Respiratory Control
Voluntary vs Involuntary Control
Pathways
• Voluntary control pathways pass from
motor cortex to lower motor neurons – this
pathway bypasses the brainstem centers.
• Involuntary control centers are located in
the pons-medulla
• Spinal or brainstem damage can abolish
the involuntary pathway without damaging
the voluntary pathway – creating a
condition called Ondine’s Curse
The Respiratory Rhythm
• Respiratory centers in pons-medulla generate a
basic respiratory rhythm of bursts of APs
• TV is determined by the number of motor
neurons active and their rates of activity
• The combination of RR and TV that gives an
appropriate Valv is optimized to minimize the
total work of respiration – this computation
requires feedback from lung-chest wall stretch
detectors that course in the vagus nerve and
exert a burst-terminating inhibition.
• Appropriate Valv is determined by integration of
inputs that provide respiratory drive.
Central and Peripheral Sources of
Respiratory Drive
Central:
– Central chemoreceptors that respond to
arterial Pco2 indirectly – they actually measure
the pH of the CSF. This works well because
dissolved CO2 readily diffuses across the BB
barrier and then redissociates in the poorly
buffered CSF, whereas ionized acids and
bases do not enter the brain readily.
– Reticular activating system and other brain
centers, including various sensory inputs.
Peripheral sources of respiratory drive
• Aortic and carotid bodies that are mainly
sensitive to arterial PO2 but also to arterial pH
and PCO2.
Arterial PCO2 is the main source of
respiratory drive under resting conditions at
sea level
Relative ventilation
Arterial PO2 becomes really important only
when it falls below a threshold value
Inputs from central and peripheral
chemoreceptors are synergistic
In these three
experiments, PO2 is varied
while PCO2 is held constant
at a high, normal or low
value. At the arrow, you
can see that decreasing
alveolar PO2 by 10 mm Hg
hardly changes ventilation,
while increasing alveolar
PCO2 by 10 mmHg
increases ventilation by
4.5X.
PO2
Altitude Sickness
• At high altitude, both PO2 and PCO2 decrease in
proportion to the decrease in Patm
• As a result, simultaneous conditions of hypoxia (low
arterial PO2) and hypocapnia (low arterial PCO2) exist.
This causes the symptoms of acute mountain sickness.
• This leads to a conflict between the inputs from the
peripheral and central chemoreceptors. In the short term
of hours to days, it is not possible for the respiratory
centers to increase ventilation sufficient to counteract the
deficit of oxygen delivery, because they are being
inhibited by the central chemoreceptors.
Altitude Adaptation
• CNS adaptation results as the choroid plexus,
which produces the CSF, adjusts the pH of the
CSF to a more acid value. This removes the
inhibition of respiration caused by the
hypocapnia, and PO2 now becomes the most
important source of respiratory drive.
• The hypoxia results in increased secretion of 2,3
DPG, which improves O2 unloading by rightshifting the Hb-O2 dissociation curve, but this
also further compromises O2 loading.
Adaptation to respiratory disease
• If the disease results in an alveolar ventilation problem (as in
asthma)
– Both hypoxia and hypercapnia will result
• If the disease results in a loss of pulmonary diffusing capacity
(fibrotic lung disease, pulmonary edema or emphysema)
– O2 uptake will be affected well before CO2 unloading is,
because of the difference in the diffusion coefficients.
Hyperventilation will result, with consequent hypocapnia.
Over time, adaptation will occur and the patient’s hypoxia
will become the primary source of his respiratory drive.
Be careful with patients that have adapted to
chronic hypocapnia
– The patient may well stop breathing if
– He is anesthetized – O2-based
respiratory drive is weaker than CO2 –
based drive.
– He is switched from breathing room air
to breathing pure O2, - this removes his
sole remaining reason to breathe.
Erythrocyte synthesis and the
hematocrit are affected by hypoxia
• Hypoxia stimulates release of erythropoietin (EPO) from
various tissues (the kidney is a major source).
• Increased synthesis of RBCs increases the hematocrit
(polycythemia) and thus the blood oxygen carrying
capacity – this is the reason that endurance athletes like
to train at high altitude, and also why use of EPO and
autologous packed-cell transfusion are issues in
competitive endurance sports like cycling and Nordic ski
racing.
• In some individuals who spend prolonged time at high
altitude, the hematocrit can rise so high that RBCs tend
to sludge in capillaries – this causes chronic mountain
sickness.
Death at high altitude
• A disproportionate fraction of people who
die suddenly while mountain climbing at
high altitude turn out to have a patent
foramen ovale – a perforation of the atrial
septum that normally closes shortly after
birth. There is a flap that effects the
closure, and this normally fuses to close
the FO permanently. In some individuals,
the fusion does not occur.
The sequence of events leading to death runs as
follows:
1.
2.
3.
4.
Systemic arterioles dilate (due to low blood oxygen
and exercise), so TPR falls.
Pulmonary arterioles constrict (low oxygen levels in
alveolar gas and pulmonary blood), so pulmonary loop
resistance rises.
If pulmonary resistance rises above TPR, the flap that
normally closes the foramen ovale can be pushed
open, creating a left-to-right shunt.
The shunt has two drastic effects:
Pulmonary hypertension leading to pulmonary
edema
A drop in effective output of the left heart
A thought question
• In competitive swimming, ability to travel a long
distance underwater in one’s initial dive is
advantageous
• Swimmers were able to increase breath-holding
time by voluntary hyperventilation just before
diving – why?
• However, some of these swimmers became
unconscious underwater (why?) and died, and
this practice is no longer recommended.