PLASMA PROTEINS

FUNCTIONS NUTRITIVE

BINDING &TRANSPORT

FLUID EXCHANGE

BLOOD COAGULATION

RESERVEPROTEINS

VISCOSITY OF BLOOD

BUFFER

DEFENCE OF BODY

ENZYMES

HORMONES

1. NUTRITIVE FUNCTION OF PLASMA PROTEINS

Simple proteins and a good source of proteins

Macrophages split plasma proteins into amino acids for tissue protein synthesis

2. PLASMA PROTEINS AS RESERVE PROTEINS

Occurs in following conditions - malnutrition - starvation - fasting - hypoproteinaemia

Amino acids released from broken plasma proteins distributed throughout body to form cellular protein molecules

Used as a last source of energy

3. PLASMA PROTEINS FOR FLUID EXCHANGE

Exert colloid osmotic pressure

Play an important role in distribution of water between blood and tissues

AT ARTERIAL END OF CAPILLARIES: Hydrostatic pressure > osmotic pressure. Hence, fluid driven out of vessels into tissue spaces. Plasma proteins, however, do not leave capillaries because of their large size.

AT VENOUS END OF CAPILLARIES: Osmotic pressure > hydrostatic pressurebecause of presence of plasma proteins in capillaries. Hence, fluid is drawn from tissue spaces into vessels.

This allows exchange of fluids and dissolved materials between blood and tissue spaces (STARLING HYPOTHESIS)

4. PLASMA PROTEINS AS BUFFERS

Amphoteric molecules

In acidic pH. Amino group of plasma proteins combine with a proton and becomes positively charged

In alkaline medium, carboxyl group of plasma proteins donate a proton and becomes negatively charged

In this way, plasma proteins maintain a constant pH of the medium.

5. TRANSPORT FUNCTION OF PLASMA PROTEINS

Binds to and transport various substances throughout body

Eg. 1) Albumin transport ions, drugs, penicillin, gases, pigments, ect

2) lipoproteins transport lipid fractions and fat-soluble vitamins

3) haptoglobin transport free haemoglobin

4) transferrin transport iron

7. ROLE OF PLASMA PROTEINS IN VISCOSITY OF BLOOD

Makes blood viscous

Albumin, globulins and fibrinogen mainly responsible

Due to the large size and asymmetrical structure of plasma proteins

Viscosity provides resistance to blood flow in vessels

This maintains blood pressure in normal range

8. PLASMA PROTEINS FOR BODY DEFENCE

Gamma-globulins also known as immunoglobulin

Act as antibodies against antigens to protect body against infections like diphtheria, thyroid, streptococcal infections, mumps, influenza, measles, hepatitis, rubella, poliomyelitis, ect.

9. PLASMA PROTEINS AS ENZYMES

Enzymes are proteins (except ribozymes)

Eg. 1) Amylase 2) transaminase 3) dehydrogenase 4) lipase 5) phosphatase

10. PLASMA PROTEINS AS HORMONES

Certain hormones are proteins

Eg. 1) Oxytocin 2) Vasopressin 3) insulin 4) Parathormone 5) TSH 6) ACTH

11. ROLE OF PLASMA PROTEINS IN BLOOD COAGULATION

Plasma contains fibrinogen, enzymes and clotting factors

These participate in coagulation of blood

Prevent excessive loss of blood during injury

CLINICAL SIGNIFICANCE OF PLASMA PROTEINS

Normal plasma protein level = 6-8 g%

Increase in plasma protein levels

Decrease inPlasma protein levels

HYPERPROTEINAEMIA

HYPOPROTEINAEMIA

HYPERPROTEINAEMIA

Increase in total amount of plasma proteins in the body

Occurs in following 2 situations: 1) Haemoconcentration - due to dehydration - both albumin and globulin are increased - A:G ratio remains unchanged

2) Diseases such as hypergammaglobulinaemia - high levels of plasma globulins - albumin level normal or reduced - A:G ratio reversed if albumin reduced

HYPERGAMMAGLOBULINAEMIA

POLYCLONAL GAMMOPATHIES

MONOCLONAL GAMMOPATHIES

Chronic infections like TB, leprosy, kalaazar, etc

Chronic liver disease like cirrhosis or chronic active hepatitis

Sarcoidosis

Autoimmune diseases like rheumatoid arthritis

POLYCLONAL GAMOPATHIES

MONOCLONAL GAMMOPATHIES

MALIGNANT BENIGN

Multiple myeloma

Macroglobulinaemia

Lymphoreticular malignancieslike lymphosarcoma, leukemia, hodgkin’s disease

Secondary to diabetes mellitus, Chronic infections, etc

Idiopathic

HYPOPROTEINAEMIA

Haemodilution

Hypoalbuminaemia

Hypogammaglobulinaemia

HAEMODILUTION

Cause may be Water intoxication

Both albumin and globulin are decreased

A:G ratio remains unaltered

Results in edema because of low plasma proteins in capillaries to exert colloid osmotic pressure

HYPOALBUMINAEMIA

1) LOSS OF ALBUMIN FROM THE BODY - RENAL: Nephrotic syndrome - GIT: Protein losing enteropathy - SKIN: Burns and other skin lesions

2) DECREASED SYNTHESIS OF ALBUMIN - SEVERE LIVER DISEASES: cirrhosis of liver , chronic hepatitis - NON-AVAILABILITY OF PRECURSORS: Malabsorption syndrome, protein calorie malnutrition - GENETIC DEFICIENCIES: Analbuminaemia

3) MISCELLANEOUS - Acute or chronic illnesses - infections - malignancy - pregnancy

HYPOGAMMAGLOBULINAEMIA

1) LOSS OF GAMMA-GLOBULINS FROM BODY - RENAL: Nephrotic syndrome - GIT: Protein losing enteropathy - SKIN: Burns and other skin lesions

2) DECREASED SYNTHESIS OF GAMMA-GLOBULINS - TRANSIENT: Neonates/infants - PRIMARY: Genetic deficiency - SECONDARY: AIDS, LEUKEMIA 3) MISCELLANEOUS - Pregnancies

ALBUMIN

Structure of Albumin.

Most abundant and fairly homogeneous protein of plasma.

Half of the total plasma protein is made up of albumin.

Plasma protein composition

Single polypeptide chain.

Contain 585 amino acids.

Have 17 interchain disulfide (s-s) bonds.

Molecular weight : 69 000

Low isoelectric pH (pI = 4.7)

Precipitates last in salting out or alcohol precipitation method.

Normal value: 3.5 – 5.5 mg/dL

Normal pattern of serum proteins on electrophoresis

Normal values % of total proteins•Albumin 50 - 70 •α globulin 7 - 17•β gobulin 7 - 16•γ globulin 11 - 22

Synthesis of albumin

Exclusively synthesised by the liver.

Liver produces approximately 12g albumin per day which represents 25% of the total hepatic protein synthesis.

Albumin has a half life of 20 days.

Albumin

67 % α helix 10 % β turn

Amino acid composition

Amino Acid Composition

Aspartic Acid 36

Asparagine 17

Threonine 28

Serine 24

Glutamic Acid 62

Glutamine 20

Proline 24

Glysine 12

Alanine 62

Valine 41

Cystine 35

Methionine 6

Isoleucine 8

Leucine 61

Tyrosine 18

Phenyalanine 31

Lysine 59

Histidine 16

Tryptophan 1

Arginine 24

TOTAL 585

Functions of albumin:

Osmotic FunctionDue to its high concentration and low molecular weight, albumin contributes to 75 – 80% of the total plasma osmotic pressure.Thus, albumin plays a predominant role in maintaining blood volume and body fluid distribution.

Transport FunctionPlasma albumin binds to several biochemically important compounds and transports them in the circulation. These include free fatty acids which is transported to the liver, bilirubin, steroid hormones, calcium and copper.

Nutritive FunctionAlbumin serves as a source of amino acids for tissue protein synthesis to a limited extent, particularly in nutritional deprivation of amino acids.

Buffering FunctionAmong the plasma proteins, albumin has the maximum buffering capacity.

Exerts low viscocity

Plays an important role in exchange of water between tissue fluid and blood.

Certain drugs also bind to albumin.e.g sulphonamides, aspirin, penicillin.These drugs are directly transported to the target organ.

Clinical significance

Hypoalbuminemia

Hyperalbuminemia

Hypoalbuminemia

•Occurs due to a decrease in concentration of albumin, i.e when it is less than 2.5 gm%

Causes

(1) Loss from the body

• Loss of albumin in urine in nephrotic syndrome• In burns, albumin is loss through the unprotected skin

surface.

(2) Decreased synthesis of albumin

• Severe liver diseases: chronic hepatitis, cirrhosis liver.• Non-availability of the precursor: malabsorption syndrome, protein calorie malnutrition• Genetic deficiency: Analbuminaemia

(3) Others

•Chronic illness•Infections•Malignancy•pregnancy

Decrease in albumin concentration leads to oedema formation.

Oedema is a situation where tissue swelling takes place.

Treatment of oedema:

increasing blood protein level in patient with a nutritional deficiency.

Diuretic treatment – kidney is made to excrete excess fluid from the body.

hyperalbuminemia

•Occur when albumin level is high, i.e greater than 5.5 gm%

• Seen in the absence of dehydration.

•Frequent in obese men.

Summary

• Classification of plasma protein.

•Functions of plama protein.

• Albumin.

•Clinical significance.

Bibliography

• Wikipedia

• Textbook of medical physiology – MN Chatterjea, Rana Shinde

• google images

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