Blood: Cells and Plasma Proteins

Beth A. BouchardBIOC 212: Biochemistry of Human Disease

Spring 2005

I. Major functions of blood and its components: transport and distribution of essential nutrients to

tissues removal of waste products defense against internal insult repair of damaged tissues

II. Two major components of blood: liquid phase and formed elements

Plasma - blood treated with anticoagulants to prevent clot formation then centrifuged to remove the cells

Serum - blood that is allowed to form a fibrin clot then centrifuged to remove the cells and the clot

Plasma

“Buffy coat”

Red blood cells

Plasma

Buffy coat

Red blood cells

Red Blood Cells(Erythrocytes)

1011 produced per day

Anucleate

Lack intracellular organelles (incapable of protein synthesis and repair)

Contain specific proteins and ions

Transport oxygen, and remove CO2 and H+

Finite life span of 60-120 days beforebeing destroyed in the spleen

2-3 m in diameter

150-400 x 106/mL blood

Normal subcellular structures except they lack a nucleus

Capable of mitochondrial protein synthesis

Platelet function is dependent upon their activation

Involved in blood clotting

Contain secretory organelles called alpha-granules, which contain proteins important in blood clotting

Circulate for 10 days before being destroyed

Platelets

Plasma proteins

Synthesized by liver or produced by plasma (B) cells

A. AlbuminB. TransferrinC. CeruloplasminD. Enzymes – coagulation enzymes, complement factorsE. C-reactive protein – acute phase reactantF. Immunoglobulins – humoral immunity

Transport proteins

66 kDa

ALBUMIN

Accounts for ~50% of the total plasma protein and ~ 50% of the total liver protein production

Half-life ~ 20 days

Highly polar

At pH 7.4 it is anionic with 20 negative charges per molecule

Transport of long chain fatty acids & sterols Transport of bilirubin Binding and solubilization of drugs

Functions of Albumin

Regulation of colloidal pressure

Decreases in albumin concentration cause edema

Gaw: Clinical Biochemistry; Churchill Livingstone (1999), p. 44.

Causes of decreased plasma albumin:I. Decreased synthesis

A. malnutrtionB. malabsorptionC. advanced chronic liver disease

II. Abnormal distribution or dilutionA. overhydrationB. increased capillary permeability like in septicemia

III. Abnormal excretion or degradationA. nephrotic syndromeB. burnsC. hemorrhageD. certain catabolic statesE. protein losing enteropathies

IV. Rare congenital defects A. hypoalbuminemia B. analbuminemia

TRANSFERRIN

Transports iron in plasma as ferric ions (Fe3+) – each transferrin molecule binds 2 Fe3+

Protects the body against the toxic effects of free iron

Normally 30% saturated with Fe3+ - increased or decreased saturation is indicative of iron overload or deficiency, respectively

Decreased in inflammatory states due to excessive degradation of transferrin- Fe3+ complexes

CERULOPLASMIN

Major copper transport protein

Regulates oxidation-reduction, transport and utilization of iron

Increased concentrations are found in active liver disease or tissue damage

Decreases are sometimes observed in individuals with Wilson’s disease

ENZYMES

Enzymes of the coagulation and complement cascade have a defined function in blood

Others reside elsewhere in the body and appear incidentally in the blood – their measurement is of diagnostic value

Acid phosphatase Amylase

Creatine kinaseAlanine

aminotransferase

C-REACTIVE PROTEIN (CRP)

Major component of the acute phase response and a marker of bacterial infection

Mediates the binding of foreign polysaccharides, phospholipids and complex polyanions, as well as the activation of complement

<1 mg/mL in normal plasma

Slightly elevated levels of CRP are indicative of chronic, low-grade inflammation and have been correlated with an increased risk of cardiovascular disease

IMMUNOGLOBULINS

Proteins produced and secreted by B cells specific for the foreign particle that stimulated their synthesis

Five classes of Ig

Multiple myeloma: arises from the aberrant proliferation of a single B cell. Light chains of Igs are produced in excess of heavy chains = paraproteins.

Elevated serum protein levels are usually due to an increase in the Ig fraction and may indicate the presence of a paraprotein.