Physiology: gas pressures / HB

Question 1

What is pressure?

Answer 1

force/unit area = N/m²

1 pascal = 1 N/m²
1kPa = 1000N/m²

Commonly expressed in mmHg (close to Torr)

1mmHg = 0.133kPa
1kPa = 7.55mmHg

Atmospheric pressure = 101.3kPa (760mmHg)

Question 2

What is partial pressure?

Answer 2

Individual pressure exerted by a gas
In a mixture of gases, each gas exerts individual partial pressure (partial pressure independent of other gases in mixture)

Total pressure = sum of component partial pressures

Dalton’s Law = PT =P₁+P₂+P₃+P₄

PATM = PN2 +PO2 +PCO2 +PCO +PH2O

O₂ constitutes 21% of air, so if atmospheric pressure ~100kPa, PO₂ = 21%

Question 3

How is concentration of a gas in solution determined?

Answer 3

Henry’s Law
[gas] = partial pressure x solubility coefficient

Each gas has individual coefficient (e.g. CO2 ~ 20x more soluble than O2)

Solubility also dependent on factors e.g temperature

Question 4

What are the values of PaO₂, Hb saturation and O₂ content in arteriole and mixed blood?

Answer 4

PaO₂: 13.3kPa (100mmHg), 5.3kPa (40mmHg)

Hb sat: 97-98%, 75%

O₂ content: 200ml/l, 150ml/l

Question 5

What are the two forms that oxygen is carried in?

Answer 5

Dissolved in plasma: described by Henry’s law - directly related to PaO₂ (PaO₂ = arteriole partial pressure)

Bound to Hb: normal range =

female: 11.5-16.0g/100ml
male: 13.5-18.0g/100ml

Question 6

How much O₂ is consumed at rest? [O₂] dissolved in arteriole blood?

Answer 6

250ml/min

~ 3ml/l

Question 7

How does O₂ enter blood/reach tissues?

Answer 7

Diffuses from alveolar air (PO₂ ~13.3kPa) to blood (venous blood PO₂ = 5.3kPa)

Diffuses from arteriole blood (PO₂ ~13.3kPa) to interstitial fluid (PO₂ ~5.3kPa) to mitochondria (PO₂ ~ 0.1kPa)

Question 8

Outline the structure of haemoglobin

Answer 8

4 sub-units, each ~17kDa
each subunit = a haem group (porphyrn ring), a globin chain (peptide)

each subunit will bind 1 molecule of O₂
saturated Hb therefore will bind 4O₂

Question 9

How much oxygen does 1g Hb bind? If [Hb] = 15g/100ml - what is O₂ content?

Answer 9

1.36ml

15 x 1.36 = 24ml/100ml = 204ml/l

Question 10

Outline the types of globin chains in Hb

Answer 10

Adult haemoglobin (HbA)
2 alpha (141 amino acids), 2 beta (146 amino acids)

HbA₂ ~ 2% of adult Hb
2 alpha, 2 delta

Fetal haemoglobin (HbF) ~ 1% adult Hb
2 alpha, 2 gamma

Question 11

What is fetal Hb?

Answer 11

2a and 2 gamma chains
embryonic forms replaced by HbF from 13 weeks at gestation

At birth the majority of Hb is still HbF
HbA = 20%, HbF = 80%

Switch to adult forms occurs between 3-6 months old
HbF not fully replaced as approximately 1% of adult Hb

Question 12

What genetic defects can occur in globin chains?

Answer 12

Thalassaemias: defect in the synthesis of the globin chains

Sickle cell disease: defect in the structure of chains

Question 13

What is thalassaemia?

Answer 13

Inherited defects in globin chain synthesis
Either a or beta-thalassaemia
Leads to imbalance of chains - decreased erythropoiesis
Increased haemolysis of mature cells

Question 14

What is sickle cell disease?

Answer 14

Specific mutation in beta chain (A to T - valine for glutamine at codon 6)

Heterozygous (Hb AS) - sickle cell trait:
generally asymptomatic
anoxia manifests in stress e.g. air travel
confers protection against malaria

Homozygous (Hb SS) - sickle cell anaemia
symptoms vary from none to death
increased turnover of cells can cause severe haemolytic anaemia
severe pain (bone and spleen common) due to vaso-occlusive crises and infarction

Hb S decreased flexibility of cell - characteristic sickle shape
Sickling - shortened erythrocyte survival, impaired flow through the microcirculation