List the physiological factors that increase respiratory rate. Include an explanation of the mechanism by which each achieves this increase.

[Click here to toggle visibility of the answers]

College Answer

The main points candidates were expected to cover included:
· A description of the central and peripheral chemoreceptors, their predominant stimuli and
effect on ventilation.
· PaCO2 as the main influence on normal ventilation, the near-linear relationship to minute
ventilation around the normal range, and how CO2 produces this effect.
· PaO2 and pH and their sites of action.
· Other stimuli to ventilation – exercise, pregnancy, temperature, baroreceptors.
Candidates frequently confused central and peripheral receptor activities and failed to provide
any relative significance to the major factor(s). The use of a graph relating the main factors
to minute ventilation would have been helpful.

Reference: Nunn 6th edition 60-68
Kam 1st edition 92-98

Discussion

This question is essentially identical to Question 6 from the first paper of 2010.

Physiological Factors which Influence the Respiratory Rate

Physiological factor Mechanism Physiological effect
PaCO2

Sensed by peripheral chemoreceptors:
- Carotid bodies (glossopharyngeal nerve)
- Aortic bodies (vagus nerve)

Increased PaCO2 increases the respiratory rate and tidal volume 

Decreased PaO2 increases the respiratory rate
(rapidly acting breath-to-breath control of respiration)
- this response to hypoxia is triphasic

PaO2
pH

Sensed by central chemoreceptors in the medulla

Decreased pH in the CSF increases the respiratory rate and tidal volume
(slow acting, steady state control; adjustments occur over minutes)
Temperature

Increased sensitivity of periphperal chemoreceptors to O2

Increased sensitivity of central chemoreceptors to changes in pH

A rise in temperature will increase the minute volume at any given PaCO2 and PaO2 level

Responses to hypoxia and hypercapnia are
amplified by hyperthermia

Exercise

Descending control of muscle activity simultaneously simulates the central respiratory control centres

The ventilatory response of exercise is increased ventilation, and because this is not a feedback mechanism the increase in ventilation is simultaneous with the beginning of exercise, or actually slightly precedes it. 
Pregnancy

Progesterone acts directly on central integrative control of ventilation

During pregnancy, minute volume increases and the stable PaCO2  baseline progressively decreases, producing the respiratory alkalosis of pregnancy
Blood pressure

Sensed by aortic chemoreceptors and carotid sinus baroreceptors

Hypertension decreases the respiratory rate and hypotension increases it.

With a sufficient acute hypertensive event, respiration may briefly cease ("adrenaline apnea")

References

References

Wolff, Christopher B. "The physiological control of respiration." Molecular aspects of medicine 13.6 (1992): 445-567.

Henderson, V. E., and E. Horne Craigie. "On the respiratory centre." American Journal of Physiology-Legacy Content115.3 (1936): 520-529.

Remmers, John E. "A century of control of breathing." American journal of respiratory and critical care medicine172.1 (2005): 6-11.

 Richter, D. W., F. Heyde, and M. Gabriel. "Intracellular recordings from different types of medullary respiratory neurons of the cat." Journal of neurophysiology 38.5 (1975): 1162-1171.

Milne, J. A. "The respiratory response to pregnancy." Postgraduate medical journal 55.643 (1979): 318-324.

López-Barneo, J., et al. "Carotid body oxygen sensing." European Respiratory Journal 32.5 (2008): 1386-1398.

Schuitmaker, J. J., et al. "Ventilatory responses to respiratory and metabolic acid-base disturbances in cats." Respiration physiology 67.1 (1987): 69-83.

Fulop, M. "The ventilatory response in severe metabolic acidosis." Clinical Science 50.5 (1976): 367-373

Mitchell, R. A., and M. M. Singer. "Respiration and cerebrospinal fluid pH in metabolic acidosis and alkalosis." Journal of applied physiology 20.5 (1965): 905-911..

Borgbjerg, F. Molke, Kurt Nielsen, and Jan Franks. "Experimental pain stimulates respiration and attenuates morphine-induced respiratory depression: a controlled study in human volunteers." Pain 64.1 (1996): 123-128.

Arita, Hideho, Naoki Kogo, and Kiyoshi Ichikawa. "Locations of medullary neurons with non-phasic discharges excited by stimulation of central and/or peripheral chemoreceptors and by activation of nociceptors in cat.Brain research 442.1 (1988): 1-10.

Sarton, Elise, et al. "Influence of acute pain induced by activation of cutaneous nociceptors on ventilatory control." Anesthesiology: The Journal of the American Society of Anesthesiologists 87.2 (1997): 289-296.

Baker, Jason F., Robert C. Goode, and James Duffin. "The effect of a rise in body temperature on the central-chemoreflex ventilatory response to carbon dioxide." European journal of applied physiology and occupational physiology 72.5-6 (1996): 537-541.

Natalino, Michael R., Clifford W. Zwillich, and John V. Weil. "Effects of hyperthermia on hypoxic ventilatory response in normal man." The Journal of laboratory and clinical medicine89.3 (1977): 564-572.

Heistad, D., et al. "Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation." Journal of Applied Physiology 39.3 (1975): 411-416.

Biscoe, T. J., G. W. Bradley, and M. J. Purves. "The relation between carotid body chemoreceptor discharge, carotid sinus pressure and carotid body venous flow." The Journal of physiology 208.1 (1970): 99-120.

Ohtake, PATRICIA J., J. K. Walker, and DONALD B. Jennings. "Renin-angiotensin system stimulates respiration during acute hypotension but not during hypercapnia." Journal of Applied Physiology 74.3 (1993): 1220-1228.

Trelease, Robert B., et al. "Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats." Experimental neurology 90.1 (1985): 173-186.

Hoff, Hebbel E., C. G. Breckenridge, and J. E. Cunningham. "Adrenaline apnea in the medullary animal." American Journal of Physiology-Legacy Content 160.3 (1950): 485-489.

Grunstein, M. M., J-Ph Derenne, and J. Milic-Emili. "Control of depth and frequency of breathing during baroreceptor stimulation in cats." Journal of applied physiology 39.3 (1975): 395-404.

LoMauro, Antonella, and Andrea Aliverti. "Respiratory physiology of pregnancy: Physiology masterclass." Breathe11.4 (2015): 297-301.

Castro, Renata Rodrigues Teixeira de, et al. "Minute-ventilation variability during cardiopulmonary exercise test is higher in sedentary men than in Athletes." Arquivos brasileiros de cardiologia 109.3 (2017): 185-190.

Folinsbee, LAWRENCE J., et al. "Exercise respiratory pattern in elite cyclists and sedentary subjects." Medicine and science in sports and exercise 15.6 (1983): 503-509.

Conde, Silvia Vilares, and Chris Peers. "Carotid body chemotransduction gets the human touch." The Journal of physiology 591.Pt 24 (2013): 6131.

Piskuric, Nikol A., and Colin A. Nurse. "Expanding role of ATP as a versatile messenger at carotid and aortic body chemoreceptors." The Journal of physiology 591.2 (2013): 415-422.

Conde, S. V., A. Obeso, and C. Gonzalez. "Low glucose effects on rat carotid body chemoreceptor cells' secretory responses and action potential frequency in the carotid sinus nerve." The Journal of physiology 585.3 (2007): 721-730.

Ortega‐Sáenz, Patricia, et al. "Cellular properties and chemosensory responses of the human carotid body." The Journal of physiology 591.24 (2013): 6157-6173.

Eldridge, Frederic L., David E. Millhorn, and Tony G. Waldrop. "Exercise hyperpnea and locomotion: parallel activation from the hypothalamus." Science 211.4484 (1981): 844-846.