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Introduction to Haematology > Microcytic Anaemia > Flashcards

Microcytic Anaemia Flashcards

1
Q

what is anaemia?

A

the primary pathological condition of the red blood cell (RBC). occurs when there are too few RBCs or a problem with their function. Defined as a decrease in the competence of blood to carry O2 to tissues.

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2
Q

what are the risk factors for anaemia:

A

extremes of age
female gender: pregnancy, lactation, menstruation
babies born prematurely
long term or serious illness
poor diet

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3
Q

what is the WHO definition of anaemia

A

Hb below 130g/L in men over 15 years
Hb below 120g/L in non-pregnant women over 15 years
Hb below 110g/L in pregnant women

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4
Q

what is the major problem of anaemia

A

the inability to deliver sufficient oxygen

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5
Q

what are the symptoms of anaemia usually directly proportional to?

A

the extent of the disease

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6
Q

what are some of the signs of anaemia

A

pallor
tachycardia
glossitis (inflammation of tongue)
koilonychia- spooned nails
dark urine

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7
Q

symptoms of anaemia

A

fatigue
weakness
dizziness
palpitation
shortness of breath
tired all the time
rarely - headaches, tinnitus, tase distrurbance

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8
Q

severe signs and symptoms of anaemia

A

jaundice
splenomegaly
angina
hepatomegaly
cardiac failure
fever

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9
Q

what are the 2 mechanisms that cause anaemia?

A

reduction in RBC formation
reduced RBC survival

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10
Q

what can cause reduction in red blood cell formation?

A

deficiency (e.g. Fe (HB), b12, fol) - effect on cell division

cell destruction during formation - e.g. sickle cell

leukaemia - suppresses production of RBCs

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11
Q

what can cause reduced RBC survival

A

haemolytic anaemias - e.g. hereditary spherocytosis

chronic blood loss - e.g. after trauma

enlarged spleen - e.g. leukaemia

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12
Q

what MCV is classed as microcytic anaemia

A

MCV<80

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13
Q

What MCV is classed as normocytic anaemia?

A

MCV 80-96

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14
Q

What MCV is classed as macrocytic anaemia

A

MCV>95

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15
Q

Examples of a microcytic, hypochromic anaemia?

A

iron deficiency
thalassemia

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16
Q

what is MCH is classed as hypochromic?

A

<27pg

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17
Q

what MCH is classed as normochromic

A

MCH ≥ 27pg

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18
Q

what is an example of normocytic, normochromic anaemia?

A

many haemolytic anaemias

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19
Q

example of a macrocytic anaemia

A

megaloblastic - vb12 / folate def

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20
Q

what is the main function of RBCs?

A

carry o2 to the tissues and return co2 to the lungs

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21
Q

how many hb molecules does each rbc contain

A

640 million hb molecules

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22
Q

what is the structure of hb

A

quaternary structure of hb with 4 protein chains, each folded around a haem molecule. the haem molecule is composed of a ring-like organic compound called porphyrin, surrounding an iron atom.

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23
Q

how many polypeptides does hb contain?

A

4

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24
Q

what does each polypeptide in heam have?

A

a haem prosthetic group

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25
Q

what does each heam molecule have?

A

an iron atom at its centre and can bind 1 oxygen molecule

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26
Q

how many o2 molecules can each haem molecule bind?

A

1

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27
Q

how many heam groups are there per hb molecule?

A

4 haem groups that together bind 4 o2 molecules

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28
Q

how many o2 molecules can each hb molecule bind

A

4

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29
Q

what is the haem prosthetic group?

A

a protoporphyrin IX complexed with ferrous iron (Fe2+)

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30
Q

what is protoporphyrin?

A

organic compound made of 4 pyrole rings

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31
Q

what does protoporphyrin do?

A

binds o2 reversibly without oxidation of the haem

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32
Q

what is the total iron conc in the body?

A

40-50mg of iron/kg of body weight

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33
Q

where is most of the iron in the body found?

A

the erythroid bone marrow and in mature erythrocytes

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34
Q

where is iron for new RBC synthesis primarily supplied by?

A

reticuloendothelial macrophages

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35
Q

what is circulating iron bound to?

A

transferrin

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36
Q

what % of total body iron is found in the transit compartment - transferrin?

A

~0.1%

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37
Q

what does transferrin do?

A

delivers iron to developing erythroid precursors as well as to other tissues of the body.

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38
Q

where is stored iron primarily found?

A

the hepatocytes of the liver ~1g

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39
Q

how is iron lost?

A

from sloughing of mucosal and skin cells or during bleeding

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40
Q

is there a regulated mechanism for iron excretion in the body?

A

no

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41
Q

what are the 2 forms of dietary iron

A

non-haem iron (ferric, Fe3+)
Haem iron (ferrous, Fe2+)

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42
Q

where can non-haem iron be found?

A

veg
whole grains

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43
Q

is non-haem iron easily absorbed?

A

no

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44
Q

what are sources of haem iron?

A

red meats

45
Q

are haem irons readily absorbed?

A

yes

46
Q

which type of iron non-haem/haem is most easily absorbed?

A

haem iron (ferrous fe2+)

47
Q

what helps non-haem iron to be absorbed?

A

vit c helps absorption

48
Q

how much iron is needed daily for the haemoglobin synthesis

A

20-25mg of iron

49
Q

the iron demand for new RBCs accounts for

A

~80% of iron demand in humans

50
Q

why does iron need transport proteins?

A

it cannot freely diffuse across membranes

51
Q

how do mammals absorb dietary iron

A

through the duodenal epithelium of the SI

52
Q

what happens to non-haem ferric iron to allow it to be absorbed?

A

when fe3+ reaches the intestine it comes into contact with the cells lining the gut (enterocytes). fe3+ is reduced to the ferrous form fe2+ by the reductase duodenal cytochrome b (DCytB), located at the apical enterocyte membrane. the fe2+can then be transported across the membrane by the divalent metal transporter 1 DMT1 (an integral membrane protein).

53
Q

how can iron be stored

A

as ferritin

54
Q

how is dietary haem iron absorbed

A

transported by the haem carrier protein HCP1. once inside the cell, haem oxygenase releases iron from protoporphyrin. it enters the same pool as non-haem iron

55
Q

how is iron transported from the enterocyte membrane?

A

ferroportin (IREG1) transports the iron across the enterocyte basolateral membrane. this is facilitated by hephaestin. hephaestin is an oxidase that oxidises the iron to fe3+- this allows for binding to transferrin

56
Q

what is the primary tissue where excess iron is stored?

A

the liver

57
Q

what are the largest non-haem stores?

A

ferritin
haemosiderin

58
Q

what is the major function of ferritin?

A

to provide a store of iron

59
Q

what is the structure of ferritin

A

hollow sphere

60
Q

how many molcules of fe3+ can ferritin store?

A

4500 molecules of fe3+

61
Q

what is ferritin

A

ferritin is the bodys primary iron storage compound

62
Q

where is ferritin found

A

it is found in then bone marrow, liver and spleen

63
Q

where are haemosidering stores primarily found?

A

in macrophages

64
Q

what is haemosiderin an aggregate of?

A

iron, carbohydrate, lipid, protein

65
Q

how is iron released from haemosiderin?

A

it is released slowly and is not readily available for cellular metabolism

66
Q

when do bone marrow macrophages contain haemosiderin?

A

if iron stores are normal / increased

67
Q

what is hepcidin?

A

a key component of systemic iron metabolism
a negative regulator of iron transport
master iron-regulating hormone

68
Q

where is hepcidin expressed

A

in the liver

69
Q

how does hepcidin regulate iron homeostasis?

A

by binding to cell surface ferroportin - causing its degradation

70
Q

what is hepcidin synthesis affected by?

A

infection, hypoxia, inflammation, status and erythropoietic activity

71
Q

when can iron overload occur

A

absorption abnormally increases
individual receives multiple transfusions
individuals receives iron injections

72
Q

iron deficiency can occur if:

A

there is insufficient dietary intake of iron
absorption is impaired
increased loss of iron through bleeding

73
Q

what is the most common cause of anaemia?

A

iron deficiency anaemia

74
Q

% of men and women estimated to have IDA in UK

A

3% of men and 8% of women

75
Q

causes of iron deficiency

A

occult GI blood loss
malabsorption of iron
non-GI blood loss
iron store depletion

examples of each are on slideshow (pg 30)

76
Q

initial investigations for anaemia and typical results:

A

FBC - low Hb, low RBC count, low HCT, mean corpuscular volume <, mean corpuscular hb <, may also see low reticulocytes
Peripheral blood film

77
Q

what would you expect to see on a peripheral blood film with IDA?

A

microcytic, hypochromic red cells, small with large centre of pallor
anisocytosis
occasional target cells
poikilocytes

78
Q

FBC results and blood films are able to diagnose IDA?

A

no, they are not enough

79
Q

other diagnostic investigations for IDA?

A

serum ferritin
serum iron
total iron binding capacity
transferrin saturation

80
Q

what is ferritin?

A

ferritin is the bodys primary iron storage compound

81
Q

what is the correlation between total amount of stored iron and the serum ferritin concentration in normal individuals?

A

there is a good correlation between stored and serum ferritin

82
Q

is serum ferritin usually low or high in IDA?

A

low

83
Q

what is the most common way for serum ferritin to be measured?

A

ELISA

84
Q

How is serum iron measured?

A

colourimetric method
all protein-bound iron is released by the addition of a reagent that changes the the pH of the sample
centrifugation releases any remaining iron bound to proteins
colour change is proportional to ambient iron concentration

85
Q

what are the disadvantages of testing serum iron?

A

cannot be used alone to diagnose IDA
variation seen in normal individuals
serum iron also low in patients with anaemia of chronic disease
can be falsely elevated if haemolysis is present

86
Q

serum iron is typically…

A

low in IDA

87
Q

How saturated with iron can transferrin be?

A

nearly 1/3 saturated

88
Q

what does total iron-binding capacity (TIBC) indicate?

A

the maximum amoun of iron needed to saturate transferrin

89
Q

how is TIBC routinely determined?

A

by saturation of transferrin with an excess predetermined amount of iron. Removal of the unbound iron, and measurement of the iron that is dissociated from transferrin

90
Q

TIBC is typically …

A

high in IDA

91
Q

What can be used to calculate the % of transferrin saturation?

A

the ratio of the serum iron to the TIBC

92
Q

what is the equation for % transferrin saturation?

A

serum iron (ug/dL) x 100% / TIBC (ug/dL)

93
Q

what do transferrin saturations of less than 20% indicate?

A

iron deficiency

94
Q

what do transferrin saturations of more than 50% suggest

A

iron overload

95
Q

results summary for IDA - Biochem

A

serum ferritin - low
serum iron - low
total iron-binding capacity (TIBC) - increased
transferrin saturation - less than 20%

96
Q

how can haemosiderin stores be assessed?

A

using the Perl’s iron stain, this is the classic method for demonstrating iron in tissues

97
Q

how are iron stored in the bone marrow identified?

A

marrow smear is treated with potassium ferricyanide (Prussian blue) which stains the iron within reticuloendothelial cells blue

98
Q

a severe IDA patient will have

A

no visible Iron stores

99
Q

what is zinc protoporphyrin (ZPP)?

A

ZPP is a normal metabolite formed in trace amounts during haem biosynthesis

99
Q

what is the level of ZZP?

A

<40umol/mol haem

99
Q

what happens with zinc in cases of iron deficiency and lead poisoning?

A

zinc is incorporated into protoporphyrin IX instead of iron and zinc protoporphyrin (ZZP) is produced instead of haem

100
Q

levels of ZZP in patients with IDA

A

Are increased

101
Q

treatment of IDA

A

establish and treat the underlying cause
all pts with established IDA are treated with elemental iron supplementation:
- correct anaemia
- replenish body stores
200mg ferrous sulphate, twice daily
alternatives: ferrous fumerate/ferrous gluconate
3 months

102
Q

treatment options for those intolerant/non-responsive to oral supplements?

A

parenteral iron treatment by intravenous infusion or intramuscular injection

counselling: diet and lifestyle

transfusions

103
Q

what are the risks associated with IV iron infusion / IM injection?

A

high costs
side effects
some adverse reactions

104
Q

who are transfusions reserved for in IDA?

A

patients with symptomatic anaemia following iron therapy
those at risk of cardiovascular instability because of their degree of anaemia

105
Q

management of IDA:

A

if pt is responding to iron therapy, this will be reflected in FBC results
- retic count should peak at 1-2 weeks
- hb should show improvement at 3-4 weeks
- hb levels should return to normal after 2-4
months
- replacement of iron stored after 6 months

106
Q

what kind of blood film is common during treatment?

A

dimorphic blood film is common during treatment indicates response to therapy
normocytic and normochromic
microcytic and hypochromic

Introduction to Haematology (10 decks)

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