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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.

A

Apoptosis

25
Q

During the sequential process of apoptosis, the following morphologic changes can be seen:

A

A. Condensation of the nucleus
B. Nucleolar disintegration
C. Shrinkage of cell volume with concomitant increase in cell density & compaction of cyyoplasmic organelles

26
Q

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.

A

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
Q

Older FasL-bearing erythroid precursors cross-link with ______ which are stimulated to undergo apoptosis

A

Fas-marked immature erythroid precursors

28
Q

Cell that has the most EPO receptors and is most sensitive to EPO rescue

A

CFU-E

29
Q

Phosphorylates the STAT5 pathway, leading now to the production of antiapoptotic molecule

A

Activated JAK2

30
Q

Antiapoptotic molecule produced by the activation the phosphorylation of STAT5 by activated JAK2

A

Bcl-XL
(Bcl-2-like protein 1)

31
Q

Transcription factor that mediates the effects of EPO

A

GATA1

32
Q

The major way in which EPO increases RBC mass

A

Apoptosis rescue

33
Q

EPO induces erythroid precursors to secrete __________, which acts on hepatocytes to decrease hepcidin production.

A

erythroferrone

34
Q

Shift reticulocytes are also called?

A

Stress reticulocytes

35
Q

Other stimuli to erythropoiesis

A

Testosterone
Pituitary & thyroid hormone

36
Q

This is the major method by which RBCs die normally.

A

Eryptosis

37
Q

process of cellular aging

A

Senescence

38
Q

Changes that occur as the RBC ages:

A

Alteration in the membrane
Decreased ATP levels
Increased Calcium
Appearance f senescent antigen
Decreased pH

39
Q

RBC destruction outside blood vessel by splenic
macrophage

A

Macrophage-Mediated Hemolysis (Extravascular
Hemolysis)

40
Q

90% of aged red cell destruction

A

Macrophage-Mediated Hemolysis (Extravascular
Hemolysis)

41
Q

Macrophage-Mediated Hemolysis (Extravascular
Hemolysis)

Serum:

A
  1. ↑ total bilirubin and indirect
    (unconjugated) bilirubin
  2. Slightly ↑ lactate dehydrogenase activity
  3. Sightly ↓ haptoglobin and hemopexin
  4. Slightly ↑ free hemoglobin
42
Q

Macrophage-Mediated Hemolysis (Extravascular
Hemolysis)

Urine:

A
  1. ↑ urobilinogen
  2. Free hemoglobin: Negative
  3. Methemoglobin: Negative
43
Q

Spherocytes are often present
Associated with Rh incompatibility

A

Macrophage-Mediated Hemolysis (Extravascular
Hemolysis)

44
Q

• RBC rupture within the blood vessel
• 10% of aged red cell destruction
• Schistocytes are often present
• Associated with ABO incompatibility

A

Mechanical Hemolysis (Fragmentation or
Intravascular Hemolysis)

45
Q

Mechanical Hemolysis (Fragmentation or
Intravascular Hemolysis)

Serum:

A
  1. ↑ total bilirubin and indirect (unconjugated) bilirubin
  2. ↑ lactate dehydrogenase activity
  3. ↓ haptoglobin and hemopexin
  4. ↑ free hemoglobin
46
Q

Mechanical Hemolysis (Fragmentation or
Intravascular Hemolysis)

Urine:

A
  1. ↑ urobilinogen
  2. Free hemoglobin: Positive
  3. Methemoglobin: Positive
47
Q

Mechanical Hemolysis (Fragmentation or
Intravascular Hemolysis)

Urine:

A
  1. ↑ urobilinogen
  2. Free hemoglobin: Positive
  3. Methemoglobin: Positive
48
Q

In intravascular hemolysis, the rupture of RBCs results in the release of RBC contents (particularly hemoglobin) which leads to the presence of ___________

A

free plasma hemoglobin

49
Q

Three ways to salvage free plasma hemoglobin:

A
  1. binding of haptoglobin to free plasma hemoglobin
  2. Binding of hemopexin to metheme
  3. Binding of metheme to albumin
50
Q

Actions of Primary oxygen-sensing system

A
  • Ability to sense whether there is adequate O2 supply to the tissues
  • they influence/trigger EPO production
51
Q

Actions of Primary oxygen-sensing system

A
  • Ability to sense whether there is adequate O2 supply to the tissues
  • they influence/trigger EPO production
52
Q

Gene for EPO is located at

A

chromosome 7

53
Q

regulates ↑ EPO production (due to hypoxia)

A

Hypoxia-inducible factors (HIFs)

54
Q

EPO = _______
EPOR = ________

A

ligand
receptor for EPO

55
Q

EPO is mediated by

A

GATA1

56
Q

→primary source of EPO

A

Kidneys (peritubular interstitial cells)

57
Q

also secretes EPO (10%-15%)
primary source of EPO in the unborn

A

Liver

58
Q

Cellular aging in RBCs is mainly due to?

A

loss of glycolytic enzymes

59
Q

Cellular aging in RBCs is mainly due to loss of glycolytic enzymes which leads to?

A

↓ ATP production along with
↓ amount of glucose.

Hema1 (3 decks)

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