Plasma Proteins - Specific Protein Abnormalities

Question 1

List the proteins which are involved in specific protein abnormalities

Answer 1

Alpha-1-antitrypsin (ATT)

Transferrin (TF)

Caeruloplasmin (CP)

Acute Phase Reactants (APR)

C-Reactive Protein

Procalcitonin (PCT)

Question 2

Write a note on alpha-1-antitrypsin
(5)

Answer 2

Its 53 kDa big

The most important proteinase inhibitor in serum

Synthesised by the liver

Inactivates several serine proteases by irreversibly forming an inhibitor complex

There are various isoforms the most common being PiMM

Question 3

What is alpha-1-antitrypsin and what does it do

Answer 3

A proteinase inhibitor in serum

Inactivates several serine proteases by irreversibly forming an inhibitor complex

Question 4

What serine proteases does AAT work on?
(6)

Answer 4

Leukocyte elastase

Trypsin

Chymotrypsin

Collagenase

Plasmin

Thrombin

Question 5

What is the clinical significance of AAT
(3)

Answer 5

It’s an important acute phase reactant which is found elevated in inflammatory processes

Elevated levels used to help diagnose inflammation of the liver parenchymal cells -> other acute phase reactants aren’t raised by this

Deficiency of AAT is caused by genetics

Question 6

In your own words what does AAT do?

Answer 6

Inhibits proteases

Protects self cells from the work of wbcs during infection

Question 7

What does a deficiency of AAT do?
(2)

Answer 7

When infection occurs there is no alpha 1 to protect cells -> Elastin in lungs is damaged by chemicals produced by wbcs

Some genetic defects result in AAT being unable to get out of the liver -> this results in liver damage

Question 8

Write a note on transferrin
(6)

Answer 8

79.6 kDa

Transports iron in plasma as ferric ions (Fe3+)

Each transferrin molecule binds 2 Fe3+

This protects the body against the toxic effects of free iron

Transferrin normally 30% saturated with Fe3+ -> increase or decrease indicates iron overload or deficiency

Transferrin is decrease in inflammatory states due to excessive degradation of transferrin Fe3+ complexes

Question 9

What does an increase in transferrin saturation indicate

Answer 9

Iron overload

Question 10

What does a decrease in transferrin saturation indicate

Answer 10

Iron deficiency

Question 11

When is transferrin levels decreased

Answer 11

In inflammatory states

Question 12

Why is transferrin decreased in inflammation

Answer 12

Due to excessive degradation of transferrin Fe3+ complexes

Question 13

What is the clinical significance of transferrin?
(3)

Answer 13

Transports iron in plasma, and its rate of synthesis in the liver can be altered in accordance with the body’s iron requirements and iron reserves, and by oestrogen (e.g., during pregnancy).

Measurement of TF indicates latent and manifest iron deficiency and iron overload.

It is also a negative acute phase protein with low
concentrations present in inflammatory diseases as well as in protein-losing enteropathy, malnutrition, nephrotic syndrome and in disorders of haemoglobin synthesis

Question 14

What controls levels of transferrin synthesis

Answer 14

Rate of synthesis in the liver can be altered in accordance with the body’s iron requirements and iron reserves, and by oestrogen (e.g., during pregnancy).

Question 15

Is transferrin a positive or negative acute phase protein

Answer 15

Negative phase protein -> hence low levels in inflammation

Question 16

When are low levels of transferrin seen
(5)

Answer 16

Inflammatory diseases

Protein-losing enteropathy

Malnutrition

Nephrotic Syndrome

Disorders of haemoglobin synthesis

Question 17

Write a note on caeruloplasmin (CP)

Answer 17

151 kDa

A multifunctional protein synthesised in the liver

Very high copper content but is not a copper transporter in circulation

It is essential in the regulation of redox potential and utilisation of iron

Has an antioxidative action, which prevents the oxidation of lipids in the cell membrane through its ferroxidase activity

Question 18

Caeruloplasmin has an antioxidative action, what does this mean

Answer 18

It prevents the oxidation of lipids in the cell membrane through its ferroxidase activity

Question 19

When is low caeruloplasmin seen

Answer 19

Most cases of Wilson’s disease

Low in Menkes’ kinky hair syndrome

Question 20

Write a note on Wilson’s disease
(2)

Answer 20

Decreased ability to incorporate copper into apoceruloplasmin

As a result free copper levels in serum and in tissue especially liver, pancreas and brain are greatly increased

Question 21

Write a note on menke’s kinky hair syndrome
(low caeruloplasmin)

Answer 21

The defect is secondary to poor absorption and utilization of dietary copper, from protein loss in the nephrotic syndrome, protein-losing enteropathy and malabsorption, and from decreased synthesis in advanced liver disease

Question 22

What are the functions of caeruloplasmin

Answer 22

Regulates oxidation-reduction, transport and utilisation of iron

Question 23

When would you see increased concentrations of caeruloplasmin

Answer 23

Active liver disease or tissue damage

Question 24

Write a note on acute phase reactants
(3)

Answer 24

Group of proteins which rise significantly (<25%) during acute inflammation

Presumed to play a role in complex defensive process of inflammation

There are nine acute phase reactants

Question 25

List the nine acute phase reactants

Answer 25

C-reactive protein (CRP) complement activator

a1-antichymotrypsin

a1-acid glycoprotein (AAG)

a1 - antitrypsin

Haptoglobin (binds Hb released by local haemolysis)

C4

Fibrinogen

C3

Ceruloplasmin

Question 26

What activates acute phase reactants

Answer 26

Increased proteins synthesis in the liver in response to peptide mediators or cytokine (interleukins, interferons, tumour necrosis factor)

Question 27

What effects does an increase in acute phase proteins have
(3)

Answer 27

Rise in a1 and a2 globulin fractions

Increases blood viscosity and therefore erythrocyte sedimentation rate

Decrease in the synthesis of negative acute phase reactants

Question 28

Why is it useful to measure C reactive protein

Answer 28

Better than erythrocyte sedimentation rate in bacterial infections and acute inflammataory conditions

Question 29

List the three negative acute phase reactants

Answer 29

Prealbumin
Albumin
Transferrin

Question 30

Write a note on C-Reactive protein
(3)

Answer 30

Recognises foreign pathogens and damaged cells and cell fragments and initiates their removal by the macrophages

Major component of the APR and a marker of bacterial infection

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

Question 31

What does slightly elevated CRP indicate

Answer 31

Slightly elevated levels of CRP are indicative of chronic, low-grade inflammation and have been correlated with an increased risk of cardiovascular disease (i.e. cigarette smoking)

Question 32

By how much does CRP increase during inflammation
(5)

Answer 32

Its the most sensitive APP

It increases several hundredfold

Its rise and clearance is exponential with a half-life of 17 hours

Peak levels usually reached within 48-72 hours

Usually returns to normal levels within a week

Question 33

What does persistent CRP indicate

Answer 33

Indicates continuation of the pathological process or a complication

Question 34

Why is CRP not used to diagnose disease?

Answer 34

CRP occurs in all diseases involving tissue damage or inflammation

Question 35

Why do we investigate CRP in healthy people

Answer 35

Because of its extreme sensitivity its used to screen blood donors or outpatients for the presence of disease

Its a very sensitive index if ongoing inflammation

Question 36

What is the main use of CRP

Answer 36

The monitoring of infectious diseases with the goal to minimise the use of antibiotics

i.e. a low CRP in subjects with an infection indicates that probably there will be no need for antibiotics

Question 37

When are the highest CRP levels seen
(3)

Answer 37

In bacterial infections

Lower in fungal and parasitic

Viral infections are less likely to cause substantial elevations

Question 38

Write a note on procalcitonin
(4)

Answer 38

12.6 kDa

Procalcitonin is a prohormone that is proteolytically split to form calcitonin in the C-cells of the thyroid gland

PCT is degraded by proteolysis in healthy individuals => PCT is usually present in healthy persons only at very low concentrations

There is indication that macrophages and monocytic cells of various organs e.g. the liver are involved in the synthesis and release of PCT under the conditions of a systemic inflammatory response

Question 39

When might macrophages make PCT?

Answer 39

During systemic inflammatory response

Question 40

What does high levels of PCT indicate

Answer 40

Severe infection, sepsis or multiple organ dysfunction syndrome

Question 41

What might cause an elevation of PCT
(3)

Answer 41

Major surgical procedures

Polytrauma or burns

Prolonged circulatory failure

Question 42

Why is PCT an important APP
(3)

Answer 42

PCT increases earlier than all other APPs

PCT reaches its maximum at 12-24 hours

PCT has a short half-life which makes it suitable for monitoring the evolution of the underlying disease

Question 43

Why might PCT and CRP be measured together

Answer 43

Together they seem to be useful for the early diagnosis of bacterial and mycotic infection as well as sepsis and multiple organ failure