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1.2 Haematology > Haemoglobin Structure & Synthesis > Flashcards

Haemoglobin Structure & Synthesis Flashcards

1
Q

What is Haemoglobin?

A

An iron containing protein synthesised by erythroblast precursors in bone marrow

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2
Q

What is Haemoglobin composed of?

A

2 dissimilar pairs of polypeptide chains which encloses an iron containing porphyrin ring called haem

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3
Q

What are the functions of the components of Haemoglobin?

A

Haem - O2 transport
Globin - Protects haem from oxidation, renders molecule soluble, variation in O2 affinity

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4
Q

What are the 3 stages of Haemoglobin synthesis?

A

Embryonic, foetal, & adult

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5
Q

What differs between different haemoglobin structures?

A

Globin chains

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6
Q

What 2 chromosomes are responsible for haemoglobin synthesis?

A

11 & 16

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7
Q

What are the types of Haemoglobin

A

~A
~A2
~F (Foetal)
~Gower 1
~Gower 2
~Portland 1
~Portland 2

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8
Q

Where in the early embryo is haemoglobin synthesised?

A

Yolk sac

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9
Q

What types of Haemoglobin are synthesised at week 5?

A

Gower 1, Gower 2, Portland 1, Portland 2

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10
Q

When are other forms of haemoglobin synthesised?

A

6 weeks

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11
Q

The formation of what Haemoglobin is essential for life?

A

Gower 2

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12
Q

During weeks 10-12 where is haemoglobin synthesised and what type is synthesised?

A

~Liver & spleen
~Foetal haemoglobin & haemoglobin A (later)

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13
Q

What takes over haemoglobin synthesis from the liver and spleen in later foetal development?

A

Bone marrow

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14
Q

What happens when bone marrow takes over haemoglobin synthesis?

A

Increased production of Haemoglobin A

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15
Q

Healthy levels (%) of haemoglobin A, A2 and F in adults?

A

A: ~97%
A2: 2.0-3.3%
F: 0.2-1.0%

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16
Q

How much iron should be in the body?

A

Male: 50 mg/kg
Female: 35 mg/kg

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17
Q

How much of the body’s iron is in haemoglobin?

A

65%

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18
Q

What is haemoglobin used for in RBC precursor cells?

A

Erythropoiesis

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19
Q

Where else is iron stored in the body?

A

~Ferritin and it’s insoluble form haemosiderin (macrophage of bone marrow, liver, spleen) ~30%
~Myoglobin in muscles
~Cytochrome enzymes in cells

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20
Q

Dietary sources

A

Red meat (especially liver), animal & fish products, leafy greens (poor source), legumes, fortified cereals & milks

21
Q

What is the average amount of iron consumed in the Western diet

A

10-15mg - 5-10% absorbed

22
Q

What percentage of dietary iron is absorbed during iron deficiency and pregnancy?

A

20-30%

23
Q

What forms can dietary iron he found in?

A

Ferrous (Fe2+) & Ferric (Fe3+) states

24
Q

What is the haem form of iron?

A

-Red meat & fish
-Ferrous state - quicker to absorb
-Released from the gut by haemoxygenase 1

25
Q

What is the non-haem form of iron?

A

-Vegetables & cereals
-Ferric state - slow to absorb
-Enzymes & acids release iron from protein complexes in food
-Ferroreductase convert ferric ions to ferrous ions to be easily absorbed
-Same process as Haem iron digestion after

26
Q

What controls iron absorption?

A

Amount of iron in diet, availability and the form, the bodies stores and requirements

27
Q

What causes iron to be lost?

A

Menstruation, GI bleeds, epithelial cells in skin, gut, urinary tract

28
Q

What is the main source of iron in the body?

A

The breakdown of RBCs

29
Q

What happens to old RBCs?

A

Broken down by macrophages of RE system - iron is released into the plasma - provides iron for transport protein transferrin - carries to be used to make new RBC

30
Q

What can the amount of iron being carried by transferrin tell us?

A

General iron status

31
Q

Where are transferrin receptors found?

A

On the lining of cells involved in erythropoiesis and iron storage

32
Q

What is the function of transferrin receptors?

A

Bind to transferrin - facilitates release of iron into cell
-Increased during iron deficiency (low ferritin) to bind to more transferrin
-Some are shed into plasma and can be measured

33
Q

What stages of erythropoiesis does haemoglobin get synthesised at?

A

Erythroblast stage - 65%
Reticulocyte stage - 35%

34
Q

Where is haem synthesised?

A

Mitochondria

35
Q

Where is globin synthesises?

A

Ribosome

36
Q

Haem structure

A

-Pigment - porphyrin class
-4 pyrrole rings linked by methene bridges each bound to central ferrous ion

37
Q

Haem synthesis

A

-Synthesised in most cells - most importantly in erythroblasts
-Enzymes involved are Succincyl Co Enzyme A transferase, aminolaevulininic acid synthase (ALAS)
-Haem synthase/Ferrocheletase - catalyses insertion of iron into haem in the mitochondria
-Sychronised with globin synthesises - haem synthesis increases = globin synthesises increases
-Needs entry of iron into the cell to occur

38
Q

Globin synthesis

A

-chains of amino acids
-adults - 2 alpha (chromosome 16) & 2 beta (chromosome 11)
-different globin chains in embryo and foetus

39
Q

Primary Structure of Globin

A

Amino acid chain - sequence & identities known

40
Q

Secondary Structure of Globin

A

9 non-helical sections & 8 helical sections

41
Q

Tertiary Structure of Globin

A

Folding of individual chains into 3D shapes

42
Q

Quaternary Structure of Globin

A

4 subunits join together (globin & haem ring) - tetramer

43
Q

Functions of haemoglobin

A

Transport 02 to tissues, transport CO2 to lungs

44
Q

What are the 3 different forms of CO2 that exist in the body for removal?

A

Bicarbonate ions 78%
Haemoglobin 13%
Solution in plasma 9%

45
Q

3 Stages of iron deficient anaemia

A

1 iron stores depleted
2 RBC synthesis altered
3 Isn’t enough iron to make haemoglobin

46
Q

Markers of iron deficient anaemia

A

-Microcytic hypochromic RBCs
-Decrease in RBC, Hb, MCV, MCH, MCHC
-Decrease in ferritin

47
Q

Symptoms of iron-deficient anaemia

A

-Pale or yellow scaly skin
-Fatigue
-Shortness of breath & chest pain after exercise
-hearaches, dizziness, light headedness
-Cold hands & feet
-inflammation of tongue
-Brittle nails

48
Q

Treatment of iron deficient anaemia

A

-Oral administration of iron (II) salt or iron (III) - 100-200mg/ day for 3 months - increase of 0.2-0.3 g/dl/day
-Parenteral iron treatment (iron saccharate complex or ferric carboxymaltose

1.2 Haematology (8 decks)

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