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POM 3 Haematology > 3.1 Red Blood Cells > Flashcards

3.1 Red Blood Cells Flashcards

1
Q

What do all blood cells originate from?

A

Haematopoetic stem cells

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2
Q

Where does foetal haematopoeisis start?

A

The yolk sac in the first 3 weeks of gestation

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3
Q

When does the liver take over as the main site of haemopoiesis?

A

6-8 weeks of gestation

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4
Q

How does the site of haemopoiesis change at 10 weeks gestation?

A

Bone marrow becomes main site

Especially in the pelvis, femur and sternum

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5
Q

Which bones in children does haematopoiesis occur in?

A

All bones

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6
Q

Which bones in adults does haematopoiesis occur in?

A

Long bones – femur, pelvis, sternum

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7
Q

What are the two characteristics of HSC and what does this allow?

A

The can self renew and differentiate

Maintains adequate population of mature blood cells and controls population of each blood cell type

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8
Q

What are the two cells that HSC differentiate into?

A

Common Lymphoid Progenitor and Common Myeloid Progenitor

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9
Q

What is the intravascular life span of red blood cells?

A

120 days

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10
Q

What is the intravascular life span of neutrophils?

A

7-10 hours

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11
Q

What is the intravascular life span of monocytes?

A

Several days

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12
Q

What is the intravascular life span of eosinophils?

A

Slightly shorter than neutrophils (7-10 hrs)

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13
Q

What is the intravascular life span of lymphocytes?

A

Very variable

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14
Q

What is the intravascular life span of platelets?

A

10 days

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15
Q

Where does erythropoiesis occur?

A

Bone marrow

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16
Q

Outline the timeline of erythropoiesis

A

Proerythroblast
Early → intermediate → late erythroblast
Polychromatic RBC
RBC

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17
Q

How do erythroblasts become mature erythrocytes?

A

Lose their nucleus

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18
Q

What does seeing nucleated RBCs in blood mean?

A

High demand for RBCs, thus immature RBCs are released prematurely into circulation

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19
Q

Why do polychromatic RBCs have a blue tinge?

A

Due to high RNA content on new methylene blue stain

They are still reticulocytes (immature RBCs) that lose their ribosomes after a few days

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20
Q

What happens to RBCs as differentiation progresses?

A

Self renewal and lineage plasticity decrease

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21
Q

What are the 4 essentials of erythropoiesis?

A

Erythropoietin
Iron
Vitamin B12
Folic acid

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22
Q

What is haem iron also known as?

A

Ferrous iron – Fe2+

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23
Q

What is non-haem iron also known as?

A

Ferric iron – Fe3+

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24
Q

What is erythropoietin?

A

Glycoprotein growth factor made in the kidneys

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25
Q

When is erythropoietin made and what does this create?

A

In response to hypoxia and anaemia

Creates a demand-supply feedback loop

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26
Q

How does EPO work?

A

Interacts with EPO receptors on RBC progenitors in bone marrow to increase RBC production

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27
Q

What affect do phytates have on iron absorption?

A

They bind to iron and reduce its absorption

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28
Q

What organs is excess iron toxic to?

A

Heart and liver

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29
Q

Where is ferroportin found?

A

In duodenum enterocytes

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30
Q

How do we lose iron if it is high?

A

High iron leads to release of hepcidin which binds to and blocks ferroportin so iron cannot leave duodenum enterocytes

Iron in the enterocytes is bound to ferritin and is lost from the body when the enterocyte dies

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31
Q

What does inflammation do to hepcidin?

A

Increases hepcidin and reduces iron supply, leading to anaemia of chronic disease

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32
Q

Why do we need Folate and Vitamin B12?

A

Both are involved in dTTP synthesis thus DNA synthesis

B12 – integrity of nervous system
Folate – homocysteine metabolism

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33
Q

What can a Vitamin B12 and folate deficiency cause?

A

Megaloblastic erythropoiesis

This is because the cells keep dividing but lack the DNA, thus the cell matures and cytoplasm grows while the nucleus hasn’t matured

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34
Q

Name three sources of folate

A

Green vegetables, yeast, fruits

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35
Q

Name four sources of B12

A

Meat, fish, eggs, milk

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36
Q

What does B12 combine with so it can be absorbed?

A

Intrinsic factor which is made in the gastric parietal cells

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37
Q

What does B12-IF bind to for absorption?

A

Receptors in the ileum of the small intestine

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38
Q

What are 4 causes of vitamin B12 deficiency?

A

Inadequate intake
Pernicious anaemia (inadequate IF seretion)
Achlorydria (lack of stomach acid)
Malabsorption (coeliac disease)

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39
Q

What is pernicious anaemia?

A

Inadequeate intrinsic factor production

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40
Q

Why do red blood cells have a life span of 120 days?

A

When they move through capillaries and blood vessels, the walls bend and stretch meaning they get damaged

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41
Q

Where are the red blood cells destroyed and how?

A

In the spleen by reticular endothelial macrophages which phagocytose them

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42
Q

What are the RBCs broken down into?

A

Haem and globin

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43
Q

What happens to the haem part of the RBC after it is destroyed?

A

Gets broken down into bilirubin

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44
Q

What happens to the iron that is released from the haem ring when an RBC is destroyed?

A

Bound to transferritin and sent to bone marrow for recyclin

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45
Q

Why is bile important?

A

Contains bile salts which are needed for the emulsification of fats so they can be absorbed

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46
Q

What are the three types of granulocytes?

A

Neutrophil, basophils and eosinophil

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47
Q

What does hypochromia mean?

A

Cells are flatter and have larger central pallor due to lower Hb content

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48
Q

What is hypochromia associated with?

A

Microcytosis since iron deficiency and thalassaemia are common causes

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49
Q

What is polychromasia?

A

Blue tinge to RBC cytoplasm indicating that the cell is young

Thus the cell is also larger than normal

50
Q

What can polychromasia cause?

A

Macrocytosis

51
Q

What are reticulocytes?

A

Young developing RBCs that may be present due to bleeding or haemolysis

52
Q

How do we detect reticulocytes?

A

Stain with new methylene blue for higher RNA content

53
Q

What are target cells?

A

When you have an accumulation of haemoglobin in the area of central pallor

54
Q

What causes the presence of target cells?

A

Obstructive jaundice, liver disease, hyposplenism, haemoglobinopathies

55
Q

What does anisocytosis mean

A

Variation in size

56
Q

What does poikilocytosis mean

A

Variation in shape

57
Q

What causes sickle cells?

A

Due to the polymerisation of HbS which forms tachtoids that distort the shape of the RBC

58
Q

What is the mutation that causes sickle cell disease?
(Sickle cell six)

A

Charged glutamic acid residue at positive 6 in beta Hb gene is replaced by uncharged valine

59
Q

“Normal” Hb is determined by many things like..

A

Gender and physiological status eg altitude

60
Q

What type of distribution fo Hb concentrations show?

A

Gaussian distribution

61
Q

An infant with sickle cell anaemia (HbSS) develops symptoms of fatigue and pain. Blood tests reveal anaemia with thrombocytopenia. Examination reveals a mass on the left-hand side of his abdomen. Given this information, what could be the most likely explanation for his symptoms?

A

Pooling of blood in the spleen - splenic sequestration

62
Q

What is Crohn’s Disease?

A

inflammatory bowel disease which often involves ulcer formation in the mucosal layer of the intestines.

63
Q

How can Crohn’s disease lead to iron-deficiency anaemia?

A

Crohn’s disease can lead ulcer formation in the stomach, meaning internal bleeding can occur. This may result in iron-deficiency anaemia due to blood loss

64
Q

What regulates the proliferation and differentiation of Haematopoietic stem cells?

A

Haematopoietic growth factors

65
Q

A 28-year old female has some tests carried out following a full blood count that subsequently reveal that she is folate deficient. What changes in the red blood cells would you expect to see.

A

Macrocytic cells

66
Q

Which cells do myeloid stem cells give rise to?

A

Red blood cells, granulocytes, monocytes, mast cells and basophils

67
Q

What is the function of a platelet?

A

Haemostasis

68
Q

What is the function of a monocyte?

A

Defense against infection by phagocytosis

69
Q

What is the function of a neutrophil?

A

Defense against infection by phagocytosis and killing of micro-organisms

70
Q

What are haematopoietic growth factors?

A

Glycoprotein hormones which bind to cell surface receptors
Regulate proliferation and differentiation of HSCs
Regulate function of mature blood cells

71
Q

What is the haematopoietic growth factor which influences red cell production?

A

Erythropoietin

72
Q

What are the haematopoietic growth factors which influence granulocyte and monocyte production?

A

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

73
Q

Which common progenitor do megakaryocytes derive from?

A

Myeloid

74
Q

What causes microcytic anaemia?

A

Defects in haem synthesis (iron deficiency and anaemia of chronic disease)

Defects in globin synthesis (alpha and beta thalassaemia)

75
Q

What are microcytic cells?

A

Smaller than normal with areas of central pallor

76
Q

What can cause lack of iron leading to microcytic anaemia?

A

Blood loss
Reduced intake
Increased iron requirement
Anaemia of chronic disease

77
Q

What anaemia does B12/folate deficiency cause?

A

Macrocytic anaemia

78
Q

What are macrocytic cells?

A

Larger than normal with areas of central pallor

79
Q

Apart from B12 and folate deficiency, what can cause macrocytic anaemia?

A

Liver disease and ethanol toxicity

Haemolysis (polychromasia)

Pregnancy and drugs that affect DNA synthesis

80
Q

How does B12/folate deficiency cause macrocytic anaemia?

A

Inhibits DNA synthesis, causing megaloblastic erythropoiesis

This affects all rapidly dividing cells in the bone marrow and epithelial surfaces in the mouth, gut and gonads

81
Q

What is normocytic anaemia?

A

RBCs are of a normal size but still have anaemia

82
Q

What can cause normocytic anaemia?

A

Recent blood loss

Failure of RBC production

Pooling of RBCs in spleen

83
Q

What is iron deficiency anaemia?

A

Ferritin is reduced, reflecting low body iron stores

84
Q

What can cause iron deficiency anaemia?

A

Increased blood loss (e.g. hookworm, menorrhagia)

Insufficient intake and malabsorption

Increased iron requirements due to pregnancy or infancy

85
Q

What are some clinical features of iron deficiency anaemia?

A

Pallor, fatigue, breathlessness

Impaired intellectual development in children

Features of underlying causes of deficiency

86
Q

What are other clinical features of iron deficiency anaemia?

A

Koilonychia – concave nails

Angular cheilitis – inflammation of both corners of mouth

87
Q

What is reduced in anaemia?

A

Hb concentration
RBC
Hct/PCV

Due to a decrease in the absolute amount of Hb in blood

88
Q

What are the two main functions of iron?

A

Oxygen transport in haemoglobin

Mitochondrial proteins

89
Q

What mitochondrial proteins is iron used for?

A

Cytochromes a, b, c for ATP production

Cytochrome P450 for hydroxylation reactions

90
Q

Why is ferric (Fe3+) iron not as easily absorbed?

A

Requires action of reducing substances (e.g. ascorbic acid, vitamin C) for absorption

91
Q

How does anaemia of chronic disease/inflammation occur?

A

Pro-inflammatory cytokines (IL-1, TNF-a, IL-6, IFN-gamma) increase EPO which increases hepcidin which binds ferroportin

This decreases iron absorption in the gut as iron is trapped in enterocytes and lost when they die

92
Q

During what situations do the requirements for folic acid increase?

A

During pregnancy and during red cell production

93
Q

What three things does erythrocyte function depend on?

A

Integrity of the membrane
Haemoglobin structure and function
Cellular metabolism

94
Q

What structures help to maintain the integrity, shape and elasticity of RBCs?

A

The membrane is a lipid bilayer supported by a protein cytoskeleton with transmembrane proteins

95
Q

What are the transmembrane proteins found in red cell membrane?

A

Band 3 and rhesus

96
Q

What are the skeletal proteins found in red blood cells membrane?

A

Spectrin and junctional

97
Q

What causes hereditary spherocytosis?

A

Disruption to ankyrin/spectrin vertical linkages

98
Q

What happens to spherocytes?

A

Premature removal and haemolysis by the spleen due to less flexibility

99
Q

What would be seen on a blood film of a patient with hereditary spherocytosis?

A

Rounded, with a regular outline and lacking central pallor

100
Q

What causes hereditary elliptocytosis?

A

Disruption of ankyrin/spectrin horizontal linkages

Can also occur in iron deficiency

101
Q

How does deficiency in glucose-6-phosphate dehydrogenase affect RBCs?

A

G6PD is an important enzyme in the hexose monophosphate shunt which is responsible for glutathione metabolism

Glutathione normally protects RBCs from oxidant damage during infection or drug use

102
Q

What protects the red cells from oxidant damage?

A

Glutathione

103
Q

What does G6PD deficiency cause?

A

G6PD deficiency usually causes intermittent, severe intravascular haemolysis (RBC breakdown in blood vessels) as a result of infection or exposure to an exogenous oxidant

104
Q

What are episodes of intravascular haemolysis in G6PD deficiency associated with the appearance of?

A

Irregularly contracted cells (bite cells) with no central pallor

Hb is denatured and forms round inclusions called Heinz bodies

105
Q

What molecule modulates Hb O2 affinity and how?

A

2,3-DPG

By competing with O2 for Hb binding

106
Q

What causes a right shift in the O2 dissociation curve?

A

Decreased pH
Increased CO2
Increased 2,3-DPG
Increased temperature

Thus more O2 unloading due to decreased affinity

107
Q

What causes a left shift in the O2 dissociation curve?

A

Increased pH
Decreased 2,3-DPG and temperature
Increase in CO and HbF

Thus more O2 loading due to increased affinity

108
Q

What is polycythaemia?

A

Too many RBCs in circulation

109
Q

What can cause polycythaemia?

A

Blood doping or overtransfusion

Appropriately increased EPO due to hypoxia

Inappropriate EPO use or renal tumour secreting EPO

Causes independent of EPO

110
Q

What is polycythaemia vera?

A

Myeloproliferative disorder of the bone marrow

111
Q

What does polycythaemia vera cause?

A

Hyperviscosity leading to thrombosis requiring venesection

112
Q

How can polycythaemia vera be treated?

A

Drugs can be given to reduce bone marrow RBC production

113
Q

What is MCV and its formula?

A

Average volume of each RBC

114
Q

What is MCH and its formula?

A

Average mass of Hb in each RBC

115
Q

What is MCHC and its formula?

A

Average concentration of Hb in each RBC

116
Q

Compare iron deficiency anaemia and thalasseamia in terms of Hb

A

Iron deficiency – normal or decreased
Thalassaemia – normal or mildly decreased

117
Q

Compare iron deficiency anaemia and thalasseamia in terms of MCV

A

Iron def – low in proportion to Hb
Thal – lower for same Hb

118
Q

Compare iron deficiency anaemia and thalasseamia in terms of MCH

A

Iron def – low in proportion to Hb
Thal – low for same Hb

119
Q

Compare iron deficiency anaemia and thalasseamia in terms of MCHC

A

Iron def – low
Thal – relatively preserved

120
Q

Compare iron deficiency anaemia and thalasseamia in terms of RBC count

A

Iron def – low
Thal – increased

121
Q

Compare iron deficiency anaemia and thalasseamia in terms of Hb electrophoresis

A

Iron def – normal
B-thal – Hb A2 is raised
a-thal – normal

122
Q

Compare iron deficiency anaemia and thalasseamia in terms of ferritin

A

Iron def – low
Thal – normal

POM 3 Haematology (10 decks)

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