Serum Proteins Flashcards
1
Q
describe normal values of albumin and the half life
A
- albumin is synthesized in the liver with high amounts (14g/day) and released into blood
- normal blood value is 3.5-5g/dL
- it has a half life of 20 days and represents 66% of all serum proteins
2
Q
name the 3 main functions of albumin
A
- maintenance of the osmotic pressure in the blood
- transport of lipophilic molecules like free FAs, bilirubin, some hormones and drugs
- binding and transport of Ca ions in the blood
3
Q
name causes of hypoalbuminemia
A
-
decreased synthesis of albumin
- kwashiorkor
- liver cirrhosis
-
increased loss of albumin
- kidney disease
- damage to the GBM
- severe burns
- kidney disease
4
Q
name the α1 globuin proteins
A
6-7% of serum proteins
- α1 antitrypsin
- α fetoprotein
- transcortin
- retinol binding protein
5
Q
describe α1 antitrypsin
A
- represents more than 90% of the α1 fraction
- α1 antitrypsin inhibits neutrophil elastase in lung alveoli
- hereditary disorder:
- 15% of the normal amount of α1AT is secreted
- decreased in lung and increased in liver (stuck in liver)
- leads to pulmonary and liver desease
- 15% of the normal amount of α1AT is secreted
- the reduced amount of α1AT in the blood can lead to excessive degradation of elastin in the lung and can lead to emphysema
6
Q
describe how smoking affects α1AT
A
- smoking activates neutrophils which release neutrophil elastase
- smoke modifies (oxidizes a methionine) the structure of α1AT and reduces its binding to elastase
- this leads to elevated neutrophil elastase which is no longer inhibited and this results in tissue damage to alveoli
7
Q
describe α fetoprotein (AFP)
A
- in an α1 globulin that is abundant in fetal plasma (similar to albumin in fetal life)
- AFP level is low in healthy adults but it increases in liver cancer
8
Q
describe maternal serum AFP
A
- in serum of pregnant women (and aminiotic fluid) AFP is used as a marker for possible fetal abnormalities
- high = neural tube defects
- low = Down syndrome
9
Q
describe transcortin and retinol binding protein (RBP)
A
- transcortin is the main transport protein for cortisol and binds 75% of this steroid hormone
- retinol binding protein (RBP) transports retinol (vit. A) in blood from the liver to the peripheral tissues
- retinyl esters from the diet are stored in the liver and then are distributed to cells via the blood
10
Q
name the α2 globulin proteins
A
α2 globulin fraction = 8-9% of serum proteins
- α2 macroglobulin
- ceruloplasmin
- haptoglobin
11
Q
describe α2 macroglobulin
A
- inhibits proteases (ex: plasmin and thrombin)
- nephrotic syndrome leads to protein loss in urine due to damage of the basement membrane of the glomerulus
- albumin serum level is strongly reduced
- the loss of α2 macroglobulin into urine is prevented by its large size whereas albumin is small and lost
12
Q
describe ceruloplasmin
A
- apoceruloplasmin binds copper in the liver and forms ceruloplasmin which transports 95% of copper in blood
- also functions as an enzyme that uses copper as a cofactor in its ferroxidase activity
- macrophages release ferrous iron > ceruloplasmin converts ferrous into ferric iron > ferric iron can now be bound to transferrin and transported in blood
13
Q
describe Wilson disease
A
- copper is not bound to apoceruloplasmin resulting in the protein being released without copper where it is prematurely degraded
- patients have very low blood levels of ceruloplasmin
- patients have a deficiency of a copper-transporting ATPase which is needed to link copper to apoceruloplasmin and release copper into bile
- damage due to copper accumulation occurs in: the liver, brain, eyes (Kayser-Fleischer rings) and kidney
14
Q
describe haptoglobin
A
- binds to free hemoglobin (dimers) in circulation
- haptoglobin-hemoglobin complex cannot be excreted by the kidneys and this prevents the loss of hemoglobin (iron and globin)
- in acute hemolysis the haptoglobin-hemoglobin complex is taken up by macrophages resulting in a low serum free haptoglobin level
- SPEP is used to monitor the progress in patients with hemolytic anemia
15
Q
name the B globulin proteins
A
B globulin fraction = 14% of serum proteins
- transferrin
- hemopexin
- B-lipoprotein
16
Q
describe transferrin
A
- transferrin is a B-globulin which transports ferric iron in blood
- transferrin can bind to Fe3+ atoms for transport
- 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
- because high serum iron leads to increased binding to the binding sites
17
Q
describe hemopexin
A
- B-globulin that binds to free heme and prevents the loss of the complex heme-iron in the kidneys
- heme-hemopexin is taken up into hepatocytes
18
Q
name the immunoglobulins
A
- IgM: first antibody produced in response to an infection
- IgG: produced by repeated exposure to same atigen
- IgG can cross placenta and give passive immunity to fetus
- IgE: found in lung, skin, mucus membranes and is secreted in allergic reactions
- IgA: found in body secretions and protects body surfaces
- increased levels in cirrohsis
19
Q
name the positive acute phase reactants (increased synthesis)
A
- α1 globulin fraction:
- α1AT results in less inflammation
- α2 globulin fraction:
- ceruloplasmin facilitates formation of ferric iron which binds to ferritin
- haptoglobin
- B globulin fraction:
- hemopexin which binds free heme
20
Q
describe CRP
A
- normally not found in blood but synthesized and released during inflammation
21
Q
describe graph
A
acute inflammation
-
albumin peak is reduced due to less hepatic synthesis
- negative acute phase reactant
- alpha-1 pieak is elevated
- due to positive acute phase reactant a1-AT
- alpha-2 peak is elevated
- due to positive acute phase reactants; haptoglobin, ceruloplasmin and alpha2 macroglobulin
- B-globulin peak appears the same
22
Q
describe graph
A
long standing inflammation
- albumin peak is reduced much more than in acute inflam.
- alpha2 peak elevated
- positive acute phase reactants; haptoglobin, ceruloplasmin, alpha2 macroglobulin
- B-globulin peak elevated due to even more hemopexin
- gamma-globulin peak strongly increased
- mainly IgG
23
Q
describe graph
A
liver cirrhosis
- albumin peak is reduced due to less synthesis and damaged hepatocytes
- a1 peak is not elevated due to hepatic damage
- a2 peak reduced due to hepatic damage
- B-globulin and gamma-globulins forms the B-Gamma bridge
- all immunoglobulins are elevated
- IgA is found in liver cirrhosis
24
Q
A
multiple myeloma
- characterized by presence of high amounts of single immunoglobulin produced by a malignant monoclonal plasma cell
25
Q
A
nephrotic syndrome
- damage to the basement membrane of the glomerulus in the kidney resulting in loss of proteins with exception of alpha2-macroglobulin
- albumin peak strongly reduced
- alpha2-macroglobulin is not lost due to its large size and has a 10-fold increase
26
Q
A
hypogamma-globulinemia
- gammaglobulin fractions are absent
- IgM = first response to an infection
- IgG = produced with repeated exposure to same antigen
27
Q
A
A1AT deficiency
- normal pattern with exception of a1-peak which is nearly absent
- A1AT normally inhibits neutrophil elastase
