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Haematology > Anaemia > Flashcards

Anaemia Flashcards

1
Q

What is anaemia?

A

Reduced RCB mass

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2
Q

How can RBC be measured?

A

Haemoglobin conc
RBC conc
Mean Cell Volume

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3
Q

What are the normal ranges of haemoglobin conc?

A

Males- Hb 130-180g/L

Females- Hb 120-160g/L

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4
Q

How do you measure haemoglobin conc?

A

Spectrophotometer

Lyse cells, conjugate Hb into stable form, measure optical density at 540nm, increased density = increased conc

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5
Q

What is haematocrit a measure of?

A

% of blood that is RBC

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6
Q

How do you measure RBC conc?

A

Haematocrit

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7
Q

What are some issues with measuring haematocrit?

A

Massive haemorrhage means low RBC but normal ratio

Saline can increase blood volume therefore apparent ratio reduction.

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8
Q

What are the normal ranges of haematocrit?

A

Males- 38-52%

Females- 37-47%

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9
Q

What blood measurements can be calculated?

A

Mean cell haemoglobin

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10
Q

What is blood film used to look at?

A

Cell morphology

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11
Q

What is a reticulocyte count a measure of?

A

RBC production

Bone marrow activity

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12
Q

What are some general symptoms of anaemia?

A 
Fatigue
Headache
Presyncope
SOB
Angina
Palpitations
Tachycardia
Pallor
Reticulocytosis
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13
Q

How long after the onset of anaemia does it take reticulocytosis to start?

A

Several days

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14
Q

When should a reticulocyte count be conducted?

A

If suspect haemolytic anaemia

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15
Q

How can reticulocyte count vary?

A

Increased/appropriate

Decreased/inappropriate

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16
Q

What causes an increased reticulocyte count?

A

Haemolysis

Blood loss

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17
Q

What should you look for if you see an increased reticulocyte count?

A

Bleeds

Haemolysis- increased breakdown products

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18
Q

What breakdown products suggest haemolysis?

A

Unconjugated serum bilirubin
Urinary urobiliongen
Splenomegaly

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19
Q

Why does reticulocyte count increase in haemolysis?

A

Trying and succeeding to cover blood loss.

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20
Q

What is haemolysis?

A

Premature RBC breakdown

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21
Q

What makes RBC very susceptible to breakdown?

A

Large surface area
Rely on glycolysis
Can’t generate new proteins.

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22
Q

What does haemolysis often do to RBC?

A

Create spherocytes

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23
Q

What is a spherocyte?

A

Spherical RBC

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24
Q

Why are spherocytes created?

A

Damaged RBC pass through spleen where damaged membrane is removed thus decreasing surface area.

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25
Q

What are the severities of haemolysis?

A

Compensated

Uncompensated

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26
Q

What is another name of uncompensated haemolysis?

A

Haemolytic anaemia

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27
Q

What two locations can haemolysis occur?

A

Extravascular

Intravascular

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28
Q

Where does extravascular haemolysis occur?

A

Reticuloendothelial system (spleen and liver)

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29
Q

What are the symptoms of extravascular haemolysis?

A

Hyperplasia at site of breakdown- hepatomegaly/splenomegaly

Release of protoporphyrin- Normal breakdown products but abnormal quantities

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30
Q

What are protoporphyrins?

A

Breakdown products of Hb

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31
Q

Give two examples of protoporphyrins

A

Unconjugated billirubin

Urobilinogenuria

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32
Q

What can unconjugated bilirubin cause?

A

Jaundice

Gallstones

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33
Q

Where does intravascular haemolysis occur?

A

Blood vessels

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34
Q

How dangerous is intravascular haemolysis?

A

May be life threatening

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35
Q

What can intravascular haemolysis give rise to?

A

Schistocytes

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36
Q

What are schistocytes?

A

Fragments of RBC

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37
Q

What are the symptoms of intravascular haemolysis?

A

Haemoglobinaemia- Free Hb in blood stream
Methaemalbuminaemia- Hb on albumin
Haemoglobinuria
Haemosiderinuria- Met to this by kidneys

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38
Q

What is haemoglobinaemia?

A

Free Hb in the blood stream

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39
Q

What is mathaemalbuminaemia?

A

Hb on albumin

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40
Q

What is haemoglobinuria?

A

Hb in urine

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41
Q

How does haemoglobinurea present?

A

Pink urine that turns black on standing

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42
Q

What can cause intravascular haemolysis?

A 
ABO mismatch
G6PD deficiency
Falciparum malaria (Blackwater Fever)
Paroxysmal nocturnal hemoglobinuria
Paroxysmal cold hemoglobinuria
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43
Q

Describe Paroxysmal cold hemoglobinuria

A

Intravascular haemolysis after cold exposure

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44
Q

What categories of things can cause haemolysis?

A

Immune or mechanical premature destruction of normal RBC
Abnormal RBC membrane
Abnormal RBC metabolism
Abnormal haemoglobin

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45
Q

What can cause abnormal haemoglobin?

A

Sickle cell disease (HbS)

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46
Q

What two metabolic factors failure of which in the RBC can lead to abnormal RBC metabolism haemolysis?

A

Failure to cope with oxidative stress

Failure to generate ATP

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47
Q

What condition can cause a failure of RBC to cope with oxidative stress?

A

G6DP deficiency

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48
Q

What is G6DP needed for?

A

To produce antioxidants

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49
Q

What is a sign of G6DP deficiency?

A

Heinz bodies

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50
Q

What are Heinz bodies made of?

A

Denatured Hb

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51
Q

What do Heinz bodies cause?

A

Bite cells

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52
Q

What is a bite cell?

A

A RBC with a chunk taken out where Heinz body has been removed.

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53
Q

Can a normal RBC metabolically fail?

A

Yes is sufficiently stressed- dapsone (used for leprosy)

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54
Q

What acquired conditions can cause an abnormal cell membrane?

A

Liver Disease (Zieve’s Syndrome)
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria
Toxins- Arsenic, Clostridium welchii

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55
Q

What toxins can cause an abnormal cell membrane?

A

Arsenic

Clostridium welchii

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56
Q

Describe Paroxysmal Nocturnal Haemoglobinuria

A

Cell surface membrane proteins make it more likely to lyse.

IgG lyses cells in the central circulation.

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57
Q

How do you detect Paroxysmal Nocturnal Haemoglobinuria?

A

Ham’s test

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58
Q

What is Paroxysmal Nocturnal Haemoglobinuria associated with?

A

Measles, mumps and chickenpox.

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59
Q

How common is an acquired cell membrane defect?

A

Rare

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60
Q

What are some symptoms of liver disease (Zieve’s syndrome) associated cell membrane defects?

A

Anaemia
Polychromatic macrocytes
Irregularly contracted cells

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61
Q

What are some causes of congenital cell membrane defects?

A

Hereditary Spherocytosi
Hereditary elliptocytosis
Reduced membrane deformability
Increased transit time through spleen

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62
Q

How is hereditary spherocytosis inherited?

A

Autosomal dominantly

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63
Q

Describe hereditary spherocytosis?

A

Lose part of membrane as pass through spleen therefore become spheroid.
Less able to pass through spleen so destroyed.

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64
Q

What are some symptoms of hereditary spherocytosis?

A

Jaundice
Anaemia
Splenomegaly
Pigmented gallstones

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65
Q

How do you diagnose hereditary spherocytosis?

A

Spherocytes and reticulocytes
Haemolysis evidence
Osmotically fragile
Coomb’s negative

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66
Q

How do you treat hereditary spherocytosis?

A

Splenectomy

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67
Q

What should you give to someone with a splenectomy?

A

Immunization

Lifelong penicillin prophylaxis

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68
Q

What is Hereditary elliptocytosis?

A

Similar to spherocytosis but less severe

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69
Q

What can cause Immune or mechanical premature destruction of normal RBC?

A

Autoimmune haemolysis
Alloimmune haemolysis
Mechanical

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70
Q

What mechanical stimuli can cause RBC destruction?

A 
Metallic heart valve
Coagulation- Due to burns
Haemolytic uraemic syndrome- E. Coli 0157
Infection- Malarea
March haemoglobinurea
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71
Q

Describe march haemoglobinurea

A

RBC damaged as pass through small vessels overlying feet during long distance marching.
Leads to haemoglobinurea.

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72
Q

What infection can cause RBC destruction?

A

Malaria

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73
Q

What can cause Haemolytic uraemic syndrome?

A

E. Coli 0157

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74
Q

What can cause alloimmune haemolysis?

A

Immune response
Passive transfer of Ab
Organ transplant

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75
Q

What is alloimmune haemolysis?

A

Ab against someone else’s blood

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76
Q

How can an organ transplant cause alloimmune haemolysis?

A

Donor lymphocytes reside in transplanted material.

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77
Q

Give an example of passive transfer of Ab

A

Haemolytic disease of the newborn

78
Q

Describe Haemolytic disease of the newborn

A

Maternal ABO or RhD Ab transfer to foetus via placenta

79
Q

What is the only Ab that can cross the placenta?

A

IgG

80
Q

How does the mother produce Ab in Haemolytic disease of the newborn?

A

Foeatal RBC pass into mothers circulation (usually during birth so doesn’t affect 1st pregnancy but sensitizes and affects 2nd).

81
Q

What are some symptoms of Haemolytic disease of the newborn?

A 
Mild haemolytic anaemia to intrauterine death
Hydrops fetalis (oedema in 2+ compartments of: subcut, pleura, pericardium, ascities), brain damage (due to high levels of bilirubin)
Deafness
82
Q

How do you investigate Haemolytic disease of the newborn?

A

Test mother for abnormal Ab and monitor to check not rising.

83
Q

How do you treat Haemolytic disease of the newborn?

A

Anti-D etc if appropriate.

Postnatal treatment: Phototherapy (convert bilirubin to biliverdin), transfusion

84
Q

What kind of immune response can cause an alloimmune reaction?

A

Haemolytic transfusion reaction

85
Q

What are the two forms of Haemolytic transfusion reaction?

A

Immediate (IgM) predominantly intravascular

Delayed (IgG) predominantly extravascular

86
Q

What characterises autoimmune haemolysis?

A

Spherocytes

87
Q

How do you detect autoimmune haemolysis?

A

Coomb’s test

88
Q

What are the two categories of autoimmune haemolysis?

A

Warm (IgG)

Cold (IgM)

89
Q

Give some causes of Warm (IgG) autoimmune haemolysis?

A

Idiopathic (commonest)
Autoimmune disorders (SLE or Ra)
Drugs (penicillins, etc)
Infection

90
Q

Who is most likely to suffer from Warm (IgG) autoimmune haemolysis?

A

Middle age women (any age and sex can theoretically suffer)

91
Q

Describe the progress of Warm (IgG) autoimmune haemolysis

A

Short remitting and relapsing

92
Q

Give some symptoms of Warm (IgG) autoimmune haemolysis

A

Palpable spleen.
Haemolytic anaemia
Autoimmune thrombocytopenia

93
Q

How do you treat Warm (IgG) autoimmune haemolysis

A

Corticosteroids (prednisolone 1mg/kg daily), Splenectomy (if no response to steroids or maintained), Immunosuppresive drugs (azathioprine and rituximab). Blood transfusion in severe anaemia.

94
Q

What can cause Cold (IgM) autoimmune haemolysis?

A

Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders
Increased age- Slow onset

95
Q

Describe Cold (IgM) autoimmune haemolysis symptoms

A

Mild to moderate transient haemolysis

96
Q

How do you treat Cold (IgM) autoimmune haemolysis?

A 
Treat underlying cause, 
Avoid cold exposure. 
Rituximab may help. 
Blood transfusion (warm environment).
Steroids and splenectomy normally ineffective.
97
Q

Describe Paroxysmal Nocturnal Haemoglobinuria

A

Cell surface membrane proteins make it more likely to lyse.

98
Q

What genetics is Paroxysmal Nocturnal Haemoglobinuria associated with?

A

PIG-A gene

99
Q

What Ab are Paroxysmal Nocturnal Haemoglobinuria associated with?

A

Anti-CD55 and Cd59 Ab (IgG)

100
Q

What are the symptoms of Paroxysmal Nocturnal Haemoglobinuria?

A 
Intravascular haemolysis (precipitated by iron therapy, infection or surgery), 
Venous thrombosis (in uncommon plaes, eg. Liver- Budd-Chiari syndrome), 
Haemoglobinurea (only urine during night or first thing in morning is dark)
101
Q

How do you treat Paroxysmal Nocturnal Haemoglobinuria?

A

Blood transfusion (severe anaemia, use leukocyte depleted blood),
Eculizmab,
Long term anticoag,
Bone marrow transplant.

102
Q

How can you diagnose haemolysis?

A

FBC + Film
Increased RBC production- Reticulocyte Count
Detection of breakdown products

103
Q

What are some breakdown products of RBC?

A

Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

104
Q

How can you identify the cause of haemolysis?

A

History and exam
Blood film
Antibodies- Direct Coomb’s

105
Q

What are you looking for on the blood film to ID the cause of haemolysis?

A 
Membrane damage (spherocytes)
Mechanical damage (red cell fragments)
Oxidative damage (Heinz bodies)
HbS (sickle cells)
106
Q

How can you measure the bone marrow response?

A

Reticulocytosis- Increased RBC production

Erythroid hyperplasia

107
Q

Is reticulocytosis diagnostic of haemolysis?

A

No

108
Q

What can be seen in reticulocytosis cells?

A

Polychromia

109
Q

What is Erythroid hyperplasia?

A

Bone marrow hyperplasia

110
Q

What does erythroid hyperplasia cause?

A

Increased bone marrow RBC production.

111
Q

What can cause a reduced reticulocyte count?

A

Hypoproliferation

Maturation abnormalities

112
Q

What do RBC look like in hypoproliferative anaemia?

A

Normocytic

Normochromatic

113
Q

What can cause a hypoproliferative anaemia?

A 
Anaemia of chronic disease
Chronic kidney disease
Hypometabolic
Marrow infiltration
Marrow failure
114
Q

What can cause bone marrow failure?

A

Aplastic anaemia

Drug

115
Q

What can infiltrate bone marrow?

A

Fibrosis

Metastatic

116
Q

How can chronic kidney disease cause a hypoproliferative anaemia?

A

Reduces EPO production

117
Q

How can chronic disease cause anaemia?

A

Inflammation (infection and chronic disease) increases ferritin and hepcidin synthesis (blocks iron release). Increases iron stores and decreases functional iron. Occurs to reduce supply of iron to pathogens.

118
Q

How does chronic inflammation cause anaemia?

A

Increased hepcidin- Decreased iron release/Reduced iron availability
Increases RBC breakdown
Inhibits EPO release
Inhibits erythroid proliferation

119
Q

What does hepcidin cause anameia?

A

Decrease iron release from stores.

120
Q

What can induce hepcidin release?

A

Il-6

121
Q

What two categories of maturation abnormalities are there?

A

Microcytic (Low MCV)

Macrocytic (High MCV)

122
Q

What causes a microcytic anaemia?

A

Cytoplasm defects

Problems with haemoglobin

123
Q

Describe the RBC in microcytic anaemia

A

Small

Hypochromatic

124
Q

How can cytoplasmic defects lead to microcytic anaemia?

A

RBC precursors keep dividing until certain Hb level reached. If lacking Hb then will keep dividing and get small.

125
Q

Where is Hb synthesised and from what?

A

Hb synthesized in the cytoplasm from globins and haem (Fe2+ and porphyrin ring). Shortage of any part results in microcytic anaemia.

126
Q

What parts of the Hb molecule can be affected causing microcytic anaemia?

A

Haeme- Iron or porphyrin ring

Globin

127
Q

What are the components of haeme?

A

Iron

Porphyrin ring

128
Q

What is a defect/deficiency of the globin called?

A

Thalassemia

129
Q

What can inhibit porphyrin synthesis?

A

Lead poisoning

Pyridoxine responsive anaemias

130
Q

How common is porphyrin synthesis failure?

A

Very rare

131
Q

What is the most common form of anaemia?

A

Iron deficient

132
Q

Define iron deficient anaemia

A

A combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin).

133
Q

What can cause iron deficient anaemia?

A

Diet
Blood loss
Malabsorption- Coeliac disease
Chronic disease

134
Q

What two forms of iron can be absorbed?

A 
Plant based
Animal based (haeme)
135
Q

What is needed for plant based iron to be absorbed?

A

Acidic enviroment

136
Q

Can iron be transferred through milk?

A

Breast yes

Cow no

137
Q

What can inhibit iron absorption?

A

Tea (tannins)

138
Q

What can promote iron absorption?

A

VC

139
Q

What are some major causes of blood loss?

A

Menorrhagia (>60ml is heavy)
Gastrointestinal- Occult
Haematuria

140
Q

What are the two types of iron deficient anameia?

A

Relative deficiency

Absolute deficiency

141
Q

Describe a relative iron deficiency

A

Normally have enough iron but going through situation (growing, pregnancy) where need more.

142
Q

Describe an absolute iron deficiency

A

Don’t have enough iron

143
Q

What are some complications of iron deficient anaemia?

A

Dry skin

Koilonychia

144
Q

How do you treat iron deficient anaemia?

A

Treat underlying cause
Iron supplements- Symptoms but doesn’t sort problem
Iron infusion- If can’t absorb (coeliacs)
Transfusion- Only if life threatening

145
Q

What are some side effects of iron suppliments?

A

Constapation, diarrhoea, N+V

146
Q

How do you check if iron suppliments are being taken/working?

A

Reticulocyte count

147
Q

How do you asses iron levels?

A 
Functional Iron- Haemoglobin conc
Transported Iron
  Serum iron
  Transferrin
  Transferrin saturation
Stored Iron- Serum ferritin
148
Q

How is iron stored?

A

Serum ferritin (macrophages)

149
Q

What form does functional iron take?

A

Haemoglobin conc

150
Q

How is iron transported?

A

Serum iron
Transferrin
Transferrin saturation

151
Q

How much iron is normally absorbed and lost a day?

A

1mg of each

152
Q

How much iron is there in the body normally?

A

4g

153
Q

How does ferritin store iron?

A

Intracellular protein storing up to 4000 iron atoms.

154
Q

What does transferrin do?

A

Transports Iron from macrophages, hepatocytes and intestinal cells to marrow

155
Q

What can transferrin be used to measure?

A

Measure of iron supply (not great)- decreased in anaemia

156
Q

What does low ferritin mean?

A

Low iron stores

157
Q

What can abnormally increase serum ferritin?

A

Inflammation (acute phase protein)

158
Q

What is Sideroblastic anaemia?

A

Body can’t use iron therefore it gathers in mitochondria.

159
Q

What causes Sideroblastic anaemia?

A

Genetics

160
Q

What do RBC look like in sideroblastic anaemia?

A

Gives a ringed appearance to nucleus (sideroblast- diagnostic)

161
Q

How do you treat sideroblastic anaemia?

A

Pyridoxine
Treat folate def
Stop drugs or alcohol- May help

162
Q

What causes macrocytic anaemia?

A

Nuclear defects impair cell division

Leads to problems with maturation

163
Q

How do RBC differ in macrocytic anaemia?

A

RBC larger than normal- macrocytes (>100fl).
Normal RBC is the same size as a small lymphocyte nucleus, macrocytes bigger.
Normchromatic

164
Q

What can cause spurious macrocytic anaemia?

A

Reticulocytosis

Cold-agglutinins

165
Q

What is spurious macrocytic anaemia?

A

Red cell volume is normal but MCV is high.

166
Q

How can reticulocytosis cause spurious macrocytic anaema?

A

Machines don’t sort reticulocytes from RBC.

Lots of reticulocytes (acute bleed or heamolysis) increases average.

167
Q

What two categories of genuine macrocytic anaemia are there?

A

Megaloblastic

Non-megaloblastic

168
Q

How do nuclear defects cause macrocytic anaemia?

A

Due to maturation problems erythroblasts cannot replicate DNA.
Divide into one large nucliated cell and one anucliate which apoptoses.
Large nucliated cell with immature nuclius called megalblast.
Still gather Hb so eventually stop dividing but are large immature nucliated cells few in number.

169
Q

What are RBC like in macrocytic anaemia?

A 
Low numbers (due to lack of division)
Larger than normal
170
Q

What is a macrocyte?

A

Large mature RBC.

Occurs when megaloblast enucliates (loses its nucleus).

171
Q

What can cause macrocytic anaemia?

A

B12 deficiency
Folate deficiency
Drugs- Chemotherapy
Rare inherited abnormalities- Myelodysplasia

172
Q

What is Myelodysplasia?

A

Mutation causing problems with cell division.

173
Q

Where is folate absorbed and what is it got from?

A

Jejunem both passively and actively

Live and leafy veg

174
Q

How long is folate stored for?

A

4 months of stores.

175
Q

What can cause a folate deficiency?

A

Diet- Alcoholics
Malabsorption- Coeliac’s and Crohn’s
Overuse
Anticonvulsants

176
Q

What can cause folate overuse?

A

Haemolysis
Exfoliating dermatitis
Pregnancy
Malignancy

177
Q

What are folate and B12 needed for?

A

B12 and folate work in tandem for DNA synthesis and regulate gene activity in the nervous system (create myelin sheaths).

178
Q

What can cause a B12 deficiency?

A

Diet- Vegans at risk
Chronic pancratitis
Stomach problems
Ileal problems- Crohn’s and resection

179
Q

What stomach problems can cause B12 deficiency?

A

Pernicious anaemia
Gastrectomy/bypass
PPI
Atrophic gastritis

180
Q

What causes pernicious anaemia?

A

Autoimmune destruction gastric parietal cells.

Causes intrinsic factor deficiency.

181
Q

What are the symptoms of pernicious anaemia?

A 
Slow onset anaemia
Lemon yellow skin- Pallor and jaundice
Glottitis- Red sore tongue 
Angular stomatitis 
Polyneuropathy
182
Q

What foods can B12 be found in?

A

Meat (liver), eggs and dairy products.

183
Q

How is B12 absorbed?

A

Ingested and combines with haptocorrin in acidic environments (stomach).
B12/Hapto complex enters small intestine with intrinsic factor (gastric parietal cells).
Pancreatic secretions raise pH causing B12 and Hapto separation.
B12 combines with intrinsic factor and B12 absorbed in distal SM (iron absorbed in proximal SI).

184
Q

What is another name for B12?

A

Cobalamin

185
Q

What are some symptoms of a combines B12/Folate deficiency?

A

Anaemia
Weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems

186
Q

What is a specific problem of B12 deficiency?

A

Neurological problems

Posterior/dorsal column abnormalities, neuropathy, dementia- all irreversible.

187
Q

Why should B12 supplements be given when giving a folate supplement to someone with low-normal B12?

A

Due to B12 being needed for myelin production.

Get B12 drop as folate used.

188
Q

How do you diagnose megoblastic macrocytic anaemia?

A 
Low cell count
Macrovalocytes- Oval shaped cells
Hypersegmented neutrophils- 5-8 segments
Serum B12 and folate levels- not the most reliable
Autoantibodies
189
Q

What auto antibodies are associated with megoblastic macrocytic anaemia?

A

Anti-intrinsic factor (IF)- Specific not sensitive

Anti gastric-parietal cell (GPC)- Sensitive not specific

190
Q

How do you treat megoblastic macrocytic anaemia?

A

Treat underlying cause:

  • B12/folate replacement
  • Red cell transfusion- Only if life threatening
191
Q

What is non-megoblastic anaemia?

A

RBC membrane changes.

Normoblastic

192
Q

What can cause non-megoblastic anaemia?

A 
Lipid abnormalities
  Alcohol
  Liver disease
Hypothyroidism
Marrow failure

Haematology (12 decks)

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