Chapter 5 ERYTHROKINETICS Flashcards

1
Q

dynamics of RBC production and destruction

A

Erythrokinetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

name given to the collection of all stages of erythrocytes throughout the body

A

Erythron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

the developing precursors in the bone marrow and the circulating erythrocytes in the peripheral blood and vascular spaces within organs, such as the

A

spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When the term erythron is used, it conveys the concept of a
The erythron is the entirety of erythroid cells in the body

A

unified functional tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The erythron is distinguished and refers only to the cells in circulation

A

RBC mass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

If tissue oxygen is inadequate, RBC production and the functional efficiency of existing cells must be

A

enhanced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

primary oxygen-sensing system of the body is located in

A

peritubular fibroblasts of the kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

too little tissue oxygen, is detected by the peritubular fibroblasts, which then produce erythropoietin (EPO)

A

Hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

major stimulatory cytokine for RBCs

A

erythropoietin (EPO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

increased RBC destruction, or other factors that diminish the oxygen-carrying capacity of the blood, the production of EPO is increased

A

hemorrhage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Increased EPO production, caused by hypoxia, is regulated by a family of transcription factor proteins, called

A

hypoxiainducible factors (HIFs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Erythropoietin: Structure

EPO is a thermostable, nondialyzable, glycoprotein hormone with a molecular weight of

A

34 kD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Erythropoietin: Structure

both of which play a role in the biologic activity of the hormone

A

carbohydrate unit and a terminal sialic acid unit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Erythropoietin: Action

EPO is a true hormone, being produced at one location and acting at a distant location

A

one location (kidney) and acting at a distant location (bone marrow)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Erythropoietin: Action

It is a growth factor (or cytokine) that initiates an intracellular message to the developing erythroid cells; this process is called

A

signal transduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The interaction of EPO with its receptor initiates a cascade of intracellular events that ultimately leads to increased cell division and maturation

A

increased intestinal iron absorption and hemoglobin synthesis, and more RBCs entering the circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

signal transducers that are associated with the cytoplasmic domains of the EPO receptor

A

Janusactivated tyrosine kinase 2 (JAK2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

EPO has three major effects:

A

(1) allowing early release of reticulocytes from the bone marrow,
(2) preventing apoptotic cell death, and
(3) reducing the time needed for cells to mature in the bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

EPO induces changes in the adventitial cell layer of the bone marrow/sinus barrier that increase the width of the spaces for RBC egress into the sinus.

A

Early release of reticulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

reticulocytes that are still very basophilic because they have not spent as much time degrading their ribosomes and RNA or making hemoglobin as they normally would before entering the bloodstream. These are called
because they have been shifted from the bone marrow early

A

shift reticulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

can be released early in cases of extreme anemia when the demand for RBCs in the peripheral circulation is great

A

nucleated RBCs (i.e., erythroblasts or normoblasts)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

decreasing apoptosis, the programmed death of RBC progenitors

A

Inhibition of apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

18 to 21 days to produce an RBC from stimulation of the earliest erythroid progenitor (BFU-E) to release from the bone marrow

A

Apoptosis: programmed cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

instead of storing mature cells for emergencies

A

body produces more CFU-Es than needed at all times

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

the erythroid progenitors have about an 8- to 10-day head start in the production process

A

increased demand for RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

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

not associated with inflammation

A

Apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

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

A

condensation of the nucleus,
causing increased basophilic staining of the chromatin;
nucleolar disintegration; and
shrinkage of cell volume with concomitant increase in cell density and compaction of cytoplasmic organelles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

produces nuclear DNA fragments consisting of multimers of 180 to 185 base pair segments

A

last stage of degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

many erythroid progenitors will undergo apoptosis
One effect of EPO is an indirect avoidance of apoptosis by removing an apoptosis induction signal

A

Evasion of apoptosis by erythroid progenitors and precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

cell production should be at a low rate because hypoxia is not present. The excess early erythroid
precursors should undergo apoptosis

A

EPO levels are low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

A second mechanism for escaping apoptosis exists for erythroid progenitors:

A

direct EPO rescue from apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

able to stimulate production of various antiapoptotic molecules, which allows the cell to survive and mature

A

EPO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

EPO’s effect is mediated by the transcription
factor, _____ which is essential to red cell survival

A

GATA1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Apoptosis rescue is the major way in which EPO increases RBC mass, that is by increasing the number of erythroid cells that survive and mature to enter the circulation

A

Reduced marrow transit time

35
Q

EPO induces erythroid precursors to secrete ______
which acts on hepatocytes to decrease hepcidin production. This allows more iron to be absorbed
from the intestines to support the increased hemoglobin synthesis

A

erythroferrone

36
Q

These shift reticulocytes are also called
because they exit the marrow early during conditions of bone marrow “stress,” such as in certain anemias

A

stress reticulocytes

37
Q

PO also can reduce the time it takes for cells to mature in the bone marrow by

A

reducing individual cell cycle time

38
Q

This effect is only about a 20% reduction, however, so that the normal transit time in the marrow of approximately 6 days from pronormoblast to erythrocyte can be shortened by

A

only about 1 day by this effect

39
Q

EPO can be measured by

A

chemiluminescence

40
Q

sufficient to maintain steady-state erythropoiesis in a healthy adult

A

10 to 30 U/L

41
Q

used as therapy in certain anemias such as those associated with chronic kidney disease and chemotherapy. It is also used to stimulate RBC production before autologous blood donation
and after bone marrow transplantation.

A

Recombinant EPO

42
Q

The use of EPO is one of the methods of

A

blood doping

43
Q

aside from being banned in organized sports events, it increases the RBC count and blood viscosity to dangerously high levels and can lead to fatal

A

arterial and venous thrombosis

44
Q

directly stimulates erythropoiesis, which partially explains the higher hemoglobin concentration in men than in women

A

testosterone

45
Q

have been found to affect the production of EPO and so have indirect effects on erythropoiesis

A

pituitary and thyroid hormones

46
Q

essential to hematopoiesis

A

cytokines

47
Q

occurs in marrow cords, essentially a loose arrangement of cells outside a dilated sinus area between the arterioles that feed the bone and the central vein that returns blood to efferent veins

A

Hematopoiesis

48
Q

erythroid islands within the bone marrow. These islands consist of a central macrophage surrounded by erythroid precursors

A

Erythropoiesis

49
Q

central macrophages provided iron directly to the normoblasts for the synthesis of

A

hemoglobin

50
Q

are now known to elaborate cytokines that are vital to the maturation process of erythroid precursors and to phagocytize expelled nuclei

A

Macrophages

51
Q

There are three components to the anchoring system:

A

stable matrix of accessory and stromal cells to which normoblasts can attach, bridging (adhesive) molecules for that attachment, and receptors on the normoblast membrane.

52
Q

major cellular anchor for the developing normoblasts

A

macrophage

53
Q

normoblasts are anchored to the extracellular matrix of the bone marrow, chiefly by

A

fibronectin

54
Q

Most cells are able to replenish needed enzymes and continue their cellular processes.

A

ERYTHROCYTE DESTRUCTION

55
Q

mature erythrocyte is unable to generate new proteins, such as

A

enzymes

56
Q

as its cellular functions decline, the cell ultimately approaches

A

death

57
Q

average RBC has sufficient enzyme function to live

A

120 days

58
Q

RBCs lack mitochondria, they rely on glycolysis for production of

A

adenosine triphosphate (ATP)

59
Q

The loss of glycolytic enzymes is central to this process of cellular aging, called

A

senescence

60
Q

senescence culminates in phagocytosis by

A

macrophages

61
Q

The pH is low, which promotes

A

iron oxidation

62
Q

In this hostile environment, aged RBCs succumb to various

A

stresses

63
Q

leads to oxidation of membrane lipids and proteins

A

Lack of ATP

64
Q

RBCs must remain highly flexible to exit the spleen by squeezing through the so-called

A

splenic sieve

65
Q

formed by the endothelial cells lining the venous sinuses and the basement membrane

A

splenic sieve

66
Q

are rigid and are not able to squeeze through the narrow spaces

A

Spherical RBCs

67
Q

erythrocyte death as a nonnucleated cell version of apoptosis, termed

A

eryptosis

68
Q

precipitated by oxidative stress, energy depletion, and other mechanisms that create membrane signals that stimulate phagocytosis

A

eryptosis

69
Q

When an RBC lyses within a macrophage, the major components are catabolized. Iron is removed from the

A

heme

70
Q

intravascular rupture of RBCs from purely mechanical or traumatic stress results in fragmentation and release of the cell contents into the blood; this is called

A

fragmentation or intravascular hemolysis

71
Q

the body still has a system of plasma proteins, including haptoglobin and hemopexin, to salvage the released hemoglobin so that its iron is not lost in the

A

urine

72
Q

morphologically identifiable precursors of mature RBCs in order from youngest to oldest, are the

A

pronormoblast, basophilic normoblast, polychromatic normoblast, orthochromic normoblast, and polychromatic erythrocyte or reticulocyte.

73
Q

Hypoxia of peripheral blood is detected by the

A

peritubular fibroblasts of the kidney

74
Q

primary hormone that stimulates the production of erythrocytes, is able to rescue the CFU-E from apoptosis

A

EPO

75
Q

which upregulates transcription of the EPO gene to increase the production of erythropoietin (EPO)

A

peritubular fibroblasts of the kidney

76
Q

mechanism by which an appropriate normal production level of RBCs is controlled

A

Apoptosis

77
Q

the death receptor, is expressed by young erythroid precursors

A

Fas

78
Q

survival of erythroid precursors in the bone marrow
depends on adhesive molecules, such as

A

fibronectin, and cytokines that are secreted by macrophages

79
Q

they lose adhesive molecule receptors, which allows their egress from the bone marrow

A

erythroid precursors mature

80
Q

semipermeable membrane becomes more permeable to water, so the cells

A

swell and become spherocytic and rigid

81
Q

They become trapped in the _________, where they are readily phagocytized by macrophages.

A

splenic sieve

82
Q

accounts for most normal RBC death. The signals to macrophages that initiate RBC ingestion may include binding of autologous immunoglobulin G (IgG), expression of phosphatidylserine on the outer membrane, cation balance changes, and binding of CD47 to thrombospondin-1.

A

Extravascular or macrophage mediated hemolysis

83
Q

results when mechanical factors rupture the cell membrane while the cell is in the peripheral circulation. This pathway accounts for a minor component of normal destruction of RBCs

A

Fragmentation or intravascular hemolysis