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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

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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 PPSMEASUREMENT 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.

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Types of Plasma Proteins

prealbumin albuminα1-

Globulins

a1-Antitrypsin

α-fetoprotein

α2-Globulins

Ceruloplasmin haptoglobin

β-Globulins

C-reactive protein(CRP)

transferrinβ2-

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.

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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, DrugsA 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 (nephroticsyndrome)

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.

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-Synthesized by the liver and macrophages

-An acute-phase protein that inhibits proteases

(Proteases are produced endogenously and from leukocytes andbacteria)

-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 cancerAn 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

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α2-GlobulinsSynthesized 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 hemoglobinare 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.

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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)

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γ-Globulins

HypergammaglobulinemiaMay 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 largein electophoresis

Clinical condition: multiple

myeloma

Clinical conditions: acute and chronic infections, autoimmune diseases, chronic liver diseases

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Acute Phase Proteins

Positive Acute Phase Proteins:Plasma protein levels increase in:

Infection, inflammation , malignancy, trauma, surgeryThese 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 walls2. Activate complement system3. Stimulate phagocytosis

Negative Acute Phase Proteins:These proteins decrease in inflammation:

Albumin, prealbumin, transferrinMediated by inflammatory response via cytokines and hormonesSynthesis 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

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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

MCQS1)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

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

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

Omar faisal

Abdulaziz Alsaud

Mohammad Alotaibi

Najla Al-draiweesh

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