Introduction to anaemia & microcytic anaemia Flashcards

1
Q

What is anaemia?

A

Reduced total red cell mass
(Haemoglobin and haemtocrit are good markers)

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1
Q

What is the definition of anaemia in adult males and females for haemoglobin?

A

Males Hb <130g/L
Females Hb <120g/L

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2
Q

What is the definition of anaemia in terms of haematocrit levels for adult males and females?

A

Males Hct <0.38
Females Hct <0.37

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3
Q

Where does RBC production take place?

A

Bone marrow

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4
Q

How can we measure Hb concentration?

A

Using a spectrophotometric method because Hb is red

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5
Q

Describe how Hb concentration is measured by spectrophotometric method

A
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6
Q

How do we measure haematocrit?

A
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7
Q

In what rare situations is Hb/hct not good markers of anaemia?

A
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8
Q

What is the normal response to anaemia?

A

Increase RBC production -> reticulocytosis

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9
Q

What are reticulocytes?

A

Red cells that have just left the bone marrow (larger than average RBCs)

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10
Q

How do reticulocytes look like?

A

Stain purple /deeper red as a consequence because they have remnants of protein making machinery (RNA)

Blood film appears polychromatic

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11
Q

Upregulaton of reticulocyte production by the bone marrow in response to anaemia takes how long?

A

A few days

Note: There may be an initial burst of marrow reticulocytes (a store in bone marrow) in acute haemorrhage, but takes a few days for reticulocyte production

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12
Q

What can automated analysers tell us about red cells?

A

Physical principles - e.g. cell seize and light-scattering properties

Rapid and reproducible

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13
Q

An automated analyser can measure what red cell indices?

A

Haemoglobin concentration
Number of red cells (concentration)
Size of red cells (mean cell volume (MCV))

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14
Q

What can automated analysers calculate?

A

Haematocrit
Mean cell hemoglobin
Mean cell hemoglobin concentration

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15
Q

What are pathophysiological classification of anaemia?

A

Decreased production (low reticulocyte count)
- Hypoproliferative anaemia (reduced amount of erythropoiesis)
- Maturation defect (erythropoiesis is active but ineffective)
- Failure to produce Hb (a cytoplasmic defect)
- Failure of cell division (a nuclear defect)

Increased destruction (increased reticulocyte count)
- Blood loss
- Haemolysis

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16
Q

What is the more practical way of identifying the cause of anaemia?

A

Based on RBC size and haemoglobin content

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17
Q

Mean cell volume (MCV) is useful for?

A

Distinguishing cytoplasmic and nuclear defects

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18
Q

If MCV is low (microcytic), what problems do we consider?

A

Problems with haemoglobinisation

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19
Q

If MCV is high (macrocytic), what problems should we consider?

A

Consider problems with cell division i.e. maturation

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20
Q

Where does haemoglobin synthesis occur?

A

In cytoplasm of red cell precursors - defects results in small cells

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21
Q

Haemoglobin is synthesised in?

A

Cytoplasm

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22
Q

What do we need to make haemoglobin?

A

building blocks - iron, porphyrin ring, globins

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23
Q

If one of the building blocks for haemoglobin is missing, i.e. iron, globin or porphyrin rings, what does this result in?

A

Microcytic anaemia

24
Q

Describe what microcytic anaemia leads to

A

Building blocks (iron, globin, porphyrin ring) lacking -> microcytic anaemia -> nuclear machinery still intact so cells keep dividing -> one of the signals to stop dividing is Hb accumulation which is delayed -> more cell divisions occur and the cells are smaller (microcytic) -> and contain little Hb so are hypo chromic (lack colour)

25
Q

What is the order of erythropoiesis?

A
26
Q

Hypochromic microcytic anaemias mean what is happening?

A

Deficient haemoglobin synthesis - a cytoplasmic defect

27
Q

What are causes of hypochromic microcytic anaemias (TAILS)?

A
  1. Haem deficiency
    - Lack of iron for erythropoiesis
    a) Iron deficiency (low body iron)
    b) Some cases of anaemia of chronic disease (normal body iron but lack of available iron) - most anaemia of chronic disease is normocytic
    - Problems with porphyrin synthesis
    a) Lead poisoning
    b) Congenital sideroblsatic anaemias
  2. Globin Deficiency
    - Thalassemia (trait, intermedia, major)
28
Q

Iron can exist in what states?

A

Fe2+ or Fe3+ states

29
Q

Iron is essential for?

A

Oxygen transport - haemoglobin, myoglobin
Electron transport - mitochondrial production of ATP

30
Q

Iron is potentially toxic so needs to be handled safely by the body? How?

A

Free iron can generate free radicals (Fenton reaction)
Iron needs a chaperone molecule

31
Q

What is the iron metabolic pathway?

A
32
Q

Circulating iron is bound to?

A

Transferrin

33
Q

Where is transferrin bound iron transferred to?

A

Bone marrow macrophages that regulate iron uptake by transferrin receptor expression

Feed iron to red cell precursors

34
Q

Iron is stored in the liver in the form of?

A

Ferritin

35
Q

What types of iron exist?

A

Functional iron - haemoglobin
Transported iron - serum iron, transferrin, transferrin saturation
Storage iron - serum ferritin

36
Q

Transferrin has how many binding sites for iron?

A

2

37
Q

What does transferrin do?

A

Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)

38
Q

% saturation of transferrin with iron is a measure of? In what cases is it reduced?

A

Iron supply

Reduced in iron deficiency, reduced in anaemia of chronic disease, increased in genetic haemachromatosis

39
Q

What is ferritin?

A

Large intracellular protein
Spherical protein stores up to 4000 ferric ions

40
Q

How much ferritin is found in serum and what does it reflect?

A

Tiny amount
Reflects intracellular ferritin synthesis in response to iron status of the host

41
Q

Serum ferritin is easily measured but an indirect measure of?

A

Storage iron

42
Q

Low ferritin means?

A

Iron deficiency

43
Q

Draw ferritin, transferrin, and iron in haemoglobin into the iron metabolic pathway

A
44
Q

Iron deficiency can be confirmed by a combination of?

A

Anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)

45
Q

What are sequential consequences of negative iron balance?

A

Exhaustion of iron stores (ferritin falls)
Iron deficienct erythropoiesis then starts (MCV starts to fall)
Anaemia then develops
Epithelial changes (late effects in other sites of the chronic lack of iron) - skin, koilonychia, angular chelitis

46
Q

What are causes of iron deficiency?

A

Insufficient dietary iron in diet
Losing iron - GI but others like menstrual, urinary causes
Malabsorption (coeliac disease, achlorhydria)

47
Q

What are causes of chronic blood loss?

A

Menorrhagia
GI - tumours, ulcers, NSAIDs
Haematuria

48
Q

Menstrual blood loss and GI blood loss can outstrip the maximum what?

A

Maximum dietary iron absorption of iron and then result in microcytic anaemia

49
Q

Iron deficiency anaemia is a symptom, not a condition. True or false?

A

A symptom - iron replacement therapy may relieve anaemia without treating underlying cause.

50
Q

What can be initial measures to treat iron deficiency anaemia?

A

Review diet - haem and non haem iron
Improve gastric acidity
Review other medications like PPIs and anticoagulants

51
Q

What is the aim of treating iron deficiency anaemia?

A

Normalise Hb and restore iron stores
Ferritin will not rise until Hb returns to normal
MCV will rise as new well haemoglobinised red cells are made
Newly made red cells are reticulocytes
Rise in Hb is limited by the ability of marrow to up regulate production of RBCs
- Healthy marrow can increase Hb concentration by 7-10g/L per week if well supplied with iron
- rise less if ongoing blood loss

52
Q

What kind of iron preparations exist?

A

Oral & parenteral (IV) forms

53
Q

When should iron preparations be taken?

A

Best absorption is 30 minutes before a meal or 2 hours before taking other medications
Avoid milk, calcium, and antacids and high fibre foods or caffeine

54
Q

What is sodium feredetate (sytron)?

A

Liquid preparation with lower elemental iron concentration and used in paediatrics

55
Q

What side effects with oral iron preparations exist?

A

Constipation, nausea, vomiting, abdo pains, dark stools
Can result in poor compliance

56
Q

When should parenteral (IV) iron preparations be considered?

A

Only when oral is unsuccessful
- Poor tolerance of oral iron
- Poor compliance with oral iron
- Malabsorption issues (rare)
- Specific situations (e.g. renal anaemia)

Requires IV and is expensive

57
Q

How are parenteral (IV) iron preparations made?

A
58
Q

How do we monitor response to iron supplementation?

A