Plasma Proteins: Types and Function

• The presentation focuses on plasma proteins, their functions, and acute phase reactants
• It outlines the functions and characteristics of plasma proteins, measurement methods for diagnosing diseases, electrophoretic patterns, and acute phase proteins

Plasma Proteins

• Plasma contains over 300 different proteins
• Pathological conditions frequently influence plasma protein levels
• Most plasma proteins are synthesized in the liver
• Some plasma proteins originate from other sites
• Normal adult plasma contains around 70 g/L of plasma proteins

Functions

• Key functions include transport, maintenance of oncotic pressure, defense, and clotting/fibrinolysis
• Transport is facilitated by albumin, prealbumin, and globulins
• Albumin maintains plasma oncotic pressure
• Immunoglobulins and complement provide defense
• Thrombin and plasmin aid clotting and fibrinolysis

Plasma Protein Types

• Specific types: prealbumin, albumin, α1-globulins, α2-globulins, β-globulins, and γ-globulins
• α1-globulins include α1-antitrypsin and α-fetoprotein
• Ceruloplasmin and haptoglobin are α2-globulins
• CRP, transferrin, and β2-microglobulin are β-globulins

Measurement

• Measurement of plasma proteins can be quantitative, for a specific protein, using chemical or immunological reactions
• It can also be semiquantitative by electrophoresis, where proteins are separated by electrical charge
• Electrophoresis yields five separate protein bands that change in disease

Prealbumin (Transthyretin)

• Transports thyroid hormones and retinol (vitamin A)
• Migrates faster than albumin during electrophoresis
• Can be separated by immunoelectrophoresis
• Lower levels are present in liver disease, nephrotic syndrome, acute phase inflammatory response, and malnutrition
• The half-life is short at 2 days

Albumin

• Most abundant plasma protein in adults, at approximately 40 g/L
• Synthesized in the liver as preproalbumin and secreted as albumin
• Maintains oncotic pressure, which regulates fluid distribution between cells/plasma and the circulatory system, with albumin maintaining 80%
• Has a half-life of 20 days
• Decreases rapidly during injury, infection, and surgery
• Acts as a non-specific carrier for hormones, calcium, free fatty acids, and drugs
• Tissue cells uptake albumin by pinocytosis, hydrolyzing it into amino acids
• Useful in treating liver diseases, hemorrhage, shock, and burns

Hypoalbuminaemia

• Hypoalbuminaemia leads to edema because of low oncotic pressure
• Albumin level drops in liver disease, causing low oncotic pressure and resultant fluid accumulation in interstitial spaces
• Transport of drugs and protein-bound calcium are also reduced.
• Total plasma calcium level drops, while ionized calcium levels may remain normal
• Possible causes: decreased albumin synthesis from liver cirrhosis or malnutrition, or increased losses from infections, kidney excretion (nephrotic syndrome), bowel loss, or severe burns

Hyperalbuminaemia

• Hyperalbuminaemia's only cause is dehydration
• No clinical conditions are known to cause the liver to increase production

α1-Antitrypsin

• Synthesized by the liver and macrophages
• Acute-phase protein inhibiting proteases produced endogenously, or from leukocytes and bacteria
• Digestive enzymes (trypsin, chymotrypsin) and other proteases (elastase, thrombin) can be inhibited
• Infection causes the release of proteases from bacteria and leukocytes
• Over 30 types
• Most common is M type
• Genetic deficiency leads to synthesis of defective α1-antitrypsin which the liver cannot secrete
• α1-Antitrypsin accumulates in hepatocytes, causing a deficiency in plasma & neonatal jaundice, childhood liver cirrhosis and pulmonary emphysema in young adults can result
• Diagnosis is made by lack of α1-globulin band in electrophoresis, and quantitative measurement

α-Fetoprotein (AFP)

• AFP is synthesized in the developing embryo and fetus by liver parenchymal cells
• It decreases gradually during intrauterine life, reaching adult levels at birth
• AFP's function is unknown, but it may protect the fetus from the mother's immunologic attack
• No known adult physiological function
• Elevated levels in the mother can indicate neural tube defects or anencephaly
• Decreased levels may indicate increased risk of Down's syndrome and is a tumor marker for hepatoma and testicular cancer

Ceruloplasmin

• Synthesized by the liver and contains over 90% of serum copper
• Functions as an oxidoreductase inactivating ROS, preventing tissue damage in acute phase responses
• Important for iron absorption from the intestine
• Low plasma levels lead to Wilson’s disease and can be tested
• Copper accumulates in the liver and brain

Haptoglobin

• Synthesized by the liver
• Binds free hemoglobin, forming complexes metabolized in the RES
• Limits iron losses by preventing hemoglobin loss from the kidneys
• Plasma levels decrease during hemolysis

Transferrin

• A major iron-transport protein normally 30% saturated with iron
• Plasma levels drop in malnutrition, liver disease, inflammation, and malignancy
• Iron deficiency increases hepatic synthesis
• It is a negative acute phase protein

β2-Microglobulin

• Component of human leukocyte antigen (HLA) and present on lymphocytes/nucleated cells
• Filtered by the renal glomeruli but mostly reabsorbed
• Elevated serum levels indicate impaired kidney function or overproduction in disease, so function can be tested.
• Can be a tumor marker for leukemia, lymphomas, and multiple myeloma

C-Reactive Protein (CRP)

• CRP is an acute-phase protein synthesized by the liver which is important for phagocytosis and can be tested
• High plasma levels are found in inflammatory states like rheumatoid arthritis
• Marker for ischemic heart disease

Hypergammaglobulinaemia

• Hypergammaglobulinaemia can be caused by B cell stimulation (polyclonal) or monoclonal proliferation
• Polyclonal hypergammaglobulinemia causes stimulation of many B cell clones, producing many antibodies which appear large in electrophoresis
• Clinical conditions linked include acute/chronic infections, autoimmune diseases, and chronic liver diseases

Monoclonal Hypergammaglobulinaemia

• Involves proliferation of a single B-cell clone, producing a single Ig type
• Appears as a separate, dense band (paraprotein or M band) in electrophoresis
• Paraproteins indicate malignant B-cell proliferation
• A clinical condition that can be identified is multiple myeloma

Acute Phase Proteins

• Plasma protein levels increase in infection, inflammation, malignancy, trauma, and surgery
• These proteins are called acute phase reactants that are synthesized in response to injury
• Mediators like cytokines (IL-1, IL-6), tumor necrosis factors α and β, interferons, and platelet-activating factor cause these proteins to increase after injury
• Examples include α1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, and c-reactive protein

Functions of acute phase proteins

• These proteins bind to polysaccharides in bacterial walls
• They also activate the complement system and stimulate phagocytosis

Negative Acute Phase Proteins

• Decrease in inflammation
• Albumin, prealbumin, and transferrin are all negatively affected
• Mediated by inflammatory response via cytokines and hormones
• Synthesis of these proteins decreases to save amino acids for positive acute phase proteins