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CR2 > Erythropoeisis & Anaemia > Flashcards

Erythropoeisis & Anaemia Flashcards

Iron absorption Sites & stages of Erythropoiesis RBC Count Removal and recycling of senescent red cells Classification of anaemias based on RBC size Causes of iron deficiency anaemia Distinguishing between different types of iron deficiency anaemia

1
Q

What is erythropoiesis?

A

The formation and life cycle of red blood cells

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2
Q

How many RBCs are replaced in an adult every second?

A

2.5 million

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3
Q

What are the stages of RBC formation before birth?

A

Mesoblastic stage
Hepatic stage
Myeloid stage

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4
Q

What is the mesoblastic stage?

A

3rd week before births RBCs are nucleated still and form in the yolk sac and mesothelial layers of the placenta

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5
Q

What happens in the hepatic stage?

A

Before birth, at 6 weeks erythropoiesis usually occurs in the spleen and liver

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6
Q

What is the myeloid stage?

A

Before birth, from the 3rd month onwards the bone becomes the source of RBCs

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7
Q

What is the average diet for iron?

A

15mg/day

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8
Q

What is the total body iron volume?

A

3-5g

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9
Q

How much iron is absorbed and excreted each day?

A

1g absorbed and 1g excreted

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10
Q

Where is most of the iron in the body?

A

Circulating as part of haemoglobin - 2g.

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11
Q

Where is the majority of iron absorbed?

A

Duodenum by enterocytes

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12
Q

How is iron absorbed in the duodenum?

A

Ferroportins (transporter proteins) on enterocytes allow iron movement into body

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13
Q

In what form can iron be absorbed?

A

Fe2+ ion or as part of a protein

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14
Q

What is the role of ferric reductase?

A

on the brush border of the eneterocytes and reduces Fe3+ into Fe2+

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15
Q

What is the function of transferrin?

A

Iron-binding blood plasms glycoproteins which regulate free ion levels in plasms and ECF.

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16
Q

What is the mechanism of transferrin?

A

Takes up iron from enterocytes in the form Fe3+ and transported in blood to bone marrow and other cells. Transferrin binds to transferrin receptors on erythroblasts for example and get transported into the cell via endocytosis. it then releases the iron ions which are taken up by ferritin or HB to store. The empty transferrin gets transported back to the cell surface and released to repeat.

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17
Q

What is ferritin?

A

A very large hollow polyprotein made up of 24 apoferritin subunits, stores many iron Fe3+ ions.

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18
Q

What is the role of ferritin?

A

Acts as a buffer against iron deficiency and iron overload by releasing iron into cells in a controlled way.

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19
Q

What is myeloid tissue?

A

Bone tissue

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20
Q

What do myeloid cells do?

A

Take up transferrin to allow them to deposit iron to Hb.

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21
Q

Where does most erythropoiesis occur?

A

red bone marrow

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22
Q

Where does erythropoiesis occur after birth up to 5 years?

A

In all bone marrow

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23
Q

Where does erythropoiesis occur between ages 5 and 20-25

A

Marrow of the long bones

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24
Q

Where does erythropoiesis occur from above the age of 25?

A

marrow of membranous bones - vertebrae, sternum, ribs, cranial bones and ilium

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25
Q

What does erythropoiesis start with?

A

haematopoietic stem cell/haemocytoblast

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26
Q

What happens to the haematopoietic stem cell/haemocytoblast?

A

Differentiates into a stem cell called a common myeloid progenitor/proerthryoblast

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27
Q

What happens to a proerythroblast?

A

Undergoes a series of transformations where nucleus shrinks/condenses and cytoplasm fills with Hb and nucleus is expelled so it becomes a reticulocyte and is released into the blood or stays in marrow.

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28
Q

What happens to reticulocytes?

A

Mature into erythrocytes which squeezes through pores in marrow capillary membrane into blood via diapedesis.

29
Q

What produces erythropoietin?

A

Fibroblast interstitial cells in the kidney around the PCT.

30
Q

Why does the kidney produce erythropoietin?

A

oxygen levels in and around the PCT are not altered by exercise or blood pressure changes and so purely determined by Hb levels. They are hypoxia sensitive so know when to stimulate EPO for more RBC production or not.

31
Q

What does EPO do?

A

Acts on erythropoietic stem cells to increase RBC production. Increases speed of maturation of committed bone marrow cells.

32
Q

Why do men have slightly higher Hb levels than women?

A

testosterone increase EPO production

33
Q

What is the consequence for RBCs not having mitochondria?

A

They cannot use oxidative metabolism to make ATP

34
Q

What do RBCs need ATP for?

A

To power sodium pumps in the membrane

Power GLUT1 transporters which take up glucose

35
Q

How do RBC’s make ATP?

A

Anaerobic Glycolysis

36
Q

Why do erythrocytes have a negative surface charge?

A

Glycoproteins containing siliac acid

37
Q

Why is it useful that erythrocytes have a negative surface charge?

A

Ensures they repel each other electrostatically and don’t all stick and clump together in capillaries

38
Q

What are roleaux?

A

Stacks of clumped RBCs

39
Q

If RBCs have a negative charge how do they clump together?

A

Inflammatory reactions or bacteria in the blood increase fibrinogen which binds RBC membranes so they adhere.

40
Q

What is ESR?

A

Erythrocyte sedimentation rate - increases when there are rouleaux

41
Q

What does a raised ESR mean?

A

Non specific marker of infection

42
Q

What is the life time of RBCs?

A

120 days

43
Q

What happens to RBCs after 120 days?

A

Removed from the blood by macrophages and pass through spleen

44
Q

How are RBCs recycled?

A

Spleen detects senescent RBCs by lack of deformability as more rigid. They get trapped in spleen capillaries and engulfed by spenic macrophages and broken up by osmotic lysis. Haem group removed and broken by haemoxygenase enzyme, iron atoms collected by transferrin which takes it to liver then bone marrow to re-use for new Hb.

45
Q

What are you left with when an old RBC has been removed of its haem group?

A

BILVERDIN - greenish in colour (opened porphyrin ring minus its iron atom)

46
Q

What happens to biliverdin?

A

Reduced to bilirubin (yellow in colour) in macrophage by biliverdin reductase

47
Q

What are biliverdin and bilirubin examples of?

A

Antioxidants

48
Q

How does bilirubin become unconjugated?

A

Bilirubin bound to albumin in splenic macrophages and then gets released into blood.

49
Q

How does bilirubin become conjugated?

A

Released into blood unconjugated and reaches liver where it attaches to glucuronic acid by hepatocytes to increase its solubility

50
Q

How does urobilinogen form?

A

Conjugated bilirubin passes in the bile to the small intestine where bacteria converts it into urobilinogen

51
Q

What happens to urobilinogen?

A

Most passes out as feces but 10% passes back in portal vein to liver and leaves in venous blood to be recycled.

52
Q

What makes urine yellow?

A

Recycled urobilinogen passing through kidney from liver.

53
Q

What is the definition of anaemia?

A

Hb below reference for that age and gender

54
Q

What are some symptoms of anaemia?

A

Tiredness, fainting, SOB, worsening angina, rapid heart beats

55
Q

What are some signs of anaemia?

A

bounding pulse, cardiac failure, systolic flow mumur, retinal haemorrhages, rapid heart rate, pallor

56
Q

What are the 3 common causes of anemiea?

A

Low production of RBCs
High level of destruction of RBCs
Increased loss of RBCs

57
Q

What are the causes of poor production of RBCs?

A 
Iron deficiency
B12 deficiency
marrow infiltration
chronic disease - rheumatoid/cancer
infections
58
Q

Why might there be high destruction of RBCs

A

haemolytic anaemia
immune destruction
disorders of RBC membrane/enzyme/Hb

59
Q

Define microcytic, normocytic and macrocytic.

A

Microcytic - <76 femtolitres so RBCs too small
normocytic - 76-96fl
macrocytic - >96 fl so RBCs too big

60
Q

What is an example of microcytic anaemia?

A

iron deficiency

61
Q

What features make up iron defiency anaemia?

A

microcytic RBCs
Hypochromic - reduced amounts of Hb
caused by low iron diet/reduced RBC synthesis/excess iron loss (bleeding)

62
Q

Why are animals a better source of iron than plants?

A

Plant iron has powerful chelators which are chemicals than hold iron and prevent absorption whereas haem iron is in animals and has highest bioavailabiluty

63
Q

How can you enhance absorption of iron/

A 
Haem iron in meat
ferrous salts containing Fe2+
acid stomach pH
pregnancy 
hypoxia
64
Q

How can absorption be impaired?

A 
Non haem iron from plants
ferric salts containg Fe 3+
alkaline stomach pH
iron overload
inflammatory disorders
PPIs may reduce stomach acid so reduce absorption
65
Q

What are the RF for developing iron deficiency anaemia?

A 
age - elderly
sex - females
reproduction - menorrhagia
GI
Drugs - aspirin/NSAIDs
social vegan diet
pregnancy/infancy/breastfeeding
66
Q

What are some causes of iron deficiency anaemia?

A 
menorrhagia
GI bleeding
Gi malabsorption
pregnancy
growth spurts
elderly
vegans
hookworm
67
Q

How do you confirm iron defieinct anaemia?

A

low RBC
microcytic and hypochromic RBCS (blood film)
low serum ferritin
Low serum iron total iron binding capacity (TIBC)

68
Q

How do you treat iron defieincy anaemia?

A

1 - improve diet
2 - ferrous sulphate tablets
3 - avoid blood transfusion
4 - continue iron supplements for 3 months once Hb is normal

69
Q

How can anaemia occur normocytically?

A

From acute blood loss (transfusion needed)
From chronic disease
From abnormal haemolysis

CR2 (35 decks)

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