Chapter 9 Control of breathing
Department of Pathophysiology, the School of Medicine, Shandong University
Zhongrui Yuan, Ph.D. [email protected] Control of breathing
Neuronal control of breathing:
Chemical control of breathing: • Neuronal control of breathing:
• Minute ventilation VE = VT × f
VT: the tidal v. of each individual breath f: the frequency of breathing
We unconsciously “choose” a particular patter, which is the province of neuronal control of breathing. Ⅰ Respiratory Centers
Breathing is a rhythmic process, which originates in the brainstem: Medulla Pons
Respiratory Centers Medulla
Inspiratory center (dorsal respiratory group, DRG): neurons are continuously active (spontaneous)
Expiratory center (ventral respiratory group, VRG) involved in forced expiration Rhythmic Ventilation: inspiratory off-switch mechanism •Starting inspiration –More and more neurons are activated in DGR •Stopping inspiration –DRG Neurons receive input from pontine group and stretch receptors in lungs. –Inhibitory neurons activated and relaxation of respiratory muscles results in expiration. –Inspiratory off switch. Ⅱ Reflex regulations of respiratory 1. Hering-Breuer Reflex or Pulmonary Stretch Reflex 黑-伯反射或肺牵张反射
• 感受器: 位于从气管道细支气管的平滑肌中
１．肺扩张反射： 肺充气或扩张时， 抑制吸气的反射。 有助于防止肺过度 扩张。
２．肺萎陷反射： 肺萎陷时，促进 吸气的反射。 有助于防止肺萎陷。 2. Chemical control of breathing The “objective” of respiration is homeostasis of arterial blood in terms of O2 and CO2 (which is closely related to [H+]).
This is achieved by matching ventilation to the metabolic activity of the body.
This matching require monitoring of the chemical composition of arterial blood, and the sensors which act as monitors are known as chemoreceptors Two types of chemoreceptors
• Central chemoreceptors: most sensitive to excess Fig 9.1
CO2
• Peripheral chemoreceptors: most sensitive to
lack of O2
Excess CO2 and lack of O2 usually occur together. 1) Peripheral chemoreceptors ： Sense lack of O2 in arterial blood
Sinus nerve
Respir- ation
Cardio- vascular Carotid Body
• An extremely high metabolic rate:
(3 times of brain’s, 8 ml O2/min/100g) • High perfusion rate: (2000ml/min/100 g, brain: 54ml/min/100 g)
• Tiny a-v O2 difference:
• Receptor cells monitor PaO2, not CaO2: anemia ,CO poisoning → no response
Responsiveness begins at PaO2 (not the oxygen content) below about 60 mmHg (8 kPa) . Hypoxic stimulation
PO2↓ Ventilation per minute carotid body perfusate The frequency of discharge
recording electrode Hypoxic stimulation
100 mmHg:13.3 kPa 60 mmHg: 8 kPa 30 mmHg: 4 kPa 40 mmHg: 5.33 kPa Hypoxia and breathing
• PaO2 must be reduced considerably (to about half normal, below about 60 mmHg/8 kPa) before breathing is stimulated. • It would be a waste of time having a more sensitive detector of 8 kPa oxygen lack due to the shape of HbO2 13.3kPa dissociation curve. Hypoxia and breathing
• Peripheral chemoreceptors are the only mechanism in the body by which low O2 tension can stimulate breathing • Hypoxic stimulation of breathing is also apposed by + changes in CO2 and [H ].
• Hypocapnic brake: Increased ventilation caused by hypoxia washes out CO2, the reduced PaCO2 reduces drive to breathe (fig 9.4). Hyperventilation
Hyperventilation is an important compensatory response for acute hypoxia
---PaO2 60~100 mmHg：No alteration
---PaO2<60 mmHg: Peripheral chemoreceptors
☆significance ：a. PAO2 ↑→PaO2 ↑ PaCO2↓(limit) b. negative intrathoracic pressure↑ →venous return↑ → CO and pulmonary blood flow ↑ → ↑ Oxygen obtaining and transport ☆Respiratory alkalosis, to inhibit respiratory center Hypercapnic stimulation
• Increased levels of PaCO2 (hypercapnia) also stimulates peripheral chemoreceptors, probably by increasing [H+]. Peripheral chemoreceptors
are much less sensitive to increase in PaCO2 than the central chemoreceptors 2) The central chemoreceptors: Sense Carbon dioxide excess in arterial blood
Hypercapnia:high level of CO2
Hypocapnia: low level of CO2
The PaCO2 of the blood reaching the brain is the major chemical factor normally regulating ventilation. The central chemoreceptors: to detect the level of
PaCO2 Central chemoreceptor responses
Perfusing with acidic solutions or solutions with a high PCO2 stimulates breathing. the specific stimulus to the DRG Central chemoreceptor neurons is intracellular [H+], which is determined primarily by the PCO2 of the cerebrospinal fluid.
Any increase in inhaled CO2, unlike reductions in PaO2, stimulates breathing in a linear manner (Fig 9.7) , until levels are reached which act as an effective anasthetic.
Small and acute decrease in blood CO2, caused by singing, for example, do not depressing breathing Fig 9.7 because of the horizontal part of the PCO2/VE curve.
On arerage, increasing people’s PaCO2 by 0.3 kPa doubles their min ventilation. Central chemoreceptor responses
They are not stimulated by hypoxia. In fact, severe hypoxia depresses breathing in adults by a direct action on the respiratory complex in the brainstem.
The response of them to PaCO2 takes about 5 min to reach equilibrium, whereas within seconds for the peripheral chemoreceptors.
Central chemoreceptors are responsible for about 80% of our sensitivity to CO2. Central chemoreceptor responses
• Increasing arterial [H+] does not have a great effect on central chemoreceptors (the central chemoreceptors are protected from changes in arterial [H+] by the blood- brain barrier/BBB) but stimulates peripheral chemoreceptors. Blood/CSF relationships BBB Arterial CSF
CO 2 CO2 H 2O
HCO3 H Central
slow ?? Chemoreceptor H+ H+ ??? • PaCO2 (N:40mmHg, 5.33kPa) ↑→ pH of ESF↓ →to stimulate central chemoreceptor →☆ the respiratory center→ventilation↑
• PaCO2 >60mmHg (8kPa) →ventilation↑10 times
but, PaCO2 >80mmHg (10.7kPa) → respiratory center in the brainstem ，called as carbon dioxide narcosis Blue bloater，紫肿 • Patients with COPD, have marked arterial hypoxaemia
and CO2 retention but do not seem to be breathless. • “Blue bloater”: blue : cyanosed ; bloated: congestive heart failure.
• These patients have adapted to high PaCO2, and so the
majority of their drive to breathe comes from O2 lack detected by the peripheral chemoreceptors. So we
should give the patients O2 with low concentration and low flow rate to avoid the deprivation of stimulation
from O2 lack to breathing. •These patients are particularly at risk if they require a general anesthetic. The peripheral chemoreceptors are extremely sensitive to inhalation anasthetics （fig 9.6).
MAC: minimal alveolar concentration for anaesthesia
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