The document provides an overview of plasma proteins, including their classification, functions, and clinical significance. It discusses the synthesis of plasma proteins, their roles in inflammation, transport functions, and therapeutic uses, as well as specific proteins such as albumin, ceruloplasmin, and α1-antitrypsin. Additionally, it explains the implications of protein levels in various diseases and conditions, including the importance of albumin in maintaining osmotic pressure and the role of acute phase proteins in response to inflammation.

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. Electrophoretic
separation
-
+

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,
α2 -macroglobulin
β-globulin 8-12%
β1Transferrin, LDL
β2  β2 microglobulin
γ-
globulin
12-22% Immunoglobulins
ALBUMIN 55-60%
Pre-albumin ?

6. • TTR- Transthyretin
• Transports thyroxine and
retinol
• 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

15. 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

16. • PCT levels >0.25μg/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

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

18. 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

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

20. α1–Antitrypsin/ AAT/
α- anti-proteinase
• Inhibits serine proteases like trypsin, elastase
(enzymes having a serine at their active sites)
SERPINS (serine protease inhibitors )
• Synthesised from liver
• Major component of α1 fraction of human
plasma
• Deficiency of AAT
Emphysema

21. Infections/pneumonia
↑neutrophils
Infections/pneumonia
↑neutrophils

22. 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

23. AAT deficiency and smokers
• A particular Methionine residue (at position
358) of α1 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

24. Ceruloplasmin
• α2- globulin synthesized in liver
• Carries 90% of the copper present in plasma; Rest
10% of binds to Albumin
• Copper dependent oxidase activity
(oxidation of Fe2+ to Fe3+ in transferrin)
Acts as important anti-oxidant
• ↓Ceruloplasmin : liver disases especially
WILSON’S DISEASE
• ↑ceruloplasmin : inflammatory conditions.

25. 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

26. 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)

28. • 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.

29. 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.

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

31. Plasmapherseis

33. Thank you