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CR2 > Macrocytic And Haemolytic Anaemias > Flashcards

Macrocytic And Haemolytic Anaemias Flashcards

1
Q

What mechanisms can cause anaemia

A

Decr/dysfunctional erythropoiesis
Abnormal Haem synthesis
Abnormal globin chain synthesis
Abnormal RBC structure
RBC mechanical damage
Abnormal RBC metabolism
Excessive bleeding
Increased removal

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2
Q

How can vitamin deficiencies cause anaemia

A

Reduce erythropoiesis

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3
Q

Anaemia

A

Hb level below reference level for age and sex

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4
Q

What are the 3 classes of anaemia based on RBC size

A

Macrocytic
Normocytic
Microcytic

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5
Q

3 types of macrocytic anaemia

A

Megaloblastic anaemia
Macronormoblastic erythropoiesis
Stress erythropoiesis

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6
Q

When does stress erythropoiesis occur

A

After haemorrhage

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7
Q

Characteristics of megaloblasts

A

Bigger than normal RBCs
Large immature nuclei

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8
Q

What causes megaloblastic anaemia

A

Interference with DNA synthesis during erythropoiesis

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9
Q

Why do erythrocytes continue growing to form megaloblasts in megaloblastic anaemia

A

Cell division delayed due to delayed nucleus development

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10
Q

What can lead to megaloblastic anaemia

A

Vitamin B12 deficiency
Folate deficiency
Drugs
Some erythroid leukaemias

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11
Q

How are erythroblast abnormal in macronormoblastic erythropoiesis

A

Larger than normal

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12
Q

What conditions can lead to macronormoblastic anaemia

A

Liver disease
Alcohol toxicity
Some myelodysplastic syndromes

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13
Q

What is Stress erythropoiesis and what type of cell has a higher than normal count when it occurs

A

Increased erythropoiesis in response to blood loss
Reticulocyte

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14
Q

What causes expanded and accelerated erythropoiesis in stress erythropoiesis

A

High erythropoietin levels

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15
Q

What can lead to stress erythropoiesis

A

Recovery from Blood loss/haemorrhage
Recovery from haemolytic anaemia

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16
Q

What foods are high in folate

A

Green leafy veg
Citrus
Avocados
Other veg
Fortified cereals

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17
Q

Where is folate mainly absorbed

A

Duodenum
Jejenum

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18
Q

Which cells convert folate to tetrahydrofolate

A

Intestinal cells

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19
Q

Where is folate taken up and stored

A

Liver

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20
Q

What is folate needed for

A

Provide carbon for metabolic reactions - nucleotide base synthesis, DNA synthesis, RNA synthesis

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21
Q

Folate deficiency causes

A

Dietary deficiency
Increased requirements
Disease of duodenum or jejenum
Drugs which inhibit dihydrofolate reductase
Alcoholism
Liver disease
Heart failure

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22
Q

Folate deficiency symptoms

A

Anaemia related symptoms
Reduced sense of taste
Diarrhoea
Numbness and tingling in hands and feet
Muscle weakness
Depression

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23
Q

When and how much folic acid should be taken in regards to pregnancy

A

400ug/day
Before conception - 12wks

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24
Q

Why should folic acid be taken in early pregnancy

A

Prevents neural tube defects

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25
Q

What role does vitamin b12 play in DNA synthesis

A

Cofactor

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26
Q

What is vitamin B12 needed for

A

DNA synthesis
Erythropoiesis
CNS myelination
BCAA metabolism
FA metabolism

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27
Q

Which foods are sources of vitamin b12

A

Foods of animal origin

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28
Q

Which people require daily vitamin b12 supplements

A

Vegans

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29
Q

What does vitamin b12 bind to in the stomach

A

Haptocorrin

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30
Q

Where is intrinsic factor produced

A

Gastric parietal cells in stomach

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31
Q

Where does intrinsic factor bind to vitamin b12

A

Small intestine

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32
Q

Where is vitamin b12 taken up by the body

A

Terminal ileum

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33
Q

How is vitamin b12 taken up into cells

A

Receptor mediated endocytosis via Cubam receptor

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34
Q

What does vitamin b12 bind to in the blood for transport

A

Transcobalamin

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35
Q

Where is the majority of vitamin b12 stored

A

Liver

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36
Q

Vitamin b12 deficiency causes

A

Dietary deficiency
Lack of intrinsic factor
Disease of ileum
Lack of transcobalamin
Chemical inactivation of b12
Parasitic infestation
Intrinsic factor chelating drugs

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37
Q

Pernicious anaemia

A

Autoimmune disease that creates antibodies to intrinsic factor or parietal cells

38
Q

What drug can chemically inactivate vitamin b12

A

Nitrous oxide

39
Q

B12 deficiency symptoms

A

Anaemia related symptoms
Glossitis
Mouth ulcers
Diarrhoea
Paraesthesia
Disturbed vision
Irritability
Mental status change

40
Q

Paraesthesia

A

Burning/prickling sensation usually felt in hands feet arms or legs

41
Q

Is pernicious anaemia more common in men or women

A

Women

42
Q

What does pernicious anaemia lead to

A

Gastric atrophy
Decreased acid
Decreased intrinsic factor secretion

43
Q

How can folate deficiency affect the nervous system

A

Neural tube defects in pregnancy

44
Q

How can vitamin b12 deficiency affect the nervous system

A

Focal demyelination
Reversible peripheral neuropathy
Subacute combined degeneration of the cord

45
Q

Subacute combined degeneration of the cord

A

Degeneration of posterior and lateral columns of the spinal cord caused by b12 deficiency

46
Q

Subacute degeneration of the cord symptoms

A

Gradual onset weakness
Numbness and tingling in arms legs and trunks
Mental state changes

47
Q

How do vitamin b12 or folate deficiencies cause megaloblastic anaemia

A

Defective DNA synthesis -> nucleus matures slower than cytoplasm -> nucleus keeps getting bigger -> megaloblastic cells

48
Q

How can elevated folate intake mask vitamin b12 deficiency

A

Alleviates anaemia caused by b12 deficiency by providing continual supply of active folate, as b12 needed to regenerate active folate

49
Q

Why is folate masking of vitamin b12 deficiency dangerous

A

B12 deficiency may still cause Irreversible neurological damage

50
Q

What is seen in a peripheral blood smear of a patient with megaloblastic anaemia

A

Large RBCs w large immature nuclei
Hyper segmented neutrophils

51
Q

How is megaloblastic anaemia diagnosed

A

Blood smear
Check vitamin b12 and folate
Full blood count
Check for anti intrinsic factor antibodies

52
Q

How is folate deficiency treated

A

Oral folic acid

53
Q

How is vitamin b12 deficiency due to pernicious anaemia treated

A

Intramuscular hydroxycobalamine for life

54
Q

How is vitamin b12 deficiency not related to pernicious anaemia treated

A

Oral cyanocobalamine

55
Q

How long does it take for neuropathy caused by vitamin b12 deficiency to resolve after treatment begins

A

3-6 months
May not resolve if deficient for too long

56
Q

What can blood transfusions cause in patients with sever anaemia from b12 deficiency

A

High output cardiac failure

57
Q

What causes haemolytic anaemia

A

Abnormal haemolysis

58
Q

Intravascular haemolysis

A

RBC breakdown in blood vessels

59
Q

Extravascular haemolysis

A

RBC breakdown in spleen and wider RES

60
Q

How can bone marrow compensate for abnormal haemolysis to prevent haemolytic anaemia

A

Increase RBC production up to a point

61
Q

Inherited causes of haemolytic anaemia

A

Glycolysis defect
Pentose P pathway defect
Membrane protein defect
Haemoglobin defect

62
Q

Acquired haemolytic anaemia causes

A

Mechanical damage to cells
Antibody damage to cells
Oxidant damage to cells
Heat damage to cells
Enzymatic damage to cells

63
Q

What laboratory findings are linked to haemolytic anaemia

A

Raised reticulocytes
Raised bilirubin
Raised LDH

64
Q

Pathology at which 3 sites can can haemolytic anaemia

A

RBC membrane
haemoglobin
RBC enzymes

65
Q

Haemolytic anaemia signs and symptoms

A

Jaundice
Pigment gallstones
Splenomegaly

66
Q

What causes jaundice

A

Accumulation of bilirubin

67
Q

What causes splenomegaly in haemolytic anaemia

A

Extramedullary hematopoiesis in red pulp spleen

68
Q

Extramedullary hematopoiesis

A

Making blood outside bone marrow

69
Q

What can be caused by massive sudden haemolysis

A

Cardiac arrest
Hyperkalaemia

70
Q

What are 3 inherited defects in RBC membranes that can cause haemolytic anaemia

A

Hereditary spherocytosis
Hereditary eliptocytosis
Hereditary pyropoikilocytosis

71
Q

What shape are RBCs in hereditary spherocytosis

A

Spherical

72
Q

What shape are RBCs in herditary eliptocytosis

A

Elliptical

73
Q

What shape are RBCs in herditary pyropoikilocytosis

A

Elliptical

74
Q

What defects cause hereditary spherocytosis

A

Ankyrin, spectrin, protein 4.2, band 3

75
Q

What protein is defective in hereditary eliptocytosis and hereditary pyropoikilocytosis

A

Spectrin

76
Q

What is the more severe form of hereditary eliptocytosis

A

Hereditary pyropoikilocytosis

77
Q

What are RBCs abnormally sensitive to in hereditary pyropoikilocytosis

A

Heat

78
Q

What enzyme deficiencies can cause haemolytic anaemia

A

Pyruvate kinase
Glucose 6 phosphate dehydrogenase

79
Q

How can pyruvate kinase deficiency cause haemolytic anaemia

A

Stops final step of glycolysis decreasing ATP production, which prevents ATPase pump functioning causing loss of K+ and H2O, causing dehydrating and cell death

80
Q

Why does pyruvate kinase deficiency usually only cause mild haemolytic anaemia

A

Still some enzyme activity present
Increased 2,3 DPG levels

81
Q

How does glucose 6 phosphate dehydrogenase deficiency cause haemolytic anaemia

A

Limits pentose phosphate pathway -> decreased NADPH levels ->glutathione not kept in reduced state -> RBCs very affected by oxidative stress -> haemolysis

82
Q

Heinz bodies

A

Clumps of oxidised haemoglobin

83
Q

How can Heinz bodies damage RBCs

A

May detach and damage membrane

84
Q

Which conditions cause Heinz body formation

A

Glucose 6 phosphate dehydrogenase deficiency
Thalassaemias

85
Q

What causes microangiopathic anaemias

A

Mechanical damage to RBCs

86
Q

How can RBCs be mechanically damaged

A

Shear stress from passing through defective heart valves
Snagging on fibrin strands in small vessels with increased activation of clotting cascade

87
Q

What acquired damage to RBCs can cause haemolytic anaemia

A

Mechanical damage
Heat damage
Osmotic damage

88
Q

Schistocytes

A

RBC fragments from mechanical damage

89
Q

How can autoimmune RBC destruction cause haemolytic anaemia

A

Autoantibodies bind to RBCs -> spleen removes antibody bound cells

90
Q

What is autoimmune haemolytic anaemia classified as warm or cold based on

A

Temperature antibodies react most strongly under laboratory conditions

91
Q

What conditions can cause autoimmune haemolytic anaemia

A

Drugs
Connective tissue disease
Lond transfusion
Cancer of lymphoid system
Infections

92
Q

Can b12 deficiency cause neurological symptoms without causing anaemia

A

Yes

CR2 (33 decks)

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