Red Blood Cells Flashcards
1
Q
Where are blood cells derived from?
A
haemopoietic stem cells (HSCs) and produced throughout life in the bone marrow
2
Q
What is haemopoiesis?
A
The production and differentiation of blood cells
3
Q
What do the haemopoietic stem cells (HSCs) give rise to?
A
Lymphoid stem cells + myeloid stem cells
different mature blood cell types and tissues
4
Q
What is derived from myeloid stem cells ?
A
RBCs, granulocytes, monocytes + platelets
5
Q
What is haemopoiesis regulated by?
A
a number of genes, transcription factors, growth factors + the microenvironment
6
Q
How many blood cells does a person produce each day?
A
500 billion
7
Q
what ability do the HSC have?
A
self-renew
- some of their daughter cells remain as HSCs
- pool of HSCs not depleted
8
Q
what is the other ability of HSC?
A
differentiate to mature descendants
- other daughter cells follow a different differentiation pathway
9
Q
Can the mature differentiated cells renew?
A
no. they are committed down that differentiation pathway
10
Q
What do multipotent hematopoietic stem cells give rise to?
A
populations of precursor cells
11
Q
What do precursor cells give rise to ?
A
cells that are increasingly commited to the production of a single type of mature blood cell
12
Q
What are granulocytes?
A
mylocytes that contain granules
basophil, neutrophil, eosinophil
13
Q
Where are haematopoietic stem cells (HSCs) derived from in the embryo?
A
mesoderm
14
Q
Where are primitive red blood cells + platelet precursors + macrophages initially formed?
A
in the vasulature of the extraembryonic yolk sac before the liver takes over( btw 6-8 weeks of gestation)
15
Q
Until when does the liver continue being the main source of blood in the foetus?
A
shortly before birth
16
Q
When does the bone marrow start developing haemopoietic activity?
A
from 10 weeks gestation
17
Q
Which is the sole site of haemapoiesis?
A
the bone marrow
18
Q
Where does haemapoeisis occur in children?
A
almost in all bones
19
Q
Where is haemapoeisis restricted to by adulthood?
A
the bone marrow of the: pelvis
vertebrae
sternum
proximal ends of the long bones of the thigh and arm, femur + humerus
20
Q
What cells are distributed across the bone marrow?
A
Haemopoietic stem cells progenitor cells mesenchymal cells endothelial cells the vasculature with which the HSCs interact
21
Q
What can the disruption of the regulation of pluripotent HSCs lead to?
A
disturb the balance between proliferation and differentiation –> may lead to leukaemia / bone marrow failure
22
Q
What are Haemopoietic growth factors?
A
Glycoprotein hormones which bind to cell surface receptors
23
Q
What do Haemopoietic growth factors regulate?
A
proliferation and differentiation of HSCs
+
function of mature blood cells
24
Q
What is the influence under which red cells are produced?
A
Erythropoietin (EPO)
25
Where is Erythropoietin (EPO) synthesised?
in the kidney
26
What is the production of granulocytes and monocytes under the influence of?
G-CSF, G-M CSF, cytokines e.g. interleukins
27
What is the production of platelets under the influence of?
thrombopoietin
28
What produces the haepoietic growth factors?
cells of the bone marrow
29
Lymphoid differentiation steps to B cells
Pluripotent HSC -->
Common lymphoid progenitor -->
B cell progenitors in bone marrow-->
mature B cells (antibody-producing)
30
Lymphoid differentiation steps to T cells
Pluripotent HSC -->
Common lymphoid progenitor -->
T cell progenitors thymus-> bone marrow-->
mature T cells (cytokine-producing)
31
What response are B cells part of?
humoral immune response
32
What response are T cells part of?
cellular immune response
33
Formation of red cells steps?
Pluripotent HSC -->
common myeloid progenitor --> granulocyte-monocyte + MEP
MEP--> erythroid + megakaryocyte
34
summary of erythropoiesis
```
Proerythroblast -->
Early erythroblast-->
Intermediate erythroblast-->
Late erythroblast-->
Polychromatic erythrocyte-->
mature erythrocyte
```
35
What are reticulocytes?
RBCs stained with methylin blue
36
When do we see nucleated RBCs in the blood?
rarely, when there is a high demand for blood cells to be produced in the bone marrow and immature RBCs are being released into the circulation prematurely
37
What is required for erythropoiesis?
iron
folate
vitamin B12
erythropoeitin
38
What happens when theres low iron/ B12/ folate in the blood?
```
anaemia
either microcytic (iron deficiency)
or macrocytic (B12/folate deficiency)
```
39
How do RBCs look like when theres less iron (microcytic anaemia)?
smaller
40
How do RBCs look like when theres less B12/ folate (macrocytic anaemia)?
larger
| they can grow but are unable to divide
41
What is erythropoietin?
a glycoprotein that is synthesised mainly in the kidney in response to hypoxia
42
What does erythropoietin stimulate?
the bone marrow to produce more RBCs
43
When is erythropoietin synthesised?
when there is a reduction in the oxygen supply of the kidney
44
What happens when a person has hypoxia/ anaemia?
hypoxia + anaemia increase erythropoietin synthesis --> increased bone marrow activity --> increased RBC production
increases the oxygen carrying capacity of the blood
45
What are the 2 major functions of iron?
- Oxygen transport in haemoglobin
- Mitochondrial proteins
- energy metabolism enzymes, respiration, DNA synthesis, cell cycle
- healthy skin, mucous membranes, hair and nails
46
Where is iron absorbed?
duodenum
47
In what form is iron best absorbed?
Haem iron (i.e. animal derived) is in ferrous (Fe2 +)
red meat, poultry and fish
48
What is the form of iron in food? (requires a lot of action of reducing substances)
Non-haem iron is present mainly in ferric (Fe3 +)
grains, beans, vegetables, nut and seeds, animal meat, dairy
49
What are phytates?
Sources of non-haem iron such as soya beans often contain phytates, reducing absorption
50
What happens when theres excess iron?
potentially toxic to organs such as the heart and liver
as it forms free radicals
there is no mechanism to regulate iron excretion
51
Is there a change in iron absorption in the gut?
iron absorption is increased when stores are low or when there is a need for increased erythropoiesis
52
how is iron transported in the plasma?
bound to transport protein transferrin
53
Where is iron stored?
liver
54
how is iron excreted from the body?
it isnt. its recycled
| only a small portion of it is lost by the shedding of the skin
55
What is hepcidin?
regulating hormone of iron absorption
Absorption and release of storage iron is blocked by hepcidin
56
An increase in need for erythropoiesis?
leads to a reduction in hepcidin and more absorption
57
What regulates hepcidin synthesis?
Hepcidin synthesis is suppressed by erythropoietic activity: this ensures iron supply by increasing ferroportin in the duodenum enterocyte, which increases iron absorption
58
What happens when the body iron stores are full?
increased hepcidin secretion by liver
- hepcidin binds to ferroportin
- ferroportin is degraded
- prevents the efflux of iron from the enterocyte, so it is lost when the cell is shed into the gut lumen (dies)
59
Hepcidin production is increased in inflammatory states. How does this cause anaemia?
REDUCTION IN IRON SUPPLY. THE RESULTANT ANAEMIA IS KNOWN AS ANAEMIA OF CHRONIC DISEASE
60
What does interferon do?
results in reduction of erythropoiesis
61
What do pro-inflammatory cytokines do?
reduce the production of erythropoietin
62
What is B12 and folate needed for?
for dTTP synthesis, necessary for the synthesis of thymidine
63
What does a B12 and folate deficiency result in?
inhibits DNA synthesis
64
What cells does a B12 and folate deficiency affect?
affects all rapidly dividing cells
- bone marrow: cells can grow but are unable to divide normally
- epithelial surfaces of mouth and gut
- gonads
65
What are the sources of vitamin B12?
```
exclusively food of animal origin
Meat
Liver & kidney
Fish
Oysters & clams
Eggs
Milk & cheese
Fortified cereals
```
66
What are the sources of folic acid?
```
Green leafy vegetables
Cauliflower
Brussels sprouts
Liver & kidney
Whole grain cereals
Yeast
Fruit
```
67
What happens to vitamin B12 in the stomach?
B12 combines with Intrinsic factor (IF) made in the gastric parietal cells
IT IS CLEAVED by HCl
68
What happens to vitamin B12 in the small intestine?
B12-IF binds to receptors in the ileum
69
What is the intrinsic factor?
highly resistant to digestion enzymes
70
Vitamin B12 deficiency may result from?
- inadequate intake e.g. veganism
- lack of acid in stomach (achlorhydria)
- inadequate secretion of IF: pernicious anaemia (an autoimmune disorder)
- Malabsorption e.g. coeliac disease
71
Where is folic acid absorbed?
small intestine
72
When do the body requirements for folic acid increase?
- during pregnancy
| - increased RBC production (sickle cell anaemia)
73
how long do RBCs circulate for?
120 days
- - Ultimately it is destroyed by the phagocytic cells of the spleen (macrophages)
- - Iron from haem returns to the bone marrow where it is recycled
74
What does the metabolism of haem produce?
bilirubin which is excreted in bile (yellow compound)
75
What does erythrocyte function depend on?
- Integrity of the membrane
- Haemoglobin structure and function
- Cellular metabolism
A defect in any of these results in shortened erythrocyte survival (haemolysis)
76
What is haemolysis?
shortened erythrocyte survival
77
What is the shape or erythrocytes?
biconcave in shape, which helps their manoeuvrability through small blood vessels to deliver oxygen
78
What is the membrane of erythrocytes made up of?
lipid bilayer supported by protein cytoskeleton and contains transmembrane proteins
79
What is the role of the membrane of RBCs?
maintain the integrity, shape and elasticity/deformability of the red cell
80
What is hereditary spherocytosis?
| autosomal dominant
Disruption of vertical linkages in membrane (usually ankyrin/spectrin)
81
What are spherocytes?
cells that are approximately spherical in shape
- loss of cell membrane without the loss of an equivalent amount of cytoplasm so the cell is forced to round up
- become less flexible and are removed prematurely by the spleen –haemolysis
82
What is Hereditary Elliptocytosis?
Disruption of horizontal
| linkages in membrane
83
Where can elliptocytes also occur?
in iron deficiency
84
What is haemoglobin A made up of?
4 subunits, each composed of a globin chain (2 α, 2 β) bound to a haem group
Each haem group consists of a ferrous iron ion (Fe2+) held in a ring known as a porphyrin
- each Fe2+ can bind to 1 oxygen molecule
85
What is fetal haemoglobin?
HAS 2 α AND 2 γ GLOBIN CHAINS
86
What does a Hb dissociation curve show?
oxygen carrying capacity of Hb at different partial pressures of O2
87
Why is the curve sigmoid?
the binding of one O2 molecule facilitates the binding of the second molecule- cooperativity
due to the induced conformational change in the structure of the haemoglobin molecule by the binding of an oxygen molecule
88
What is p50
the partial pressure of O2 at which haemoglobin is half saturated with O2
89
What does the normal position of the Hb dissociation curve depend on?
H+ ion concentration (pH)
CO2 in red blood cells
Structure of Hb
Concentration of 2,3-DPG
90
What is the Bohr effect?
increases in CO2 partial pressure of blood or decreases in blood pH result in a lower affinity of haemoglobin for O2
91
When does the Hb dissociation curve shift right?
- High CO2 - low pH – ‘Bohr effect’
- High 2,3-DPG
- HbS (sickle Hb) --> less O2 reaches the tissues
92
When does the Hb dissociation curve shift left?
- HbF (fetal Hb)
| - CO
93
What is the importance of red cell metabolism?
- Generation of ATP to meet energy requirements
- Maintenance of:
- - haemoglobin function
- - membrane integrity and deformability
- - RBC volume
94
G6PD
-Important enzyme in the hexose monophosphate (HMP) shunt
-HMP shunt is tightly coupled to Glutathione metabolism, which
protects red cell from oxidant damage
- Oxidants may be generated in the blood stream, e.g. during infection, or may be exogenous e.g. drugs, broad beans
- Deficiency of G6PD causes red cells to be vulnerable to oxidant damage
95
2,3-Diphosphoglycerate (2,3-DPG)
- Produced by Rapaport-Luebering shuttle
- Allosteric effector - modulates haemoglobin oxygen affinity
- Binds to -globin chain in central cavity of haemoglobin molecule
- Role in adaptive response to anaemia, hypoxia and high altitude
96
What is G6PD defficiency?
- enzyme disorder
- X-linked inheritance
- causes intermittent , severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
97
What is a microcytic RBC?
red cells that are smaller than normal or an anaemia with small red cells
98
What is a normocytic RBC?
red cells that are of normal size or an anaemia with normal sized red cells
99
What is a macrocytic RBC?
red cells that are larger than normal or an anaemia with large red cells
100
What are the causes of microcytosis?
- Defect in haem synthesis
Iron deficiency
Anaemia of chronic disease
- Defect in globin synthesis (thalassaemia)
Defect in α chain synthesis (α thalassaemia)
Defect in β chain synthesis (β thalassaemia)
101
What are the types of macrocytosis?
- Round macrocytes
- Oval macrocytes
- Polychromatic macrocytes
102
What are the causes of macrocytosis?
- Lack of vitamin B12 or folic acid (megaloblastic anaemia)
- Liver disease and ethanol toxicity
- Haemolysis (polychromasia)
- Pregnancy
103
What is the colour of RBCs?
about a third of the diameter that is pale
| - is a result of the disc shape of the red cell; the centre has less haemoglobin and is therefore paler
104
What is hypochromia?
cells have a larger area of central pallor than normal
- lower haemoglobin content and concentration and a flatter cell
* Hypochromia and microcytosis often go together
105
What is polychromasia?
an increased blue tinge to the cytoplasm of a red cell
| --> red cell is young
106
Why is polychromasia one of the causes of macrocytosis?
Polychromatic cells are larger than normal red cells
107
How do we detect young RBCs?
```
special stain (new methylene blue) for reticulocytes
* this stains their higher RNA content
```
108
What is reticulocytosis?
the presence of increased numbers of reticulocytes
109
When does reticulocytosis occur?
as a response to bleeding or red cell destruction (haemolysis)
110
What is anisocytosis?
– red cells show more variation in size than is normal
111
What is poikilocytosis?
– red cells show more variation in shape than is normal
112
What are the variety of shapes of poikilocytes?
```
Target cells
Spherocytes
Elliptocytes
Irregularly contracted cells
Sickle cells
Fragments
```
113
What are target cells?
cells cells with an accumulation of haemoglobin in the centre of the area of central pallor
114
What conditions do target cells occur in?
- obstructive jaundice
- liver disease
- haemoglobinopathies
- hyposplenism
115
What do sickle cells result from?
the polymerisation of haemoglobin S, which in the deoxygenated form is much less soluble than haemoglobin A
Haemoglobin S occurs when one or two copies of an abnormal β globin gene (βS) are inherited
116
What causes sickle cell?
a mutation in the β-globin gene: a charged glutamic acid residue in position 6 is replaced by an uncharged valine molecule
117
What are RC fragments or schistocytes?
small pieces of red cells
| They indicate that a red cell has fragmented
118
What do red cell fragments result from?
from a shearing process caused by the platelet-rich blood clots in the small blood vessels e.g. disseminated intravascular coagulopathy
119
What is a reference range for blood counts and films?
range is derived from a carefully defined reference population:
Samples are collected from healthy volunteers with defined characteristics
They are analysed using the instrument and techniques that will be used for patient samples
The data are analysed by an appropriate statistical technique
(A normal range is a much vaguer concept)
120
Not all results outside the reference range are abnormal
Not all results within the normal range are normal
121
What should you examine and describe the rbc
Size
Shape
Age (polychromasia)
? Poikilocytes
