regulation of the respiration

Regulation of breathing

What is This Lecture About?

What makes the inspiratory muscles contract and relax rhythmically? How could the respiratory activity be modified? How could the expiratory muscles be called on during active expiration? How could the arterial PO2 and PCO2 be maintained within narrow limits? What is the role of the respiratory system in regulating blood H+ concentration?

The Neural & Chemical Control of Respiration

To answer these questions we need to understand:

Neural control The motor neurons that stimulate the respiratory muscles are controlled by two major descending pathways: one that controls voluntary breathing and another that controls involuntary breathing. The unconscious rhythmic control of breathing is influenced by sensory feedback from receptors sensitive to the PCO2, pH, and PO2 of arterial blood.


Inspiration and expiration are produced by the contraction and relaxation of skeletal muscles in response to activity in somatic motor neurons in the spinal cord. The activity of these motor neurons is controlled, by descending tracts from neurons in the respiratory control centers in the medulla oblongata and from neurons in the cerebral cortex.

Fairly normal ventilation retained if section above medulla

Ventilation ceases if section below medulla
 medulla is major rhythm generator The Rhythm: inspiration followed by expiration
anterior

Neural control of Respiration

It is believed that the breathing rhythm is generated by a network of neurons called the Pre-Brotzinger complex. These neurons display pacemaker activity. They are located near the upper end of the medullary respiratory centre

Neural control of Respiration

PONS
MEDULLA
SPINAL CORD
Dorsal respiratory group neurones (inspiratory)
Fire in bursts
Firing leads to contraction of inspiratory muscles - inspiration
When firing stops, passive expiration

What gives rise to inspiration?

Increased firing of dorsal neurones excites a second group:
Ventral respiratory group neurones
Excite internal intercostals, abdominals etc
Forceful expiration
In normal quiet breathing, ventral neurones do not activate expiratory muscles

What about “active” expiration during hyperventilation?

“pneumotaxic centre” (PC) Stimulation terminates inspiration
PC stimulated when dorsal respiratory neurones fire
Inspiration inhibited
-
+

The rhythm generated in the medulla can be modified by neurones in the pons:

Apneustic centre
Impulses from these neurones excite inspiratory area of medulla
Prolong inspiration
Conclusion?
Rhythm generated in medulla modified by inputs from pons

The “apneustic centre”

Pulmonary stretch receptors Activated during inspiration, afferent discharge inhibits inspiration - Hering-Breuer reflex Do they switch off inspiration during normal respiratory cycle? Unlikely - only activated at large >>1 -1.5 litre tidal volumes Maybe important in new born babies May prevent over-inflation lungs during hard exercise?

Reflex modification of breathing

Chemical Control of Respiration


An example of a negative feedback control system Chemoreceptors sense the values of the gas tensions central and peripheral The activity of the respiratory centers is regulated by the O2, CO2 and H+ content of the blood.


Chemical regulation of respiration Central chemoreceptors Carbon dioxide and H+ are most important. CO2 dissolves in cerebrospinal fluid (CSF) which bathes receptors sensitive to H+ on the ventral aspect of the medulla. Stimulation of these receptors is responsible for about 70% of the increase in the rate and depth of respiration in response to increased CO2. Respond to the [H+] of the cerebrospinal fluid (CSF) CSF is separated from the blood by the blood-brain barrier Relatively impermeable to H+ and HCO3- CO2 diffuses readily CSF contains less protein than blood and hence is less buffered than blood

Increase in CO2 increasesH+ concentration in CSF(CO2 + H2O in CSF H2CO3 HCO3– + H+) Stimulates H+ receptors
Stimulates RESPIRATORY CENTERS
Increases rate and depth of breathing
Fall in blood CO2 slightly depresses breathing



Сarotid and aortic bodies are responsible for the other 30% of the response to raised to CO2. They also increase ventilation in response to a rise in H+ or a large drop in PaO2 ( to below 60 mmHg).


Arterial PaO2, normally 100 mmHg, has to fall to 60 mmHg to stimulate chemoreceptors. Severe lack of O2 depresses respiratory center. CHEMO-REFLEXES: in addition to the effect of CO2 and O2 on center, rise in H+ of blood stimulates carotid and aortic bodies.
Lack of O2
Stimulates CHEMORECEPTORS(‘Oxygen-lack’ receptors)in carotid bodyand aortic body Reflexly stimulates respiration


The chemical and nervous means of regulating the activity of respiratory centers act together to adjust rate and depth of breathing to keep the PaCO2 close to 40 mmHg. This automatically sets the PaO2 to an appropriate value depending on the partial pressure of O2. For example, exercise causes increased requirement for O2 and the production of more CO2. ventilation is increased to get rid of the extra CO2 and keep the alveolar PaCO2 at 40 mmHg. More oxygen is used by the tissues. The alveolar PO2 and PCO2 both remain constant.

Voluntary and reflex factor in the regulation of respiration

There is a separate voluntary system for the regulation of ventilation. It originates in the cerebral cortex and sends impulses to the nerves of the respiratory muscles via the corticospinal tracts. In addition, ingoing impulses from many parts of the body modify the activity of the respiratory centers and consequently alter the outgoing impulses to the respiratory muscles to coordinate rhythm, rate or depth of breathing with other activities of the body.


Proprioreceptors stimulated during muscle movements send impulses to respiratory center ↑↑ rate and depth of breathing. This occurs with active or passive movements of limbs.) Peripheral proprioceptors found in muscles, tendons, joints, and pain receptorsMovement stimulates hyperpnea.Moving limbs, pain, cold water all stimulate breathing in patients with respiratory depression


Anesthesia greatly depresses the respiratory center J receptors A few sensory nerve endings in the alveolar walls in juxtaposition to the pulmonary capillaries They are stimulated when the pulmonary capillaries become engorged or when pulmonary edema occurs as in congestive heart failure. (their excitation may give the person a feeling of dyspnea).



Irritant Receptors in the Airways The epithelium of the trachea, bronchi, and bronchioles is supplied with sensory nerve endings called pulmonary irritant receptors when stimulated cause coughing and sneezing. They may also cause bronchial constriction in such diseases as asthma and emphysema.

Joint receptors Impulses from moving limbs reflexly increase breathing Probably contribute to the increased ventilation during exercise

Factors That May Increase Ventilation During Exercise

Reflexes originating from body movement Increase in body temperature Adrenaline release Impulses from the cerebral cortex Later: accumulation of CO2 and H+ generated by active muscles

Carotid bodies

Aortic bodies
Sense tension of oxygen and carbon dioxide; and [H+] in the blood

Peripheral Chemoreceptors

Hypoxic Drive of Respiration



The effect is all via the peripheral chemoreceptors Stimulated only when arterial PO2 fall less than 60mmHg Is not important in normal respiration May become important in patients with chronic CO2 retention (e.g. patients with COPD) It is important at high altitudes

The H+ Drive of Respiration

The effect is via the peripheral chemoreceptorsH+ doesn’t readily cross the blood brain barrier (CO2 does!)The peripheral chemoreceptors play a major role in adjusting for acidosis caused by the addition of non-carbonic acid H+ to the blood (e.g. lactic acid during exercise; and diabetic ketoacidosis)Their stimulation by H+ causes hyperventilation and increases elimination of CO2 from the body (remember CO2 can generate H+, so its increased elimination help reduce the load of H+ in the body) This is important in acid-base balance


In summary very marked increase in ventilation caused by an increase in Pco2 in the normal range between 35 and75 mm Hg. By contrast, the change in respiration in the normal blood pH range between 7.3 and 7.5 is less than one tenth as great.


Changes in oxygen concentration have virtually no direct effect on the respiratory center itself to alter respiratory drive (although oxygen changes do have an indirect effect, acting through the peripheral chemoreceptors


Abnormal Breathing Patterns Apnea Absence of breathing. (Ap-knee-a) Eupnea Normal breathing (Eup-knee-a) Orthopnea Only able to breathe comfortable in upright position (such as sitting in chair), unable to breath laying down, (Or-thop-knee-a) Dyspnea Subjective sensation related by patient as to breathing difficulty.


Hyperpnea Increased volume with or without and increased frequency (RR), normal blood gases present


Hyperventilation"Over" ventilation - ventilation in excess of the body's need for CO2 elimination. Results in a decreased PaCO2, and a respiratory alkalosis


Tachypnea Increased frequency without blood gas abnormality. Cheyne-Stokes respirations Gradual increase in volume and frequency, followed by a gradual decrease in volume and frequency, with apnea periods of 10 - 30 seconds between cycle

Regulation of Respiration During Exercise

In strenuous exercise, O2 consumption and CO2 formation can increase as much as 20-fold. in the healthy athlete,alveolar ventilation ordinarily increases almost exactly in step with the increased level of oxygen metabolism. The arterial Po2, Pco2, and pH remain almost exactly normal.

Chemical Factors and Nervous: in the Control of Respiration During Exercise

Direct nervous signals stimulate the respiratory center almost the proper amount to supply the extra oxygen required for exercise and to blow off extra carbon dioxide; Then chemical factors play a significant role in the final adjustment of respiration required to keep the oxygen, carbon dioxide, and hydrogen ion concentrations of the body fluids as nearly normal as possible.


What causes intense ventilation during exercise? The brain, on transmitting motor impulses to the exercising muscles at the same time collateral impulses into the brain stem to excite the respiratory center. This is analogous to the stimulation of the vasomotor center of the brain stem during exercise that causes a simultaneous increase in arterial pressure.