Integrated human response to hypoxia Flashcards
percentage of nitrogen in the air
78.08%
percentage of oxygen in the air
20.95%
percentage of co2 in the air
0.04%
percentage of argon in the air
0.93%
barometric pressure
total pressure of air, from mixture of the different gases
partial pressure
partial pressure of a gas in a mixture is the pressure that gas would exert if it occupied that volume alone
fractions concentration x barometric pressure = partial pressure
Dalton’s law
total pressure of a gas mix
sum of all their partial pressures
PO2 cascade at sea level
PO2 decreases from atmospheric air to alveoli because
- addition of water vapour
- gas exchange with CO2
PO2 decreases further in capillary blood because
- gas exchange with tissues
change in PO2 from ambient air -> inspired air -> alveolar gas
dry ambient air quickly becomes saturated with water as it passes through airways
- water has its own partial pressure which must be accounted for
- PH2O changes with temp, at body temp is 6.35kPa/47mmHg
PH2O at body temp
6.35kPa // 47mmHg
PAO2 can be calculated with what equation
alveolar gas equation
PAO2= {fractional [O2] x (barometric pressure - PH2O)} - (PaCO2/R)
aka PO2 entering alveoli - PO2 leaping alveoli
R = respiratory quotient =VCO2/VO2
R
respiratory quotient =VCO2/VO2
normally 0.8 at rest with normal diet
V
flow of gas across a diffusion barrier
flow of gas cross a diffusion barrier is proportional to
- diffusabilty of gas (d)
- area (A)
- thickness (1/T)
- partial pressure gradient (P1-P2)
= Fick’s law
V=d x A/T x (P1-P2)
Fick’s law
V=d x A/T x (P1-P2)
- diffusabilty of gas (d)
- area (A)
- thickness (1/T)
- partial pressure gradient (P1-P2)
what must respiratory gases diffuse through
gaseous and liquid phase
uptake of oxygen in pulmonary capillaries and extraction of oxygen at tissues is influenced by
- partial pressure gradient
- properties of diffusion barrier
- relationship between PO2 and Hb saturation
when is it important to consider the partial pressure gradient for oxygen uptake and extraction
high altitudes
when do the properites of diffusion barrier to oxygen change
they are fixed in health but change in disease
relationship between amount of oxygen in blood and Hb saturation
sigmoidal
functional significance of flat part of sigmoidal curve
association region
- even if oxygen levels reduce in the lungs, we still get almost complete loading of Hb
- we are not impaired by blood oxygen content
functional significance of steep part of sigmoidal curve
dissociation region
- ensures adequate delivery of oxygen to tissues whilst maintaining arterial PO2
- if PO2 in tissues reduces, Hb will release lots of oxygen
what is a key fact about the relationship between amount of oxygen in the blood and Hb saturation
it is not a fixed relationships. oxygen binding affinity for Hb varies
what causes a shift to the right for the Hb dissociation curve
- increase in PCO2
- decrease in pH
= Bohr effect - increase in temperature
what causes a shift to the left for the Hb dissociation curve
- decrease in PCO2
- increase in pH
- Decrease in temperature
Lung PO2
~13 kPa (far right of curve)
tissue PO2
~4 kPa (Left of curve)
auto regulated oxygen delivery to tissues
- increased tissue metabolism
= shift to the right due to PCO2, pH and temperature change
= increased oxygen delivery to the site of increased metabolism
why is oxygen needed at tissues
final electron acceptor in ETC
helps creation of proton gradient either side of inner mitochondrial embrace to drive oxidative phosphorylation in the production of ATP
why does PO2 change at high altitude
bariatric pressure reduces and so inspired PO2 will also be reduced
PO2 cascade at altitude
low PO2 is transfered all the way along oxygen cascade
- if low enough = hypoxia and cellular function may be compromised
is acute exposure to low atmospheric PO2 compatible with life
no
how can we survive summiting without oxygen supplementation of acute exposure to low atmospheric PO2 isn’t compatible with life
acclimatisation
what kind of response is acclimatisation
integrated, slow developing response which requires adjustments from three systems
- cardiac, hours
- respiratory, days
- haematological, weeks/months
what systems must adjust for acclimatisation
- cardiac, hours
- respiratory, days
- haematological, weeks/months
systemic oxygen delivery
DO2 = CO X CaO2
Systemic O2 delivery = cardiac output x O2 content of arterial blood
CaO2
O2 content of arterial blood
DO2
Systemic O2 delivery
when partial pressure of inspired oxygen decreases:
CaO2 and therefore DO2 will reduce
first line of defence against reduced PO2
increase CO to maintain DO2
- immediate increase in HR upon hypoxic exposure
- SV remains constant
change in HR at 4500m
10-15% higher
change in HR at 7600m
100% higher
methods of restoring CaCO2
- ventilatory adjustments
- haematological adjustments
what is hyperventilation
where CO2 is eliminated in expired rate at a faster rate than it is produced, causing a reduction in PaCO2
NOT exercise hyperpnoea
does hyperventilation occur in exercise
not commonly, that is hyperpnoea.
But, above anaerobic threshold hyperventilation can occur
why does hyperventilation occur
hypoxic stimulation of arterial chemoreceptors
= most important feature of acclimatisation to high altitudes
what is the most important feature of acclimatisation to high altitudes
hyperventilation
why does hyperventilation cause CO2 blow off
increase in ventilation = decrease in alveolar CO2
- PO2 is proportionate to CO2 production
- PO2 is inversely proportionate to alveolar ventilation
how is hyperventilation beneficial
- increase in CO2 blow off leads to increased alveolar PO2
= counteracts the lower barometric pressure - alveolar PO2 and PCO2 are inversely related
relationship between PO2 and PCO2
inverse
development of hyperventilation during climb
- as altitude increases, PO2 decreases and so hypoxic ventilatory drive increases
= reduction in PCO2 for more PO2 - at certain altitudes, response aims to keep PO2 above certain threshold e.g 35mmHg
- this causes extreme hyperventilation
= PCO2 reduced to as low os <10mmHg
hyperventilation in numbers
- at pikes peak, PaO2 has halved
- but, hyperventilation can cause ventilation to double
- therefore PCO2 has doubled
- now PaO2 has only reduced by 25%
a double in ventilation caused only half the reduction in PAO2
- inverse relationship
respiratory alkalosis with altitude
likely how summiting Everst is possible
- hyperventilation causes PC2 to drop and alkalosis
- alkalosis reduces stimulation of central chemoreceptors
- this has negative feedback on ventilatory drive
= hyperventilation inhibited
what inhibits hyperventilation
respiratory alkalosis
how is negative feedback of hyperventilation reduced
metabolic compensation
- body removes bicarbonate ions which returns pH to normal
- once pH returns to normal, inhibitor is reduced
= hyperventilation
metabolic compensation
removes negative feedback on hyperventilation
- hyperventilation produces H+
- H+ buffered by HCO3
- after days, HCO3 transported out of CFS
- pH returns to normal
- inhibition of hyperventilation is removed
- simultaneously HCO3 reabsorption in kidneys is reduced so excreted in urine
- Urine pH increases, blood pH returns to normal
is metabolic compensation beneficial
yes because it supports hyperventilation
BUT it may hinder ascent at extreme altitudes because alkalosis may be beneficial, because it causes a left shift
is alkalosis beneficial
no, because it inhibits hyperventilation
BUT at extreme altitudes it may be useful because it causes a left shift
how is alkalosis beneficial at extreme altitudes
left shift enhances the landing of oxygen in the pulmonary capillaries
what would happen after days at extreme altitudes
after several days, renal HCO3 removal will cause pH to return to normal and loss of advantageous left shift
strategy to summit Everest
- acclimatise at lower camps
- ensure final summit is as rapid as possible
= ensures acclimatisation ot high altitude, but also takes advantage of an uncompensated alkalosis by summiting quickly (left shift)
which method of CaO2 restoration takes longest
haematological adjustment
[Hb] =
total Hb (g) / total plasma (L)
how can [Hb] be increased
- decrease plasma volume
- increase total Hb
when is plasma volume decreased to increase [Hb]
acute response to altitude over hours-days
how is total Hb increased
erythropoiesis - slow response that takes weeks
How does erythropoiesis work
- cells in kidney and liver sense reduced PO2 via HIF
- respond to HIF by releasing EPO
- EPO stimulates bone marrow to produce more RBC
= more Hb
what is HIF
hypoxia-inducible factor
it is an oxygen-sensing transcription factor
oxygen-sensing transcription factor
HIF
where is HIF
Liver and kidneys
what happens to HIF in normoxia
-HIF alpha submits are hydroxylated by PH
- tagged with ubiquitin by VHL
= labelled for degradation
what happens to HIF in hypoxia
- HIF alpha subunits are stabilised
- translocated into nucleus
- # this increases transcription of several genesEPO
VEGF
glycolytic & gluconeogenic enzymes
glucose transporters
what does HIF increase transcription of in hypoxia
EPO
VEGF
glycolytic & gluconeogenic enzymes
glucose transporters
what increases transcription of these & when
EPO
VEGF
glycolytic & gluconeogenic enzymes
glucose transporters
HIF in hypoxia
Summary of acclimatisation
3 pathways
- alternations in ANS to increase HR and CO
- stimulation of arterial chemoreceptors to increase ventilation which is maintained by metabolic compensation when alkalosis occurs
- HIF signalling in kidney and liver cells to produce more EPO for Hb production
all work to maintain DO2
what decreases the most during ascent to everest, after acclimatisation
PaO2, becuase of gradient from atmosphere to blood
what happens to levels in [Hb} durng ascent to Everest in acclimatised person
increase
what is universally accepted bout acclimatisation
the ability to acclimatise to high altitude is achieved by increasing CaCO2 to sea level values or above
what is still not completely understood about altitude
- exercise performance at altitude
- susceptibility of high altitude illness
what happens to exercise capacity at high altitude
severely reduced
- at 500m, VO2 max is 60% os sea level
at everest, VO2 max is 35%
how does changing CaO2 at altitude effect physical performacne
they don’t
exercise capacity is still significantly reduced despite relatively normal DO2
- not understood
other possible factors related to cellular VO2 or alterations of oxygen movement at tissue cell level for further research
- changes in mitochondrial enzymes
- o2 diffusion from capillaries to mitochondria
- local distribution of blood flow to exercising muscle
does sea level performance predict high altitude performance
nope, confused.com
