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Hematology > 1. Normal Blood Components, Production And Erythrocytes > Flashcards

1. Normal Blood Components, Production And Erythrocytes Flashcards

1
Q

What is included in the hematopoiesis system?

A

Bone marrow, liver, spleen, thymus, and lymph nodes

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2
Q

What are three cells maintained by hematopoiesis?

A

Erythropoiesis- production of erythrocytes
Leukopoiesis - production of leukocytes
Thrombopoiesis - production of thrombocytes

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3
Q

What are Myeloid cells?

A

Blood cells that are normally produced in the bone marrow. Include, erythrocytes, platelets, neutrophils, eosinophils, basophils, and monocytes .

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4
Q

What are non-Myeloid cells?

A

Cells produced outside the marrow. Include, lymphocytes.

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5
Q

What is medullary hematopoiesis?

A

Production of myeloid cells in the bone marrow

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6
Q

What is extra-medullary hematopoiesis?

A

Production of myeloid cells outside the bone marrow, usually in spleen or liver. Normal in a fetus, abnormal in adults.

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7
Q

Name the three phases of hematopoiesis.

A

Mesoblastic Phase
Hepatic phase
Myeloid phase

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8
Q

What is red marrow?

A

Active marrow, has active cells and fat in it.

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9
Q

What happens in the mesoblasic phase?

A

2nd - 12th week of gestation

Primitive blood stem cells are formed in embryo and yolk sac
By the end of the 4th week blood vessels and heart grows, pumping blood cells

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10
Q

What happens in the hepatic phase?

A

6th week of gestation - 2 weeks postpartum

Liver and spleen involved in production
Lymph nodes begin producing large amounts of lymphocytes
Bone and bone marrow begins to form at 8 weeks

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11
Q

What happens in the myeloid phase?

A

20th week of gestation - death

Lymph nodes continue to produce lymphocytes
All other blood cells now produced in the marrow
Liver and spleen retain the ability for hematopoiesis but are inactive

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12
Q

What is hematopoiesis?

A

Production and development of blood cells, characterized by the constant restoration of cells in the blood.

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13
Q

Where are the production locations for myeloid cells?

A

Anterior and posterior iliac crests of pelvis
Sternum
Proximal ends of long bones
Spinous processes of the vertebrae

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14
Q

What is yellow bone marrow?

A

Inactive
Little hematopoiesis
Few blood cells and lots of fat

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15
Q

What are the roles of the liver, spleen, thymus, and lymph nodes in hematopoiesis?

A

Liver - extra-medullary hematopoiesis
Spleen - production of cells, removal of old and damaged cells, storage of platelets
Thymus - production and maturation of T-lymphocytes (B-cells & T-cells)
Lymph node- formation of lymphocytes

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16
Q

What are blast cells?

A

The earliest stages of blood cells that can be seen microscopically

Undergo periodic mitosis in a enriched bone marrow environment

Blasts are not seen in a normal adults blood (is they are there is a disorder of hematopoiesis)

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17
Q

What are cytokines?

A

A chemical mediator that interacts with their target cells, either inducing or inhibiting cellular RNA or protein synthesis.

Are cell growth factors

Produced mainly by T-lymphs or monocytes/macrophage

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18
Q

What are the three most important cytokines that aid in the growth of cells in hematopoiesis?

A

Colony stimulating factors/interleukins

Erythropoietin

Thrombopoietin

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19
Q

How is hematopoiesis regulated by cytokines?

A

Reticulum cell differentiates slightly into a CFU-S stem cell. The growth factors CSF colony stimulating factors and interleukins differentiate cells into a CFU - GEMM or a CFU-L. If cell differentiates into CFU-L it is now a lymphoid stem cell and eventually produces lymphocytes.
If cell differentiates into a CFU-GEMM cell CSF can cause it it differentiate into either BFU- E, BFU-Meg, CFU-GM, CFU-Eo, or CFU-bas. Erythropoietin first stimulates BFU-E to differentiate into CFU-E then becomes a pronormoblast, where it then stimulates it again to produce a RBC. Thrombopoietin stimulates BFU-Meg to differentiate into CFU-Meg which becomes a megakaryoblast, in which it is stimulated again into a megakaryocyte platelet.

SEE MODULE PAGE 7 FOR DIAGRAM

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20
Q

What is Interleukin- 1?

A

Produced in monocytes and macrophages

Activate and stimulate cytokine production by T lymphocytes and bone marrow stromal cells

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21
Q

What is interleukin- 3?

A

Produced by T-lymphocytes

Induce differentiation (maturation) and mitosis of the CFU-S (stem cell) into either a CFU-GEMM (myeloid stem cell) or a CFU-L (lymphoid stem cell)

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22
Q

What is interleukin- 5?

A

Induces eosinophil growth and function

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23
Q

What is the granulocyte/monocyte stimulating factor?

A

Induces differentiation and mitosis of the CFU-GEMM into several series committed stem cells: CFU-Eo, CFU-GM, CFU-baso, BFU-E, BFU-meg.

Also stimulates the phagocytic and cytotoxic functions of neutrophils and macrophages.

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24
Q

What is erythropoietin?

A

Induces maturation and mitosis in BFU-E, CFU-E, pronormoblast and developing NRBC

raises concentration of EPO over long periods of time
Induces increased production of other myleoid cells

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25
Q

What is thrombopoietin?

A

Induces maturation and mitosis in the CFU-meg and developing megakaryocytes

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26
Q

What are the different reticulum cells?

A

CFU-S
CFU-L
CFU-GEMM - changes into any myleoid cell: CFU-Eo, CFU-baso, CFU-GM, CFU-G, CFU-Meg, BFU-Meg, CFU-E, BFU-E

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27
Q

What is effective vs. Ineffective hematopoiesis?

A

Effective - normal, 85% or more of developing blood cells in the bone marrow are successfully produced and released into circulation

Ineffective - abnormal, less than 85% of blood cells are produced normally and release into blood. More than 15% die before being released.

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28
Q

What is the cell maturation and lifespan for all blood cells?

A

Normoblast 5 days in marrow, reticulocyte 3 days in marrow 1 day in blood, erythrocyte 1 day in marrow and 120 days in blood.

Platelets 8-10 days in blood, megakaryocytes 7 days in marrow

Neutrophils 5-7 days in marrow, 8 hrs in blood, up to 6 days in tissue

SEE PAGE 9 IN MODULE FOR CHART

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29
Q

When there is an increased demand for blood cells, bone marrow can increase production in which four ways?

A

Releasing - immature forms are released into blood eg. Nucleated RBCs and band cells

Increasing - number of mitoses in the developing cells

Decreasing - accelerating the maturation (differentiation) time between mitoses

Expanding - hematopoiesis into inactive areas of the spleen and liver

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30
Q

What is the mitosis maturation sequence? What is amplification?

A

Starts as a single stem cell, ends with 16 neutrophils

SEE PAGE 10 IN MODULE FOR DIAGRAM

Amplification is the ability of the marrow to produce many mature cells from a single blast cell

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31
Q

What are the general morphologic features seen in all blood cells during maturation?

A

Changes in cell size
Changes in nuclear/cytoplasmic ratio
Changes in nucleus
Changes in cytoplasm

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32
Q

What are the cellular steps in the development of a blood cell?

A 
Pronormoblast
Basophilic normoblast
Polychromatic normoblast 
Orthochromic normoblast 
Polychromatophilic (reticulocyte)
Erythrocyte
33
Q

What is a pronormoblast?

A

Size: 12-24 micro meters
Nucleus: round central reddish purple unclumped chromatin, few nucleoli
N/C Ratio 8:1-6:1
Cytoplasm: small, deep blue, no granules

34
Q

What is a basophilic normoblast?

A

Size: 12-17 micrometers
Nucleus: round or oval, clumping slightly coarser, parachromatin
N/C ratio 6:1-4:1
Cytoplasm: small, deep blue or purple, no granules

35
Q

What is a polychromatic normoblast?

A

Size: 10-15 micro meters
Nucleus: round, central, deep purple/black, heavily condensed chromatin, parachromatin, no nucleoli
N\C Ratio 4:1-2:1
Cytoplasm: decreased in size but increased relative to nucleus, polychromatic

36
Q

What is an orthochromic normoblast?

A

Size: 8-12 micro meters
Nucleus: round, central, pyknotic (nucleus so dense it’s been spit out), homogeneous, no chromatin structure
N/C Ratio 1:1-2:1
Cytoplasm: moderate amount, bluish-pink, no granules

37
Q

What is a Polychromatophilic/reticulocyte?

A

Size: 7-10 micro meters
No nucleus
Cytoplasm: clear grey-blue
Polychromatic to pink

38
Q

What is an erythrocyte?

A

Biconcave
Size: 7-8 micro meters
Cytoplasm: pink

39
Q

What are the parts of a plasma membrane?

A

Lipids, proteins, carbohydrates

Double lipid bilayer
ATP enzymes
Fluid mosaic model

40
Q

What is the function of the plasma membrane?

A 
Selective permeability
Diffusion
Facilitated diffusion
Active transport 
Sodium potassium pump
Calcium pump
41
Q

What does the cytoplasm consist of?

A

90% hemeglobin

10% other organelles, enzymes, electrolytes, carbs, lipids, and proteins

42
Q

What is hemoglobin production dependent on?

A

An adequate supply of IRON

43
Q

A single molecule of hemoglobin consists of what?

A

Globin 4 polypeptide chains and 4 heme molecules

44
Q

Where is heme synthesized?

A

In the mitochondria and cytoplasm of the developing nucleated RBCs

45
Q

How is heme synthesized in the mitochondria?

A

SEE PAGE 17 IN MODULE

Glycine+succinylCoA
Add: vitamin B6, heme inhibitor, ALA synthetase enzyme, EPO activator

Produces include: coproporphyrinogen III, protoporphyrinogen IX, protoporphytin IX
Add Iron
Produces HEME (ferropotoporphyrin IX) Fe2+

46
Q

Where does globin synthesis occur?

A

In ribosomes, amino acids are assembled into polypeptide chains, is genetic

Alpha
Beta
Gamma
Delta
Epsilon
Zeta
47
Q

What are the components of hemoglobin?

A

4 globin, 4 heme, 4 iron in reduced state

48
Q

What are the different types of hemoglobin?

A

Hb Gower1
Hb Portland
Hb Gower2

HbF

HbA2
HbA

49
Q

What are the characteristics of Hb Gower1?

A

4 epsilon or 2 zeta and 2 epsilon

Produced in first 12 weeks of gestation in embryo and early fetus
Do not carry oxygen

50
Q

What are the characteristics of Hb Portland?

A

2 zeta 2 gamma

Produced in first 12 weeks of gestation in embryo and early fetus
Do not carry oxygen

51
Q

What are the characteristics of Hb Gower2?

A

2 alpha 2 epsilon

Produced in first 12 weeks of gestation in embryo and early fetus
Do not carry oxygen

52
Q

What are the characteristics of HbF?

A

2 alpha 2 gamma

> 75% at birth
Higher affinity for oxygen
Not evenly distributed in all RBCs

53
Q

What are the characteristics of HbA2?

A

2 alpha 2 delta

54
Q

What are the characteristics of HbA?

A

2 alpha 2 beta

Major component in adults
96-98% of total Hb

55
Q

What is HbA1c?

A

HbA plus a glucose molecule instead of oxygen

Also called glycosylated hemoglobin
Used to test for diabetes

56
Q

What is reduced hemoglobin?

A

HbA in which the iron atoms of the Hemes are in a reduced (ferrous) state Fe2+

57
Q

What is oxyhemoglobin?

A

Reduced HbA that is carrying oxygen bound to some or all of the iron atoms of the hemes

58
Q

What is deoxyhemoglobin?

A

Is reduced HbA that is not carrying oxygen

59
Q

What is methemoglobin/oxidized hemoglobin?

A

HbA in which the iron is in ferric state (Fe3+) and cannot bind to oxygen

60
Q

What is carboxyhemoglobin?

A

HbA binds with carbon monoxide instead of oxygen because the affinity is stronger

61
Q

What is Sulfhemoglobin?

A

HbA reacts with soluble inorganic sulphides and H2O2, prevents binding with oxygen

62
Q

What are the two pathways that can be involved in the metabolism of an erythrocyte?

A

The Embden-Meyerhof Pathway

The Pentose Shunt Pathway

63
Q

What are the products of the Embden-Meyerhof Pathway?

A

2 molecules of ATP - used for transport

2 molecules of NADH - used to reduce iron

64
Q

What is the product of the Pentose Shunt Pathway?

A

Per molecule of glucose, 1 molecule of NADPH is generated - protects cell from oxidation

65
Q

What are the three main functions of erythrocytes?

A

Oxygen transport
Carbon dioxide transport
Nitric oxide transport

66
Q

How many oxygen molecules can one hemoglobin carry?

A

Maximum of 4

67
Q

What are the 3 factors that affect the amount of oxygen carried by hemoglobin?

A

Availability of enough oxygen
Availability of enough reduced hemoglobin
Oxygen affinity of hemoglobin - bonding attractiveness

68
Q

What are the 4 factors that determine oxygen affinity for hemoglobin?

A

Heme-Heme interaction
Temperature
The Bohr Effect (pH)
2,3 Biphosphoglycerate (BPG)

69
Q

What is Heme-Heme interaction?

A

As oxygen molecules attach one at a time to hemes, the structure changes with each bonding and each time the structure changes it affects the affinity for oxygen

1st binding increases affinity for oxygen for a 2nd and 3rd binding of oxygen, once the 3rd one binds the affinity for the 4th one decreases

70
Q

What is the oxygen dissociation curve of hemoglobin?

A

When low, releases oxygen to tissues
When high attaches to oxygen in lungs
There is a regular resting point

SEE PAGE 27 OF MODULE FOR GRAPH

71
Q

How does temperature affect oxygen affinity for hemoglobin?

A

Oxygen affinity varies inversely with temp changes
Temp increases, affinity decreases
Temp decreases, affinity increases

72
Q

What is the Bohr Effect?

A

The oxygen affinity varies directly with the pH of the blood plasma

pH decreases, affinity decreases
pH increases, affinity increases

Height affinity in lungs, lower affinity in tissues

73
Q

What is 2,3 BPG Concentration?

A

2,3 Biphosphoglycerate is a by-product of the Embden-Meyerhof pathway

Produced in response to hypoxia in the tissues, it binds to the Hb molecule and immediately changes the shape of hemoglobin decreasing oxygen affinity and causes oxygen to be released for diffusion into the tissues.

Also called desaturation of Hb.
SEE PAGE 29 OF MODULE FOR GRAPH

74
Q

What happens in CO2 transport?

A

When carbon dioxide is added to plasma it will react with water producing hydrogen atoms and bicarbonate molecules.

In the tissues, carbon dioxide diffuses rapidly into the plasma portion of a RBC

SEE PAGE 30 IN MODULE FOR DIAGRAM

75
Q

What is carbonic anhydrase and what is its role in CO2 transport?

A

Is an enzyme that acts as a catalyst for the carbon dioxide reaction with water in either direction

76
Q

What happens to hydrogen, bicarbonate, and carbon dioxide gas in the CO2 transport system?

A

H+ ions bond to amino acids in the globin polypeptides - called the buffering action of hemoglobin (prevents change in pH)

Bicarbonate ion diffuses through the cell along with Cl- (chloride shift) until concentration equilibrium is achieved

10% is carried as carbamino hemoglobin
5% dissolves as CO2 gas in plasma

77
Q

What happens when RBCs die?

A

Most die of old age after about 120 days in circulation and are removed extravascularly by macrophages

A small portion can be destroyed intervascularly while circulating by hard collisions

78
Q

What happens in extravascular hemolysis?

A

Hb is digested by lysosomes
Hemes are detached from globin
Globin is broken back down into its component amino acids
Iron is detached from the photoporphyrin and is stored or moved to the plasma to be delivered back to bone marrow
Photoporphyrin is oxidized into biliverdin and moves into plasma and reduced to bilirubin
Plasma albumin attaches to bilirubin and carried to liver, where it eventually moves to the intestines and is excreted
SEE PAGE 34 OF MOD TO SEE DIAGRAM

79
Q

What happens in intravascular hemolysis?

A

Hemolysis occurs while in circulation
Hemoglobin is released directly into the plasma, the free Hb in plasma is immediately bound but haptoglobin (Hp) forming a Hb-Hb complex and goes to the liver and spleen and is removed by macrophages

Hematology (2 decks)

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