plasma proteins, classification and functions.pptx

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1. PLASMA PROTEINS

2. Objectives: To know the classification and functions of plasma proteins An overview of their clinical significance in health and diseases To discuss the therapeutic uses of plasma and its components

3. Water (89%) Electrolytes Metabolites Hormones Proteins (6%) Simple proteins Glycoproteins Lipoproteins Immunoglobulins Plasma vs serum ?

4. Electrophoreticseparation - +

5. GLOBULINS α -1 globulin 2-4% α -1 antitrypsin, α -1 acid glycoprotein, Thyroid Binding Globulin (TBG), Transcortin , HDL α -2 globulin 6-12% Haptoglobin , Ceruloplasmin , α 2 -macroglobulin β - globulin 8-12% β 1  Transferrin, LDL β 2  β 2 microglobulin γ - globulin 12-22% Immunoglobulins ALBUMIN 55-60% Pre-albumin ?

6. TTR- Transthyretin Trans ports thy roxine and retin ol Called Pre-albumin or TBPA (thyroid binding pre-albumin) as it ran faster than albumin on gel TTR has binding sites for thyroxine (T4) and carries retinol due to its association with RBP (retinol binding protein) Total serum proteins 6-8 g/dL Albumin 3.5-5 g/dL Globulin 2.5-3.5g/dL A/G ratio 1.2-1.5:1 Reversed A/G ratio ??

7. Most plasma proteins are synthesised in liver Exception: Immunoglobulins (plasma cells), factor III (endothelium), vWF & VIII (platelets & endothelium) Most plasma proteins are glycoproteins except albumin Each plasma protein has a characteristic half life in circulation IgA CRP

8. ALBUMIN Major plasma protein (60%) 69kDa 3.5-5 g/ dL Synthesized by liver Chief component responsible for the osmotic pressure of human plasma

9. ALBUMIN EDEMA Important role in determining the distribution of fluid between blood and tissues

10. Serves as low specificity transport protein It can bind and transport many diverse molecules . Various ligands which bind albumin : Metal ion: such as calcium Free fatty acid: Albumin binds to free fatty acid released by adipose tissue and facilitates their transfer to other tissue. Unconjugated bilirubin Hormones: steroid hormones Certain drugs : Sulphonamides , Penicillin G, Dicoumarol , Aspirin

11. Nutritional function Therapeutic uses ↓ Albumin levels (hypoalbuminemia) Liver diseases Malnutrition Nephrotic syndrome Protein losing enteropathies

12. ACUTE PHASE PROTEINS There are certain proteins in plasma which play role in body’s response to inflammation Their levels in blood changes in various Inflammatory states or secondary to certain type of tissue damage or in some cancers. POSITIVE ACUTE PHASE PROTEINS: levels are increased C-Reactive Protein (CRP) can stimulate classic complement pathway Fibrinogen  promotes endothelial repair, pro-coagulation state Alpha-1 Antitrypsin (AAT)  neutralises certain proteases released during acute inflammatory states Alpha-2 Macroglobulin (AMG)  Pan protease inhibitor Ceruloplasmin, hepcidin, ferritin Procalcitonin

13. One of the widely used clinical measures of acute inflammation are CRP & ESR

14. Procalcitonin has been proposed as a sensitive marker for sepsis & pneumonia and can be used to guide antibiotic treatment Rationale: Normally procalcitonin is produced by  Parafollicular (C) cells of thyroid glandconverted into calcitonin & released During inflammations medaitors  activate procalcitonin gene in other tissues like liver, kidney, adipocytes, pancreas, colon etc directly released in circulation

15. PCT levels >0.25 μ g/L  correlate with bacterial infections After 2-3 days of treatment PCT levels can facilitate the decision to discontinue antibiotic treatment PCT levels could be used as a guide for antibiotic treatment

16. NEGATIVE ACUTE PHASE PROTEIN : Levels decrease in inflammatory states e.g. Albumin, Transferrin, Antithrombin

17. C-Reactive Protein Synthesised in Liver Has a role in stimulating complement activity and macrophage phagocytosis So named because it reacts with C-polysaccharide of capsule of pneumococci . When inflammation subsides, the levels of CRP quickly fall

18. Has a positive correlation in predicting the risk of coronary artery diseases.

19. α 1 –Antitrypsin/ AAT/ α - anti-proteinase Inhibits serine proteases like trypsin, elastase (enzymes having a serine at their active sites) SERPINS ( ser ine pr otease in hibitors ) Synthesised from liver Major component of α 1 fraction of human plasma Deficiency of AAT Emphysema

20. Infections/pneumonia ↑neutrophils Infections/pneumonia ↑neutrophils

21. AAT deficiency Different mutations are known to cause the AAT deficiency Most common being: GAG AAG (single purine base mutation) Substitution of lysineGlutamic acid at position 342 Polymerisation of the mutated protein in ER of the hepatocytes  ↓ secretion of AAT from liver (cirrhosis of liver may also occur) Emphysema

22. AAT deficiency and smokers A particular Methionine residue (at position 358) of α 1 antitrypsin is involved in its binding to proteases Smoking oxidizes this methionine and thus inactivates it Unable to neutralize proteases Emphysema becomes inevitable in smokers

23. α 2 - Macroglobulin (AMG) Large plasma glycoprotein (720 kDa ) Major component of “ α 2-globulin” of human plasma. About 10% of the Zinc is transported by the α 2 - Macroglobulin; rest by albumin Synthesised by monocytes , hepatocytes , astrocytes . α 2 - Macroglobulin binds many proteases. An important PAN-PROTEASE INHIBITOR.

24. α 2 - Macroglobulin-protease complex Rapidly cleared from plasma by a receptor located on many cell types Also binds many cytokines -- platelet derived growth factor(PDGF) -- transforming growth factor β (TGF β ) targets them to particular cells.

25. In NEPHROTIC SYNDROME, this fraction markedly rises in blood where other proteins are lost.

26. Ceruloplasmin α 2 - globulin synthesized in liver Carries 90% of the copper present in plasma; Rest 10% of binds to Albumin Copper dependent oxidase activity (oxidation of Fe 2+ to Fe 3+ in transferrin) Acts as important anti-oxidant ↓ Ceruloplasmin : liver disases especially WILSON’S DISEASE ↑ ceruloplasmin : inflammatory conditions.

27. TRANSPORT PROTEINS PLASMA PROTEIN COMPOUNDS TRANSPORTED Albumin Fatty acids, Calcium, Drugs, Unconjugated Bilirubin Pre-Albumin ( Transthyretin ) Thyroxine , Retinol, Steroid hormones Retinol binding protein (RBP) Retinol Thyroxine binding globulin (TBG) Thyroxine Transcortin ; cortisol binding globulin (CBG) Cortisol Haptoglobin Hemoglobin Transferrin Iron Hemopexin Free heme

28. HAPTOGLOBIN Glycoprotein Binds extra-corpuscular Hb  Hp- Hb complex Prevents free Hb to pass through glomerulus (conserves Iron) ↓Hp seen in haemolyitc anemias Half life of Hp =5days, but half-life of Hb-Hp complex is 90 min ( Hb-Hp complex rapidly cleared from plasma by hepatocytes)

29. Fresh Frozen Plasma (FFP): (shock due to massive haemorrhage, burns, liver diseases – coagulants found in plasma aid in decreasing bleeding time & stabilise the patient) Plasma Protein derivative (PPD): 1. Factor VIII concentrate- in specific clotting factor deficiency 2. Albumin infusion- peritonitis, nephrotic syndrome 3. Immunoglobulins ( IvIG )- In primary or secondary immune deficiency states.

30. 4. Hyperimmune plasma- Hyper-immune plasma is collected from donors: who have been actively immunized with specific antigens such as rabies, tetanus, hepatitis B Or Can also be obtained from donors with naturally occurring antibodies such as cytomegalovirus (CMV), varicella (VZV), hepatitis A. For the prevention in the persons who are not vaccinated, if vaccination is not possible, or in whom the vaccination has not resulted in a sufficient protective antibody plasma level.

31. 5. Platelet Rich Plasma (PRP): Autologous blood with platelet concentrate being used in sports injuries and derma/hair procedures

32. Plasmapherseis

33. Thank you