Physiology, Respiratory Drive


Article Author:
Joshua Brinkman


Article Editor:
Sandeep Sharma


Editors In Chief:
Laurie Graham
Andrew Wilt
Mary Cataletto


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
3/16/2019 2:24:03 PM

Introduction

The primary purpose of the pulmonary system is to facilitate the diffusion of essential chemicals and gases between the circulatory system and environmental air. The substances of primary concern include the intake of oxygen and the removal of carbon dioxide from the body.  Maintenance of these elements facilitates metabolism on a cellular level throughout the body and plays an important role in the overall physiological pH maintenance of the body. Diffusion on a human scale is facilitated and accelerated through several mechanisms to increase respiratory ventilation rate and volume and in doing so increase the overall efficiency of gas exchange to meet the body’s metabolic demand. 

In the example, as the body exercises, its demand for oxygen will increase to maintain the aerobic metabolism of fuel to produce energy.  Furthermore, the level of metabolic carbon dioxide will increase.  Should at any point the available oxygen supply not meet the necessary demand, aerobic metabolism will no longer be possible, and energy production will fail. Likewise, if carbon dioxide levels are allowed to accumulate without disposal, the blood will become more acidic, leading to cellular damage on a systemic scale, which may ultimately lead to organ failure or death. Neither outcome is desirable. To negate the constantly changing demands of the body, respiration is modulated to match its drive to the overall demand of the body. In overarching terms, respiratory drive is moderated by neural and chemical sensory input from both central and peripheral sources into the respiratory centers of the brain to determine the needed rate of ventilation to lung tissue as well as the total effective volume of inhalation.[1][2][3][4]

Function

Respiratory drive is a system that can be broken down into three components: the neural central control system, the sensory input systems, and the muscular effect systems. The neural central control system is an intrinsic pacemaker for the rate of ventilation as well as the volume of the air intake. The sensory systems offer input to the central nervous system to modulate the total rate and volume of breathing. Finally, a uniform signal is sent to muscles of respiration to put the respiratory drive into a mechanical effect of exchanging air. Together these processes function to expel low oxygen, high carbon dioxide air from within the alveoli of the lung and to intake high oxygen, low carbon dioxide air from the atmosphere to facilitate gas exchange on a cellular level. [5][6]

Mechanism

Intrinsic Respiratory drive

The respiratory center of the brain is comprised of three neuron groupings in the brain: the dorsal and ventral medullary groups and the pontine grouping. The pontine grouping further classifies into the pneumotaxic and apneustic centers. The dorsal medulla is responsible for inhalation, the ventral medulla is responsible for exhalation, and the pontine groupings are responsible for modulating the intensity and frequency of the medullary signals where the pneumotaxic groups limit inhalation and the apneustic centers prolong and encourage inhalation. Each of these groups communicates with one the other in a concerted effort as the pace making potential of respiration.[7][8]

Thoracic neural receptors

Mechanoreceptors located in the airways, trachea, lung, and pulmonary vessels exist to provide sensory information to the respiratory center of the brain regarding the volume of the lung space. There are two primary types of thoracic sensors: slow adapting stretch spindles and rapid adapting irritant receptors. Slow acting spindle sensors convey only volume information; however, the rapid-acting receptors respond to both the volume of the lung information and chemical irritation triggers such as foreign harmful agents that may be present. Both types of mechanoreceptors signal via cranial nerve X (the Vagus Nerve) to the brain to increase the rate of breathing, volume of breathing, or to stimulate errant coughing patterns of breathing secondary to irritants in the airway.

Peripheral Chemoreceptors

These consist of the carotid and the aortic bodies. Both sites function to monitor the partial pressure of arterial oxygen in the blood. However, hypercapnia and acidosis increase the sensitivity of these sensors, thus playing a partial role in the receptor’s function. The carotid bodies are located at the common carotid artery bifurcation, and the aortic bodies are located within the aortic arch. Once stimulated by hypoxia, they send a signal via cranial nerve IX (the glossopharyngeal nerve) to the nucleus tractus solarius in the brain which in turn stimulates excitatory neurons to increase ventilation. It has been estimated that the carotid bodies comprise 15% the total driving force of respiration.[9]

Central Chemoreceptors 

Central chemoreceptors hold the majority of the remaining control over respiratory drive. They function through sensing pH changes within the central nervous system. Primary locations within the brain include the ventral surface of the medulla and the retrotrapezoid nucleus. pH change within the brain and surrounding cerebrospinal fluid is derived primarily by increases or decreases in carbon dioxide levels. Carbon dioxide is a lipid-soluble molecule that freely diffuses across the blood-brain barrier. This characteristic proves to be rather useful in that rapid changes in pH within the cerebrospinal fluid are possible. Chemoreceptors responsive to pH change are located across the ventral surface of the medulla. As these areas become more acidic, sensory input is generated to stimulate hyperventilation and carbon dioxide within the body is reduced through the increased ventilation. When pH rises to more alkalotic levels, hypoventilation occurs and carbon dioxide levels decrease secondary to decreased ventilation.

Integration of Receptor Input

Respiratory centers located within the medulla oblongata and pons of the brainstem are responsible for generating the baseline respiratory rhythm. However, the rate of respiration is modified by allowing for aggregated sensory input from the peripheral sensory system, which monitors oxygenation, and the central sensory system, which monitors pH and, indirectly, carbon dioxide levels along with several other portions of the cerebellar brain modulate to create a unified neural signal which is then sent to the primary muscles of respiration, the diaphragm, external intercostals, and scalene muscles along with other minor muscles of respiration. The total input from all sensors culminates in a respiratory rate for an average adult of approximately 12 breaths per minute while at rest.[5][6][10][11][12][13][14]

Related Testing

Evaluation of Respiratory Drive

Assessment of a patient with hypercapnia, hypoxia, or abnormal ventilation should always begin with a thorough history and clinical examination to ascertain a root cause. However, if necessary, pulmonary function testing, arterial blood gas values, and pulse oximetry may be indicated to determine whether parenchymal, neuromuscular, or chest wall sources can explain the patient's abnormalities.

Other tests of respiratory control are primarily used for research purposes or under special circumstances when pulmonary function testing and respiratory muscle strength have failed to provide an explanation for abnormal levels of arterial oxygen and carbon dioxide levels. Various tests include measurement of hypoxic and hypercapnic ventilatory response, mouth occlusion pressure, elastic and resistive load testing, and analysis of the patient's breathing pattern. These tests should not be routinely performed because they may cause harm or discomfort to the patient without significant benefit.  [15][16]

Clinical Significance

Various disease states induce alterations in the rate and rhythm of respiratory drive. These aberrant respiratory drives are induced via feedback mechanisms through PaO2, PaCO2, or pH thus augmenting the sensory drive from the central or peripheral control mechanisms. These alterations manifest in the form of increased tidal volume or respiratory rate. [9]

Asthma

During acute attacks, there is severe inflammation within the lungs. This leads to air trapping and failure of the efficient gas exchange. Subsequently, there is hypoxia. Hypoxia triggers for increased ventilation rate that rapidly leads to hypocapnia. It is important to note that in asthmatics, paradoxical normalization of carbon dioxide level is an indication that muscular fatigue is setting in and total respiratory failure is imminent.

Chronic Obstructive Pulmonary Disease

This illness is similar to asthma in that it is characterized by air trapping within the lungs, which facilitates poor gas exchange and causes hypoxia and hypercapnia. However, because these are chronic processes, the body adapts and develops resistance to the new pathologic levels of carbon dioxide within the blood. The central sensory system is the primary site where adaptation is manifested. The medullary sensors no longer respond to change in pH as it would in a healthy counterpart. As a result, hypercapnia no longer acts as the primary drive for respiratory rate. Instead, respiration is reliant on hypoxia input through the carotid bodies. So, in acute exacerbations it is actually detrimental to fully supplement oxygenation to correct hypoxia as this leads to downregulation of respiration and worsens the underlying illness.

Obesity Hypoventilation (also known as Pickwickian syndrome)

In simple terms, the weight of their chest leads to muscular fatigue thus inhibiting ventilation of the lungs. This leads to hypoxia and hypercapnia; both of which appropriately drive the control centers to increase ventilator rate. These patients tend to have decreased tidal volume and increased respiratory rate. 

Neuromuscular Disease

This is a broad classification of illnesses that include amyotrophic lateral sclerosis and multiple sclerosis. The core common concept is that respiratory control centers are intact and attempt to respond appropriately to hypoxia and hypercapnia. However, the muscular ability to respond to a hypoxic and hypercapnic stimulus is lost secondary to demyelination of neuronal muscular fibers. Therefore, the muscular system loses the ability to function entirely. Unaided, this leads to hypoxia and hypercapnia and ultimately death due to ventilator failure.

Drugs

Inhalational anesthetics, narcotics, and minor tranquilizers are the most notorious pharmaceuticals for causing respiratory depression.  Inhaled anesthetics decrease response to increased carbon dioxide and decreased oxygenation, thus blunting respiratory drive adjustments.  Benzodiazepines act on GABA receptors in the central nervous system and effectively decrease all neural functions, thus reducing the inherent respiratory pacemaking system of respiration. Similarly, opioid narcotics act on mu opioid receptors in the central nervous system, primarily within the pacemaking system of respiration, thus reducing the underlying drive for breathing. Alcohol is a nonpharmaceutical that depresses respiratory drive by blunting the body’s response to increased carbon dioxide.[17][18][10]


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Physiology, Respiratory Drive - Questions

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The abdominal recti and the internal intercostals are used during which of the following?



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Which position facilitates better respiratory excursion and decreased pulmonary effort?



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Which of the following statements about the respiratory center in the brainstem is correct?



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Which of the following gasses primarily controls the respiratory center under normal conditions?



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Which of the following is not a part of the respiratory center of the cortex?



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Which part of the brain houses the voluntary respiratory centers?



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What is termed the maximal exhalation after maximal inhalation?



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Which of the following is not true about the respiratory system at rest?



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Which of the following may play some part in the initiation of respiration after delivery?



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The basic pathophysiologic process accounting for retraction of the intercostal spaces is:



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Usually, during a deep inspiration:



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Which of the following do the aortic and carotid bodies primarily sense?



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What sensory information to the respiratory center is supplied by slow adapting spindle fibers in the airways, trachea, lung, and pulmonary vessels?



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A 46-year-old male presents with complaint of shortness of breath. He was working in the garden this afternoon when he began to "suffocate" and was unable to catch his breath. He smokes 2.5 packs per day, consumes 2 to 3 beers per week, and works in the coal mines as a heavy equipment operator. He has a past medical history significant for diabetes mellitus type 2, coal workers pneumoconiosis, hyperlipidemia, and chronic obstructive pulmonary disease. He is on high flow oxygen supplementation in the emergency room. Vitals show temperature 97.8 F, BMI 39, respiratory rate 16, blood pressure 155/110 mmHg, heart rate 85 bpm, and oxygen saturation 85%. Exam shows mild cyanosis of the lips, and he is sluggish to answer questions. Why is his respiratory rate not elevated in hypoxia?



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Physiology, Respiratory Drive - References

References

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