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Block 2 > Haematopoiesis > Flashcards

Haematopoiesis Flashcards

1
Q

What is the composition of blood?

A

Cells and plasma

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2
Q

What does blood plasma contain?

A 
Water
Small organic compounds and electrolytes 
Proteins 
-albumin
-a,b,y globulins
-fibrinogen
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3
Q

What 3 cells are granulocytes?

A

Basophil
Neutrophil
Eosinophil

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4
Q

Describe a monocyte

A

Can differentiate into macrophages as part of the immune response
Large

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5
Q

Describe a lymphocyte

A

Can differentiate into T cells and B cells

Large nucleus, small cytoplasm

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6
Q

Describe a neutrophil

A

Granulocyte

3 part nucleus

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7
Q

Describe an eosinophil

A

Granulocyte

2 part nucleus

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8
Q

What is an erythrocyte?

A

Red blood cell

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9
Q

What is the most common blood cell present in the blood?

A

Erythrocyte (99%)

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10
Q

Which type of white blood cell is most common?

A

Neutrophil

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11
Q

What is the lifespan of a erythrocyte?

A

4 months

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12
Q

Why can lymphocytes have long lifespans?

A

Can be memory cells (immunity)

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13
Q

What is haematopoiesis?

A

The production of all types of mature blood cells:
RBCs
WBCs
Platelets

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14
Q

How are RBCs made?

A

Erythropoiesis

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15
Q

How are WBCs made?

A

Myelopoiesis and lymphopoiesis

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16
Q

How are platelets made?

A

Thrombopoiesis

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17
Q

Haemopoietic stem cells give rise to all haemopoietic cell lineages through:

A

Proliferation
Differentiation
Maturation

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18
Q

What is the haemopoietic cell lineage dependent on?

A

Glycoprotein growth factors (bone stromal cells)
Erythropoietin (kidneys)
Thrombopoietin (liver)

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19
Q

Totipotent stem cell

A

Can differentiate into any cell type, including embryonic and extraembryonic
e.g. fertilised egg

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20
Q

Pluripotent stem cell

A

Can differentiate into any cell type of the embryo

Not placenta or embryonic fluid

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21
Q

Multipotent stem cell

A

Can differentiate into several different, but related cell types

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22
Q

Oligopotent stem cell

A

Can differentiate into a small number of very closely related cell types

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23
Q

Unipotent stem cell

A

Can produce more cells of identical cell type

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24
Q

What lineage do erythrocytes (RBCs) come from?

A

Myeloid lineage

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25
Q

What lineage do leukocytes (WBCs) come from?

A

Myeloid and lymphoid lineage

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26
Q

Where does the most haematopoeisis occur?

A

Bone marrow

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27
Q

Where does later development of T cells occur?

A

Thymus

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28
Q

What is the difference between monocytes and macrophages?

A

Monocytes circulate in the blood, macrophages are found in the tissues and are 5-10x larger.

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29
Q

What ‘-potent’ are the common myeloid progenitor and the common lymphoid progenitor?

A

Oligopotent

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30
Q

Where do platelets/thrombocytes come from?

A

Megakaryocytes –> common myeloid progenitor –> multipotential haematopoietic stem cell

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31
Q

What ‘-potent’ is the myeloblast?

A

Oligopotent

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32
Q

Erythrocyte maturation involves:

A

Decrease in cell size
Haemoglobin production
Loss of organelles (incl. nucleus)
Acquisition of biconcave disc shape

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33
Q

Describe the precursors to erythrocytes (erythropoiesis)

A

Proerythroblast
Erythroblast
Reticulocyte
Erythrocyte

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34
Q

How is erythropoiesis controlled?

What does it require?

A

Erythropoietin (EPO)

Requires - iron, folic acid, vitamin B12

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35
Q

Name the 3 types of erythroblasts in order of least to most mature

A

Erythroblast basophilic
Erythroblast polychromatic
Erythroblast orthochromatic

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36
Q

Why do erythrocytes have a biconcave disc shape?

A

Maximises surface area
Minimises distance from surface
Increases flexibility

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37
Q

Describe an erythrocyte

A

Biconcave disc shape
Structural proteins to maintain shape
Simplified internal structure (lack of organelles
Simplified metabolism

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38
Q

What are the requirements for erythropoiesis?

A

DNA synthesis

Haemoglobin synthesis

39
Q

What are the requirements for erythrocyte DNA synthesis?

A

Folic acid (B9)
Cobalamin (B12)
Intrinsic factor

40
Q

What are the requirements for erythrocyte Hb synthesis?

A

Globins - alpha and beta protein chains

Haem (contains iron) - Vitamin B6, Fe2+

41
Q

Describe the relationship between B12 and folic acid?

A

B12 is required for the recycling of folic acid

42
Q

What can lack of B12 or folic acid lead to?

A

Megaloblastic anaemia

43
Q

Where is folic acid absorbed?

A

Duodenum and jejunum

44
Q

Where is B12 absorbed?

A

Terminal ileum

45
Q

How can folic acid deficiency arise?

A

Inadequate intake, malabsorption, increased demand, drugs (alcohol)

46
Q

How does cobalamin B12 deficiency happen?

A

Malabsorption

47
Q

What does B12 bind to in the stomach?

A

Pepsin (from gastric parietal cells)

48
Q

What is intrinsic factor?

A

A glycoprotein

49
Q

What does lack of vitamin b12 lead to?

A

Pernicious anaemia

50
Q

What is the most common cause of pernicious anaemia?

A

Autoimmune response to parietal cells

51
Q

What form of anaemia is pernicious anaemia?

A

Megaloblastic anaemia (large cells but fewer of them)

52
Q

What are the inherited disorders of the globulin chains?

A

a- or b thalassemia

Sickle cell anaemia

53
Q

Why is B6 important in producing Hb?

A

It is a co-enzyme in the pathway to produce Hb in the mitochondria and cytoplasms

54
Q

What are inherited disorders in haem synthesis called?

A

Porphyrias

55
Q

What is sickle cell anaemia?

A

Single base pair change in gene DNA that codes for HbA (normal) to HbS (abnormal) A and T base pairs are flipped.

56
Q

What are the two forms of iron and their sources?

A 
Heme iron (meat)
Non-heme iron (green veg)
57
Q

How is iron absorbed from the intestinal lumen into the epithelial cell?

A

In a complex with ferritin

58
Q

How is iron transported across the basolateral membrane?

A

Ferroportin transporter

59
Q

How is iron transported in the blood?

A

Transferrin

60
Q

Where is most of the absorbed iron transported to?

A

Bone marrow

61
Q

Where is the rest of our absorbed iron stored?

A

Liver and spleen

62
Q

Which hormone regulates iron absorption?

A

Hepcidin - released by the liver with iron levels are too high.

63
Q

How does hepcidin work?

A

Inhibits iron absorption by decreasing ferroportin activity in the basolateral membrane of intestinal epithelial cells

64
Q

Describe iron deficiency anaemia and its causes

A

Deficiency of iron leads to decreased amounts of haemoglobin; low levels of haemoglobin in turn decreases the production of RBCs

Blood loss, diet low in iron, poor absorption of iron

65
Q

Describe pernicious anaemia and B vitamin deficiency anaemia and its causes

A

RBCs do not develop as they normally would because of a lack of B vitamins (B12 and folic acid), which leads to decreased production of RBCs

Lack of intrinsic factor, diet low in B vitamins, decreased absorption of B vitamins

66
Q

Describe aplastic anaemia and its causes

A

Bone marrow is unable to produce enough blood cells; a life threatening condition

Cancer therapy, exposure to toxic substances, autoimmune disorders, viral infections

67
Q

Describe haemolytic anaemia and its causes

A

RBCs are destroyed faster than the bone marrow can replace them

Inherited causes include sickle cell and thalassemia

68
Q

Describe anaemia of chronic disease and its causes

A

Various illnesses over a long time can reduce the production of RBCs

Rheumatoid arthritis, kidney disease, diabetes, tuberculosis or HIV

69
Q

Describe macrocytic anaemia

A

Large erythrocytes, but in low number and/or with low Hb content per cell

70
Q

Describe microcytic anaemia

A

Small erythrocytes and usually low Hb content per cell

71
Q

Describe normocytic anaemia

A

Erythrocytes of normal size, but usually present in inadequate number

72
Q

Give 3 examples of microcytic, hypochromic anaemia

A

Iron deficiency
Thalassaemia
Anaemia of chronic disease (some cases)

73
Q

Give 4 examples of normocytic, normochromic anaemia

A

Acute blood loss
Haemolytic anaemias
Anaemia of chronic disease (some cases)
Bone marrow failure

74
Q

Describe macrocytic anaemia

A

Vit B12/B9 deficiency
Aplastic anaemia
Liver disease
Excessive alcohol intake

75
Q

Define leukocytosis

A

High white cell count

76
Q

Define neutrophilia

A

Acute bacterial infections, inflammation, tissue necrosis, drugs, neoplasms,

77
Q

Define eosinophilia

A

Allergic disorders such as asthma, hay fever, etc.

78
Q

Define lymphocytosis

A

Viral infections, etc.

79
Q

Define leukopenia

A

Low white cell count - aplastic anaemia, hypersplenism, sepsis, infection, drugs

80
Q

Describe the precursors to thrombocytes (thrombopoiesis)

A

Megakaryoblast
Promegakaryocyte
Megakaryocyte
Thrombocyte (platelet)

81
Q

Where do megakaryocytes in the bone marrow sit adjacent to?

A

Blood sinusoids

82
Q

How are thrombocytes formed from megakaryocytes?

A

Segments of megakaryocyte cytoplasm protrude into the blood sinusoid. The blood flow splits off cytoplasmic fragments which become platelets.

83
Q

Where are 40% of thrombocytes found?

A

The spleen

84
Q

How long do platelets circulate in the blood for?

A

7-10 days

85
Q

What is thrombocytosis?

A

High platelet count

86
Q

What causes primary thrombocytosis?

A

Myeloproliferative disorders

87
Q

What causes secondary thrombocytosis?

A

Infection, neoplasms

88
Q

What is thrombocytopenia?

A

Low platelet count

89
Q

What causes a decreased production in platelets?

A

Genetic disorder

Folate/cobalamin deficiency

90
Q

What causes an increased destruction in platelets?

A

Hypersplenism
Immune destruction
Infection
Drugs

91
Q

What releases EPO?

A

Fibroblasts in the kidneys

92
Q

What does EPO stimulate?

A

Erythropoiesis in the bone marrow.

It binds to a specific receptor on proerythroblasts/basophilic erythroblasts and promotes cell survival

93
Q

Where is thrombopoietin produced?

A

The liver

94
Q

What does thrombopoietin do?

A

Stimulates the differentiation of megakaryocytes and thrombocytes.
There is a negative feedback loop between thrombocytes and thrombopoietin levels

Block 2 (10 decks)

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