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Respiratory Regulation

Human cells are reliant on aerobic metabolism. Obtaining O2 from the environment and transporting it to the tissues while excreting the byproduct of cellular respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy (CO2) are processes key to survival and must be closely regulated. Chemoreceptors in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and tissues sense changes in the concentration of respiratory gasses and send messages to the CNS, which, in turn, modifies breathing parameters such as the respiratory rate Respiratory rate The number of times an organism breathes with the lungs (respiration) per unit time, usually per minute. Pulmonary Examination or tidal volume Tidal volume The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are tv or V with subscript t. Ventilation: Mechanics of Breathing to compensate for any imbalance. Disruption of this control mechanism can be caused by severe disease and also result in severe disease.

Last updated: Sep 1, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Respiratory Centers

Respiratory centers are specialized neuron clusters located in the medulla oblongata Medulla Oblongata The lower portion of the brain stem. It is inferior to the pons and anterior to the cerebellum. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities. Brain Stem: Anatomy. They regulate 2 respiratory parameters in response to changing demands:

  • Respiratory frequency (rate): determined by how long the respiratory center is active
  • Depth of breath ( tidal volume Tidal volume The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are tv or V with subscript t. Ventilation: Mechanics of Breathing): determined by how the respiratory center stimulates the respiratory muscles

Anatomy

  • Dorsal respiratory group neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (DRG)
  • Ventral respiratory group neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (VRG)
  • Pneumotaxic center
  • Apneustic center 
  • Pre-Bötzinger complex

Respiratory groups

  • DRG: 
    • Sets rhythm and frequency of inhalation, and thus also the respiratory rate Respiratory rate The number of times an organism breathes with the lungs (respiration) per unit time, usually per minute. Pulmonary Examination (during quiet breathing, exhalation is passive and does not require stimulus)
    • Intrinsic oscillator:
      • Spontaneously sends repetitive signals
      • Induces repetitive contraction of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy, creating negative pleural pressure and inflation of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
  • VRG:
    • Not used during normal quiet breathing, only engaged in forced exhalation
    • Stimulates abdominal muscles to forcefully exhale during increased respiratory need
  • Pneumotaxic center:
    • Switches off inspiratory signal produced by DRG
    • Limits inspiration Inspiration Ventilation: Mechanics of Breathing duration setting the depth of breathing and determining rate of respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
  • Other respiratory centers:
    • Cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: Anatomy: conscious override of autonomous control of breathing
    • Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. Limbic System: Anatomy: override the breathing cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation during fear or excitement
Respiratory control centers respiratory regulation

Respiratory control centers

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Regulation of the Respiratory Centers

Respiratory centers set the rate and depth of breathing. Changes in O₂, CO₂, and H+ concentrations are sensed by central and peripheral chemoreceptors, which regulate the activity of the respiratory centers to match metabolic and situational needs.

Regulation of respiratory centers by central chemoreceptors

Central chemoreceptors are located in the medulla oblongata Medulla Oblongata The lower portion of the brain stem. It is inferior to the pons and anterior to the cerebellum. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities. Brain Stem: Anatomy and regulate respiratory center activity based on changes in blood gases.

  • PCO₂: 
    • Increase → increase of H+ in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification ( carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors action on CO₂ permeating the blood– brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification barrier) → stimulation of central chemoreceptors → stimulation of respiratory centers → increased depth and rate of breathing → decrease PCO₂
    • Decrease → decreased respiratory rate Respiratory rate The number of times an organism breathes with the lungs (respiration) per unit time, usually per minute. Pulmonary Examination or even apnea 
  • Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of O₂ (PO₂): no direct effect on respiratory centers 
  • A decrease in arterial pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance can increase ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing even if PO₂ and PCO₂ are normal.

Regulation of respiratory centers by peripheral chemoreceptors

Peripheral chemoreceptors are located in the carotid bodies and aortic bodies and are more responsive to blood gases than central chemoreceptors.

  • PCO₂:
    • Sensed directly and indirectly as H+ by peripheral chemoreceptors
    • Has similar effects on respiratory centers as central chemoreceptors
    • Much less potent stimulus than direct stimulation of central chemoreceptors
  • PO₂:
    • Decrease → depolarization Depolarization Membrane Potential of type I (glomus) cells → activation of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane → docking and fusing of neurotransmitters by intracellular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytespicked up by afferents and send a signal to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification → increase in the rate of breathing
    • Has a modest effect on ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing, primarily when PO₂ is 30–60 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg

Regulation of respiratory centers by other receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy

  • Irritant receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
    • Sense: 
      • Dust
      • Cold air
      • Chemical irritants
    • Cause:
      • Cough
      • Bronchoconstriction
  • Muscle and joint receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
    • Sense position of the chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. Chest Wall: Anatomy during respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
    • Provide feedback about adequacy of rate and depth of breathing
  • Stretch receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
    • Sense extent of inflation of the lung parenchyma
    • Terminate inspiration Inspiration Ventilation: Mechanics of Breathing before damage is done to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
  • J receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
    • Sense pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
    • Cause shallow breathing
Receptors along the respiratory tract

Receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors along the respiratory tract, and in muscles and joints of the thorax

Image by Lecturio. License: CC BY-NC-SA 4.0

References

  1. Hall, J.E., Hall, M.E. (2021). Guyton and Hall Textbook of Medical Physiology (14th ed.). Elsevier.
  2. Powers, K.A., Dhamoon, A.S. Physiology, pulmonary ventilation, and perfusion (2021). StatPearls. Treasure Island (FL): StatPearls Publishing.
  3. J. Gordon Betts et al. Anatomy and Physiology. Retrieved April 26, 2021, from https://openstax.org/details/books/anatomy-and-physiology

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