This document summarizes several key physiological concepts related to high altitude physiology: 1. At high altitudes, the lower atmospheric pressure results in lower oxygen levels in the blood (hypoxemia). The body responds through acclimatization mechanisms like increased respiration and red blood cell production. 2. Initially, the low oxygen causes increased breathing while the loss of carbon dioxide inhibits breathing, creating an imbalance. Over time, the kidneys and bone marrow help restore balance. 3. If ascending too quickly, acute mountain sickness can occur from cerebral or pulmonary edema due to the body's inability to properly acclimate to the conditions. Proper acclimatization takes weeks to establish different compensatory mechanisms.

1. Physiology of high
altitude

2. Review cont.
 Plasma membranes
separates the inside of a
cell (in this case a neuron)
from the outside
 It contain proteins that act
as channels (gateways) for
certain ions
 The channels are small
 The channels only allow
specific ions to pass
through them

3. Resting membrane potential
 All cells have a negatively charged inside compared to their outside.
 How do cells maintain their resting membrane potential?
Outside
the cell
Inside
the cell
Lots of Na+ ions outside of cell
Lots of K+ ions inside of cell

4. Sodium-Potassium pump
 At rest Sodium-potassium
pumps function to
maintain the negative
internal environment of the
cell
 How?
 Sodium potassium pump
pumps out three Na+
ions for every two K+
ions it takes in
 Net negative charge
inside as compared to
the outside of the cell

5. Normal Pressures
 Normally atmospheric pressure or
pressure is about 760 mmHg
barometric
 Out of this, contribution of oxygen is 21% that is
pressure of oxygen is 160 mmHg (out of 760 mmHg)
 Alveolar PO2 is 104 mmHg
 As per diffusion, the PO2 should be same in
atmosphere and alveoli. Why it is not same?

6. Why??
 As oxygen coming down into the lungs
 It mixes with water vapor
 So you loose some oxygen in this process
 That’s why the PO2 of alveoli is lower than PO2
of atmosphere

7. What happens in high altitudes
 Pressure of oxygen in the atmosphere drops (less
than 160 mmHg)
 Imagine it becomes 130 mmHg
 PO2 of alveoli decreases significantly
 Imagine it may decrease to 60 mmHg or less
 What is the problem??

8. Recall Respiratory centers
1. Dorsal Respiratory Group
2. Ventral Respiratory Group
3. Pneumotaxic Center
4. Apneustic center

9. Normal mechanism
1. DRG and VRG send signals
2. Stimulation of cell bodies of neurons supplying
respiratory muscles
3. Contraction of respiratory muscles
4. Inspiration
5. Relaxation of muscles
6. Expiration

10. PO2 normal
1. Atmospheric PO2 is 160 mmHg
2. Alveolar PO2 is 104 mmHg
3. PO2 of the Blood entering the lungs is 40 mmHg
4. PO2 of the Blood leaving the lungs is 104 mmHg

11. PO2 at high altitude
1. Atmospheric PO2 is 130 mmHg
2. Alveolar PO2 is 60 mmHg
3. PO2 of the Blood entering the lungs is 40 mmHg
4. PO2 of the Blood leaving the lungs is 60 mmHg
5. This is called hypoxemia - abnormally low level of
oxygen in the blood.

12. CO2 – Normal
Mechanism

13. CO2 – Normal
Mechanism
 CO2 easily cross Blood brain barrier
 When PCO2 increases in interstitial fluid of medulla
and CSF, the CO2 reacts with water of the tissues and
forms carbonic acid
 Carbonic acid dissociates and releases hydrogen ions
 Hydrogen ions stimulates the chemo sensitive area
and thus respiration

14. CO2 –Mechanism at high
altitude
 PCO2 decreases
 Decrease in H+ ions
 Inhibition of central chemo receptors
 Inhibition of DRG
 Inhibition of VRG
 Decrease in the frequency of action potentials
 Decrease in the alveolar ventilation
 Decrease in the rate and depth of respiration

15. What is
happening
 Initially there is hypoxemia
 Increase in ventilation
 Brings PO2 back to normal
 In this process more CO2 moves out
 PCO2 decreases
 Inhibition of CCR
 Decrease in the ventilation
 OPPOSITE ACTIONS

16. Lost more CO2 from
body?
 If we breath out more CO2
 Respiratory alkalosis
 PH is very high due to low PO2

17. How your body deals this
condition?
 Acclimatization
 Kidney comes into the role
 kidney consists of intercalated cells
 When PH increases in blood (decrease in H+ ions)
 Intercalated cells pumps H+ ions out (into blood)
 Increase in H+ ions (PH back to normal)
 Stimulation of CCR
 Stimulation of respiratory centers
 Increase in the rate and depth of respiration

18. Is this
enough?
 No …. Not enough
 Kidney again comes into the role
 When the PO2 decreases (hypoxia)
 When PH increases in blood (decrease in H+ ions)
 Hypoxia inducing factor is released from PCT
 Production of hormone - erythropoietin
 Stimulation of bone marrow
 Increase in RBC (polycythemia) – increase in HB
 Increase in oxygen carrying capacity

19. Is this
enough?
 No …. Not enough
 Due to polycythemia there is
perfusion
increase in the
 Due to hypoxemia there is increase
ventilation
 Increase in ventilation and perfusion
 Good V/P coupling there
in the
 Efficient gaseous exchange

20. Is this
enough?
 Yes for short periods stay
 If stay for longer periods angiogenesis takes place
 Angiogenesis - formation of new blood vessels

21. Angiogenesi
s
 In high altitude PO2 decreases
 Less oxygen supply to tissues
 Endothelial cells of blood vessels
vascular endothelial growth factor (VGF)
 Sprouts blood vessels
 More blood vessels
 Angiogenesis
releases

22. Is this
enough?
 If stay still very longer periods the shape of chest
wall also changes to large or barrel shape.
 Increase in the diffusion capacity due to increase in
the pulmonary capillary blood volume and increase
in the lung air volume.
 In permanent natives of high altitudes, the number
of mitochondria and cellular enzymes is plentiful
than the sea level habitants. (cellular
acclimatization)

23. Acclimatizatio
n
1. Increase in the rate and depth of respiration
2. Increase in the RBC (polycythemia)
3. Normal V/P ratio (efficient gas exchange)
4. Angiogenesis
5. Change in shape of chest

24. How long it takes to climb
Everest
1. Entire climb takes 6-9 weeks
2. First week – arrive to base camp
3. Next 3-4 weeks – going up and down the
mountain to establish camps with food, fuel and
oxygen
4. Acclimatization process can not be rushed

25. If you climb Everest very
fast???
 Acclimatization will not takes place
 Cerebral edema
 Pulmonary edema
 Called as Acute mountain sickness

26. Cerebral edema at high
altitude?
 Low PO2 in systemic circulation
 Vasodilation of blood vessels
 Increase in the blood flow through cerebral blood
vessels
 More fluid loss
 Increase in fluid accumulation
 Cerebral edema

27. Cerebral edema at high
altitude?
 Increase in intra cranial pressure
 Head ache
 Increase in Pulse rate
 Herniation of brain that compresses the respiratory
centers
 Death

28. What medications should I
carry?
 Acetazolamide (inhibits carbonic anhydrase) and
increases CO2 (stimulates RC)
 Mannitol (relieves cerebral edema)
 Dexamethasone (steroid) – relieves
edema
cerebral
 Oxygen supplements

29. pulmonary edema at high
altitude?
 Low PO2 in pulmonary circulation
 Vasoconstriction of blood vessels
 Blood is diverted to medium constricted or normal
blood vessels
 Increase in blood flow
 Increase in leak of fluid
 Accumulation of fluid
 Pulmonary edema

30. Chronic mountain
sickness
 Seen in individuals who stays for long at high altitudes
 Polycythemia increases viscosity of blood and decreases
the blood flow to the tissues ( oxygen delivery decreases)
 All alveoli now becomes low oxygen state, so
vasoconstriction of all pulmonary blood vessels results in
increase in the arterial pressure and failure of right side of
heart.
 Poorly oxygenated blood
 These individuals recover within days or weeks when they
are moved to low altitudes

31. Deep sea
diving
 Descending beneath the sea, the pressure
increases tremendously
 To prevent collapse of lungs, air must be supplied at
very high pressures
 This will expose the blood in the lungs to extremely
high pressure – hyper-barism
 Beyond certain limits, these high pressures cause
major alterations in the body physiology and can be
lethal

32. Physiological effects of deep
sea diving
 Nitrogen narcosis at high nitrogen pressure
 Oxygen toxicity at high pressure
 Carbon dioxide toxicity due to deep sea diving

33. Nitrogen
narcosis
 At the sea level pressure, the nitrogen has no significant
effect on body functions
 When the diver remains beneath the sea for an hour or
more and breathing compressed air, the depth at which
the first symptom occurs is 120 feet
 At 120 feet, diver begins to be jovial
 At 150-200 feet, he becomes drowsy
 At 200-250 feet, his strength wanes
unable to do required work)
 Beyond 250 feet, he becomes useless
considerably (

34. Nitrogen
narcosis
 Similar as alcoholic intoxication
 Also called raptures of the depths
 Mechanism is same as any other gas anesthetics
 Nitrogen dissolves in the fatty substances in the
neural membranes, alters the neuronal excitability

35. Oxygen toxicity at high
pressures
 When PO2 of blood increases (say 100 mmHg), there
will be increase in the dissolved oxygen in addition to
that bound to hemoglobin
 Extremely high PO2 (when oxygen is breathed at high
pressures) is detrimental to body tissues
 Causes brain seizures and coma in 30-60 minutes
 These seizures occurs with out warning sign and are
lethal
 Nausea, muscle twitchings, dizziness, disturbance of
vision, irritability and disorientation

36. Oxygen toxicity at high
pressures
 Molecular oxygen converts into active form of oxygen called
oxygen free radicals
 One of the most important form of oxygen free radicals is
super oxide free radical and other is peroxide free radical
 Even at normal PO2, these free radicals will be continuously
formed
 Body is equipped with enzymes to remove these free radicals
(oxidases, catalases, superoxide dismutase)
 But when PO2 is above the critical levels, there will be
excessive oxygen free radicals

37. Oxygen toxicity at high
pressures
 Free radicals oxidizes the polyunsaturated fatty
acids that are essential components of many of cell
membranes
 Also oxidizes cellular enzymes and damages the
cellular metabolic processes
 Nervous tissues are highly susceptible due to
high lipid content
 Most lethal effect of oxygen toxicity is brain
dysfunction

38. Carbon dioxide
toxicity
 Depth alone does not increase the rate of CO2 production in
the body
 As long as diver continues to breath normal tidal volume and
expires the CO2 as it is formed, Alveolar PCO2 will be
normal.
 In certain types of diving gear, diving helmet and some type
of rebreathing apparatus, CO2 will build up.
 Beyond 80 mmHg PCO2, the respiratory centers will be
depressed.
 Respiratory acidosis, narcosis, lethargy and even anesthesia.

39. Decompression
sickness
 If a diver stays longer periods beneath the sea,
nitrogen is dissolved in the body
 If he comes to surface suddenly, nitrogen bubbles
are formed in the body fluids (intra or extra cellular)
 Cause minor to serious damage to any area of the
body
 This is called as Decompression sickness
 Also called as Bends, compressed air sickness,
Caisson disease, Diver’s paralysis, Dysbarism

40. Symptoms of
Decompression
sickness
 Gas bubbles blocks many blood vessels in different
tissues
 Tissue ischemia and death
 In 85-90% of people, pain in the joints and muscles
of legs and arms (bends)
 In 5-10% of people, paralysis, dizziness or
unconsciousness
 in 2% of people, chokes, shortness of breath,
pulmonary edema and death

41. Prevention and management
of Decompression
sickness
 Slow ascent
 Tank decompression
 Using helium oxygen mixture in spite of nitrogen
 Why??

42. Why
helium??
 Has only one-fifth of narcotic effect of nitrogen
 The amount of helium dissolves in the body is less
when compared to nitrogen
 Low density of helium keeps the airway resistance
minimum (work of breathing less)

43. SCUBA
 Self Contained Under Water Breathing Apparatus
 Designed by French explorer Jacques Cousteau
 Advantage- Only required amount of air enters the
mask and on expiration, the air can not go back to
tank but instead is expired into the sea
 Limitation – only limited time one can remain
beneath water

44. SCUBA