1.3 Hypoxia-Inducible factors

• What are hypoxia-inducible factors (HIFs)?

  DNA-binding transcription factors responding to low oxygen
• What is the primary role of HIFs in the body?

  To activate genes for oxygen delivery and metabolism
• In which species are HIFs found?

  All oxygen-breathing species
• What are some genes controlled by HIFs?

  • Vascular endothelial growth factor (angiogenesis)
  • Erythropoietin (red blood cell production)
  • Mitochondrial genes (energy utilization)
  • Glycolytic enzyme genes (anaerobic metabolism)
  • Genes increasing nitric oxide availability (pulmonary vasodilation)
• What does vascular endothelial growth factor stimulate?

  Angiogenesis
• What is the function of erythropoietin?

  Stimulates red blood cell production
• What role do mitochondrial genes play?

  Involved with energy utilization
• What do glycolytic enzyme genes facilitate?

  Anaerobic metabolism
• How do genes that increase nitric oxide availability affect the body?

  They cause pulmonary vasodilation
• What happens to HIF subunits in the presence of adequate oxygen?

  They are downregulated and inactivated
• What is the role of HIF hydroxylases in oxygen presence?

  They inactivate HIF subunits
• What occurs to HIF hydroxylases during hypoxia?

  They become inactive
• What is the result of inactive HIF hydroxylases in hypoxia?

  Formation of a transcriptionally active HIF complex
• How do HIFs function as a "master switch" in response to hypoxia?

  They allow appropriate gene activation for hypoxia
• At what altitudes do many native human beings in the Andes and Himalayas live?

  Above 13,000 feet
• What altitude does a group in the Peruvian Andes live and work at?

  They live at 17,500 feet and work at 19,000 feet
• How do the natives' acclimatization compare to lowlanders?

  Natives are superior in all aspects of acclimatization
• When does acclimatization begin for the natives?

  In infancy
• What changes occur in the chest and body size of high-altitude natives?

  Chest size increases, body size decreases
• How does the heart size of natives compare to lowlanders?

  Natives have larger hearts than lowlanders
• How is O2 delivery by blood to tissues in high-altitude natives?

  It is highly facilitated
• What is the arterial PO2 in high-altitude natives?

  40 mm Hg
• How does the quantity of O2 in arterial blood of high-altitude natives compare to lowlanders?

  It is greater than that in lowlanders
• What is the venous PO2 in high-altitude natives compared to lowlanders?

  15 mm Hg less than lowlanders
• What does the venous PO2 indicate about O2 transport in high-altitude natives?

  O2 transport to tissues is exceedingly effective
• What mental effect does hypoxia have on individuals at high altitudes?

  It causes mental depression
• How is work capacity affected by hypoxia?

  It is greatly decreased
• What is the relationship between work capacity and maximum rate of O2 uptake?

  Work capacity is reduced in proportion to O2 uptake
• What is the work capacity percentage of unacclimatized individuals at 17,000 feet?

  50%
• What is the work capacity percentage of acclimatized individuals after 2 months at 17,000 feet?

  68%
• What is the work capacity percentage of natives living at 13,200 feet but working at 17,000 feet?

  87%
• How does the daily work output of naturally acclimatized natives compare to lowlanders at sea level?

  It is almost equal
• Can well-acclimatized lowlanders achieve the same work output as natives at high altitude?

  No, they can almost never achieve this