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POM Haematology > Red Blood Cells > Flashcards

Red Blood Cells Flashcards

1
Q

Define haemopoiesis

A

The formation and development of red blood cells

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2
Q

Where do blood cells of all type originate from?

A

Bone marrow

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3
Q

What do HSCs (haemopoietic stem cells) give rise to?

A

lymphoid stem cells and myeloid stem cells

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4
Q

What are all blood cells derived from?

A

pluripotent HSCs

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5
Q

What is the major function of erythrocytes?

A

Oxygen transport

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6
Q

How long does an erythrocyte circulate for?

A

120 days

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7
Q

What 2 things do HSCs have the ability to do?

A

Self-renew

Differentiate to mature progeny

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8
Q

Where are HSCs generated?

A

Yolk sac (mesoderm)

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9
Q

Where does haemopoiesis in adults mainly occur?

A

bone marrow

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10
Q

After how long does the bone marrow start developing haemopoietic activity

A

10 weeks into gestation

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11
Q

Which organs are the site of haemopoiesis in a foetus in order?

A

Mesoderm => Liver (HSC maintenance and expansion) => Bone marrow

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12
Q

What regulates megakaryocytopoiesis and platelet production?

A

Thrombopoietin

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13
Q

What is required for erythropoeisis?

A

Iron
Folate
Erythropoietin
Vitamin B12

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14
Q

What does the common myeloid progenitor give rise to that eventually becomes an erythrocyte?

A

proerythroblast > erythroblast > polychromatic erythrocyte > mature erythrocyte

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15
Q

What is erythropoietin?

A

Glycoprotein synthesised mainly in kidney in response to hypoxia

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16
Q

Where is eryhtropoietin mainly synthesised?

A

Kidney

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17
Q

What does erythropoeitin do?

A

Stimulates the bone marrow to produce more red blood cells

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18
Q

What are the 2 major functions of iron?

A

Oxygen transport
Mitochondrial proteins - cytochromes a,b and c for production of ATP
cytochrome P450 for hydroxylation reactions

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19
Q

What does iron deficiency cause?

A

Microcytic anaemia

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20
Q

What does vitamin B12 and folate deficiency cause?

A

Macrocytic anamia

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21
Q

Where is iron absorbed?

A

Duodenum

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22
Q

What is the best absorbed form of iron?

A

ferrous (Fe2+) => Haem Iron

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23
Q

What form is non-haem iron mainly present?

A

ferric (Fe3+)

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24
Q

What reducing substances are required for absorption of non-haem iron?

A

ascorbic acid and vitamin C

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25
Q

What reduces absorption of non-haem iron?

A

Phytates

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26
Q

Why is excess iron potentially toxic to organs such as the heart and liver?

A

No physiological mechanism by which iron is excreted

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27
Q

What regulates absorption of iron in the gut according to body stores?

A

Hepcidin

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28
Q

What suppresses hepcidin synthesis?

A

erythropoietic activity - ensures iron supply by increasing ferroportin in duodenum enterocyte, which increase iron absorption

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29
Q

When is hepcidin synthesis increased?

A

When storage iron is high

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30
Q

Explain the mechanism of hepcidin

A

binds and degrades ferroportin in duodenum enterocyte

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31
Q

What is another name for vitamin B12?

A

Cobalamin

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32
Q

What are B12 and folate needed for?

A

dTTP synthesis, necessary for synthesis of thymidine

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33
Q

Apart from macrocytosis, what else can B12 and folate deficiency lead to?

A

Inhibition of DNA synthesis

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34
Q

What rapidly dividing cells does B12 and folate deficiency affect?

A

Bone marrow
epithelial surfaces of mouth and gut
gonads

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35
Q

What does B12 combine with in the stomach?

A

Intrinsic factor (IF)

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36
Q

Where is IF made?

A

Gastric parietal cells

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37
Q

What is pernicious anaemia?

A

Inadequate secretion of IF

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38
Q

What is achlorhydia?

A

lack of acid in stomach

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39
Q

What may vitamin B12 deficiency result from?

A

Inadequate intake
Lack of stomach acid
Inadequate secretion of IF
Malabsorption (coeliac disease)

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40
Q

Where is folic acid absorbed?

A

small intestine

41
Q

When do the requirements of folic acid increase?

A

during pregnancy

increased red cell production e.g. sickle cell anaemia

42
Q

Where do erythrocytes undergo phagocytosis?

A

Spleen

43
Q

What does catabolism produce and where is this product excreted?

A

Bilirubin; bile

44
Q

What 3 things doe erythrocyte function depend on?

A

Integrity of membrane
Haemoglobin structure and function
Cellular metabolism

45
Q

What shape are erythrocytes and why does this help them?

A

Biconcave; helps their manoeuvrability through small blood vessels to deliver oxygen

46
Q

What does the red cell membrane consist of?

A

Lipid bilayer, supported by protein cytoskeleton and contains transmembrane proteins

47
Q

What is the function of the transmembrane proteins in the red cell membrane?

A

Maintain the integrity, shape and elasticity of the red cell

48
Q

What causes hereditary spherocytosis?

A

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

49
Q

Describe a spherocyte

A

Spherical in shape; lack central pallor

50
Q

What do spherocytes result from?

A

loss of cell membrane without loss of an equivalent amount of cytoplasm so the cell is forced to round up

51
Q

Why are spherocytes removed prematurely by the spleen?

A

Red cell becomes less flexible

52
Q

What causes hereditary elliptocytosis?

A

Disruption of horizontal linkages in membrane

53
Q

Where else may elliptocytes occur?

A

Iron deficiency - microcytic anaemia

54
Q

How many Hb molecules does each erythrocyte contain?

A

~300 million

55
Q

Describe the structure of HbA in adults?

A

Tetramer - 4 subunits > globin chain (2 alpha and 2 beta) bound to a haem group

56
Q

What does each haem group consist of?

A

Ferrous iron (Fe2+) held in a porphyrin ring

57
Q

How does haemoglobin differ at birth?

A

HbF - 2 alpha and 2 gamma globin chains

58
Q

What things does the normal position of the oxygen Hb dissociation curve?

A 
pH (H+ conc)
CO2 in red cells 
Structure of Hb
Concentration of 2,3-DPG
Temp.
59
Q

Explain the Bohr Effect

A

High CO2 causes low pH (easier oxygen delivery > right shift)

60
Q

What does right shift on the oxygen Hb dissociation curve mean?

A

Easier oxygen delivery, Hb has a lower affinity for oxygen

61
Q

What does left shift on the oxygen dissociation curve represent?

A

Hb has a higher affinity for oxygen hence gives up oxygen less readily

62
Q

What causes right shift on Hb dissociation curve?

A 
Low pH
High CO2 
High 2,3-DPG
High temperature 
(HbS)
63
Q

What causes high affinity on the Hb dissociation curve?

A

High HbF

High CO

64
Q

What is 2,3-diphosphoglycerate produced by?

A

Rapaport-Luebering shuttle

65
Q

What is 2,3-diphosphoglycerate?

A

Allosteric effector - modulates haemoglobin oxygen affinity

  • Binds to Beta-globin chain in central cavity of haemoglobin molecule
  • Role in adaptive response to anaemia, hypoxia and high altitude
66
Q

Why is glucose-6-phosphate dehydrogenase important in red cell metabolism?

A

Hexose monophosphate (HMP) shunt

HMP shunt is tightly coupled to Glutathione metabolism, which
protects red cell from oxidant damage

67
Q

What does deficiency of G6PD cause in red blood cells?

A

Causes red blood cells to be vulnerable to oxidant damage

68
Q

What type of inheritance is G6PD deficiency?

A

X-linked inheritance

69
Q

What does G6PD deficiency usually cause?

A

severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant

70
Q

What do episodes of intravascular haemolysis in G6PD show on a blood film?

A

A lot of irregularly contracted cells (These are irregular in outline but are smaller than normal cells and have lost their central pallor)

71
Q

What do irregularly contracted cells usually result from?

A

oxidant damage to the cell membrane and to the haemoglobin

72
Q

What happens to haemoglobin in G6PD deficiency?

A

Haemoglobin is denatured and forms round inclusions known as Heinz bodies

73
Q

What is specialised language used to describe in haematology?

A

Blood films and counts

74
Q

What are some causes of microcytosis?

A

Iron deficiency
Anaemia of chronic disease
Defect in globin synthesis (thalassaemia)

75
Q

What is Beta-thalassaemia?

A

Defect in beta-globin chain synthesis

76
Q

What is Alpha-thalassaemia?

A

Defect in alpha-globin chain synthesis

77
Q

What does the term ‘major’ refer to in terms of thalassaemia?

A

significant impairment of globin chain (beta/alpha) synthesis

78
Q

What specific types can macrocytes be?

A

Round
Oval
Polychromatic

79
Q

What are some causes of macrocytosis?

A

Lack of vitamin B12 or folic acid
Liver disease and ethanol toxicity
Haemolysis (polychromasia)
Pregnancy

80
Q

What portion of the red blood cell has less haemoglobin and is therefore paler?

A

a third of the diameter from the centre (less Hb therefore less red and more pale)

81
Q

What does the term hypochromia refer to?

A

Means that eryhthrocytes have a larger area of central pallor than normal

82
Q

What often comes with hypochromia?

A

Microcytosis

iron deficiency and thalassaemia being common causes

83
Q

What does the term polychromasia refer to?

A

Describes an inreased blue tinge to the cytoplasm of a red cell

84
Q

What does a blue tinge in a blood film indicate?

A

That the red cell is young

85
Q

What is polychromasia a cause of?

A

Macrocytosis

86
Q

What are young red cells known as?

A

Reticulocytes

87
Q

What stain can you use to detect young cells?

A

New methylene blue (this stains for their higher RNA content)

88
Q

What does reticulocytosis refer to?

A

Refers to the presence of increase numbers of reticulocytes

89
Q

When may reticulocytosis occur?

A

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

90
Q

What does the term anisocytosis refer to?

A

red cells showing more variation in size than normal

91
Q

What does the term poikilocytosis refer to?

A

red cells showing more variation in shape than normal

92
Q

What conditions may target cells occur in?

A 
obstructive jaundice 
Liver disease
haemoglobinopathies 
hyposplenism
SCD
93
Q

What are target cells?

A

Red cells with an accumulation of Hb in the centre of the area of central pallor

94
Q

What do sickle cells result from?

A

Result from polymerisation of HbS, which in the deoxygenated form is much less soluble than HbA.

95
Q

When do sickle cells occur?

A

When one or two copies of an abnormal Beta-globin gene are inherited

96
Q

What is SCA caused by?

A

Mutation in Beta-globin gene.

Charged glutamic acid residue in position 6 is replaced by an uncharged valine molecule.

97
Q

What are red cell fragments also known as and what are they?

A

Schistocytes

Small pieces of red cells that indicate a red cell has fragmented.

98
Q

What may red cell fragmentation result from?

A

Shearing process caused by the platelet-rich blood clots in the small blood vessels e.g. DIC

99
Q

Reference range

A

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.

POM Haematology (10 decks)

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