hypoxic pulmonary vascular response in HAPE-
susceptible individuals (Bärtsch et al., 1991; Bärtsch
et al., 2005; Bärtsch and Gibbs, 2007). Mechanisms
for the hypoxic constriction of arterioles resulting
in edema include irregular vasoconstriction with
regional over-perfusion and reduced fluid clearance
from the alveolar space. decreased incidence of HAPE from 74% to 33%
providing further evidence for the inhibition of ENaC
in HAPE pathology (Vivona et al., 2001; Sartori et al.,
2002; Sartori et al., 2004; Bärtsch and Gibbs, 2007).
Hypoxic pulmonary vasoconstriction (HPV) is
the homeostatic mechanism responsible for
vasoconstriction of intrapulmonary arteries in
response to alveolar hypoxia; at high altitude the
hypoxia is environmental, thus HPV is diffuse.
Diffuse HPV results in increased PAP and initiates
pulmonary hypertension (PH) contributing to
HAPE development. ROS release is dynamically
changed by the mitochondria in the pulmonary
artery smooth muscle cells (PASMC) in response to
alveolar hypoxia which results in vasoconstriction
of the intrapulmonary arteries. Non-uniform
pulmonary vasoconstriction results in increased
intravascular pressure, and thus, perfusion of fluid
across the intrapulmonary artery membranes leading
to abnormal accumulation of fluid in the lungs –
pulmonary edema. Reduced bioavailability of the
messenger molecules, NO and cGMP, is thought to
contribute to increased HPV. Increased expression of
endothelial nitric oxide synthase (NOS) – responsible
for producing NO – has been shown to inhibit
hypoxia-induced dysfunction of the endothelium
(Bärtsch et al., 2005; Bärtsch and Gibbs, 2007). The classical understanding of acclimatisation
describes the restoration of oxygen delivery back to
sea-level values. Oxygen delivery is considered to be
the product of cardiac output – the product of heart
rate and stroke volume – and arterial oxygen content
–the sum of oxygen bound haemoglobin (Hb) and
plasma dissolved Hb. As previously stated, ascent to
altitude without acclimatisation results in reduction
of arterial PO2 and SO2, and thus a reduction in
oxygen delivery. Physiological changes to counteract
this reduction according to the classical explanation
include; increasing cardiac output, restorating arterial
SO2, and increasing Hb concentration (Martin
and Windsor, 2008). The classical explanation of
acclimatisation is dependent on the improvement
of oxygen delivery to the tissues, however, there
are other mechanisms capable of restoring the
physiological oxygen balance. These mechanisms
include reducing cellular oxygen consumption and
improving metabolic efficiency for the generation of
energy.
Active transport of charged sodium atoms (Na+)
across the alveolar epithelium is necessary to ensure
fluid-free lungs. Vivona et al (2001) demonstrated
hypoxia-inhibited activity and expression of the
alveolar epithelial cell Na+ transporters in rats. The
effect was particularly pronounced in the apical
membrane epithelial Na+ channel (ENaC) and the
basolateral membrane Na+/K+-ATPase resulting in a
reduction of Na+ transport and fluid clearance from
the alveoli, via the alveolar epithelial membrane.
Sartori et al (2002) found that prophylactic
stimulation of the ENaC transport mechanism
increased Na+ transport across the alveolar
epithelium and alveolar fluid clearance resulting in Rapid ascent to altitude is the primary risk factor
in the development of altitude sickness therefore
reduced ascent rate is considered to be the most
effective method for altitude sickness prevention.
Acclimatisation involves a series of physiological
changes that mitigate the effects of hypobaric
hypoxia and the resultant hypoxaemia. Whilst
optimal acclimatisation may take weeks, or even
months, to achieve, the initial acclimatisation
process occurring in the first few days after ascent
is usually enough to be protective against altitude
sickness. The recommended ascent rate is no more
than 300-500m ascent per day – sleeping altitude
– with a rest day every 1000m or every 3-4 days.
36
Prophylaxis
Acclimatisation