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Hema1 > Erythrokinetics > Flashcards

Erythrokinetics Flashcards

1
Q

It is the term describing the dynamics of RBC production and destruction

A

Erythrokinetics

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2
Q

The collection of all stages of erythrocytes throughout the body

A

Erythron

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3
Q

When the term erythron is used, what does it conveys?

A

The concept of a unified functional tissue

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4
Q

Erythron is distinguished from?

A

RBC mass

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5
Q

It is the entirety of erythroid cells in the body

A

Erythron

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6
Q

Refers only to the cells in the circulation

A

RBC mass

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7
Q

The stimulus to RBC production

A

Hypoxia

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8
Q

Location of the primary O2-sensing system of the body

A

Peritubular fibroblasts of the kidney

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9
Q

The major stimulatory cytokine for RBCs

A

EPO

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10
Q

Approximately what percent of RBCs die normally each day

A

1%

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11
Q

Increased EPO is regulated by what transcription factor proteins?

A

hypoxia-inducible factore (HIFs)

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12
Q

How does HIFs respond to hypoxia?

A

HIFs binds to kidney hypoxia responsive elements located at the 5’ flanking region of the EPO gene

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13
Q

Structure of EPO

A

Thermostable
Nondialyzable
Glycoprotein hormone

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14
Q

What does EPO consist of?

A

Carbohydrate unit
Terminal sialic acid unit

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15
Q

True or false:

EPO is a true hormone, being produced at one loca- tion (kidney) and acting at a distant location (bone marrow)

A

True

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16
Q

EPO must bind to ____________ on the surface of EPO-responsive immature erythroid cells to initiate signal/message

A

Erythropoietin receptors

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17
Q

When RBC production needs to maintain a steady state erythropoiesis, the cells requiring only __________ of EPO respond

A

Low levels

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18
Q

A transmembrane protein homodimer with extracellular and cytoplasmic domains

A

EPOR

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19
Q

The binding of EPO to EPOR activates what signal transducers?

A

Janus activated tyrosine kinase 2 (JAK2)

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20
Q

3 major effects of EPO

A
  1. Allowing early release of reticulocytes from the BM
  2. Preventing apoptotic cell death
  3. Reducing the time needed for cells to mature in the BM
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21
Q

Cells that are release early from the bone marrow

A

Shift reticulocytes

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22
Q

second, and probably more important, mechanism by which EPO increases the number of circulating RBCs is by increasing the number of cells that will be able to mature into circulating erythrocytes.

A

Inhibition of apoptosis

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23
Q

How many days does it take to produce an RBC from stimulation of the BFU-E to release from the bone marrow?

A

18-21 days

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24
Q

is a sequential process characterized by, among other things, the degradation of chromatin into fragments of varying size that are multiples of 180 to 185 base pairs long; protein clustering; and activation of transgluta- mase.

25
During the sequential process of apoptosis, the following morphologic changes can be seen:
A. Condensation of the nucleus B. Nucleolar disintegration C. Shrinkage of cell volume with concomitant increase in cell density & compaction of cyyoplasmic organelles
26
Among the crucial molecules in the external messaging system is the ______________ on the membrane of the earliest erythroid precursors, whereas its ligand, ________, is expressed by more mature erythroid precursors.
Among the crucial molecules in the external messaging system is the death receptor Fas on the mem- brane of the earliest erythroid precursors, whereas its ligand, FasL, is expressed by more mature erythroid precursors.
27
Older FasL-bearing erythroid precursors cross-link with ______ which are stimulated to undergo apoptosis
Fas-marked immature erythroid precursors
28
Cell that has the most EPO receptors and is most sensitive to EPO rescue
CFU-E
29
Phosphorylates the STAT5 pathway, leading now to the production of antiapoptotic molecule
Activated JAK2
30
Antiapoptotic molecule produced by the activation the phosphorylation of STAT5 by activated JAK2
Bcl-XL (Bcl-2-like protein 1)
31
Transcription factor that mediates the effects of EPO
GATA1
32
The major way in which EPO increases RBC mass
Apoptosis rescue
33
EPO induces erythroid precursors to secrete __________, which acts on hepatocytes to decrease hepcidin production.
erythroferrone
34
Shift reticulocytes are also called?
Stress reticulocytes
35
Other stimuli to erythropoiesis
Testosterone Pituitary & thyroid hormone
36
This is the major method by which RBCs die normally.
Eryptosis
37
process of cellular aging
Senescence
38
Changes that occur as the RBC ages:
Alteration in the membrane Decreased ATP levels Increased Calcium Appearance f senescent antigen Decreased pH
39
RBC destruction outside blood vessel by splenic macrophage
Macrophage-Mediated Hemolysis (Extravascular Hemolysis)
40
90% of aged red cell destruction
Macrophage-Mediated Hemolysis (Extravascular Hemolysis)
41
Macrophage-Mediated Hemolysis (Extravascular Hemolysis) Serum:
1. ↑ total bilirubin and indirect (unconjugated) bilirubin 2. Slightly ↑ lactate dehydrogenase activity 3. Sightly ↓ haptoglobin and hemopexin 4. Slightly ↑ free hemoglobin
42
Macrophage-Mediated Hemolysis (Extravascular Hemolysis) Urine:
1. ↑ urobilinogen 2. Free hemoglobin: Negative 3. Methemoglobin: Negative
43
Spherocytes are often present Associated with Rh incompatibility
Macrophage-Mediated Hemolysis (Extravascular Hemolysis)
44
• RBC rupture within the blood vessel • 10% of aged red cell destruction • Schistocytes are often present • Associated with ABO incompatibility
Mechanical Hemolysis (Fragmentation or Intravascular Hemolysis)
45
Mechanical Hemolysis (Fragmentation or Intravascular Hemolysis) Serum:
1. ↑ total bilirubin and indirect (unconjugated) bilirubin 2. ↑ lactate dehydrogenase activity 3. ↓ haptoglobin and hemopexin 4. ↑ free hemoglobin
46
Mechanical Hemolysis (Fragmentation or Intravascular Hemolysis) Urine:
1. ↑ urobilinogen 2. Free hemoglobin: Positive 3. Methemoglobin: Positive
47
Mechanical Hemolysis (Fragmentation or Intravascular Hemolysis) Urine:
1. ↑ urobilinogen 2. Free hemoglobin: Positive 3. Methemoglobin: Positive
48
In intravascular hemolysis, the rupture of RBCs results in the release of RBC contents (particularly hemoglobin) which leads to the presence of ___________
free plasma hemoglobin
49
Three ways to salvage free plasma hemoglobin:
1. binding of haptoglobin to free plasma hemoglobin 2. Binding of hemopexin to metheme 3. Binding of metheme to albumin
50
Actions of Primary oxygen-sensing system
- Ability to sense whether there is adequate O2 supply to the tissues - they influence/trigger EPO production
51
Actions of Primary oxygen-sensing system
- Ability to sense whether there is adequate O2 supply to the tissues - they influence/trigger EPO production
52
Gene for EPO is located at
chromosome 7
53
regulates ↑ EPO production (due to hypoxia)
Hypoxia-inducible factors (HIFs)
54
EPO = _______ EPOR = ________
ligand receptor for EPO
55
EPO is mediated by
GATA1
56
→primary source of EPO
Kidneys (peritubular interstitial cells)
57
also secretes EPO (10%-15%) primary source of EPO in the unborn
Liver
58
Cellular aging in RBCs is mainly due to?
loss of glycolytic enzymes
59
Cellular aging in RBCs is mainly due to loss of glycolytic enzymes which leads to?
↓ ATP production along with ↓ amount of glucose.

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