Anaemia Flashcards
1
Q
What is anaemia?
A
haemoglobin levels 2 standard deviations below the normal for age and sex
Anaemia is a common condition that results in impaired oxygen delivery to body tissues due to reduced haemoglobin
2
Q
What is the normal range for female Hb?
A
115-165 g/L
3
Q
What is the normal range for male Hb?
A
130-180 g/L
4
Q
How can anaemia be classified?
A
according to the average size of the red blood cells (RBC), referred to as mean corpuscular volume (MCV)
5
Q
What are the 3 categories of anaemia according to mean corpuscular volume?
A
- Microcytic anaemia
- Normocytic anaemia
- Macrocytic anaemia
6
Q
What is the MCV threshold for microcytic anaemia?
A
<80
7
Q
What is the MCV range for normocytic anaemia?
A
80-100
8
Q
What is the MCV range for macrocytic anaemia?
A
> 100
9
Q
Give 6 general presentations associated with anaemia :
A
- Pallor
- Fatigue
- Breathlessness
- dizziness
- Palpitations
- cold feet and hands
10
Q
What is the most common cause of microcytic anaemia?
A
iron deficiency
11
Q
What causes smaller RBCs in microcytic anaemia?
A
lower haemoglobin causes an extra division of RBCs to maintain an adequate haemoglobin content
12
Q
What is the word used to describe pale RBCs with small nuclei?
A
hypochromic
13
Q
Give 3 potential causes of iron deficiency:
A
1) chronic blood loss (e.g. menorrhagia)
2) malabsorption(e.g. gastrectomy or Coeliac)
3) increased requirements (pregnancy, childhood)
14
Q
What do patients over 40 with iron deficiency require?
A
an upper and lower endoscopy
15
Q
Is total iron binding capacity high or low in iron deficiency anaemia?
A
high
16
Q
Is ferritin high or low in iron deficiency anaemia?
A
Low
17
Q
Give 3 types of microcytic anaemia:
A
1) iron deficiency anaemia
2) sideroblastic anaemia
3) thalassaemia
18
Q
What is sideroblastic anaemia?
A
where defective protoporphyrin synthesis results in low haemoglobin
19
Q
Describe the cause of congenital sideroblastic anaemia:
A
a deficiency of aminolaevulinic acid synthetase (ALAS) enzyme which is the rate determining enzyme for protoporphyrin synthesis, results in low haemoglobin
20
Q
Give 3 examples of causes of acquired sideroblastic anaemia:
A
- Alcoholism
- Lead poisoning
- Vitamin B6 deficiency
21
Q
Why is vitamin B6 deficiency a cause of acquired sideroblastic anaemia?
A
it is a cofactor for the ALAS enzyme, the rate determining enzyme for protoporphyrin synthesis
22
Q
Are iron levels high, low or normal in sideroblastic anaemia?
A
Normal
23
Q
What is a characteristic sign of sideroblastic anaemia on blood film?
A
sideroblasts
24
Q
What are sideroblasts?
A
abnormal red blood cells that have a ring around the nucleus due to iron building up in the mitochondria
25
An inherited mutation in what gene causes thalassaemia?
Globin gene
26
What is thalassaemia major?
the most severe type of thalassaemia - requires regular transfusions
27
What is alpha thalassaemia?
where the alpha globin chains are affected by a mutation
28
What is beta thalassaemia?
where the beta globin chains are affected by a mutation
29
What is thalassaemia trait?
carrier for thalassaemia - may be asymptomatic or experience mild symptoms
30
Where does thalassaemia frequently occur?
Mediterranean, Africa, Western and Southeast Asia, as well as India and Burma.
31
What is thalassaemia protective against?
Plasmodium falciparum malaria
32
What facial dysmorphia is associated with thalassaemia?
chipmunk facies (high bulging check bones with protrusion or the anterior teeth)
33
Give 3 genes associated with thalassaemia:
1) HBB
2) HBA1
3) HBA2
34
Will ferritin be high, low or normal in thalassaemia?
normal
35
True or false: normocytic anaemia is normally normochromic
True
36
What are the three broad causes of normocytic anaemia?
1) haemolysis
2) underproduction of red blood cells
3) Anaemia of chronic disease
37
What does haemolysis in normocytic anaemia refer to?
Haemolysis is the premature destruction of red blood cells that are of normal size but are being destroyed faster than they can be replaced.
38
What are the two types of haemolysis?
1. Intrinsic
2. Extrinsic
39
Where does extravascular haemolysis primarily occur?
Spleen
40
what is intravascular haemolysis?
These are disorders that originate within the red blood cell, causing them to be destroyed prematurely, leading to the release of free haemoglobin into the blood
41
Give 6 types of haemolytic normocytic anaemia:
1) hereditary spherocytosis
2) sickle cell anaemia
3) paroxysmal nocturnal haemoglobinuria
4) glucose-6-phosphate dehydrogenase deficiency
5) immune haemolytic anaemia
6) microangiopathic haemolytic anaemia
42
What is meant by extrinsic haemolysis?
These causes stem from factors outside the red blood cell that lead to its premature destruction
43
Give 3 broad causes of anaemia of chronic disease:
1. Malignancy
2. Chronic infections
3. Autoimmune disease
44
Describe the pathophysiology of anaemia of chronic disease:
chronic diseases can cause the liver to produce more hepcidin which stimulates the storage of serum iron as ferritin, reducing the availability of iron in serum
45
Is anaemia of chronic disease typically macro, normo or microcytic?
normocytic (but can progress to microcytic)
46
Are serum iron levels high, low or normal in anaemia of chronic disease?
low
47
Why are serum levels of iron low in anaemia of chronic disease?
Increased Hepcidin Production: In response to inflammation, the liver produces more hepcidin, a protein that inhibits iron absorption from the intestine and prevents iron release from macrophages and the liver. This leads to iron sequestration, where iron is stored in the reticuloendothelial system (macrophages) and is not available for red blood cell production.
48
Are serum ferritin levels high, low or normal in anaemia of chronic disease?
high
49
Why are serum ferritin levels high in anaemia of chronic disease?
In anaemia of chronic disease, ferritin levels are high due to the body's response to inflammation. Ferritin acts as an acute-phase reactant, and inflammation leads to increased ferritin production. However, while ferritin is elevated, the iron stored in ferritin is not available for red blood cell production, contributing to anaemia. Thus, the high ferritin levels in ACD reflect inflammation and iron sequestration rather than iron overload.
50
Is total iron binding capacity high, low or normal in anaemia of chronic disease?
low
51
Why is total iron binding capacity low in anaemia of chronic disease?
In anaemia of chronic disease, TIBC is low because of the following factors:
Reduced transferrin production by the liver in response to inflammatory cytokines.
Increased hepcidin levels, which reduce iron availability and decrease the need for transferrin.
Iron sequestration in storage (macrophages and liver) reduces the amount of iron available for transferrin to bind.
In essence, in ACD, the body is trying to restrict the availability of iron to pathogens and to prioritize iron storage rather than iron transport, leading to decreased TIBC.
52
What causes hereditary spherocytosis?
an inherited defect of red blood cell cytoskeleton membrane proteins such as ankyrin and spectrin
53
Is serum uric acid high, low or normal in hereditary spherocytosis?
high
54
Are reticulocytes high, low or normal in hereditary spherocytosis?
high
55
What causes haemolysis in hereditary spherocytosis?
abnormal spherocytes are haemolysed by the spleen
56
What is the inheritance pattern of sickle cell anaemia?
autosomal recessive
57
What protein is affected in sickle cell anaemia?
beta globin chain
58
What change in amino acids causes sickle cell anaemia?
valine replaces glutamic acid
59
True or false; there is both intravascular and extravascular haemolysis seen in sickle cell anaemia
true
60
What are reticulocytes?
Reticulocytes are immature red blood cells (RBCs) that are newly produced by the bone marrow and released into the bloodstream. They are considered the precursors to fully mature red blood cells, and their presence in the blood is an important indicator of bone marrow activity and the body's ability to produce RBCs.
61
Are reticulocytes high, low or normal in sickle cell anaemia?
high
62
Is serum uric acid high, low or normal in sickle cell anaemia?
high
63
Give 3 signs of sickle cell anaemia on a blood film:
1. Sickling of erythrocytes
2. Target cells
3. Howell-jolly bodies
64
What molecule is defective in paroxysmal nocturnal haemoglobinuria?
glycosylphosphatidylinositol (GPI)
65
Describe the pathophysiology of paroxysmal nocturnal haemoglobinuria: (3)
1) an acquired defect in GPI makes red blood cells more susceptible to the complement system
2) shallow breathing during sleep can cause CO2 retention and therefore mild respiratory acidosis
3) this acidosis targets the complement system which lyses red blood cells
66
Are reticulocytes high, low or normal in paroxysmal nocturnal haemoglobinuria?
normal
67
Is serum uric acid high, low or normal in paroxysmal nocturnal haemoglobinuria?
high
68
What does G6PD stand for?
glucose-6-phosphate dehydrogenase
69
Describe the pathophysiology of G6PD deficiency haemolysis:
G6PD produces NADPH which reduces glutathione - a protector form oxidative injury - a deficiency causes intravascular haemolysis due to destruction via oxidative stress
70
Does G6DP cause intravascular or extravascular haemolysis?
intravascular
71
Are reticulocytes high, low or normal in G6DP deficiency?
high
72
Is serum uric acid high, low or normal in G6DP deficiency?
high
73
Does IgG mediated haemolysis cause intravascular or extravascular haemolysis?
extravascular
74
Does IgM medicated haemolysis cause intravascular or extravascular haemolysis?
intravascular
75
Describe the pathophysiology of microangiopathic haemolytic syndrome:
red blood cells are destroyed by structural issues within vasculature such as microthrombi, prosthetic heart valves or aortic stenosis
76
What are schistocytes?
Fragmented RBCs
77
In which type of anaemia are schistocytes seen?
microangiopathic haemolytic anaemia
78
Give 2 causes of underproduction of red blood cells?
1) bone marrow failure
2) erythropoietin deficiency
79
Are reticulocytes high, low or normal in underproduction of RBCs?
normal
80
Is serum uric acid high, low or normal in underproduction of RBCs?
normal
81
What are the two types of macrocytic anaemia?
1) megaloblastic (impaired DNA synthesis)
2) non-megaloblastic
82
Give 4 causes of folate deficiency:
1) poor diet
2) malabsorption
3) increased demand (e.g. pregnancy, haemolytic anaemia, cancer)
4) use of folate antagonists (e.g. trimethoprim)
83
Why does folate deficiency result in megaloblastic anaemia?
folate is required for purine synthesis
84
Is serum homocysteine high, low or normal in folate deficiency anaemia?
high
85
Is serum methylmalonic acid high, low or normal in folate deficiency anaemia?
normal
86
Why is it uncommon to see vitamin B12 deficiency?
the body has a large hepatic store of vitamin B12 which takes a while to become depleted
87
What cofactor enables absorption of vitamin B12 in the terminal ileum?
intrinsic factor
88
What cells produce intrinsic factor?
gastric parietal cells
89
What is pernicious anaemia?
where parietal cells are destroyed through an autoimmune process, impairing the production of intrinsic factor and therefore the absorption of vitamin B12
90
What is the most common cause of vitamin B12 deficiency anaemia?
pernicious anaemia
91
Other than pernicious anaemia, give three causes of vitamin B12 deficiency:
1) vegan diet
2) pancreatic insufficiency
3) damage to terminal ileum
92
Is serum methylmalonic acid high, low or normal in vitamin B12 deficiency anaemia?
high
93
Is serum homocysteine high, low or normal in vitamin B12 deficiency anaemia?
high
94
True or false: vitamin B12 deficiency causes neurological symptoms alongside megaloblastic anaemia?
True
95
Give 3 causes of non-megaloblastic macrocytic anaemia:
1) alcoholism
2) hypothyroidism
3) drugs like fluorouracil
96
Is serum homocysteine high, low or normal in non-megaloblastic macrocytic anaemia?
normal
97
Is serum methylmalonic acid high, low or normal in non-megaloblastic macrocytic anaemia?
normal
