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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
What lineage do leukocytes (WBCs) come from?
Myeloid and lymphoid lineage
26
Where does the most haematopoeisis occur?
Bone marrow
27
Where does later development of T cells occur?
Thymus
28
What is the difference between monocytes and macrophages?
Monocytes circulate in the blood, macrophages are found in the tissues and are 5-10x larger.
29
What '-potent' are the common myeloid progenitor and the common lymphoid progenitor?
Oligopotent
30
Where do platelets/thrombocytes come from?
Megakaryocytes --> common myeloid progenitor --> multipotential haematopoietic stem cell
31
What '-potent' is the myeloblast?
Oligopotent
32
Erythrocyte maturation involves:
Decrease in cell size Haemoglobin production Loss of organelles (incl. nucleus) Acquisition of biconcave disc shape
33
Describe the precursors to erythrocytes (erythropoiesis)
Proerythroblast Erythroblast Reticulocyte Erythrocyte
34
How is erythropoiesis controlled? | What does it require?
Erythropoietin (EPO) Requires - iron, folic acid, vitamin B12
35
Name the 3 types of erythroblasts in order of least to most mature
Erythroblast basophilic Erythroblast polychromatic Erythroblast orthochromatic
36
Why do erythrocytes have a biconcave disc shape?
Maximises surface area Minimises distance from surface Increases flexibility
37
Describe an erythrocyte
Biconcave disc shape Structural proteins to maintain shape Simplified internal structure (lack of organelles Simplified metabolism
38
What are the requirements for erythropoiesis?
DNA synthesis | Haemoglobin synthesis
39
What are the requirements for erythrocyte DNA synthesis?
Folic acid (B9) Cobalamin (B12) Intrinsic factor
40
What are the requirements for erythrocyte Hb synthesis?
Globins - alpha and beta protein chains Haem (contains iron) - Vitamin B6, Fe2+
41
Describe the relationship between B12 and folic acid?
B12 is required for the recycling of folic acid
42
What can lack of B12 or folic acid lead to?
Megaloblastic anaemia
43
Where is folic acid absorbed?
Duodenum and jejunum
44
Where is B12 absorbed?
Terminal ileum
45
How can folic acid deficiency arise?
Inadequate intake, malabsorption, increased demand, drugs (alcohol)
46
How does cobalamin B12 deficiency happen?
Malabsorption
47
What does B12 bind to in the stomach?
Pepsin (from gastric parietal cells)
48
What is intrinsic factor?
A glycoprotein
49
What does lack of vitamin b12 lead to?
Pernicious anaemia
50
What is the most common cause of pernicious anaemia?
Autoimmune response to parietal cells
51
What form of anaemia is pernicious anaemia?
Megaloblastic anaemia (large cells but fewer of them)
52
What are the inherited disorders of the globulin chains?
a- or b thalassemia | Sickle cell anaemia
53
Why is B6 important in producing Hb?
It is a co-enzyme in the pathway to produce Hb in the mitochondria and cytoplasms
54
What are inherited disorders in haem synthesis called?
Porphyrias
55
What is sickle cell anaemia?
Single base pair change in gene DNA that codes for HbA (normal) to HbS (abnormal) A and T base pairs are flipped.
56
What are the two forms of iron and their sources?
``` Heme iron (meat) Non-heme iron (green veg) ```
57
How is iron absorbed from the intestinal lumen into the epithelial cell?
In a complex with ferritin
58
How is iron transported across the basolateral membrane?
Ferroportin transporter
59
How is iron transported in the blood?
Transferrin
60
Where is most of the absorbed iron transported to?
Bone marrow
61
Where is the rest of our absorbed iron stored?
Liver and spleen
62
Which hormone regulates iron absorption?
Hepcidin - released by the liver with iron levels are too high.
63
How does hepcidin work?
Inhibits iron absorption by decreasing ferroportin activity in the basolateral membrane of intestinal epithelial cells
64
Describe iron deficiency anaemia and its causes
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
Describe pernicious anaemia and B vitamin deficiency anaemia and its causes
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
Describe aplastic anaemia and its causes
Bone marrow is unable to produce enough blood cells; a life threatening condition Cancer therapy, exposure to toxic substances, autoimmune disorders, viral infections
67
Describe haemolytic anaemia and its causes
RBCs are destroyed faster than the bone marrow can replace them Inherited causes include sickle cell and thalassemia
68
Describe anaemia of chronic disease and its causes
Various illnesses over a long time can reduce the production of RBCs Rheumatoid arthritis, kidney disease, diabetes, tuberculosis or HIV
69
Describe macrocytic anaemia
Large erythrocytes, but in low number and/or with low Hb content per cell
70
Describe microcytic anaemia
Small erythrocytes and usually low Hb content per cell
71
Describe normocytic anaemia
Erythrocytes of normal size, but usually present in inadequate number
72
Give 3 examples of microcytic, hypochromic anaemia
Iron deficiency Thalassaemia Anaemia of chronic disease (some cases)
73
Give 4 examples of normocytic, normochromic anaemia
Acute blood loss Haemolytic anaemias Anaemia of chronic disease (some cases) Bone marrow failure
74
Describe macrocytic anaemia
Vit B12/B9 deficiency Aplastic anaemia Liver disease Excessive alcohol intake
75
Define leukocytosis
High white cell count
76
Define neutrophilia
Acute bacterial infections, inflammation, tissue necrosis, drugs, neoplasms,
77
Define eosinophilia
Allergic disorders such as asthma, hay fever, etc.
78
Define lymphocytosis
Viral infections, etc.
79
Define leukopenia
Low white cell count - aplastic anaemia, hypersplenism, sepsis, infection, drugs
80
Describe the precursors to thrombocytes (thrombopoiesis)
Megakaryoblast Promegakaryocyte Megakaryocyte Thrombocyte (platelet)
81
Where do megakaryocytes in the bone marrow sit adjacent to?
Blood sinusoids
82
How are thrombocytes formed from megakaryocytes?
Segments of megakaryocyte cytoplasm protrude into the blood sinusoid. The blood flow splits off cytoplasmic fragments which become platelets.
83
Where are 40% of thrombocytes found?
The spleen
84
How long do platelets circulate in the blood for?
7-10 days
85
What is thrombocytosis?
High platelet count
86
What causes primary thrombocytosis?
Myeloproliferative disorders
87
What causes secondary thrombocytosis?
Infection, neoplasms
88
What is thrombocytopenia?
Low platelet count
89
What causes a decreased production in platelets?
Genetic disorder | Folate/cobalamin deficiency
90
What causes an increased destruction in platelets?
Hypersplenism Immune destruction Infection Drugs
91
What releases EPO?
Fibroblasts in the kidneys
92
What does EPO stimulate?
Erythropoiesis in the bone marrow. | It binds to a specific receptor on proerythroblasts/basophilic erythroblasts and promotes cell survival
93
Where is thrombopoietin produced?
The liver
94
What does thrombopoietin do?
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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