1
Q
Name the different types of blood cells
A
- white
- red
- platelets
2
Q
What is haematopoiesis
A
- production of blood from bone marrow
- derived from pluripotent stem cells
3
Q
What is red cells dervived from?
A
- pluripotent stem cells
4
Q
Where does haematopoiesis occur in the embryo? and then when at birth?
A
- embryo = yolk sac, then liver, then bone marrow
- adult = bone marrow, liver, spleen
5
Q
Which bone marrow is responsible for the production of red blood cells?
A
- the axial skeleton
6
Q
Explain the formation of blood cells from the stem cells?
A
- proliferation
- differentiaion
- haematopoietic trees
7
Q
What are the 2 main routes in the haematopoietic tree and their final product
A
- cmp (myeloid) -> granulocytes, erythrocytes, platelets, macrophages
- CLP (lymphoid) -> B cells, T cells and NK cells
8
Q
What state do most stem cells lie in?
A
- quiescent state
9
Q
Term given to red cell production, different from blood cell production
A
- erythropoiesis
10
Q
What is the primary cell called of erythropoiesis?
A
- pronormoblast
- early normoblast
- intermediate normoblast
- late normoblast
- reticulocyte
- erythrocyte
11
Q
What is the difference between a reticulocyte and a erythrocyte?
A
- a reticulocyte is more immature and contains a nucleus and is found in bone marrow
- erythrocyte has no nucleus and has entered blood streem
12
Q
Explain platelet formation
A
- nucleus replicated but no cell division
- forms a megakaryocyte
- budding off -> platelets released
13
Q
3 main granulocytes?
A
- eosinophils
- basophills
- neutrophils
14
Q
Describe neutrophils
A
- most numerous white cell
- fine granules
- lobbed nucleus
- short lived
15
Q
What may cause an increase in neutrophils?
A
- infection
- trauma
- infarction
16
Q
Describe the appearance of eosinophils
A
- bi-lobbed
- bright red granules
- involved in hypersensitivity
17
Q
Describe appearance of basophils?
A
- large purple granules
- basic staining
- release histamine
18
Q
Monocytes vs macrophages
A
- monocytes = in the blood stream
- macrophages = in the tissue
19
Q
Describe the appearance of lymphocytes
A
- big nucleus
20
Q
3 ways of sampling blood in haematology?
A
- immunophenotyping
- bio-assay
- bone marrow samples
21
Q
Explain immunophenotyping
A
- looking at surface proteins of cells
- much quicker method
22
Q
Structure of RBC
A
- 2 alpha
- 2 beta
- 4 porphyrin rings with Fe2+
- biconcave
- no nucleus
- no mitochondria
23
Q
Why are RBC limited to 120days?
A
- they have no nucleus or mitochondria
- unable to repair proteins
24
Q
What is present on the cell membrane of a RBC
A
- Sodium potassium ATP pump
25
What is the disadvantage of Fe3+
- unable for O2 to bind
- must be in Fe2+ form
NADH generated in glycolysis helps protect Fe2+
26
Role of haemoglobin
- delivers oxygen to tissue
- acts as a buffer for H+ ions
- Co2 transport
27
Explain the stem cell process
- multipoint haematopoetic cell
- common myeloid progenitor cell (CMP)
- common lymphoid progenitor celll (CLP)
28
What do CMP cells become
- erythrocytes
- platelets
- macrophages
- basophils
- eosinophils
- neutrophils
29
What do CLP cells become
- NK cells
- b cells
- t cells
30
B cells further differentiate into what?
- plasma cells
31
What happens to red blood cells as they mature?
- they become smaller in size
32
Where is hypoxia sensed and what is the consequence
- sensed in the kidney
- erythropoietin hormone secreted
- stimulation of RBC formation
33
Where does normal RBC breakdown occur
- the spleen or liver
34
Explain RBC breakdown
- haemoglobin - heme and globin
- globin - amino acids
- heme - porphyrin (bilirubin) and iron
35
What is heme broken down to
- porphyrin (bilirubin)
| - iron
36
Glycolysis role in the formation of RBC
- Generates ATP
- generated NADH (Prevents Fe2+ oxidising to Fe3+)
- free radical formation
37
Free radical formation may cause what?
- dangerous
- can cause Fe2+ to become Fe3+
- can damage cell membrane
- NADH acts as an electron donor to prevent Fe oxidation
38
Name a reactive oxygen species
- hydrogen peroxide
39
What is the risk associated with hydrogen peroxide
- damage to proteins
40
What is vital for protection of hydrogen peroxide (reactive oxygen species)
- glutathione (GSH)
| - Forms water and an oxidised GSH (GSSG)
41
How is oxidised glutathione regenerated to glutathione
- NADPH
42
What is the rate limiting step in the hexose monophosphate shunt
- G-6-PD
| - Glucose 6 phosphate dehydrogenase
43
Role of NADPH in GSSG
- Recycles to for GSH
44
How is carbon dioxide transported
- dissolved
- carbamino compound in Hb
- bicarbonate
45
What enters the RBC when CO2 leaves in order to preserve the potential
- Cl-
46
Explain the oxygen dissociation curve
- sigmoid
- allosteric cooperative binding
- a drop in Po2 at a lower level results in a greater % saturation drop than a higher
47
What can cause the oxygen dissociation curve to shift to the right and what will that cause
- increase in temp
- decrease pH
- Increase 2,3-BPG
- causes oxygen to be released at a tissue level
- lesser % saturation bound
48
What can cause the oxygen dissociation curve to shift to the left and what are its consequences
- decrease temp
- increaser ph
- decreased 2,3-BPG
- Less o2 released at same PO2
- Greater % saturation bound
49
Describe fetal Hb compared to adult
- 2 alpha and 2 gamma
| - greater o2 saturation in haemoglobin at the same o2
50
Explain the affect of 2,3-BPG on the oxygen dissociation curve
- increased 2,3BPG = Shift to the right
- more released
- less bound
- decreased 2,3-BPG = shift to the left
- less released
- more bound
51
What affect on 2,3-BPG will occur in chronic anaemia?
- up regulation
52
What is termed the machinery of RBC
- The erythron
53
Raw materials of RBC production
- iron
- b12
- folate
54
What is released from the kidneys due to low oxygen levels
- erythropoietin
55
Which stem cell has the higher self-renewing ability and why is that useful
- the long term stem cells
| - good for transplant patients
56
Pathway of RBC production from pronormoblasts
- pronoromblast
- early normoblast
- intermediate normoblast
- late normoblast
- reticulocyte
- erythrocyte
57
Why is iron essential?
- oxygen transport
- electron transport
- present in haemoglobin, myoglobin, enzymes
58
Iron dangerous?
- oxidative stress
| - free radical formation
59
Where does iron absorption take place?
- in the duodenum
| - uptake into cells of duodenal mucosa
60
What enhances iron uptake?
- haem irons
- ascorbic acid
- alcohol
61
What reduces iron uptake?
- tannins
- phylate
- caclcium
62
What reduces Fe3+ to Fe2+
- duodenal cytochrome B
63
What transports Fe2+ from the lumen of duodenum into duodenal cells?
- Divalent metal transport 1
64
What transports iron from the duodenal cell into the body?
- ferroprotein
65
What regulates iron
- hepcidin
- negative regulator
- levels decrease in anaemia = increase iron absorption
66
How can iron status be analysed?
- functional iron (hb concentration)
- transport iron (transferrin saturation)
- storage iron (ferritin)
67
When might ferritin be increased?
- inflammation or malignany
| - increased in anaemia of chronic disease
68
Microcytic anaemias are deficiencies in _____ synthesis
- haemoglobin
69
What is sideroblastic anaemia?
- excess iron build up in the mitochondria and not incorporated into haemoglobin
70
How is iron deficiency anaemia defined?
- anaemia + low iron
71
Explain pathophysiology of anaemia of chronic disease?
- increased ferritin
- increased plasma hepcidin
- decreased iron release from macrophages
72
Causes of primary iron overload
- hereditary haemochromatosis
73
Explain hereditary haemochromatosis?
- HFE gene
- increased Hepcidin
- increased iron absorption
74
Treatment of primary haemochromatosis?
- venesection
75
Treatment of iron overload?
- iron chelating agents
| e. g. desferrioxamine
