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Blood Plasma

Anti-coagulated blood
is Centrifuged: Plasma -
92% water
•clear plasma at top 7% proteins
1% solutes
(55%)
•Plasma : 92% water

7% proteins
1% solutes
Separation of Plasma Proteins
Hundreds of different proteins are present in
plasma.
The Most Important Plasma Proteins are :
Albumin – 60%
Globulins – 35%
Clotting proteins – 4%
Enzymes– 1%
Normal A/G Ratio - 1.7:1
Electrophoresis: separates plasma proteins into 5
bands: Albumin, alpha 1globulin, alpha 2 globulin, Beta
globulin and gamma globulin.
Ultracentrifugation Method- Different plasma proteins
have diff densities is the basis of this technique. This also
determines molecular weight of plasma proteins:
Albumin- 69,000, Globulin-1,56,000, Fibrinogen-4,00,000
Protein Normal Examples
Albumin value
55.8-60% Prealbumin, Albumin
Alpha 1 2.2 -4.6% α1-Antitrypsin, Thyroxin Binding Globulin
Alpha 2 8.2-12.5% etc
Haptoglobulin, Ceruloplasmin, α2-
Beta 7.2-14.5% macroglobulin
Transferin, Low density lipoprotein,
(1+2) Complement.
Gamma 11.5-18.5% IgG, IgA. IgM, IgD, IgE
Characteristics of Plasma
Proteins
 Most of plasma proteins are synthesized in the
Liver cells & move into blood
 The exception is of the Immunoglobulins which
are synthesized by B Lymphocytes and some
complement proteins which are synthesized by
macrophages.
 Plasma Proteins > 60,000 m.wt .are not filtered
and excreted while those < 60,000 m.wt. pass
through glomerulus into urine
Albumin
 Normal plasma level: 3.5 - 5.0 g/dl, Molecular Wt.= 65,000
 Half Life of plasma clearance-19 days, Acts as a binding protein for
many substances in plasma.
 CappilaryHydrostatic Pressure exerted by extracellular
fluid present inside cappilaries on cappilary wall cause
leakage of fluid out of cappilaries at arteriolar end. The fluid
leaked out is reabsorbed due to the Oncotic Pressure in
cappilaries created by Albumin.
 Colloid(Oncotic)osmotic pressure created by albumin in
the bloo capillaries as they are not permeable to albumin&
it pulls tissue fluid back into capillaries. This is important to
maintain normal blood volume and blood pressure.
 Starling Hypothesis –Net Filtration through capillary
membrane is proportional to the hydrostatic pressure
difference across the membrane (Pc-Pi) minus the
oncotic pressure difference (Pic-Pii),where Pc &Pi are
hydrostatic pressures in cappilary wall & interstitial fluid
respectively and Pic & Pii are Oncotic Pressures inside
Clinical Significance of Albumin
Hypoalbuminaemia: Causes
a.. Protein loss-
 Nephrotic Syndrome: Defect in glomerular
basement membrane leads to proteinuria
(albuminuria), hypoalbumnemia, Hyperlipidaemia&
generlaized edema
 Burns: Loss of albumin due to plasma leakage
from damaged blood vessels from burnt tissues
b. Decreased synthesis- Liver disease
c. Inadequate dietary intake –Malnutrition

Consequence of hypoalbuminaemia:
 Swelling of body → oedema
α1-Antitrypsin
 Role: α 1-antitrypsin inhibits Trypsin,
Elastase, and Collegenase & other
proteolytic Enzymes released during
inflammation
 Clinical Significance: α -antitrypsin
1
Deficiency :
 Hereditary disorder
 Lack of α -antitrypsin →→ uninhibited tissue
1
breakdown during inflammation
 Causes pulmonary emphysema (decreased
area of gas exchange due to loss of alveoli)
in adults and cirrhosis in children.
Thyroxine Binding Globulin
It is the major transport protein for thyroid
hormone.
99.7% of thyroxine is bound to TBG and
only 0.3% is free and active at cellular
level.
Clinical Significance: A complete
deficiency in causes Thyrotoxicosis as it
increases level of free thyroxine in blood
and symptoms of Graves’ disease.
Haptoglobin
 It binds with ‘free’ hemoglobin & prevents
loss of hemoglobin in urine as this complex
can not pass through renal glomeruli
 Haptoglobin + hemoglobin complex is
removed from circulation by
reticuloendothelial system. In liver ⇒
components are recycled- Haptoglobin is
destroyed
 Hemoglobin is broken down to globin and
heme and then further to iron and bilirubin
 Clinical Significance: Haptoglobin level falls in
hemolytic states.
Ceruloplasmin
 Cu transport protein,
 Clinical Significance: Wilson’s Disease: an
autosomal recessive disorder.
(a) Cu is deposited in the liver due to reduced biliary
excretion- result- Liver enlargement, jaundice, Liver failure
(b) Deficiency of ceruloplasmin results in deposition of Cu in
tissues and low plasma copper concentrations- CNS
dysfunction, arthritis, Kaysher Fleischer Ring Around
cornea in eyes.
(c) Cu filtered through glomeruli ⇒ urinary copper excretion ↑

Treatment:
 D-penicillamine -a copper-chelating agent → reduce tissue
copper concentrations
Alpha -2 Macroglobulin

A major plasma proteinase


inhibitor.
Clinical Significance- Its level is
increased in Nephrotic Syndrome
Transferin
 An Iron transport protein.
 Free iron is toxic so all iron is protein-bound:
transferrin, ferritin, haemosiderin, hemoglobin
 Only 0.1% of total body iron circulates in plasma:
as Fe3+ bound to transferrin
 Clinical significance of transferin:
 ↑↑ in iron deficiency
 ↓↓ in iron overload
 ↓↓↓↓ in nephrotic syndrome ⇒ because low mwt
transferrin is lost in urine.
Lipoproteins
Low Density Lipoproteins (LDL) transports
cholesterol from the liver to the tissues of the
body. LDL cholesterol is therefore considered the
"bad" cholesterol as high levels of LDL cholesterol
is associated with high risk of
cardiovascular disease
High-density lipoprotein (HDL) removes
cholesterol from atheroma within arteries and
transport it back to the liver for excretion or re-
utilization—so HDL is called good cholesterol“.

A high level of HDL protect against


cardiovascular diseases, and low HDL cholesterol
Complement System
The complement system consists of a number of small
proteins found in the circulating blood .
Over 20 proteins and protein fragments make up the
complement system,.
The following are the basic functions of the complement
1. Lysis of cells, bacteria and viruses.
2. Opsonization for phagocytosis of foreign antigens.
3. Immune Clearance, which removes immune complexes
from immune system.

Clinical Significance: Deficiency in complement system


plasma proteins- AutoImuune Disorers, Infections
Acute Phase Reactant –C
Reactive Proteins
 C-Reactive Proteins (CRP): The
proteins react with the C-
polysaccahrides of pneumoccocci ⇒
thus its name
 Plasma concentration of CRP rises

rapidly in response to acute


inflammation & bacterial infections. It
is normal in Viral infections.
Fibrinogen
 It is an acute phase reactant
 Most abundant of the coagulation factors
 Forms the fibrin clot
 Helps in platelet aggregation
Proteins of immune system
 Immunoglobulins
 Synthesized by B lymphocytes,

 Differentiation of B lymphocytes ⇒ plasma cells

secreting immunoglobulins
 Two Identical Heavy Chains

 2 Idenical Light -Chains linked by dilsuphide bonds

 5 Types

 IgG
 IgM
 IgA
 IgE
 IgD
Plasma immunoglobulins
IgG Major (75%), crosses placenta, complement fixation

IgM First line of defence; produced in acute stage of infection ,


largest Immunoglobulin, Fix complementcan be synthesized by
fetus
IgA Present in secretions like saliva, tears, sweat, & colostrum,
tears., Prevents attachment of bacteria & viruses to mucus
membranes
IgD Found surface of many B Lymphocytes, role is
uncertain
IgE Allergic response, Lysis of Worms
Raised in: eczema, Hay fever, Asthma, Anaphylactic
shock
Immunoglobulin deficiencies

 IgM deficiency – predisposes to


septicaemia
 IgG deficiency – recurrent pyogenic
infections of tissues (lung, skin) by toxin-
producing organisms, e.g. staphylocci,
streptococci
 IgE – symptomless or recurrent, mild
respiratory tract infections
MULTIPLEMYELOMA
Multiple myeloma is a cancer of plasma cells that
produce monoclonal immunoglobulin (Protein M)
and invade and destroy adjacent bone tissue.
Oncotic & hydrostatic pressures

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