Lecture 31

Question 1

What are some changes that may reduce O2 demand or increase O2 delivery in high altitudes

Answer 1

• Respiratory changes (increased lung volumes, increased alveolar ventilation rates)
• Cardiovascular changes (Increased cardiac output)
• Increased Hb-O2 affinity
• Decrease in average muscle fiber diameter (short diffusion distance between blood capillaries and muscle fiber mitochondria)
• Increase in the concentration of myoglobin in muscle cells (facilitates diffusion of O2 into them)
• Suppression of metabolism in some tissues (reducing O2 demand)
• Switch towards greater use of glucose as a metabolic fuel which increased the ATP yield per O2 molecule.

Question 2

What physiological adaptations do people from highland Tibetan populations have to hypoxia (compared to native lowlanders?)

Answer 2

• Adaptations that increase alveolar ventilation, which maximizes O2 supply
  (Increased chest circumference and vital capacities- deeper breaths and more surface area for diffusion)
  (High resting breathing rate)
• Adaptations that minimize O2 demand by tissues: higher glucose uptake and use as metabolic fuel by cardiac and skeletal muscles
• Adaptations that prevent harmful(?) chronic responses to hypoxia: Do not display increased hematocrit and do not display pulmonary hypertension at altitude (some people living at higher altitudes do- but not all)

Question 3

Why can it be harmful to display increased hematocrit?

Answer 3

IF there is an increase in hematocrit, there is more viscous blood, which leads to a higher TPR
- increases in BP and it is harder to pump more viscous blood in the circulatory system

Question 4

What does the HIF pathway do?

Answer 4

Regulates hematocrit
- When there is low Oxygen, there HIF increases and the bone marrow will make more red blood cells.
- Negative feedback, more red blood cells present= HIF decreases.

Question 5

Compare the EPAS1 Function in Tibetan people and lowlanders

Answer 5

For Tibetan ancestry, the HIF pathway is turned off (regulated by the EPAS1 gene) Theres a mutation that even in low oxygen environments, there no significant increase in hematocrit

The normal function is that during low O2 environments, the EPAS1 gene is up-regulated, produces a EPAS1 protein that regulates downstream genes, leading to an increase in hematocrit.

Question 6

How could less activity of HIF pathways be adaptive for Tibetans, given the low PO2 of the Tibetan Plateau?

Answer 6

Usually, the blood problem causing low O2 is anemia/hemorrhage. An increase in hematocrit usually helps restore hematocrit.
The Low air PO2 is an environmental cause leading to an elevation of hematocrit that could have other chronic physiological problems.

Question 7

How do our racial categories actually map onto biological (eg genetic) diversity?

Answer 7

Only 0.01% of human DNA sites are variable
- races are not biological populations

Question 8

How is that small amount of genetic variation distributed among humans?

Answer 8

• we are ancestrally african and began migrating from there
• The variation that exists generally appears to be adaptation to local environmental conditions (temperature, light regime, available diet)

Question 9

Explain skin pigment physiology (clinical adaptation to light environment)

Answer 9

People living closer to the equator have darker skin and people who live further away have lighter skin

Question 10

If UV exposure is dangerous, why do any humans have light skin

Answer 10

• Minimal UV radiation is needed for vitamin D, but too much can degrade folate (TRADE OFF)
• People who live in low UV environments have lighter skin so they can synthesis vitamin D and also they don’t have to worry about folate degradation
• People who live closer to the equator have darker skin so that they can block off the UV radiation and also synthesize vitamin D