Altitude Physiology

Question 1

Altitude sickness

Answer 1

Occurs above 3,000m, 8-48 hours upon arrival causing light headnesses and lethargy before acclimatising after several days or developing pulmonary and cerebral oedema.

Question 2

What is the limit for altitude acclimatisation?

Answer 2

Above 5-6km which is the death zone.

Question 3

Cause of altitude sickness

Answer 3

Low pO2 causes hyperventilation dropping CO2 levels with a negative feedback on respiration causing cyclic increased and decreased ventilation.

Question 4

What happens upon altitude acclimatisation?

Answer 4

Hyperventilation to 5-7x normal in spite of lower pCO2.

Question 5

What does blowing off CO2 allow?

Answer 5

Higher lung pO2.

Question 6

Minimum survivable pO2 with hyperventilation

Answer 6

1/4 pO2 at sea level, or the peak of Mount Everest.

Question 7

Effect of high altitude on haemoglobin

Answer 7

ppO2 is lower than sea level so human haemoglobin is 80% saturated in artery blood so respond with increased erythropoietin secretion and RBC synthesis so total O2 carrying capacity of blood is restored.

Question 8

Issue with human response to high altitude

Answer 8

Causes issues with blood viscosity and doesn’t overcome issue of increasing oxygen availability to tissues.

Question 9

Two groups of high altitude humans

Answer 9

Tibetans/Nepalese sherpas and Andeans.

Question 10

Tibetans

Answer 10

Normal
haemoglobin/haematocrit with smaller diameter muscle fibres similar to Caucausian high-altitude climbers with greater capillary density and tortuous capillaries.

Question 11

Andeans

Answer 11

Larger lungs and hearts, smaller bodies and increased capillary density.

Question 12

Tibetan haemoglobin concentration

Answer 12

At 4km they have the same haemoglobin concentration as Americans at sea level.

Question 13

Tibetan birth weight

Answer 13

It is much higher than the neighbouring ethnic Han at 4km.

Question 14

Tibetan genetic changes

Answer 14

Altered EPAS-1 and EGLN1.

Question 15

EPAS1

Answer 15

Component of HIF-alpha.

Question 16

EGLN1

Answer 16

PHD enzyme involved in HIF-alpha turnover.

Question 17

HIF-alpha

Answer 17

A transcription factor induced by lower pO2 that regulates genes involved in erythropoiesis, iron homeostasis and vascular permeability.

Question 18

HIF-alpha at normal oxygen

Answer 18

It is hydroxylated by PHD causing ubiquitination and then degradation.

Question 19

HIF-alpha at hypoxia

Answer 19

It binds with HIF-Beta allowing it to enter nucleus and alter gene expression.

Question 20

Llama and Alpaca adaptations

Answer 20

Haemoglobin is 100% saturated at 0.08atm ppO2 maximising oxygen delivery to tissues but this alone is insufficient, also uses myoglobin.

Question 21

Bar headed geese adaptation of haemoglobin

Answer 21

They live and hatch young at Tibetan lakes at 4-6km and migrate over Himalayas with a 4 amino acid difference in haemoglobin compared to Greylag goose.

Question 22

Andean geese adaptation of haemoglobin

Answer 22

Live at 5-6km and have a 16 amino acid difference in haemoglobin compared to Greylag goose.

Question 23

What allows for haemoglobin adaptations?

Answer 23

It has a low and high O2 affinity forms with a shift from one to the other based on subunit rotation, maintained by VdW forces.

Question 24

What does a weaker VdW force allow?

Answer 24

Easier shift to high affinity form.

Question 25

Greylag amino acids

Answer 25

Alpha119 is Proline and Beta55 is Leucine.

Question 26

Bar-headed amino acids

Answer 26

Alpha119 is Alanine and Beta55 is Leucine.

Question 27

Andean goose amino acids

Answer 27

Alpha119 is Proline and Beta55 is Serine.

Question 28

How did the geese reach similar effects of haemoglobin?

Answer 28

Convergent evolution.

Question 29

What stress are bar-headed geese under?

Answer 29

Transient hypoxic stress.

Question 30

What stress are Andean geese under?

Answer 30

Permanent hypoxic stress.

Question 31

Mammals that have adapted haemoglobin

Answer 31

Llamas, alpacas, guanaco and the vicuna.