Chapter 5 ERYTHROKINETICS

Question 1

dynamics of RBC production and destruction

Answer 1

Erythrokinetics

Question 2

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

Answer 2

Erythron

Question 3

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

Answer 3

spleen

Question 4

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

Answer 4

unified functional tissue

Question 5

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

Answer 5

RBC mass

Question 6

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

Answer 6

enhanced

Question 7

primary oxygen-sensing system of the body is located in

Answer 7

peritubular fibroblasts of the kidney

Question 8

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

Answer 8

Hypoxia

Question 9

major stimulatory cytokine for RBCs

Answer 9

erythropoietin (EPO)

Question 10

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

Answer 10

hemorrhage

Question 11

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

Answer 11

hypoxiainducible factors (HIFs)

Question 12

Erythropoietin: Structure

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

Answer 12

34 kD

Question 13

Erythropoietin: Structure

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

Answer 13

carbohydrate unit and a terminal sialic acid unit

Question 14

Erythropoietin: Action

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

Answer 14

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

Question 15

Erythropoietin: Action

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

Answer 15

signal transduction

Question 16

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

Answer 16

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

Question 17

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

Answer 17

Janusactivated tyrosine kinase 2 (JAK2)

Question 18

EPO has three major effects:

Answer 18

(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.

Question 19

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.

Answer 19

Early release of reticulocytes

Question 20

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

Answer 20

shift reticulocytes

Question 21

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

Answer 21

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

Question 22

decreasing apoptosis, the programmed death of RBC progenitors

Answer 22

Inhibition of apoptosis

Question 23

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

Answer 23

Apoptosis: programmed cell death

Question 24

instead of storing mature cells for emergencies

Answer 24

body produces more CFU-Es than needed at all times

Question 25

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

Answer 25

increased demand for RBCs

Question 26

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

Answer 26

Apoptosis

Question 27

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

Answer 27

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

Question 28

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

Answer 28

last stage of degradation

Question 29

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

Answer 29

Evasion of apoptosis by erythroid progenitors and precursors

Question 30

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

Answer 30

EPO levels are low

Question 31

A second mechanism for escaping apoptosis exists for erythroid progenitors:

Answer 31

direct EPO rescue from apoptosis

Question 32

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

Answer 32

EPO

Question 33

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

Answer 33

GATA1

Question 34

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

Answer 34

Reduced marrow transit time

Question 35

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

Answer 35

erythroferrone

Question 36

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

Answer 36

stress reticulocytes

Question 37

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

Answer 37

reducing individual cell cycle time

Question 38

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

Answer 38

only about 1 day by this effect

Question 39

EPO can be measured by

Answer 39

chemiluminescence

Question 40

sufficient to maintain steady-state erythropoiesis in a healthy adult

Answer 40

10 to 30 U/L

Question 41

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.

Answer 41

Recombinant EPO

Question 42

The use of EPO is one of the methods of

Answer 42

blood doping

Question 43

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

Answer 43

arterial and venous thrombosis

Question 44

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

Answer 44

testosterone

Question 45

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

Answer 45

pituitary and thyroid hormones

Question 46

essential to hematopoiesis

Answer 46

cytokines

Question 47

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

Answer 47

Hematopoiesis

Question 48

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

Answer 48

Erythropoiesis

Question 49

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

Answer 49

hemoglobin

Question 50

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

Answer 50

Macrophages

Question 51

There are three components to the anchoring system:

Answer 51

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

Question 52

major cellular anchor for the developing normoblasts

Answer 52

macrophage

Question 53

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

Answer 53

fibronectin

Question 54

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

Answer 54

ERYTHROCYTE DESTRUCTION

Question 55

mature erythrocyte is unable to generate new proteins, such as

Answer 55

enzymes

Question 56

as its cellular functions decline, the cell ultimately approaches

Answer 56

death

Question 57

average RBC has sufficient enzyme function to live

Answer 57

120 days

Question 58

RBCs lack mitochondria, they rely on glycolysis for production of

Answer 58

adenosine triphosphate (ATP)

Question 59

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

Answer 59

senescence

Question 60

senescence culminates in phagocytosis by

Answer 60

macrophages

Question 61

The pH is low, which promotes

Answer 61

iron oxidation

Question 62

In this hostile environment, aged RBCs succumb to various

Answer 62

stresses

Question 63

leads to oxidation of membrane lipids and proteins

Answer 63

Lack of ATP

Question 64

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

Answer 64

splenic sieve

Question 65

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

Answer 65

splenic sieve

Question 66

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

Answer 66

Spherical RBCs

Question 67

erythrocyte death as a nonnucleated cell version of apoptosis, termed

Answer 67

eryptosis

Question 68

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

Answer 68

eryptosis

Question 69

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

Answer 69

heme

Question 70

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

Answer 70

fragmentation or intravascular hemolysis

Question 71

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

Answer 71

urine

Question 72

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

Answer 72

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

Question 73

Hypoxia of peripheral blood is detected by the

Answer 73

peritubular fibroblasts of the kidney

Question 74

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

Answer 74

EPO

Question 75

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

Answer 75

peritubular fibroblasts of the kidney

Question 76

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

Answer 76

Apoptosis

Question 77

the death receptor, is expressed by young erythroid precursors

Answer 77

Fas

Question 78

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

Answer 78

fibronectin, and cytokines that are secreted by macrophages

Question 79

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

Answer 79

erythroid precursors mature

Question 80

semipermeable membrane becomes more permeable to water, so the cells

Answer 80

swell and become spherocytic and rigid

Question 81

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

Answer 81

splenic sieve

Question 82

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.

Answer 82

Extravascular or macrophage mediated hemolysis

Question 83

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

Answer 83

Fragmentation or intravascular hemolysis