Lec8 Plasma and Plasma Proteins PDF

Composition of Plasma and plasma proteins  Learning objectives By the end of the lecture students will be able to know about: Explain the composition of plasma and plasma proteins Explain the difference between plasma and serum Discuss the separation techniques of plasma...

Composition of Plasma and plasma proteins  Learning objectives By the end of the lecture students will be able to know about: Explain the composition of plasma and plasma proteins Explain the difference between plasma and serum Discuss the separation techniques of plasma proteins Describe the individual plasma proteins and their biological functions Discuss the clinical abnormalities related to plasma proteins  Your patient A 50 year old women is coming to ER in unconscious condition, she was anemic and had pale face. On examination it revealed that she had edema on her feet. Her blood was taken and sent for lab investigation. Blood Composition  Plasma Proteins (pps) Plasma contains >300 different proteins Many pathological conditions affect level of pps Mostly synthesized in the liver Some are produced in other sites A normal adult contains ~70 g/L of pps  Plasma consists of water, electrolytes, metabolites, nutrients, proteins and hormones The concentration of total protein in human plasma is about 6-8.3g/dl. A complex mixture that includes not only simple proteins but also conjugated proteins such as glycoproteins and various types of lipoproteins Separation of plasma proteins Salting out method: 3 major groups Fibrinogen, albumin and globulin, by the use of varying concentrations of sodium or ammonium sulfate. Electrophoresis: 5 major fractions Albumin α1 & α2 globulins β globulin γ globulin Plasma proteins  Abnormal electrophoretic pattern Nephrotic syndrome: All low mol wt prt lost in urine & bigger prt macroglobulin Cirrhosis of liver: Albumin synthesized in liver ↓with a compensatory excess synthesis of globulin by reticulo- endothelial system Chronic Infection, Myelogenous & monocytic leukemia &Chronic lymphatic leukemia : γ globulin ↑ Rheumatoid arthritis: γ & α2 globulin ↑ Multiple myeloma: In paraproteinemia a sharp spike (M band) due to monoclonal origin of Ig Alpha-1-antitrypsin deficiency: thin or missing band of alpha 1  Prealbumin (Transthyretin) A transport protein for: – Thyroid hormones – Retinol (vitamin A) Migrates faster than albumin in electrophoresis Separated by immunoelectrophoresis Lower levels found in: – liver disease, nephrotic syndrome, acute phase inflammatory response, malnutrition Short half-life (2 days)  Function It carries thyroid hormone, thyroxin & tri- iodo thyronine. Involve in the transport of retinol from major storage site to liver to extra hepatic tissues, where it binds with RBP In Blood RBP forms a ternary complex, imp BCZ RBP can easily filtered at glomeruli & lost in urine …..complex can not cross through kidney.  Albumin A 69 Kda is the major protein of plasma (3.4-4.7g/dL) Makes 60% of the total plasma protrein. About 40% of body albumin is present in the plasma and the rest 60% is in the extracellular space. Half life of albumin is about 20 days. Synthesis of Albumin Liver produces about 12 g of albumin everyday, Showing 25% of total hepatic protein synthesis. Albumin is initially synthesized as a preproprotein. Its signal peptide is removed as it passes into the cisternae of the rough endoplasmic reticulum and a hexapeptide at the resulting amino terminal is cleaved off farther along the secretary pathway. Function of Albumin Colloidal osmotic pressure. Responsible for 75-80% of the osmotic pressure of human plasma due to its low molecular weight Plays a key role in maintaining blood volume and body fluid distribution. Hypoalbuminemia leads to retention of fluid in the tissue spaces (edema)  Colloid osmotic pressure Low albumin, causing edema.  Clinical aspects 1. Albumin binds different drugs and strongly affects the pharmacokinetics of these drugs.  For example, sulfonamides can cause the release of unconjugated bilirubin from albumin by competitive binding. If given to infants, sulfonamides may lead to kernicterus(deposition of the pigment bilirubin in the brain) 2. In cases of liver disease or starvation, albumin synthesis decreases.  This lead to edema.  Clinical aspects 3. Hypoalbuminemia – lowered plasma albumin – in malnutrition, nephrotic syndrome and cirrhosis of liver. 4. Albuminuria – albumin is excreted into urine – in nephrotic syndrome and certain inflammatory conditions of urinary tract. 5. Albumin is therapeutically useful for the treatment of burns and hemorrhage.  Transporter function via binding with various ligands, including Free fatty acids Calcium Steroid hormones Bilirubin Copper A variety of drugs including sulfonamides, pencillinG, dicoumarol, phenytoin and aspirin  Albumin serves as a source of amino acid for tissue protein synthesis to a limited extent, specially in nutritional deprivation. Buffering action, it has a maximum buffering capacity due to its high concentration and the presence of large number of histidine residues which contributes in acid base balance maintenance. Viscosity- it Exerts low viscosity.  Globulins Globulins are separated by half saturation with ammonium sulphate. Molecular weight ranges from 90, 000 to 1300, 000. Electrophoresis separation gives α1 – globulin α2 – globulin β – globulin γ – globulin Synthesis of Globulins α and β globulins are synthesized in the liver. γ globulins are synthesized in the plasma cells and B-cells of lymphoid tissues (reticulo-endothelial system). Synthesis of γ globulins is increased in chronic infections, liver disease, leukemia, lymphomas and various other malignancies.  α1 Globulins Glycoprotein in nature. Based on electrophoretic mobility, they are sub classified as α1 and α2 globulins. Examples. α1 antitrypsin α1 acid glycoprotein α1 feto protein (AFP)  α1- antitrypsin Also known as α1-antiprotease Single chain protein of 394 aa contaning 3 oligosaccaride chains. It is the major component(>90%) of the α1 fraction of human plasma. It is synthesizes by hepatocytes and macrophages and is the principal serine protease inhibitor of human plasma. – during the acute phase increases  inhibition of degradation of connective tissue by elastase – deficiency  proteolytic lung damage (emfyzem)  Clinical significance 1. Emphysema: used to represent the abnormal distension of lungs. – About 5% is due to the deficiency of α1–AT. – This is associated with lung infection and increase the activity of macrophage to release elastase that damage lungs tissue. Smoking can cause oxidation of Met358 to methionine sulfoxide and inactivate α1–AT. 2. α1 –antitrypsin deficiency liver disease due to mutant α1antitrypsin accumulates and aggregates to form polymers, by unknown mechanism, cause liver damage followed by accumulation of collagen fibrosis resulting in (cirrhosis).  α1- acid glycoprotein Concentration in plasma is about 0.6-1.4g/dl Carbohydrate content is about 41% Marker of inflammation Act as a transporter of progesterone. Transport carbohydrate at the site of tissue injury. ↑in, inflammatory diseases, cirrhosis of liver and in malignant condition. ↓in liver diseases, malnutrition and in nephrotic syndrome.  α1- fetoprotein Present in higher concentration in fetal blood during mid pregnancy. Normal concentration in healthy adult