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Macrocytic And Haemolytic Anaemias Flashcards

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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
What role does vitamin b12 play in DNA synthesis
Cofactor
26
What is vitamin B12 needed for
DNA synthesis Erythropoiesis CNS myelination BCAA metabolism FA metabolism
27
Which foods are sources of vitamin b12
Foods of animal origin
28
Which people require daily vitamin b12 supplements
Vegans
29
What does vitamin b12 bind to in the stomach
Haptocorrin
30
Where is intrinsic factor produced
Gastric parietal cells in stomach
31
Where does intrinsic factor bind to vitamin b12
Small intestine
32
Where is vitamin b12 taken up by the body
Terminal ileum
33
How is vitamin b12 taken up into cells
Receptor mediated endocytosis via Cubam receptor
34
What does vitamin b12 bind to in the blood for transport
Transcobalamin
35
Where is the majority of vitamin b12 stored
Liver
36
Vitamin b12 deficiency causes
Dietary deficiency Lack of intrinsic factor Disease of ileum Lack of transcobalamin Chemical inactivation of b12 Parasitic infestation Intrinsic factor chelating drugs
37
Pernicious anaemia
Autoimmune disease that creates antibodies to intrinsic factor or parietal cells
38
What drug can chemically inactivate vitamin b12
Nitrous oxide
39
B12 deficiency symptoms
Anaemia related symptoms Glossitis Mouth ulcers Diarrhoea Paraesthesia Disturbed vision Irritability Mental status change
40
Paraesthesia
Burning/prickling sensation usually felt in hands feet arms or legs
41
Is pernicious anaemia more common in men or women
Women
42
What does pernicious anaemia lead to
Gastric atrophy Decreased acid Decreased intrinsic factor secretion
43
How can folate deficiency affect the nervous system
Neural tube defects in pregnancy
44
How can vitamin b12 deficiency affect the nervous system
Focal demyelination Reversible peripheral neuropathy Subacute combined degeneration of the cord
45
Subacute combined degeneration of the cord
Degeneration of posterior and lateral columns of the spinal cord caused by b12 deficiency
46
Subacute degeneration of the cord symptoms
Gradual onset weakness Numbness and tingling in arms legs and trunks Mental state changes
47
How do vitamin b12 or folate deficiencies cause megaloblastic anaemia
Defective DNA synthesis -> nucleus matures slower than cytoplasm -> nucleus keeps getting bigger -> megaloblastic cells
48
How can elevated folate intake mask vitamin b12 deficiency
Alleviates anaemia caused by b12 deficiency by providing continual supply of active folate, as b12 needed to regenerate active folate
49
Why is folate masking of vitamin b12 deficiency dangerous
B12 deficiency may still cause Irreversible neurological damage
50
What is seen in a peripheral blood smear of a patient with megaloblastic anaemia
Large RBCs w large immature nuclei Hyper segmented neutrophils
51
How is megaloblastic anaemia diagnosed
Blood smear Check vitamin b12 and folate Full blood count Check for anti intrinsic factor antibodies
52
How is folate deficiency treated
Oral folic acid
53
How is vitamin b12 deficiency due to pernicious anaemia treated
Intramuscular hydroxycobalamine for life
54
How is vitamin b12 deficiency not related to pernicious anaemia treated
Oral cyanocobalamine
55
How long does it take for neuropathy caused by vitamin b12 deficiency to resolve after treatment begins
3-6 months May not resolve if deficient for too long
56
What can blood transfusions cause in patients with sever anaemia from b12 deficiency
High output cardiac failure
57
What causes haemolytic anaemia
Abnormal haemolysis
58
Intravascular haemolysis
RBC breakdown in blood vessels
59
Extravascular haemolysis
RBC breakdown in spleen and wider RES
60
How can bone marrow compensate for abnormal haemolysis to prevent haemolytic anaemia
Increase RBC production up to a point
61
Inherited causes of haemolytic anaemia
Glycolysis defect Pentose P pathway defect Membrane protein defect Haemoglobin defect
62
Acquired haemolytic anaemia causes
Mechanical damage to cells Antibody damage to cells Oxidant damage to cells Heat damage to cells Enzymatic damage to cells
63
What laboratory findings are linked to haemolytic anaemia
Raised reticulocytes Raised bilirubin Raised LDH
64
Pathology at which 3 sites can can haemolytic anaemia
RBC membrane haemoglobin RBC enzymes
65
Haemolytic anaemia signs and symptoms
Jaundice Pigment gallstones Splenomegaly
66
What causes jaundice
Accumulation of bilirubin
67
What causes splenomegaly in haemolytic anaemia
Extramedullary hematopoiesis in red pulp spleen
68
Extramedullary hematopoiesis
Making blood outside bone marrow
69
What can be caused by massive sudden haemolysis
Cardiac arrest Hyperkalaemia
70
What are 3 inherited defects in RBC membranes that can cause haemolytic anaemia
Hereditary spherocytosis Hereditary eliptocytosis Hereditary pyropoikilocytosis
71
What shape are RBCs in hereditary spherocytosis
Spherical
72
What shape are RBCs in herditary eliptocytosis
Elliptical
73
What shape are RBCs in herditary pyropoikilocytosis
Elliptical
74
What defects cause hereditary spherocytosis
Ankyrin, spectrin, protein 4.2, band 3
75
What protein is defective in hereditary eliptocytosis and hereditary pyropoikilocytosis
Spectrin
76
What is the more severe form of hereditary eliptocytosis
Hereditary pyropoikilocytosis
77
What are RBCs abnormally sensitive to in hereditary pyropoikilocytosis
Heat
78
What enzyme deficiencies can cause haemolytic anaemia
Pyruvate kinase Glucose 6 phosphate dehydrogenase
79
How can pyruvate kinase deficiency cause haemolytic anaemia
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
Why does pyruvate kinase deficiency usually only cause mild haemolytic anaemia
Still some enzyme activity present Increased 2,3 DPG levels
81
How does glucose 6 phosphate dehydrogenase deficiency cause haemolytic anaemia
Limits pentose phosphate pathway -> decreased NADPH levels ->glutathione not kept in reduced state -> RBCs very affected by oxidative stress -> haemolysis
82
Heinz bodies
Clumps of oxidised haemoglobin
83
How can Heinz bodies damage RBCs
May detach and damage membrane
84
Which conditions cause Heinz body formation
Glucose 6 phosphate dehydrogenase deficiency Thalassaemias
85
What causes microangiopathic anaemias
Mechanical damage to RBCs
86
How can RBCs be mechanically damaged
Shear stress from passing through defective heart valves Snagging on fibrin strands in small vessels with increased activation of clotting cascade
87
What acquired damage to RBCs can cause haemolytic anaemia
Mechanical damage Heat damage Osmotic damage
88
Schistocytes
RBC fragments from mechanical damage
89
How can autoimmune RBC destruction cause haemolytic anaemia
Autoantibodies bind to RBCs -> spleen removes antibody bound cells
90
What is autoimmune haemolytic anaemia classified as warm or cold based on
Temperature antibodies react most strongly under laboratory conditions
91
What conditions can cause autoimmune haemolytic anaemia
Drugs Connective tissue disease Lond transfusion Cancer of lymphoid system Infections
92
Can b12 deficiency cause neurological symptoms without causing anaemia
Yes

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