Altitude physiology typically focuses on people above 2500 m; ∼8000 ft. Altitudes above that are sometimes subdivided into very high (3500–5500 m; ∼11,500–18,000 ft) and extreme (>5500 m; >18,000 ft). An estimated 40 million people travel each year to altitudes >2500 m (∼8000 ft),1 and as many or more travel to altitude for leisure and sports, and work in mines, military or border operations, and the like. Altitude medicine considers the clinical disorders associated with acclimatization by the travelers, workers and migrants, and with adaptation by people with lifetimes or populations with millennia of residence (an estimated 83 million people). With a hurried ascent, many (∼80%) will report a transient headache (high-altitude headache or [HAH]), and some will develop one of three forms of acute high-altitude illness: acute mountain sickness (AMS) and HAH, high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). AMS and HAH are annoying and interfere with activity and work, however, HACE and HAPE can be fatal with mortality rates approaching 30%. Among some residents, chronic mountain sickness (CMS) and right ventricular hypertrophy develop over months to years of residence at altitude. Birth weights are generally lower and the rate of small-for-gestational-age babies and congenital heart defects are higher than that in lowland populations.

1. HIGH ALTITUDE
PHYSIOLOGY
Dr Kamal Bharathi. S
Department of Pulmonary Medicine
Sri Manakula Vinayagar Medical college and Hospital

2. Hypoxia
• defined as deficiency of o2 at the tissue level.
Types
• Hypoxic hypoxia
• Anemic hypoxia
• Stagnant hypoxia
• Histotoxic hypoxia

3. • Hypoxic hypoxia- PO2 of arterial blood is
reduced.
• Eg. high altitude, ascend rapidly to 3000m or
10,000 ft hypoxia develops due to decline in
alveolar PO2 to about 60mmHg.

4. Chemoreceptor- Carotid Bodies
• Special features
- receive unusually high blood flow
- high metabolic rate
• easily detect minor changes in P02, PC02 and pH of blood.
-Type 1- glomus cells
-Type 2- sustentacular cells
• Glomus cells- chemosensitive cells, neuroectodermal in
origin, structurally resemble chromaffin cells of adrenal
medulla, cytoplasm containing catecholamines.
• Dopamine are released from glomus cells in response to
hypoxia - acts on D2 receptors present on membrane of 9th
nerve ending and triggers AP in carotid sinus nerve

6. Hypoxia
• major stimulus for activation of peripheral
chemoreceptors.
• Mechanisms of less rise in ventilation when PO2
falls from 100 to 60 mmHg:
- Hb is less saturated with 02- Oxy Hb is a stronger
acid- fall in arterial P02- fall in H+ inhibits
respiration.
- Increased ventilation due to hypoxia decreases
PCO2 that in turn inhibits ventilation.
• Response is most effective at P02 less than 60
mm Hg- hypoxic drive.

7. • Hypoxia inhibits K+ channel.
• The accumulation of K+ in the glomus cell results
in depolarization activates voltage gated Ca+
channels. ↑Ca influx causes neurotransmitter
secretion that stimulates the afferent nerve.
• Mechanism: (inhibits K+ channels)
- Heme-containing protein loses its 02
- Hypoxia increases cAMP
- Hypoxia inhibits mitochondrial NADPH oxidase

8. The French physiologist
Paul Bert first recognized
that the harmful effects
of high altitude are
caused by low oxygen
tension.

10. Mount Everest
29,028 ft (8848mt)
• Atmospheric
Pressure=255mmHg
• PO2= 53mmHg
• Inspired PO2 =44mmHg
Unacclimatized person
• Unconscious in 45
seconds
• Dead in 4 to 6 mins

11. Physiologic changes in High Altitude
I) Acute responses (accommodation)
II) Long term responses (acclimatization)
Accomodation
• Refers to immediate reflex adjustments of
respiratory and cardiovascular system to hypoxia
Acclimatization
• Refers to changes in body tissues in response to
long term exposure to hypoxia

12. Accommodation at high altitude
Immediate reflex responses of the body to acute hypoxic
exposure.
Hyperventilation
• Decrease arterial PO2 → stimulation of peripheral
chemoreceptors → increased rate & depth of breathing
Tachycardia
• Also stimulate peripheral chemo. receptors → increase
Cardiac output → increase oxygen delivery to the tissues.
Increased 2,3-DPG conc. in RBC
• within hours, ↑deoxy-Hb conc. → locally ↑pH → ↑2,3-DPG
→ ↓oxygen affinity of Hb → tissue O2 tension maintained at
higher than normal level

13. Acclimatization at high altitude
• Various physiological readjustments and
compensatory mechanisms in body that
reduces the effects of hypoxia in permanent
residents at high altitude.

15. RESPONSES TO HYPOBARIC HYPOXIA
Ventilatory Adaptations
• Hyperventilation - ↓alveolar CO2 in order to
↑PAO2
• Sensor- Carotid body- afferent activity ↑,
PaO2 falls <60 mm Hg.
• stimulated by decreasing the [ATP]/[ADP][Pi]
ratio.

16. Hypoxia inducible factors

17. THE PULMONARY CIRCULATION
• Moderate-to-severe pulmonary hypertension
• supplied with sympathetic & parasympathetic
fibers- regulation of vasomotor tone
• altitude is a model of whole lung hypoxic,
hypocapnic pulmonary vascular
vasoconstrictive responses

18. FLUID HOMEOSTASIS
• Dermal edema is seen in faces
• Pulmonary edema, cerebral edema, and
peripheral edema are the hallmarks of
disease.

19. ERYTHROPOIESIS AND HEMOGLOBIN
AFFINITY
• ↑ RBC occurs -acute exposure ↑ in EPO
synthesis in response to HIF-1 and HIF-2
• ↑ ventilation- ↓ PACO2, PaCO2 and arterial [H+];
concomitantly, serum levels of 2,3-DPG ↑
• While the reductions in PaCO2 and [H+] –
↑ hemoglobin affinity for O2, ↑ in 2,3-DPG
diminish the affinity; loading and unloading of O2
from hemoglobin depends- balance of these
factors.

20. COMMON CLINICAL DISORDERS OF
HIGH ALTITUDE
• HIGH-ALTITUDE HEADACHE
• ACUTE MOUNTAIN SICKNESS
• HIGH-ALTITUDE CEREBRAL EDEMA
• HIGH-ALTITUDE PULMONARY EDEMA
• CHRONIC MOUNTAIN SICKNESS

21. HIGH-ALTITUDE HEADACHE
• very common
• exacerbated by insufficient hydration in the
setting of increased water loss with
hyperventilation, overexertion, and
insufficient energy intake
• Vasodilation may also contribute.
• Acetaminophen or ibuprofen with hydration
will improve this symptom

23. ACUTE MOUNTAIN SICKNESS
• occurs after 4 to 36 hours of altitude
exposure.
• headache (usually frontal), nausea, vomiting,
irritability, malaise, insomnia, and poor
climbing performance.
• Sleep-disordered breathing - severity of AMS.
• self-limited

24. Mechanisms for AMS, HACE, and HAPE

25. Lake Louise Symptom Score Self-Report Questionnaire

26. ACUTE MOUNTAIN SICKNESS
• most common and useful self administered -
determine the severity of AMS.
• 1 (mild)
• 4 (severe)
• 10 and > (very severe)- immediate
intervention

27. ACUTE MOUNTAIN SICKNESS
Risk Factors
• the altitude and speed of ascent
• Old age
• history of migraine, persistence of a patent
foramen ovale, Down syndrome, congenital
pulmonary abnormalities, perinatal
pulmonary vascular insult, and Holmes–Adie
syndrome, a rare disorder of autonomic
control.

28. ACUTE MOUNTAIN SICKNESS
Prevention
• Exercise-induced asthma- exacerbated
• more than mild severity (COPD, sleep apnea,
heart failure, etc.)
• chronic kidney disease- arterial hypoxemia

29. ACUTE MOUNTAIN SICKNESS
Preacclimatization in hypobaric chambers and
normobaric hypoxic rooms - risk of acquiring
altitude illness.
• key element- elevation change per day to less
than 400 m/d.
Prophylactic administration
• acetazolamide (250 mg at bedtime or 125 mg
bid)
• Corticosteroids (dexamethasone at a dose of 4
mg every 6 hours)

30. ACUTE MOUNTAIN SICKNESS
Acetazolamide- carbonic anhydrase inhibitor, hence
causing the accumulation of carbonic acid
• widely used drug
• renal failure (reduced elimination- ↑metabolic
acidosis),
• hepatic insufficiency (ammonium ion toxicity),
• COPD (dyspnea),
• pregnant women (accumulating effect with natural
higher progesterone levels →dyspnea).
• Patients taking aspirin (acetylsalicylic acid) ↓
acetazolamide elimination ↑ CNS penetration -toxicity.

31. ACUTE MOUNTAIN SICKNESS
• sildenafil and tadalafil
• Adequate hydration -2 L of extra fluid per day
is a common rule of thumb.
• A suggested rule is that above 3000 m (10,000
ft), ascent should be at a rate less than 300 m
(1000 ft) per day, with a “rest” day (i.e., no
additional ascent) every 3 days.

32. ACUTE MOUNTAIN SICKNESS
Treatment
• self-limiting and usually lasts about 3 days-
not mandatory.
• Descend
• Acetazolamide- first-line treatment;
dexamethasone
• Temazepam is effective in reducing recurrent
central apnea.

33. HIGH-ALTITUDE CEREBRAL EDEMA
Symptoms
• Dizziness
• Severe unbearable headache
• Vomiting
• Ataxia
• Positive Romberg sign
• Somnolence, stupor, and changes in pupillary
responsiveness- onset of a fatal stage.
• coma and mortality

34. HIGH-ALTITUDE CEREBRAL EDEMA
• Pathophysiology
Hypoxia induces neurohumoral & hemodynamic
responses resulting in…
• over perfusion of microvascular beds
• elevated hydrostatic pressure
• capillary leakage
• edema

35. Awaiting Evacuation
• Supplemental oxygen.
• portable hyperbaric chamber- life-saving.
• Dexamethasone (4–8 mg), IM in severe cases,
or orally in less severe cases- reduce cerebral
edema (repeated every 6 hrs)

36. Portable hyperbaric chamber- Gamow bag

37. HIGH-ALTITUDE PULMONARY EDEMA
• symptoms are like pulmonary edema at sea
level.
• Prevalence 0.5% to 2.0%
Mechanism
• migration of fluid into extravasal space
through endothelial damage along with shear
stresses produced by increased cardiac output
and pulmonary artery pressure.

38. HIGH-ALTITUDE PULMONARY EDEMA
Presentation
• A typical patient -fit young man- climbed rapidly-
energetic on arrival. Moderate sx> breathlessness,
cough develops- initially dry >productive of frothy
white sputum> blood tinged. PR & RR ↑, auscultation-
crackles at the bases. An elevated JVP and peripheral
edema may be seen, and a right ventricular heave and
accentuated pulmonary component of the 2nd heart
sound- detected. patient’s condition may deteriorate
further PR & RR ↑. As breathing becomes “bubbly”
due to pulmonary edema, cyanosis develops. In the
absence of definitive treatment, hypoxemia >RF >coma
>death.

39. HIGH-ALTITUDE PULMONARY EDEMA

40. HIGH-ALTITUDE PULMONARY EDEMA
Prevention
• Nifedipine prophylactically (SR 20 mg twice daily
prior to ascent, then three times daily)- smooth
muscle relaxation.
• inhaled β-agonist
Treatment
• Descent is critical for survival
• Nifedipine (10 mg sublingually)
• sildenafil and tadalafil
• portable hyperbaric chamber

41. CHRONIC MOUNTAIN SICKNESS
or Monge's disease
• Excessive erythrocytosis associated with a lower oxygen saturation
and hypoxic ventilatory response with relative hypercapnia are the
main features of CMS
• defining feature is extreme polycythemia, with Hb conc., > 23 g/dL
& hematocrits >83%.
• Poor exercise tolerance.
• Patients may have vague neuropsychological complaints-
• Headache,
• Dizziness,
• Somnolence,
• Fatigue,
• Difficulty in concentration,
• Loss of mental acuity,
• Irritability, Depression, Hallucinations

42. CHRONIC MOUNTAIN SICKNESS
• more common in males, middle & later life.
• Descent to sea level is the definitive
treatment.
• Phlebotomy and administration of
supplemental oxygen are beneficial
• Medroxyprogesterone - some success
• Acetazolamide – lacking in prevention.

43. • Thank You…!!!