PLASMA PROTEINS AND THEIR DISORDERS

Question 1

Discuss protein metabolism
How are plasma proteins made?

Answer 1

• Hepatocytes synthesize many plasma proteins
• Macrophages synthesis complement proteins
  Immunoglobulins are mainly derived from the B lymphocytes of the immune system.
  Most plasma proteins are taken up by pinocytosis into capillary endothelial cells or mononuclear phagocytes, where they are catabolized.
  Small-molecular-weight proteins are lost passively through the renal glomeruli and intestinal wall
  Some are reabsorbed, either directly by renal tubular cells or after digestion in the intestinal lumen
  Others are catabolized by renal tubular cells.

Question 2

Functions of Plasma Proteins

Answer 2

• Peptide hormones and blood clotting factors
• Control of extracellular fluid distribution
• Transport
• Inflammatory response and control of infection

Question 3

What are the Methods of assessing plasma proteins?

Answer 3

As concentrations (for example g/L
As activities of those proteins that have defined functions such as clotting times for prothrombin or enzyme activity
Abnormal forms of protein may be present at normal concentration such as C1 inhibitor
Proteins are measured in forms of total serum protein, assay specific proteins and identity and quantify serum proteins by serum electrophoresis.

Question 4

Discuss Total Plasma Proteins?
Which proteins are likely to alter total protein concentrations significantly?

Answer 4

• Acute changes in proteins (levels in the blood) are often due to loss from, or gain by, the vascular compartment of protein-free fluid, rather than of protein.
  [It’s usually because there’s a movement of fluid (which normally doesn’t have proteins in it) into or out of the bloodstream (the vascular compartment)]
• Only marked changes of major constituents, such as albumin and immunoglobulins, are likely to alter total protein concentrations significantly.
• The acute-phase response can result in rapid albumin extravasation and thus hypoalbuminaemia.
• Total plasma protein may be normal in the presence of quite marked changes in the constituent proteins
• Raised plasma total protein concentrations may be due to loss of protein-free fluid, or excessive stasis during venepuncture,
• Or a major increase in the concentration of one or more of the immunoglobulins including paraproteins.
• The difference between serum total protein and albumin concentration is termed the serum globulin concentration
• Low plasma total proteins concentrations may be due to dilution, hypoalbuminaemia or severe immunoglobulin deficiency

Question 5

Discuss Qualitative methods for studying plasma and urinary proteins: Electrophoresis

What are the 5 main groups of proteins identified?

Answer 5

• Electrophoresis is a technique that separates compounds such as proteins according to their different electrical charges.
• It is usually performed by applying a small amount of serum to a strip of cellulose acetate or agarose and passing a current across it for a standard time.
• In this way, five main groups of proteins are identified ; albumin, α1, α2 ,β and γ globulins
• This may be distinguished after staining or visually compared with those in a normal control
  Each of the globulin fractions contains several proteins

Question 5

Discuss Protein electrophoresis in normal individual

Answer 5

• Albumin, usually a single protein, makes up the most obvious band.
• α1-globulins consist almost entirely of α1-antitrypsin and α1-antichymotrypsin.
• α2-globulins consist mainly of α2- macroglobulin and haptoglobin.
• Β-globulins often separate into two; Β1 consists mainly of transferrin with a contribution from low density lipoprotein and Β2 consists of the C3 compliment factor
• γ-globulins are immunoglobulins
  Some immunoglobulins are also found in the α2 and β regions.
• If plasma rather than serum is used, fibrinogen appears as a distinct band in the β–γ region

Question 6

Describe Chronic inflammation on electrophoresis

Answer 6

• The usual increase in immunoglobulin synthesis may be visible as a diffuse rise in γ-globulin
• If there is an active inflammatory reaction, the increased density in the γ-globulin region is associated with an increase in the α1 and α2 fractions of the acute-phase response.

Question 7

Describe Nephrotic Syndrome on electrophoresis

Answer 7

• Plasma protein changes depend on the severity of the renal lesion.
• In early cases, a low plasma albumin concentration may be the only abnormality,
• In established cases there are reduced albumin, α1-globulin and sometimes γ-globulin bands and an increase in α2-globulin concentration due to a relative or absolute increase in the high-molecular-weight α2- macroglobulin.
• If the syndrome is due to conditions such as systemic lupus erythematosus (SLE), the γ-globulin concentration may be normal or raised.

Question 7

Describe Liver Cirrhosis on electrophoresis

Answer 7

Albumin and often a globulin concentrations are reduced and the γ-globulin concentration is markedly raised with apparent fusion of the β and γ bands because of an increase in plasma IgA concentrations.

Question 8

Discuss albumin:
where is it synthesized?
what’s the t1/2?

Answer 8

• Albumin is synthesized by the liver.
• It has a normal plasma biological half-life of about 21 days.
• About 60 per cent in the extracellular fluid is in the interstitial compartment.
• The concentration gradient across the capillary membrane is important in maintaining plasma volume

Question 8

What are the inherited abnormalities of albumin synthesis?

Answer 8

• Bisalbuminaemias, in which two forms of albumin are present
  There are usually no clinical consequences,
• Analbuminaemia, in which there is deficient synthesis of the protein; clinical consequence is oedema, although is surprisingly mild.
• An abnormally high plasma albumin concentration is found only artefactually in a sample taken with prolonged venous stasis or after loss of protein-free fluid.

Question 9

What are Causes of hypoalbuminaemia?

Answer 9

1. Dilutional hypoalbuminaemia ( This specifically refers to low albumin levels caused by an increase in blood plasma volume (more fluid in the blood vessels) – diluting the albumin concentration)
   Redistribution of albumin from plasma into the interstitial fluid space, results from
   - Recumbency: plasma albumin concentrations may be 5–10 g/L lower in the recumbent than in the upright position because of the redistribution of fluid.
   - Increased capillary membrane permeability: this is the usual cause of the rapid fall in plasma concentration found in many circumstances, for example postoperatively and in most illnesses.
2. Decreased synthesis of albumin
3. Increased loss of albumin from the body: In abnormal membrane permeability
4. Increased catabolism of albumin: in sepsis, hyperthyroidism etc

Question 10

What are the Consequences of hypoalbuminaemia?

Answer 10

• Fluid distribution abnormality resulting to oedema
  Binding functions abnormality resulting in poor transport of albumin binding hormones etc

Question 10

What is Paraproteinaemia?

Answer 10

The term paraprotein (or also called M protein) refers to the appearance of an abnormal, narrow, dense band on the electrophoretic strip.

It is found most commonly in the γ region, but may be anywhere from the α2 to the γ region.

Paraproteins can often be shown to be monoclonal.