Week 10 Flashcards
Respiratory control center
Breathing originates from a central pattern generator in the brainstem (medulla and pons)
How can CPG be divided?
- Sites that generate breathing rhythm
- Downstream sites that form the motor pattern and synapse with efferent motor neurons
Central Rhythm generator
Rhythmic groups of neurons that area active during inspiration (prebotC), post-inspiration (PiCo), and expiration (pF)
Ventral Respiratory Group
Includes the central rhythm generator and the motor pattern generators neurons
- Controls the activity of respiratory muscles
Pontine respiratory group
Modulates output from the ventral respiratory group
What nerves innervate the respiratory muscles?
- Diaphragm: phrenic nerve
- External intercostals: External intercostal nerves
- Internal Intercostals: Internal intercostal nerves
- Airway muscles are also controlled by the CPG via cranial nerves
Sensory input to central pattern generators
- Peripheral sensory receptors send afferent information to the NTS in the dorsal medulla
- Interneurons connect sensory afferents in the NTS to the ventral respiratory group and thus modulate its output
- Also have central chemoreceptors in the medulla that modulate VRG output
Hypoxic Ventilatory Response
- Reductions in arterial PO2 lead to an increase in ventilation
- Small declines in PO2 below normal arterial values can be fully corrected by increasing ventilation
- Larger declines in arterial PO2 cannot be fully compensated, but the increase in ventilation reduces the magnitude of PO2 decline
Peripheral O2 Chemoreceptors
- Primary O2 chemoreceptors are located in the carotid bodies, but the aortic bodies also play a role in the HVR
- Afferent neurons form synapse with interneurons in the NTS, which transmit the sensory information to the central pattern generator
How do the carotid bodies become activated and send AP
- Not well understood sensor in membrane of the carotid body glomus cell activated by decrease in PO2
- Closing on K+ channels
- Depolarization (K+ can’t leave)
- Opening of voltage-gated Ca2+ channels
- Vesicles release ACh and ATP
- Increase AP frequency
How will reducing blood haemoglobin concentration affect the hypoxic ventilatory response
- No change
- Corotid bodies sense partial pressure
- decrease in partial pressure drives O2 into cell - decrease in PO2 = decrease in O2 t cell
Ventilatory Response to CO2/H+
- Increase in arterial PCO2 or decrease in pH lead to increase in ventilation
- Breathing is more sensitive to changes in PCO2 than PO2 in air breathing vertebrates
- Response results from both peripheral and central chemoreceptors
Central CO2/H+ chemoreceptors
- Central Chemoreceptors in the medulla sense CO2 and H+ cerebral spinal fluid, which are related via the carbonic anhydrase reaction
- CO2 can cross the blood-brain barrier, but H+ cannot, so arterial CO2 is also sensed by these receptors
- Central receptors contribute more than peripheral chemoreceptors to the ventilatory response to arterial CO2, but only peripheral chemoreceptors respond to changes in arterial pH
How is a decrease in both PO2 and PCO2 accounted for by alveolar ventilation
At a given PCO2, the greater the PO2 the less ventilation will occur in compensation
- A decrease in pH will shift the curves to the left to increase ventilation at a given PCO2 and PO2 value
How will the hypoxic ventilatory response affect arterial CO2?
- Decreases in PO2 cause subsequent decreases in PCO2
- Increases in PO2 causes increases in PCO2 due to decrease in alveolar ventilation
- Implies a restrained response to hypoxia - can’t exhale too much CO2 (prominent Vasodilator)
How will experimentally maintaining arterial PCO2 affect the hypoxic ventilatory response?
- Result in a more pronounced homeostatic response
- Effectors regulate more than 1 variable leading to trade off in homeostatic regulation under normal conditions
How does ventilation respond to increased metabolism?
Strong positive correlation between increases in metabolism and increased ventilation
What 3 factors are responsible for the changes in ventilation in response to an increase in metabolism
- Central Command
- Produces initial overshooting for ventilation causing reduction in pCO2 - Feedback form active tissues
- Activated as ventilation reaches peak as mitochondrial mechanisms take time to kick in - Feedback from chemoreceptors
- Activated second in response to changes in arterial partial pressures
Ventilation-Perfusion Relationships
Reductions in V/Q lead to large decreases in the partial pressure of O2 in the alveoli, but increases in V/Q lead to only modest increases in alveolar PO2
- This is true across entire lungs and for individual alveoli
Ventilation-Perfusion Inequality
- Regional variation in ventilation between lung regions or between alveoli affects the overall effectiveness of gas exchange
- Having the same ventilation ratio across all alveoli is more effective for gas exchange than having some under-ventilated and some over-ventilated
How is the distribution of ventilation and prefusion examined
By quantifying the proportion of ventilation or blood flow across a range of V/Q ratios
- in healthy individuals the distributions are tightly centered at 1 (most of the ventilation and blood flow is well matched)
How does emphysema affect the distribution of ventilation and perfusion
Causes bimodal distribution in perfusion with smaller lump on smaller ratio and main lump shifted slightly right
Mechanisms of Ventilation-perfusion Matching
- Pulmonary arterioles constrict in response to low partial pressure of O2
- Vasoconstriction increases vascular resistance and reduces local blood flow in flavor of other lung regions with higher PO2
Global Hypoxia in Lung disease
- Chronic vasoconstriction throughout the entire lungs leads to hypertrophic remodeling that increases arterial wall thickness
- Contributes to hypoxic pulmonary hypertension
- HPH can lead to edema and increases workload on the RV, leading to RV hypertrophy and in sever cases RV failure and death
