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anaemias Flashcards

1
Q

what is haemoglobin?

A

A haemoprotein composed of globin and haem that gives red blood cells their characteristic colour.

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2
Q

what is the function of haemoglobin?

A

It’s function is primarily to transport oxygen from the lungs to the body tissues

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3
Q

what is the structure of haemoglobin?

A

a normal adult human haemoglobin is a tetramer made up of 4 polypeptide chains.

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4
Q

what are the 4 polypeptide chains in haemoglobin?

A

2 alpha chains and 2 beta chains

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5
Q

what is haem?

A

an iron containing molecule.

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6
Q

where is haem found in haemoglobin?

A

haem is located in a hydrophobic cavity in each of the globin chains.

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7
Q

what in haem has the ability to bind oxygen?

A

Iron

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8
Q

how does haem unload its oxygen?

A

Unloads its oxygen changing from ferrous state (Fe++ ) to its ferric state (Fe+++ )and back again

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9
Q

how many haemoglobin molecules are in a red blood cell?

A

Each red blood cell contains 640 million haemoglobin molecules

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10
Q

What must red cells be able to do?

A

Be able to pass repeatedly through the microcirculation

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11
Q

how many miles do Red blood cells travel in their 120 day lifespan?

A

300 miles

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12
Q

what must red blood cells do?

A

Have to come into close contact with the tissues
Maintain haemoglobin in its reduced ferrous state (Fe++)
Maintain osmotic equilibrium

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13
Q

how is the red cell adapted to be able to carry out its function?

A

biconcave disc
generates energy as ATP
generates reducing power as NADPH

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14
Q

how do RBC generate ATP?

A

Embden-Meyerhof pathway

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15
Q

How do RBC generate NADPH?

A

hexose-monophosphate pathway

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16
Q

what does iron play a role in?

A

Plays a vital role in normal function/metabolism of almost every cell in the body

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17
Q

what is iron essential for?

A

iron is essential for haemoglobin production

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18
Q

what does transferrin do?

A

transports iron to developing red cells which have transferrin receptors

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19
Q

what are transferrin receptors?

A

they are present on blood cell to form transferrin/iron complex

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20
Q

how much of the body’s iron is stored as ferritin?

A

66%

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21
Q

where is ferritin stored?

A

mainly in liver and some stored in bone marrow, spleen and muscles

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22
Q

how much of the body iron is stored as haemosiderin?

A

33%

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23
Q

where is haemosiderin found?

A

found in cells not in the circulating blood

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24
Q

how much iron is found in the average western diet?

A

10-15mg iron daily

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25
Q

how much iron is absorbed?

A

5-10%

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26
Q

where is iron absorbed?

A

through the small intestine

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27
Q

what happens to iron absorption?

A

it is adjusted to body needs

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28
Q

which iron is more easily absorbed - iron from animal products or iron from vegetables?

A

iron from animal products is more readily absorbed

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29
Q

why is dietary iron needed?

A

Dietary iron makes up from daily loss of about 1mg in hair, skin, urine, faeces and menstrual blood loss

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30
Q

what are some sources of dietary iron?

A

red meat, fish, egg yolk, wholemeal bread, vegetables, fortified foods…

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31
Q

what are some characteristics of normal red cells?

A

Anucleate
6.7-7.7µm
Biconcave disc
Central area of pallor- about 1/3rd of red cell diameter

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32
Q

what is anaemia?

A

A below normal level of haemoglobin

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33
Q

what is the normal haemoglobin range for adult males?

A

130-170g/l

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34
Q

what is the normal haemoglobin range for adult females?

A

120-155g/l

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35
Q

how is anaemia classified?

A

By the size of the red cells (Mean Cell Volume)

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36
Q

what are the classifications of anaemia (3)?

A

Microcytic – small red cells (MCV<78fl)
Macrocytic - large red cells (MCV>100fl)
Normocytic - normal size red cells (MCV 78-100fl)

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37
Q

what are the microcytic anaemias?

A

Iron deficiency
Thalassaemia
Other haemoglobin defects
Anaemia of chronic disease

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38
Q

what are the 2 subtypes of macrocytic anaemias?

A

megaloblastic anaemia

non megaloblastic anaemia

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39
Q

what are some megaloblastic anaemias?

A

Folic acid deficiency
B12 deficiency
Auto immune disease-pernicious anaemia

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40
Q

what are some causes of non megaloblastic anaemia?

A 
Myelodysplastic syndromes(MDS)
Liver disease
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41
Q

what are examples of normocytic anaemia?

A

Haemolytic anaemia
Acute blood loss
Anaemia of chronic disease

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42
Q

how much of the worlds population suffer from iron deficiency anaemia?

A

25%

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43
Q

what are characteristics of iron deficiency anaemia?

A

MCV (Mean cell volume)-reduced - small red cells

MCH (mean cell haemoglobin)-reduced - pale/empty red cells

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44
Q

when does iron deficiency anaemia occur?

A

when supply of iron doesn’t meet demand.

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45
Q

what are the 3 phases of iron deficiency?

A

iron replete - ferritin levels are going down
iron deplete - ferritin stores are empty
iron deficient - no iron/ferritin left

46
Q

what are some causes of iron deficiency anaemia?

A

chronic blood loss, increased demands, malabsorption, poor diet

47
Q

what is the development rate of iron deficiency anaemia?

A

develops slowly

48
Q

what are some clinical features of iron deficiency anaemia?

A 
Pallor
Sore mouth
Brittle nails
Dysphagia
Glossitis
Abnormal appetite
Hair thinning
Lassitude
Fatigue
Tachycardia
49
Q

what can be seen in lab findings of iron deficiency anaemia?

A 
hypochromic microcytic anaemia
raised platelet count 
reduced serum ferritin level 
low serum iron level 
raised serum transferrin receptor
50
Q

what does a bone marrow test show in terms of iron deficiency anaemia?

A

absence of stored iron

erythroblasts with ragged irregular cytoplasm

51
Q

what is the treatment for iron deficiency anaemia?

A

oral iron 3 times daily

52
Q

how long after oral iron supplements does reticulocyte response begin?

A

within 7 days

53
Q

how long should oral iron be given as treatment?

A

4-6 months

54
Q

when is IV iron given to patients?

A

if they suffer from malabsorption

55
Q

what are some side effects of oral/IV iron?

A

they can cause abdominal pain, diarrhoea or constipation

56
Q

what is vitamin B12 also known as?

A

Cobalamin

57
Q

what makes up vitamin B12?

A

cobalt atom situated in centre of a orrin nucleus

58
Q

what is the function of vitamin B12?

A

a coenzyme for 2 biochemical reactions

59
Q

what are the biochemical reactions that vitamin B12 play a role in?

A

Methylation of homocysteine to methionine

Converts methylmalomyl coenzyme A to succinyl coenzyme A

60
Q

what would happen without the vitamin B12 reactions?

A

Without these reactions the body has a reduced supply of the precursors required for:

  • DNA synthesis.
  • Myelin production
61
Q

what is the effect of abnormal DNA synthesis on red cell production?

A

Erythroblasts in bone marrow show abnormal maturation
Maturation of nucleus being delayed relative to cytoplasm
No reticulocytes produced

62
Q

what is the adult daily requirement of B12?

A

1 µg

63
Q

how much B12 in a normal mixed diet?

A

10-15µg

64
Q

where is B12 stored?

A

Stored largely in the liver

65
Q

how much B12 is stored in the body?

A

enough for 2-4 years

66
Q

where is B12 absorbed?

A

in the ileum

67
Q

how is B12 absorbed?

A

attached to intrinsic factor

68
Q

where is intrinsic factor secreted?

A

in the stomach

69
Q

how is B12 lost from the body?

A

Lost through urine, faeces and excretion of bile.

70
Q

how is B12 transported in the plasma?

A

bound to transcobalamin

71
Q

what are some dietary sources of B12?

A

Liver, Kidney, Heart, Clams, Oysters, egg, cheese, yoghurt

72
Q

what are causes of B12 deficiency?

A 
Inadequate diet-vegans
Malabsorption
Intestinal causes
Excess utilisation
Liver disease
Drug treatments
73
Q

what are the Clinical features of B12 deficiency-Megaloblastic anaemia?

A 
Mild jaundice
Glossitis
Tingling in feet or hands
Difficulty in gait
Visual disorders
Psychiatric disorders
May be asymptomatic
74
Q

what is the onset duration of B12 deficiency-Megaloblastic anaemia?

A

gradual onset of anaemia

75
Q

what are found in the laboratory findings of B12 deficiency-Megaloblastic anaemia?

A 
Absence of reticulocytes
Hypersegmented neutrophils
Moderately reduced white blood cell count
Moderately reduced platelet count
Raised bilirubin
Raised serum methylmalonic acid
Raised serum homocysteine levels
76
Q

How is B12 deficiency-Megaloblastic anaemia treated?

A

1 mg hydroxycobalamin intramuscularly

77
Q

how often is hydroxycobalamin given to patients?

A

Every 3 days until six injection have been given

Then every 3 months for life unless cause of deficiency has been treated.

78
Q

what is different in treatment of severe B12 deficiency-megaloblastic anaemia?

A

In severe cases potassium supplements are given at the same time as the B12

79
Q

what is vitamin B12 neuropathy?

A

subacute degeneration of the cord

progressive damage to peripheral sensory nerves - spinal cord, brain and peripheral nerves

80
Q

what does vitamin B12 neuropathy affect?

A

Affects lower limbs
optic atrophy
psychiatric symptoms

81
Q

what is the cause of vitamin B12 neuropathy?

A

Accumilation of homocysteine and reduction of methionine in the nervous tissues –>
Defective methylation of myelin –>
Causes abnormal fatty acids to form around cells and nerves.

82
Q

what is pernicious anaemia?

A

autoimmune disease - B12 deficiency

83
Q

how is pernicious anaemia an autoimmune disease?

A

auto antibodies attack the gastric parietal cells

84
Q

what do the gastric parietal cells do?

A

secrete intrinsic factor

85
Q

what happens after destruction of parietal cells?

A

no intrinsic factor is secreted meaning that B12 cannot be absorbed

86
Q

what is folic acid (B9) also known as?

A

pteroglutamic acid

87
Q

can humans synthesise folic acid?

A

no humans cannot synthesise folic acid

88
Q

where is folic acid absorbed?

A

in the jejunum

89
Q

when can folic acid deficiency be seen?

A

often in diseases of small intestine e.g. coeliac, tropical sprue, Crohn’s disease

90
Q

how much folic acid does the body store?

A

3 months worth

91
Q

what biochemical reactions need folic acid?

A

homocysteine-methinione
Serine-glycine
Synthesis of DNA precursers

92
Q

what is the role of folic acid?

A

Necessary for production of new cells
Deficiency hinders DNA synthesis/cell division
Substrate in the important reactions that involves B12

93
Q

what are some sources of Folic acid?

A 
leafy vegetables 
Turnip
Lettuce
Beans
Peas
Breakfast cereals
Fruit
liver
94
Q

what are the clinical feature of folate deficiency?

A

same as B12 deficiency but often less severe

95
Q

why does folate deficiency develop rapidly?

A

because there is low body stores of folate.

96
Q

does folate deficiency cause neuropathy like B12 deficiency?

A

no

97
Q

what is the cause of spina bifida?

A

B12 or folic acid deficiency in early pregnancy

Lower maternal serum B12 or folate, greater the incidence

98
Q

why does B12 or folic acid deficiency cause spina bifida?

A

Build up of homocysteine in foetus –>

Impairs methylation of various proteins and lipids

99
Q

how can spina bifida be prevented?

A

Dietary supplements in early pregnancy reduce incidence by 75%

100
Q

what are some other tissue abnormalities associated with B12/Folic acid deficiency?

A
  • sterility (either sex)
  • Morphological abnormalities of cervix, bladder and other epithelia
  • cleft lip and palate in the foetus/newborn
  • widespread reversible melanin pigmentation
  • associated with cardiovascular and malignant disease
101
Q

what are normocytic anaemias?

A

caused when there are normal size red cells but not enough of them

102
Q

what are some causes of normocytic anaemias?

A
  • acute blood loss
  • premature destruction of red cells –> haemolytic anaemia
  • chronic disease e.g. arthritis, cancer, kidney disease
103
Q

what is haemolytic anaemia?

A

The anemias that result from the increased rate of red cell destruction

104
Q

how is haemolytic anaemia classified?

A

classified as hereditary or acquired

105
Q

what are some of the causes of hereditary haemolytic anaemias?

A

red cell membrane defects
defective red cell metabolism
disorders of haemoglobin synthesis

106
Q

what are the extra corpuscular causes of acquired haemolytic anaemias?

A
  • Haemolytic disease of the newborn
  • Autoimmune haemolytic anaemia
  • Disseminated Intravascular Coagulation (DIC)
  • Heart valve replacements
107
Q

what are the environmental causes of acquired haemolytic anaemias?

A
  • Drug induced
  • March haemoglobinuria
  • Infections such as malaria and E.coli 0157
108
Q

what are the clinical features of haemolytic anaemias?

A

pallor and mild fluctuating jaundice

109
Q

what are the lab findings of increased RBC breakdown?

A

raised bilirubin, raised LDH and reduced haptoglobin

110
Q

what are the lab findings of increased RBC production?

A

reticulocytosis

bone marrow erythroid hyperplasia

111
Q

what are the lab findings of damaged red cells?

A

morphology shows fragments, microspherocytes, elliptocytes

Haematology (7 decks)

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