C&b 5 - Haemoglobin & Blood

Front 1

no. of O2 molecules each haem can bind.

Back 1

1 O2, so 4 haem = 4 O2

Front 2

Primary globin structure

Back 2

α, β, γ, δ globins

9 conserved amino acids for O2 to bind

 

Front 3

Secondary globin structure

Back 3

70% α helix

Front 4

Tertiary globin structure

Back 4

folding due to hydrophobic forces of inward facing non-polar groups

Front 5

Quarternary globin structure

Back 5

1 dimer sites on top of other dimer

subunits interact = Cooperative binding of O2

Front 6

Haem structure

Back 6

Proptoporphyrin ring with iron in centre

Front 7

Haem synthesis location?

Back 7

In mitochondria and cytoplasm of RBC precursors

Front 8

Haem synthesis how?

Back 8

glycine and succinate condense forming d-ALA

d-ALA forms protoporphyrin ring

iron inserted into ring

Front 9

Role of ALA synthase in haem synthesis?

Back 9

Makes ALA

Rate controlled

(stimulated by iron, inhibited by haem)

Front 10

What 3 things can Haemoglobin transport?

Back 10

- O2

- CO2

- H+

Front 11

Cooperative binding

Back 11

easier for subsequent bindings of O2

Front 12

myoglobin

Back 12

higher affinity for O2 than Hb

So it can be saturated even at low PO2 (muscle)

Front 13

Hb is open and taut when...

Back 13

Deoxygenated

Front 14

Hb is compact and relaxed when...

Back 14

Oxygenated

Front 15

CO2 carried in blood

Back 15

- as carbonic acid

- as carbamate by Hb

- Carbamino compounds

Front 16

Haldane effect

Back 16

Deoxygenated blood has increased CO2 carrying capacity

Oxygenated blood has reduced CO2 carrying capacity

Front 17

H+ carried in blood

Back 17

binds and stabilises deoxygenated form of Hb so its not as taut.

Front 18

Bohr effect

Back 18

Haemoglobin's affinity for O2 weaker when theres acid or CO2

So, it can release O2 to be used when needed.

Front 19

DPG carried in blood

Back 19

- 1Hb needed to bind 1DPG

- DPG binds and stabilises deoxygenated form

Front 20

What use is DPG?

Back 20

Can decr O2 affinity in Hb to aid release O2 

Synthesised in response to:

- altitude

- lung disease

Front 21

Factors that decrease Hb affinity for O2

Factors that shift curve to right

Back 21

"CADET face RIGHT"

 

CO2

Acid

DPG

Exercise

Temperature

Front 22

sickle cell trait has a _________________________ over malaria.

Back 22

Heterozygote advantage

Front 23

e.g. of structural Hb disorder?

Back 23

Sickle cell anaemia

Front 24

e.g. of decreased globin synthesis Hb disorder?

Back 24

Thalassemia

Front 25

Thalassemia

Back 25

reduced α/β globin production

Excess globin precipitates:

- RBC haemolysis

- ineffective erythropoiesis in marrow

Front 26

How does iron overload affect soft tissues

Back 26

- generates more free hydroxyl radicals

- incr non-transferrin bound iron in plasma

Front 27

β thalassemia trait (heterozygote)

Back 27

β+ = some globin synthesis

β0 = no globin synthesis 

Front 28

β thalassemia (homozygote)

Back 28

major - transfusion dependent

Front 29

clinical features of thalassemia

Back 29

"LABS"

- liver damage

- anaemia

- bone marrow expansion

- splenomagaly

Front 30

treating thalassemia

Back 30

- blood transfusion to incr Hb

- Chelation of excess plasma iron

- Monitor serum ferritin and liver iron conc.

Front 31

Sickle cell disease

Back 31

- autosomal recessive

- abnormal β-globin conformation causes it to crystallise at low PO2

Front 32

Precipitating factors of Sickle cell disease

Back 32

"PADI"

 

Pyrexia

Acidosis

Dehydration

Infection

Front 33

Diagnose Sickle cell disease using...

Back 33

1. Blood film

2. Any anaemia signs

3. PCR- HbS on gel electrophoresis

Front 34

Clinical features of sickle cell

Back 34

"CIS"

-Chronic anaemia (haemolytic)

- Infarctive crises due to vaso-occlusion

- Sequestration crises

Front 35

treating sickle cell

Back 35

- Try and prevent acute crises

- prevent organ damage

- transfusion/hydroxyurea to prevent sickling

Front 36

Henry's law

Back 36

1. Gas will dissolve in a liquid in proportion to its partial pressure and solubility coefficient

 

2. Will dissolve until equilibrium is achieved

Front 37

Oxygen in blood, proportion carried

Back 37

in solution - 1%

by Hb - 99%

Front 38

Why is it hard for Hb to bind first O2

Back 38

large number salt bridges to break down

Front 39

Why is it easy for Hb to bind 2nd & 3rd O2

Back 39

salt bridges broken already

Front 40

Why is it hard for Hb to bind 4th O2

Back 40

Almost fully saturated

Front 41

P50

Back 41

PO2 where Hb is 50% saturated

26.6mmHg for health people

Front 42

What causes DPG release (to help Hb release O2)

Back 42

- Chronic hypoxia

- Chronic alkalosis

- Hormones

- Sickle cell

Front 43

features of foetal Hb (HbF)

Back 43

2 α & 2 γ

increased O2 affinity so foetus is prioritised

HbA ---O2---> HbF

Front 44

Myoglobin

Back 44

Monomeric haem

increased O2 affinity

muscles

Front 45

myoglobin is 95% saturated at what PO2?

Back 45

40 mmHg

Front 46

CO2 released from RBC in lungs

Back 46

H2CO3 diffuses back into RBC and Carbonic anhydrase converts CO2 and H2O