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HEMATOLOGY 1 > Erythrokinetics > Flashcards

Erythrokinetics Flashcards

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1
Q

Collection of all stages of
RBC throughout the body in the
bone marrow, peripheral blood,
vascular spaces within organs

A

Erythron

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2
Q

All RBCs regardless of their stage
throughout the body

A

Erythron

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3
Q

refers only to the cells in circulation

A

RBC Mass

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4
Q

STIMULUS TO RED BLOOD CELL PRODUCTION

A

Hypoxia

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5
Q

Location of the Primary oxygen-sensing system

A

Peritubular fibroblast of the kidney

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6
Q

Peritubular fibroblast is also known as
___________________ because they are primarily located in the interstitium of the kidney.

A

Peritubular interstitial cells

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7
Q

Actions of Primary oxygen-sensing System

A

Ability to sense whether
there is adequate O2 supply to the
tissues (particularly in kidney); once
inadequacy of O2 supply is
detected, they influence/trigger
EPO production

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8
Q

Two important functions of the primary
oxygen-sensing system

A

To sense inadequacy in oxygen

Subsequently influence or stimulate EPO Production

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9
Q

First human hematopoietic
growth factor to be identified

A

Erythropoietin

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10
Q

Gene for EPO is located at

A

chromosome 7

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11
Q

EPO is regulated by

A

Hypoxia-inducing Factors (HIFs)

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12
Q

How does hypoxia influence EPO
production?

A
  1. Once there is hypoxia, HIFs bind with the EPO gene.
  2. Binding of HIFs and EPO gene results in the transcription of EPO gene to EPO encoding and
    production.
  3. After EPO production, EPO is secreted by peritubular fibroblasts
  4. Secreted EPO binds with EPOR through the extracellular domains. Once it binds, there occurs conformational change in the receptor.
  5. Once conformational change in the receptor happens, it activates Janus Activated Kinase 2 (JAK-2) signal transducer
  6. Once JAK-2 is activated, it activates the signal transduction pathway and STAT5 pathway which results to transcription of specific genes in nucleus, enabling erythroid progenitor to differentiate or younger erythroid precursor cells to mature.
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13
Q

How does EPO influence RBC
production?

A
  • For every ligand (substance that
    binds to the receptor), there is a
    corresponding receptor. Hence,
    for every EPO receptor (EPOR),
    there is a corresponding EPO ligand
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14
Q

Two domains of EPOR

A

Extracellular and Cytoplasmic domain

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15
Q

EPO activates this signal transducer located in the cytoplasmic domain of EPOR

A

Janus Activated Kinase 2 (JAK-2)

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16
Q

It is activated by JAK-2

A

Signal transduction and STAT5 pathway

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17
Q

Mediates the EPO (an intrinsic factor)

A

GATA1

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18
Q

EPO is produced primarily by

A

primarily in the kidneys (peritubular interstitial cells) in adult

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19
Q

Produced also EPO but in minimum amount

A

Liver

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20
Q

Structure of EPO

A

Thermostable, nondialyzable

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21
Q

Liver is a primary source of EPO in the glycoprotein hormone that has

A

carbohydrate unit and terminal sialic acid

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22
Q

Actions of EPO

A

■ Promotes early release of reticulocytes from the BM (SHIFT/ STRESS RETICS)
■ Preventing apoptosis cell death (major), thereby increasing the number of cells that will be able to mature into circulating RBCs
■ Reducing the time needed for cells to mature in the BM (↑ rate of cellular processes, ↓ cell cycle times)

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23
Q

How many days does Reticulocyte stay in the BM prior to their release?

A

1-2 days

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24
Q

Once Reticulocyte is in the Circulation, how many hours will it take to mature?

A

24 hours

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25
shift in the release of the reticulocyte is termed as
Shift Reticulocyte
26
Called as _____________ because in the event of physiological stress, such as anemic stress, the body requires increased production of RBCs.
Stress Reticulocytes
27
How does EPO force the release of reticulocytes from the hematopoietic cords?
- Reticular adventitial cells and endothelial cells - layer of cells that serves as barrier that separates the developing cells in the hematopoietic cords from that of the vascular sinuses. - The developing cells must go through the layers of cells before going to the circulation from the bone marrow
28
Two Mechanisms of EPO in Promoting Early Release of Reticulocytes
1. Creates conformational change in the adventitial cell layer 2. Down regulates the receptor for adhesive molecules located in the membrane of developing cells
29
an adhesive molecule, is a composition of ECM secreted by stromal cells which anchors developing cells. This holds EPO in place.
Fibronectin
30
Mechanism to prevent apoptosis by EPO:
1. Indirect Avoidance of Apoptosis 2. Direct Avoidance of Apoptosis 3. Induces production of anti-apoptotic molecule
31
two proteins needed to facilitate cell death:
- fasL (ligand) - fas (receptor)
32
located or expressed by more mature erythroid precursor cells (polychromatophilic normoblast, orthochromic normoblast, and polychromatophilic erythrocyte)
fasL
33
located or expressed by younger erythroid precursor cells (pronormoblast and basophilic normoblast)
fas
34
How does Indirect Avoidance of Apoptosis of EPO happens?
● depletes the number of mature erythroid precursor cells from bone marrow by promoting early release of these cells expressing fasL
35
lack of ____ inhibits apoptosis of fas-bearing receptors among younger cells.
fasL
36
● reduced production of fasL in more mature erythroid precursor cells to inhibit apoptosis thus the younger cells avoid the apoptotic signal from the older cells
Direct Avoidance of Apoptosis
37
Expressed anti-apoptotic molecules prevent the release of ______________
cytochrome C
38
initiator of apoptosis in the cell
cytochrome C
39
Activation of ______ activates the _______________ which produces anti-apoptotic molecules in cells bearing EPOR.
JAK-2 ; STAT5 pathway
40
Does hastened process of maturation affect the quality of the cells?
No, there are no general consequences to the quality of the cells since they still follow the process only that it is sped up.
41
have more basophilic cytoplasm because their stay in the bone marrow is not enough to dismantle organelles, amount of rRNA, as well as the basophilia of cytoplasm.
Premature reticulocytes
42
Erythrocyte Destruction
Eryptosis
43
process of cellular aging
Senescence
44
Changes that occur as the RBC ages:
● Alteration in the membrane – loss of sialic acid and lipids ● ↓ ATP levels – due to loss of glycolytic enzymes** ● ↑ calcium ● Appearance of senescent antigen – which makes RBCs more susceptible to destruction ● ↓ pH – promotes iron oxidation
45
Because RBCs lack mitochondria, they rely on ___________ which are needed for glycolysis (anaerobic pathway) for. production of adenosine triphosphate (ATP).
glycolytic enzymes
46
As the RBC mature/ages, the glycolytic enzymes become exhausted, hence ____ is also depleted
ATP
47
uncontrolled movement of calcium inside the cell
calcium influx
48
Example of enzyme that regulate the concentration and movement of cations in and out of the cell
Calcium ATPase
49
Once there is a calcium influx, the cell will lose its
deformability or flexibility
50
The acidic pH will now promotes oxidation of iron (ferrous to ferric), hence _________ is formed which is incapable of transporting oxygen
methemeglobin
51
2 Ways in which RBC is Damaged (RBC being destroyed in the process is NORMAL, aged RBC must be removed from the circulation)
Macrophage-Mediated Hemolysis (Extravascular Hemolysis) Mechanical Hemolysis (Fragmentation or Intravascular Hemolysis)
52
 RBC destruction outside blood vessel by splenic macrophage  90% aged red cell destruction
Macrophage-Mediated Hemolysis
53
 ↑ Unconjugated bilirubin, Urine/fecal urobilinogen  Spherocytosis, RH incompatibility
Macrophage-Mediated Hemolysis
54
 RBC rupture within the blood vessel  10% aged red cell destruction
Mechanical Hemolysis
55
 ↓ Haptoglobin, Hemopexin  Schistocytes  ABO incompatibility
Mechanical Hemolysis
56
An increased in hemolysis extravascularly, will result to increased release of the protoporphyrin ring will be metabolized into
Bilirubin
57
spherocytes are present in this hemolysis
Extravascular Hemolysis
58
Major site of RBC destruction is the
red pulp of the spleen
59
serve as the major site of production after your RBC is being damaged due to normal aging
Spleen
60
serve as active site of RBC destruction specifically for those RBC that are severely damaged
Liver
61
Volume of blood that circulates in the spleen is approximately
350ml
62
Movement through the red pulp is usually
sluggish
63
In extravascular hemolysis, the available glucose in the surrounding blood is depleted quickly as cell flow stagnates causing
slow down of glycolysis
64
RBC utilizes ______________ in order to generate ATP.
plasma glucose
65
e responsible for maintaining the high level of intracellular potassium while pumping sodium out of the cells
Sodium Potassium pump
66
IN Extravascular Hemolysis, The discoid shape is lost and the cell becomes a
Spheroid (Spherocytes)
67
the ability of cells to pass through narrow capillaries or small splenic spores that are even smaller than the size of RBC
Deformability
68
When an RBC lyses within a macrophage, _____ is removed from the heme. It can be stored in the macrophage as ______
Iron ; ferritin
69
The ___________ component of heme is degraded through several intermediaries to bilirubin, which is released into the blood and ultimately excreted by the liver in bile.
protoporphyrin
70
Fragmented cells are called
Schistocytes
71
❖ 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
72
❖ Three ways to salvage free plasma hemoglobin:
1. binding of haptoglobin to free plasma hemoglobin 2. binding of hemopexin to metheme 3. metheme binds to albumin
73
binding of haptoglobin to free plasma hemoglobin will form
haptoglobin-Hb complex
74
Heme portion of methemoglobin is called
metheme/hemin
75
When hemopexin is not yet available, metheme binds to
albumin

HEMATOLOGY 1 (12 decks)

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