plasma proteins

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Plasma Proteins : 

Plasma Proteins Dr. Siva Prabodh, MD, Assistant Professor

Total Volume of Blood is around 4- 5 liters : 

Total Volume of Blood is around 4- 5 liters Blood mainly contains liquid medium and cell components. Blood containing anticoagulant after centrifugation liquid medium (Plasma) is separated, while the cells remain at bottom. While serum is separated from the clotted blood. Serum does not contain fibrinogen and other clotting factors.

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I. Major functions of blood and its components: ? transport and distribution of essential nutrients to tissues ? removal of waste products ? defense against internal insult ? repair of damaged tissues II. Two major components of blood: liquid phase and formed elements

Plasma vs. serum : 

Plasma vs. serum Anticoagulated Clotted

Hundreds of different proteins are present in plasma. : 

Hundreds of different proteins are present in plasma. The plasma protein concentration is around 6-8 gm/dl The important Plasma Proteins are Albumin Globulins Fibrinogen These plasma proteins are separated by electrophoresis into 5 bands Albumin, ?1, ?2 ? and ? bands.

Characteristics of Plasma Proteins : 

Characteristics of Plasma Proteins Most of the Plasma proteins are synthesized in the Liver and move into blood stream. Almost all plasma proteins are glycoprotein's Some plasma proteins concentration differs by disease states and they are called as Acute phase proteins (APP) Polymorphism

ALBUMIN : 

ALBUMIN Albumin is a small globular protein with mol.wt 69 kD It is abundant protein found in plasma. Albumin is synthesized by the Liver. Its synthesis rate is controlled primarily by Colloid Osmotic Pressure, secondarily by Proteins intake. In addition synthesis is ? by Inflammatory cytokines

Functions : 

Functions Osmotic pressure Transport Nutritive Buffer Clinical Significance: levels in Acute Dehydration Where as levels in Analbuminemia, Inflammation, Hepatic disease, Urinary loss, GI loss, PEM

Globulins : 

Globulins Globulins constitute several proteins and are separated into four bands ?1, ?2, ?, and ? on Electrophoresis. 1) . ?1 Antitrypsin (AAT) (?1 proteinase inhibitor) mol.wt is 54 kD, Major constituent of ?1 globulin It concentration is 200 mg/dl. This protein inhibits Trypsin, Elastase and other protease enzymes. Clinical Significance: It is positive Acute Phase Protein. Its concentration is decreased in Neonatal respiratory distress syndrome, Neonatal Cholestasis, cirrhosis, Hepatocellular Carcinoma

?1 Acid Glycoprotein (AAG) : 

?1 Acid Glycoprotein (AAG) It is highly soluble and posses high net –ve charge AAG binds and inactivates basic lipophilic hormones.. Clinical Significance: AAG is a +ve APP, especially in GI Inflammatory diseases and Malignant Neoplasms. ?2 Macroglobulin It is major plasma proteinase inhibitor. Its mol wt is 725 kD Clinical significance: Its concentration is elevated in Nephrotic syndrome.

Ceruloplasmin ( Ferroxidase) : 

Ceruloplasmin ( Ferroxidase) It is Blue colored ?2 globulin with Mol.wt 160 kD. Clinical Significance – Wilson Hepatolenticular degeneration Normal range is 25-50 mg/dl, in this disorder usually less then 20mg/dl is seen. It is an Inherited autosomal recessive disorder, Defect is associated with Chromosome – 13, the gene coding copper binding ATPase is mutated. Cirrhosis, Lenticular degeneration and Kf ring.

C-reactive protein : 

C-reactive protein It reacts with c-polysaccharide of capsule of pnuemococci It can stimulate complement activity and macrophage phagocytosis It is +ve Acute Phase Protein

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Haptoglobulins Its molecular weight is 90 Kd It is an Acute Phase Protein Functions It binds with free Hb The Hp- Hb complex( mol wt 155 kDa) cannot pass through glomuruli, so this binding prevents Hb loss Clinical significance Hp levels decrease in Hemolytic anemia's

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Immune Response When a foreign particle introduced in the body, immediately that is destroyed by our Immune system. Cell Mediated Immunity Humoral Immunity Antibody dependent cell mediated cytolysis Macrophages

Immunoglobulins : 

Immunoglobulins Structure – 2 identical H chains 2 identical L chains, these are combined through disulphide linkage Immunoglobulins are classified as five groups depending on changes in H chain.

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IgG Major (75 – 80%), crosses placenta, complement fixation IgA Mostly found in secretions like saliva, tears , sweat and colustrum.It prevents attachment of bacteria and viruses to mucous membranes IgM - Produced in primary response to antigen Largest Immunoglobulin, pentamer, Fixes complement IgD - Uncertain found on surface of many B cells. IgE - immediate Hypersensitivity by causing release of mediators from mast cells and basophils upon exposure to antigen Does not fix complement.

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I. IgG Structure: Monomer Percentage serum antibodies: 80% Location: Blood, lymph, intestine Half-life in serum: 23 days Complement Fixation: Yes Placental Transfer: Yes Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.

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II. IgM Structure: Pentamer Percentage serum antibodies: 5-10% Location: Blood, lymph, B cell surface (monomer) Half-life in serum: 5 days Complement Fixation: Yes Placental Transfer: No Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

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III. IgA Structure: Dimer Percentage serum antibodies: 10-15% Location: Secretions (tears, saliva, intestine, milk), blood and lymph. Half-life in serum: 6 days Complement Fixation: No Placental Transfer: No Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

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IV. IgD Structure: Monomer Percentage serum antibodies: 0.2% Location: B-cell surface, blood, and lymph Half-life in serum: 3 days Complement Fixation: No Placental Transfer: No Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

Slide 23: 

V. IgE Structure: Monomer Percentage serum antibodies: 0.002% Location: Bound to mast cells and basophils throughout body. Blood. Half-life in serum: 2 days Complement Fixation: No Placental Transfer: No Known Functions: Allergic reactions. Possibly lysis of worms.

Complement system : 

Complement system The complement system comprises about 20 plasma proteins and is involved in cell lysis, Inflammation and other processes Major proteins are C1 - C9

Multiple Myeloma ( Plasmacytoma) : 

Multiple Myeloma ( Plasmacytoma) . Definition: B-cell malignancy characterised by abnormal proliferation of plasma cells able to produce a monoclonal immunoglobulin ( M protein ) Incidence: 3 - 9 cases per 100000 population / year more frequent in elderly modest male predominance Multiple Myeloma characterized by para proteinemia, Anemia, Lytic bone lesions, proteinuria. Bence-Jones proteins - In Multiple Myeloma monoclonal light chains are excreted in urine

Slide 27: 

Homeostasis is cessation of bleeding from cut vessel, this occurs in 4 steps. Constriction of vessel Aggregation of platelets Formation of fibrin mesh that bind to platelet aggregate. Complete of partial dislocation of clots.

Clotting factors : 

Clotting factors

Anti coagulants – which inhibit clotting : 

Anti coagulants – which inhibit clotting Ca++ is important for clotting The substances which bind with Ca++ are effective anticoagulants Ex. Oxalate, fluoride, EDTA etc

Clinical Significance : 

Clinical Significance Defects in clotting factors are seen in various Inherited and acquired disorders Important disorders are – Hemophilia A Hemophilia B Von Willibrand disease Afibrinogenemia