plasma chon

7/27/2019 Plasma Chon

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PLASMA PROTEINS AND

IMMUNOGLOBULINS


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OUTLINE

PLASMA

ALBUMIN

HAPTOGLOBULIN TRANSFERRIN

FERRITIN

CERULOPLASMIN

IMMUNOGLOBULINS


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PLASMA PROTEINS & IMMUNOGLOBULINS

PLASMA

consists of water, electrolytes, metabolites, nutrients,proteins, hormones

total CHON in plasma: 7-7.5 g/dL

most common method of analyzing plasma CHON:electrophoresis


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STARLING FORCES

ARTERIAL END:

BHP- 37mmHg

IFHP-1 mmHg

BOP- 25 mmHg

VENOUS END:

BHP- 17mmHg

IFHP-1 mmHg

BOP- 25 mmHg

37

125

11

9

25 1

17


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PLASMA CHONs.

are mostly synthesized in the liver

generally synthesized on membrane-bound

polyribosomes are mostly glycoproteins

many exhibit polymorphism

each has a characteristic half-life in the circulation

levels may increase during acute inflammatorystates or secondary to certain types of tissuedamage


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ALBUMIN


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Albumin is the major CHON in plasma

60% of plasma CHON

produced in the liver

comprises about half of the blood serum protein

synthesized in the liver as preproalbumin whichhas an N-terminal peptide that is removed beforethe nascent protein is released from RER

proalbumin cleaved in the Golgi vesicles toproduce the secreted albumin


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Functions of Albumin

Maintains oncotic pressure Transports thyroid hormones Transports other hormones, particularly fat

soluble ones Transports fatty acids to the liver Transports unconjugated bilirubin Transports many drugs and serum albumin levels

can affect the half-life of drugs Competitively binds calcium Buffers pH


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Haptoglobin

abbreviated as Hp in blood plasma: binds free Hb released from

erythrocytes with high affinity and therebyinhibits its oxidative activity

haptoglobin-hemoglobin complex removed by thereticuloendothelial system

Clinical use used to screen for and monitor intravascular hemolytic anemia

In intravascular hemolysis: free hemoglobin released intocirculation haptoglobin binds the Hbdecline in Hp levels

in extravascular hemolysis: the RES phagocytoses the erythrocytesand hemoglobin is not released into circulation normalhaptoglobin levels


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Haptoglobin

FUNCTIONS

-bind free plasma hemoglobin which allows

degradative enzymes to gain access to thehemoglobin

-prevents loss of iron through the kidneys

-protects the kidneys from damage by hemoglobin

-acute phase reactant: levels increased ininflammatory state


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Transferrin


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Transferrin

blood plasma protein for iron delivery

glycoprotein that binds iron very tightly butreversibly

iron bound to transferrin is less than 0.1% (4 mg) ofthe total body iron, it is the most important ironpool, with the highest rate of turnover (25 mg/24 h)

has a molecular weight of ~76 kD

contains 2 specific high-affinity Fe(III) binding sites


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Transferrin

main source is the liver

main role: deliver iron from absorption centres in theduodenum to all tissues

decreases in inflammationCLINICAL SIGNIFICANCE:

increased in patients with iron deficiency anemia

decreased in iron overload diseases and proteinmalnutrition


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FERRITIN


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FERRITIN

globular protein complex consisting of 24 proteinsubunits

primaryintracellular iron-storage protein in bothprokaryotes and eukaryotes

keeps iron in a soluble and non-toxic form

Ferritin that is not combined with iron is called

apoferritin


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FERRITIN

serves to transport iron to areas that it is required presence of iron itself is a major trigger for the productionof ferritin

apoferritin binds to free ferrous iron and stores it in theferric state

as ferritin accumulates within cells of the RES, proteinaggregates are formed as hemosiderin

CLINICAL SIGNIFICANCE under steady state conditions, serum ferritin level

correlates with total body iron stores


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Ceruloplasmin

Blue in color due to high copper content


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Ceruloplasmin


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Kayser-Fleisherring


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PLASMA IMMUNOGLOBULINS

2 major components

1. B lymphocytes

-mainly bone marrow derived-synthesis of circulating humoral antibodies

called immunoglobulins

2. T lymphocytes

-thymic origin

-cell mediated immunologic processes


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GENERAL FUNCTIONS OF IMMUNOGLOBULINS

A. Antigen binding

Ig bind specifically to one or a few closely relatedantigens

primary function of antibodies and can result inprotection of the host

valency of antibody refers to the number ofantigenic determinants that an individual

antibody molecule can bind


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GENERAL FUNCTIONS OF IMMUNOGLOBULINS

B. Effector Functions

1. Fixation of complement results in lysis of cells and release of biologically active

molecules2. Binding to various cell types Ie. phagocytic cells, lymphocytes, platelets, mast cells,

and basophils

some immunoglobulins also bind to receptors onplacental trophoblasts, which results in transfer of theIg across the placentatransferred maternalantibodies provide immunity to the fetus and newborn


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BASIC STRUCTURE OF IMMUNOGLOBULINS

A. Heavy and Light Chains All Ig have a 4 chain

structure as their basic unit

composed of two identicallight chains (23kD) and twoidentical heavy chains (50-70kD)


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B. Disulfide bonds1. Inter-chain disulfide bonds

heavy and light chains and the 2 heavy chains are heldtogether by inter-chain disulfide bonds and by non-covalent interactions

No. of inter-chain disulfide bonds varies amongdifferent immunoglobulin molecules

2. Intra-chain disulfide bonds Within each of the polypeptide chains there are also

intra-chain disulfide bonds.


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C.Variable (V) and Constant (C)Regions

both the heavy and light chain couldbe divided into 2 regions based on

variability in the amino acidsequences. These are the:

1. Light Chain - VL (110 amino acids) andCL (110 amino acids)

2. Heavy Chain - VH (110 amino acids)and CH (330-440 amino acids)


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D. Hinge Region region at which the arms of

the antibody molecule

forms a Y called the hinge region

because there is someflexibility in the molecule at

this point


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IMMUNOGLOBULIN FRAGMENTS:

STRUCTURE/FUNCTION RELATIONSHIPS

produced by proteolytic digestion

A. Fab antigen binding or Fab fragments

contained the antigen binding sites of theantibody each Fab fragment is monovalent whereas

the original molecule was divalent combining site of the antibody is created

by both VH and VL

different combinations of a VH and VLresult in antibodies that can bind adifferent antigenic determinants.


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IMMUNOGLOBULIN FRAGMENTS: STRUCTURE/FUNCTION

RELATIONSHIPS

B. Fc

Fc =easily crystallized

mediates effector functions Ig


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HUMAN IMMUNOGLOBULIN CLASSES


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HUMAN IMMUNOGLOBULIN CLASSES

Immunoglobulin classes-divided into 5 different classes, based on

differences in the amino acid sequences in the constantregion of the heavy chains All Ig within a given class will have very similar heavy chain

constant regions. These differences can be detected bysequence studies or more commonly by serological means(i.e. by the use of antibodies directed to these differences).

1. IgG - Gamma heavy chains

2. IgM - Mu heavy chains 3. IgA - Alpha heavy chains 4. IgD - Delta heavy chains 5. IgE - Epsilon heavy chains


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STRUCTURE AND SOME PROPERTIES OF IG CLASSES

A. IgG1. Structure

monomers subclasses differ in the number of disulfide bonds and length of

the hinge region

2. Propertiesmost versatile immunoglobulin because it is capable

of carrying out all of the functions of immunoglobulinmolecules.

a) IgG is the major Ig in serum - 75% of serum Ig is IgG b) IgG is the major Ig in extra vascular spaces c) Placental transfer

only class of Ig that crosses the placenta


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B. IgM

Structure normally exists as a pentamer but it can also exist as a monomer the pentameric form all heavy chains are identical and all light

chains are identicalProperties a) 3rd most common serum Ig. b) 1st to be made by the fetus and 1st Ig to be made by a

virgin B cells when it is stimulated by antigen. c) good complement fixing Igvery efficient in leading to

the lysis of microorganisms. d) As a consequence of its structure, IgM is also a good

agglutinating Ig.


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C. IgA

1. Structure

Serum IgA is a monomer but IgA found insecretions is a dimer2. Properties a) IgA is the 2nd most common serum Ig.

b) IgA is the major class of Ig in secretions -tears, saliva, colostrum, mucusimportant inlocal (mucosal) immunity.


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D. IgD

1. Structureexists only as a monomer.

2. Properties a) found in low levels in serum; its role in serum

uncertain

b) primarily found on B cell surfaces where itfunctions as a receptor for antigen


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E. IgE

1. Structureexists as a monomer

2. Properties

a) IgE is the least common serum Ig since it bindsvery tightly to Fc receptors on basophils and mast

cells even before interacting with antigen. b) Involved in allergic reactions

c) plays a role in parasitic helminth diseases


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CLINICAL IMPLICATIONS OF HUMAN IMMUNOGLOBULIN CLASSES

IgG1. Increases in:

a) Chronic granulomatous infectionsb) Infections of all typesc) Hyperimmunizationd) Liver diseasee) Malnutrition (severe)f) Dysproteinemia

g) Disease associated withhypersensitivity granulomas,dermatologic disorders, and IgGmyelomah) Rheumatoid arthritis

2. Decreases in:

a) Agammaglobulinemia

b) Lymphoid aplasia

c) Selective IgG, IgAdeficiency

d) IgA myeloma

e) Bence Jones proteinemia

f) Chronic lymphoblastic

leukemia


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CLINICAL IMPLICATIONS OF HUMAN IG CLASSES

2. Decreases in:

a) Agammaglobulinemia

b) Lymphoproliferative disorders

(certain cases)c) Lymphoid aplasia

d) IgG and IgA myeloma

e) Dysgammaglobulinemia

f) Chronic lymphoblastic leukemia

IgM

1. Increases (in adults) in:

a) Waldenstrm's

macroglobulinemia

b) Trypanosomiasisc) Actinomycosis

d) Carrin's disease (bartonellosis)

e) Malaria

f) Infectious mononucleosis

g) Lupus erythematosush) Rheumatoid arthritis


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IgA

1. Increases in:a) Wiskott-Aldrich syndrome

b) Cirrhosis of the liver (most cases)c) Certain stages of collagen andother autoimmune disorders such asrheumatoid arthritis and lupuserythematosusd) Chronic infections not based onimmunologic deficienciese) IgA myeloma

2. Decreases in:a) Hereditary ataxia telangiectasiab) Immunologic deficiency states (e.g.,dysgammaglobulinemia, congenitaland acquired agammaglobulinemia,and hypogammaglobulinemia)c) Malabsorption syndromesd) Lymphoid aplasia

e) IgG myelomaf) Acute lymphoblastic leukemiag) Chronic lymphoblastic leukemia


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IgD 1. Increases in: a) Chronic infections

b) IgD myelomasIgE

1. Increases in: a) Atopic skin diseases such as eczema

b) Hay feverc) Asthmad) Anaphylactic shock

e) IgE-myeloma 2. Decreases in: a) Congenital agammaglobulinemia

b) Hypogammaglobulinemia due to faulty metabolism orsynthesis of immunoglobulins


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SUMMARY

Plasma contains many proteins with variety of function

Albumin is the major CHON and is the principaldeterminant of intravascular osmotic pressure

Haptoglobulin binds extracorpuscular hemoglobin

Transferrin binds iron, transporting it to sites where it isrequired

Ceruloplasmin binds copper

Immunoglobulins play a key role in the immune defense

plasma chon

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