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T1 - Integrated (Full Review) > Biochemistry - Cardiology Block (III) > Flashcards

Biochemistry - Cardiology Block (III) Flashcards

1
Q

Why is hemoglobin a necessary component of efficient oxygen transport within the body?

A

O2 is relatively insoluble

(as are all nonpolar gases)

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2
Q

Which is more soluble in blood (and any aqueous solution), polar or nonpolar gases?

A

Polar gases

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3
Q

At what pH is O2 / hemoglobin binding increased, high or low?

A

High pH

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4
Q

At what pH is O2 / hemoglobin binding decreased, high or low?

A

Low pH

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5
Q

Which of the following affect myoglobin affinity for O2?

pH

2,3-DPG

CO2

A

None of them

(myoglobin not regulated by pH or modifying molecules as hemoglobin is)

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6
Q

Hemoglobin is made up of how many subunits?

Myoglobin is made up of how many subunits?

A

4;

1

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7
Q

What are the two contributing portions of a heme molecule?

A

The protoporphyrin IX ring

+

Fe2+ (ferrous iron)

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8
Q

How many bonds can a single ferrous iron atom make?

To what structure(s) is one ferrous iron atom bound in a single heme molecule?

A

6;

4 bonds to the protoporphyrin IX ring,

1 bond to a posterior histidine (from helix F),

1 potential bond to oxygen

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9
Q

Binding of O2 to the ferrous iron in a heme molecule leads to _______ movement of what amino acid also bound to the ferrous iron?

A

Lateral;

histidine

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10
Q

Ferrous iron is notated as ___?

Is this an oxidized or reduced form of Fe?

A

Fe2+;

reduced (as opposed to oxidized, ferric iron –> Fe3+)

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11
Q

True/False.

Ligand binding to molecules such as hemoglobin is all of the following: specific, reversible, and transient.

A

True.

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12
Q

What is the Kd in regards to ligands for a molecule like myoglobin?

A

The concentration [L] of the ligand (mM) at which 50% of the available binding sites are occupied (on average)

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13
Q

A ligand with high affinity for its substrate protein (e.g. hemoglobin) will have what type of Kd, high or low?

A

Low

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14
Q

A Kd in ligand binding is equivalent to what type of constant in Michaelis-Menten kinetics?

A

Km

  • (low Kd = high affinity;*
  • high Kd = low affinity)*
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15
Q

What does sigma represent in the attached graph?

(Note: the graph shows myoglobin O2 binding in relation to partial pressure of O2)

A

θ = binding sites filled

(in this case, by O2)

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16
Q

Which is indicative of high ligand affinity in a graph comparing binding sites to partial pressure of the gas in question, a right shift or a left shift?

A

Left shift

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17
Q

A right shift in a graph showing hemoglobin-O2 binding would indicate what type of affinity, high or low?

A

Low

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18
Q

The hemoglobin-O2 binding curve is ___________, indicating cooperativity.

The myoglobin-O2 binding curve is ___________, indicating no cooperativity.

A

Sigmoidal;

hyperbolic

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19
Q

The myoglobin-O2 binding curve is hyperbolic, indicating no __________.

The hemoglobin-O2 binding curve is sigmoidal, indicating __________.

A

Cooperativity;

cooperativity

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20
Q

In the T state, the Fe2+ in heme is where?

A

Pulled out of the plane of the protoporphyrin IX ring

(low affinity for O2​)

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21
Q

In the R state, the Fe2+ in heme is where?

A

In-plane with the protoporphyrin IX ring

(high affinity for O2)

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22
Q

The histidine that binds the heme group Fe2+ is attached to which hemoglobin subunit, α or β?

A

α

(from helix F)

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23
Q

In which hemoglobin state (tense or relaxed) is the Fe2+ pulled out of plane with the protoporphyrin ring (by histidine)?

A

Tense (T)

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24
Q

In which hemoglobin state (tense or relaxed) is the Fe2+ pulled into plane with the protoporphyrin ring (by histidine)?

A

Relaxed (R)

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25
Q

How many O2 molecules can bind one hemoglobin molecule?

A

4

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26
Q

What type of bonds allow for hemoglobin conformational change from T to R and back?

How many of these bonds?

A

Ionic bonds;

8 (2 intrachain; 6 interchain)

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27
Q

For each single O2 molecule that binds hemoglobin, how many ionic bonds are broken (of the 8 involved in conformational change)?

A

2

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28
Q

Describe which concentration changes in the following would likely lead to a right shift (decreased affinity) in hemoglobin-O2 binding:

H+

2,3-BPG

CO2

CO

A

H+ - Increased

2,3-BPG - Increased

CO2 - Increased

CO - Decreased

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29
Q

How does increased [H+] lead to increased O2 unloading from hemoglobin?

A

Decreased pH leads to stronger ionic interactions between hemoglobin subunits (favoring the T state)

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30
Q

Describe which concentration changes in the following would likely lead to a left shift (increased affinity) in hemoglobin-O2 binding:

H+

2,3-BPG

CO2

CO

A

H+ - Decreased

2,3-BPG - Decreased

CO2 - Decreased

CO - Increased

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31
Q

In what direction does a high CO concentration shift the hemoglobin-O2 binding curve?

A

To the left

(high CO increases Hb-O2 binding)

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32
Q

Does 2,3-BPG increase or decrease O2 binding to hemoglobin?

A

Decrease

(causes O2 unloading)

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33
Q

Describe the three methods by which CO2 is transported in the blood and what percentage of CO2 follows each method.

A

Dissolved in the blood (10%)

As carbaminohemoglobin (~20%)

As bicarbonate (~70%)

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34
Q

How much of CO2 is simply dissolved in the blood?

A

10%

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35
Q

How much of CO2 is transported as carbaminohemoglobin?

A

~20%

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36
Q

How much of CO2 is transported as bicarbonate?

A

~70%

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37
Q

Where does CO2 bind hemoglobin to form carbaminohemoglobin?

A

The amino-terminal end of each subunit

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38
Q

What two effects does CO have on O2-hemoglobin interactions?

A
  1. It replaces O2

(binds with 250x the affinity of O2)

  1. It causes a left shift and decreased O2 unloading

(stabilizes the R state)

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39
Q

How does CO poisoning manifest?

How does severe CO poisoning manifest?

How can CO poisoning be treated?

A

Flu-like syndromes (headache, nausea, vertigo);

seizures, coma and death;

pure oxygen delivery (can be hyperbaric)

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40
Q

Ingestion of nitrates (e.g. bismuth nitrate or from well water) or oxidixing medications can have what effect on hemoglobin?

What is this condition called in infants?

How is it treated (in general)?

A

Oxidation of Fe2+ to Fe3+

(methemoglobinemia);

blue-baby syndrome;

methylene blue

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41
Q

Prolonged periods of time spent at high altitudes will have what two effects on the blood?

A

Increased 2,3-BPG;

increased Hb and RBCs

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42
Q

How are γ Hb subunits different from β Hb subunits?

(I.e. how are infant hemoglobin (α2γ​2) different from adult hemoglobin (α2β2)?)

A

Less affinity for 2,3-BPG

(specifically, 2 serine residues are replaced with 2 histidine granules)

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43
Q

Why does fetal Hb (α2γ​2) have a higher affinity for O2 than adult Hb (α2β2)?

A

γ subunits has less affinity for 2,3-BPG than β subunits

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44
Q

What is the mechanism of the Bohr effect?

A

As acidity increases, protons attach to hemoglobin histidines

—> cause a conformational change in Hgb and O2 unloading

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45
Q

What enzyme combines CO2 and H2O to form carbonic acid and a proton?

Which is the predominant tissue in which this reaction take place?

A

Carbonic anhydrase;

erythrocytes

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46
Q

How much of CO2 is transported in the blood as bicarbonate?

How much of CO2 is transported in the blood as dissolved CO2?

How much of CO2 is transported in the blood bound to Hgb as carbaminohemoglobin?

A

~70%

~10%

~20%

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47
Q

Which has a stronger affinity for Hgb, O2 or CO?

How much stronger is its affinity?

A

CO

250x

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48
Q

True/False.

A single bound CO destabilizes the R state of Hgb.

A

False.

It stabilizes the Hgb

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49
Q

Sickle cell anemia results due to what genetic defect?

A

Glutamate6 change to valine6 in both β-hemoglobin chains

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50
Q

True/False.

A single mutation in the gene coding for the sixth glutamic acid in β-hemoglobin is all it takes to result in sickle cell anemia.

A

False.

The disorder is autosomal recessive. A mutation in both genes (SS, homozygous) is necessary.

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51
Q

Sickle cell anemia results from a mutation in the __ glutamic acid in β-Hgb to ________.

Hemoglobin C disease results from a mutation in the __ glutamic acid in β-Hgb to ________.

A

6th, valine;

6th, lysine

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52
Q

True/False.

Sickle cell vasocclusive crises can affect any organ system.

A

True.

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53
Q

What inheritance pattern does sickle cell anemia follow?

A

Autosomal recessive

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54
Q

What is the first-line treatment for the disorder shown here?

Via what mechanism does it function?

A

Hydroxyurea;

increasing HgbF concetrations

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55
Q

HgbS is most likely to form fibers and sickle RBCs when it is in what state?

What are the implications?

A

The deoxygenated state;

hypoxic conditions (e.g. exercise, high altitudes) can exacerbate the condition

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56
Q

Through what mechanism does hydroxyurea improve the signs/symptoms of sickle cell anemia?

A

HgbF levels increase;

HgbF gets incorporated into HgbS chains and halts their continued polymerization

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57
Q

Is sickle cell anemia a hemolytic anemia?

A

Yes.

The sickle cells are rigid and inflexible and become jammed and/or lysed in capillary beds

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58
Q

Besides hydroxyurea, what other treatments exist for sickle cell anemia in certain situations?

A

Blood transfusions,

prophylactic antibiotics,

pain management,

bone marrow transplants

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59
Q

The glutamic acid that is changed to valine in sickle cell anemia is at what amino acid position and in which hemoglobin chain?

The glutamic acid that is changed to lysine in hemoglobin C disease is at what amino acid position and in which hemoglobin chain?

A

6, β-Hgb;

6, β-Hgb

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60
Q

What treatments are typically needed for hemoglobin C disease?

A

None;

it is basically a much less severe form of sickle cell anemia

(glutamic acid6 –> lysine6 instead of valine)

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61
Q

What form of HbS (Sickle cell hemoglobin) is protective against malaria?

A

The heterozygous form

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62
Q

During weeks 3 - 8 of embryonic development, what organ is producing erythrocytes?

What kind of hemoglobin is produced? What two subunits are used?

A

Yolk sac;

hemoglobin E (HbE), ε2ζ2 (epsilon, zeta)

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63
Q

At week 9 of embryonic development, which organ takes over erythrocyte production?

What kind of hemoglobin is produced? What two subunits are used?

A

The liver;

hemoglobin F (HbF), α2γ2

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64
Q

What are the three main types of hemoglobin found in adults?

In what percentages?

A

Adult Hb (HbA) α2β2 >95% of adult Hb

Adult Hb (HbA2) α2δ2 <3% of adult Hb

Fetal Hb (HbF) α2γ2 <3% of adult Hb

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65
Q

What are the two forms of adult hemoglobin?

A

HbA α2β2 (>95%)

HbA2 α2δ2

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66
Q

What type of hemoglobin predominates in the embryonic period?

What type of hemoglobin predominates in the fetal period?

What type of hemoglobin predominates in the adult period?

What type of hemoglobin is present in adults but never predominates at any stage?

A

HbE ε2ζ2

HbF α2γ2

HbA α2β2

HbA2 α2δ2

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67
Q

About 5% of adult hemoglobin does not come from HbA (α2β2). This 5% comes from a mix of what two other types of hemoglobin?

A

HbA2 α2δ2

HbF α2γ2

68
Q

Although most cases of methemoglobinemia result from exposure to nitrates or certain drugs, what two genetic changes can also cause it?

A

Certain mutations in the α- or β-globin chains (autosomal dominant);

mutated NADH-cytochrome B5 reductase (diaphorase I) (reduces met-Hb to Hb in normal cells)

69
Q

What enzyme is responsible for reducing methemoglobin back to hemoglobin in normal RBCs?

A

NADH-cytochrome B5 reductase (diaphorase I)

70
Q

Hemoglobin normally has iron in its ___________ (oxidized/reduced) state, Fe?.

Methemoglobin has iron in its ___________ (oxidized/reduced) state, Fe?​.

A

Reduced, Fe2+ (ferrous);

oxidized, Fe3+ (ferric)

71
Q

True/False.

Individuals with sickle cell anemia are at an increased risk for infection.

A

True.

72
Q

What is a very prominent sign of methemoglobinemia?

What is this called when found in infants?

A

Blue-brown skin;

blue baby syndrome

73
Q

What are the two main causes of ‘blue baby syndrome?’

A

Methemoglobinemia;

congenital cyanotic heart diseases

74
Q

True/False.

Some individuals have a congenitally high level of HbF (α2γ2) as high as 30%.

A

True.

Hereditary persistence of fetal hemoglobin (HPFH)

75
Q

What are the two types of α-globin chain?

What are the two types of β-globin chain?

A

α (alpha), ζ (zeta)

β (beta), γ (gamma), δ (delta), ε (epsilon)

76
Q

Describe the transition in hemoglobin type from yolk sac production to post-natal hemoglobin.

A
77
Q

How is methemoglobinemia treated?

A

IV methylene blue

78
Q

What gene can be edited to increase HbF (α2γ2) and improve the symptoms of sickle cell anemia?

A

HS-1 (γ-silencing region)

79
Q

Define thalassemia.

What inheritance pattern do thalassemias follow?

A

A mutation that diminishes or eliminates the production of one of the two chains of hemoglobin;

autosomal recessive

80
Q

What population(s) is most affected by β-thalassemia?

What population(s) is most affected by α-thalassemia?

A

Mediterranean;

Southeast Asian, Middle Eastern, African

81
Q

True/False.

Thalassemias can be caused by mutations in the coding or regulatory genes for α- or β-globin.

A

True.

82
Q

How are the hemoglobin genes controlled?

On what chromosome are the genes coding for α-globin located?

On what chromosome are the genes coding for β-globin located?

A

by locus control regions;

16;

11

83
Q

In what order are the various β-globin genes organized on chromosome 11?

A

In the order in which they become useful

(starting with the locus control region; epsilon –> gamma –> delta –> beta)

84
Q

A newborn presents in the first year of life with severe microcytic hypochromic anemia.

What autosomal recessive disorder might this child have and why are they at an increased risk of heart failure as early as the second or third decade of life?

A

β°-thalassemia major (Cooley’s anemia)

buildup of iron in the heart and other organs

85
Q

A symptomatic patient has both β-hemoglobin genes inactivated. What disorder is this?

An asymptomatic patient has a single β-hemoglobin genes inactivated. What disorder is this?

A symptomatic patient has a single β-hemoglobin genes inactivated. What disorder is this?

A

β°-thalassemia major (Cooley’s anemia);

β-thalassemia minor;

β-thalassemia intermedia

86
Q

What is β+-thalassemia?

A

Decreased β-hemoglobin production due to a mutation in the locus control region

87
Q

In what order are the various α-globin genes organized on chromosome 16?

A

In the order in which they become useful

(starting with the locus control region; zeta –> alpha)

88
Q

What type of α-thalassemia is fatal in-utero and is characterized by virtually no α-globin production? (All 4 genes deleted)

What type of heterozygous, severe α-thalassemia is characterized by only 25% of normal α-globin production? (3 genes deleted)

What type of mildy symptomatic α-thalassemia presents similarly to an iron deficiency? (2 genes deleted)

What type of α-thalassemia is asymptomatic? (1 gene deleted)

A

α-thalassemia major (hemoglobin Bart) (hydrops fetalis) (Hgb γ4)

Hemoglobin H disease (Hgb β4 + Hgb γ4)

α-thalassemia trait (cis or trans)

α-thalassemia silent

89
Q

What type of α-thalassemia is fatal in-utero and is characterized by virtually no α-globin production? (All 4 genes deleted)

How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?

A

α-thalassemia major (hemoglobin Bart) (hydrops fetalis) (Hgb γ4);

4

90
Q

What type of heterozygous, severe α-thalassemia is characterized by only 25% of normal α-globin production?

How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?

A

Hemoglobin H disease (Hgb β4 + Hgb γ4)

3

91
Q

What type of mildy symptomatic α-thalassemia presents similarly to an iron deficiency?

How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?

A

α-thalassemia trait (cis or trans)

92
Q

What type of α-thalassemia is asymptomatic?

How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?

A

α-thalassemia silent;

1

93
Q

What are the three most abundant classes of plasma proteins?

A

Albumin (60%)

Immunoglobulins (18%)

Fibrinogens (4%)

94
Q

What are albumin’s two main functions?

A

To maintain oncotic pressure;

to transport substances in the blood

95
Q

Define antigen.

A

Foreign molecule that is selectively bound by antibodies

96
Q

Define immunogen.

A

Molecules that induce antibody production (e.g. carbohydrates, proteins, nucleic acids)

97
Q

Define antigenic determinant.

What is its alternate name?

A

A small region of a larger molecule that elicits production of a specific antibody;

epitope

98
Q

Define epitope.

What is its alternate name?

A

A small region of a larger molecule that elicits production of a specific antibody;

antigenic determinant

99
Q

Epitopes (antigenic determinants) are usually only large enough for an immunoglobulin region of what size to bind them?

A

6 - 7 amino acids

(the hypervariable regions)

100
Q

Name the different terms that line up with each of the following definitions.

    1. Molecules that induce antibody production (e.g. carbohydrates, proteins, nucleic acids)*
    1. A small region of a larger molecule that elicits production of a specific antibody*
    1. Foreign molecule that is selectively bound by antibodies*
A
  1. Immunogen
  2. Antigenic determinant; epitope
  3. Antigen
101
Q

Describe the basic structure of an immunoglobulin.

A
102
Q

Where are the main bonds combining heavy and light chains?

What type of bond are they?

A

Heavy-heavy (x2)

Heavy-light (x1 each)

103
Q

What are the two types of antibody light chain?

A

Lambda and kappa

(λ and κ)

104
Q

The Fc end of the immunoglobulin ends in which terminus?

The antigen-binding end of the immunoglobulin ends in which terminus?

A

Fc –> carboxy(C)-terminus

Antigen-binding –> amino(N)-terminus

105
Q

How many domains make up an antibody heavy chain?

Describe them.

A

4;

1 variable (VH), 3 constant (CH1, CH​2, CH​3)

106
Q

How many domains make up an antibody light chain?

Describe them.

A

2;

1 variable (VL), 1 constant (CL)

107
Q

True/False.

A single immunoglobulin molecule can have a kappa light chain and a lambda light chain.

A

False.

While it may have either type, it will have either two kappa light chains or two lamda light chains (i.e. there is no mixing or matching of light chain types)

108
Q

Describe which classes of antibody can take on different forms (e.g. monomer, dimer, tetramer, pentamer, etc.).

A
109
Q

What is the supersecondary structure of an immunoglobulin?

A

A beta sandwhich (immunoglobulin fold)

  • (constant region: 4-3 arrangement*
  • variable region: 5-4 arrangement)*
110
Q

How many complementary determining regions (CDRs) exist per single variable domain (of which, there are four per monomeric antibody)?

A

3

  • (yielding 12 per immunoglobulin monomer and*
  • 60 per IgM pentamer)*
111
Q

Describe the structure of an antigen-binding cleft (pocket).

A

3 heavy chain loops + 3 light chain loops

= 1 barrel-shaped pocket

112
Q

The constant domain will be identical within each ____ of antibody.

A

Class (IgG, IgA, IgM, IgD, IgE)

113
Q

What defines the class of an antibody?

What are the classes?

A

The constant domain;

IgG, IgA, IgM, IgD, IgE

114
Q

Name the classes of antibody from most to least prevelant in the serum.

Put their relative domains in parentheses next to them.

A

IgG (γ), 12 mg/ml

IgA (α), 3 mg/ml

IgM (μ), 1 mg/ml

IgD (δ), 0.1 mg/ml

IgE (ε), 0.001 mg/ml

115
Q

IgG, IgA, IgM, IgD, and IgE class immunoglobulins are defined by which constant domains, respectively?

A

γ (IgG)

α (IgA)

μ (IgM)

δ (IgD)

ε (IgE)

116
Q

Which immunoglobulin class is the first seen in acute immune responses?

A

IgM

117
Q

Which immunoglobulin is found in mucosal secretions?

A

IgA

118
Q

Which immunoglobulin class is present on lymphocyte cell surfaces but its function is not yet clear?

A

IgD

119
Q

Which is the most abundant immunoglobulin class in serum?

A

IgG

120
Q

Which immunoglobulin class is found most abundantly on mast cell surfaces?

A

IgE

121
Q

What are complementary determining regions (CDRs)?

How many does each immunoglobulin have?

A

The part of the antibody that binds an antigen;

12 (12 possible specificities per antibody)

122
Q

What are some examples of non-immunoglobulin proteins that have similar structural motifs to immunoglobulins?

A

Fibronectin, cell adhesion molecules, T cell receptors, MHCs

123
Q

What is another name for the complementary determining regions (CDRs) on antibodies?

How many does each immunoglobulin have?

A

Hypervariable regions;

12

124
Q

What test uses either antibodies to look for complementary antigen binding or antigens to look for complementary antibody binding?

A

ELISA (enzyme-linked immunosorbent assay)

125
Q

How does a Western blot (immunoblot) work?

A

Proteins are run on an SDS gel

–> the gel is incubated in an antibody-containing substance to show presence of a specific protein

126
Q

Attached is an image showing various crossovers between human and mouse (or other animal) immunoglobulins for therapeutic monoclonal antibodies to be produced.

Describe the convention for naming antibodies of these four types.

A

Murine Antibodies: -momab

Chimeric Antibodies: -ximab

Humanized Antibodies: -zumab

Fully Human Antibodies: -mumab

127
Q

What antibody-mediated test shows the relative amount of a substance in solution?

What antibody-mediated test shows the relative size of a specific protein?

What antibody-mediated test can be used to isolate a single protein-bound DNA sequence for amplification?

A

ELISA;

immunoblot (Western blot);

Chip

128
Q

A drug ends in -momab. This drug is a ____________ ____________ that is completely ____________.

A

monoclonal antibody (mab);

murine (mo) (meaning mouse)

129
Q

A drug ends in -ximab. This drug is a ____________ ____________ that is ____________.

A

monoclonal antibody (mab);

chimeric (xi) (murine/mouse + human)

130
Q

Which of these monoclonal antibodies is the body most likely to mount a resistance against?

A

Murine > chimerized >> humanized >>>> human

131
Q

A drug ends in -zumab. This drug is a ____________ ____________ that is ____________.

A

monoclonal antibody (mab);

humanized (zu) (partially murine/mouse)

132
Q

Why is it best to use antibodies with the least amount of murine (mouse) (or other organism) protein involved?

A

There is less likelihood that the body will mount an immune response against the antibody

133
Q

A drug ends in -mumab. This drug is a ____________ ____________ that is completely ____________.

A

monoclonal antibody (mab);

human (mu)

134
Q

What are polyclonal antibodies?

What are monoclonal antibodies?

A

Antibodies produced by various B cells to respond to multiple epitopes on a single antigen (normal bodily function);

antibodies produced by clonal B cells to respond to a single epitope on a single antigen (usually done in culture)

135
Q

Which represents normal bodily antibody production, polyclonal or monoclonal antibodies?

A

Polyclonal

(multiple types of plasma cell producing antigens to various epitopes on a target antigen)

136
Q

Why is monoclonal antibody production safer for clinical/therapeutic use?

A

As there is only a single epitope target, there is less likelihood of interaction with other bodily tissues

137
Q

What is an example of a disease caused by monoclonal antibody production?

What is this antibody called?

What is found in the urine?

A

Multiple myeloma;

M protein;

Bence Jones proteins

138
Q

What are Bence Jones proteins?

A

M protein light chains secreted in the urine

(multiple myeloma)

139
Q

What are the four main signs/symptoms of multiple myeloma?

A

CRAB

Ca2+ elevation

Renal failure

Anemia

Bone lesions

140
Q

Why do the plasma cells in multiple myeloma result in monoclonal antibody production when most antibody production in the body is polyclonal (multiple plasma cell types creating multple antibodies)?

A

The multiple myeloma cells are immortal and outlast / outcrowd the other plasma cells

141
Q

What are the two largest classes of therapeutics?

A
  1. Vaccines
  2. Monoclonal antibodies
142
Q

In what cultures or organisms are most therapeutic monoclonal antibodies produced?

A

Bacterial or insect cultures

143
Q

What does it mean if a therapeutic agent’s name ends in ‘-mab?’

(E.g. abciximab)

A

Monoclonal antibody

144
Q

What are the two general categories of reasons a person might have erythrocytosis?

A

EPO elevation (external cause)

(e.g. hypoxia [high altitudes, lung disorders]; EPO-secreting tumor; supplemental EPO or androgens);

consitutional overactivation of JAK/STAT (internal cause)

(e.g. myeloproliferative disorders such as polycythemia vera)

145
Q

What is the JAK protein?

What does it activate?

How does its pathway work?

A

A tyrosine kinase;

STAT proteins;

EPO –> myeloid stem cell receptor –> JAK/STAT activation –> erythrocyte differentiation

146
Q

What is the purpose of PCR?

What are the three steps?

A

To amplify DNA fragments;

heating/denaturation, annealing of primers, /replication

147
Q

What is a myeloproliferative disorder involving JAK2 activation and mainly erythrocytosis?

What is a myeloproliferative disorder involving JAK2 activation and mainly thrombocytosis?

What is a myeloproliferative disorder involving JAK2 activation and mainly granulocytosis?

A

Polycythemia vera;

thrombocytosis;

CML

148
Q

True/False.

Bone marrow fibrosis is often associated with JAK2 inactivations and myeloproliferative disorders.

A

False.

Bone marrow fibrosis is often associated with JAK2 activations and myeloproliferative disorders.

149
Q

What lab should you order to assist in determining the cause of erythrocytosis?

A

EPO

150
Q

What is the mnemonic for EPO-secreting tumors?

A

“Ah, PHUCK. I have an EPO tumor.”

Pheochromocytoma

Hepatoma

Uterine leiomyoma

Cerebellar hemangioblastoma

Kidney

151
Q

What do kidney tumors often secrete?

A

EPO

(due to VHL degradation)

152
Q

Erythropoeitin, thrombopoeitin, and other hematopoeitic substances all bind receptors on what type of cell to induce differentiation down the various hematopoeitic lineages?

A

Hematopoeitic stem cells

153
Q

What transcription factor is activated in the renal tubules to cause EPO release?

What stimulates this dimerization?

A

HF-1α dimerizes to HF-1β;

hypoxia

154
Q

What molecular effect does hypoxia have on the renal tubules?

A

HF-1α dimerizes to HF-1β

(transcription factors)

–>

increased EPO synthesis and secretion

155
Q

What are HF-1α and HF-1β?

A

The renal transcription factors that increase EPO secretion in hypoxic conditions

156
Q

What protein inhibits HF-1α during non-hypoxic times, inhibiting EPO synthesis?

Via what mechanism?

A

VHL

(von Hippel-Lindau);

increased ubiquination/degradation of HF-1α

157
Q

What is VHL (von Hippel-Lindau) protein’s function in the renal tubules?

A

To bind HF-1α and prevent EPO synthesis

158
Q

What hypoxia-induced transcription factor causes increased EPO secretion from the renal tubular epithelium?

What protein inhibits this transcription factor through ubiquination in non-hypoxic conditions?

A

HF-1α;

VHL

159
Q

Upon HF-1α mediated synthesis and release of EPO from the kidneys, what happens next?

A

EPO travels hematogenously to reach hematopoeitic stem cells in the bone marrow

–>

it binds JAK2 receptors (dimerization)

–>

JAK is phosphorlated

–>

STAT is phosphorlyated

–>

Erythrocyte differentiation is stimulated

160
Q

HF-1α is responsible for EPO synthesis in hypoxic conditions.

It also increases synthesis of what other signaling molecule?

A

VEGF

(vascular endothelial growth factor)

161
Q

What is a SNP?

A

A single nucleotide polymorphism

(allelic change)

162
Q

JAK-activating mutations result in what type of disorder?

A

Myeloproliferative neoplastic disorders

163
Q

What does the monoclonal antibody ending -‘zumab’ signify?

A

A humanized monoclonal antibody

164
Q

What does the monoclonal antibody ending -‘momab’ signify?

A

A fully murine (mouse) monoclonal antibody

165
Q

What does the monoclonal antibody ending -‘ximab’ signify?

A

A chimeric monoclonal antibody

166
Q

What does the monoclonal antibody ending -‘mumab’ signify?

A

A fully human monoclonal antibody

167
Q

Name the monoclonal antibody suffix for each of the following:

a chimeric monoclonal antibody

a fully murine (mouse) monoclonal antibody

a fully human monoclonal antibody

a humanized monoclonal antibody

A
  • ximab
  • momab
  • mumab
  • zumab

T1 - Integrated (Full Review) (29 decks)

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