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erythropoeisis and microcytic anaemia Flashcards

1
Q

how much iron is in the daily diet?

A

15mg/day

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2
Q

what is the usual total body iron?

A

3-5g

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3
Q

how is the total body iron maintained in its normal range?

A

1mg is absorbed and 1mg is excreted every day

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4
Q

what is most of the iron in the body in the form of?

A

circulating Hb and some other proteins

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5
Q

in which area of the body is iron absorbed?

A

duodenum

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6
Q

what cells absorb iron?

A

enterocytes

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7
Q

what are the 3 main proteins enterocytes use to absorb, store and remove iron

A

DMT-1 - divalent metal transported 1 - apical transporter
ferritin - intracellular binding protein
ferroportin - basolateral transporter

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8
Q

what is DMT-1 and what does it stand for?

A

divalent metal transporter 1

apical transporter in the microvilli

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9
Q

in what form is iron absorbed by enterocytes?

A

free iron - Fe2+ (NOT Fe3+)

iron as part of a protein like haem

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10
Q

where is ferric reductase enzyme found and what does it do?

A

found on enterocytes’ brush border and changes Fe3+ to Fe2+

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11
Q

what is ferritin?

A

a big hollow polyprotein made of 24 apoferritin subunits

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12
Q

what is the function of ferritin?

A

stores inactive Fe3+ and releases it in a controlled way when needed
acts as a buffer for iron deficiency/overload

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13
Q

where is ferritin found?

A

mostly as a cytosolic protein but some is secreted into serum to be an iron carrier

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14
Q

what is plasma ferritin an in direct marker of?

A

total amount of iron in the body

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15
Q

what is serum ferritin used as a diagnostic test for?

A

iron deficiency anaemia

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16
Q

what do ferroportin molecules do?

A

basolateral iron transporters

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17
Q

what are transferrins and what is their function?

A

iron binding blood plasma glycoproteins that can carry 2 molecules of Fe3+

regulate free iron levels in the plasma and ecf and transport iron to other cells e.g. bone marrow

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18
Q

explain how iron enters a cell and is stored

A

iron filled transferrins bind to transferrin receptors on cell surfaces
enter in vesicles via endocytosis
endosome has lower pH than the cell
transferrin releases iron ions for Hb or ferritin molecules
transferrin released from the empty transferrin/receptor complex

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19
Q

when are serum transferrin levels measured?

A

in cases of suspected iron deficiency and iron overload disorders

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20
Q

what is myeloid tissue?

A

bone marrow

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21
Q

why do myeloid cells take up a large part of circulating transferrin?

A

to incorporate iron into Hb in erythrocyte precursor cells

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22
Q

what is yellow marrow composed of?

A

lots of fat droplets and cells

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23
Q

where does most erythropoiesis occur in adults?

A

red bone marrow

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24
Q

what are the three stages of of fetal rbc formation?

A

mesoblastic
hepatic
myeloid

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25
what happens in the mesoblastic stage?
at week 3 nucleated RBCs form in yolk sac and mesothelial layer of the placenta
26
what happens in the hepatic stage?
at week 6 erythropoiesis happens in the liver and spleen
27
what happens in the myeloid stage?
3rd month onwards bone marrow becomes primary source of RBCs
28
where does rbc formation occur up to 5 years?
bone marrow of all bones
29
where does rbc formation occur from 5-25 years?
bone marrow of the long bones
30
where does rbc formation occur after 25 years?
bone marrow of membranous bones such as vertebrae, sternum, ribs, cranial bones and ilium
31
what is a haemocytoblast?
haemopoietic stem cell
32
what is a proerythroblast?
common myeloid progenitor – stem cell
33
describe the stages of erythropoiesis?
haemocytoblast --> proerythroblast --> erythroblast --> nucleus shrinks, cytoplasm fills w Hb until nucleus is expelled --> reticulocyte --> mature RBC
34
what is diapedesis?
RBC squeezes through pores in marrow capillary membrane into blood
35
what controls erythropoiesis?
erythropoietin (EPO)
36
where is EPO made?
protein made in fibroblast interstitial cells around PCT of kidneys
37
why is EPO made in the kidneys?
kidney O2 levels arent altered by exercise/changes in blood pressure - mainly determined by Hb levels in arterial blood so any hypoxia in the kidneys is defo bc of reduced carriage of oxgen
38
what are EPO secreting cells sensitive to?
hypoxia
39
what is the function of EPO?
acts on erythropoietic stem cells to increase the speed of maturation of committed bone marrow cells
40
why do men have higher Hb levels than women?
bc testosterone increases EPO production
41
why do RBCs need ATP?
membrane Na+ pumps - stop RBCs from swelling and bursting | GLUT1 transporters - take up glucose
42
explain how RBCs make ATP?
anaerobic glycolysis pyruvate from glycolysis reacts with NADH to make lactic acid and NAD+ (instead of pyruvate going into the citric acid cycle) which is then used to make ATP
43
what is done with the lactate made in anaerobic glycolysis in RBCs?
exported by the RBC and taken up by the liver or muscle cells converted back to glucose which then gets re-exported into the blood
44
why do RBCs have a negative surface charge?
bc of membrane glycoproteins containing sialic acid
45
why do RBCs need a negative surface charge?
so they repel each other and dont stick together in capillaries
46
why does esr increase in inflammatory reactions?
inflammatory reactions/bacteria in the blood increase fibrinogen levels in the plasma reduces -ve surface charge so RBCs stick together and form rouleaux which increase ESR
47
define ESR
the distance, in mm, RBCs fall in 1 hour
48
what is ESR an indicator for?
a non-specific marker for infection in the blood
49
how do you calculate the normal esr?
age (+10 in female)/2
50
what is the normal lifespan of RBCs
120 days
51
how are RBCs removed from the blood?
in the spleen by macrophages spleen detects lack of deformability of RBCs when they get stuck in capillaries - shows they're old macrophages engulf and break open RBCs by osmotic lysis and break down the contents
52
how is Hb broken down by splenic macrophages?
- haem prosthetic groups are removed from globin proteins - globin proteins --> amino acids - haem broken open by haemoxygenase enzyme and iron is removed and collected by transferrin - opened porphyrin ring w/o iron is biliverdin
53
where does iron from broken down RBCs go?
transferrins transport it to the liver and then the bone marrow where it's then reused to make new Hb
54
what is the difference between biliverdin and bilirubin?
bilirubin has an extra hydrogen atom
55
how is biliverdin converted to bilirubin?
reduced by biliverdin reductase in the splenic macrophage
56
what is unconjugated bilirubin?
bilirubin binds to albumin in splenic macrophages
57
what is conjugated bilirubin and how is it made?
made when unconjugated bilirubin reaches the liver and has glucuronic acid attached by hepatocytes to make it more soluble
58
how does conjugated bilirubin leave the body?
enters small intestine through the bile converted to urobilinogen by bacteria most urobilinogen leaves body through the faeces 10% passes back in the portal vein to the liver where it leaves via venous blood and is excreted in the urine
59
what gives urine its yellow colour?
urobilinogen from venous blood from the liver
60
define anaemia
Hb level below the reference range for that age, and gender
61
list symptoms of anaemia
tiredness, fainting, shortness of breath, worsening angina/claudication, rapid heart beat (palpitations)
62
list signs of anaemia
pallor e.g. palmar creases, nail bed, conjunctivae (all unreliable), rapid heart rate, bounding pulse, systolic flow murmur, cardiac failure, retinal haemorrhages
63
what are the main reasons for anaemia?
decreased production of red cells increased destruction of red cells increased loss of red cells
64
what causes decreased production of red cells?
iron deficiency, B12/folate deficiency, marrow infiltration e.g. cancer, any chronic diseases e.g. rheumatoid/cancer, infections e.g. HIV, parvovirus
65
what causes increased destruction of red cells?
haemolytic anaemia a. Disorders of RBC membrane/enzyme/haemoglobin b. Immune destruction
66
what causes increased loss of red cells?
bleeding
67
what are the types of anaemia and how are they categorised?
microcytic (<80fl), normocytic (80-96fl) or macrocytic (>96fl)
68
what is the threshold for microcytic anaemia in 2-12 year olds?
<76fl
69
what is microcytic anaemia?
iron deficiency anaemia
70
what are some causes of microcytic anaemia in developed and developing countries?
o Developing countries – linked to nutrition, hookworm infestation etc Developed societies – GIT bleeding and other sources of blood loss, malabsorption. IDA prevalent in infants/kids, adolescent girls, pregnant/lactating/premenopausal women
71
how much iron in 1ml of blood?
0.5mg
72
how much blood loss per day will cause iron deficiency?
10ml/day
73
describe RBCs and amounts of Hb in microcytic anaemia
RBCs are small | Reduced amounts of Hb - hypochromic
74
what are some causes of microcytic anaemia?
low iron in diet reduced RBC synthesis excess iron loss (bleeding)
75
what foods are major sources of haem iron?
food of animal origin
76
what factors enhance iron absorption?
haem iron (meat), ferrous salts (Fe2+), acid stomach pH, iron deficiency, pregnancy, hypoxia
77
what factors impair iron absorption?
non-haem iron (veg), ferric salts (Fe3+), alkaline stomach pH, iron overload, inflammatory disorders
78
what are proton pump inhibitors used for?
used for acid reflux or indigestion
79
what effect can PPIs have on stomach acid and iron absorption?
reduce stomach acid and decrease iron absorption
80
what are some of the causes of iron deficiency anaemia?
* Reproductive (menorrhagia) * GI tract bleeding – varices, ulcer, inflamm bowel, cancer * GI tract malabsorption – coeliac, atrophic gastritis * Physiological – growth spurts, pregnancy * Dietary – poor diet in elderly * Worldwide – hookworm – parasitic worm which inhabits the intestines. Mouth attaches to gut wall, punctures blood vessels and feeds on RBCs and uses up Fe
81
how can you confirm IDA?
* Full blood count (low RBC number) * Blood film (microcytic, hypochromic RBCs) * Serum ferritin (is it low?) * Serum iron total iron binding capacity (TIBC) (is it low?)
82
how is iron deficiency anaemia treated?
* Improve Diet (include haem-containing proteins * Iron tablets (ferrous sulphate) * Avoid blood transfusion * Once Hb normal continue iron supplements for ~3 months

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