INDIVIDUAL ASSIGNMENT

Respiration
2 year / 4 Semester / 2021 / FMUI 2020
st st

Mohamad Arbian Karim

2006489400 – Group A

PBL Trigger 1

Breathing Regulation by The Nervous System

Introduction

The lungs are a pair of basic respiratory organs located in the thoracic cavity next to the
mediastinum. The pleura is a thin double-layered serous membrane that covers them. The
lungs are an important part of the pulmonary circulation, which transports deoxygenated
blood from the right ventricle of the heart through the pulmonary arteries to the alveolar-
capillary beds of the lung for gaseous exchange.1

The lungs are the fundamental organs of the respiratory system, facilitating gas exchange
from the environment into the circulation. The alveoli transfer oxygen into the capillary
network, where it can enter the arterial system and eventually perfuse tissue. The nose,
oropharynx, larynx, trachea, bronchi, bronchioles, and lungs make up the majority of the
respiratory system. The lungs are further subdivided into lobes, which are further subdivided
into about 300 million alveoli.2

Breathing is a complicated process that is strongly reliant on the coordinated activity of the
respiratory muscles and the control center in the brain. The lungs' principal purpose is to
allow gas exchange between inspired air and the circulatory system. It aids in the transport of
oxygen into the blood and the removal of carbon dioxide from the organism. Oxygen is
required for healthy cellular metabolism, but carbon dioxide is required for optimum PH
levels. There are several measures in place to guarantee a strict balance between supply and
demand. The pulmonary system adjusts to changes in blood gases by altering breathing
patterns to assist fulfill the body's metabolic needs. Exercise, for example, increases oxygen
demand while decreasing carbon dioxide generation. If the available oxygen supply fails to
match the required demand at any moment, aerobic metabolism stops and energy generation
decreases. Similarly, if carbon dioxide accumulates without being properly disposed of, the
blood becomes more acidic, causing cellular damage and eventually organ failure. Because
neither scenario is ideal, multiple systems exist to fit respiration to the constantly changing
needs. To assist adjust respiratory drive, central and peripheral chemoreceptors, as well as
mechanoreceptors in the lungs, send neurological and sensory feedback to the brain. In
response, the respiratory center modifies its firing pattern to adjust breathing rate and
volume.3–5

In this LTM, I will be discussing about the breathing mechanism using the nervous system to
understand more on how our nervous system impacts the way we breath.
Topics Discussion
A. Introduction to The Breathing Mechanism

Breathing is an instinctive and rhythmic act that is performed by neural networks in

the hindbrain (the pons and medulla). The brain networks control the muscles that
create the thoracic and abdominal walls, as well as the pressure gradients that flow air
into and out of the lungs. The respiratory rhythm and length of each respiratory phase
are determined by the reciprocal stimulatory and inhibitory connections of these
brain-stem neurons.6

The capacity of the human respiratory system to modify breathing patterns to changes
in both the internal and exterior environment is an essential feature. Ventilation rises
and falls in accordance to variations in carbon dioxide generation and oxygen intake
induced by metabolic rate fluctuations. The respiratory system can also adjust for
perturbations that influence breathing mechanics, such as airway constriction during
an asthmatic episode. Breathing is also adjusted when the mechanical advantage of
the respiratory muscles changes due to postural changes or movement.6

This flexibility in breathing patterns is largely due to sensors located throughout the
body that convey information to respiratory neural networks in the brain.
Chemoreceptors detect changes in blood oxygen levels and affect blood and brain
acidity. Mechanoreceptors detect lung expansion, airway size, the power of
respiratory muscle contraction, and the amount of muscular shortening.6

Although the diaphragm is the primary breathing muscle, it is helped and increased by
a complex assemblage of other muscle groups. Intercostal muscles, abdominal
muscles, and muscles such as the scalene and sternocleidomastoid, which connect to
both the ribs and the cervical spine at the base of the skull, all play vital roles in the
exchange of air between the atmosphere and the lungs. Furthermore, during both
inspiration and expiration, laryngeal muscles and muscles in the oral and nasal
pharynx modify the resistance of gas passage in the upper airways. Because
"respiratory" muscles are used in nonrespiratory processes, breathing may be
regulated by higher brain centers and even controlled deliberately to some extent. The
capacity to pause breathing by holding one's breath is an excellent example of
intentional control. Input from higher brain centers into the respiratory control system
may assist optimize breathing such that not only are metabolic demands fulfilled by
breathing, but ventilation is also performed with little use of energy.6
 B. Central Neural Control
The pons and medulla govern the respiratory center in the brain. These cerebral
control centers collaborate to govern inspiration and exhale. The cerebral cortex
regulates the brain's respiratory centers, allowing conscious (i.e., breath holding) or
unconscious (i.e., talking, singing, coughing) breathing to be controlled.7

Fig 1. Control of respiration. (a) The respiratory center in the brain regulates several
aspects of respiratory drive, such as inhalation, airway defense, exhalation, and breathing
patterns. (b) The sensory input systems are made up of mechanoreceptors, metaboreceptors,
and peripheral and central chemoreceptors that detect chemical changes and regulate several
aspects of respiration such as breathing, lung space, and irritation triggers. (c) To govern the
mechanical features of breathing, neuronal processes and sensory input systems interface
with the respiratory muscles and lungs.7

1. Medullary Groups
The dorsal medulla controls inhalation and airway defense, whereas the ventral
medulla controls exhalation. The intensity of the dorsal medulla signal can alter
respiration, with greater frequency resulting in stronger muscular contractions and
deeper breathing, and lower frequency resulting in passive expiration. To establish
respiratory rhythm, the dorsal medulla connects with the ventral medulla by
integrating input from central and peripheral receptors before passing information
to respiratory muscles. The pre-Bötzinger complex is a collection of neurons in
the brainstem positioned between the ventral respiratory group and the Bötzinger
complex that also controls inspiration. The pre-Bötzinger complex interacts with
respiratory centers to provide a smooth transition between breathing phases while
also preventing opposing muscle units from activating. Glutamate, gamma-
aminobutyric acid (GABA), and glycine are the primary neurotransmitters
involved in influencing the formation and transmission of respiratory rhythms.7

2. Pontine Grouping
The pontine grouping permits the strength and frequency of medullary impulses to
be modulated to control breathing patterns while facilitating a seamless transition
between inspiration and expiration. More precisely, the pneumotaxic center in the
upper pons controls breathing speed, transmits inhibitory impulses to the
respiratory center, and is involved in respiratory rate fine-tuning. The apneustic
center in the lower pons coordinates breathing speed but can be overridden by the
pneumotaxic center to halt inhalation; this region is largely responsible for
transmitting stimulatory impulses to the inspiratory area (prolonging inhalation).
Suprapontine regions contribute to respiration by reacting to changes in internal or
external environmental variables such as exercise, hypoxia, hypercapnia, and
temperature changes, as well as other actions such as swallowing and coughing.
Incoming sensory input systems influence these neural processes.7

C. Sensory Input Systems

Sensory input systems are made up of mechanoreceptors, metaboreceptors, and
peripheral and central chemoreceptors, which work along with other components of
the respiratory response system to govern breathing.7

1. Mechanoreceptors and Metaboreceptors

Mechanoreceptors are found in the airways, trachea, lungs, and pulmonary arteries
throughout the respiratory system. They send sensory information to the brain's
respiratory center about the mechanical state of the lungs and chest, such as
breathing rate, lung space, and discomfort triggers. Slowly adapting pulmonary
stretch receptors are engaged during lung inflation and play an important part in
the Hering–Breuer reflex (termination of inspiration and prolonging of
expiration), whereas fast adapting receptors begin protective respiratory reflexes
in response to irritants. Bronchopulmonary C-fiber receptors are also involved in
the initiation of protective respiratory reflexes in response to inhaled irritants or
sudden changes in lung capacity. Metaboreceptors, which are present in skeletal
 muscle, are triggered by metabolic byproducts to encourage breathing during
exercise7

2. Peripheral Chemoreceptors
Peripheral chemoreceptors are fast-acting carotid and aortic bodies that monitor
arterial O2 partial pressure and respond to hypercapnia or acidosis. Carotid body
chemoreceptors are found at the bifurcation of the common carotid arteries and
are in charge of the bulk of peripheral ventilation regulation. Carotid bodies may
also detect arterial gas concentrations and pH, triggering a quick reaction (within
1–3 seconds) by activating breathing via connection with medullary response
neurons. Aortic bodies are found near the aortic arch and serve an important
function in controlling circulation as well as responding to variations in gas
concentrations.7

3. Central Chemoreceptors
Central chemoreceptors are found on the ventral surface of the medulla and
retrotrapezoid nucleus and are responsible for perceiving changes in the
concentrations of pH, O2, and CO2 in the brain and cerebrospinal fluid. An acidic
environment in the brain (increased hydrogen ions) causes the respiratory center
to constrict the diaphragm and intercostal muscles. As a result, the rate and depth
of respiration increase, enabling more CO2 to be exhaled and lowering blood CO2
levels and hydrogen ions. Low amounts of CO2 in the blood, on the other hand,
induce low levels of hydrogen ions in the brain, resulting in a decrease in the rate
and depth of ventilation and a slowing of breathing. These mechanisms work
together to normalize pH. Central chemoreceptors are assumed to have main
control over breathing, which is eventually performed by respiratory muscles and
the lungs.7

4. Muscle and Lung Receptors

Breathing patterns can also be influenced by receptors in the respiratory muscles
and the lung. These receptors are especially essential when lung function is
compromised because they can assist maintain normal tidal volume and
ventilation.6

The force that a muscle may produce when stimulated is affected by changes in its
length. In general, there is a length where the force created is greatest. When
increased lung stiffness or resistance to air flow caused by illness prevents
muscular shortening, receptors in the respiratory muscles called spindles assess
muscle length and enhance motor discharge to the diaphragm and intercostal
muscles. Tendon organs, another kind of muscle receptor, detect variations in the
force produced by muscular contraction. Excessive force activates tendon organs,
resulting in decreased motor output to the respiratory muscles and perhaps
preventing the muscles from injuring themselves.6

In animals, a reaction reported by German biologist Ewald Hering and Austrian

scientist Josef Breuer stops breathing. Lung expansion causes stretch receptors in
the airways to fire, triggering the Hering-Breuer response. Stimulation of these
receptors, which are activated by the vagus nerve and transmit signals to the
medulla, shortens inspiratory durations as tidal volume (the volume of air
 inspired) increases, hence increasing the frequency of breathing. When lung
inflation is inhibited, the reflex allows for a longer inspiratory period, which aids
in the preservation of tidal volume.6

Fig. 2 Respiration is mediated by communication among central neural control, sensory input
systems, respiratory muscles, and the lungs. Neuronal and sensory input systems coordinate
with respiratory muscles and the lungs to control the mechanical aspects of respiration.7

Summary

Breathing is an automatic and rhythmic act produced by networks of neurons in the hindbrain
(the pons and medulla). The neural networks direct muscles that form the walls of the thorax
and abdomen and produce pressure gradients that move air into and out of the lungs. The
respiratory rhythm and the length of each phase of respiration are set by reciprocal
stimulatory and inhibitory interconnection of these brain-stem neurons.

References

1. Khan YS, Lynch DT. Histology, Lung. [Updated 2021 May 10]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK534789/.
2. Haddad M, Sharma S. Physiology, Lung. [Updated 2021 Jul 22]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK545177/.
3. Song G. Cytoarchitecture of Pneumotaxic Integration of Respiratory and
Nonrespiratory Information in the Rat. J Neurosci [Internet]. 2006 Jan 4;26(1):300–10.
Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.3029-
05.2006
4. Mortola JP. How to breathe? Respiratory mechanics and breathing pattern. Respir
Physiol Neurobiol [Internet]. 2019 Mar;261:48–54. Available from:
https://linkinghub.elsevier.com/retrieve/pii/S1569904818303161
5. Patel S, Sharma S. Respiratory Acidosis. 2021 Jun 24. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 29494037.
6. Cherniack N. Muscle and lung receptors [Internet]. Encyclopædia Britannica.
Encyclopædia Britannica, inc.; [cited 2022May13]. Available from:
https://www.britannica.com/science/human-respiratory-system/Muscle-and-lung-
receptors Goblet cells [Internet]. Ph.
7. Webster LR, Karan S. The Physiology and Maintenance of Respiration: A Narrative
Review. Pain Ther [Internet]. 2020 Dec 6;9(2):467–86. Available from:
https://link.springer.com/10.1007/s40122-020-00203-2
8. Weil BR, Neelamegham S. Selectins and Immune Cells in Acute Myocardial
Infarction and Post-infarction Ventricular Remodeling: Pathophysiology and Novel
Treatments. Front Immunol [Internet]. 2019 Feb 27;10. Available from:
https://www.frontiersin.org/article/10.3389/fimmu.2019.00300/full