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HEMATOLOGY 1 > Erythrokinetics > Flashcards

Erythrokinetics Flashcards

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
Q

shift in the release of the reticulocyte is termed as

A

Shift Reticulocyte

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26
Q

Called as _____________ because
in the event of physiological stress, such
as anemic stress, the body requires
increased production of RBCs.

A

Stress Reticulocytes

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27
Q

How does EPO force the release of
reticulocytes from the hematopoietic
cords?

A
  • 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
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28
Q

Two Mechanisms of EPO in Promoting Early Release of Reticulocytes

A
  1. Creates conformational change in the adventitial cell layer
  2. Down regulates the receptor for adhesive molecules located in the membrane of developing cells
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29
Q

an adhesive molecule, is a composition of ECM secreted by stromal cells which anchors developing cells. This holds EPO in place.

A

Fibronectin

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30
Q

Mechanism to prevent apoptosis by EPO:

A
  1. Indirect Avoidance of Apoptosis
  2. Direct Avoidance of Apoptosis
  3. Induces production of anti-apoptotic molecule
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31
Q

two proteins needed to facilitate cell death:

A
  • fasL (ligand)
  • fas (receptor)
32
Q

located or expressed by more mature erythroid precursor cells (polychromatophilic
normoblast, orthochromic normoblast, and polychromatophilic erythrocyte)

A

fasL

33
Q

located or expressed by younger erythroid
precursor cells (pronormoblast and basophilic normoblast)

A

fas

34
Q

How does Indirect Avoidance of Apoptosis of EPO happens?

A

● depletes the number of mature erythroid
precursor cells from bone marrow by promoting early release of these cells expressing fasL

35
Q

lack of ____ inhibits apoptosis of fas-bearing
receptors among younger cells.

A

fasL

36
Q

● 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

A

Direct Avoidance of Apoptosis

37
Q

Expressed anti-apoptotic molecules prevent the release of ______________

A

cytochrome C

38
Q

initiator of apoptosis in the cell

A

cytochrome C

39
Q

Activation of ______ activates the _______________ which produces anti-apoptotic molecules in cells bearing EPOR.

A

JAK-2 ; STAT5 pathway

40
Q

Does hastened process of maturation affect the quality of the cells?

A

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
Q

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.

A

Premature reticulocytes

42
Q

Erythrocyte Destruction

A

Eryptosis

43
Q

process of cellular aging

A

Senescence

44
Q

Changes that occur as the RBC ages:

A

● 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
Q

Because RBCs lack mitochondria, they rely on
___________ which are needed for glycolysis (anaerobic pathway) for. production of adenosine triphosphate (ATP).

A

glycolytic enzymes

46
Q

As the RBC mature/ages, the glycolytic
enzymes become exhausted, hence ____
is also depleted

A

ATP

47
Q

uncontrolled movement of calcium inside the cell

A

calcium influx

48
Q

Example of enzyme that regulate the concentration and movement of cations in and out of the cell

A

Calcium ATPase

49
Q

Once there is a calcium influx, the cell will lose its

A

deformability or flexibility

50
Q

The acidic pH will now promotes oxidation of iron (ferrous to ferric), hence _________ is formed which is incapable of transporting oxygen

A

methemeglobin

51
Q

2 Ways in which RBC is Damaged
(RBC being destroyed in the process is
NORMAL, aged RBC must be removed
from the circulation)

A

Macrophage-Mediated Hemolysis (Extravascular Hemolysis)

Mechanical Hemolysis (Fragmentation or
Intravascular Hemolysis)

52
Q

 RBC destruction outside blood vessel by splenic macrophage
 90% aged red cell destruction

A

Macrophage-Mediated Hemolysis

53
Q

 ↑ Unconjugated bilirubin, Urine/fecal
urobilinogen
 Spherocytosis, RH incompatibility

A

Macrophage-Mediated Hemolysis

54
Q

 RBC rupture within the blood vessel
 10% aged red cell destruction

A

Mechanical Hemolysis

55
Q

 ↓ Haptoglobin, Hemopexin
 Schistocytes
 ABO incompatibility

A

Mechanical Hemolysis

56
Q

An increased in hemolysis extravascularly, will result to increased release of the protoporphyrin ring will be metabolized into

A

Bilirubin

57
Q

spherocytes are present in this hemolysis

A

Extravascular Hemolysis

58
Q

Major site of RBC destruction is the

A

red pulp of the spleen

59
Q

serve as the major site of production after your RBC is being damaged due to normal aging

A

Spleen

60
Q

serve as active site of RBC
destruction specifically for those RBC
that are severely damaged

A

Liver

61
Q

Volume of blood that circulates in the
spleen is approximately

A

350ml

62
Q

Movement through the red pulp is
usually

A

sluggish

63
Q

In extravascular hemolysis, the available glucose in the surrounding blood is
depleted quickly as cell flow stagnates causing

A

slow down of glycolysis

64
Q

RBC utilizes ______________ in order to generate ATP.

A

plasma glucose

65
Q

e responsible for maintaining the high level of intracellular potassium while pumping sodium out of the cells

A

Sodium Potassium pump

66
Q

IN Extravascular Hemolysis, The discoid shape is lost and the cell becomes a

A

Spheroid (Spherocytes)

67
Q

the ability of cells to pass through narrow capillaries or small splenic spores that are even smaller than the size of RBC

A

Deformability

68
Q

When an RBC lyses within a macrophage, _____ is removed from the heme. It can be stored in the macrophage as ______

A

Iron ; ferritin

69
Q

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.

A

protoporphyrin

70
Q

Fragmented cells are called

A

Schistocytes

71
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

72
Q

❖ Three ways to salvage free plasma
hemoglobin:

A
  1. binding of haptoglobin to free plasma hemoglobin
  2. binding of hemopexin to metheme
  3. metheme binds to albumin
73
Q

binding of haptoglobin to free plasma hemoglobin will form

A

haptoglobin-Hb complex

74
Q

Heme portion of methemoglobin is
called

A

metheme/hemin

75
Q

When hemopexin is not yet available, metheme binds to

A

albumin

HEMATOLOGY 1 (12 decks)

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