What is hypobaric hypoxia?
Hypoxia associated with low pressures
What is acclimatisation?
Short term changes in response to changes in the environment
e.g. Hyperventilation
What is adaptation?
Long term change or modification to organism
- To become better suited to the environment
- Occurs over time
What is high altitude deterioration?
- Negative characteristics associated with high altitude
- Muscles wasting, Lethargy, Lower BP
What are 5 acclimation characteristics to high altitude?
- Heart rate change
- Hyperventilation
- CO2 response (Cheyne-stokes breathing)
- Increased in RBC
- Increase in capillary density
What changes occur in response to hyperventilation at high altitude?
- Detection of low CO2 in the CSF by chemoreceptors in the carotid body
- Reduction in ventilation to increase CO2 conc
- Cheyne-stokes breathing, intermittent breathing
How are the numbers of RBC increased?
- Erythropoietin release from the kidney
- Acts on bone marrow
- Increase in RBC production
How can capillary density be increased?
- Increase in angiogenesis
- Decrease in muscle fibres
What is the alveolar gas equation?
Arterial O2 = Inspired O2 - Arterial CO2 (fraction +(1-fraction O2)/RQ)
What are the key components of the alveolar gas equation that change in response to high altitude?
Inspired O2 levels drop
- would generate -ve arterial O2
HOWEVER
Hyperventilation causes a drop in arterial CO2
- generating an arterial O2 of around 30mmHg
What changes occur to arterial O2 at high altitude and why? How does the body respond to maintain sufficient levels?
Decrease in arterial O2
- Reduced partial pressures of oxygen in the air
- Leads to lower Hb saturation
Response
- Increase in RBC
- Hyperventilation
- Vasoconstriction
What changes occur to VO2 max at high altitude? And what are the limiting factors?
Max consumption of O2 decreases
- Cardiovascular = max heart rate begins to decline
- Diffusion rate = Requires pressure gradient and the gradient is no longer as steep. As seen in Wagner’s graph of venous PO2 against O2 uptake
- Efficiency of oxygen transport e.g Hb saturation and conc
What changes to mitochondria occur at high altitude?
- Reduction of 15% of the volume
- Non-uniform reduction, greater at the sarcolemma
- Mitochondria become smaller and more fragmented
- Potentially due to a build up of lipofuscin
- Greater ROS production
What controls HIF-1α?
Hypoxia Inducible Factors 1α
- Always present, however degraded in normoxia
- Degradation by hydroxylation
What are the effects of HIF-1α?
- Regulates EPO (production of RBC)
- VEGF, capillary formation
- PG1α promotes mitochondria biogenesis
- Bnip3 promotes mitochondria degradation (proapoptotic found in rats Regula et al., 2012)
What genetic factors suggest that certain low altitude dwellers are more adapted for high altitude?
ACE allele
I (insertion) allele
- Homozygous leads to better endurance adaptation
- Potentially due to suppressed levels of ACE which leads to lower blood pressure
DD = present in strength athletes
Compare and contrast adaptations in the Sherpa and Andean populations
(3 diff)
Similarities
- Increase NOS and so NO production
Differences
- Sherpa decrease [Hb], Andean increased
- Sherpa lower mitochondria vol
- Sherpa higher resting ventilation
What 4 advantageous genes have been naturally selected by Tibetans and in some cases Andean populations?
EPAS1
- Encodes HIF-1α
NOS1/2
- Increase NO
VEGFA and VEGFC
- Increased capillary density
PPARA
- reduced fatty acid β-oxidation
- decrease in UCP3 (Levett et al., 2012)
How has the Andean population adapted to overcome challenges associated with pregnancy at high altitude?
- Increased blood flow to the placenta
- Greater protection against oxidative stress
- Greater Hb content
What are the causes and cure for cerebral and pulmonary oedema caused by high altitude?
Cerebral - inability to remove fluid due to changes in drainage
Pulmonary - vasoconstriction due to hypoxia, causes hypertension greater release of fluid
CURE: Dexamethasone and descending
What is an example of chronic sickness due to high altitude and what are the causes?
Monge’s disease
- Present in Andean population
- Caused by an increased haematocrit, which increases viscosity of blood
- Develops with age
What are examples of different high altitude training regimes and their effectiveness?
High and High (LHTH)
- However detraining can occur as fatigue is reached and VO2 max is decreased
Low live and high train (LLTH)
- No real benefit
High live and Low train (LHTL)
- Some benefit due to erythropoiesis over night
Where is temperature sensed?
At nerve endings that have Transient Receptor Potential (TRP)
- which are cations that are sensitive to temp, allow movement of Na and Ca
Where is the control point for temperature?
Preoptic and anterior hypothalamus (PO/AH)
= Sympathetic -> NA -> Vasoconstriction
= Somatic motor -> Shivering
= PVN, pituitary -> TSH
