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Haematology > Anaemia > Flashcards

Anaemia Flashcards

1
Q

Define anaemia

A

A reduced total red cell mass

Usually considered as level below 95% range for the population

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2
Q

What markers are used to look for anaemia (red cell mass)

A

Haemoglobin concentration - surrogate maker
Will be decreased in anaemia
Haemocrit can also be used

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3
Q

How are histocytes involved in red cell production

A

They feed iron to the surrounding RBC precursors to help them develop

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4
Q

How is haemocrit measured

A

Proportion of the whole blood sample that is made up of RBC
Expressed as ratio or percentage
Analysed by machines now

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5
Q

When are haemocrit and haemoglobin not effective markers of anaemia

A

If not in a steady state
If someone is losing blood quickly then the blood they have left that you measure has not yet been diluted by the compensatory mechanisms (extracellular fluid) so the Hb will appear the same

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6
Q

Describe haemodilution

A

If someone gets too much fluid their blood can become diluted and their haemocrit will reduce (lower % of RBC)

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7
Q

What is reticulocytosis

A

Increased production of new RBC
Reticulocyte levels will rise
Occurs to compensate for anaemia
Suggests there is a normal marrow response

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8
Q

How long does the reticulocyte response take

A

A couple of days

Then levels will rise

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9
Q

How does the body respond to anaemia

A

It tries to produce more blood cells - reticulocytosis

Kidneys can release EPO to trigger this

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10
Q

What tests can be done on RBC

A

Hb concentration
The number of red cells
The size of RBC - MCV

Can then calculate:
Haemocrit
Mean cell haemoglobin

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11
Q

What are the pathophysiological classifications of anaemia

A

Decreased production:

  • hypo proliferative
  • maturation abnormalities

Increased loss or destruction:

  • bleeding
  • haemolysis
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12
Q

Describe hypo proliferative anaemia

A

There is reduced erythropoiesis - fewer red cells are produced

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13
Q

Describe anaemia caused by maturation defects

A

Erythropoiesis is present but is ineffective
Cytoplasmic defects: impaired haemoglobinisation
Nuclear defects: impaired cell division

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14
Q

What type of anaemia leads to a low MCV

A

Microcytic

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15
Q

What type of anaemia leads to a high MCV

A

Macrocytic

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16
Q

What underlying issue should you consider with microcytic anaemia

A

Issue with haemoglobinisation

haemoglobin synthesis

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17
Q

What underlying issue should you consider with macrocytic anaemia

A

Problems with maturation

It is an issue with DNA synthesis

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18
Q

Where is haemoglobin synthesised

A

In the cytoplasm

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19
Q

What is needed for Hb synthesis

A

Globins

Haem - porphyrin ring and iron (fe2+)

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20
Q

How do cells in microcytic anaemia appear

A

Small
Low Hb content
Hypochromic - lacking in colour

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21
Q

What can cause hypochromic microcytic anaemias

A

Lack of iron - most common
Problems with porphyrin synthesis
Globin deficiencies - thalassaemia

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22
Q

What can lead to iron deficiency anaemia

A

Low body iron - diet, lack of absorption (coeliac or Crohns), blood loss or physiological (growing child or pregnancy)
Chronic disease - lack of available iron but normal levels

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23
Q

What can cause problems with porphyrin synthesis

A

Very rare
Lead poisoning
Congenital sideroblastic anaemia

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24
Q

What causes a globin deficiency

A

Thalassaemia

Can have trait, intermedia or major

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25
Q

What is iron used for in the body

A

O2 transport

Electron transport - mitochondrial ATP production

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26
Q

Why is iron always chaperoned in the body

A

It can cause damage as it is potentially toxic

Generates free radicals

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27
Q

How is iron stored in the body

A

As ferritin

In the liver and macrophages

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28
Q

How is most of the iron in the body used

A

In Hb

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29
Q

Describe iron metabolism

A

Only able to absorb a small amount of iron - absorbed in proximal gut
Circulating iron is bound to transferrin.
It is transferred to the bone marrow macrophages that ‘feed it’ to red cell precursors
Iron is stored in ferritin mainly in the liver

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30
Q

How can you test iron levels

A

Functional iron- haemoglobin
Transported iron - serum iron, transferrin and transferrin saturation
Storage iron - serum ferritin
Ferritin is the best test

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31
Q

What is transferrin

A

Protein with two binding sites for iron atoms

Transports iron from donor tissues (macrophages or hepatocytes) to tissue that needs it

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32
Q

When is transferrin decreased

A

Iron deficiency

Anaemia of chronic disease

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33
Q

When is transferrin increased

A

Genetic haemochromatosis

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34
Q

What is ferritin

A

A large intracellular protein which stores a large amount of iron
It is also an acute phase reactive protein – therefore in acute illness the levels will increase (infection etc)

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35
Q

What does low ferritin suggest

A

Iron deficiency

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36
Q

How can you confirm a diagnosis of iron deficiency

A

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

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37
Q

What are the consequences of iron deficiency

A 
Exhaustion of iron stores
Iron deficient erythropoiesis - Falling red cell MCV
Microcytic Anaemia
Epithelial changes - skin
and koilonychia
38
Q

How do you treat iron deficiency anaemia

A

Iron replacement therapy

Must treat the underlying cause if there is one

39
Q

What is macrocytic anaemia

A

Anaemia in which the red cells have a larger than normal volume

40
Q

How can you recognise macrocytes on the blood film

A

Can compare the size of RBC to nucleus of mature lymphocyte – should be the same

41
Q

What are the causes of microcytosis

A

Megaloblastic
Non-megaloblastic
Spurious - false

42
Q

Describe the development of RBC

A

Between pronormoblast and late normoblast – cell is getting smaller, gaining Hb, nucleus shrinks
Then becomes a reticulocyte which enters the blood - has no nucleus but some RNA
Then matures into an erythrocyte

43
Q

What is a megaloblast

A

An abnormally large nucleated red cell precursor with an immature nucleus
An immature nucleus isn’t as dense

44
Q

What characterises a megaloblastic anaemia

A

A lack of red cells due to predominant defects in DNA synthesis and nuclear maturation
RNA and Hb synthesis are preserved
The precursor cells increase but the following divisions fail so the cells undergo apotosis before they mature
Cells aren’t getting bigger, they are failing to get smaller

45
Q

If macrocytes still have Hb then why do you get anaemia

A

Overall there are fewer red cells than normal so it is not sufficient

46
Q

What can cause megaloblastic anaemia

A

B12 deficiency
Folate deficiency
Certain drugs
Rare inherited abnormalities

47
Q

Why are B12 or folate important

A

They are essential co-factors in linked biochemical reactions regulating DNA synthesis, nuclear maturation, DNA modification and gene activity

48
Q

How is B12 absorbed

A

In the presence of acid the B12 dissociates from the meat
It binds to a protein haptecorin
In response to the presence of food, intrinsic factor is secreted from the parietal cells
In proximal gut, pancreatic factors raise the pH
This causes the haptecorin to unbind from B12 and allows intrinsic factor to bind instead
This complex allows the B12 to be absorbed by the ilial epithelium

49
Q

What can cause B12 deficiency

A 
Vegan diet 
Atrophic gastritis 
PPIs 
Gastrectomy or bypasses 
Chronic pancreatitis 
Coeliac disease
Crohns 
Gut resections 
Inherited deficiencies
50
Q

What is pernicious anaemia

A

Autoimmune condition with resulting destruction of gastric parietal cells
Cannot produce intrinsic factor so cannot absorb B12 properly
This leads to a deficiency

51
Q

What other conditions is pernicious anaemia associated with

A

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

52
Q

How is folate absorbed

A

Dietary folates converted to monoglutamate

Absorbed in jejunum (diffusion and actively)

53
Q

Where do we get B12 and folate from

A

B12 - animal products

Folate - liver, leafy veg, fortified cereals

54
Q

How long can B12 stores last

A

2-4 years

Deficiency can take a while to present

55
Q

How long can folate stores last

A

4 months

Issues present quicker than B12

56
Q

What can cause folate deficiency

A

Inadequate intake
Malabsorption - coeliac and crohns
Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy or malignancy
Drugs - anticonvulsants
Alcohol excess can lead to folate deficiency

57
Q

What are the clinical features of B12 and folate deficiency

A

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

B12 can also lead to neurological problems which are often irreversible

58
Q

How can you diagnose a B12 or folate deficiency

A

Macrocytic anaemia (red cell count is low)
Pancytopenia (all cells low) in some patients
MCV is high but RBC low
Blood film shows macrovalocytes (large oval shaped RBC) and hypersegmented neutrophils
Assay B12 and folate levels in serum
Autoantibody screen

59
Q

Which autoantibodies should you look for in b12 and folate deficiency

A

Anti- intrinsic factor
Anti-gastric parietal cell

Can have the antibodies but not the condition

60
Q

How do you treat megaloblastic anaemia

A

Treat the cause where possible
Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia
Folic acid tablets
Transfuse red cells if anaemia is life threatening

61
Q

What can cause non-megaloblastic microcytosis

A

Alcohol
Liver disease
Hypothyroidism
These may not be associated with anaemia

Also seen in marrow failure (myelodysplasia, myeloma, aplastic anaemia)
These patients will have anaemia

62
Q

What is spurious microcytosis

A

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

63
Q

What can cause spurious microcytosis

A

Reticulocytosis - these are larger than mature cells so raise MCV
Cold agglutinins

64
Q

What is cold agllutinins

A

Cold temperatures cause clumping of RBC due to abnormal proteins
This confuses the machine and counts the clump as one very large blood cell

65
Q

Why can patients with pernicious anaemia appear jaundiced

A

They have intramedullary haemolysis

There is ineffective production of RBC so they are broken down

66
Q

What are the common causes of macrocytosis

A 
B12 or folate deficiency 
Can be due to vegan diet 
Alcoholism (most common cause)
Autoimmune conditions - pernicious anaemia 
Malabsorption - coeliac
67
Q

Why do cells become large with a folic acid or B12 deficiency

A

Due to lack of folic acid, there is DNA damage and failure of red cell maturation. Therefore, the cells do not divide correctly and there are fewer but larger RBCs produced

68
Q

What happens to reticulocyte count in iron deficiency

A

Decreases

69
Q

If an adult presents with iron deficiency anaemia but no obvious cause, what tests should be done

A

Upper GI endoscopy followed by barium enema or colonoscopy

Pregnancy test

70
Q

What are the most common causes of iron deficiency in adults

A

Menstrual blood loss and gastrointestinal bleeding

71
Q

What are the side effects of iron supplements

A

Side effects include constipation, diarrhoea, bloating, nausea, black stools

72
Q

What is the therapy of choice for iron deficiency

A

Iron replacement
Usually given as oral ferrous fumarate tablets
Can give iron IV if they cannot cope with the side effects of oral preparation

73
Q

What can increase the absorption of iron

A

Orange juice - due to ascorbic acid

Alcohol

74
Q

What can decrease the absorption of iron

A

Drinking tea - tannins
Phytates - cereals, bran etc
Calcium - dairy

75
Q

How does iron therapy correct anaemia

A

Gives you enough of the raw materials to create the haemoglobin for new blood cells which increases the oxygen carrying capacity

76
Q

How quickly should Hb normalise after commencing iron therapy

A

Hb should normalise in around 6-8 weeks

Expect a rise of 7-10g per week

77
Q

How can you measure response to iron therapy

A

Can measure reticulocytes around 7-10 days after starting treatment as there is usually a peak in their production

78
Q

How can you treat pernicious anaemia

A 
B12 injections (hydroxocobalamin) 
Given roughly every 3 months but can be more frequent depending on patient
79
Q

Why does iron deficiency cause microcytosis

A

The cells do not contain enough Hb due to lack of iron
There is a particular level of Hb that needs to be reached for the cell to denucleate and stop dividing
If that isn’t reached (e.g. due to lack of iron) then the cells keep dividing and getting smaller

80
Q

How can the red cells compensate for poor oxygen delivery due to anaemia

A

Shift the oxygen dissociation curve to the right so that O2 is released at the tissues more easily
This can be done by 2,3 BPG getting in between the globin chains, more acidic pH (increased H+) and increased CO2

81
Q

What are the effects of a B12 deficiency

A

Macrocytic anaemia
Can cause diarrhoea as there is rapid turnover of the GI cells
Inflamed tongue - beefy
Can also affect the skin
Can lead to myelin degeneration and issues in the dorsal column of the spine (some of this damage is irreversible)

82
Q

Is Hb reduced in B12 deficiency

A

NO

The production of Hb is not affected as you still have the iron and globin

83
Q

If MCV is normal or high in macrocytic anaemia, why are they anaemic

A

The cells are larger but there isn’t enough of them

Still a net hypoxia

84
Q

Which sex has higher haemoglobin

A

Men

May be because they have less blood loss (no menstruation) and testosterone can increase RBC production

85
Q

How can you diagnose anaemia

A 
history/examination/clinical context- the main tool!
full blood count indices
reticulocyte count
blood film features
haematinics (ferritin/B12/folate)
bone marrow biopsy
Specialised tests (Hb A2, HLPC)
86
Q

What are the signs of haemolysis

A

Increased unconjugated serum bilirubin
May present with jaundice
Increased urinary urobilinogen

87
Q

What can cause normochromic, normocytic anaemia

A

Marrow failure - drug induced, aplastic anaemia (can be macrocytic)
Hypometabolic (can be macrocytic)
Marrow infiltration (metastatic malignancy, fibrosis)
Renal impairment
Chronic disease (infective, inflammatory, malignant)

88
Q

What is the cause of renal anaemia

A

Seen in chronic disease

Caused by a failure of erythropoietin production so RBC production isn’t triggered

89
Q

What is anaemia of chronic disease

A

A multifactorial pathophysiology with inflammation a central process
SO several ways disease can cause anaemia but inflammation is key
2nd most common cause of anaemia

90
Q

How does chronic disease lead to anaemia

A

Chronic inflammation from infections, autoimmune diseases or cancer activates the monocytes and T cells
These cells produce inflammatory cytokines
Hepatocytes produce more hepcidin which inhibits iron release
Less EPO release leads to a decrease in bone marrow response – hypoproliferative
Also get shortened red cell survival

91
Q

Why can anaemia of chronic disease sometimes be microcytic

A

If the predmoninat mechanism is hepcidin stimulation then there is lack of iron released which leads to reduced Hb stimulation and therefore small cells

Haematology (8 decks)

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