis
    — Quantitative measurement of α1-Antitrypsin by:
    — Radial immunodiffusion, isoelectric focusing or
    nephelometry
    α-Fetoprotein (AFP)
    — Synthesized in the developing embryo and fetus
    by the parenchymal cells of the liver
    — AFP levels decrease gradually during intra-uterine
    life and reach adult levels at birth
    — Function is unknown but it may protect fetus
    from immunologic attack by the mother
    — No known physiological function in adults
    α-Fetoprotein (AFP)
    — Elevated maternal AFP levels are associated with:
    — Neural tube defect, anencephaly
    — Decreased maternal AFP levels are associated
    with:
    — Increased risk of Down’s syndrome
    — AFP is a tumor marker for:
    Hepatoma and testicular cancer
    Ceruloplasmin
    — Synthesized by the liver
    — Contains >90% of serum copper
    — An oxidoreductase that inactivates ROS causing
    tissue damage in acute phase response
    — Important for iron absorption from the intestine
    — Wilson’s disease:
    — Due to low plasma levels of ceruloplasmin
    — Copper is accumulated in the liver and brain
    Haptoglobin
    — Synthesized by the liver

    — Binds to free hemoglobin to form complexes


    that are metabolized in the RES

    — Limits iron losses by preventing Hb loss from


    kidneys

    — Plasma level decreases during hemolysis


    Transferrin
    — A major iron-transport protein in plasma
    — 30% saturated with iron

    — Plasma level drops in:


    — Malnutrition, liver disease, inflammation,
    malignancy

    — Iron deficiency results in increased hepatic


    synthesis

    — A negative acute phase protein


    β2–Microglobulin
    — A component of human leukocyte antigen (HLA)
    — Present on the surface of lymphocytes and most
    nucleated cells
    — Filtered by the renal glomeruli due to its small
    size but most (>99%) is reabsorbed
    — Elevated serum levels are found in
    — Overproduction in disease
    — May be a tumor marker for:
    — Leukemia, lymphomas, multiple myeloma
    C-Reactive Protein (CRP)
    — An acute-phase protein synthesized by the liver

    — Important for phagocytosis

    — High plasma levels are found in many inflammatory


    conditions such as rheumatoid arthritis

    — A marker for ischemic heart disease


    Hypergammaglobulinemia
    — May result from stimulation of
    — B cells (Polyclonal hypergammaglobulinemia)
    — Monoclonal proliferation (Paraproteinemia)

    Polyclonal hypergammaglobulinemia:
    — Stimulation of many clones of B cells produce a
    wide range of antibodies
    — γ-globulin band appears large in electophoresis
    — Clinical conditions: acute and chronic infections,
    autoimmune diseases, chronic liver diseases
    Monoclonal
    Hypergammaglobulinemia
    — Proliferation of a single B-cell clone produces
    a single type of Ig
    — Appears as a separate dense band (paraprotein
    or M band) in electrophoresis
    — Paraproteins are characteristic of malignant
    B-cell proliferation
    — Clinical condition: multiple myeloma
    Positive Acute Phase Proteins
    — Plasma protein levels increase in:
    — Infection, inflammation , malignancy, trauma,
    surgery

    — These proteins are called acute phase reactants

    — Synthesized due to body’s response to injury


    — Examples: α1-Antitypsin, haptoglobin,
    ceruloplasmin, fibrinogen, c-reactive protein
    Positive Acute Phase Proteins
    — Mediators cause these proteins to increase after
    injury

    — Mediators: Cytokines (IL-1, IL-6), tumor necrosis


    factors α and β , interferons, platelet activating
    factor

    Functions:
    1. Bind to polysaccharides in bacterial walls
    2. Activate complement system
    3. Stimulate phagocytosis
    Negative Acute Phase Proteins

    — These proteins decrease in inflammation


    — Albumin, prealbumin, transferrin
    — Mediated by inflammatory response via cytokines
    and hormones
    — Synthesis of these proteins decrease to save
    amino acids for positive acute phase proteins
    References
    — Lecture Notes in Clinical Biochemistry 7th edition,
    pages 92-98
    — Clinical Biochemistry An Illustrated Colour Text pages
    48-51

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