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PLASMA PROTEINS

BIOCHEMISTRY

mprasadnaidu
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PLASMA PROTEINS

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  1. PLASMA PROTEINS M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

  2. INTRODUCTION • Total blood volume is 4.5-5 litres. • If blood containing anticoagulants (e.g.heparin , potassium oxalate) is centrifuged , the plasma separates out as a supernatant while the cells remain at the bottom. • About 55-60% of blood is plasma • The packed cell volume or hematocritis about 40-45%

  3. Introduction Plasma is the clear straw coloured fluid portion of the blood minus its cellular elements. It constitutes about 55% of the blood volume. Serum is plasma minus clotting factors (fibrinogen & prothrombin ). The defribrinated plasma is called serum

  4. COMPOSITION OF PLASMA WATER: Is the main constituent of Plasma – 91% SOLIDS: 9% of the plasma (1% inorganic molecules & 8% organic molecules) PLASMA contains the following composition:

  5. OTHER ORGANIC MOLECULES Carbohydrates: Glucose ( 100-120 mg%) Fats: neutral fats, phospholipids (150-300mg%) Cholesterol(150-240 mg%)

  6. Non protein nitrogenous substances: ammonia, amino acids, creatine, creatinine (0.6-1.2 mg%) xanthine, hypoxanthine, urea (20-40 mg%) & uric acid (2-4 mg%). • Hormones enzymes & antibodies.

  7. Inorganic molecules are sodium, potassium, calcium, magnesium, chloride, iodide, iron, phosphates & copper. Gases presents in the plasma are O2 ,Co2,& N2 .

  8. plasma proteins… - forms 7% of the solids in plasma - their normal valves – 7.4 gm% ranges from (6.4 – 8.3 gm%) • INCLUDES: ALBUMIN GLOBULINS FIBRINOGEN

  9. NORMAL VALUES Total protein content of normal plasma is 6 - 8 g/100ml The plasma proteins consist of : 1)albumin (3.5-5 g/dl) 2)globulins (2.5-3.5 g/dl) 3)fibrinogen (200-400 mg/dl)

  10. The albumin : globulin ratio is usually between 1.2 :; 1 to 1.5 :1 • Almost all plasma proteins , except immunoglobulins are synthesized in liver

  11. SEPARATION OF PLASMA PROTEINSUSING SALTS In clinical laboratory, separation is usually done by salts. Thus , fibrinogen is precipitated by 10% and globulins by 22% concentration of sodium sulphate Ammonium sulphate will precipitate : albumin by full-saturation globulin by half-saturation

  12. ESTIMATION OF PLASMA PROTEINS In clinical laboratory , total proteins of patients are estimated by Biuret method. Albumin is quantitated by Bromo cresol green (BCG) method , in which the dye is preferentially bound with albumin , and the colour intensity is measured colourimetrically.

  13. OTHER METHODS: • Lowry’s method • Kjeldahl’s method • Dye-binding method • UV-absorption method

  14. ELECTROPHORESIS The most common method of analyzing plasma proteins is by electrophoresis. The term electrophoresis refers to themovement of chargeD particles through an electrolyte when subjected to an electric field

  15. In clinical laboratory , cellulose acetate is widely used as a supporting medium. • Its use permits resolution , after staining , of plasma proteins into five bands , designated albumin , α1 , α2 , β and γ fractions, respectively

  16. The stained strip of cellulose acetate is called electrophoretogram. The amounts of these five bands can be conveniently quantified by use of Densitometric scanning machines. Characteristic changes in the amounts of one or more of these five bands are found in many diseases.

  17. ABNORMAL PATTERNS IN CLINICAL DISEASES Various abnormalities can be identified in the electrophoretic pattern 1) CHRONIC INFECTIONS: The gammaglobulins are increased

  18. 2)MULTIPLE MYELOMA : • In para-proteinemias , a sharp spike is noted and is termed as M-band. • This is due to monoclonal origin of immunoglobulins

  19. PRIMARY IMMUNE DEFICIENCY : The gamma globulin fraction is reduced NEPHROTIC SYNDROME : All proteins except very big molecules are lost through urine , and α-2-fraction will be very prominent

  20. CIRRHOSIS OF LIVER : • Albumin synthesis by liver is decreased , with a complementary excess synthesis by globulins by reticuloendothelial system

  21. CHRONIC LYMPHATIC LEUKEMIA: Gamma globulin fraction is reduced ALPHA-1-ANTITRYPSIN DEFICIENCY: The alpha-1 band is thin or even missing

  22. ALBUMIN Albumin (69 kDa) is the major protein in human plasma(3.4-4.7 g/dl) It makes up approximately 60% of the total plasma protein. About 40% of albumin is present in the plasma, and the other 60% is present in the extracellular space.

  23. The liver produces about 12g of albumin per day , representing about 25% of total hepatic protein synthesis Albumin can come out of vascular compartment. So albumin is present in CSF and interstitial fluid.

  24. FUNCTIONS OF ALBUMIN 1)COLLOID OSMOTIC PRESSURE OF PLASMA: The total osmolality of serum is 278-305 mosmol/kg. This is exerted mainly by salts, which can pass easily from intravascular to extravascular space. Therefore, the osmotic pressure exerted by electrolytes inside and outside the vascular compartments will cancel each other.

  25. But proteins cannot easily escape out of blood vessels, and therefore , proteins exert the ‘effective osmotic pressure’. It is about 25mm Hg, and 80% of it is contributed by albumin. The maintenance of blood volume is dependent on this effective osmotic pressure

  26. Regulation of colloidal pressure Gaw: Clinical Biochemistry; Churchill Livingstone (1999), p. 44.

  27. TRANSPORT FUNCTION: Albumin is the carrier of various hydrophobic substances in the blood such as: i)bilirubin & non-esterified fatty acids ii)drugs (sulpha,aspirin,salicylate,) iii)hormones(steroid hormones,thyroxine) iv)metals (calcium,copper,heavy metals)

  28. 3)BUFFERING ACTION : Albumin has maximum buffering capacity amongst all proteins It has a total of 16 histidine residues which contribute to this buffering action.

  29. 4)NUTRITIONAL FUNCTION: • All tissue cells can take up albumin by pinocytosis. • It is then broken down to amino acid level. • So albumin may be considered as the transport form of essential amino acids from liver to extrahepatic cells.

  30. CLINICAL APPLICATIONS 1)BLOOD-BRAIN BARRIER: Albumin-fatty acid complex cannot cross blood-brain barrier and hence fatty acids cannot be taken up by brain.

  31. 2)PROTEIN-BOUND CALCIUM: • Calcium level in blood is lowered in hypo-albuminemia • Thus , even though total calcium level in blood is lowered, ionised calcium level may be normal, so tetany may not occur.

  32. 3) THERAPEUTIC USE: Human albumin is therapeutically useful to treat burns,hemorrhage and shock. 4)EDEMA: Hypo-albuminemia will result in tissue edema Eg: a)malnutrition b)nephrotic syndrome c)cirrhosis of liver d)chronic congestive cardiac failure.

  33. HYPO-ALBUMINEMIA CIRRHOSIS OF LIVER: Synthesis is decreased. MALNUTRITION: Availability of amino acids is reduce and so albumin synthesis is affected. NEPHROTIC SYNDROME: Permeability of kidney glomerular membrane is defective , so that albumin is excreted in large quantities.

  34. PROTEIN LOSING ENTEROPATHY: Large quantities of albumin is lost from intestinal tract.

  35. ALBUMINURIA: Presence of albumin in urine is called albuminuria. It is always pathological. Seen in: a)Nephrotic syndrome(large quantities) b)Acute nephritis c)Inflammatory conditions of urinary tract. Detection of albumin in urine is done byheat and acetic acid test.

  36. MICRO-ALBUMINURIA: In micro-albuminuria or minimal albuminuria or plauci-albuminuria , small quantity of albumin (30-300 mg/dl) is seen in urine It is estimated by RIA Increased levels of microalbuminuria is an indication of early involvement of renal tissue in diabetic patients

  37. Albumin-globulin ratio : In hypo-albuminemia, there will be a compensatory increase in globulins which are synthesized by the reticulo-endothelial system(plasma cells). Albumin-globulin ratio (A/G ratio) is thus altered or even reversed.

  38. Hypoproteinemia : Since albumin is the major protein present in the blood, any condition causing lowering of albumin will lead to reduce total proteins in blood

  39. HYPERALBUMINEMIA : Increased levels of plasma albumin are present only in acute dehydration and have no clinical significance ANALBUMINAEMIA : Analbuminemia is a rare hereditary abnormality in which plasma albumin concentration is usually less than 1.0gm/L

  40. GLOBULINS Globulins are bigger in size than albumin . Globulins constitute several fractions. These are: α1- globulin α2- globulin β- globulin γ- globulin

  41. α1- GLOBULINS Retinol binding protein(RBP) α1 – fetoprotein(AFP) α1 – protease inhibitor (API) α1 - acid glycoprotein (AAG) High density lipopprotein (HDL) Prothrombin

  42. RETINOL BINDING PROTEIN (RBP) Retinol (vitamin A) is transported in plasma bound to RBP. Most retinol RBP in the plasma is reversibely complexed with transthyretin (thyroxine binding protein) α1- FETOPROTEIN (AFP) This is present in the tissues and plasma of the fetus It may play animmunoregulatory role during pregnancy.

  43. α1- PROTEASE INHIBITOR (API) / α1- ANTITRYPSIN (AAT) : API is one of the plasma proteins, that inhibits activity of proteases particularly elastase, which degrades elastin, a protein that gives elasticity to the lungs α1-ACID GLYCOPROTEIN (AAG) AAG also known as orosomucoid, contains a high percentage of carbohydrate with a large number of sialic acid residues It is synthesized by liver parenchymal cells.

  44. PROTHROMBIN It is synthesized by liver with the help of vitamin K and involved in blood clotting

  45. α2- GLOBULINS Ceruloplasmin(ferro-oxidase) Transcortin / corticosteroid binding globulin Haptoglobin Thyroxine binding globulin(TBG) α2 - macroglobulin (AMG)

  46. CERULOPLASMIN (FERRO-OXIDASE) This is a copper containing protein. It has oxidase activity Ceruloplasmin is the major transport protein for copper, an essential trace element. It is also essential for the regulation of oxiation-reduction , transport and utilization of iron Plasma ceruloplasmin level is reduced in Wilson’s diseasein patients with malnutrition and in the nephrotic syndrome.

  47. TRANSCORTIN /CORTICOSTEROID BINDING GLOBULIN: This binds cortisol It is synthesized in liver and synthesis is increased by oestrogen HAPTOGLOBIN: It plays an important role in the conservation of iron by preventing its loss in the urine Haptoglobin binds free Hb to form a complex which is too large to be filtered by the kidney and thus prevents the loss of iron in the urine.

  48. THYROXINE-BINDING GLOBULIN (TBG) TBG is synthesized in liver TBG has a electrophoretic mobility between α1 & α2 globulins It transports thyroxine hormone(T3 & T4) α2 - MACROGLOBULIN(AMG) This is major α2 - globulin , which is a natural inhibitor of endopeptidases such as trypsin, chymotrypsin, plasmin, thrombin .etc.

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