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26
Central Control of Ventilation
73
Pharmacology
Undergraduate 1
12/23/2016

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Term
What is the primary role of the respiratory system?
Definition
to match alveolar ventilation to perfusion so that the oxygen needs of the respiring tissues is met
Term
How are arterial partial pressures of O2 and CO2 maintained?
Definition
regulation of minute alveolar ventilation
(Minute alveolar ventilation depends on the both the rate and depth of breathing)
Term
What type of muscle are the respiratory muscles and what are they innervated by?
Definition
skeletal muscles
somatic motor neurones
Term
What nerve innervates the diaphragm?
Definition
the phrenic nerve

GRAPH
Term
What nerve innervates the intercostal muscles?
Definition
internal and external intercostal nerves

GRAPH
Term
Which part of the breathing cycle is passive?
Definition
quiet breathing expiration
Term
What does quiet breathing expiration rely on?
Definition
the elastic recoil of the lungs and chest wall
Term
Which part of the breathing cycle is active?
Definition
always inspiration
active breathing expiration
Term
What does inspiration rely on?
Definition
involving the diaphragm and external intercostals
Term
What does active breathing expiration rely on?
Definition
involving the internal intercostals and, often, the abdominal muscles
Term
Where are respiratory control regions present?
Definition
the medulla and pons of the brainstem (although it is thought that the true situation is more complex, and that respiratory control regions may also be present in other areas of the brain)
Term
What neurones exist in the respiratory control centres?
Definition
inspiratory neurones and expiratory neurones, which generate action potentials during inspiration and expiration respectively
Term
Which respiratory control centres are located on the medulla?
Definition
1. The ventral respiratory group (VRG)
2. The dorsal respiratory group (DRG)
Term
Which neurones are found in in the VRG?
Definition
2 groups of primarily expiratory neurones and one region of primarily inspiratory neurones
Term
Which neurones are found in in the DRG?
Definition
The DRG contains primarily inspiratory neurones
Term
What is it thought that the inspiratory neurones in the VRG and DRG 'control'?
Definition
the motor neurones that control the inspiratory muscles
Term
What do neurones in the inspiratory areas of the VRG and DRG exhibit?
Definition
an intrinsic rhythm pattern of activity
Term
When do the inspiratory neurones exhibit little of no activity?
Definition
during expiration and when the respiratory system is 'at rest'
Term
Describe the events inspiratory neurones at the onset of inspiration
Definition
1. AP frequency is low
2. 'ramp increase' as inspiration proceeds, reaching a crescendo at the peak of inspiration
Term
Describe the events inspiratory neurones at the end of inspiration
Definition
the end coincides with an abrupt termination of inspiratory neuronal activity, and expiration begins
Term
What correlated with the AP frequency of the inspiratory neurones in the VRG and DRG?
Definition
- activity in the motor neurones innervating the inspiratory muscles
- the force of contraction of these muscles
Term
What are the pontine respiratory group neurones thought to primarily affect?
Definition
the inspiratory neurones in the medulla
Term
What are the pontine respiratory group neurones formally referred to?
Definition
the apneustic and pneumotaxic centres
Term
What could the function of the PRG neurones be?
Definition
The function of the PRG neurones may be to regulate respiratory rate and depth and to ‘ fine tune’ the respiratory rhythm
Term
Are PRG neurones stimulatory or inhibitory?
Definition
both!
Term
Describe how PRG neurones can be stimulatory
Definition
Some PRG neurones apparently have an excitatory effect, tending to prolong the burst of action potentials of the medullary inspiratory neurones
Term
Describe how PRG neurones can be inhibitory
Definition
Other PRG neurones appear to ‘switch off’ or inhibit inspiration
Term
Draw the brainstem and label the PRG, DRG and VRG
Definition
See diagram
Term
List the inputs for the central pattern generator
Definition
1. Sensory
- central chemoreceptors
- peripheral chemoreceptors
- pulmonary stretch receptors
- irritant receptors
- proprioceptors
2. pons
3. cortex (voluntary control)
Term
Where is the central pattern generator?
Definition
medulla
Term
What is a hypothesis for respiratory rhythm generation?
Definition
- a network of neurones (medulla) is responsible
- certain neurones have pacemaker activity (similar to cells in SAN), although no such have been identified
Term
What is the output of the central pattern generator?
Definition
-->
to inspiratory neurones of DRG and VRG (medulla)
-->
breathing rhythm
Term
Where are pulmonary stretch receptors located?
Definition
within airway smooth muscle and the pleura
Term
What are pulmonary stretch receptors activated by?
Definition
distension of the lung (lung inflation)
Term
What is the main reflex effect of pulmonary stretch receptor activation?
Definition
Hering-Breuer inflation reflex
Activation of the pulmonary stretch receptors (via the vagus nerve) results in inhibition of the inspiratory stimlus in the medulla, and thus inhibition of inspiration and initiation of expiration.
Term
Describe the Hering-Breuer inflation reflex
Definition
The pneumotaxic center of the pons sends signals to inhibit the apneustic center of the pons, so it doesn't activate the inspiratory area (the dorsal medulla), and the inspiratory signals that are sent to the diaphragm and accessory muscles stop. This is called the inflation reflex.
Term
What have experiments shown?
Definition
inflation of the lungs tends to inhibit further inspiratory muscle activity; the opposite response is also seen (i.e. deflation of the lung tends to initiate inspiratory activity)
Term
What were Hering-Breuer reflexes thought to play a major role in?
Definition
determining the rate and depth of breathing by modulating the activity of PRG neurones
Term
What have more recent experiments regarding Hering-Breuer reflexes shown?
Definition
that these reflexes are largely inactive in adult humans (except at high lung volumes), but that they are important in other animal species (and possibly in newborn babies)
Term
When is ventilation stimulated?
Definition
Once PaO2 falls below about 60 mmHg
Term
What are the effects of ventilation?
Definition
This increases PAO2 because the alveolar air is replaced with ‘fresh’ inspired air more rapidly, thus bringing PAO2 closer to PIO2
Term
What does high altitude cause respiratory alkalosis?
Definition
- At rest, CO2 production at altitude is not significantly different from sea level
- Therefore, increased ventilation ‘blows off’ CO2, reducing PACO2 (one of the reasons why PAO2 increases).
- This drives the equation to the left which results in respiratory alkalosis
Term
Why is the initial increase in ventilation is less than 2-fold, even at extreme altitudes?
Definition
increased ventilation reduces PACO2 so increased or even hyperventilation would further this
Term
Therefore what are the chemical effects of increased ventilation at altitude?
Definition
decreased PaCO2 and [H+]
Term
How are these chemical effects detected?
Definition
Decreased PaCO2 is detected by central chemoreceptors and decreased arterial [H+] is detected by peripheral chemoreceptors
Term
What is the outcome of these inputs?
Definition
These inputs combine to inhibit ventilation via negative feedback
Term
When is Cheyne-Stokes Respiration most common? What mantra does it inspire?
Definition
This breathing pattern is most common at night, where it often results in sleep disturbances, hence the climbers maxim ‘Climb high, sleep low’
Term
Describe the Cheyne-Stokes Respiration pattern
Definition
ycles of respiration that are increasingly deeper then shallower with possible periods of apnoea.
Term
What shifts the Haemoglobin-O2 Dissociation Curve to the left?
Definition
- decreased PaCO2 (the carbamino effect)
- increased pH (the Bohr effect)
Term
What are the effect of a shifted Haemoglobin-O2 Dissociation Curve to the left?
Definition
- favours O2 association in the lungs (good news)
- inhibits O2 unloading in the systemic capillaries (bad news)
Term
How is respiratory alkalosis compensated?
Definition
- pH is restored towards normal by decreased reabsorption of HCO3-
- Plasma [HCO3-] is further depressed
Term
What is altitude acclimatisation?
Definition
describes the adaptive responses that improve one’s tolerance to altitude hypoxia
Term
When do altitude acclimatisation occur?
Definition
- progressively to each increase in altitude
- Some adjustments occur almost immediately; others develop much more slowly
Term
When does full acclimatisation occur?
Definition
many weeks or even months
Term
What are the two most important immediate adjustments to altitude?
Definition
1. hyperventilation
2. increased CO at rest and during submaximal exercise
Term
What causes hyperventilation?
Definition
the hypoxic respiratory drive
Term
How much can sub maximal CO and HR increase by?
Definition
up to 50% above sea level values
SV is a little changed
Term
What does increased CO do?
Definition
). This increases systemic and pulmonary blood flow and goes some way to compensating for the reduced arterial O2 content
Term
What can lead to moderate dehydration?
Definition
Increased respiratory fluid loss and a decreased thirst sensation
Term
What does increased ventilation seen at altitude leads to?
Definition
respiratory alkalosis
Term
How is respiratory alkalosis compensated?
Definition
renal
Term
What does renal compensation result in?
Definition
increased excretion of HCO3-, leading to a partial restoration of blood pH
Term
What are the consequences of loss of HCO3-?
Definition
1. Osmotic diuresis which leads to further fluid loss from the body. This leads to a reduction in plasma volume and a consequent increase in haematocrit.
2. There is a reduction in the blood’s buffering capacity for non-carbonic acids such as lactic acid. This reduces the critical level of exercise that can be tolerated without the accumulation of blood lactate
Term
How much does ventilation increase by?
Definition
- initially, increase in ventilation at altitude is less than 2-fold
- over a period of 2 – 3 weeks at altitude it increases further, up to a maximum of 5 – 7 times its sea level value
Term
What causes the initial increase in ventilation?
Definition
increased breathing frequency
Term
What causes the secondary increase in ventilation?
Definition
increases in tidal volume, i.e. the depth of breathing increases, which is a more efficient way of increasing alveolar ventilation
Term
What is the most important factor in altitude acclimatisation?
Definition
the greater the alveolar ventilation, the greater the uptake of O2 at any given altitude
Term
What removes the 'brake' on ventilation, to allow for the observed second rise in ventilation?
Definition
- renal compensation for respiratory alkalosis contributes
- this effect is too small and too slow-developing to fully account though
- the full answer is not known
Term
What are the other hypotheses?
Definition
1. Increases in the sensitivity of peripheral chemoreceptors to low PaO2 occur over the first few days at altitude
2. A gradual restoration of a near-normal CSF pH may occur, reducing the indirect effect of low PaCO2 on the central chemoreceptors
Term
What causes the initial increase in HCt?
Definition
a decrease in plasma volume (and in total blood volume
Term
What are the effects of a decreased plasma volume?
Definition
It increases the O2-carrying capacity of each litre of blood, but is of dubious benefit because of its effect on stroke volume (Starling mechanism)
Term
What are the effects in the kidneys? how does this affect the HCt?
Definition
Hypoxia stimulates the kidneys to release the hormone erythropoietin (EPO) within 15 hours of ascent to altitude. Over the next few weeks, this results in a progressive increase in RNC synthesis, leading to increased numbers of circulating RBCs
Term
Does the HCt ever increase?
Definition
Yes
When RBC formation increases, plasma volume returns to near normal, resulting in an increase in both blood volume and HCt (compared to sea level values). HCt can increase from ~40% to as much as 60% in fully acclimatized individuals
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