Plasma Proteins - Specific Protein Abnormalities Flashcards
List the proteins which are involved in specific protein abnormalities
Alpha-1-antitrypsin (ATT)
Transferrin (TF)
Caeruloplasmin (CP)
Acute Phase Reactants (APR)
C-Reactive Protein
Procalcitonin (PCT)
Write a note on alpha-1-antitrypsin
(5)
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
What is alpha-1-antitrypsin and what does it do
A proteinase inhibitor in serum
Inactivates several serine proteases by irreversibly forming an inhibitor complex
What serine proteases does AAT work on?
(6)
Leukocyte elastase
Trypsin
Chymotrypsin
Collagenase
Plasmin
Thrombin
What is the clinical significance of AAT
(3)
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
In your own words what does AAT do?
Inhibits proteases
Protects self cells from the work of wbcs during infection
What does a deficiency of AAT do?
(2)
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
Write a note on transferrin
(6)
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
What does an increase in transferrin saturation indicate
Iron overload
What does a decrease in transferrin saturation indicate
Iron deficiency
When is transferrin levels decreased
In inflammatory states
Why is transferrin decreased in inflammation
Due to excessive degradation of transferrin Fe3+ complexes
What is the clinical significance of transferrin?
(3)
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
What controls levels of transferrin synthesis
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).
Is transferrin a positive or negative acute phase protein
Negative phase protein -> hence low levels in inflammation
When are low levels of transferrin seen
(5)
Inflammatory diseases
Protein-losing enteropathy
Malnutrition
Nephrotic Syndrome
Disorders of haemoglobin synthesis
Write a note on caeruloplasmin (CP)
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
Caeruloplasmin has an antioxidative action, what does this mean
It prevents the oxidation of lipids in the cell membrane through its ferroxidase activity
When is low caeruloplasmin seen
Most cases of Wilson’s disease
Low in Menkes’ kinky hair syndrome
Write a note on Wilson’s disease
(2)
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
Write a note on menke’s kinky hair syndrome
(low caeruloplasmin)
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
What are the functions of caeruloplasmin
Regulates oxidation-reduction, transport and utilisation of iron
When would you see increased concentrations of caeruloplasmin
Active liver disease or tissue damage
Write a note on acute phase reactants
(3)
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
List the nine acute phase reactants
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
What activates acute phase reactants
Increased proteins synthesis in the liver in response to peptide mediators or cytokine (interleukins, interferons, tumour necrosis factor)
What effects does an increase in acute phase proteins have
(3)
Rise in a1 and a2 globulin fractions
Increases blood viscosity and therefore erythrocyte sedimentation rate
Decrease in the synthesis of negative acute phase reactants
Why is it useful to measure C reactive protein
Better than erythrocyte sedimentation rate in bacterial infections and acute inflammataory conditions
List the three negative acute phase reactants
Prealbumin
Albumin
Transferrin
Write a note on C-Reactive protein
(3)
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
What does slightly elevated CRP indicate
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)
By how much does CRP increase during inflammation
(5)
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
What does persistent CRP indicate
Indicates continuation of the pathological process or a complication
Why is CRP not used to diagnose disease?
CRP occurs in all diseases involving tissue damage or inflammation
Why do we investigate CRP in healthy people
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
What is the main use of CRP
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
When are the highest CRP levels seen
(3)
In bacterial infections
Lower in fungal and parasitic
Viral infections are less likely to cause substantial elevations
Write a note on procalcitonin
(4)
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
When might macrophages make PCT?
During systemic inflammatory response
What does high levels of PCT indicate
Severe infection, sepsis or multiple organ dysfunction syndrome
What might cause an elevation of PCT
(3)
Major surgical procedures
Polytrauma or burns
Prolonged circulatory failure
Why is PCT an important APP
(3)
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
Why might PCT and CRP be measured together
Together they seem to be useful for the early diagnosis of bacterial and mycotic infection as well as sepsis and multiple organ failure
