1. High Altitude Illness
David Gonzales, MD

2. Medicine You Will Probably Never Use in Texas
Guadalupe Peak, 8,749 feet
Might as well be in New Mexico

3. Outline Challenges of High Altitude
Physiologic Response to Hypobaric Hypoxia
High Altitude Syndromes
Acute Mountain Sickness/ High Altitude Cerebral Edema
High Altitude Pulmonary Edema

4. Oxygen = Good
Amount of oxygen available to breathe is a function of the percentage of oxygen in the air and barometric pressure.
Earth’s atmosphere is 21% oxygen
Barometric pressure at sea level = 760 mm Hg
Pressure of inspired oxygen =149 mm Hg

5. Less oxygen = bad Denver = 5000 feet Santa Fe = 7000 feet
PiO2 = 124 mm Hg
Santa Fe = 7000 feet
PiO2 = 115 mm Hg
Highest human habitation = 18,000 ft.
PiO2 = 73 mm Hg
Mt. Everest = 29,528 ft
PiO2 = 42 mm Hg (about ¼ that of sea level)

6. Oxygen saturation does not decrease until PaO2 reaches approximately 60 torr
Corresponds to an altitude of 10,000 ft.

7. Physiologic Response to Hypoxia
Acclimatization
A gradual process (days to weeks) whereby individuals respond to hypoxia in order to adapt and increase performance
Rate varies among individuals
Mediated through sympathetic nervous system

8. Ventilatory Response
Carotid body senses decreased PaO2; signals medulla to increase ventilation
Respiratory alkalosis ensues, decreasing ventilation
Subsequent HCO3 diuresis occurs through the kidney and ventilation subsequently increases again
This process stabilizes after 4-7 days, provided altitude does not change
Plasma volume decreases as much as 12% over the 1st 24 hours

9. Cardiovascular Response
Heart rate increases, leading to a moderate rise in cardiac output
Pulmonary artery pressure increases secondary to hypoxic vasoconstriction
Cerebral blood flow increases
These last 2 adaptations may become pathologic (more on this later)

10. At moderate altitude, curve does not shift
Extreme altitude leads to severe alkalosis and a leftward shift
PCO2 may decrease to 10 torr
This left shift increases oxygen saturation and is believed to be advantageous at altitude.
Persons with variant Hemoglobin that has a left-shift curve had less tachycardia, dyspnea, and exercise tolerance di d not change when exposed to moderate altitude

11. Pathologic Syndromes Acute Mountain Sickness (AMS)
A headache + (any of the following)
Nausea/vomiting
Fatigue
Dizziness
Sleep disturbance
1st off, not a very specific diagnosis. We have all had these symptoms. Food poisoning, Saturday morning. For gosh’s sake just camping can do this. Hangover is easily excluded by history; dehydration may improve with fluid challenge where AMS will not.
-Headache is throbbing, bitemporal

15. Diagnosis Suspect in non-acclimatized persons above 8,200 feet
Rapid ascent
Mountain climbers going to extreme altitudes live by the mantra of climb high, sleep low.
Clues include history
dehydration should respond to fluids
hangover has obvious history
food poisoning may have diarrhea, an uncommon finding in
AMS
; a insensitive finding may be lack of increased urine output, indicating that normal diuresis is not occuring and acclimatization may not be occurring well.

16. AMS Pathophysiology
Not so much hypoxia, rather your body’s response to it
Lag time between onset of symptoms; acclimatization cures
AMS may occur at altitudes of 8,000 feet, well within a “normal” O2 saturation; studies attempting to correlate pulse oximetry with occurrence/severity of AMS have not shown anything; same group did find that increased HR did correlate with increased incidence of AMS

17. Pathophysiology of AMS
Low ventilatory response increases risk
Fluid retention
Evidence suggests vasogenic cerebral edema plays a central role, however cellular mechanisms not yet elucidated
Big brain, small skull
Persons with documented low HVR are more likely to develop AMS; those who have a high HVR seem to be protected. Experiments using chemical destruction of noradrenergic portions of the locus ceruleus in rats have located a specific portion that is responsible for increased ventilatory response to hypoxia (not used in normoxia)
As previously mentioned, lack of diuresis to altitude may predict AMS; premenstrual women in water-retention phase may also be at incr. Risk for AMS
Evidence for vasogenic edema:
steroid responsive- hypoxia is documented to increase amount of reactive oxygen species, endothelial-leukocyte interactions- dexamethatsone decreases these interactions (at least in rats)
cerebral capillary pressure is documented to rise
?loss of vascular autoregulation with increased BBB permeability- numerous molecular signaling factors (NO, VEGF, cytokines)
It has been suggested that persons with smaller CSF capacity may not be as able to tolerate changes in brain size that occur with ascent and that part of the pathology of AMS is anatomic

18. Treatment of AMS Prevention is best treatment Acetazolamide (Diamox)
Avoid abrupt ascent to sleeping altitudes >10,000 feet
Don’t increase sleeping altitude by more than 2000 ft. per night
Climb high, sleep low philosophy
Acetazolamide (Diamox)
125 to 250 mg po bid
Carbonic anhydrase inhibitor
Diuresis
Metabolic acidosis  increased breathing
Decreases CSF production
Meta analysis for prophylaxis- data quality was fair; average trial size had 15 participants; prophylaxis best if rate of ascent is >500 meters a day (about 1,600 feet); otherwise, don’t bother as side effects of increased urination and occasional paresthesias likely outweigh potential benefits

19. Treatment of AMS Supportive analgesics, antiemetics Minimize exertion
Diamox to hasten acclimatization
Minimize exertion
Low flow oxygen if available
Consider dexamethasone
Failure of symptoms to improve with treatment or progression of symptoms despite 24 hours of acclimatization is an indication to descend.

20. High Altitude Cerebral Edema (HACE)
A progression of AMS to a severe, life-threatening condition
AMS +
Ataxia
Altered consciousness
Severe lassitude
Cerebral edema is cytotoxic rather than vasogenic
Other clinical signs include cyanosis, retinal hemmorhages, and exaggerated hypoxemia on ABG or pulse ox. Focal neurologic deficits may occur
As vasogenic edema increases, distance between capillaries and cells increases, leading to ischemia

21. High Altitude Cerebral Edema (HACE)
Cellular swelling thought to be caused in part by NMDA-receptor mediated calcium influx.
Trial using magnesium infusion (an NMDA blocker) were clinically unsuccessful in treating AMS; prophylaxis with Mg citrate only caused diarrhea

22. Treatment of HACE Early recognition is key Oxygen 2-4 liters
Dexamethasone
Immediate Descent
Dex may decrease the amount of inflammation occurring (rat model)

23. Gamow Bag
An impermeable bag that can be inflated to simulate a lower altitude
Patient placed inside but reassessed periodically
HAPE = 2 to 4 hours of treatment
HACE = 4 to 6 hours of treatment

24. Gamow Bag
2 psi equals a drop of about 1500 feet. Few hours can help feel better. Access to patient may be difficult

25. Portable Altitude Chamber
Zipper placement makes it easier to use than Gamow
Low, low price of $1,200
Recent case report/ abstract detailing use of specially-designed CPAP machine in a climber who developed HAPE. Detailed success, but report was at a relatively low altitude (about 10,000 feet)

26. High Altitude Pulmonary Edema (HAPE)
Most common cause of high-altitude related death
Easily treated/prevented with prompt recognition
<1 in 10,000 in Colorado skiers
1 in 50 in climbers on Mt. McKinley
Risk factors include individual susceptibility, rapid ascent, exertion, altitude reached
In previous days, many reports of people dropping ill with pneumonia-likely HAPE
Prototypical victim is fit, young man who does too much too soon.

27. Manifestations of HAPE
Decreased exercise performance
Dyspnea at rest; often occurs during sleep
AMS (50%)
Dry cough
Cyanosis
RLL crackles
Pink, frothy sputum (late sign)

28. Manifestations of HAPE
Temperature >38.5
Ulcers on tongue
Sinus tachycardia
Other signs of acute pulmonary hypertension
RBBB
RAD
RVH voltage
Ulcers painless, don’t bleed; related to severity and rapidly disappear with O2 administration

29. Manifestations of HAPE
Respiratory Alkalosis
Severe hypoxemia
Fluffy infiltrates
Autopsy consistent with noncardiogenic pulmonary edema
Acid base picture may be mixed because lots of subjects are on Diamox prophylaxis
Mean P02 in 1 study was 28 torr with a mean O2 sat of 56%
Classically, infiltrates are peripheral; not usual CHF (no cardiomegaly, no Kerley B lines (indicates venous prominence; note the prominent pulmonary artery; worse cases usually have worse x-rays
Autopsy findings include bloody, foamy fluid in lungs that are 2-4x normal weight, hyaline membranes, inflammation. Pulmonary artery and R atrium are often distended, but pulmonary veins and L-side of heart are normal
BAL fluid shows protein content equal to that of serum in addition to

30. Pathophysiology of HAPE
Pulmonary Hypertension-A fact of life at high altitude
Global hypoxic pulmonary vasoconstrictor response
When is it pathologic?
Increased Capillary Permeability
Shear forces vs. endothelial dysfunction
Decreased HVR
Role in nighttime hypoxia
Gene mapping correlates a polymorphism in the ACE pathway with increased high altitude pulmonary hypertension but study did not correlate with development of HAPE
Further hypothesis is that HPVR is actually uneven and that those sections that are relatively dilated are subject to increased pressure, flow, and edema- suggested by patchiness seen in CXRs; typically, however, hydrostatic edema tends to be low-protein
Persons susceptible to HAPE produce less NO during hypoxia; gene mapping has shown some polymorphisms of the NOS gene and its pathway to be associated with HAPE; seems like endothelial dysfunction is going to be crucial, but exact mechanisms have not yet been elucidated
Similar to AMS, those with low HVR are more susceptible to HAPE while those with brisk HVR are somewhat protected. Thought that low HVR may permit extreme hypoxia at sleep (people rely more on O2 to drive as pC02 is depressed secondary to acidosis Cheyne-Stokes)

31. Treatment of HAPE Early recognition should lead to evacuation/descent
This will limit severity and hasten recovery
O2 if available; Gamow bag
Vasodilators as adjuncts
Nifedipine
Salmeterol
Ounce of prevention

32. Summary Altitude acclimatization is a highly individualized process
Mild AMS is best treated supportively
HACE and HAPE require more aggressive treatment
Common sense and adequate preparation go a long way