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Haematology Year 3 > Anaemia > Flashcards

Anaemia Flashcards

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
Q

function of transferrin

A

takes iron from donor tissues (macrophages, hepatocytes) to tissues expressing transferrin receptors

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26
Q

how many binding sites for iron does transferrin have

A

2

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27
Q

what does % saturation of transferrin with iron measure

A

iron supply

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28
Q

what does changes in transferrin suggest when reduced/increased

A

Reduced in iron deficiency and anaemia of chronic disease

Increased in genetic haemachromatosis

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29
Q

what does low ferritin indicate

A

iron deficiency

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30
Q

causes of iron deficiency

A

not eating enough
blood loss (usually GI- tumours, ulcers, NSAIDs)
Malabsorption (coeliac disease)
Menorrhagia (>60mls)

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31
Q

where is iron absorbed in the bowel

A

duodenum

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32
Q

consequences of negative iron imbalance

A
  1. exhaustion of iron stores
  2. iron deficient erythropoiesis - falling red cell MCV
  3. Microcytic anaemia
  4. Epithelial changes e.g. koilonychia
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33
Q

what is important to remember about iron deficiency anaemia

A

it is a symptom not a diagnosis- needs investigating

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34
Q

what is macrocytic anaemia

A

anaemia where red cells have a larger than normal mean cell volume

35
Q

what is a megaloblast

A

an abnormally large nucleated red cell precursor with an immature nucleus

36
Q

what are megaloblastic anaemias characterised by

A

defects in DNA synthesis and nuclear maturation with preservation of RNA and Hb synthesis

37
Q

consequences of megaloblastic changes

A

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
Q

in summary, what causes the larger cell size in megaloblastic anaemia

A

cell failure to become smaller

39
Q

what causes megaloblastic anaemia

A

B12 deficiency
Folate deficiency
Drugs
Rare inherited abnormalities

40
Q

why does a lack of B12/folate cause megaloblastic anaemia

A

B12 and folate are essential co-factors for nuclear maturation
They enable chemical reactions that provide enough nucleosides for DNA synthesis

41
Q

what cycle is B12 responsible for

A

methionine cycle

42
Q

what cycle is folate responsible for

A

folate cycle

43
Q

what does the methionine cycle produce

A

s-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates

44
Q

what is the folate cycle important for

A

nucleoside synthesis (e.g. uridine to thymidine conversion)

45
Q

what is the pathway of B12 absorption

A
  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
Q

causes of B12 deficiency

A 
dietary (e.g. vegan) 
pernicious anaemia 
atrophic gastritis 
chronic pancreatitis 
coeliac disease
crohns disease
47
Q

what are dietary folates converted to and where are they absorbed

A

converted to mono glutamate

absorbed in the jejunum

48
Q

how long do body stores of B12 and folate last

A

B12- 2-4 years

Folate- 4 months

49
Q

causes of folate deficiency

A

inadequate intake
malabsorption (coeliac, crohns)
Excess utilisation (haemolytic, pregnancy, malignancy)
drugs (anti-convulsants)

50
Q

features of B12/Folate deficiency

A

symptoms/signs of anaemia (fatigue, dyspnoea, headache, palpitations)
weight loss, diarrhoea, infertility, jaundice, developmental problems

51
Q

what symptom is specific to B12 deficiency

A

neurological problems:

  • posterior/dorsal column abnormalities
  • neuropathy
  • dementia
  • Psychiatric manifestations
52
Q

what spinal problem is seen in B12 deficiency

A

subacute combined degeneration of the spinal cord

53
Q

what is pernicious anaemia

A

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
Q

what conditions are associated with pernicious anaemia

A

atrophic gastritis, hypothyroidism, vitiligo, Addison’s disease

55
Q

blood results seen in pernicious anaemia

A

Macrocytic anaemia (red cells large + low)
Pancytopenia (all cells low)
Macrovalocytes (enlarged, oval shaped erythrocytes)
Hypersegmented neutrophils

56
Q

What should be checked in pernicious anaemia

A

Serum folate and B12

Autoantibodies:
anti gastric-parietal cells: autoimmune gastritis
Anti-intrinsic factor

57
Q

treatment of megaloblastic anaemia

A

Treat the cause
For pernicious anaemia- vit B12 injections for life
Folic acid 5mg oral daily

58
Q

what is injections of vitamin b12 called

A

hydroxycobalamin

59
Q

what are causes of macrocytosis split into

A

Genuine: megaloblastic/non-megaloblastic

Spurious

60
Q

Non-megaloblastic causes of macrocytosis

A

Alcohol
Liver disease
Hypothyroidism
(these may not be associated with anaemia)

Marrow failure: Myelodysplasia, Myelomo, Aplastic anaemia

61
Q

what is meant by megaloblastic anaemia

A

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
Q

what is spurious macrocytosis

A

The size of the mature read cell is normal but the MCV is high

63
Q

causes of spurious macrocytosis

A

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
Q

If the reticulocyte count is raised, what should you consider

A

haemorrhage

haemolysis

65
Q

if the reticulocyte count is low in a macrocytosis, what investigation should be done next

A

serum B12 + Folate

66
Q

If serum B12 and/or folate is high, what causes should be considered

A

Myelodysplasia
Myeloma
Aplastic anaemia

67
Q

If serum B12 and/or folate is low, what is the likely diagnosis

A

megaloblastic anaemia

68
Q

why can liver disease cause a low platelet count

A

leads to hypersplenism – increased destruction

69
Q

what can people with pernicious anaemia present with

A

mild jaundice due to intramedullary haemolysis

70
Q

why do people get jaundice in pernicious anaemia

A

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
Q

what can complicate severe megaloblastic anaemia

A

pancytopenia

72
Q

What are the two headings for classifications of anaemia

A

Decreased production (would see reticulocytopenia) Increased loss or destruction of RBCs (would see reticulocytosis)

73
Q

what is seen in increased haemolysis of RBCs

A

Increased unconjugated serum bilirubin
Increased urinary urobilinogen
Result is anaemia + jaundice, sometimes with splenomegaly

74
Q

commonest cause of hypo chromatic microcytic anaemia

A

iron deficiency

75
Q

what is the platelet count in iron deficiency anaemia

A

low

76
Q

other less common causes of microcytic anaemia

A

Thalassaemia

77
Q

investigation of thalassaemia

A

electrophoresis

HPLC

78
Q

nutritional causes of macrocytic anaemia

A 
B12 deficiency 
Folate deficiency 
(This causes megaloblastic anaemia)
79
Q

causes of macrocytic anaemia

A 
myelodysplasia 
myeloma
aplastic anaemia 
reticulocytosis 
cold agglutinins
80
Q

when can you see a macrocytosis without anaemia

A

alcohol
liver disease
hypothyroid

81
Q

what are the causes of normochromatic normocytic anaemia

A 
Acute blood loss/early iron deficiency
Hypoproliferative:
-Chronic diseases
- Anaemia of renal failure
-Hypothyroidism 
- Marrow failure
82
Q

How is EPO production affected in renal failure

A

It decreases

83
Q

what is the big differentiating factor for anaemia caused by iron deficiency and anaemia of chronic disease

A

Iron deficiency = reduced ferritin

Chronic disease = normal/increased ferritin

Haematology Year 3 (21 decks)

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