Altitude Physiology Flashcards
Altitude sickness
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.
What is the limit for altitude acclimatisation?
Above 5-6km which is the death zone.
Cause of altitude sickness
Low pO2 causes hyperventilation dropping CO2 levels with a negative feedback on respiration causing cyclic increased and decreased ventilation.
What happens upon altitude acclimatisation?
Hyperventilation to 5-7x normal in spite of lower pCO2.
What does blowing off CO2 allow?
Higher lung pO2.
Minimum survivable pO2 with hyperventilation
1/4 pO2 at sea level, or the peak of Mount Everest.
Effect of high altitude on haemoglobin
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.
Issue with human response to high altitude
Causes issues with blood viscosity and doesn’t overcome issue of increasing oxygen availability to tissues.
Two groups of high altitude humans
Tibetans/Nepalese sherpas and Andeans.
Tibetans
Normal
haemoglobin/haematocrit with smaller diameter muscle fibres similar to Caucausian high-altitude climbers with greater capillary density and tortuous capillaries.
Andeans
Larger lungs and hearts, smaller bodies and increased capillary density.
Tibetan haemoglobin concentration
At 4km they have the same haemoglobin concentration as Americans at sea level.
Tibetan birth weight
It is much higher than the neighbouring ethnic Han at 4km.
Tibetan genetic changes
Altered EPAS-1 and EGLN1.
EPAS1
Component of HIF-alpha.
EGLN1
PHD enzyme involved in HIF-alpha turnover.
HIF-alpha
A transcription factor induced by lower pO2 that regulates genes involved in erythropoiesis, iron homeostasis and vascular permeability.
HIF-alpha at normal oxygen
It is hydroxylated by PHD causing ubiquitination and then degradation.
HIF-alpha at hypoxia
It binds with HIF-Beta allowing it to enter nucleus and alter gene expression.
Llama and Alpaca adaptations
Haemoglobin is 100% saturated at 0.08atm ppO2 maximising oxygen delivery to tissues but this alone is insufficient, also uses myoglobin.
Bar headed geese adaptation of haemoglobin
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.
Andean geese adaptation of haemoglobin
Live at 5-6km and have a 16 amino acid difference in haemoglobin compared to Greylag goose.
What allows for haemoglobin adaptations?
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.
What does a weaker VdW force allow?
Easier shift to high affinity form.
Greylag amino acids
Alpha119 is Proline and Beta55 is Leucine.
Bar-headed amino acids
Alpha119 is Alanine and Beta55 is Leucine.
Andean goose amino acids
Alpha119 is Proline and Beta55 is Serine.
How did the geese reach similar effects of haemoglobin?
Convergent evolution.
What stress are bar-headed geese under?
Transient hypoxic stress.
What stress are Andean geese under?
Permanent hypoxic stress.
Mammals that have adapted haemoglobin
Llamas, alpacas, guanaco and the vicuna.
