A. If an unacclimatized person ascends rapidly to great heights, (or more likely, if an airplane were to rapidly lose cabin pressure), he or she would experience a deterioration of cerebral functions:
Cortical: sleepiness, laziness, false sense of well-being; impaired judgement; blunted pain perception, increasing errors on simple tasks, decreased visual acuity
Neuromuscular coordination: clumsiness, tremors, increased reaction time, etc.
These symptoms are primarily a result of hypoxia.
B. An unacclimatized person at moderate altitude experiences a group of symptoms known as Acute Mountain Sickness:
Headache, dizziness, breathlessness at rest, weakness, nausea, sweating, palpitation, dimness of vision, partial deafness, sleeplessness, and dyspnea on exertion.
These symptoms are due to hypoxemia, hypocapnia, respiratory alkalosis, and fluid and electrolyte changes.
C. At very high altitudes pulmonary edema (HAPE) and cerebral edema (HACE) may develop.
II. Response of unacclimatized individuals to acute altitude exposure
A. Initial respiratory response of an unacclimatized person:
The problem (Levitzky Fig. 11-2):
Low barometric pressure→Low PIO2→ Low PAO2 →Low PaO2. CO2 production (initially) normal.
The sensor: Arterial chemoreceptors only.
The response is increased depth and possibly rate (Levitzky Fig. 9-10) to bring PAO2 and PaO2 closer to PIO2. (At a PAO2 of 45, E is approximately doubled.)
AsE, PaCO2(Levitzky Fig. 3-10), pHa(Levitzky Fig. 8-1).
Within a minute or so, the central chemoreceptors seePCSFCO2 and pHCSF, so their activity decreases (Levitzky Fig. 9-8).
1. Effect on mechanics of breathing - Increased work of breathing
a. Work = P x V ( x breathing frequency):
Greater transpulmonary pressures necessary to develop greater tidal volumes (may also be decreased pulmonary compliance due to vascular engorgement) Alveoli less compliant at greater volumes (Levitzky Fig. 2-6) Greater frequency
b. Active expiration - contraction of abdominal muscles, internal intercostals
c. Greater airways resistance work:
Forced expiration → dynamic compression of airways (Levitzky Fig. 2-19)
Hypoxia causes reflex parasympathetically mediated bronchoconstriction
More turbulent flow (Levitzky Fig. 2-16) although gas density may be decreased, velocity and radius
2. Effect on alveolar ventilation: VT x n →E and A
a. Anatomic dead space decreases due to bronchoconstriction, due to both arterial chemoreceptor stimulation and from the local response to decreased PCO2, but increases on inspiration somewhat due to increased depth. Minor effect
b. As A increases, PACO2 decreases, pH increases (Levitzky Figs. 3-10, 8-1). This decrease in PACO2 (and therefore PaCO2) and increase in pHa (respiratory alkalosis) lead to many of the symptoms of mountain sickness.
c. May be a slightly more uniform regional distribution of alveolar ventilation as expire more fully. Also, if any atelectasis present deep breaths should open alveoli.
3. Effect on diffusion: Low alveolar PO2 sets low upper limit for arterial PO2 (Levitzky Fig.6-2).
a. Decreased PO2 gradient: Alveolar PO2 is decreased more than mixed venous PO2.
b. Increased surface area for diffusion - recruitment of new capillaries due to increased cardiac output and increased pulmonary artery pressure.
c. May be slight decrease in thickness due to higher lung volumes.
d. Decreased time for diffusion: Higher cardiac output decreased time in capillary for RBC (e.g. .75 sec→ .25 sec). May have diffusion limitation of gas transfer.
4. Effects on pulmonary blood flow and ventilation-perfusion ratio:
a. Increased cardiac output (and systemic blood pressure) due to chemoreceptor stimulation.
b. Recruitment of new pulmonary capillaries (Levitzky Fig. 4-6).
c. Hypoxic pulmonary vasoconstriction and sympathetic vasoconstriction of large vessels (Levitzky Fig. 4-10C).
d. a and c above tend to increase mean pulmonary artery pressure, abolish zone 1 (if any; Levitzky Fig.4-9), and decrease the perfusion gradient in the upright lung.
e. Therefore A/ should be more uniform (Levitzky Figs. 5-6, 5-7) for whole lung. However, there is no evidence that this occurs.
f. Work load of right ventricle greatly increased because of increased preload and afterload. (Positive inotropic effects due to sympathetic stimulation 2° to chemoreceptors). High pulmonary artery pressure may lead to pulmonary edema (High Altitude Pulmonary Edema; Levitzky Fig. 4-11).
5. Effect on O2 - CO2 dissociation curves
a. May no longer be on flat part of HbO2 dissociation curve (Levitzky Fig. 7-1).
b. Hypocapnia allows for some increase in O2 loading at pulmonary capillaries but no help unloading at tissue capillaries (Levitzky Fig.7-2A, B)
c. Increased cardiac output increases O2 delivery somewhat.
d. Increased 2,3 DPG may help alleviate the leftward shift of the oxyhemoglobin dissociation curve by shifting it toward the right (Levitzky Fig.7-2D).
6. Effect on the special circulations
a. Cerebral - although hypocapnia may cause a cerebral vasoconstriction, the hypoxemia produces cerebral vasodilation and hyperperfusion. This vasodilation and hyperperfusion may contribute to the headaches and other cerebral dysfunction, and may lead to cerebral edema (High Altitude Cerebral Edema).
b. Coronary - coronary blood flow greatly increased due to hypoxemia and increased work load.
B. Prevention of acute mountain sickness
1. Acetazolamide - a carbonic anhydrase inhibitor taken for a few days before going to altitude can be effective in preventing acute mountain sickness in many people. The mechanism is not clear because acetazolamide decreases renal reabsorption of bicarbonate (which could help compensate for alkalosis) and it is a diuretic (so it may help prevent fluid retention and cerebral edema).
2. Slow ascent in stages, especially for high altitude, to allow for acclimatization.
III. Acclimatization - both to hypoxia and secondary hypocapnia
1. Hypoxic chemoreflex stimulation persists indefinitely, although may be somewhat diminished. The "hyperventilation" therefore persists, indefinitely. (The sympathetically mediated cardiovascular changes regress after a few days.)
2. CO2 - ventilatory response curve shifts to the left. Probably due to central acid-base changes.
B. Cerebral hyperperfusion and edema are relieved in a few days. Mechanism has not been determined.
C. Alterations in acid-base balance
1. CSF: HCO3- is pumped or diffuses out of the CSF. This takes a few days
2. Respiratory alkalosis compensated for by renal excretion of base
D. Improvement in oxygenation
1. Erythropoiesis - Increased O2 carrying capacity. Increased hematocrit increases viscosity and increases afterload.
2. DPG - may help unload O2 at tissues (Levitzky Fig. 7-2D).
E. Cardiovascular changes
1. Although the increased cardiac output and heart rate return to normal after days to months, the hypoxic pulmonary vasoconstriction persists; the increased hematocrit increases blood viscosity and increases the right ventricular afterload.
2. This increased right ventricular work load leads to right ventricular hypertrophy and may lead to cor pulmonale.
IV. Summary (Levitzky Table1 1-2)
Copyright 2000 M. G. LEVITZKY
Last updated Tuesday, November 25, 2003 2:48 PM
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