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COMPOSITION OF BLOOD:
PLASMA COMPONENTS AND PROTEINS
Learning Objectives
Discuss the components of plasma.
Discuss about of plasma proteins.
Explain the role of plasma proteins in human body.
List the diseases in which plasma proteins are raised or decreased.
Components of Plasma
Functions of Plasma
1. Water:
* Transport medium; carries heat
2. Electrolytes:
* Membrane excitability
* Osmotic distribution of fluid b/t ECF & ICF
* Buffering of pH changes
3. Nutrients, wastes, gases, hormones:
– No function – just being transported
4. Plasma Proteins (See Next Slide)
Plasma Proteins
Plasma Proteins: (albumins, globulins, fibrinogen)
1. Maintaining colloid osmotic balance (albumins)
2. Buffering pH changes
3. Transport of materials through blood (such as water insoluble
hormones)
4. Antibodies (e.g. gamma globulins, immunoglobulins)
5. Clotting factors (e.g. fibrinogen)
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Introduction
Over 70% of plasma solids are plasma proteins primarily immunoglobulin
(Circulating Anti bodies), serum albumin, apoliproteins involved in transport
of lipids, transferrin (For iron transport) & blood clotting proteins such as
fibrinogen & prothrombin.
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Serum Albumin
VLDL
HDL
Immunoglobulins
Fibrinogen
Prothrombin
Transferrin
Albumin
about half of total serum proteins non covalently binds as many as 10 fatty
acid per protein monomer.
Bound to this soluble protein the otherwise insoluble fatty acid are carried to
tissues such as skeletal muscle, heart & renal cortex.
fatty acid dissociate from albumin & are transported into cells to serve as
fuel.
synthesized by liver (8 – 14 gram / daily).
Total exchangeable pool in body is 280 – 350 g.
About 1/3 is in plasma.
About 2/3 in extravascular extracellular spaces.
Concentration of albumin in
plasma is 40 – 50 g/l which is
much higher than in the
extracelluar space.
This concentration difference
accounts for its important role in
determining the distribution of
water in body.
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Hypo Albuminemia
Is the feature of advance chronic liver disease.
often taken as indication of reduced hepatic albumin synthesis.
In some cases albumin synthesis is normal while the distribution or
redistribution of albumin in the body is altered.
Types of Globulin
α1 TBG, transcortin, glycoprotein, lipoprotein, antitrypsin.
α2 Heptaglobin, glycoprotein, Macroglobulin, Ceruloplasmin
β Transferrin, Lipoprotein, Glycoprotein,
γ γ G , γ D, γ M , γ E , γ A
Globulin
The globulin proteins include enzymes, protein
carriers, and gamma globulin, or antibodies,
something the body produces to fight infection and
disease.
While most plasma proteins are made in the liver,
gamma globulins are made by lymphocytes called
plasma cells.
Globulins fall into one of four groups based on their
size and electrical charge: gamma, beta, alpha-1 and
alpha-2.
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Serum Immunoglobulins
1gG = Raised in chronic active hepatitis.
1gA = Raised Alcoholic liver disease.
Ceruloplasmin increased in cholestasis decreased in Wilson’s disease.
Serum Proteins, Liver & Blood Coagulation
The liver forms a large proportion of blood substances utilized in coagulation
process. These are fibnogen, prothrombin, accelarotor factors.
Vitamin K is required by the metabolic processes of liver for formation of
prothrombin & factors VII, IX & X.
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Albumin
Hemoglobin
β1 Globulin
γ – Globulin
α 1 - Lipoprotein
β1 Lipoprotein
Fibrinogen
MOL. WT. OF PLASMA Proteins
=
69,000
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64,500
=
90,000
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156,000
=
200,000
=
1,300,000
=
340,000
Fibrinogen
a soluble plasma glycoprotein, synthesized by the
liver.
converted by thrombin into fibrin during blood
coagulation.
Fibrin specifically binds the activated coagulation
factors factor Xa and thrombin and entraps them in
the network of fibers
Fibrinogen Factor 1
Mol.Wt. 340,000 is a soluble plasma glycoprotein
47.nm in length that consist of 3 non-identical pairs of polypeptide chains
(Aa B B, y)2
covalently linked by disulfide bridges.
All 3 chains are synthesized in liver.
3 structural gene involved are on same chromosome & their expression is coordinately regulated in human.
Transferrin
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B-1 globulin
Conc. 3g/l (Plasma)
Transports iron in plasma as ferric ions Fe3+, each transferrin molecule binds
2Fe3+
Protects against the toxic effects of free iron.
Normally 30% saturated with Fe3+, increased or decreased saturation is
indicative of iron overload or deficiency.
Decreased in inflammatory states due to excessive degradation of transferrin
- Fe3+ complexes.
Ceruloplasmin
Major copper transport protein.
Regulates oxidation – reduction transport and utilization of iron.
Increased concentrations are found in active liver disease or tissue damage.
Decreased amounts are seen in individuals with Wilson’s disease.
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C – Reactive Protein
Major components of acute phase response and a marker of bacterial
infection.
Mediates binding of foreign polysaccharides, phospholipids and complex
polyanions as well as activation of complement.
<1mg/ml in plasma.
Slightly elevated levels of CRP are indicative of chronic, low grade
inflammation and have been correlated with increased risk of cardiovascular
disease.
Prothrombin
Gla
Kringle Kringle Cleavage Sites Serine Protease.
Modular Structure of Prothrombin
“Cleavage of two peptide bonds yields thrombin all carboxyglutamate
residues are in gla domain”
Thrombin is synthesized as zymogen called prothrombin.
Prothrombin has 4 domains with the serine protease domain at its carboxy
terminius.
These domains work in concert to keep prothrombin in an inactive from and
to target it to appropriate sites for its activation by factor Xa (a serine
protease) and factor V a (a stimulatory protein).
Activation is accomplished by proteolytic cleavage of bond b/w arginine 274
& threonine 275 to release a fragment containing the first three domain & by
cleavage of the bond between arginine 323 & isoleucine 324 to yield active
thrombin.
Fibrinolysis requires plasminogen & tissue plasminogen activator to produce
plasmin for fibrinolysis.
Lysis of fibrin clot occurs through action of enzyme plasmin.
Plasmin exists in blood in zymogen form, plasminogen, plaminogen has a high
affinity for the fibrin clot and regions of porous fibrin network.
Plasminogen is activated to plasmin by action of another protease, tissue
plasminogen activator frequently referred as t-PA or TPA.
Plasma protein & Different diseases associated with it.
a) Albumin 3.5 – 5.5 g/dl
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↑ in Dehydration, shock, hemoconcentration
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↓ in Malnutrition , Malabsorption, Nephrosis
b) Globulin 2 – 3.6 g/dl
↑ in liver Diseases, Cirrhosis, Malaria, Lymphoproliferative
disorders.
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c) Fibrinogen 0.2 - 0.6 g/dl
↑ in glomemlonephritis, nephrosis
↓ in DIC, Placental injury, Meningitis
Summary of Blood Plasma Composition
• Water
• 90% by volume
• Solutes
• Plasma Proteins
• 8% by weight
• all contribute to osmotic pressure
• Albumin
• 60% of plasma proteins
• produced in liver
• main contributor to osmotic pressure
• Globulins
• 36% of plasma proteins
• alpha and beta produced in liver
• proteins that bnd to lipids, metal ions and fatsoluble vitamins
• gamma - antobodies released by plasma cells
during immune response
• Fibrinogen
• 4% of plasma proteins
• produced in liver
• forms fibrin threads during clotting
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REFERENCES
Lippincott's Illustrated Reviews: Biochemistry.
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Harper's Illustrated Biochemistry.
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