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Year 3 - Haematology > Anaemia > Flashcards

Anaemia Flashcards

1
Q

How does anaemia present?

A 
Fatigue 
Presyncope
Dyspnoea
Angina
Palpitations
Intermittent claudication
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2
Q

Koilonychia indicates which kind of anaemia?

A

Iron def

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3
Q

Jaundice indicates which kind of anaemia?

A

Haemolytic

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4
Q

How is anaemia investigated?

A 
FBC and blood film 
Reticulocyte count
MCV
Bone marrow assessment 
Iron stores
B12 and folate
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5
Q

Give examples of causes of iron deficiency?

A 
Menorrhagia 
Occult blood loss
Increased demand 
Dietary 
Decreased absorption
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6
Q

What is responsible for reducing ferric iron to ferrous iron from the duodenum?

A

Duodenal cytochrome B

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7
Q

What transports ferrous iron into duodenal enterocytes?

A

DMT1 (or natural resistance associated macrophage protein)

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8
Q

What transports ferrous iron out of the enterocyte?

A

Ferroportin 1

Hephaestin

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9
Q

Which factors may increase iron absorption?

A

Ascorbic acid

Alcohol

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10
Q

Which factors may decreased iron absorption?

A

Tannins
Calcium
Phytates

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11
Q

What is the major negative regulator of iron uptake?

A

Hepcidin

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12
Q

Where is hepcidin produced?

A

Liver

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13
Q

What is the action of hepcidin?

A

Binds to a degrades ferroportin

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14
Q

What causes a fall in hepcidin levels?

A

Anaemia

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15
Q

Why is furosemide less effective in renal impairment?

A

Reduced GFR causes large proteins in the urine

These bind to furosemide and it is therefore not active

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16
Q

What is the specific transporter for haem iron?

A

Haem carrier protein 1

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17
Q

Where is iron stored?

A

Hb
Hepatocytes
Skeletal muscle
Reticuloendothelial cells

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18
Q

What is iron mostly stored as?

A

Ferritin

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19
Q

What is 1/3 of iron stored as?

A

Haemosiderin

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20
Q

What is ferritin?

A

Water soluble iron and protein complex

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21
Q

What is haemosiderin?

A

Insoluble iron and protein complex

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22
Q

How do you assess iron status?

A

%ferritin saturation

Apotransferrin : Holotransferrin

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23
Q

What is transferrin?

A

Protein with 2 binding sites for iron

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24
Q

How does iron deficiency anaemia present?

A 
Brittle nails
Koilonychia
Atrophy of tongue papillae
Brittle hair
Angular stomatitis
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25
Q

How is iron deficiency investigated?

A

Serum ferritin
Serum transferrin receptors
Serum iron

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26
Q

How is iron deficiency anaemia managed?

A

Ferrous fumarate

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27
Q

What are the main side effects of ferrous fumarate?

A

Nausea, diarrhoea or constipation

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28
Q

Why does anaemia occur in chronic disease?

A

Decreased release of iron to bone marrow

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29
Q

How is anaemia of chronic disease investigated?

A

Hepcidin levels (tends to be overactive)

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30
Q

How is anaemia of chronic disease treated?

A

Recombinant erythropoietin and management of chronic disease

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31
Q

What is a sideroblastic anaemia?

A

Disorders characterised by excess iron; hypochromic cells and sideroblast rings

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32
Q

What causes disordered haem synthesis in sideroblastic anaemia?

A

Accumulation of iron in mitochondria

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33
Q

How may sideroblastic anaemia be acquired?

A

Myeloproliferative disorders
Isoniazid
Alcohol misuse
Lead toxicity

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34
Q

In which conditions may normocytic anaemia be seen?

A

Chronic disease
Endocrine dysfunction
Haemolytic anaemia

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35
Q

What causes the cells to be larger in megaloblastic anaemia?

A

Failure in DNA synthesis leading to impaired proliferation

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36
Q

Big cells with twisted nuclei are know as what?

A

Metamyelocytes

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37
Q

Give three examples of causes of megaloblastic change?

A

Vit B12 def
Folic acid def
Myelodysplasia

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38
Q

How do B12 and folate work to facilitate DNA synthesis?

A

Methylate promotor genes to cause switching on and off of appropriate genes

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39
Q

What is vit b12 otherwise known as?

A

Cobalamin

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40
Q

Give examples of vit b12 sources

A

Meat
Fish
Eggs
Milk

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41
Q

Approx how much B12 is stored in the liver of a healthy adult?

A

2-3mg

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42
Q

How much B12 is used per day in a normal healthy adult?

A

1-2micrograms

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43
Q

Give examples of causes of B12 deficiency

A

Vegan diet
PA
Gastrectomy
IF def

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44
Q

What is the role of the folate cycle?

A

Coverts uridine to thymidine

Promotes nucleotide synthesis

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45
Q

What is the role of the methionine cycle?

A

Produces methyl donors

S-adenosyl-methionine

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46
Q

What does B12 bind to when it is ingested?

A

R protein

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47
Q

What cleaves B12 from R protein?

A

Pancreatic enzymes

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48
Q

What causes pancreatic enzymes to be secreted to cleave b12?

A

pH increase on ingestion of food

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49
Q

Which cells secrete intrinsic factor?

A

Gastric parietal

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50
Q

What carries b12 to the cubulin receptors in the ileum?

A

IF

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51
Q

Which transports carries B12 out of ileal cells to bone marrow?

A

Glycoprotein transcobalamin II (TCII)

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52
Q

What is “active B12”?

A

B12 bound to TCII

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53
Q

What is “active B12” otherwise known as?

A

Holotranscobalamin

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54
Q

What is pernicious anaemia?

A

Autoimmune condition involving destruction of the gastric parietal cells

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55
Q

Which type of anaemia is pernicious anaemia?

A

Macrocytic

56
Q

How does pernicious anaemia affect b12 levels?

A

No IF secreted so cannot be transported to cubulin receptors to be absorbed

57
Q

How does pernicious anaemia present?

A 
Insidious onset
Jaundice 
Glossitis
Angular stomatitis
Peripheral polyneuropathy 
Progressive weakness and ataxia
Psychiatric features
58
Q

What does a blood film show in macrocytic megaloblastic anaemia?

A

Megaloblasts and hypersegmented neutrophils

59
Q

What would endoscopy reveal in pernicious anaemia?

A

Achlorhydria

60
Q

Which antibodies are present in pernicious anaemia?

A

Anti-IF

Anti-gastric parietal cell

61
Q

How is life-threatening PA treated?

A

Red cell transfusion

62
Q

How is non-life-threatening PA treated?

A

Vit B12 injections (Hydroxocobalamin)

63
Q

How quickly does B12 therapy show clinical improvement in PA?

A

48 hours

64
Q

What is dietary folic acid converted to?

A

Monoglutamate

65
Q

Where is folic acid absorbed?

A

Jejunum and duodenum

66
Q

Give examples of sources of folate?

A

Leafy green veg

Fortified cereals

67
Q

How long may body stores of folic acid last?

A

4 months

68
Q

Which mechanisms may cause folate deficiency?

A

Inadequate intake
Malabsorption
Excess utilisation
Iatrogenic

69
Q

Give examples of drugs which cause folate deficiency?

A

Phenytoin
Methotrexate
Trimethoprim

70
Q

In which scenarios may there be excess utilisation of folate?

A

Haemolysis
Pregnancy
Malignancy

71
Q

How is folic acid deficiency managed?

A

5mg per day for 4 months

72
Q

In which physiological scenarios may macrocytic non-megaloblastic anaemia occur?

A

Pregnancy

Newborn

73
Q

Give examples of pathological causes of macrocytic non-megaloblastic anaemia?

A

Alcoholism
Liver disease
Hypothyroidism
Marrow failure

74
Q

What do investigations show in aplastic anaemia?

A

FBC - pancytopenia

Bone marrow aspirate - hypocellular

75
Q

Which rare condition is an inherited form of aplastic anaemia?

A

Fanconi’s anaemia

76
Q

Give examples of causes of acquired aplastic anaemia

A

Chemicals
Antibiotics
Insecticide
Infection

77
Q

How does aplastic anaemia present?

A

Anaemic features
Bleeding (epistaxis, gums, ecchymoses)
Recurrent infection

78
Q

How is aplastic anaemia treated?

A

Treat the cause

Stem cell infusion

79
Q

What is a spurious macrocytosis?

A

False macrocytosis

80
Q

Give causes of spurious macrocytosis

A

Reticulocytosis

Cold agglutinins

81
Q

What does blood film show with Reticulocytosis?

A

Polychromasia

and retics, obvs

82
Q

Where are red cells normally broken down?

A

Macrophages of spleen, liver and bone marrow

83
Q

What is erythroid hyperplasia?

A

Increasing the cells in the bone marrow which are dedicated to erythropoiesis
Marrow can extend into cortical bone

84
Q

Through which mechanisms is haemolysis compensated for?

A

Erythroid hyperplasia

Early retic release

85
Q

Where does extravascular haemolysis mostly take place?

A

Spleen

86
Q

When Hb is freed in circulation what does it bind to?

A

Haptoglobin

87
Q

Free Hb in the kidneys is broken down to….

A

Haemosiderin

88
Q

Describe the normal cell membrane of a red cell

A

Lipid bilayer crossed by integral proteins

Underlying protein spars and ankyrin to keep it together

89
Q

How is hereditary spherocytosis inherited?

A

AD

90
Q

Where is the defect most commonly found with hereditary spherocytosis?

A

Ankyrin

91
Q

How does hereditary spherocytosis present?

A

Anaemic features
Splenomegaly
Leg ulcers

92
Q

What does the blood film show on hereditary spherocytosis?

A

Spherocytes (obvs)

93
Q

How is hereditary spherocytosis managed?

A

Splenectomy
Immunisations
Prophylactic penicillin

94
Q

How is hereditary elliptocytosis inherited?

A

AR

95
Q

What is hereditary elliptocytosis?

A

Milder form of HS

Weakness of horizontal membrane proteins

96
Q

Warm autoimmune haemolytic anaemia is associated with which antibody?

A

IgG

97
Q

Cold autoimmune haemolytic anaemia is associated with which antibody?

A

IgM

98
Q

Give causes of warm autoimmune haemolytic anaemia

A

SLE
CLL and other malignancy
Penicillins
Idiopathic

99
Q

Give causes of cold autoimmune haemolytic anaemia?

A

Infection
Lymphoma
Idiopathic

100
Q

How does warm autoimmune haemolytic anaemia present?

A

Anaemia symptoms which relapse and remit
Splenomegaly
Infection

101
Q

What do investigations show in warm autoimmune haemolytic anaemia?

A

Spherocytes on blood film
Anaemia on FBC
Raised bilirubin
Coomb’s test positive

102
Q

How is warm autoimmune haemolytic anaemia managed?

A

Prednisolone 1mg/kg

Splenectomy if this is unsuccessful

103
Q

Describe the pathogenesis in cold autoimmune haemolytic anaemia

A

At low temp, IgM causes agglutination of red cells in peripheries which haemolyse when they return to central circulation

104
Q

What is paroxysmal cold haemoglobinuria associated with?

A

Childhood infection

105
Q

Which antibody is associated with paroxysmal cold haemoglobinuria?

A

IgG

106
Q

How is paroxysmal cold haemoglobinuria treated?

A

Red cell transfusions

107
Q

What is the mechanism of haemolytic disease of the newborn?

A

Alloimmune

108
Q

How is paroxysmal nocturnal haemoglobinuria inherited?

A

X-linked

109
Q

Where is the mutation in paroxysmal nocturnal haemoglobinuria?

A

PIG-A

110
Q

Roughly what does paroxysmal nocturnal haemoglobinuria do to red cells?

A

Makes them more susceptible to complement

111
Q

What are the clinical features of paroxysmal nocturnal haemoglobinuria?

A

VT in abnormal sites
Haemoglobinuria
Urine voided in night/first thing is dark in colour

112
Q

What does paroxysmal nocturnal haemoglobinuria show on investigation?

A

Increased plasma Hb
Haemosiderinuria
Low haptoglobin
Hypoplastic bone marrow on aspirate

113
Q

How is paroxysmal nocturnal haemoglobinuria managed?

A

Blood transfusions

Eculizumab

114
Q

What is Zieve’s syndrome?

A

Haemolysis due to changes in liver metabolism

115
Q

What does blood film show in Zieve’s syndrome?

A

Polychromatic macrocytes

Reticulocytosis

116
Q

Approx how much iron is lost per day in the faeces?

A

0.5-1mg

117
Q

Approx. how much iron is used per day in pregnancy?

A

1-2mg

118
Q

What does hereditary haemochromatosis cause?

A

Increased iron absorption

119
Q

By approx. how much should Hbh rise per week on treatment of iron def?

A

10mg

120
Q

Which reaction shows a ring of iron granules around the mitochondria in sideroblastic anaemia?

A

Perl’s

121
Q

What acute situation would cause normocytic anaemia?

A

Blood loss

122
Q

What does peripheral blood film show in macrocytic anaemia?

A

Hyper-segmented polymorphs

123
Q

Which system (other than the haematological system) does B12 def affect?

A

Neurological and psychiatric

124
Q

What does Schillings test determine?

A

How well B12 is absorbed

125
Q

What would indicate that B12 is absorbed out of the GI tract in Schillings test?

A

B12 in urine

126
Q

How is folic acid found in the serum?

A

As methyl THF monoglutamate

127
Q

Approx how long do stores last before folic acid deficiency presents?

A

4 months

128
Q

How long after treatment for folic acid def can reticulocytosis be seen on blood film?

A

2-3 days

129
Q

What may occur in the first few weeks of treatment of folic acid def?

A

Iron def

130
Q

How long may polyneuropathies from B12 def take to heal?

A

6-12m

Spinal cord damage is irreversible

131
Q

What is aplastic anaemia?

A

Pancytopenia with hypocellular bone marrow and no other abnormality

132
Q

What results in aplastic anaemia?

A

Reduction in number of stem cells combined with a flaw in the remaining ones or an immune process against them

133
Q

What does a positive Schumm’s test indicate?

A

Intravascular haemolysis

134
Q

How is hereditary elliptocytosis inherited?

A

AD

135
Q

What causes hereditary elliptocytosis??

A

Defects of 4.1 or spectrin/actin/4.1 complex in the membrane

136
Q

What are stomatocytes?

A

Red cells with a slit-like, pale central area

Year 3 - Haematology (17 decks)

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