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Anaemia Flashcards

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1
Q

What is anaemia?

A

Reduced total red cell mass

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2
Q

What are haemoglobin concentration and haematocrit in terms of anaemia markers?

A

Surrogate markers

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3
Q

What are the normal levels of Hb and Hct for males?

A

<130g/l, 0.38-0.52

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4
Q

What are the normal levels of Hb and Hct for females?

A

<120g/l, 0.37-0.47

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5
Q

What type of method is used to measure Hb concentration?

A

Spectrophotomeric

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6
Q

How is Hg measured?

A

Lyse the RBCs to create Hb solution
Stabilise the Hb molecules
Measure optical density at 540nm
OD proportional to concentration (Beer’s Law)
Hb concentration calculated against known reference standard cyan-metHb solution

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7
Q

What is the response to anaemia?

A

Reticulocytosis

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8
Q

What are Reticulocytes?

A 
RBCs that have just left the bone marrow
Large than average red cells
Still have RNA remnants
Stain purple/deep red as a result
Blood film appears polychromatic
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9
Q

How long does up regulation of reticulocyte production by the bone marrow in response to anaemia take?

A

A few days

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10
Q

What red cell indices are measured?

A

Hb concentration
No. of red cells
Size of red cells (MCV)

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11
Q

What red cell indices are calculated?

A

Hct
Mean cell Hg
Mean cell Hg concentration

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12
Q

How is anaemia classified?

A

Pathophysiology or Morphology (practical and useful)

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13
Q

What may cause anaemia due to decreased production of red cells (low reticulocyte count)?

A

Hypoproliferative- reduced amount of erythropoiesis
Maturation abnormality- erythropoiesis present but ineffective: cytoplasmic defects (impaired haemoglobinisation), nuclear defects (impaired cell division

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14
Q

What may cause anaemia due to an increased loss or destruction of red cells (high reticulocyte count)?

A

Bleeding

Haemolysis

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15
Q

What is a useful tool in distinguishing cytoplasmic and nuclear defects?

A

MCV
If low consider problems with haemoglobinisation
If high consider problems with maturation

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16
Q

Where does Hg synthesis occur?

A

Cytoplasm

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17
Q

What do you need to make Hb?

A

Globins

Haem- porphyrin ring, Iron (Fe2+)

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18
Q

What does shortage of the products required to make Hb result in?

A

Small red cells with low Hb content

Cells are microcytic and hypochromic

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19
Q

What will be the cause of hypochromic microcytic anaemias?

A

Deficient Hb synthesis due to cytoplasmic defect

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20
Q

What can cause a haem deficiency?

A

Lack of iron for erythropoiesis- iron deficiency (low body iron), some causes of anaemia of chronic disease (normal body iron but lack of available iron, most normocytic)
Problems with porphyrin synthesis (rare)- lead poisoning, pyridoxine responsive anaemias
Congenital siderobastic anaemia (rare)

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21
Q

What can cause a globin deficiency?

A

Thalassaemia (trait, intermedia, major)

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22
Q

What is iron essential for?

A

Oxygen transport- Hb, myoglobin

Electron transport- mitochondrial production of ATP

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23
Q

In what forms can Iron exist?

A

Fe 2+ or 3+

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24
Q

What does iron generate making it potentially toxic?

A

Free radicals

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25
Describe the structure of an adult haemoglobin
4 globin sub units, each containing a single haem molecule Haem groups contains a single Fe2+ ion Each haem group can bind one O2 molecule
26
When fully saturated, how much O2 will 1g Hb bind?
1.34ml
27
How much iron do we absorb and lose each day?
1mg
28
How much iron is stores in parenchymal tissues?
500mg (liver, other)- as ferritin
29
How much iron is in plasma?
4mg
30
How much iron is in erythyroid marrow?
150mg
31
How much iron is in red cell Hb?
2500mg
32
How much iron is in macrophage (reticuloendothelial) stores?
500mg- as ferritin
33
What is circulating iron bound to?
Transferrin
34
What tests are available to test functional iron?
Hg
35
What tests are available to test transported iron?
Serum ion Transferrin Transferrin saturation
36
What tests are available to test storage iron?
Serum ferritin
37
What is transferrin?
Protein with two binding sites for iron atoms
38
What does transferrin do?
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (esp. erythroid marrow)
39
What does % saturation of transferrin with iron measure?
Iron supply
40
When would transferrin saturation be reduced?
Iron deficiency | Anaemia of chronic disease
41
When would transferrin saturation be increased?
Genetic haemochromatosis
42
What is ferritin?
Large spherical intracellular protein that stores up to 4000 ferric ions
43
How much ferritin is present in the serum?
Tiny amount- reflects intracellular ferritin synthesis in response to iron status of the host
44
What is serum ferritin a measure of?
Indirect measure of storage iron
45
What does low ferritin mean?
Iron deficiency
46
What can iron deficiency be confirmed by?
A combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)
47
What are the causes of iron deficiency?
1. Not eating enough: Relative deficiency- esp women of child bearing age and children Absolute- vegetarian diets Unlikely in men 2. Losing too much- blood loss (usually GI) 3. Not absorbing enough- malabsorption (coeliac, achlorhydria)
48
What are some causes of chronic blood loss?
Menorrhagia GI- tumours, ulcers, NSAIDs Haematuria
49
How much iron is lost in menstruation?
30-40ml blood/month, so 15-20mg iron/month
50
What are the sequential consequences of -ve iron balance?
Exhaustion of iron stores Iron deficient erythropoiesis- falling red cell MCV Microcytic anaemia Epithelial changes- skin, koilonychia
51
How does occult blood loss outstrip the maximum dietary iron absorption of iron?
Small volume GI blood loss can occur without any symptoms or signs Results in anaemia Iron absorption can be increased by supplements
52
Is iron deficiency anaemia a diagnosis or symptom?
Symptom
53
What are the true causes of macrocytosis?
Megaloblastic | Non-megaloblastic
54
What is an erythroblast?
A normal red cell precursor with a nucleus
55
What is the difference between precursors of red cells and reticulocytes?
Have a nucleus | Marrow-based
56
Name each cell in erythropoiesis from pronormoblast to erythrocyte
``` Pronormoblast Basophilic/early normoblast Polychromatophilic/ intermediate normoblast Orthochromatic/late normblast Reticulocyte Erythrocyte ```
57
Between what stages does enucleation occur in erythrocyte?
Late normoblast and reticulocyte
58
What is a megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus
59
What are megaloblastic anaemias characterised by?
Predominant defects in DNA synthesis and nuclear maturation with relative preservation of RNA and Hb synthesis
60
What do defects in DNA synthesis and nuclear maturation cause for the cell?
Cytoplasm has developed and becomes mature enough to divide, but nucleus is still immature Leads to bigger than normal red cell precursor Cell can sense it has enough Hb and doesn't need to divide anymore
61
What are the causes of megaloblastic anaemia?
B12 deficiency Folate deficiency Others- drugs, rare inherited abnormalities
62
Why does lack of B12 or folate cause megaloblastic anaemia?
They're essential co-factors for nuclear maturation, enable chemical reactions that provide enough nucleosides for DNA synthesis
63
What does the B12 methionine cycle produce?
S-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates
64
What is the folate cycle important for?
Nucleoside synthesis
65
What are the causes of B12 deficiency?
``` Veganism Atrophic gastritis PPIs/H2 receptor antagonist Gastrectomy/bypass Chronic pancreatitis Bacterial overgrowth Coeliac Duodenum resection Crohn's Inherited cubulin deficiency ```
66
What are dietary folates converted to?
Monoglutamate
67
Where is folate absorbed?
Jejunum (diffusion and actively) | Duodenum
68
What is the source of B12?
Animals
69
What is the source of folate?
Leafy veg, yeast | Destroyed by cooking
70
How long is B12 stored for?
2-4y
71
How long is folate stored for?
4 months
72
Where is B12 absorbed?
Ileum
73
What is the daily requirement for B12 and folate?
1-3μgday and 100μgs/day respectively
74
What are the causes of folate deficiency?
Inadequate intake (more likely than B12) Malabsorption- Coeliac, Crohn's Excess utilisation- haemolysis, exfoliating dermatitis, pregnancy, malignancy Drugs- anticonvulsants
75
What are the clinical features of B12/folate deficiency?
``` Symptoms/signs of anaemia Weight loss, diarrhoea, infertility Sore tongue, jaundice Developmental problems Neuro problems (B12 deficiency)- posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations ```
76
What is pernicious anaemia?
AI condition with resulting destruction of gastric parietal cells
77
What is pernicious anaemia associated with?
Atrophic gastritis and personal or FHx of other AI disorders (e.g. hypot, vitiligo, Addison's)
78
What is seen on lab diagnosis in pernicious anaemia?
Macrocytic anaemia (red cells low) Pancytopenia in some patients Blood film shows macrovalocytes and hypersegmented neutrophils (normally 3-5 nuclear segments) Assess B12 and folate levels Check for auto-antibodies (anti GPC and anti IF)
79
What is the treatment of megaloblastic anaemia?
Treat cause where possible Vitamin B12 injections for life in pernicious anaemia Folic acid tablets (5mg per day orally Only if life-threatening, transfuse red cells
80
What are the causes of non-megaloblastic macrocytosis?
Alcohol Liver disease Hypothyroidism (All 3 may not be assoc. with anaemia, due to red cell membrane changes) Marrow failure- myelodysplasia, myeloma, aplastic anaemia
81
What will be seen in spurious macrocytosis?
Size of mature red cell is normal, but MCV measured as being high
82
What are the causes of spurious macrocytosis?
When there is an increase in reticulocyte numbers as a marrow response to acute blood loss or red cell breakdown (haemolysis) Reticulocytes are bigger than mature red cells and are analysed along with these for MCV measurement Cold-agglutinins

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