High altitude physiology

1. HIGH ALTITUDE PHYSIOLOGY
Dr. Shahnawaz
Alam Assistant
Professor(Physiology)

2. Hypoxia
•defined as deficiency of oxygen 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 is 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=255mm
Hg
• 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

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.

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
• 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
• 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
• 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.

31. 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.

32. 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

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

34. 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)

35. Portable hyperbaric chamber- Gamow
bag

36. 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.

37. HIGH-ALTITUDE PULMONARY EDEMA

38. 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

39. 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

40. 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.

41. • Thank
You…!!!