Proteins in plasma

1. 1
PLASMA PROTEINS
Overview:
• Functions and characteristics of
plasma proteins
• Measurement of plasma proteins
and diagnosis of diseases
• Electrophoretic patterns of plasma
proteins
• Acute phase proteins
*IMPORTANT *EXTRA CORRECTIONS LINK

2. 2
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 ~70g/L of pps
PLASMA PROTEINS (PPS)
Transport (Albumin, prealbumin,
globulins)
Maintain plasma oncotic pressure*
(Albumin)
Defense (Immunoglobulins and
complement)
Clotting and fibrinolysis (Thrombin and
plasmin)
 FUNCTIONS OF PPS
MEASUREMENT OF PPS
Quantitative measurement of a specific
protein:
Chemical or immunological reactions
Semiquantitative measurement by
electrophoresis:
Proteins are separated by their electrical charge in
electrophoresis
Five separate bands of proteins are observed
These bands change in diseases.
EXTRA
The major types of proteins
present in plasma are:
 Albumin>>formed in the liver.
 Fibrinnogen>>formed in the
liver.
 Globulins>>
-50-80% in liver
- the remaining are almost
entirely by the lymphoid tissue.
*this function is done by all plasma proteins, but since albumin has the
highest level among the plasma proteins it's the most imp.

3. 3
Types of Plasma Proteins
prealbumin albumin
α1-
Globulins
a1-
Antitrypsin
α-
fetoprotein
α2-
Globulins
Ceruloplasmin haptoglobin
β-
Globulins
C-reactive
protein(CRP)
transferrin
β2-
microglobulin
γ-
Globulins
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)%
*This is why it is called pre-albumin NOT because it is the albumin precursor, albumin
precursor is PreProAlbumin which is converted to ProAlbumin then secreted as albumin.

4. 4
ALBUMIN
 Most abundant plasma protein (~40 g/L) in
normal adult
 It is synthesized in the Liver as PreProAlbumin &
secreted as Albumin
 Decreases rapidly in Injury, Infection and Surgery
 Half-life in Plasma is 20 days
•The Osmotic pressure exerted by plasma proteins that
pulls water into the circulatory system
•Maintains fluid distribution and plasma volume in and
outside cells and plasma volume
Maintains 80% of
plasma Oncotic
pressure:
•Hormones, Ca , free fatty acids, Drugs
A non-specific
carrier for
•1) Liver Diseases 2) Hemorrhage 3) Shock
4) Burns
Useful in treatment1
•Tissue cells can take up Albumin by
Pinocytosis where it is hydrolyzed to amino
acids.
Source of amino
acids for the
tissues2
Hyperalbuminemia:
The only known clinical
cause of
hyperalbuminemia is
dehydration
Hypoalbuminemia:
Causes:
Decreased albumin synthesis:
(liver cirrhosis, malnutrition)
Increased losses of albumin:
1-Increased catabolism in infections
2-Excessive excretion by the kidneys (nephrotic
syndrome)
3-Excessive loss in bowel
4-Severe burns (plasma loss in the absence of skin barrier)
Effects:
Edema:
Albumin level drops in liver disease causing low oncotic
pressure
Fluid moves into the interstitial spaces causing edema
Reduced transport of drugs and other substances in
plasma
Reduced protein-bound calcium
-Total plasma calcium level drops
-Ionized calcium level may remain normal
 FUNCTIONS OF ALBUMIN
1-albumin is often used to replace lost fluid and help restore blood volume.
2-when the tissues become depleted of proteins.

5. 5
-Synthesized by the liver and macrophages
-An acute-phase protein that inhibits proteases
(Proteases are produced endogenously and from leukocytes and
bacteria)
-E.g. of protease:-
Digestive enzymes (trypsin, chymotrypsin)
Other proteases (elastase, thrombin)
-Infection leads to protease release from bacteria and
leukocytes
 Types of a1-Antitrypsin ( over 30 types are known)
 The most common is M type.
 Genetic deficiency of α1-Antitrypsin:-
Synthesis of the defective a1-Antitrypsin (in liver)
Which cannot be secreted.
So, a1-Antitrypsin accumulates in hepatocytes +deficient in
plasma
 Clinical Consequences of a1-Antitrypsin Deficiency:
 Neonatal jaundice with evidence of cholestasis*
 Childhood liver cirrhosis
 Pulmonary emphysema in young adults
 Laboratory Diagnosis:
-Electrophoresis: Lack of a1-globulin band in protein
electrophoresis
-Quantitative measurement of a1-Antitrypsin by:
Radial immunodiffusion,
isoelectric focusing or nephelometry
 a1-antitrypsin
α1-Globulins  a-Fetoprotein (AFP)
Synthesized in the developing embryo and
fetus by the parenchymal cells of the liver
 AFP levels decrease gradually during intra-
uterine life and reach adult levels at birth
(AFP level of less than 10 ng/mL is normal for adults)
 Function is unknown but it may protect fetus
from immunologic attack by thethe mother
(the doctor said; this protein may play a role in Gas
exchanging between mother and fetus)
No known physiological function in adults
 AFP is a tumor marker for:-
Hepatoma ,testicular cancer
An extremely high level of AFP in blood could be a
sign of liver tumors.
 Imbalance of maternal α-Fetoprotein:
 Elevated maternal AFP levels are
associated with:
Neural tube defect,Anencephaly
 Decreased maternal AFP levels are
associated with:
Increased risk of Down’s syndrome
*is a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts

6. 6
α2-Globulins
Synthesized by the liver
Contains >90% of serum copper
An oxidoreductase that inactivates
ROS causing tissue damage in
acute phase response
Wilson’s disease:
Due to low plasma levels of
ceruloplasmin
Copper is accumulated in the
liver and brain
Important for iron
absorption from the
intestine
CERULOPLASMIN
Synthesized by
the liver
Binds to free
hemoglobin to form
complexes that are
metabolized in the
RES
Plasma level
decreases during
hemolysis
Limits iron losses by
preventing Hb loss
from kidneys
Haptoglobin
EXTRA
-When red blood cells are destroyed,
the hemoglobin is released. Haptoglobin is
always present in the blood waiting to bind to
released hemoglobin.
macrophages bring
the haptoglobin-hemoglobin complex to
the liver, where haptoglobin and hemoglobin
are separated and the iron is recycled.
-In hemolytic anemia, so many red cells are
destroyed that most of the available
haptoglobin is needed to bind the released
hemoglobin. The more severe the hemolysis,
the less haptoglobin remains in the blood.

7. 7
β-Globulins
The liver is the main site
of transferrin synthesis
Iron deficiency results in
increased hepatic synthesis
“trying to compensate”
A major iron-transport
protein in plasma
30% saturated with
iron
A negative acute
phase protein
Plasma level drops in:
Malnutrition, liver disease,
inflammation, malignancy
Transferrin
A component of human leukocyte antigen
(HLA)
Present on the surface of lymphocytes and
most nucleated cells
Filtered by the renal glomeruli due to its small
size but most (>99%) is reabsorbed
May be a tumor marker for:
Leukemia, lymphomas, multiple myeloma
Elevated serum levels are found in:
Overproduction in disease
β2–Microglobulin
An acute-phase
protein synthesized
by the liver
High plasma levels are
found in many
inflammatory conditions
such as rheumatoid arthritis
Important for
phagocytosis
A marker for:
Ischemic Heart Disease
IHD)
)
C-Reactive
Protein (CRP)

8. 8
γ-Globulins
Hypergammaglobulinemia
May result from stimulation of:
-B cells (Polyclonal hypergammaglobulinemia)
-Monoclonal proliferation (Paraproteinemia)
Monoclonal
Hypergammaglobulinemia
Polyclonal
hypergammaglobulinemia
Proliferation of a single B-cell
clone produces a single type of
Ig
Stimulation of many clones of B
cells produce a wide range of
antibodies
Appears as a separate dense
band (paraprotein or M band)
in electrophoresis
*Paraproteins are characteristic
of malignant B-cell proliferation
-globulin band appears large
in electophoresis
Clinical condition: multiple
myeloma
Clinical conditions: acute and
chronic infections, autoimmune
diseases, chronic liver diseases

9. 9
Acute Phase Proteins
Positive Acute Phase Proteins:
Plasma protein levels increase in:
Infection, inflammation , malignancy, trauma, surgery
These proteins are called acute phase reactants
Synthesized due to body’s response to injury
Examples: a1-Antitypsin, haptoglobin, ceruloplasmin, fibrinogen, c-reactive protein
 Mediators cause these proteins to increase after injury
 Mediators: Cytokines (IL-1, IL-6), tumor necrosis factors a and  , interferons, platelet
activating factor
 Functions:
1. Bind to polysaccharides in bacterial walls
2. Activate complement system
3. Stimulate phagocytosis
Negative Acute Phase Proteins:
These proteins decrease in inflammation:
Albumin, prealbumin, transferrin
Mediated by inflammatory response via cytokines and hormones
Synthesis of these proteins decrease to save amino acids for positive acute phase proteins
 albumin is low because it's a negative acute
phase proteins.
 Other bands are higher because they contain
positive acute phase proteins. e.g. β-
Globulin band contains CRP

10. 10
emzyme Function Condition
Prealbumin
 Transport :-
1) Thyroid hormones.
2) Retinol.
 Lower level in :-
1) liver disease.
2) Nephrotic syndrome.
3) Malnutrition.
4) Acute phase inflammatory response.
Albumin
1) Maintain oncotic pressure.
2) Non specific carrier.
3) Useful in treatment of liver
disease & shock &
hemorrhage.
 Hypoalbuminemia :-
 Decrease albumin synthesis.
 Loss of albumin:-
• Excessive loss in bowel
• Nephrotic syndrome.
• Burns.
a1 -antitrypsin
 Genetic deficiency of a1–antitrypsin:-
 Neonatal jaundice.
 Childhood liver cirrhosis.
 Pulmonary emphysema.
a-fetoprotein
Unknown function .  Elevated maternal  neural tube defect.
 Decreased maternal  down syndrome.
 Tumor marker hepatoma &testicular cancer.
Ceruloplasmin Important in iron absorption from
intestine .
Wilson’s disease.
Haptoglbin
Bind to free hemoglobin to form
complexes to limit iron loss and to
prevent Hb loss in kidney .
Decrease during hemolysis.
B2 -Microglobulin
 Elevated level found in  overproduction in
disease.
 Tumor marker  leukemia & lymphomas &
multiple myeloma.
C-Reactive protein
Important in phagocytosis.  Elevated in:-
 Inflammation (rheumatoid arthritis).
 Marker for ischemic heart disease.
SUMMARY

11. MCQS
1)Prealbumin found in lower level in :
A. Liver disease.
B. Nephrotic syndrome.
C. Malnutrition.
D. All.
2)80 % of plasma oncotic pressure is maintained by
albumin.
A. True.
B. False.
3)Hypoalbuminemia could be carried by:-
A. Decrease in synthesis in liver.
B. Loss of albumin.
C. Sever burns.
D. All of them.
4)Clinical consequences of alpha (a)-antitrypsin
deficiency :-
A. Jaundice.
B. Pulmonary emphysema.
C. Liver cirrhosis.
D. All above.
E. A & B.
5) Ceruloplasmin important in :-
A. Iron absorption from intestine.
B. Transplant.
C. Non of them.
D. Both of them.
6)Which protein is important in prevent
Hb loss from kidney :
A. Haptoglobin.
B. Ceruloplasmin.
C. Transferrin.
D. Non of them.
7)High plasma level found in rheumatoid
arthritis.
A. Haptoglobin.
B. C-reactive protein.
C. B2 –Microglobin.
D. Ceruloplasmin.
8)Monoclonal proliferation marker for multiple
sclerosis.
A. True.
B. False.
9)Which one is true regarding transferrin :-
A. Negative acute phase protein.
B. Major iron transport .
C. Level drop in malignance.
D. Limit iron loss by prevent Hb loss from
kidney.
E. Positive acute phase protein.
F. A & B &C .
G. A &B & C & D.
Answers:
1)D
2)A
3)D
4)D
5)A
6)A
7)B
8)B
9)F

12.  what are the Functions of plasma proteins?
1. Transport.
2. Maintain plasma oncotic pressure.
3. Defense .
4. Clotting & fibrinolysis.
 What are the Types of plasma proteins?
1. Prealbumin.
2. Albumin.
3. a1 –Globulins (a1 antitrypsin, a-fetoprotein)
4. a2- Globulins (ceruloplasmin, haptoglobin)
5. B-Globulins. (CRP, transferrin, B2 –microglobulin).
6. Y-globulins
 What are the Functions of albumin?
1. Maintain oncotic pressure.
2. Non specific carrier.
3. Useful in liver disease & hemorrhage & shock and burns
4. Tissue cells take up and hydrolyzed it to amino acid.
 What are the Effects of hypoalbuminemia?
1. Edema b/c of decrease oncotic pressure.
2. Decrease transport of drugs .
3. Decrease protein bound calcium (ionized ca is intact).
SAQS

13.  What are the diseases that associated with condition of a-fetoprotein?
o Elevated maternal  neural tube defect (spina bifida).
o Decreased maternal  down syndrome.
o A tumor marker  Hepatoma, testicular cancer.
 Talk about B2 –Microblobulin briefly?
o Component of (HLA).
o Filtered by the renal glomeruli due small size but it will be reabsorbed.
o Elevated level :-
 overproduction in disease.
o Tumor marker :-
 Leukemia, lymphomas, multiple myeloma.
 What are the deferences between polyclonal hypergammaglobulinemia &
monoclonal?
Polyclonal Monoclonal
• Many clones of B cells  wide
range of antibodies.
• Y-globulin band appear large
in electrophoresis.
• Clinical condition :
acute &chronic infection.
autoimmune disease.
Chronic liver disease.
• Single B cell  single type of Ig.
• Appear as a separated dense
band.
• Clinical condition:
Multiple myeloma.
SAQS

14. Omar faisal
Abdulaziz Alsaud
Mohammad Alotaibi
Najla Al-draiweesh
14
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