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Clinical Sciences > Micro and Macrocytic anaemia > Flashcards

Micro and Macrocytic anaemia Flashcards

1
Q

Anaemia

A

A reduction of Haemoglobin concentration of the blood below the normal range
for age and sex.

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2
Q

what is the reference ranges for males (MCHC)

A

13.3-16.7 g/dL

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3
Q

what are the reference ranges for females (MCHC)

A

11.8 – 14.8 g/dL

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4
Q

Causes of anaemia

A
  • decrease in RBC production
    -increase in RC destruction
  • blood loss
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5
Q

what is the reference range for RBC level (haematocrit (HCT)) (x10 ^12/L)

A

males 4.6 - 6.5
female 3.9 -5.6

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6
Q

average mean cell volume in (fL)

A

80-95 femtoliters

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7
Q

average mean cell haemoglobin(pg)

A

27 -34 picograms

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8
Q

how can FBC used to classify anaemia

A

-Leucocyte and platelet counts help distinguish between pure anaemia
and ‘pancytopenia’(defect of marrow)
- A high reticulocyte count is indicative of anaemia(to meet high O2 demand)

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9
Q

normal reticulocyte average

A

x< 0.5 - 1.5%

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10
Q

abnormal reticulocyte range

A

x>2.5%

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11
Q

what are the reference range for Microcytic, hypochromic
anaemia

A

MCV <80fl, MCH <27pg

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12
Q

What diseases are linked to Microcytic, hypochromic
anaemia

A

Iron deficiency Thalassaemia
Lead poisoning

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13
Q

what are the reference ranges for Normocytic, and normochromic?

A

MCV 80-95fl, MCH ≥27pg

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14
Q

What diseases are linked to having Normocytic, and normochromic cells?

A

Haemolytic anaemia
Chronic anaemia
Renal disease

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15
Q

what are the reference ranges for macrocytic anaemia?

A

MCV >95fl

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16
Q

What deficiency is linked to macrocytic anaemia

A

Vitamin B12 or folate
deficiency

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17
Q

How does lead poisoning cause anaemia?

A

Pb inhibits the creation of Hb by interfering with enzymatic steps in the synthesis pathway and also causes haemolysis to occur

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18
Q

what is abnormal RBC size known as

A

anisocytosis

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19
Q

what is abnormal RBC shape known as

A

poikilocytosis

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20
Q

Symptoms of Iron Deficiency
Anaemia (Macrocytic)

A

tiredness and lack of energy
shortness of breath
noticeable heartbeats (heart palpitations)
pale skin
a sore tongue(glossitis)
wanting to eat non-food items, such as paper or ice (pica)

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21
Q

lab diagnosis of microcytic anaemia

A

MCV = < 80fL
MCH = Low
Ferritin = Low
RBCC = low
Blood Film =target and pencil cells
History of bleeding

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22
Q

why is microcytic anaemia classified as a haeme disorder?

A

RBC have less Hb and therefore less Fe

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23
Q

what is sideroblastic anaemia?

A

form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells. In sideroblastic anaemia, the body has iron available but cannot incorporate it into haemoglobin, which red blood cells need in order to transport oxygen efficiently

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24
Q

summarise the Iron cycling in healthy individuals

A
  • Fe is ingested into the body and absorbed by the intestine.
  • Fe is transported by transferrin to tissues with transferrin receptors (ex. erythroblast in BM) which incorporates Fe in BM
  • at the end of RBC life, RBCs are heamolysed by macrophages of reticular endometrium
  • Fe released from Hb enters the plasma and provides Fe for transferrin
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25
Q

how many haem molecules can transferrin carry?

A

2

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26
Q

what is Fe stored in Macrophages as

A

Feritine and haemocyurine

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27
Q

why is anaemia a common side effect of chronic kidney disease (CKD)

A

if kidneys are damaged -> less haemopoietin is produced which is needed to make more RBC so less RBC = Anaemia

Additionally, because there are fewer RBCs it affects the way the body uses Fe

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28
Q

describe how iron’s Uptake, Storage And Utilization For HB Synthesis

A

Fe 3+ (dietary) —–> Fe2+

the enzymes on the surface of enterocytes facilitate the process because Fe3+ is toxic and needs to be incorporated with haem

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29
Q

true or false is Fe 2+ readily absorbed by the Transmembrane protein DMT1

A

true

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30
Q

how does the body respond to low absorption of Fe from diet and what result does this have

A

the body uses its Fe store causing a -ve balance

31
Q

what is it called when Fe stores are depleted?

A

latent deficiency

32
Q

what does latent deficiency show

A

It is evidence of Fe deficiency however it is not indicative of anaemia as Hb levels are normal.

33
Q

what is the response to latent deficiency?

A

must be monitored as could result in Fe deficiency anaemia if not treated with Fe supplements

34
Q

causes of latent deficiency

A
  • heavy menstrual bleeding
  • low Fe supply (diet)
35
Q

what are the lab findings of microcystic anaemia?

A

FBC:
low Hb, RBCC, MCH and MCV

Blood film:
1. Microcytosis= small red blood cells
2. Hypochromia= pale red blood cells
3. Elliptocytosis= long thin cells
4. Teardrop poikilocytes= tear shaped cells
5. Anisocytosis= red blood cells are unequal in size

36
Q

what other ways are used to determine Fe deficiency

A

can investigate serum ferritin as it’s their main storage protein for Fe

(is produced in response to inflammation)

37
Q

true or false is ferritin universal

A

true, ferritin is a universal intracellular protein in all organisms (found in the cytosol)

38
Q

what do increased ferritin levels indicate

A

an iron storage disorder ((haemochromatosis) which occurs due to too much iron build-up)

39
Q

what does a normal blood film look like

A
40
Q

what does a blood film with Fe deficiency look like

A
41
Q

Treatment for Fe deficiency

A

*Iron supplements
* The most commonly prescribed supplement is ferrous sulphate
twice daily
* In severe cases - blood transfusion & iron therapy
* Vitamin C
* Birth control pills (given in cases of Fe deficiency caused my menstruation to reduce blood loss)

42
Q

Blood film of RBCs responding to treatment

A
43
Q

what are the characteristics of macrocytic anaemia?

A
  • abnormally large RBCs
  • MCV 98 fL
44
Q

describe how megaloblastic anaemia is a cause for macrocytic anaemia

A

impaired DNA synthesis so precursors for megaloblast have large nuclei and dispersed chromatin

=> causes anaemia as recognised as being abnormal and then removed from circulation early (ineffective erythropoiesis)

45
Q

what are some sources of B12 (cobalamin)

A
  • beef liver
    -salmon, tuna
  • milk
    -egg
  • plain yoghurt
46
Q

what is the RDA for adults?

A

2.4 μg

47
Q

where is B12 primarily found in animals

A

found in the liver of animals bound to proteins methylcobalamin

48
Q

To be absorbed B12 has to …

A

be liberated and extracted with a combination of proteolytic enzyme
(pepsin) and acidic enviromentof stomach

49
Q

anaemia due to B12 deficiency affects what population of people

A

vegans and vegetarians

50
Q

what two enzymes is B12 an essential cofactor for

A
  • methylmalonic mutase
  • methyltetrahydrofolate reductase
51
Q

what conversion does methylmalonic
mutase catalyse?

A

Conversion of L-methylmalonyl coenzyme A to succinyl coenzyme A (a key step in the synthesis of haem)

52
Q

what conversion does methyltetrahydrofolate reductase catalyse?

A

Methylation of homocysteine to methionine (B12 used to deliver methyl group)

53
Q

summarise B12 absorption

A
  • Released from protein-binding foods and extracted by enzymes and acid conditions in the stomach
  • Complexes with intrinsic factor (IF) 1:1
  • IF synthesised and released by gastric parietal cells stomach. IF acts as a carrier protein by delivering B12 to the Large intestine where it can be absorbed by the ileum
  • For absorption to occur, docks to the receptor on an enterocyte
    -Receptor has 3 components cubulin, megalin and amnionless
  • The IF-B12 complex binds to surface receptor cubulin
  • Binds to 2nd protein called amnionless
  • Directs endocytosis of the cubulin IF-B12 complex in the distal ileum where B12 is absorbed and IF destroyed
54
Q

how is B12 transported?

A

B12 is transported by enterocytes from intrinsic factors to transcobalamin and hatocorrin

55
Q

why is B12 transported?

A

so it can enter the bloodstream and be delivered to developing tissue such as BM.

56
Q

What percentage of B12 is bound to hatocorrin

A

80 - 90%

57
Q

what is the intrinsic factor where B12 is transported from and where is it produced?

A

intrinsic factor is the glycoprotein. is produced in the gastric epithelium and tightly binds to B12 in our GI tract.

58
Q

causes of B12 deficiency

A
  1. Malnutrition:

> Inadequate dietary intake– vegan diet- uncommon

  1. Malabsorption :

> 90% of cases lack of intrinsic factor – Pernicious Anaemia.
Gastrointestinal disease
Surgical removal on site of IF synthesis
Drug Induced
Increased requirement of vitamin- pregnancy

59
Q

what is pernicious anaemia?

A

The immune system attacks the cells in the stomach that produce the intrinsic factor, which means the body is unable to absorb vitamin B12

60
Q

what is the onset of pernicious anaemia?

A

60 years

61
Q

what can cause pernicious anaemia?

A

Helicobacter pylori infection may initiate an autoimmune gastritis which presents in younger individuals as iron deficiency and in the elderly as pernicious anaemia

62
Q

how is pernicious anaemia treated?

A

with B12 injections

63
Q

how does the lab diagnose B12 deficiency?

A
64
Q

why is folate important?

A

for the synthesis of thymidine and the development of a healthy fetus (in the spinal cord and brain)

65
Q

what food contains folate

A
  • beef and chicken liver
  • broccoli, spinach and okra
  • egg yolk
66
Q

how long do folate stores last

A

three months

67
Q

causes of folate deficiency

A
  1. Inadequate dietary intake (common), folate is heat labile
    (folate dehydrated by cooking)
  2. Intestinal malabsorption
    Coeliac disease- destruction of intestinal villi= malabsorption of folate
  3. Increased requirement
    Pregnancy
  4. Drug-induced interferes with absorption or metabolism
    Alcohol (coupled with poor diet)

Methotrexate
> inhibits dihydrofolate reductase= decreased supply of folates
> Folate aids those treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis

68
Q

explain how large cells are produced and what are the Biochemical Basis of Megaloblastic Anaemia.

A
  • Folate is necessary for nucleotides (adenosine monophosphate (AMP) /guanosine monophosphate (GMP)).
  • Inadequate amounts of (dUMP)/ (dTMP) leads to a failure of DNA synthesis as the rate-limiting step is inhibited.
  • Causes Loss of nucleus in cells with fewer cell divisions leading to larger cells
69
Q

Why is folate needed?

A

lack of folate. folate isn’t recycled so it means B12 doesn’t have a methyl group therefore homocysteine cant be converted leading to a build-up of homocysteine

70
Q

what do the lab results indicate about macrocytic anaemia

A
71
Q

what does a macrocytic blood film look like

A
72
Q

summarise how Macrocytic Anaemia is diagnosed

A
73
Q

explain (TMPRSS6 gene) transmembrane serine protease 6 as a cause of Fe deficiency anaemia

A

The most likely diagnosis is congenital iron deficiency.
▪ The TMPRSS6 gene provides instructions for making
a protein called matriptase-2.
▪ This protein is part of a signalling pathway that
controls the levels of hepcidin - a regulator of iron
balance in the body.
▪ When blood iron levels are low, this signalling
pathway reduces hepcidin production
▪ Allows more iron from the diet to be absorbed
through the intestines and transported out of storage
into the bloodstream.

74
Q

Parvovirus-induced pure red cell aplasia

A

Pure red cell aplasia or erythroblastopenia refers to a type of aplastic anaemia affecting the precursors to red blood cells. In PRCA, the bone marrow ceases to produce red blood cells.

Clinical Sciences (8 decks)

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