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High Altitude Physiology and Adaptation

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									 BIO338: Mammalian Physiology                                            L32: High Altitude Adapation                                               UNC-Asheville, s2011




   High Altitude Physiology and Adaptation                                                              ENVIRONMENTAL PHYSIOLOGY

                                                                                                                        Stressors
                                                                                                               Vary in duration and intensity

                                                                                                                                  Severe



                                                                                                             Acute                                  Chronic



                                                                                                                                   Mild

                               Village of Kibber, India (~15,000 ft)




Short-term          Physiological Responses to Stressors
                                                                                                            HIGH ALTITUDE Stressors
             Habituation
             • stress w/in tolerable limits, lose response to same stimulus
             Short-term physiological adjustments
             • quick responses (local, neural, endocrine)
             • response stops when stress removed or homeostasis achieved                                                          • Lower total atmospheric pressure
             Acclimatization                                                                                                       • Cold
             • long-term changes, including alteration of phenotype                                                                • Intense UV radiation
             • involves gene induction (hormone-mediated; bio-mechanical)                                                          • Difficult terrain
             • reversible; goes away once stress removed (time varies)                                                             • Limited vegetation
             Phenotypic Plasticity
             • long-term morphological and/or physiological changes
             • usually response to stresses during development
             • permanent – not lost when stress removed
             Genetic Adaptation
             • heritable genetic changes in a population (natural selection)
             • present regardless of stress or environment

Life-long




                                                                                                Effect of Altitude on Atmospheric Gas Concentrations

                                                                                               30,000 ft                                  P = 226    PO2 = 47     O2 Sat = 20%
                                                                                                           Highest elevation reached without extra O2 (natives)


                                                                                                           Death in unacclimated humans

                                                                                                20,000                                    P = 349     PO2 = 73    O2 Sat = 70%
                                                                                                           Highest Human Villages
                                                                                                           (unconsciousness in unacclimated humans)
        (highest Andean Villages)

     (highest Himalayan Villages)
                                                                                                10,000     Colorado ski resorts           P = 523    PO2 = 110    O2 Sat = 90%

            (Rocky Mtn ski resorts)                                                                        Mt. Mitchell

                     (Mt. Mitchell)
                                                                                                           Asheville
                        (Asheville)                                                           Sea Level                                   P = 760    PO2 = 158    O2 Sat = 98%




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BIO338: Mammalian Physiology                                        L32: High Altitude Adapation                                   UNC-Asheville, s2011




     Effect of Altitude on Alevolar Gas Concentrations                                       At high altitude, further relative decrease in % O2, N2
                                                                                                 (1) PH2O water is constant (body temp)
                        Ptotal   PN2      PO2     PCO2 PH2O                                      (2) CO2 is being constantly produced
        sea level        760     596      104      40      47                                800
                                 (75%) (14%)       (5%)   (6%)
                                                                                             700                       PN2
        20,000 ft        349     238       40      24      47
                                 (68%) (11%)       (7%)   (14%)                              600                       PH20
                                                                                                                       PCO2
                                                                                             500
                                                                                                                       PO2
  Less air (Ptotal) at high altitudes.                                                       400
  CO2 constantly produced by metabolism, stays high.                                         300
  Colder air holds less water (clouds).
                                                                                             200
  PH20 in alveoli depends on body temp, which is constant.
                                                                                             100
                                                                                               0
                                                                                                       Sea Level          20,000            50,000




               “Acute Mountain Sickness”                                                       Initial physiological responses to high altitude
                                                                                                           (short-term adjustments)
          • Headache; Malaise; Disturbed sleep
          • Loss of appetite; Nausea, vomiting                                                           Individual new to high altitude
          • Cyanosis
          • Peripheral edema                                                                       Primary Stressor?
             • Pulmonary edema (HAPE)                                                              • Hypoxia: low oxygen deliver to cells
             • Cerebral edema (HACE)                                                                     (due to low alveolar PO2)

                                                                                                   Detected through chemoreceptors (carotid body)

                                                                                                   Physiological adjustments?
                                                                                                   • increase ventilation (breathing rate & depth)
                                                                                                   • increase heart rate




                     Hyperventilation Cycle
                                                                                              ↑HR and ↑BP needed to provide constant O2 to brain
                                                                                                            (and other tissues)
                           hypoxia              chemoreceptor
                                                    reflex
                                                                                                       Can lead to pulmonary edema
                                                                                                            and cerebral edema
       ↑PCO2, ↓ pH                     ↑ ventilation and heart rate



Inhibits respiratory centers                 ↑blood PO2, but ↓PCO2
       and heart rate
                                                   = Higher pH
        (dizzy phase)

                      Respiratory Alkalosis
        High alkalinity (pH) prevents sustained hyperventilation.
   ∴ changing breathing patterns is not sufficient to meet O2 demands.




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BIO338: Mammalian Physiology                               L32: High Altitude Adapation                                    UNC-Asheville, s2011




               Acclimatization to high altitude                                                Acclimatization to high altitude

  Phenotypic and biochemical responses                                             ↑ 2,3 BPG (bisphosphoglycerate)
  Gene induction                                                                      Produced in RBCs to ↑ O2 delivery
                                                                                      has higher affinity for deoxygenated Hb;
                                                                                      helps unload O2 to tissues [shifts dissociation curve right]




               Acclimatization to high altitude
                                                                                      Aerobic athletes often train at high elevation to take
   • ↑ RBC, Hb production (↑ hematocrit)                                                   advantage of acclimatization responses.
         able to carry more O2
   • Capillary growth (capillarization)
   • ↑ myoglobin synthesis in muscle
   • heart will enlarge; ↑ lung capacity

   All reversible – effects will be lost within a few weeks after
   returning to low altitude




            Genetic Adaptations to high altitude                                            Genetic Adaptations to high altitude




                                                                                  Very difficult to sort from acclimatization
            Acclimatization                                                       • Heritability studies
            Developmental Acclimatization                                         • Comparative studies
              (phenotypic plasticity)
            Natural Selection                                                     3 populations that have lived at high altitude
              (genetic adaptation)                                                   Andes
                                                                                     Himalayas
            Genetic Drift
                                                                                     Ethiopian highlands




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BIO338: Mammalian Physiology                                 L32: High Altitude Adapation                               UNC-Asheville, s2011




                      Genetic Adaptations to high altitude:                                     Genetic Adaptations to high altitude:
                      Quechua (Andes)                                                           Tibetans (Himalaya)
                       Higher blood [Hb] = ↑ O2 saturation                                      • worse O2-saturation; normal Hb
                       Higher birth weight:                                                     • Larger lung capacity, larger hearts
                       ↑O2 delivery to placenta, ↑ placenta size                                (barrel chest)
                                                                                                • lower pulmonary BP
                       “hematological adaptations”                                                     better blood flow (NO release)
                                                                                                Higher birth weight
                                                                                                ↑ Blood flow to placenta
                                                                                                “respiratory adaptations”




     Ethiopian Highlanders                                                                    HIGH ALTITUDE Adaptations
      ???                                                                                   llama
      [neither respiratory or hematological adaptations                                             human
      have been documented]
                                                                                               Other
                                                                                               mammals




                                                                                   Llama – Hb has higher affinity for O2 than other mammals
                                                                                           Also large blood volume; lungs




Fetal circulation
                                                                                                         Fetal Hemoglobin
No working lungs; gets O2
from placenta
Pulmonary circuit by-passed:
• ductus arteriosus (arteries)
• foramen ovale (L-R atria)
Placenta is part of systemic
circuit for both mom and
fetus




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