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
what does changes in transferrin suggest when reduced/increased
reduced in iron deficiency reduced in anaemia of chronic disease increased in genetic haemachromatosis
26
what does serum ferritin show and what does low ferritin mean
storage of iron low ferritin = iron deficiency
27
what blood results are seen in iron deficiency
low Hb i.e. anaemia low serum ferritin i.e. reduced storage iron
28
what are causes of iron deficiency
not eating enough blood loss (usually GI - tumours, ulcers, NSAIDs) malabsorption (coeliac disease) menorrhagia (>60ml)
29
where is iron absorbed in the bowel
duodenum
30
what are the consequences of a negative iron balance
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
31
what is important to remember about iron deficiency anaemia
it is a Sx and requires Ix for an underlying cause
32
what is a megaloblast
An abnormally large nucleated red cell precursor with an immature nucleus.
33
what are megaloblastic anaemias characterised by
defects in DNA synthesis and nuclear maturation with preservation of RNA and haemoglobin synthesis
34
what are the consequences of megaloblastic changes
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
so in summary, what causes a larger cell size in megaloblastic anaemia
cell failure to become smaller
36
what causes megaloblastic anaemia
B12 deficiency Folate deficiency Drugs Rare inherited abnormalities
37
why does a lack of B12 or folate cause megaloblastic anaemia
B12 and folate are essential co-factors for nuclear maturation. They enable chemical reactions that provide enough nucleosides for DNA synthesis
38
what is B12 and folate responsible for
B12 = methionine cycle folate = folate cycle
39
what does the methionine cycle produce
s-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates
40
what is the folate cycle important for
nucleoside synthesis
41
what is the pathway of B12 absorption
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
causes of vitamin B12 deficiency
``` Dietary (e.g. vegan) Pernicious anaemia Atrophic gastritis Chronic pancreatitis Coeliac disease Crohn's disease ```
43
what are dietary folates converted to and where are they absorbed
converted to monoglutamate absorbed in jejunum
44
how long do body stores of B12 and folate last
``` B12 = 2-4 years Folate = 4 months ```
45
what are causes of folate deficiency
Inadequate intake malabsorption (Coeliac, Crohn's) Excess utilisation (haemolysis, pregnancy, malignancy) Drugs (anticonvulsants)
46
features of B12/folate deficiency
Symptoms/signs of anaemia weight loss, diarrhoea, infertility Sore tongue, jaundice Developmental problems
47
what Sx is specific to B12 deficiency
Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
48
what spinal problem is seen in B12 deficiency
Subacute combined degeneration of the cord
49
what is pernicious anaemia
Autoimmune condition with resulting destruction of gastric parietal cells (which produce intrinsic factor)
50
what is pernicious anaemia associated with
atrophic gastritis and personal or family history of other autoimmune disorders (eg. Hypothyroidism, vitiligo, Addison’s disease)
51
what blood results are seen in PA
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
what should be checked in PA
Serum folate and B12 Auto-antibodies (anti gastric-parietal cells and anti-intrinsic factor)
53
what is the Tx of megaloblastic anaemia
treat the cause for PA = vitamin B12 injections for life folic acid 5mg per day
54
what is injections of vitamin B12 called
hydroxycobalamin
55
what are causes of a macrocytosis split into
genuine - megaloblastic - non-megaloblastic spurious
56
what are non-megaloblastic causes of macrocytosis
- alcohol - liver disease - hypothyroidism (these 3 might not be associated with anaemia) ``` marrow failure - myelodysplasia - myeloma - aplastic anaemia (all associated with anaemia) ```
57
what is meant by megaloblastic anaemia
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
what is Spurious macrocytosis
The size of the mature red cell is NORMAL, but the MCV is measured as being high
59
what are causes of a spurious macrocytosis
- 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
if the reticulocyte is raised what should you consider
haemorrhage | haemolysis
61
why can liver disease cause a low platelet count
lead to hypersplenism >> increased destruction
62
if the reticulocyte count is low in a macrocytosis what investigation should be done next
serum B12 and/or folate level
63
if serum B12 and/or folate is high what should be considered
myelodysplasia myeloma aplastic anaemia
64
what can people with PA present with
mildly jaundiced | - due to intramedullary haemolysis
65
why do people get jaundice in PA
Red cells die prematurely in the marrow Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells Haemoglobin converted to bilirubin
66
what can complicated severe megaloblastic anaemia
pancytopenia
67
what are the two headings for classification of anaemia
Decreased production (would see reticulocytopenia) Increased loss or destruction of red cells (reticulocytosis)
68
what does it mean when there is a reticulocytosis
red cell production is increased
69
what are causes for a macrocytic anaemia
``` myelodysplasia myeloma aplastic anaemia reticulocytosis cold agglutinins ``` B12 and folate deficiency
70
when can you see a macrocytosis without anaemia
alcohol liver disease hypothyroidism
71
what are causes of a normochromic normocytic anaemia
Acute blood loss/early iron deficiency Anaemia of renal failure Hypothyroidism Marrow failure
72
what do we get an anaemia in chronic kidney disease
Epo production decreases which normally stimulates erythropoiesis by bone marrow
73
what is the big differentiating factor for anaemia caused by iron deficiency and anaemia of chronic disease
Iron deficiency = ferritin reduced chronic disease = ferritin normal/increased
74
how is the marrow in B12/folate deficiency
hypercellular
75
what is the platelet number in iron deficiency anaemia
low
76
how is thalassaemia Ix
electrophoresis | HPLC