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Hema 1 > Erythrokinetics > Flashcards

Erythrokinetics Flashcards

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1
Q

Dynamics of RBC production and destruction

A

Erythrokinetics

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2
Q

Collection of all stages of RBC throughout the body in the BM, PB, vascular spaces within organs

A

Erythron

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3
Q

The entirety of all erythroid cells (rbcs), whether it is
mature or immature

A

Erythron

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4
Q

refers only to the cells in circulation

A

RBC mass

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5
Q

a stimulus to RBC production

A

Hypoxia

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6
Q

main role of RBC

A

carry oxygen

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7
Q

It has the ability to sense adequacy of oxygen supply to tissues

A

Primary oxygen-sensing system

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8
Q

Location of primary oxygen-sensing system (be very specific)

A

Peritubular fibroblast of the kidney

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9
Q

Mechanism of POSS

A

Once inadequacy of O2 supply is detected, it triggers EPO production

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10
Q

Diminished or decrease of tissue oxygenation in our body

A

Hypoxia

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11
Q

Organ responsible in detecting oxygen adequacy in tissues

A

Kidney

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12
Q

Give 2 very important features of oxygen sensing system

A
  1. It has mechanism to detect inadequacy or adequacy if O2
  2. It has a mechanism that can influence or trigger the increase of RBC production by triggering EPO
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13
Q

Major stimulatory cytokine or stimulatory hematopoietic growth factor for RBCs

A

erythropoietin

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14
Q

most sensitive cell to EPO

A

Colony Forming Unit - E / CFU-E

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15
Q

erythroid progenitor cells that has the most EPOR

A

CFU-E

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16
Q

First human hematopoietic growth factor to be identified

A

Erythropoietin

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17
Q

Location of gene for EPO

A

Chromosome 7

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18
Q

it regulates the increase of EPO production as a response / physiologic adaptation to hypoxia

A

Hypoxia-Inducible Factors (HIFs)

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19
Q

EPO is found in the ff cells:

A

Erythroid Progenitor Cells (BFU-E and CFU-E)

Early erythroid precursor cells (Pronormoblast and Basophilic Normoblast)

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20
Q

Transcription factor that mediates EPO

A

GATA1

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21
Q

It serves as the primary source of EPO from newborn to adulthood / throughout life

A

Kidney

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22
Q

Specific part of the kidney where EPO in produced

A

peritubular insterstitial cells of kidney

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23
Q

It is primary source of EPO in the newborn

A

Liver

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24
Q

Complete the statement: EPO is a thermostable, nondialyzable, glycoprotein hormone that has ________ unit & _______ unit

A

carbohydrate ; terminal sialic acid

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25
Nice to know: molecular weight of EPO
34 kD
26
3 major actions of EPO in increasing RBC Production
1. It promotes early release of reticulocytes from the BM 2. MAJOR ACTION: Prevents apoptotic cell death 3. Reduces the time needed for cells to mature in the BM
27
Refers to reticulocytes released to the peripheral blood earlier than intended
Shift / stress reticulocye
28
In normal process, reticulocytes will stay in the BM for:
1-2 days or 2-3 days before released in circulation
29
In normal process, retics are in the circulation for a period of ___ before becoming RBCs
24 hrs / day
30
Location of developing cells in the BM
hematopoietic / extra vascular cords
31
developing blood cells are separated from the vascular sinuses by 2 layers of cells, namelyL
Adventitial Cells Endothelial Cells
32
What does the EPO does in the cells surrounding the developing RBCS in order to release shift reticulocytes
Conformational change that causes widening of spaces between the reticular adventitial cells
33
It secretes extracellular fluids that anchor developing cells
stromal cells
34
developing cells are arranged in their proper location by:
semi extracellular matrix
35
Adhesive molecule in charge of anchoring developing cells in their proper location
fibronectin
36
EPO's action to be able to release shift/stress retics despite of being anchored in the hematopoietic cord
down regulate or reduce the expression of receptors for adhesive molecules
37
Where are receptors for adhesive molecules found
membrane of reticulocytes
38
In cases where the body has increase RBC demand, the reticulocytes will be released in the circulation in _____, depending on the severity of the condition
less than 24 hours
39
these are cells with EPOR
Erythroid progenitor cells erythroid precursor cells
40
cells that respond to EPO in healthy circumstances
cells that are less sensitive to EPO
41
In case of hypoxia, what type of cells respond to EPO
cell that are highly sensitive to EPO
42
portion of EPOR where EPO binds
extracellular domain
43
binding of EPO to EPOR activates the signal transducer _____, which is associated with the cytoplasmic domain of EPOR
Janus Kinase 2 / JAK 2
44
After activation of JAK2, it will further cause the activation of diff. signal transduction pathways (STPs) going to the nucleus of the cell. One of which is the:
STAT5 Pathway / Signal transducer and activator of transcription 5
45
It bears the receptor
target cell
46
amount of RBC lost everyday
approximately 1%
47
Under normal conditions: Loss of 1% RBC Daily will result to EPO increase but only to _____
compensate
48
In severe anemia, the EPO production can increase ____ regardless of pathologic mechanism causing it
1,000-fold (1,000x)
49
EPO production fluctuates significantly or significantly increase particularly during:
hypoxic conditions or anemic stress
50
What happens to hypoxia-inducible factors in non hypoxic conditions / normal state
HIFs are being subsequently degraded because we do not need them
51
In hypoxic conditions, the one that senses / responds to it first is the:
Primary Oxygen Sensing System (POSS)
52
What happens to HIFs in hypoxic conditions?
HIFs will accumulate then will activate certain transcription genes that will promote response to adopt to hypoxic conditions
53
Binding of HIFs to EPO gene leads to
increased transcription of the EPO gene, leading to increase EPO protein production
54
Once the normal tissue oxygenation is restored back to normal, what will then happen?
The peritubular interstitial cells detects this which leads to degradation of HIFs = No HIFs to binds to EPO genes, EPO production decreases, RBC production decreases
55
other function of HIFs
enhance cellular iron intestinal absorption stimulate maturation and proliferation of erythroid progenitor cells
56
How to differentiate shift/stress reticulocyte from normal/typical reticulocytes?
Apply Wright stain. Normal polychromatic erythrocyte have pink as predominant and minimal blue. Shift retics are more baophilic
57
How long does it take for shift reticulocytes to mature in the circulation
24hrs (normal) + 48hrs = 72 hours / 3 days
58
What causes the basophilia of shift reticulocytes
Ribosomes and rRNA
59
Why can’t our body store RBCs?
All of RBCs must be in circulation because their primary function is to provide oxygen to tissues. We cannot store them because of their limited life spam of 120 days. In short, all of them will age and die.
60
Body’s compensatory mechanism in case of emergency since we cannot store RBCs
Produces excess colony forming unit E
61
Why our body produces excess CFU-E, and why not just BFU-E when it will also eventually mature into RBC?
CFU is more lineage restricted on what type of cell it will differentiate into
62
Fas is expresses on these cells
Erythroid progenitor cells such as the BFU and CFU and early erythroid precursor cells such as pronormoblast and basophilic normoblast
63
FAS L is expressed on these cells
More mature erythroid precursor cell such as the polychromatophilic normoblast, orthochromatophilic normoblast, and polychromatophilic erytheocytes
64
In normal state, how does apoptosis occur when extra RBCs are not needed?
Fas-L bearing erythroid precursor cells collide with those Fas-bearing erythroid precursor cells. Fas-L bearing (ligand) cells bind with the Fas bearing (receptor), signal will be created and received by the cells bearing the receptors, leading to its death
65
Give an example of anti-apoptotic molecule
BCL-XL
66
Where is BCL-XL produced and expressed
Mitochondrial membrane of the developing cell
67
Why is BCL-XL, an apoptotic molecule, expressed on the “mitochondrial membrane” of the developing cell
The mitochondria is capable of producing apoptotic substance, named “CYTOCHROME C”. We have to prevent release of this substance in exchange of apoptosis
68
G0 is also known as
Resting phase
69
G1 is also known as
Cell growth phase
70
How does EPO reduces the time needed for cells to mature in the BM?
cytokine (EPO) decreases the transmit time from G0 (resting phase) to G1 (cell growth phase), for faster cell division or mitosis, thus increasing the rate of normoblastic proliferation.
71
Erythrocyte destruction is termed as
Eryptosis
72
Process of cellular aging is termed as
Senescence

Hema 1 (2 decks)

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