CPR 66 - Serum Proteins and Associated Disorders

Question 1

Differentiate blood plasma from blood serum.

Answer 1

Blood plasma is the non-cellular liquid layer of the blood obtained by sedimentation and centrifugation

Blood serum is obtained by allowing blood to clot, centrifuging it, and discarding the mass at the bottom. It is blood plasma without the clotting factors.

Question 2

Describe how alpha-2, beta, albumin, gamma, and alpha-1 run on a serum protein electrophoresis (SPEP)

Answer 2

Question 3

Draw out the normal densitometry graph for a SPEP.

Answer 3

Question 4

List the proteins, and their abbreviations, found in each globulin bland on a SPEP.

Answer 4

Albumin band - only albumin

α1 band - α1-antitrypsin (A1AT)(>90% of this band), α-fetoprotein (AFP), transcortin, and retinol binding protein (RBP)

α2 band - macroglobulin (A2M)(makes up majority of band), ceruloplasmin, haptoglobin (Hp)

ß band - transferrin, hemopexin, LDL

γ band - immunoglobulins

Question 5

What are the primary functions of the serum globulin proteins?

Answer 5

• Albumin - maintain osmotic pressure and transport Ca++, fatty acids, bilirubin, hormones, and drugs
• A1AT (α1) - inhibit neutrophil elastase
• Transcortin (α1) - transport cortisol in blood
• RBP (α1) - transport retinol from liver to peripheral tissues
• A2M (α₂) - inhibits many serum proteases like plasmin and thrombin
• Ceruloplasmin (α₂) - copper transport and ferroxidase activity
• Hp (α₂) - binds free hemoglobin dimers in blood
• Transferrin (ß) - transport ferric iron
• Hemopexin (ß) - binds to free heme in blood
• γ globulins - immune response

Question 6

What tissue synthesizes albumin? What is the normal serum albumin range?

Answer 6

Albumin is extensively synthesized in the liver and its normal serum range is 3.5 - 5 g/dL

Question 7

What are the symptoms of congenital analbuminemia?

Answer 7

There are none. Patients present as normal and do not show edema because other serum proteins regulate the osmotic pressure in these individuals

Question 8

What are the most common causes of hypoalbuminemia?

Answer 8

• Decreased synthesis of albumin which can be caused by liver cirrhosis or Kwashiorkor (severe protein malnutrition)
• Increased loss of albumin which can be caused by a kidney disease that damages the glomerulus or severe burns damaging large amounts of blood vessels

Question 9

Where is A1AT synthesized and what is its primary function? What occurs if A1AT is deficient?

Answer 9

It is synthesized in hepatocytes and its primary function is to inhibit neutrophil elastase. Its deficiency can cause pulmonary and liver disease.

Question 10

Explain how smoking leads to emphysema.

Answer 10

Smoking activates neutrophils in the lungs which will release neutrophil elastase. At the same time, smoking increases ROS production which will modify the structure of A1AT to reduce its binding to elastase. As a result, there is an increase in the amount of alveolar elastin degraded by elastase.

Question 11

Facts to know about AFP.

Answer 11

• α₁ globulin that is abundant in fetal plasma and thought to function similar to albumin in real life
• AFT levels are low in healthy adults but increases in patients with liver cancer (useful serum marker)
• During pregnancy, a small amount of AFP in the amniotic fluid (most of it ends up there) can make it across the placental barrier into the maternal serum. High maternal AFP may indicate a neural tube defect while low maternal AFP may indicate Down syndrome.

Question 12

What is nephrotic syndrome and how does it affect serum protein levels?

Answer 12

Nephrotic syndrome refers to a collection of symptoms resulting from kidney damage. In nephrotic syndrome, basement membrane of the glomerulus is often damaged which allows larger proteins like albumin through. This causes albumin levels to drop significantly but A2M levels to increase significantly (since it’s still too big to be filtered out by the damaged glomerulus)

Question 13

Facts to know about the formation of ceruloplasmin.

Answer 13

Apoceruloplasmin is formed in the liver where it is then joined with copper to form mature Ceruloplasmin which is then released into the blood.

Question 14

Facts to know about ceruloplasmin’s ferroxidase activity.

Answer 14

Macrophages degrade heme and relase ferrous iron which could lead to radical formation. This is prevented by ceruloplasmin which uses copper to form ferric iron from ferrous iron. Ferric iron can then be bound to transferrin and transported in blood.

Question 15

Facts to know about Wilson’s disease.

Answer 15

• Caused by a deficiency of a copper-transporting ATPase which is needed to link copper to apoceruloplasmin and to release copper into bile
• This causes very low serum levels of ceruloplasmin and very high serum levels of apoceruloplasmin
• Damage to the liver, brain, eyes, and kidneys occurs due to copper accumulation
• Copper in the eyes can actually be seen as Kayser-Fleischer rings.

Question 16

Why is the function of Hp important? What can Hp levels be used to monitor?

Answer 16

• By binding to free Hb dimers it prevents their loss in urine
• The Hp-Hb complex is taken up by macrophages and destroyed. This means the during acute hemolysis serum Hp levels will be low (because of the increased amount of free Hb for it bind). Because of this SPEP of Hp can be used to monitor patients with hemolytic anemia

Question 17

Discuss the important clinical evaluations of serum transferrin levels.

Answer 17

• Low transferrin saturation levels is seen in patients with an iron deficiency
• High transferrin saturation levels are seen in patients with iron overload (under normal conditions not all of the transferrin binding sites are filled)

Question 18

Discribe why the function of hemopexin is important.

Answer 18

• Its binding of free heme prevents:
  
  • The loss of heme-iron
  • Heme induced damage of plasma membranes by heme insertion and hydroxyl radical formation
  • Heme usage by microbes
• The heme-hemopexin complex is taken up by hepatocytes where the ferric iron is stored safely in ferritin

Question 19

What is another name for LDLs and why?

Answer 19

ß-lipoproteins because in a SPEP they are found in the ß-globulin band due to their positively charged apo B-100 protein.

Question 20

Where do immunoglobulins come from?

Answer 20

Plasma cells (activated B-lymphocytes) synthesize immunoglobulins

Question 21

Facts to know about the immunoglobulins.

Answer 21

IgM - found in blood/lymph and is the first antibody produced in response to infection

IgG - smallest, most common, and found in all body fluids. It is produced by repeated exposure to the same antigen. IgG can cross the placental barrier.

IgE - found in the lung, skin, and mucous membranes. Secreted in response to allergic reactions

IgA - found in body secretions (human milk) and protects body surfaces.

IgD - role uncertain

Question 22

What is the acute phase reaction of the liver?

Answer 22

It a change in serum protein synthesis by the liver in response to an injury such as: infection, extreme stress, burns, major crush injury, allergic reaction, etc. Some serum protein synthesis will increase to reduce inflammation and deprive microbes of iron while other protein synthesis will be reduced to preserve amino acids.

Question 23

What are the positive and negative acute phase reactants?

Answer 23

Positive acute phase reactants are those serum proteins that will have their synthesis increased. They are A1AT, Ceruloplasmin, Haptoglobin, Hemopexin, and C-reactive protein (CRP)

Negative acute phase reactants are those serum proteins that will have their synthesis decreased. They are albumin, transcortin, RBP, and transferrin

Question 24

Facts to know about CRP

Answer 24

• Synthesized and realeased by the liver during inflammation
• Called C-reactive protein because it reacts with the C-polypeptide of pneumococcus
• The CRP test is used to monitor the process of inflammation, trauma, and infection

Question 25

How will the SPEP pattern appear for these conditions:

• Acute Inflammation
• Chronic Inflammation
• Liver Cirrhosis
• Monoclonal Gammopathy
• Nephrotic Syndrome
• Hypogammaglobulinemia
• A1AT deficiency

Answer 25

• Acute inflammation - slight decrease in albumin and an increase in α₁ & α₂ globulins
• Chronic Inflammation - large decrease in albumin and an increase in everything else
• Liver Cirrhosis (polyclonal gammopathy) - large decrease in albumin and an increase in ß & γ globulins.
• Monoclonal Gammopathy - massive increase in γ globulins
• Nephrotic Syndrome - large decrease in albumin and large increase in α₂ globulins
• Hypogammaglobulinemia - large decrease in γ globulins
• A1AT deficiency - large decrease in α₁ globulins

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