The reduced rate of oxygen diffusion from air to blood in the alveoli that accompanies decreasing barometric pressure triggers a range of physiological responses.  These mechanisms attempt to offset the reduced oxygen supply by increasing the efficiency of oxygen delivery and use to body tissues at every step of the process.  As a result physiological changes occur in ventilation within the lungs, oxygen diffusion from air to blood in the lungs, oxygen transport in the blood, oxygen diffusion from blood to tissues, and the use of oxygen in tissues.

To understand the effects of high altitude on human physiology, it is best to examine how the body adjusts to hypobaric conditions.

Early Physiological Adaptations to High Altitude

Increased Respiratory Rate The relative scarcity of oxygen causes increased ventilation (both in tidal volume and frequency).  With hyperventilation, the excessive loss of carbon dioxide from the blood raises its pH (toward alkaline) which, in turn, reduces stimulation of respiratory center causing a decrease in ventilation and oxygen absorption.  This positive feedback loop results in cycles of increased and decreased respiration.  During acclimatization, the kidney excretes bicarbonate into the urine which is later reabsorbed in the blood to maintain normal pH at the lower partial pressure of carbon dioxide (24-48 hrs after onset of hyperventilation).

courtesy of Dr. J. Bindon, University of Alabama

Increased Heart Rate As the heart rate increases, oxygen is transported from the alveoli through the circulatiory system to tissues at a faster rate.

Fluid Shifts Lower barometric pressure causes capillaries in the brain, lungs, and extremities to constrict.  The higher volume and rate of blood flow to the brain raises pressure in capillaries causing them to leak (cerebral edema).  In the lungs, the increasing capillary resistance to blood flow combined with a higher rate of circulation raises pulmonary blood pressure which may cause fluid to escape from capillaries and leak into lungs (pulmonary edema).

Advanced Adaptations to Altitude

Increased Red Blood Cell Production
Continuous oxygen deprivation eventually causes the body to increase red blood cell production (from 5 million/cm3 at sea-level to 8 million/cm3 at 4000 m).

Change in Oxygen Affinity of Blood
At altitude, humans experience a slight decrease in the oxygen affinity of blood which facilitates gas delivery to tissues at the expense of uptake in the lung.  Additionally, higher levels of the 2, 3 Diphosphoglycerate (DPG) are found in humans at altitude.  DPG is an organic phosphate that lowers the oxygen affinity of red blood cells.  Finally, the rate of diffusion increases as levels of myoglobin, the oxygen carrying protein in red blood cells, in the blood rise.

courtesy of Dr. J. Bindon, University of Alabama

courtesy of Dr. J. Bindon, University of Alabama

Increased Number of Capillaries
New capillaries facilitate diffusion by decreasing the diffusion pathway (distance) required for oxygen to reach cells.