PLASMA PROTEINS

The plasma proteins are the most frequently

analyzed of all the proteins. The major measured
plasma proteins are divided into two groups: albumin
and globulins.
There are four major types of globulins, each
with specificproperties and actions.
• transport of substances : e.g.
– albumin – fatty acids, bilirubin, calcium, drugs
– transferin – iron
– cerulplasmin – copper
– transcortin – cortisol, cortikosteron
– lipoproteins – lipids
– haptoglobin – free hemoglobin
– thyroxin binding globulin – thyroxin
– retinol binding protein - retinol
• Osmotic regulation:
– Plasma proteins are colloidal and non-diffusable and
exert a colloidal osmotic pressure which helps to
maintain a normal blood volume and a normal water
content in the interstitial fluid and the tissues.
– Albumin content is most important in regulation of
colloidal osmotic or oncotic pressure.
– Decrease in albumin level results in loss of water from
blood and its entry into interstitial fluids causing
edema.
• Catalytic function (enzymes):
– e.g lipases for removal of lipids from the blood
• Protective function:
– Immunoglobulins combine with foreign antigens and
remove them.
– Complement system removes cellular antigens.
– Enzyme inhibitors remove enzymes by forming
complexes with them. e.g. a1-antitrypsin combines with
elastase, trypsin and protects the hydrolytic damage of
tissues such as lungs.
– Some proteins increase during acute phase and protect
the body. E.g. a1-antitrypsin, a2-macroglobulins.
• Blood clotting:
– Many factors are involved in clotting mechanism and
prevent loss of excessive amount of blood; e.g. clotting
factors IX, VIII, thrombin, fibrinogen etc.
– An excess of deficiency leads to a disease; e.g.
hemophilia, thrombus formation
• Anticoagulant activity (thrombolysis):
– Plasmin breaks down thrombin and dissolves the clot
• Buffering capacity:
– Proteins in plasma help to maintain acid-base balance
 Migrates ahead of albuminand accounts for
approximately 4% of protein in the CSF
 Usually not visible on routine serum protein
electrophoresis
 Involved in the transport of thyroid hormones
(T3 and T4) and vitamin A derivatives
 Croses more easily into the CSF
 Prealbumin is decreased in:
* hepatic damage
* acute-phase inflammatory response
* tissue necrosis
* protein malnutrition
 Prealbumin is increased in:
* patients receiving steroids
* alcoholism
*chronic renal failure
Note:
Low level is also a sensitive marker of poor
malnutritional status because of its short half life.
(approximately 8 hours)
 The globulin group of proteins consists of 1,2,
and  fractions. Each fraction consists of a number of
different proteins with different functions.
1-Antitrypsin (AAT), a glycoprotein mainly
synthesized in the liver, has as its most important
function the inhibition of the protease neutrophil
elastase.
 Major protein in alpha 1- globulin zone
 An acute phase reactant or protease inhibitor

 Increased in:
* Inflammatory reactions
* Pregnancy
* Contraceptive Use
 Decreased in:
* Pulmonary emphysema
* juvenile hepatic cirhosis
 11- Fetoprotein (AFP) is synthesized in the
developing embryo and fetus and then by the
parenchymal cells of the liver.
 Synthesized initially by the fetal yolk sac and then by the
parenchymal liver cells
 Used for tumor indicator for liver cancer and certain
gonadal tumors in adults.

 Increased in:
* Amniotic fluid
* Hemolytic disease of the newborn
* Presence of twins

 Decreased in:
* Down’s Syndrome
* Trisomy 18
 Has very high carbohydrate content
 Binder pf progesterone and drugs (lidocaine)

 Increased in:
* Pregnancy
* Cancer
* Pneumonia
* Rheumatoid Arthritis
 Elevated in inflammation
 Hereditary deficiency is associated with asthma and
inflammatory disorders.
 Inter-  -trypsin Inhibitor are family of serine
protease inhibitors, assembled from two
precursor proteins: a light chain (bikunin) and
either one or two heavy chains

 Elevations are seen in inflammatory disease

* While there is only one type of light chain,

there are five different homologous heavy chains
(ITIHs).
 shows a high binding affinity for vitamin Dand actin
 Increased in:
* Third trimester of pregnancy
* Estrogen oral contraceptive therapy
 Decreased in:
* Severe liver disease
* Protein losing syndrome
Gc may be of importance for:
 Bone formation
 In the immune system

Gc may act as a co-chemotactic factor

- in facilitating chemotaxis of neutrophils and
monocytes in inflammation
 HDL transports lipids
* Triglyceride
* Cholesterol
* Phospolipid
 One of the largest non-immunoglobulin proteins in
plasma produced by hepatocytes.
 Inhibits proteases such as trypsin, pepsin, and
plasmin
 Also contributes more than one-fourth of the
thrombin inhibition normally present in the blood
 10x fold increased in nephrotic syndrome

 Increased in:
* Diabetes
* Liver disease
* Pregnancy
* Use of contraceptives
 An 2 -glycoprotein, is synthesized in the
hepatocytes, and to the small extent , in the cells of
reticuloendothelial system.
 Responsible for binding free hemoglobin by its
alpha chain.
 Increased in:
* Inflammatory conditions
* Burns
* Nephrotic syndrome
 Decreased in:
* Hemolysis
* Liver disease
 NOTE:
Certain phenotypes have been reported as an independent
risk factor for cardio vascular disease (CVD) in individuals with
type 2 diabetes mellitus.
 Copper binding protein
 Has enzymatic activities (copper oxidase,
histaminases, ferrous oxidase)
 Synthesized in the liver
 Increased in:
* Pregnancy
* Inflammatory processes
 Decreased in:
* Wilson’s Disease
* Malnutrition
 Major beta globulin
 Binds and transport iron
 Transport iron to its storage sites, where is it
incorporated into transferrin to for ferritin
 Also carries iron to cells, such as bone
marrow which synthesizes hemoglobin and
other iron-containing compounds
 Increased in:
* Iron deficiency Anemia
 Decreased in:
* liver disease
*malnutrition
 Remove circulating heme, ferriheme and
porphyrins
 Increased in:
* Diabetes mellitus
* Duchenne (type of muscular dystrophy)
* Some malagnancies (especially melanoma)
 Very-Low Density Lipoproteins (VLDL)
- migrate at the beginning of the beta
globulin fraction (pre-beta).
 Low-Density Lipoproteins (LDL)
- appears as a separate band in the beta-
globulin region.
 The light chain component of the major
histocompatibility complex (HLA)
 Found of the surface of the most nucleated
cells and is present in high concentrations on
lymphocytes
 Increased:
*as a result of impaired clearance by the
kidney or overproduction of the protein that
occurs in the number of inflammatory diseases
(such as rheumatoid arthritis, SLE)
 A collective term for several proteins that
participate in the immune reaction and serve
as a link to the inflammatory responses.
 Increased in:
* inflammatory states
 Decreased in:
* Malnutrition
* Lupus erythematosus
* Disseminated Intravascular
Coagulopathies (DIC)
 One of the largest proteins in blood plasma
synthesized in the liver
 Classified as glycoprotein because it has a
considerable carbohydrate content
 Form a fibrin clot when activated by thrombin
 Seen only in plasma and not in serum
 One of the acute phase reactants
 Increased in:
* Inflammation
* Pneumonia
* Rheumatoid fever
 Decreased in:
* values generally reflect extensive
coagulation
* liver disease and hypofibrinogenemia
 Synthesized in the liver and appears in the blood
of patients with diverse inflammatory diseases
 Recognizes and binds to molecular groups found
on a wide variety of bacteria and fungi which
promotes the binding of complements and
facilitates their uptake by phagocytes
 Highly sensitive acute phase reactants
 One of the first acute phase proteins to rise in
response to inflammatory disease
 Increased in:
* acute rheumatic fever
* bacterial infections
 Synthesized in the plasma cells wherein
synthesis is stimulated by an immune
response to foreign particles and
microorganisms
 Migrates throughout the gamma region
 Increased in:
* liver diseases
* infections
* collagen disease
 Decreased is:
*associated with an increased
susceptibility of infections and monoclonal
gammopathy
 Migrates between betta and gamma peaks
 Protects mucous membranes, found in
secretions, saliva and tears
 Polyclonal increases in serum IgA in liver
disease, infections and autoimmune diseases
 Decreased in:
* Depressed protein synthesis
* Ataxia-telangiectasia
* Hereditary Immunodeficiency disorders
 Migrates closer to the beta region
 Increased in:
* toxoplasmosis
* rubella
* herpes
* syphilis
 Decreased in:
* protein-losing conditions
* immunodeficiency disorders
 Increased in infections, liver disease,
connective-tissue disorders

IgE
 Associated with allergic and anphylactic
reactions
 A small heme protein found in skeletal and
cardiac muscle
 Transports and stores oxygen from
hemoglobin to intracellular respiratory
enzymes
 It has a higher affinity for oxygen than does
hemoglobin
 Approximately 2% of the total muscle protein
 It is measured in serum by immunoassay
 At high levels in urine (myoglobinuria)
 It produces a positive dipstick reaction for
occult blood due to pseudoperoxsidase
activity
 AMI value: >100 ug/dL
 Troponin C, Troponin I, Troponin T
 complex of three proteins (regulatory
proteins) that binds to the thin filaments of
cardiac muscles.
 Regulators of actin and myosin
 TnC binds calcium that regulate muscle
contractions
 TnI and TnT are almost absent in normal
serum
 Troponin TnT/ Tropomyosin-binding subunit of
AMI
 Useful for assessment of of early and late AMI;
elevated also in renal diseases and mascualr
dystrophy
 A sensitive marker for the diagnosis of unstable
angina (angina at rest)
 It is useful in monitoring the effectiveness of
thrombolytic therapy in AMI patients.
 It is usually found in the myocardium –
greater specificity than TnT
 Majority of proteins found in the urine arise from
the blood
 The presence of urine albumin is generally
considered abnormal even in trace amounts
 Only a small amount of protein is present in
normal excreted urine
 Some healthy individuals exhibit albuminuria
following intense exercise
 Urine protein of greater than or equal to 6 mg/dL
produces color change on urine dipstick
 Proteinuria results from either glomerular or
tubular dysfunction
 Types of Proteinuria:
a.) Glomerular Proteinuria
-most common and serious type of
abnormal proteinuria.
b.) Tubular Proteinuria
- the appearance of low molecular
mass proteins in the urine due
to defective reabsorption.
-urine albumin excretion is slightly
increased
 Types of Proteinuria:
c.) Overload Proteinuria
-includes hemoglobinuria
myoglobinuria and Bence-Jones
proteinuria.

d.) Post-Renal Proteinuria

-refers to the protein coming from
the urinary tract caused by
infection, bleeding or malignancy.
 Early indicator of glomerular dysfunction and
precedes nephropathy associated with type I
diabetes.
 It is albumin excretion of 30 ug/mg creatine to
300 ug/mg creatinine (albumin/creatinine ratio)
 An individual is said to have microalbuminuria if
2 out 3 specimens submitted for testing within a
3 to 6 months period are with abnormal findings.
 Physical exercise during the previous 24 hours
can cause a transient elevation in microalbumin
in urine
 Increased:
* Diabetic nephropathy
* Fever
* Infection
* Hypertension
 Specimen:
* Random urine (reject bloody specimen)
 Method:
* Random-spot albumin-creatinine ratio
 Reference Value:
* 0-29 ug/mg creatinine
 Microalbuminuria
* 30-300 ug/mg creatinine
 Clinical Albuminuria
* >300 ug/mg creatinine
 CSF in an ultrafiltrate of plasma formed in the
choroids plexus of ventricles of the brain.
 For CSF glucose and proteins analyses, it is
recommended that a blood sample is
analyzed concurrently.
 The CSF normally contains very little protein
because the proteins in the blood do not
cross easily in the blood brain barrier.
 CSF albumin is 10-39 mg/dL (2/3 of the CSF
total protein)
 Method:
* TCA
* SSA
* Coomassie Brilliant Blue(dye)
* Lowry
* Kinetic Biuret Reaction
 Increased:
* Bacterial
* Viral and Fungal Meningitis
* Traumatic Tap
* Multiple sclerosis
* Intracerebral hemorrhage
* Myxedema
* Toxicity
 Decreased:
* Intracranial hypertension
* Hyperthyroidism
* Leakage of CSF due to trauma
 Reference values:
* 15-45 mg/dL