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A Physiology > 5.1. Hematopoiesis. The composition of the blood. The human blood group systems. > Flashcards

5.1. Hematopoiesis. The composition of the blood. The human blood group systems. Flashcards

1
Q
  1. What is the Normal value of blood?
A

60 – 80 mL/kg
70kg adult has 5L of blood

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2
Q
  1. What are the Main functions of blood
A
  1. Transport
    - O2, CO2
    - Metabolites, nutrients and waste products
    - Hormones
    - Heat
  2. Regulation
    - Salt-water balance
    - Osmotic concentration
    - Acid-base balance
    - Body temperature
  3. Protection
    - Immune defense (pathogen, cancer cells)
    - Hemostasis (blood clotting)
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3
Q
  1. Composition of blood
    a/ What is the general composition of the blood plasma?
A

90% water
8% plasma proteins
2% other organic compounds

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4
Q
  1. Composition of blood
    b/ What are the cellular elements of the blood plasma?
A

RBCs
WBCs
Platelets

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5
Q
  1. Composition of blood
    a/ What is the general composition of the blood plasma?
A

90% water
8% plasma proteins
2% other organic compounds

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6
Q
  1. Composition of blood
    c/ What is the formula and normal value of hematocrit?
A

Hematocrit = Height of RBCs/ Total height
Normal value: 0.42 – 0.46

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7
Q
  1. Composition of blood
    d1/ Describe the permeability of capillaries to proteins? What can you conclude about the role of of proteins in blood?
A

Capillaries have low permeability to proteins
=> Proteins are responsible for the osmotic pressure gradient between intravascular and interstitial compartments

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8
Q
  1. Composition of blood
    d2/ What are the principal plasma proteins? What are their percentages?
A

Albumin: app. 80% - A major contributor to the colloid pressure
Globulins: app. 20%
Fibrinogen: app 0%

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9
Q
  1. Composition of blood
    d3/ What is the role of principal plasma proteins?
A

distribution of the total colloid osmotic pressure

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10
Q
  1. Composition of blood
    d3/ Where are principal plasma proteins produced?
A

Produced by liver (majority) and B-lymphocytes (immunoglobulins

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11
Q
  1. Composition of blood
    e1/ What is the normal value and life span of RBCs?
A

NV: 4.5 – 5 million/ µl
LS: 120 days

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12
Q
  1. Composition of blood
    e2/ What is the normal value and life span of Platelets?
A

NV: 300 000/ µl
LS: 7 – 10 days

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13
Q
  1. Composition of blood
    e3/ What is the normal value and life span of WBCs?
A

NV: 7000/ µl
LS: From 8 hours to years

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14
Q
  1. Composition of blood
    e4/ What are the 5 types of WBCs?
A

1/ Neutrophil granulocyte
2/ Lymphocyte
3/ Monocyte
4/ Eosinophil
5/ Basophil

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15
Q
  1. Composition of blood
    e5/ What is the normal value of Neutrophil granulocyte?
A

4000/ µl

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16
Q
  1. Composition of blood
    e6/ What is the normal value of Lymphocyte?
A

2000/ µl

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17
Q
  1. Composition of blood
    e7/ What is the normal value of Monocyte
    ?
A

500/ µl

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18
Q
  1. Composition of blood
    e7/ What is the normal value of Eosinophil?
A

200/ µl

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19
Q
  1. Composition of blood
    e8/ What is the normal value of Basophil?
A

50/ µl

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20
Q
  1. HEMATOPOIESIS A
    a/ Definition of hematopoiesis
A

the production of all the cellular components of the blood and blood plasma

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21
Q
  1. HEMATOPOIESIS A
    b/ What are the 2 types of hematopoiesis
A

1/ Constitutive (steady-state)
2/ Stress-induced

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22
Q
  1. HEMATOPOIESIS A
    c/ Location of hematopoiesis
A

Hematopoiesis takes place at different locations in a fetus and an adult

1/ Intrauterine (within uterus)
- Yolk sac -> Liver, spleen -> Bone marrow

2/ Extrauterine (forming outside the uterus; adult)
- Exclusively in red bone marrow within axial skeleton (pelvis, sternum, vertebrae) and long bones
- Lymphocytes in spleen and lymph nodes

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23
Q
  1. HEMATOPOIESIS A
    d/ Definition and role of Constitutive hematopoiesis
A
  1. Definition: Continuous replenishment of blood cells throughout lifetime
  2. Role: Maintain the balance (used up + produce new ones)
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24
Q
  1. HEMATOPOIESIS A
    e/ Definition of Stress-induced hematopoiesis
A

Increased output of certain blood cells induced by a stress signal

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25
Q
  1. HEMATOPOIESIS A
    f/ 2 examples of Stress-induced hematopoiesis
A

1/ Hypoxia will lead to increased production of RBCs
2/ Infection will lead to increased production of granulocytes (WBC)

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26
Q
  1. HEMATOPOIESIS A
    g1/ Structure of bone marrow
A

The bone marrow contains yellow and red bone marrow

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27
Q
  1. HEMATOPOIESIS A
    g2/ Characteristics of Yellow bone marrow
A

Yellow bone marrow contain inactive, mainly fat cells

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28
Q
  1. HEMATOPOIESIS A
    g3/ Characteristics of Red bone marrow
A

Red bone marrow contains actively producing RBCs
- Also contains hematopoietic cells, stromal cells and hematopoietic stem cells (HSC)
- Stromal cells serve as structural support, signaling and control of hematopoietic cell maturation

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29
Q
  1. HEMATOPOIESIS B
    h/ What is definition of Hematopoietic stem cells?
A

HSCs cells are cells in which all the cells of the circulating blood are derived from

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30
Q
  1. HEMATOPOIESIS B
    i/ What are the characteristics of Hematopoietic stem cells?
A

1/ Uncommitted
2/ Asymmetric division
3/ Self-renewal capacity
4/ Pluri/multipotency (able to differentiate other cells)
5/ Don’t have specific morphology (cell surface markers)

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31
Q
  1. HEMATOPOIESIS B
    j/ Role of surface markers
A

the determination of mature cells or stem cells which can be used to measure or count different types of cells

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32
Q
  1. HEMATOPOIESIS B
    k/ What are the 2 examples of surfaces markers
A

1/ CD34+ = (CD = cluster of differentiation)
- A cell migration/adhesion regulator that may help stem cells bind to marrow matrix

2/ C-kit is a receptor tyrosine kinase which binds “stem cell factor”

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33
Q
  1. HEMATOPOIESIS B
    L/ How can you find evidence for the presence of Hematopoietic stem cells (HSCs)?
A

You can find evidence of hematopoietic stem cells in bone marrow

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34
Q
  1. HEMATOPOIESIS B
    m/ What are the 3 types of Hematopoietic stem cells (HSCs)?
A

1/ LT – HSC (long term)
- Pluripotent
2/ ST – HSC (short term)
- Multipotent
3/ MPP (Multipotent progenitor)

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35
Q
  1. HEMATOPOIESIS B
    n/ What are the locations of Hematopoietic stem cells (HSCs)?
A

1/ Mainly in red bone marrow
2/ Peripheral blood (chord blood)

36
Q
  1. HEMATOPOIESIS B
    o/ What is a Pluripotent cell?
A

It is a stem cell that can develop into many different types of cells or tissues in the body
- Embryonic stem cells are considered as pluripotent

37
Q
  1. HEMATOPOIESIS B
    o/ What is a Multipotent cell?
A
  • Multipotent cell is a stem cell that can differentiate into particular cells types associated with multiple cell lineages (more limited than pluripotent)
    -> Adult stem cells are considered as multipotent
38
Q
  1. HEMATOPOIESIS C
    a/ What are the phases of hematopoiesis
A

1/ Hematopoiesis begins with HSCs and then steadily differentiate

2/ HSCs (LT-HSCs and ST-HSCs) first become MPP (multipotent progenitor cells

3/ MPP cannot self-renew, but their daughter cells will differentiate into 2 types of oligopotent progenitors which are CMP (common myeloid progenitor) and CLP (common lymphoid progenitor)
- CMP can differentiate into MEP (megakaryocytic erythroid progenitors) and GMP (granulocyte monocyte progenitor)

4/ Oligopotent progenitors will then differentiate into unipotent progenitors

5/ Unipotent progenitors will differentiate into differentiated cells

39
Q
  1. HEMATOPOIESIS C
    b/ Make a Hierarchy map of hematopoiesis
A

1/ T-cell progenitor will differentiate and complete their development into T-cells in thymus

2/ Note for the diagram
Green: pluri/multipotent cells
Blue: oligopotent
Red: unipotent
Black: differentiated/ specific cells

40
Q
  1. HEMATOPOIESIS C
    c/ What are the factors involved in regulation of hematopoiesis?
A

1/ Local humoral factors
- From developing blood cells, stromal cells
- E.g, cytokines, Hematopoietic growth factors (GFs)

2/ Local cell-cell interactions
- Bone marrow “niche”

3/ General humoral factors
- From blood steam
- E.g, hormone, cytokines, Hematopoietic growth factors (GFs)

41
Q
  1. HEMATOPOIESIS C
    d1/ How do regulatory factors involve in hematopoiesis in early phases?
A

1/ There are many regulatory factors with overlapping effects
2/ Regulatory factors involved:
- IL-3 (solute) (Interleukin 3)
- GMCSF (solute) (Granulocyte-macrophage colony-stimulating factor)
- CSF
+) Solute + cell surface
+) Receptor: C-kit

42
Q
  1. HEMATOPOIESIS C
    d2/ How do regulatory factors involve in hematopoiesis in later phases?
A

1/ There is few or 1 regulatory factors with no overlapping effects
2/ Examples of regulatory factors
- EPO (Erythropoietin)
- G– CSF (Granulocyte colony-stimulating factor (G-CSF))
- M – CSF
- Thrombopoietin (TPO)
- IL – 7 (lymphoid)

43
Q
  1. HEMATOPOIESIS C
    e/ How does Hematopoietic niche participate in Regulation of hematopoiesis ?
A

1/ The environment of the cell (cell-to-cell connections) is important in the differentiation of blood cells in the bone marrow

2/ Cells will take on certain differentiation routes (an area dedicated to a certain function like this = niche), therefore chemokines exist in the bone marrow to induce cell movement to different parts in the bone marrow (via chemotaxis)

3/ Niche = area in which stem cells are present in (1) an undifferentiated state and (2) a self-renewable state
- Divisional asymmetry: only a certain type divide, hence limited number of production
- Environmental asymmetry: some niches produce a certain type of cells more than the others

44
Q
  1. HEMATOPOIESIS C
    f1/ The definition and role of cytokines
A

1/ Definition: Glycoproteins (EC signal protein) which affects cells
2/ Their function is usually overlapping and can work for several cells (mast cells, B-cells, stem cells, etc.)
3/ Acts as local mediator in cell-cell communication (induce movement, vision)

45
Q
  1. HEMATOPOIESIS C
    f2/ Examples of cytokines
A

1/ Erythropoietin (EPO)
- Secreted by kidney in response to cellular hypoxia
2/ Granulocyte-colony stimulating factor (G-CSF) which stimulate WBCs production

46
Q
  1. HEMATOPOIESIS C
    g1/ The role of CSF (colony-stimulating factor)
A

Stimulating committed progenitor to proliferate in vitro

47
Q
  1. HEMATOPOIESIS C
    g2/ The examples of CSF (colony-stimulating factor)
A

E.g, M-CSF, G-CSF
-> Form colony of specific lineages
-> Form CFU (colony-forming unit)
-> E.g, CFU – GEMM, CFU – E

48
Q
  1. HEMATOPOIESIS D
    a/ definition of Erythropoiesis
A

Definition: erythropoiesis the the development from erythropoietic stem cell to mature RBCs

49
Q
  1. Erythropoiesis
    a/ definition of Erythropoiesis
A

Definition: erythropoiesis the the development from erythropoietic stem cell to mature RBCs

50
Q
  1. Erythropoiesis
    b/ Process of Erythropoiesis
A

1/ 7 to 10 days RBC production process occurs in erythropoietic islands
2/ Form from the myeloid lineage -> proerythroblasts-> erythroblasts
3/ Slowly gain more hemoglobin and their nuclei shrink -> orthochromatic erythroblasts
4/ A macrophage absorbs the nucleus of the erythroblast and then becomes reticulocyte, which is anuclear and also without mitochondria

51
Q
  1. Erythropoiesis
    c/ What is the location for erythropoiesis?
A

BM erythroblastic islands (IBM) which are embedded in EBI macrophages

*Note:
- Erythroblastic islands (EBIs)

52
Q
  1. Erythropoiesis
    d/ Which mechanisms are involved in erythropoiesis?
A

1/ Control of erythropoiesis – the erythropoietin
2/ ON-OFF regulation of EPO synthesis in renal EPO producing (REP) cells
3/ O2 sensing mechanism

53
Q
  1. Erythropoiesis
    d1/ How does erythropoietin participate in Regulation of erythropoiesis?
A

1/ Erythrocyte production is regulated by erythropoietin (EPO), which is mainly produced in the kidney by interstitial fibroblasts (90%).

2/ Erythropoietin (EPO) can also be produced by hepatocytes in liver (10%)

54
Q
  1. Erythropoiesis
    d2/ Definition of ON-OFF regulation of EPO synthesis in renal EPO producing (REP) cells
A

Definition: Production of EPO is a negative feedback mechanism that is regulated by O2- concentration in the kidney

55
Q
  1. Erythropoiesis
    d2/ Mechanism of ON-OFF regulation of EPO synthesis in renal EPO producing (REP) cells
A
  • Hypoxia: Low O2 content in kidneys causes hypoxia-inducible factor (HIF) to activate, causing production of EPO which leads to increased erythrocytes and then increased O2-content of kidney
  • This will lead to normoxia which in turn inhibit the synthesis of EPO
56
Q
  1. Erythropoiesis
    d3/ Characteristics of O2 sensing mechanism
A

1/ HIF-⍺ is a transcription factor that regulates the expression of EPO
2/ At the normal level, HIF-⍺ levels are low, where as HIF-⍺ levels increases in hypoxia

57
Q
  1. Erythropoiesis
    d3/ Describe O2 sensing mechanism in case of normoxia
A

1/ O2 activates proxyl hydrolyase which will then hydroxylate HIF-⍺
2/ This hydroxylation stimulates the interaction of HIF-⍺ with VHL (Von Hippel-Lindau disease tumor surpressor protein), leading to ubiquination by Ubiquitin ligase
3/ Leads to degradation of HIF-⍺ (by proteasomal degradation)

58
Q
  1. Erythropoiesis
    d3/ Describe O2 sensing mechanism in case of hypoxia
A

1/ proxyl hydrolyase are inactivated
2/ HIF-⍺ accumulates in nucleus and then interacts with hypoxia response element and form a complex with HIF-β
3/ EPO gene expression increases abnormally

59
Q
  1. Erythropoiesis
    e/ What are Dietary requirements for normal erythropoiesis?
A

1/ Amino acids
2/ Vitamin B6
3/ Iron
4/ Vitamin B12
5/ Folic acid

60
Q
  1. Erythropoiesis
    f/ Cause of Anemias
A

Deficiency in dietary requirements for normal erythropoiesis

61
Q
  1. Erythropoiesis
    g/ What are the 3 types of Anemias
A

1/ Normocytic
2/ Microcytic
3/ Macrocytic

62
Q
  1. RBCs parameters
    a/ what is the normal count value?
A

4.5 – 5 million/µl

63
Q
  1. RBCs parameters
    b/ What is the normal Hematocrit value?
A

0.42 – 0.46

64
Q
  1. RBCs parameters
    c/ What is the normal Amount of hemoglobin?
A

2.2 – 2.5 mM (tetramer)

65
Q
  1. RBCs parameters
    d/ What is the normal value of Mean corpuscular hemoglobin (MCH)?
A

0.5 fmol/ cell

(Note: fmol mean femtomole (1fmol = 10-15 moles))

66
Q
  1. RBCs parameters
    e/ What is the normal value of Mean corpuscular hemoglobin concentration (MCHC)?
A

5 mM

67
Q
  1. RBCs parameters
    f/ What is the normal value of Mean corpuscular volume (MCV)?
A

90 fL

68
Q
  1. How does Breakdown of RBCs by macrophages occur?
A
69
Q
  1. Thrombopoiesis
    a/ Definition of Thrombopoiesis
A

Thrombopoiesis is the formation of platelets in blood

70
Q
  1. Thrombopoiesis
    b/ Process of Thrombopoiesis
A

Formed from the myeloid erythrocyte progenitor
-> promegakaryoblast
-> Promegakaryocyte
-> megakaryocyte
-> immigration towards the BM sinusoids
-> shedding of platelets

71
Q
  1. Thrombopoiesis
    c/ Characteristics of megakaryoblats
A

1/ Undergo endoreduplication (replication of genome in absence of mitosis) (32n)
2/ Extremely large diameter (60μm), hold lots of duplicated DNA
3/ Lobulated nucleus
4/ Their processes extend into blood vessels and
disintegrate to become ~104 platelets

72
Q
  1. Thrombopoiesis
    d/ How is Thrombopoiesis regulated?
A
  • By using TPO (thrombopoietin) which is produced mainly in the liver (+ kidney)
  • Thrombopoietin receptor is c-mpl on megakaryocytes and platelets
    1/ If the number of platelets increases, TPO level will decreases
    2/ If the number of platelets decreases, TPO level will increases
    -> It will then bind to receptors and cause platelet production (only with megakaryocytes) along with TPO degradation (for balance)
73
Q
  1. How does Development of monocytes, macrophages, dendritic cells and osteoclast occur?
A

1/ They all develop from GMP (granulocyte-monocyte progenitors)
2/ Monoblasts can form either osteoclasts, macrophages or dendritic cells (6 days)
3/ Granulocytes take 9 to 12 days to mature, but can be sped up to 2 days in cases of infection (thanks to cytokines)
4/ Mature granulocytes exit the bone marrow and either freely circulate or they attach to the endothelial cells of blood vessels

74
Q
  1. Blood group
    a/ Characteristics of blood group
A

1/ They have genetically determined antigens (Ag) on the surface
2/ Glycoproteins, glycolipids and integral membrane proteins
3/ There are about 30 blood group system
4/ There are about 300 antigens

75
Q
  1. Blood group
    b/ Characteristics of ABO system
A

1/ Antigen is composed of glycosphingolipids
2/ Codominant inheritance
3/ Ag gene codes for monosaccharide transferase enzymes

76
Q
  1. Blood group
    c/ The role of Ag genes
A

1/ H-gene -> fucosyltransferase => H-antigen
=> Core structure
2/ O – gene -> inactive enzyme => H-antigen
3/ A-gene -> GalNac transferase => A-antigen
4/ B-gene -> Gal transferase => B-antigen

77
Q
  1. Blood group
    d/ Describe Phenotype of ABO system
A

1/ Type O: neither A nor B antigens are present.
- O is recessive

2/ Type A: only type A antigen is present

3/ Type B: only type B antigen is present

4/ Type AB: both A and B antigens are present
- Co-dominance

78
Q
  1. Blood group
    e/ The characteristics and role of antibodies ABO system?
A

1/ Characteristics: IgM type immunoglobulins (5 x 2 binding sites for antigens)

2/ Role:
- They are present in the blood
- Naturally against non-self ABO antigens

79
Q
  1. Blood group
    f/ What is Landsteiner’s rule?
A
  • If an antigen is present on RBCs of an individual, the corresponding antibody must be absent in the plasma. (Self-tolerance)
  • If an antigen is absent on RBCs of an individual, the corresponding antibody must be present in the plasma.
80
Q
  1. Blood group
    g/ Explain Antigen-antibody reaction in ABO system
A

1/ If an antigen is present on RBCs of an individual, the corresponding antibody present
=> There will be agglutination

2/ If an antigen is absent on RBCs of an individual, the corresponding antibody is absent
=> There will be no reaction

81
Q
  1. Blood group
    h/ Characteristics of The Rhesus (Rh) system
A

1/ There are 6 common types of Rh antigens, but the type D antigen is widely prevalent and more antigenic than other Rh antigens.
2/ Anyone who has the type D antigen is said to be Rh positive, and a person without it is Rh negative.

82
Q
  1. Blood group
    I/ Describe the phenomenon of The Rhesus (Rh) incompatibility
A

1/ When the mother is Rh – and the father is Rh +, the baby inherits Rh+.
2/ The mother develops anti-Rh antibodies from exposure to the fetus’s Rh antigen.
3/ Then, the mother’s antibodies diffuse through the placenta into the fetus and cause RBC agglutination.
4/ The incidence rises progressively with subsequent pregnancies.

83
Q
  1. Blood group
    L/ What are the 2 types of Hemolytic transfusion reactions?
A

1/ Acute (IgM-mediated)
2/ Delayed (IgG-mediated)

84
Q
  1. Blood group
    L/ What are the characteristics of Acute (IgM-mediated) hemolytic transfusion reactions?
A

Complement activation
- Hemolysis
- Proinflammatory mediator release
- Disseminated intravascular coagulation

85
Q
  1. Blood group
    m/ What are the characteristics of Delayed (IgG-mediated) hemolytic transfusion reactions?
A

Incomplete complement activation
- Splenic & hepatic erythrophagocytosis
- Anemia
- Jaundice

A Physiology (88 decks)

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