Regulation of Respiration

What is This Lecture About?

The nervous system adjusts the rate of alveolar ventilation to the demands of the body so that the(PO2) and(PCO2) in the arterial blood are hardly altered even during heavy exercise and most types of respiratory stress.

Respiratory Center The respiratory center is composed of3 major collections of neurons: (1) a dorsal respiratory group (DRG), located in the dorsal portion of the medulla( causes Inspiration) (2) a ventral respiratory group (VRG), located in the ventrolateral part of the medulla, ( causes expiration) and (3) the pontine centers a- pneumotaxic center, located dorsally in the superior portion of the pons, ( mainly controls rate and depth of breathing) and b- apneustic center Note The DRG of neurons plays the most fundamental role in the control of respiration.

Neural control of Respiration Until recently, it was thought the Dorsal respiratory group of neurons generate the basic rhythm of breathing It is now generally 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 anterior The Rhythm: inspiration followed by expiration Fairly normal ventilation retained if section above medulla Ventilation ceases if section below medulla  medulla is major rhythm generator

Dorsal Respiratory Group of Neurons (DRG) The DRG of neurons in medulla responsible for the basic rhythm of respiration. vagal and the glossopharyngeal nerves, transmit sensory signals into the respiratory center from: (1) peripheral chemoreceptors, (2) baroreceptors, and (3) several types of receptors in the lungs.

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

The rhythm generated in the medulla can be modified by neurones in the pons: “pneumotaxic centre” (PC) + Without PC, breathing is prolonged inspiratory gasps with brief expiration Stimulation terminates inspiration - PC stimulated when dorsal respiratory neurones fire Inspiration inhibited

The “apneustic centre” Conclusion? Impulses from these neurones excite inspiratory area of medulla Rhythm generated in medulla Rhythm can be modified by inputs from pons Prolong inspiration

The function of the pneumotaxic center is primarily to limit inspiration. This has a secondary effect of increasing the rate of breathing, because limitation of inspiration also shortens expiration and the entire period of each respiration.

Ventral Respiratory Group (VRG) Located in each side of the medulla 1.The neurons of the ventral respiratory group remain almost totally inactive during normal quiet respiration.. 2.Providing the powerful expiratory signals to the abdominal muscles during heavy expiration.

What about “active” expiration during hyperventilation? Increased firing of dorsal neurones excites a second group: In normal quiet breathing, ventral neurones do not activate expiratory muscles Ventral respiratory group neurones Excite internal intercostals, abdominals etc Forceful expiration

The Hering-Breuer Inflation Reflex Stretch receptors located in the muscular portions of the walls of the bronchi and bronchioles throughout the lungs transmit signals through the vagi into the DRG of neurons when the lungs become overstretched that “switches off” and stops further inspiration. This is called the Hering-Breuer inflation reflex.

In human the Hering-Breuer reflex is a protective mechanism & not activated until the tidal volume (greater than about 1.5 L/ breath).

Chemical Control of Respiration The goal of respiration is to maintain proper conc. of O2,CO2,H+ ions in the tissues. * ↑↑CO2 or H+ stimulate the respiratory center it self→ ↑↑strength of insp. &exp. signals to the resp. m. * O2 does not have a direct effect on the respiratory center & acts on peripheral chemoreceptors located in the carotid &aortic bodies. These in turn transmit signals to the resp. center.

Chemosensitive area is located in medulla. is highly sensitive to changes in either blood PCO2 or H+ in turn excites the other portions of the respiratory center.

Why does blood CO2 have a more potent effect in stimulating the chemosensitive neurons than do blood hydrogen ions?

CO2 can cross the blood brain barrier. But H+ cannot . If the blood PCO2↑↑, PCO2 of both the interstitial fluid of the medulla and the cerebrospinal fluid ↑↑. In both these fluids, the CO2 reacts with the H2O to form new H+ .

Respiratory center activity is increased very strongly by changes in blood CO2. A change in blood CO2 has a potent acute effect on controlling respiratory drive and a weak chronic effect so after a few days’ adaptation takes place (its effect gradually declines over the next 1 to 2 days).

Notes - very marked increase in ventilation caused by an increase in PCO2 - By contrast, the change in respiration in the normal blood pH is less.

Peripheral chemoreceptor system Peripheral chemoreceptor system important for detecting changes in oxygen in the blood 1-most of the chemoreceptors are in the carotid bodies 2-few in the aortic bodies

When the O2 concentration in the arterial blood ↓↓ the chemoreceptors become strongly stimulated. An increase in either CO2 or H+ also excites the chemoreceptors and, indirectly increases respiratory activity. (the central effect is more potent). Stimulation of peripheral chemoreceptors occurs more rapidly than central stimulation, so that the peripheral chemoreceptors important in increasing the rapidity of response to CO2 at the onset of exercise.

Chronic breathing of low oxygen stimulates respiration Acclimatization: Mountain climbers when they ascend a mountain slowly, over a period of days rather than a period of hours, they breathe much more deeply and therefore can withstand far lower atmospheric oxygen concentrations than when they ascend rapidly. within 2 to 3 days respiratory center loses its sensitivity to changes in PCO2 and H+.

Low O2 can drive the respiratory system to a much higher level of alveolar ventilation than under acute conditions, after 2 to 3 days of low oxygen; the alveolar ventilation ↑↑ and this helps in supplying additional oxygen to the mountain climber.

Regulation of respiration during exercise In strenuous exercise, O2 consumption and CO2 formation can ↑↑ as much as 20-fold. In the healthy athlete, alveolar ventilation ordinarily ↑↑ almost exactly in step with the ↑↑ level of O2 metabolism. The arterial PO2, P CO2, and pH remain almost exactly normal.

Factors that 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

What causes intense ventilation during exercise? The brain, *transmitting motor impulses to the exercising muscles *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 increase in arterial pressure).

Other factors affect respiration Voluntary control of respiration For short periods of time, respiration can be controlled voluntarily (hyperventilate or hypoventilate) to such an extent that serious derangements in P CO2, pH, and PO2 can occur in the blood.

Irritant receptors Stimulated by inhaled irritants or mechanical factors Cause bronchospasm, cough, sneeze, tachypnea, and narrowing of glottis These are vasovagal reflexes. In hospital triggered by Suctioning, bronchoscopy, endotracheal intubation

“J receptors.” A few sensory nerve endings in the alveolar walls in juxtaposition to the pulmonary capillaries ,stimulated by engorged pulmonary capillaries or in pulmonary edema as in congestive heart failure. (Their excitation may give the person a feeling of dyspnea).

Joint receptors Impulses from moving limbs reflexly increase breathing Probably contribute to the increased ventilation during exercise Anesthesia. greatly depresses the respiratory center

Effect of pH on Respiration

The effect of low arterial PO2 on alveolar ventilation is far greater under some conditions including the following: *pulmonary disease: no adequate gas exchange, too little O2 is absorbed into the arterial bl. &at same time the arterial PCO2& H+ conc. remain near normal or are ↑↑because of poor transport of CO2 through the membrane. *acclimatization to low O2

Influence of Chemical Factors on Respiration

Periodic Breathing The person breathes deeply for a short interval and then breathes slightly for an additional interval, with the cycle repeating itself over and over.

Cheyne-Stokes breathing, is characterized by slowly waxing and waning respiration occurring about every 40 to 60 seconds. The basic cause of Cheyne-Stokes breathing may occurs in everyone it can be found in congestive heart failure, uremia and in damage of respiratory center.

Cheyne-Stokes breathing, showing changing PCO2

Apnea: means absence of spontaneous breathing. Sleep Apnea Apnea: means absence of spontaneous breathing. sleep apnea: apneas occur during normal sleep, can be caused by obstruction of the upper airways, especially the pharynx, or by impaired central nervous system respiratory drive.

Periods of apnea result in significant decreases in P O2 and increases in PCO2 which greatly stimulate respiration. causes sudden attempts to breathe, which result in loud snorts and gasps followed by snoring and repeated episodes of apnea.

Summary of ventilation control Respiration is regulated by: PO2 via chemoreceptor (carotid bodies in the arteries) PCO2 via chemoreceptor for H+ in both the brain and body. pH via the same chemoreceptor in brain and body Direct voluntary control.