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POM 2 G: HAEMATOLOGY > 2.1 Red Blood Cells > Flashcards

2.1 Red Blood Cells Flashcards

1
Q

Where do all blood cells originate

A

Bone marrow

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2
Q

What are blood cells derived from

A

Pluripotent haemopoietic stem cells

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3
Q

What do HSC’s give rise to

A

Common myeloid and lymphoid progenitors (stem cells)

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4
Q

Haemopoiesis

A

Formation and development of blood cells

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5
Q

Erythrocyte function

A

Oxygen transport

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6
Q

Erythrocyte life span

A

120 days

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7
Q

Platelet function

A

Haemostasis

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8
Q

Platelet life span

A

10 days

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9
Q

Monocyte function

A

Defence against infection by phagocytosis and killing of microorganisms

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10
Q

Monocyte life span

A

Several days

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11
Q

Neutrophil function

A

Defence against infection by phagocytosis and killing of microorganisms

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12
Q

Neutrophil life span

A

7-10 hours

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13
Q

Eosinophil function

A

Defence against parasitic infection

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14
Q

Eosinophil life span

A

Little less than 7 hours

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15
Q

Lymphocyte function

A

Humoral and cellular immunity

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16
Q

Lymphocyte life span

A

Very variable

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17
Q

HSC characteristics

A
  1. Self renew
  2. Differentiate to mature progeny
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18
Q

What do common myeloid progenitors give rise to

A

Megarakaryocyte (-> platelet)
Erythrocyte
Mast cell
Myeloblast (-> granulocytes and monocytes)

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19
Q

Granulocytes

A

Basophil

Neutrophil

Eosinophil

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20
Q

What do common lymphoid progenitors give rise to

A

NK cells

Small lymphocyte (-> T and B lymphocytes,, b-> plasma cell)

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21
Q

Sites of haemopoiesis

A
  1. Yolk sac (3 wks gestation) : generation of HSC
  2. Liver (6-8wks gestation) : maintenance and expansion of HSC
  3. Bone marrow (10 wks gestation)
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22
Q

Bone marrow as a site of haemopoiesis

A

Starts developing haemopoietic activity around 10 wks gestation

Occurs in all bones in children

In adults mainly pelvis, vertebrae and sternum

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23
Q

HSC distribution

A

Ordered fashion within bone marrow amongst mesenchymal cells, endothelial cells and the vasculature which HSCs interact with

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24
Q

What is haemopoiesis regulated by

A

Number of genes, transcription factors, growth factors and the micro environment

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25
Disruption to balance of haemopoiesis
Disturb proliferation vs differentiation leading to leukaemia or bone marrow failure
26
What are haemopoietic growth factors
Glycoprotein hormones which bind to cell surface receptors and regulate proliferation and differentiation of HSC and function of mature blood cells
27
Examples of haemopoietic growth factors
Erythropoietin (EPO) - erythropoiesis Thrombopoietin (TPO) - megakaryocytopoiesis and platelet production G-CSF, G-M CSF and cytokines - granulocyte and monocyte production
28
Erythropoiesis
Development of red blood cells
29
As differentiation progresses
Self renewal and lineage plasticity decreass
30
Lineage of RBC changes
Lose nucleus Change from polychromatic
31
What is required for erythropoiesis
Iron B12 Folic acid Erythropoietin
32
Microcytic anaemia
Small RBC due to iron deficiency or low availability
33
Causes of iron deficiencies
Increased blood loss Reduced intake Increased requirement (pregnancy)
34
Causes of decreased iron availability
Anaemia of chronic disease / inflammation
35
Macrocytic anaemia
Large RBC B12/ folate deficiency (megaloblastic anaemia)
36
EPO synthesised in response to
Hypoxia
37
Demand supply feedback loop of EPO
Hypoxia -> liver inc EPO synthesis -> inc bone marrow activity <- inc red blood cell production
38
Iron functions
Oxygen transport in haemoglobin Mitochondrial proteins ( ytochromes abc)
39
Signs of low iron
Hyopchromic (pale), microcytic RBC Gloss it is (inflamed tongue) Spoon shaped nails Pale conjunctiva
40
Where is iron absorbed
Duodenum
41
Best absorbed iron
Haem iron - ferrous (2) Animal derived
42
Non haem iron
Ferric (3) Requires action of a reducing substance for absorption Sources of it reduce absorption such as soya beans which contain phytates
43
Excess iron
Potentially toxic to organs especially the heart and liver
44
How much iron per day is absorbed form diet
1-2 mg
45
How is iron transferred
As transferrin in plasma (3mg)
46
How much iron is in bone marrow
300mg
47
How much iron in RBC
2500mg
48
How much iron in reticuloendothelial system
500mg
49
Iron loss from system
1-2mg a day Via muscles and enzymes (myoglobin and enzymes)
50
How much iron in myoglobin and enzymes
300 and 150mg
51
How much iron in liver
250mg stored as ferritin
52
How much iron is absorbed in pregnancy
6mg
53
How is iron absorption regulated
Hepcidin
54
What is hepcidin secreted by
Liver (in response to high storage iron)
55
How does Hepcidin work
Blocks absorption of iron from the gut and release of storage iron
56
Anaemia of chronic disease/ inflammation
Decrease in EPO production causing a decrease in iron production and availability Pro inflammatory cytokines decrease EPO and inc Hepcidin
57
What is b12 required for
DNA synthesis Integrity of nervous system
58
What is folic acid required for
DNA synthesis Homocysteine metabolism
59
DNA synthesis with b12 and folate deficiency
Needed for dttp synthesis for thymidine Deficiency affect all rapidly dividing cells inc bone marrow. -cells can grow but are unable to divide giving megaloblastic anaemia (macrocytic)
60
Absorption of b12
Stomach (cleaved with hcl then) combined with intrinsic factor made by parietal cells Small intestine it binds to receptors in the ileum
61
Causes of b12 deficiency
Inadequate intake Inadequate secretion of IF (pernicious anaemia) Malabsorption (coeliac disease, surgery) Achlorhydria - lack of acid in stomach
62
Red cell destruction
Heme excreted as bilirubin in bile, iron from haem transferred as transferrin in plasma and returns to bone marrow where it is recycled Happens in spleen by macrophages
63
Haemolytic anaemias
Can be jaundiced due to inc bilirubin levels when actively haemolysing
64
What does erythrocyte function depend on
Integrity of membrane Haemoglobin structure and function Cellular metabolism Defect in any of these leads to shortened survival (haemolysis)
65
Central pallor size
No greater than 1/3 its diameter otherwise hypochromic
66
What’s RBC membrane made up of
Lipid bilayer supported by a protein skeleton Contains transmembranous proteins
67
Disruption to vertical linkages in RBC membrane
Causes hereditary spherocytosis (Autosomal dominant)
68
Spherocytes
Spherical shape Lack central pallor Loss of membrane without equivalent cytoplasm loss Less flexible and are removed prematurely - haemolytic anaemia
69
Disruption of horizontal linkages in RBC membrane
Produces hereditary elliptocytosis
70
Red cell metabolism includes
Generation of atp Maintenance Hb function, membrane integrity, RBC volume
71
PPP
Glucose 6 phosphate completely oxidised to CO2 Producing NADPH
72
NADPH
Provides reducing power for maintaining reduced glutathione- viral antioxidant in RBC
73
G6PD
Glucose 6 phosphate dehydrogenase maintains reducing power of NADPH Deficiency causes vulnerability of RBC to oxidant damage
74
G6PD Deficiency
Manifests in males (X linked inheritance) Causes intravascular haemolysis (see bite cells)
75
Bite cells
Irregular outline Smaller and have lost central pallor Result from oxidant damage to cell membrane and Hb Hb is denatured and forms round inclusions called Heinz bodies (on 1 Side of cell) can be detected by specific tests
76
Polycythaemia
Too many red cells in the circulation Hb, RBC and hct all increased
77
Pseudo polycythaemia
Reduced plasma volume due to dehydration etc.
78
True polycythaemia
Inc in total volume of red cells in circulation Blood doping, EPO increase
79
Polycythaemia Vera
Intrinsic bone marrow disorder where an increase in erythropoiesis is independent of EPO Myeloproliferatuve disorder Can lead to hyperviscocity (thick blood) which can cause thrombosis Blood can be removed to reduce viscosity and drugs to reduce by production

POM 2 G: HAEMATOLOGY (8 decks)

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