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POM (Principles of Medicine) > Red Blood Cells > Flashcards

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

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2
Q

What is haemopoiesis?

A

The production and differentiation of blood cells

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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

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4
Q

What is derived from myeloid stem cells ?

A

RBCs, granulocytes, monocytes + platelets

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5
Q

What is haemopoiesis regulated by?

A

a number of genes, transcription factors, growth factors + the microenvironment

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6
Q

How many blood cells does a person produce each day?

A

500 billion

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7
Q

what ability do the HSC have?

A

self-renew

  • some of their daughter cells remain as HSCs
  • pool of HSCs not depleted
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8
Q

what is the other ability of HSC?

A

differentiate to mature descendants

- other daughter cells follow a different differentiation pathway

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9
Q

Can the mature differentiated cells renew?

A

no. they are committed down that differentiation pathway

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10
Q

What do multipotent hematopoietic stem cells give rise to?

A

populations of precursor cells

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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

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12
Q

What are granulocytes?

A

mylocytes that contain granules

basophil, neutrophil, eosinophil

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13
Q

Where are haematopoietic stem cells (HSCs) derived from in the embryo?

A

mesoderm

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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)

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15
Q

Until when does the liver continue being the main source of blood in the foetus?

A

shortly before birth

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16
Q

When does the bone marrow start developing haemopoietic activity?

A

from 10 weeks gestation

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17
Q

Which is the sole site of haemapoiesis?

A

the bone marrow

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18
Q

Where does haemapoeisis occur in children?

A

almost in all bones

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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

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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
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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

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22
Q

What are Haemopoietic growth factors?

A

Glycoprotein hormones which bind to cell surface receptors

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23
Q

What do Haemopoietic growth factors regulate?

A

proliferation and differentiation of HSCs
+
function of mature blood cells

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24
Q

What is the influence under which red cells are produced?

A

Erythropoietin (EPO)

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25
Q

Where is Erythropoietin (EPO) synthesised?

A

in the kidney

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26
Q

What is the production of granulocytes and monocytes under the influence of?

A

G-CSF, G-M CSF, cytokines e.g. interleukins

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27
Q

What is the production of platelets under the influence of?

A

thrombopoietin

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28
Q

What produces the haepoietic growth factors?

A

cells of the bone marrow

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29
Q

Lymphoid differentiation steps to B cells

A

Pluripotent HSC –>
Common lymphoid progenitor –>
B cell progenitors in bone marrow–>
mature B cells (antibody-producing)

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30
Q

Lymphoid differentiation steps to T cells

A

Pluripotent HSC –>
Common lymphoid progenitor –>
T cell progenitors thymus-> bone marrow–>
mature T cells (cytokine-producing)

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31
Q

What response are B cells part of?

A

humoral immune response

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32
Q

What response are T cells part of?

A

cellular immune response

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33
Q

Formation of red cells steps?

A

Pluripotent HSC –>
common myeloid progenitor –> granulocyte-monocyte + MEP

MEP–> erythroid + megakaryocyte

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34
Q

summary of erythropoiesis

A 
Proerythroblast --> 
Early erythroblast--> 
Intermediate erythroblast--> 
Late erythroblast--> 
Polychromatic erythrocyte--> 
mature erythrocyte
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35
Q

What are reticulocytes?

A

RBCs stained with methylin blue

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36
Q

When do we see nucleated RBCs in the blood?

A

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

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37
Q

What is required for erythropoiesis?

A

iron
folate
vitamin B12
erythropoeitin

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38
Q

What happens when theres low iron/ B12/ folate in the blood?

A 
anaemia
either microcytic (iron deficiency)
or macrocytic (B12/folate deficiency)
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39
Q

How do RBCs look like when theres less iron (microcytic anaemia)?

A

smaller

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40
Q

How do RBCs look like when theres less B12/ folate (macrocytic anaemia)?

A

larger

they can grow but are unable to divide

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41
Q

What is erythropoietin?

A

a glycoprotein that is synthesised mainly in the kidney in response to hypoxia

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42
Q

What does erythropoietin stimulate?

A

the bone marrow to produce more RBCs

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43
Q

When is erythropoietin synthesised?

A

when there is a reduction in the oxygen supply of the kidney

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44
Q

What happens when a person has hypoxia/ anaemia?

A

hypoxia + anaemia increase erythropoietin synthesis –> increased bone marrow activity –> increased RBC production
increases the oxygen carrying capacity of the blood

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45
Q

What are the 2 major functions of iron?

A
  • Oxygen transport in haemoglobin
  • Mitochondrial proteins
  • energy metabolism enzymes, respiration, DNA synthesis, cell cycle
  • healthy skin, mucous membranes, hair and nails
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46
Q

Where is iron absorbed?

A

duodenum

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47
Q

In what form is iron best absorbed?

A

Haem iron (i.e. animal derived) is in ferrous (Fe2 +)

red meat, poultry and fish

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48
Q

What is the form of iron in food? (requires a lot of action of reducing substances)

A

Non-haem iron is present mainly in ferric (Fe3 +)

grains, beans, vegetables, nut and seeds, animal meat, dairy

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49
Q

What are phytates?

A

Sources of non-haem iron such as soya beans often contain phytates, reducing absorption

50
Q

What happens when theres excess iron?

A

potentially toxic to organs such as the heart and liver

as it forms free radicals

there is no mechanism to regulate iron excretion

51
Q

Is there a change in iron absorption in the gut?

A

iron absorption is increased when stores are low or when there is a need for increased erythropoiesis

52
Q

how is iron transported in the plasma?

A

bound to transport protein transferrin

53
Q

Where is iron stored?

A

liver

54
Q

how is iron excreted from the body?

A

it isnt. its recycled

only a small portion of it is lost by the shedding of the skin

55
Q

What is hepcidin?

A

regulating hormone of iron absorption

Absorption and release of storage iron is blocked by hepcidin

56
Q

An increase in need for erythropoiesis?

A

leads to a reduction in hepcidin and more absorption

57
Q

What regulates hepcidin synthesis?

A

Hepcidin synthesis is suppressed by erythropoietic activity: this ensures iron supply by increasing ferroportin in the duodenum enterocyte, which increases iron absorption

58
Q

What happens when the body iron stores are full?

A

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
Q

Hepcidin production is increased in inflammatory states. How does this cause anaemia?

A

REDUCTION IN IRON SUPPLY. THE RESULTANT ANAEMIA IS KNOWN AS ANAEMIA OF CHRONIC DISEASE

60
Q

What does interferon do?

A

results in reduction of erythropoiesis

61
Q

What do pro-inflammatory cytokines do?

A

reduce the production of erythropoietin

62
Q

What is B12 and folate needed for?

A

for dTTP synthesis, necessary for the synthesis of thymidine

63
Q

What does a B12 and folate deficiency result in?

A

inhibits DNA synthesis

64
Q

What cells does a B12 and folate deficiency affect?

A

affects all rapidly dividing cells

  • bone marrow: cells can grow but are unable to divide normally
  • epithelial surfaces of mouth and gut
  • gonads
65
Q

What are the sources of vitamin B12?

A 
exclusively food of animal origin
Meat
Liver & kidney
Fish
Oysters & clams
Eggs
Milk & cheese
Fortified cereals
66
Q

What are the sources of folic acid?

A 
Green leafy vegetables
Cauliflower
Brussels sprouts
Liver & kidney 
Whole grain cereals
Yeast
Fruit
67
Q

What happens to vitamin B12 in the stomach?

A

B12 combines with Intrinsic factor (IF) made in the gastric parietal cells
IT IS CLEAVED by HCl

68
Q

What happens to vitamin B12 in the small intestine?

A

B12-IF binds to receptors in the ileum

69
Q

What is the intrinsic factor?

A

highly resistant to digestion enzymes

70
Q

Vitamin B12 deficiency may result from?

A
  • 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
Q

Where is folic acid absorbed?

A

small intestine

72
Q

When do the body requirements for folic acid increase?

A
  • during pregnancy

- increased RBC production (sickle cell anaemia)

73
Q

how long do RBCs circulate for?

A

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
Q

What does the metabolism of haem produce?

A

bilirubin which is excreted in bile (yellow compound)

75
Q

What does erythrocyte function depend on?

A
  • Integrity of the membrane
  • Haemoglobin structure and function
  • Cellular metabolism

A defect in any of these results in shortened erythrocyte survival (haemolysis)

76
Q

What is haemolysis?

A

shortened erythrocyte survival

77
Q

What is the shape or erythrocytes?

A

biconcave in shape, which helps their manoeuvrability through small blood vessels to deliver oxygen

78
Q

What is the membrane of erythrocytes made up of?

A

lipid bilayer supported by protein cytoskeleton and contains transmembrane proteins

79
Q

What is the role of the membrane of RBCs?

A

maintain the integrity, shape and elasticity/deformability of the red cell

80
Q

What is hereditary spherocytosis?

autosomal dominant

A

Disruption of vertical linkages in membrane (usually ankyrin/spectrin)

81
Q

What are spherocytes?

A

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
Q

What is Hereditary Elliptocytosis?

A

Disruption of horizontal

linkages in membrane

83
Q

Where can elliptocytes also occur?

A

in iron deficiency

84
Q

What is haemoglobin A made up of?

A

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
Q

What is fetal haemoglobin?

A

HAS 2 α AND 2 γ GLOBIN CHAINS

86
Q

What does a Hb dissociation curve show?

A

oxygen carrying capacity of Hb at different partial pressures of O2

87
Q

Why is the curve sigmoid?

A

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
Q

What is p50

A

the partial pressure of O2 at which haemoglobin is half saturated with O2

89
Q

What does the normal position of the Hb dissociation curve depend on?

A

H+ ion concentration (pH)
CO2 in red blood cells
Structure of Hb
Concentration of 2,3-DPG

90
Q

What is the Bohr effect?

A

increases in CO2 partial pressure of blood or decreases in blood pH result in a lower affinity of haemoglobin for O2

91
Q

When does the Hb dissociation curve shift right?

A
  • High CO2 - low pH – ‘Bohr effect’
  • High 2,3-DPG
  • HbS (sickle Hb) –> less O2 reaches the tissues
92
Q

When does the Hb dissociation curve shift left?

A
  • HbF (fetal Hb)

- CO

93
Q

What is the importance of red cell metabolism?

A
  • Generation of ATP to meet energy requirements
  • Maintenance of:
    • haemoglobin function
    • membrane integrity and deformability
    • RBC volume
94
Q

G6PD

A

-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
Q

2,3-Diphosphoglycerate (2,3-DPG)

A
  • 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
Q

What is G6PD defficiency?

A
  • enzyme disorder
  • X-linked inheritance
  • causes intermittent , severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
97
Q

What is a microcytic RBC?

A

red cells that are smaller than normal or an anaemia with small red cells

98
Q

What is a normocytic RBC?

A

red cells that are of normal size or an anaemia with normal sized red cells

99
Q

What is a macrocytic RBC?

A

red cells that are larger than normal or an anaemia with large red cells

100
Q

What are the causes of microcytosis?

A
  • 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
Q

What are the types of macrocytosis?

A
  • Round macrocytes
  • Oval macrocytes
  • Polychromatic macrocytes
102
Q

What are the causes of macrocytosis?

A
  • Lack of vitamin B12 or folic acid (megaloblastic anaemia)
  • Liver disease and ethanol toxicity
  • Haemolysis (polychromasia)
  • Pregnancy
103
Q

What is the colour of RBCs?

A

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
Q

What is hypochromia?

A

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
Q

What is polychromasia?

A

an increased blue tinge to the cytoplasm of a red cell

–> red cell is young

106
Q

Why is polychromasia one of the causes of macrocytosis?

A

Polychromatic cells are larger than normal red cells

107
Q

How do we detect young RBCs?

A 
special stain (new methylene blue) for reticulocytes 
* this stains their higher RNA content
108
Q

What is reticulocytosis?

A

the presence of increased numbers of reticulocytes

109
Q

When does reticulocytosis occur?

A

as a response to bleeding or red cell destruction (haemolysis)

110
Q

What is anisocytosis?

A

– red cells show more variation in size than is normal

111
Q

What is poikilocytosis?

A

– red cells show more variation in shape than is normal

112
Q

What are the variety of shapes of poikilocytes?

A 
Target cells
Spherocytes 
Elliptocytes
Irregularly contracted cells
Sickle cells
Fragments
113
Q

What are target cells?

A

cells cells with an accumulation of haemoglobin in the centre of the area of central pallor

114
Q

What conditions do target cells occur in?

A
  • obstructive jaundice
  • liver disease
  • haemoglobinopathies
  • hyposplenism
115
Q

What do sickle cells result from?

A

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
Q

What causes sickle cell?

A

a mutation in the β-globin gene: a charged glutamic acid residue in position 6 is replaced by an uncharged valine molecule

117
Q

What are RC fragments or schistocytes?

A

small pieces of red cells

They indicate that a red cell has fragmented

118
Q

What do red cell fragments result from?

A

from a shearing process caused by the platelet-rich blood clots in the small blood vessels e.g. disseminated intravascular coagulopathy

119
Q

What is a reference range for blood counts and films?

A

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
Q

Not all results outside the reference range are abnormal

A

Not all results within the normal range are normal

121
Q

What should you examine and describe the rbc

A

Size
Shape
Age (polychromasia)
? Poikilocytes

POM (Principles of Medicine) (17 decks)

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