BIOL 4010 Lecture Notes - Lecture 15: Heart Failure, Tibetan Plateau, Effects Of High Altitude On Humans
2 May 2018
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Adaptations to High Altitude
High Altitude:
• Major change is the partial pressure of oxygen decreases
o "death zone" - not enough oxygen for body functioning
• Birds are able to migrate over death zone due to physiologic adaptations
• *see slide
• High elevation areas are located across continents
o Tibetan plateau, Andes mountains … etc.
o Can we find evidence for convergent evolution in animals living at high elevations on
different continents?
• Acute Consequences:
o Acute sickness/ acute mountain sickness (AMS)
• Pathological effect of high altitude on humans
• Caused by acute exposure to low partial pressure of oxygen
▪ Not sufficiently acclimated
▪ Commonly occurs above 2,400m
▪ Multiple non-specific symptoms resembling the flu or carbon monoxide
poisoning
▪ Headache, poor appetite, nausea, vomiting, weak, fatigue, dizziness, problem
sleeping
• Can lead to disorientation and unconsciousness
o High-altitude cerebral edema (HACE)
• Brain swells with fluid
• Fluid penetrates blood brain barrier
• Occurs in <1% of people who ascend to 4,000m
▪ Disorientation, lethargy, nausea
• Hypoxia causes:
▪ Increase in extracellular fluid --> increased vascular pressure
▪ Inflammation of vasogenic endothelium --> leakiness
▪ Increased permeability of microvasculature
o High-altitude pulmonary edema (HAPE)
• Life-threatening form of pulmonary edema (fluid accumulation in the lungs)
• Can occur in healthy mountaineers at altitudes above 2,400m
• Difficulty in breathing at rest, cough, weakness, chest tightness or congestion
• Occurs in <1% of people who ascend to 4,000m
• Hypobaric hypoxia at high altitude is the issue
o Human settlements at high altitude:
• La Rinconada is a town of 30,000 in Southern Peru at an altitude of 5,100m
• Tibetans living at 4000m for at least 25,000 years
• Aymara in Andean…
o *note: many genes in human populations living at high altitudes are different
• Also many common genes
• --> convergent evolution? Or adapting in unique ways to these environments
Physiological Adaptations to High Altitude in Humans
• Accommodation responses (acute):
o Increased ventilation, increased heart rates and vasodilation
• --> decreased blood PCO2 --> increased blood pH (alkaladosis)
▪ --> reduced breathing rate (hypoxia)\
• Acclimatization responses (over several weeks):
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o An imbalance of normal blood oxygen levels (reduced) --> kidney (and liver to a smaller
extent) releases erythropoietin
o Erythropoietin stimulates red bone marrow
o Enhanced erythropoiesis increases rbc count
• --> increases O2-carrying ability of blood
• Long term adaptations:
o Total blood volume and proportion of rbcs increase
• Enables an increase in oxygen delivery
o Changes also in…
• Heart rate (acute)
• Hyperventilation (acute)
• CO2 ventilatory response
• Haemoglobin concentration
• Capillary density
• Hypoxic ventilatory response (over life)
• Pulmonary hypoxic pressure response (over generations)
*see slide
• Costs of Adaptation:
o Chronic mountain sickness (CMS)
• Chronically high hematocrit (% of blood volume occupied by erythrocytes)
• Can develop after many years of living at high altitude
• Symptoms:
▪ "thick" blood
▪ Increase in blood clots
▪ Pulmonary hypertension leads to right ventricular hypertrophy
▪ Congestive heart failure
• Prevalence:
▪ In China:
• Tibetans: 1.21%
• Ham immigrants (~400 years): 5.6%
• *duration of existence may be associated with risk
▪ In Andes:
• In men 30-39years: 15.4%
• In men 50+ : 33%
• *age may be associated with risk of CMS
• Divergent Adaptation?
o Does differences in the degree of adaptation to high altitude reflect differences in length of
time that different populations have lived at high altitude?
• Hemoglobin concentration is greater in those living at high-altitudes for longer periods
of time ????
o What does the great degree of variation among Andean people suggest?
• Females in Andes have a far greater range of hemoglobin concentrations (compared to
male Andes and females at sea level)
• Tibetans (lived at 4000m for at least 25,000 years)
o Possible physiological mechanisms:
• Role of Nitric Oxide:
▪ NO is released from the nerve endings
▪ It switches on enzyme (guanylate cyclase) which makes cGMP
• cGMP triggers smooth muscle in the artery wall to relax so the blood
vessel dilates
▪ Tibetans have:
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
High altitude: major change is the partial pressure of oxygen decreases. Increase in extracellular fluid --> increased vascular pressure. Or adapting in unique ways to these environments. Physiological adaptations to high altitude in humans: accommodation responses (acute): -> decreased blood pco2 --> increased blood ph (alkaladosis: acclimatization responses (over several weeks): -> reduced breathing rate (hypoxia): an imbalance of normal blood oxygen levels (reduced) --> kidney (and liver to a smaller extent) releases erythropoietin, erythropoietin stimulates red bone marrow, enhanced erythropoiesis increases rbc count. *see slide: chronic mountain sickness (cms, chronically high hematocrit (% of blood volume occupied by erythrocytes, can develop after many years of living at high altitude, symptoms: Increase in blood clots: pulmonary hypertension leads to right ventricular hypertrophy, congestive heart failure, prevalence: In china: tibetans: 1. 21, ham immigrants (~400 years): 5. 6, *duration of existence may be associated with risk.
