Altitude

Question 1

Naejji et al (2010)

Answer 1

Sitaxsentan (endothelia antagonist) reduces pulmonary artery pressure at altitude and reduces the decrease in VO2 max.

Question 2

Cohen and Small (1998)

Answer 2

Colonisation of high altitude of humans is late and limited - implications in evolutionary adaption to altitude

Question 3

Schuler et al (2010)

Answer 3

Mouse study - showed that optimal haematocrit is higher than the physiological level. Gives capacity for increase with altitude, training etc

Question 4

M.P. Fitzgerald (1914)

Answer 4

Pikes peak expedition, haematocrit increases with altitude

Question 5

Hall (1937)

Answer 5

High altitude mammals such as the Llama do not have increased haematocrit compared to low land mammals

Question 6

Beall et al (1998)

Answer 6

Tibetans don’t have increased haematocrit compared to low landers

Question 7

Beall et al (2010)

Answer 7

GWAS study: shows that low haemoglobin level in Tibetans arises from HIF-2 genetic locus

Question 8

Smith, Talbot et al (2009)

Answer 8

Cerro de Pasco, Peru. Participants taken to high altitude from Lima. Intravenous iron infusion reduced the increase in pulmonary artery pressure with altitude.
Iron is involved in HIF degradation pathway -> increased iron = reduced HIF levels.

Question 9

Hodson et al (2016) 2 points

Answer 9

• HIF-2 inactivation, not HIF-1, inhibits ventilatory acclimation to altitude
• Phd inactivation increases the ventilatory response to hypoxia

Question 10

Chuvash Polychythemia response to hypoxia

Answer 10

Increased ventilatory, HPV and increase in haematocrit response to hypoxia.
This occurs due to VHL mutation which is involved in HIF degradation and thus there is increased HIF signalling.

Question 11

Kellenberg et al (2008)

Answer 11

Used MRI imaging to show that microbleeds occur in HACE.

Question 12

Grunig et al (1997)

Answer 12

Measured hypoxic pulmonary vasoconstriction (HPV) response in individuals susceptible to HAPE and those not susceptible to HAPE. Individuals that are susceptible to HAPE have a stronger HPV response to hypoxia.

Question 13

Luks et al (2017)

Answer 13

Used CT scans to show characteristic patchy pulmonary oedema in HAPE,

Question 14

West et al (1992)

Answer 14

Stress failure of capillaries in HAPE. Measured by the detection of the presence of albumin in alveoli.

Question 15

Sartori et al (1999)

Answer 15

Endothelin upregulated in HAPE susceptible climbers

Question 16

Sartori et al (2002)

Answer 16

B2 agonists improve HAPE, possibly by stimulating alveolar fluid clearance