Serum Proteins And Associated Disp4ders Flashcards
What is the blood plasma?
The non-cellular liquid layer of the blood obtained by sedimentation and Centrifugation
What is blood serum?
Prepared in laboratory
In the laboratory whole blood is allowed to coagulate before Centrifugation. The resulting fluid is blood serum.
(Blood serum is blood plasma without blood coagulating factors)
What is the function of serum protein electrophoresis(SPEP)?
Separates serum proteins regarding their overall charge
This method is often combined with densitometry
What are the main serum proteins?
Albumin
a and B globulins
y-globulins
What is the function of albumin?
Maintenance of oncotic pressure
Transport: calcium ions, free fatty acids, bilirubin, hormones and drugs
What are the functions of a and B globulins?
Enzymes
Transport
Inhibitor proteins
What are the functions of y-globulins?
Immune response
Where is albumin synth3sized?
Albumin is extremely synthesized in the liver (14 g/day) and is released into the blood
Albumin is small and the most abundant serum protein
What is the range of serum albumin?
3.5-5 g/dL
Explain the main functions of albumin
- Maintenance of the osmotic pressure in the blood and prevention of edema
- Transport of some lipids like free fatty acids, bilirubin, steroid hormones and drugs
- Binding and transport of ca”chum ions in the blood
Note: Individual”s with congenital analbunemia appear normal and do not show edema. Other serum pr9teins regulate the osmotic pressure early 9n.
What are the causes of hypoalbumpnemia?
- Decreased synthesis of albumin
- Increased loss of albumin
What are the effects of decreased synthesis of albumin?
Kwashiorkor-dietary deficiency of proteins and often infections
Liver cirrhosis -severe liver damage impairs synthesis of serum proteins
What are the effects of increased loss of albumin?
Kidney disease-loss of urine due to damage of glomerulus basement membrane
Severe burns-damage of blood vessels leads t9 huge loss 9f serum
What can be used to ind8cate a1 globulin fraction?
- a1 Antitrypsin (>90%)
- a Fetotrypsin
- Transcortin
- Retinol binding protein
What is the clinical significance of a1 antotrypsin (a1-AT)?
- a1-Antitrypsin is a serum protein released by the liver and inhibits neutrophil e”dataset in lung alveoli
- A reduced amount of a1-AT in the blood can lead to excessive degradation of elastin in the lung and to emphysema
- Hereditary deficiency of a1-AT results from a defective hepatic N-glycosylation and reduced release into the blood. This can lead to pulmonary and liver disease
How can smoking lead to emohysema?
Smoking activates neutrophils which release neutrophil elastase and at the same time ROS modify the structure of a1-AT and reduce the binding to neutrophil elastase
Elevated neutrophil elastase destroys elastin in the alveoli
What 8s the clinical significance of AFP?
AFP is an a1 globulin that is abundant in fetal plasma which has very low levels of albumin. It may have function similar to albumin in fetal life
AFP level is low in healthy adults but it increases in cancer and is used as a serum marker for liver cancer
What is the use of maternal AFP?
Maternal serum AFP is used as a marker for possible fetal abnormalities
AFP is mostly found in the amniotic fluid. A small amount of amniotic fluid can cross the placenta and AFP can be measured in maternal serum
High maternal serum AFP level can be an indicator of neural tube defects
Low maternal serum AFP level can be an indicator of Down syndrome
What are transcortin and retinol binding protein?
These are a1 globulins that transport specific lipids
Transcortin transports 75% of cortisol in blood
Retinol-binding protein transports retinol in blood from the liver to the peripheral tissues
What can be used to indicate a2 globulin fraction?
- A2 macroglobulin
- Ceruloplasmin
- Hepatoglobin
What is the significance a2 Macroglobulin?
One of the largest serum proteins
A2M is the major component of the a2 globulin fraction. It has many different functions and inhibits an enormous variety of serum proteases like plasmin (fibrinolysis) and thrombin (coagulation)
A greater than 10 fold increase (abnormal) in blood is often found in patients with Nephrotuc syndrome due to damage of the basement membrane of the glomerulus
The synthesis of a2 macroglobulin is increased and it’s loss into urine is prevented by its large size whereas albumin is very small and lost into urine in nephrotic syndrome
What color is ceruloplasmin?
A blue a2 globulin
What are the functions if ceruloplasmin?
- Copper transport in blood
2. Ferroxidase activity
Where is ceruloplasmin formed?
Formed in the liver by binding of copper to Apo ceruloplasmin. The released ceruloplasmin transports 95% of copper in blood
What is Wilson disease?
Patients with Wilson disease have a very low blood levels of ceruloplasmin as hepatic copper binding is deficient. Apo ceruloplasmin (without copper ) is released into the blood where it is degraded
What causes Wilson disease?
Patients have a deficiency of a copper-transporting ATPase (ATPase7-B) which 8s needed to form ceruloplasmin and is also needed for release 9f copper into bile
Damage due to copper accumulation in the liver, leakage into the blood and deposits in brain, eyes, kidney and skin.
Hepatic dysfunction, neurologically and psychiatric symptoms
How does ceruloplasmin impact ferroxidase?
Ceruloplasmin acting as an enzyme needs copper for its ferroxidase activity
Ferroxidase forms ferric ion
Macrophages degrade heme and release ferrous ion which could lead to radical formation (Fenton reaction)
This is prevented by ceruloplasmin which forms ferric ion that can be bound to transferrin and transported in blood
What is Haptoglobin?
An a2 globulin that binds to free hemoglobin dimers in the blood and prevents loss of Hb in urine
What is the functioning 9f haptoglobin?
Haptoglobulin-hemoglobin complex is taken up by macrophages. This explains why acute hemolysis l3ads to a low serum level 9f free haptoglobin
Serum protein electrophoresis is used to monitor the progress in patients with hemolytic anemia
What is transferrin?
Transferrin 8s a B-globulin which transports ferric ion in blood between: intestine, liver, bone marrow and spleen
Transferrin can bind two Fe3+ atoms for transport (Normally the transferrin binding sites are not all filled with iron)
What are the clinical evaluations of transferrin?
Low transferrin saturation is found in patients with iron deficiency as fewer sites of transferrin are filled
High transferrin saturation is found in patients with iron overload (High serum iron leads to increased binding)
What is hemopoxin?
Is a B-globulin that binds to free heme in the blood and prevents the loss of heme iron
What happens heme-hemopoxin?
Taken up into heoat9cytesvand the iron is bound to the storage protein ferritin
Hemopoxin prevents:
A. Heme-induced damage of plasma membranes (heme insertion and ROS)
B. Heme usage by microbes: heme is an important source of iron for pathogenic m8croorgabisms
How do LDL separate in SPEP?
They separate with B-globulins
LDLs have only apo-B100 which has an overall positive charge
LDL are also named B-lipoproteins
What are y-globulin synthesized by?
Plasma cells/activated B cells
What’s the origin of IgM?
Is found in blood and lymph and it 8s first antibody to be produced in response to an antigen (infection)
What are the origins of IgG?
Smallest and most common- found in all body fluids. It is produced By repeated exposure to the same antigen. IgG can cross the placenta giving passive immunity to the fetus and new born
What are the origins of IgE?
Is found in the lung, skin, mucous membranes and secreted in allergic reactions
Where is IgA found?
Found in body secretions and protects body surfaces. It is the main antibody found in human milk
What is the role of IgD?
Uncertain
What is the impact of serum protein electrophoresis in multiple myeloma?
Multiple myeloma is a tumor of the plasma cells and is an example of monoclonal gammopathyb
It is characterized by the presence 9f high amounts 9f a single type of immunoglobin produced by a malignant clone of the cell
Serum protein electrophoresis is an important tool that helps in diagnosis and monitoring patientswith multiple myeloma
What is an acute phase reaction of the liver?
Leases to changes in the synthesis 9f serum proteins
The hepatic acute phase reaction is an overall positive response to prevent damage following an injury such as in: Infections Extreme stress Burns Major crush injury Allergy or other
How can acute phase reactants be subdivided?
Into positive and negative reactants depending on the amounts synthesized
What are the positive reactants of acute phase ?
Serum proteins that are synthesized in larger amount as they reduce inflammation and deprive microbes of iron.
Examples: a1-antitrypsin Ceruloplasmin Haptoglobin Hemopoxin
What are the negative acute phase reactants?
Serum proteins that are synthesized in smaller amount in order to preserve amino acids for the increased synthesis of positive acute phase reactants
Examples: Albumin Transcortin Retinol-binding protein Transferrin
What is special about C-reactive protein?
It is an acute phase reactant that does not lead to a peak in SPEP
Where is C-reactive protein (CRP)?
Is synthesized and released during inflammation and was first found in blood of patients with acute inflammation. CRP was named after the fact that it reacted with the C-polypeptide of pneumococcus
CRP can increase to 30,000 times of its normal level
There is a specific test for CRP and it is used to monitor the proces of inflammation, trauma and infection
