Module 6.4: Physiology of Respiration @ High Altitudes

As altitude increases

The barometric pressure falls exponentially

-Barometric pressure drops by ½ for every 5,000 m or 18,000 ft of ascent

Left y axis shows

Barometric pressure

Right y axis shows

Partial pressure of O2

the Fraction of air is made up by

A gas that does NOT change

Fraction for O2

0.21 no matter where you’re on Earth

Ex: Hong Kong @ sea lvl

Barometric pressure is 760 mmHg

PO2 is 160 mmHg

Ex: Summit of Mount Everest

Barometric pressure is 255mmHg

PO2 is 44 mmHg

must subtract partial pressure of water vapor from

barometric pressure before applying fraction

Inspire air is warmed & humidified &

@ 37C: the saturated water vapor pressure in the lungs is 47 mmHg regardless of altitude

Pressurized cabins in passenger planes

Maintain an ambient pressure equivalent to 1,800 m of altitude in cross continental flights or 2,400 m of altitude in transoceanic flights

Most don’t need supplemental oxygen in the inspired air @ Denver or other ski resorts SO

Most passengers are NOT bothered by the slight reduction in arterial oxygen saturation that’s associated w/ these cabin pressures

-89% @ 3,000m

Passengers w/ COPD

May need to carry supplemental oxygen on a plane even if they don’t require it @ sea level

The drop in barometric pressure affects blood gas levels as altitude increases

Partial pressure drops

In proportion to the decrease in barometric pressure

-Occurs whether a person is breathing in the air or whether they’re breathing pure oxygen

Benefit of utilizing oxygen @ very high altitudes as an aviator would

Is that near a normal partial pressure of O2 can still be achieved @ 30, 000 feet above seal level

Most notable is the difference in arterial oxygen saturation levels

Which is a measure of oxygen carried by hemoglobin

If saturation values vs altitude were graphed

We see just how much of a difference it makes @ altitudes that are typical of airline travel

Whistler Blackcomb @ 5,000 ft above seal level

Altitude related sickness in healthy individuals is very rare

Machu Picchu (Peru) @8,009 ft above seal level

Travelers may experience altitude related illness depending on the rate of ascent & how high they climb

Altitude sickness normally starts @

~8,000 ft above seal lvl

Highest peak in Africa @ over 19,000 ft

-barometric pressure is less than ½ @ sea level

Extreme altitude: Peak of Mt. Everest

Which height the barometric pressure is around 1/3 that @ sea level

How would you feel after recent altitude gain to more than 8,000 ft above sea level?

-feels like a bad hangover: vomiting, weakness, dizziness, fatigue & trouble sleeping

Acute mountain sickness

If severe: can cause acute cerebral or pulmonary edema

Chronic mountain sickness

Results from the body’s adaptation to the change in elevation

-Some changes include:

-increase in Red blood cell mass

-increase in pulmonary arterial pressure

-enlargement of the right heart

CO2 levels in the blood

Is a major stimulus for controlling breathing

@ high altitudes: the drop in O2 is due to the fact that

The barometric pressure is lower than we’re accustomed to rather than due to an increase in O2 consumption from metabolism

-Would prod. Elevated CO2 in the blood

@ high altitudes: you can have a low arterial PO2

W/out a corresponding rise in arterial PCO2

Peripheral chemoreceptors

Do respond directly to a drop in oxygen

-Activation of this mech. is very important when the oxygen supply is inadequate BUT there hasn’t been an increase in CO2 production as would occur @ high altitude in an unpressurized cabin in a aircraft

Some folks that live in high altitudes (in the Andes)

Have enlarged carotid bodies as a consequence of low oxygen tension over a long term

Peripheral chemoreceptors mainly sense

A decrease in arterial PO2 levels once they drop below 60 mmHg as w/ exposure to high altitude or in diseased states

Ventilatory response to such a decrease in arterial oxygen

Is hyperventilation

-Result: In a decrease in arterial CO2 & increase in arterial O2

Conditions of hypoxia

Trigger the carotid bodies to initiate the hypoxic ventilatory response

Hypoxia in the body causes

A reflexive change in the breathing rate

There’s 4 results in response to hypoxia causing a reflexive change in the breathing rate (Hypoxic ventilatory response)

1: A 2- to 3-fold increase in the diffusing capacity (DL) occurs due to a rise in the blood

2:

Hypoxic ventilatory response 1 results in

A 2- to 3-fold increase in the diffusing capacity (DL) occurs due to a rise in the blood volume of the pulmonary capillaries

Hypoxic ventilatory response (2- to 3-fold increase in diffusing capacity) results in an increase in the pulmonary arterial pressure CAUSES

An increase in perfusion to well ventilated apex regions in the lungs

Hypoxia also promotes

The expression of oxidative enzymes in the mitochondria

-Enhances the tissues’ ability to extract O2 from the blood

Elevated ventilation rates

increase alveolar O2 & decrease CO2 in the lungs & blood which causes blood pH to rise

To compensate for these changes that were initiated by a ventilation change

The kidney increases the excretion of bicarbonate to remove excess base from the bloodstream

Sometimes: climbers take acetazolamide

A carbonic anhydrase inhibitor in the kidney that allows the kidney to get rid of extra bicarbonate

acetazolamide

Prevents the formation of protons so that the Na+ proton exchange in the rebake tubule is prevented & Na+ is then excreted along w/ bicarbonate in the urine

By preventing proton formation

acetazolamide Prevents the formation of additional bicarbonate as well

Overall: acetazolamide functions as

A diuretic that alkalinizes the urine as it removes base from the blood to bring the pH back to balance

Hypoxic condition affect

vascular system too

Erythropoietin production

Stimulated by renal hypoxia & norepinephrine

-Increases RBC & hemoglobin production to enhance the O2 carrying capacity of the blood

Byproduct of an Increase in RBC & hemoglobin production to enhance the O2 carrying capacity of the blood is

An increase in the hematocrit & blood viscosity due to reduced plasma volume

Hypoxic conditions in the vascular system STIMULATES

Hypoxia-inducible factor-1 alpha

Hypoxia-inducible factor-1 alpha

A transcription factor that activates genes involved in erythropoiesis, angiogenesis & other processes

Tissue angiogenesis occurs

w/in days of exposure to hypoxic conditions & is triggered by growth factors that’s released by hypoxic tissues like vascular endothelial growth factor, fibroblast growth factor & angiogenin

growth factors that’s released by hypoxic tissues like vascular endothelial growth factor, fibroblast growth factor & angiogenin results in

A dramatic increase in tissue vascularity caused by hypoxia

Chart shows

Various timing of the physiological changes in response to low O2 levels in the high altitude atmosphere

Left shows

The immediate response

Middle shows

Changes that would occur w/in a few days

-Includes the effects of changes to gene expression upon exposure to hypoxic conditions

Right shows

Long term change from sea level to high altitudes results in acclimatization of the body

Moving from an initial increase in ventilation rate & lower than normal hemoglobin saturation TO THE

Increased production of erythropoietin & increased vascularization of tissues to enhance O2 delivery

Major ways that the body acclimatizes to high altitudes

-Increased ventilation

-Due to decreased PO2

-Increase slowed by decreased PCO2

-Increased hematocrit (content)

-Increased diffusing capacity

-Increases capillary

Diffusing capacity increases in Acclimatization BC

The increased ventilation & therefore lung volumes cause an increase in the surface area for O2 diffusion to occur across the alveolar membrane in accordance w/ Fick’s law

Increase in RBCs & capillary density work

To enhance O2 delivery to the tissues

Decreasing PO2

Stimulates ventilation as a means of increasing arterial PO2

Increase in ventilation rate cause

increase in expiration of CO2

-Decreases arterial PCO2

Increase in ventilation rate & decrease in PO2 causes a conflict BC

In the body’s attempt to obtain O2, blowing off CO2 causes the blood pH to increase becoming alkaline

-This is why the kidney’s excretion of bicarbonate is an important adaptation to high altitudes

A drop in PO2 is sensed only by

Peripheral chemoreceptors

Symptoms of acute mountain sickness

-Fatigue

-Nausea

-Headache

Decrease in barometric pressure @ high altitudes leads to proportional decrease in PO2 & thus smaller O2 gradient across the blood-gas barrier can lead to hypoxemia

Both statements are true

A decrease in arterial PO2 @ high altitudes stimulates peripheral chemoreceptors

True

Review: increase in EPO & RBC production

Days to weeks

Review: increase in production of 2- 3- BPG in RBCs

Days

Review: respiratory alkalosis increases Hb affinity for O2

Immediate

Review: peripheral chemoreceptors respond to drop in PO2

Immediate