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Haematology SB > Anaemia > Flashcards

Anaemia Flashcards

1
Q

definition of anaemia

A

reduced total red cell mass

  • Hb concentration is a surrogate marker
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2
Q

where does red cell production take place

A

bone marrow

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3
Q

what is the bone marrows response to anaemia

A

Increase red cell 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 remnants of protein making machinery (RNA)‏

Stain purple/deeper red as a consequence

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5
Q

what are the 2 ways we classify anaemia

A

pathophysiology

morphological characteristics

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6
Q

what are the two subcategories of pathophysiology

A

decreased production (low reticulocyte count)

increased loss/destruction of RBC (high reticulocyte count)

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7
Q

what can cause decreased production of RBC

A

Hypoproliferative – reduced amount of erythropoiesis
e.g. chronic kidney disease, aplastic anemia

Maturation abnormality – erythropoiesis present but ineffective

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8
Q

what type of maturation abnormalities cause problems in the production of RBC

A

Cytoplasmic defects: impaired haemoglobinisation (result in small cells)

Nuclear defects: impaired cell division. (result in big cells)

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9
Q

what causes a loss/destruction of RBC

A

Bleeding

Haemolysis

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10
Q

how can an anaemia be classified by morphology

A

MCV low = microcytic

MCV high = macrocytic

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11
Q

where does haemoglobin synthesis occur

A

in the cytoplasm

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12
Q

what is needed to make Hb

A

Globins

Haem

  • Porphyrin ring
  • Iron (Fe 2+)‏
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13
Q

what does the inability to make Hb result in

A

small, pale red cells with a low hb content

==> microcytic and hypochromic

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14
Q

what causes a hypo chromic microcytic anaemia

A

haem deficiency
- lack of iron

globin deficiency
- thalassaemia

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15
Q

what two states can iron exist in in the body

A

Fe2+ = ferrous iron

Fe3+ = ferric iron

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16
Q

why is iron essential

A

Oxygen transport
- Hb, myoglobin

Electron transport
- Mitochondrial production of ATP

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17
Q

what does iron generate

A

free radicals

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18
Q

where is most of our body’s iron

A

in the haemoglobin

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19
Q

how is iron stored in the body

A

as ferritin in tissues, mainly the liver

and as ferritin in macrophages

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20
Q

what is circulating iron bound to

A

transferrin

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21
Q

what do the macrophages do with ferritin

A

feed it to red cell precursors

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22
Q

how can we assess iron - functional, transported and storage

A

functional
- Hb

transported

  • serum iron
  • transferrin
  • transferrin saturation

storage
- serum ferritin

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23
Q

what does transferrin do

A

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

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24
Q

what does measuring transferrin show

A

iron supply

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25
Q

what does changes in transferrin suggest when reduced/increased

A

reduced in iron deficiency

reduced in anaemia of chronic disease

increased in genetic haemachromatosis

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26
Q

what does serum ferritin show and what does low ferritin mean

A

storage of iron

low ferritin = iron deficiency

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27
Q

what blood results are seen in iron deficiency

A

low Hb i.e. anaemia

low serum ferritin i.e. reduced storage iron

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28
Q

what are causes of iron deficiency

A

not eating enough
blood loss (usually GI - tumours, ulcers, NSAIDs)
malabsorption (coeliac disease)
menorrhagia (>60ml)

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29
Q

where is iron absorbed in the bowel

A

duodenum

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30
Q

what are the consequences of a negative iron balance

A
  1. Exhaustion of iron stores (in the liver)
  2. Iron deficient erythropoiesis
    - Falling red cell MCV
  3. Microcytic Anaemia
  4. Epithelial changes
    - koilonychia (spoon nails)
    - angular stomatitis
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31
Q

what is important to remember about iron deficiency anaemia

A

it is a Sx and requires Ix for an underlying cause

32
Q

what is a megaloblast

A

An abnormally large nucleated red cell precursor with an immature nucleus.

33
Q

what are megaloblastic anaemias characterised by

A

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

34
Q

what are the consequences of megaloblastic changes

A

While the cytoplasm has developed and become mature (and big) enough to divide, the nucleus is still immature

causes a bigger than normal red cell precursor

35
Q

so in summary, what causes a larger cell size in megaloblastic anaemia

A

cell failure to become smaller

36
Q

what causes megaloblastic anaemia

A

B12 deficiency
Folate deficiency
Drugs
Rare inherited abnormalities

37
Q

why does a lack of B12 or 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

38
Q

what is B12 and folate responsible for

A

B12 = methionine cycle

folate = folate cycle

39
Q

what does the methionine cycle produce

A

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

40
Q

what is the folate cycle important for

A

nucleoside synthesis

41
Q

what is the pathway of B12 absorption

A

1 - comes as cobalamin in meat/eggs
2 - acid in the stomach makes Cbl separate and bind to Hepatocorrin (HC)
3 - intrinsic factor 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 recptors in the distal bowel (ileum)
8 - Cbl transported into the blood vessels by TC

42
Q

causes of vitamin B12 deficiency

A 
Dietary (e.g. vegan)
Pernicious anaemia 
Atrophic gastritis 
Chronic pancreatitis 
Coeliac disease
Crohn's disease
43
Q

what are dietary folates converted to and where are they absorbed

A

converted to monoglutamate

absorbed in jejunum

44
Q

how long do body stores of B12 and folate last

A 
B12 = 2-4 years 
Folate = 4 months
45
Q

what are causes of folate deficiency

A

Inadequate intake
malabsorption (Coeliac, Crohn’s)
Excess utilisation (haemolysis, pregnancy, malignancy)
Drugs (anticonvulsants)

46
Q

features of B12/folate deficiency

A

Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems

47
Q

what Sx is specific to B12 deficiency

A

Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations

48
Q

what spinal problem is seen in B12 deficiency

A

Subacute combined degeneration of the cord

49
Q

what is pernicious anaemia

A

Autoimmune condition with resulting destruction of gastric parietal cells (which produce intrinsic factor)

50
Q

what is pernicious anaemia associated with

A

atrophic gastritis and personal or family history of other autoimmune disorders (eg. Hypothyroidism, vitiligo, Addison’s disease)

51
Q

what blood results are seen in PA

A

Macrocytic anaemia (red cells low)

Pancytopenia (all cells low) in some patients

macrovalocytes (enlarged, oval-shaped erythrocytes)

hypersegmented neutrophils (normally 3-5 nuclear segments)

52
Q

what should be checked in PA

A

Serum folate and B12

Auto-antibodies (anti gastric-parietal cells and anti-intrinsic factor)

53
Q

what is the Tx of megaloblastic anaemia

A

treat the cause

for PA = vitamin B12 injections for life

folic acid 5mg per day

54
Q

what is injections of vitamin B12 called

A

hydroxycobalamin

55
Q

what are causes of a macrocytosis split into

A

genuine

  • megaloblastic
  • non-megaloblastic

spurious

56
Q

what are non-megaloblastic causes of macrocytosis

A
  • alcohol
  • liver disease
  • hypothyroidism
    (these 3 might not be associated with anaemia)
marrow failure
- myelodysplasia
- myeloma
- aplastic anaemia 
(all associated with anaemia)
57
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.

58
Q

what is Spurious macrocytosis

A

The size of the mature red cell is NORMAL, but the MCV is measured as being high

59
Q

what are causes of a spurious macrocytosis

A
  • increase in reticulocyte number as a marrow response to acute blood loss or RBC breakdown
  • cold-agglutinins [abnormal proteins that cause clumping of RBC]
60
Q

if the reticulocyte is raised what should you consider

A

haemorrhage

haemolysis

61
Q

why can liver disease cause a low platelet count

A

lead to hypersplenism&raquo_space; increased destruction

62
Q

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

A

serum B12 and/or folate level

63
Q

if serum B12 and/or folate is high what should be considered

A

myelodysplasia
myeloma
aplastic anaemia

64
Q

what can people with PA present with

A

mildly jaundiced

- due to intramedullary haemolysis

65
Q

why do people get jaundice in PA

A

Red cells die prematurely in the marrow

Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells

Haemoglobin converted to bilirubin

66
Q

what can complicated severe megaloblastic anaemia

A

pancytopenia

67
Q

what are the two headings for classification of anaemia

A

Decreased production (would see reticulocytopenia)

Increased loss or destruction of red cells (reticulocytosis)

68
Q

what does it mean when there is a reticulocytosis

A

red cell production is increased

69
Q

what are causes for a macrocytic anaemia

A 
myelodysplasia
myeloma
aplastic anaemia
reticulocytosis
cold agglutinins

B12 and folate deficiency

70
Q

when can you see a macrocytosis without anaemia

A

alcohol
liver disease
hypothyroidism

71
Q

what are causes of a normochromic normocytic anaemia

A

Acute blood loss/early iron deficiency
Anaemia of renal failure
Hypothyroidism
Marrow failure

72
Q

what do we get an anaemia in chronic kidney disease

A

Epo production decreases which normally stimulates erythropoiesis by bone marrow

73
Q

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

A

Iron deficiency = ferritin reduced

chronic disease = ferritin normal/increased

74
Q

how is the marrow in B12/folate deficiency

A

hypercellular

75
Q

what is the platelet number in iron deficiency anaemia

A

low

76
Q

how is thalassaemia Ix

A

electrophoresis

HPLC

Haematology SB (19 decks)

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