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2.2 Clinical Chemistry > Plasma Proteins - Specific Protein Abnormalities > Flashcards

Plasma Proteins - Specific Protein Abnormalities Flashcards

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1
Q

List the proteins which are involved in specific protein abnormalities

A

Alpha-1-antitrypsin (ATT)

Transferrin (TF)

Caeruloplasmin (CP)

Acute Phase Reactants (APR)

C-Reactive Protein

Procalcitonin (PCT)

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2
Q

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

A

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

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3
Q

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

A

A proteinase inhibitor in serum

Inactivates several serine proteases by irreversibly forming an inhibitor complex

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4
Q

What serine proteases does AAT work on?
(6)

A

Leukocyte elastase

Trypsin

Chymotrypsin

Collagenase

Plasmin

Thrombin

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5
Q

What is the clinical significance of AAT
(3)

A

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

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6
Q

In your own words what does AAT do?

A

Inhibits proteases

Protects self cells from the work of wbcs during infection

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7
Q

What does a deficiency of AAT do?
(2)

A

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

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8
Q

Write a note on transferrin
(6)

A

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

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9
Q

What does an increase in transferrin saturation indicate

A

Iron overload

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10
Q

What does a decrease in transferrin saturation indicate

A

Iron deficiency

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11
Q

When is transferrin levels decreased

A

In inflammatory states

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12
Q

Why is transferrin decreased in inflammation

A

Due to excessive degradation of transferrin Fe3+ complexes

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13
Q

What is the clinical significance of transferrin?
(3)

A

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

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14
Q

What controls levels of transferrin synthesis

A

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).

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15
Q

Is transferrin a positive or negative acute phase protein

A

Negative phase protein -> hence low levels in inflammation

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16
Q

When are low levels of transferrin seen
(5)

A

Inflammatory diseases

Protein-losing enteropathy

Malnutrition

Nephrotic Syndrome

Disorders of haemoglobin synthesis

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17
Q

Write a note on caeruloplasmin (CP)

A

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

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18
Q

Caeruloplasmin has an antioxidative action, what does this mean

A

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

19
Q

When is low caeruloplasmin seen

A

Most cases of Wilson’s disease

Low in Menkes’ kinky hair syndrome

20
Q

Write a note on Wilson’s disease
(2)

A

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

21
Q

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

A

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

22
Q

What are the functions of caeruloplasmin

A

Regulates oxidation-reduction, transport and utilisation of iron

23
Q

When would you see increased concentrations of caeruloplasmin

A

Active liver disease or tissue damage

24
Q

Write a note on acute phase reactants
(3)

A

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

25
Q

List the nine acute phase reactants

A

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

26
Q

What activates acute phase reactants

A

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

27
Q

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

A

Rise in a1 and a2 globulin fractions

Increases blood viscosity and therefore erythrocyte sedimentation rate

Decrease in the synthesis of negative acute phase reactants

28
Q

Why is it useful to measure C reactive protein

A

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

29
Q

List the three negative acute phase reactants

A

Prealbumin
Albumin
Transferrin

30
Q

Write a note on C-Reactive protein
(3)

A

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

31
Q

What does slightly elevated CRP indicate

A

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)

32
Q

By how much does CRP increase during inflammation
(5)

A

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

33
Q

What does persistent CRP indicate

A

Indicates continuation of the pathological process or a complication

34
Q

Why is CRP not used to diagnose disease?

A

CRP occurs in all diseases involving tissue damage or inflammation

35
Q

Why do we investigate CRP in healthy people

A

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

36
Q

What is the main use of CRP

A

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

37
Q

When are the highest CRP levels seen
(3)

A

In bacterial infections

Lower in fungal and parasitic

Viral infections are less likely to cause substantial elevations

38
Q

Write a note on procalcitonin
(4)

A

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

39
Q

When might macrophages make PCT?

A

During systemic inflammatory response

40
Q

What does high levels of PCT indicate

A

Severe infection, sepsis or multiple organ dysfunction syndrome

41
Q

What might cause an elevation of PCT
(3)

A

Major surgical procedures

Polytrauma or burns

Prolonged circulatory failure

42
Q

Why is PCT an important APP
(3)

A

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

43
Q

Why might PCT and CRP be measured together

A

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

2.2 Clinical Chemistry (28 decks)

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