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Haematology Year 3 > Anaemia > Flashcards

Anaemia Flashcards

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1
Q

definition of anaemia

A

reduced total red cell mass

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2
Q

where does red cell production take place in adults

A

bone marrow

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3
Q

what is the bone marrows response to anaemia

A

Increased RBC production- reticulocytosis

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4
Q

what are reticulocytes

A

red cells that have just left the bone marrow
larger than average red cells
still have RNA remnants
stain purple/deeper red as a result

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5
Q

what are the 2 ways anaemia can be classified

A

pathophysiology

morphological characteristics

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6
Q

what are the two categories of anaemia pathophysiology

A 
Decreased production (low reticulocyte count)
Increased loss or destruction of red cells (high reticulocyte count)
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7
Q

causes of decreased RBC production

A

hypoproliferative- reduced amount of erythropoiesis e.g. chronic kidney disease, aplastic anaemia
Maturation abnormality- erythropoiesis present but ineffective

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8
Q

name some maturation abnormalities that cause decreased RBC production

A

Cytoplasmic defects: impaired haemoglobinisation (results in small cells)
Nuclear defects: impaired cell division (results in big cells)

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9
Q

what causes loss/destruction of RBCs

A

bleeding

haemolysis

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10
Q

what is a useful tool in distinguishing cytoplasmic and nuclear defects

A

mean cell volume

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11
Q

how can anaemia be classified by morphology

A

MCV low = microcytic

MCV high = macrocytic

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12
Q

what should you consider if MCV is low

A

problems with haemoglobinisation (cytoplasmic defect)

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13
Q

what should you consider if MCV is high

A

problems with maturation

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14
Q

where does haemoglobin synthesis occur

A

in the cytoplasm

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15
Q

what is needed to make Hb

A

globins

Haem: porphyrin ring, Iron (Fe 2+)

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16
Q

what does the inability to make Hb result in

A

small, pale red cells with a low Hb content

Microcytic (small) and hypochromic (lacking in colour)

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17
Q

causes of hypochromic, microcytic anaemia

A 
Haem deficiency 
Globin deficiency (thalassaemia)
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18
Q

what 2 states can iron exist in the body

A

Fe2+ - ferrous iron

Fe3+ ferric iron

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19
Q

why iron important

A

oxygen transport- Hb, myoglobin

Electron transport- mitochondrial production of ATP

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20
Q

What does iron generate

A

free radicals

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21
Q

where is most of the iron in our bodies found

A

in the haemoglobin

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22
Q

how is iron stored in the body

A

as ferritin in tissues, mainly the liver and macrophages

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23
Q

what is circulating iron bound to

A

transferrin

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24
Q

how can we assess iron status: functional, transported and storage

A

functional: Hb
Transported: serum iron, transferrin, transferrin saturation
Storage iron: serum ferritin

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25
function of transferrin
takes iron from donor tissues (macrophages, hepatocytes) to tissues expressing transferrin receptors
26
how many binding sites for iron does transferrin have
2
27
what does % saturation of transferrin with iron measure
iron supply
28
what does changes in transferrin suggest when reduced/increased
Reduced in iron deficiency and anaemia of chronic disease | Increased in genetic haemachromatosis
29
what does low ferritin indicate
iron deficiency
30
causes of iron deficiency
not eating enough blood loss (usually GI- tumours, ulcers, NSAIDs) Malabsorption (coeliac disease) Menorrhagia (>60mls)
31
where is iron absorbed in the bowel
duodenum
32
consequences of negative iron imbalance
1. exhaustion of iron stores 2. iron deficient erythropoiesis - falling red cell MCV 3. Microcytic anaemia 4. Epithelial changes e.g. koilonychia
33
what is important to remember about iron deficiency anaemia
it is a symptom not a diagnosis- needs investigating
34
what is macrocytic anaemia
anaemia where red cells have a larger than normal mean cell volume
35
what is a megaloblast
an abnormally large nucleated red cell precursor with an immature nucleus
36
what are megaloblastic anaemias characterised by
defects in DNA synthesis and nuclear maturation with preservation of RNA and Hb synthesis
37
consequences of megaloblastic changes
while the cytoplasm has developed and become mature enough to divide, the nucleus is still immature Leads to a bigger than normal red cell precursor
38
in summary, what causes the larger cell size in megaloblastic anaemia
cell failure to become smaller
39
what causes megaloblastic anaemia
B12 deficiency Folate deficiency Drugs Rare inherited abnormalities
40
why does a lack of B12/folate cause megaloblastic anaemia
B12 and folate are essential co-factors for nuclear maturation They enable chemical reactions that provide enough nucleosides for DNA synthesis
41
what cycle is B12 responsible for
methionine cycle
42
what cycle is folate responsible for
folate cycle
43
what does the methionine cycle produce
s-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates
44
what is the folate cycle important for
nucleoside synthesis (e.g. uridine to thymidine conversion)
45
what is the pathway of B12 absorption
1. comes as cobalamin (Cbl) in meat/eggs 2. acid in the stomach makes Cbl separate and bind to hepatocorrin (HC) 3. Intrinsic factor (IF) formed in the stomach 4. they all travel together in the gut 5. pancreas raises the pH causing Cbl to separate from HC 6. Cbl now binds to IF 7. Cbl-IF binds to cubulin receptors in the distal bowel (ileum) 8. Cbl transported into the blood vessels
46
causes of B12 deficiency
``` dietary (e.g. vegan) pernicious anaemia atrophic gastritis chronic pancreatitis coeliac disease crohns disease ```
47
what are dietary folates converted to and where are they absorbed
converted to mono glutamate | absorbed in the jejunum
48
how long do body stores of B12 and folate last
B12- 2-4 years | Folate- 4 months
49
causes of folate deficiency
inadequate intake malabsorption (coeliac, crohns) Excess utilisation (haemolytic, pregnancy, malignancy) drugs (anti-convulsants)
50
features of B12/Folate deficiency
symptoms/signs of anaemia (fatigue, dyspnoea, headache, palpitations) weight loss, diarrhoea, infertility, jaundice, developmental problems
51
what symptom is specific to B12 deficiency
neurological problems: - posterior/dorsal column abnormalities - neuropathy - dementia - Psychiatric manifestations
52
what spinal problem is seen in B12 deficiency
subacute combined degeneration of the spinal cord
53
what is pernicious anaemia
autoimmune condition which results in destruction of gastric parietal cells these cells produce intrinsic factor-- results in intrinsic factor deficiency with B12 malabsorption and deficiency
54
what conditions are associated with pernicious anaemia
atrophic gastritis, hypothyroidism, vitiligo, Addison's disease
55
blood results seen in pernicious anaemia
Macrocytic anaemia (red cells large + low) Pancytopenia (all cells low) Macrovalocytes (enlarged, oval shaped erythrocytes) Hypersegmented neutrophils
56
What should be checked in pernicious anaemia
Serum folate and B12 Autoantibodies: anti gastric-parietal cells: autoimmune gastritis Anti-intrinsic factor
57
treatment of megaloblastic anaemia
Treat the cause For pernicious anaemia- vit B12 injections for life Folic acid 5mg oral daily
58
what is injections of vitamin b12 called
hydroxycobalamin
59
what are causes of macrocytosis split into
Genuine: megaloblastic/non-megaloblastic | Spurious
60
Non-megaloblastic causes of macrocytosis
Alcohol Liver disease Hypothyroidism (these may not be associated with anaemia) Marrow failure: Myelodysplasia, Myelomo, Aplastic anaemia
61
what is meant by megaloblastic anaemia
inhibition of DNA synthesis during RBC production | When DNA synthesis is impaired, it leads to continuing cell growth without division, which presents as macrocytosis
62
what is spurious macrocytosis
The size of the mature read cell is normal but the MCV is high
63
causes of spurious macrocytosis
Increase in reticulocyte numbers as marrow responds to acute blood loss or RBC break down Cold-agglutinins (abnormal proteins that cause clumping of RBC)
64
If the reticulocyte count is raised, what should you consider
haemorrhage | haemolysis
65
if the reticulocyte count is low in a macrocytosis, what investigation should be done next
serum B12 + Folate
66
If serum B12 and/or folate is high, what causes should be considered
Myelodysplasia Myeloma Aplastic anaemia
67
If serum B12 and/or folate is low, what is the likely diagnosis
megaloblastic anaemia
68
why can liver disease cause a low platelet count
leads to hypersplenism -- increased destruction
69
what can people with pernicious anaemia present with
mild jaundice due to intramedullary haemolysis
70
why do people get jaundice in pernicious anaemia
Red cells die prematurely in the bone marrow Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells Haemoglobin is converted to bilirubin
71
what can complicate severe megaloblastic anaemia
pancytopenia
72
What are the two headings for classifications of anaemia
Decreased production (would see reticulocytopenia) Increased loss or destruction of RBCs (would see reticulocytosis)
73
what is seen in increased haemolysis of RBCs
Increased unconjugated serum bilirubin Increased urinary urobilinogen Result is anaemia + jaundice, sometimes with splenomegaly
74
commonest cause of hypo chromatic microcytic anaemia
iron deficiency
75
what is the platelet count in iron deficiency anaemia
low
76
other less common causes of microcytic anaemia
Thalassaemia
77
investigation of thalassaemia
electrophoresis | HPLC
78
nutritional causes of macrocytic anaemia
``` B12 deficiency Folate deficiency (This causes megaloblastic anaemia) ```
79
causes of macrocytic anaemia
``` myelodysplasia myeloma aplastic anaemia reticulocytosis cold agglutinins ```
80
when can you see a macrocytosis without anaemia
alcohol liver disease hypothyroid
81
what are the causes of normochromatic normocytic anaemia
``` Acute blood loss/early iron deficiency Hypoproliferative: -Chronic diseases - Anaemia of renal failure -Hypothyroidism - Marrow failure ```
82
How is EPO production affected in renal failure
It decreases
83
what is the big differentiating factor for anaemia caused by iron deficiency and anaemia of chronic disease
Iron deficiency = reduced ferritin | Chronic disease = normal/increased ferritin

Haematology Year 3 (21 decks)

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