Phys Control of Ventilation (30)

• rhythmic discharge of nerve impulses originating in the brain that ultimately stimulates respiratory muscles to contract
• transection of the spinal cord above the origin of the phrenic nerves (at C1) stops breathing

• changes in arterial pH, P_O2, & P_CO2 & several non-chemical influences
• respiration is under AUTOMATIC control via centers in the medulla & under VOLUNTARY control via the cerebral cortex

normal, quiet breathing

increased respiratory rate

increased rate & depth

sensation of breathlessness, labored breathing

dyspnea at rest while recumbent

cessation of breathing

• an abnormal pattern w/ waxing & waning tidal volume & periodic apnea
• it usually indicates severe CNS disorder

a regular rapid rate w/ large tidal volume usually caused by metabolic acidosis

• highly irregular inspirations usually separated by long periods of apnea
• usually seen with lesions to the medulla

• larger than normal breaths that occur automatically at regular intervals in normal subjects
• a yawn is an exaggerated sigh

prolonged inspirations separated by brief expirations

• medullary centers: they generate respiratory rhythm
• medulla is made up of the bilateral dorsal respiratory group (DRG) & ventral respiratory group (VRG)

• these fire in phase w/ the respiratory cycle
• regular breathing continues even after transection of the brain to separate medulla from pons
• this indicates that a Central Pattern Generator exists in the medulla

• INSPIRATORY neurons
• they initiate inspiration w/ a weak burst of action potentials that gradually increase in amplitude over the next few seconds (Ramp Signal)

• connect to inspiratory muscles
• specifically they synapse w/ either Phrenic or Thoracic Spinal nerves
• the phrenic nerve connects to the diaphragm
• the thoracic spinal nerves connect to the external intercostals

• ceases for ~3 seconds to allow expiration, then the cycle begins again
• these signals correspond to the normal pattern of breathing
• the gradually rising ramp signal provides for a gradual increase in lung volume during normal inspiration
• RAMP PICTURE
• every time activity increases → air inspiration
• every time activity decreases → expiration

• originate in the DRG then go on to innervates the diaphragm to stimulate diaphragmatic contraction (pulled taught → more room as lungs expand during inhalation)
• can see from above diagram that as DRG neuron signals increase, the Phrenic n. signal gets larger as well
• the medullary center is probably stimulating the Phrenic n.

• the Botzinger Complex in the the VRG (Bot.C)
• it appears to contain pacemaker cells that spontaneously generate the respiratory rhythm & may excite or inhibit inspiratory cells in the DRG

• contains both inspiratory & expiratory neurons
• inspiratory neurons receive input from the DRG neurons
• expiratory neurons in the VRG connect to outputs of expiratory muscles (are ONLY active during FORCED expiration)
• may be active in breathing during exercise but DO NOT fire during resting breathing

• the axons of motor neurons in the VRG leave the medulla via cranial nerves V, VII, IX, X, & XI to supply the larynx, pharynx, & other structures that INCREASE the diameter of the upper airways during Inspiration
• it also sends signals down the spinal cord to the inspiratory muscles
• caudal region of the VRG sends fibers down the spinal cord to the expiratory muscles
• 

• respiratory pattern generator (Pre-Botzinger Complex?) activates inspiratory neurons in the VRG that stimulates the DRG ramp signal
• both the VRG & DRG stimulate inspiratory motor neurons in the spinal cord
• when inspiratory neurons STOP firing, the inspiratory muscles relax & allow passive expiration

• expiratory neurons in the VRG are important when large increases in ventilation are required to stimulate expiratory muscles (eg. during exercise)
• inspiratory & expiratory neurons in the medulla exhibit Reciprocal Inhibition: when inspiration is occurring, expiratory neurons are INHIBITED & vice versa

• may modulate medullary respiratory output
• are centers that exist above the DRG/VRG of the medulla in the PONS

• located in the lower pons just above the medullary centers
• electrically stimulating neurons in the apneustic center stimulate the DRG/VRG to cause more deep & rapid breathing (‘to breathe harder’)
• has a general excitatory effect on these medullary structures

• when stimulated it SHUTS OFF inspiratory activity
• is thought to ↓ inspiratory activity & ↑ expiratory activity
• (probably inhibits apneustic center, DRG, & VRG, or perhaps stimulating the VRG → forced expiration)

• Cortical Centers
• they can override the functions of the brainstem to exert VOLUNTARY control of breathing

the DRG RECEIVES input signals from peripheral cardiopulmonary sensors (peripheral CHEMOreceptors) that regulate respiratory rhythm

• 1. Arch of the Aorta, called the Aortic Bodies (entrance to the systemic circulation)
• 2. Carotid Bifurcation, called the Carotid Bodies (at the entrance to the brain)
• 
• signals from these receptors reach the DRG via the afferent fibers of cranial nerves IX (glossopharyngeal) & X (vagus)

• specialized cells that are chemosensitive
• they respond to changes in P_aO₂, P_aCO₂, & pH in arterial blood passing through the aortic arch
• we expect the P_O2 =100, P_CO2 = 40, & the pH = 7.4

• from the picture it looks like Aortic Bodies project to the Vagus (Cranial X) n. → DRG
• while Carotid Bodies project to the Glossopharyngeal (Cranial IX) → DRG
• these cranial nerves might also project to the apneustic

• Glomus cells
• 
• Type I Glomus cells are depolarized by low P_aO₂, high P_aCO₂, & low pH → they release a neurotransmitter (NT)
• the NT stimulates afferent nerve fibers of cranial nerves IX & X that signal the DRG to increase ventilation
• these cells are essentially part of the nervous system

those of the CAROTID bodies are more sensitive than aortic bodies to hypoxia (low P_aO₂)

• at normal P_aCO₂ (40 mmHg) we have normal alveolar ventilation (1)

• as the P_aCO₂ goes up there’s a STEEP rise in alveolar ventilation; this is brought about by ↑ firing of chemoreceptors

• • reaches a peak at ~100 mmHg P_aCO₂; any higher than that & a person’s in CO₂ narcosis → ventilation is depressed, receptors become poisoned by the CO₂
• 
• • y-axis = rate & depth of breathing (how much air is being brought INTO the alveoli) as a function of P_aCO₂ (x-axis, amount of CO₂ is in arterial blood)

• when the patient is asleep, the curve shifts to the right
• when under anesthesia or narcotics, both of which INHIBIT the response of the DGR, the curves are shifted right & their slopes diminished
• 
• overall, the response is linear in the physiological range of P_aCO₂ values
• normally there is a 2-5 L/min increase in ventilation for each 1 mmHg increase in P_aCO₂

• because the chemoreceptors that signal to the DRG via afferent cranial nerves are essentially non-functional
• a person’s own ventilation will be suppressed b/c the response of the chemoreceptors is suppressed under these circumstances

• chemosensors are more sensitive to P_aCO₂ when there is simultaneously decreased P_aO₂ or P_AO₂
• a rise in P_aCO₂ coupled to a drop in P_aO₂ would produce a GREATER stimulation of ventilation than either change alone
• (opposite way to say that is high P_aO₂ DECREASES the CO₂ effect)
• O₂ is often low when CO₂ is high b/c that often happens when you’re under-ventilating
• 

• b/c between a P_O2 of 100 & 75 mmHg, even though diffused O₂ has decreased, oxygen from Hemoglobin hasn’t been unloaded/used up yet
• (O₂ content hasn’t really changed EVEN THOUGH the P_O2 has dropped)
• a P_aO₂ between 75-60 mmHg is when Hb begins to fail at adequately oxygenating peripheral tissues

• when P_aO₂ is below ~60 mmHg, the activity of receptors in Aortic & Carotid Bodies increases rapidly to increase ventilation
• this response to a drop in P_O2 is INCREASED when there is simultaneously high P_aCO₂
• 

• b/c CO₂ isn’t buffered by binding to hemoglobin - there’s less wiggle-room for changes
• linear changes in P_CO2 manifest as changes in bicarbonate & carbamino hemoglobin as well
• there’s a buffer effect you see w/ O₂ that isn’t seen with CO₂

• hypoxemia + hypercapnia → marked increases in ventilation
• changes in P_CO2 also have an effect on ventilation response to hypoxemia
• 
• as P_CO2 increases, there’s an increase in ventilation as a function of arterial O₂
• a rise in CO₂ amplifies the O₂ effects on ventilation

• it will all by itself produce an INCREASE in ventilation
• addition of a non-CO₂ acid (eg. lactic) to the blood while keeping P_aCO₂ constant induces hyper-ventilation
• the response of chemo-receptors to both increased P_aCO₂ & decreased P_aO₂ is enhanced at lower pH
• 

• same as peripheral but located within the CNS, specifically the medulla
• they provide sensory input to the DRG
• are stimulated by changes in the pH of the cerebrospinal fluid (CSF)
• a ↓ in pH → ↑ in ventilation

• when ↑ CO₂ crosses into the brain from the bloodstream (CO₂ can pass through the BBB)
• ↑CO₂ → ↑[H⁺]

• occurs when overinflation of the lung sends signals via the Vagus n. → Pneumotaxic Center to TERMINATE inspiration
• slowly adapting pulmonary stretch (mechano-) receptors located in the tracheobronchial tree or the lungs themselves fire & initiate this reflex when lung volume INCREASES

an Apneustic breathing pattern, aka one that consists of deep & prolonged inspirations + short expirations

can be found in lung parenchymal tissue + extrapulmonary airways that respond to tissue distention & irritation

• in the nasal mucosa & pharynx
• those for coughing are located in the larynx, trachea, & bronchi
• stimulation of these centers cause a deep inspiration (rapid ↑ pressure in thoracic cavity) followed by a violent expulsion of gas
• for a cough, pressure first builds against a closed glottis, which then opens suddenly to allow forceful expiration of high pressure air

• are mechanoreceptors located among airway epithelial cells & respond to chemical irritants such as SO₂, NH₃, NO₂, & inhaled particles such as dust, smoke, or cold air
• they also respond to histamine & leukotrienes

• when stimulated they stimulate respiratory centers to augment respiratory activity & to CONSTRICT airways
• this promotes rapid, shallow breathing in an attempt to limit penetration of the noxious agents

• very small UNmyelinated nerve endings located right around the alveoli & alveolar capillaries
• [a rich network of small axons that innervate receptors (juxtacapillary or J receptors) within the alveoli & small conducting airways]

• interstitial edema & engorgement of pulmonary capillaries
• they cause RAPID shallow breathing (& mediate the closure of the larynx → apnea)
• they also mediate tachypnea in response to pulmonary embolism

• they detect impediments to breathing in the chest wall & stimulate increased inspiratory activity
• include proprioceptive (positional) input from joints, tendons, & muscle spindles in the ribs + inspiratory muscles
• some spindle fibers project to the brain cortex to provide conscious sensation of respiratory movements
• eg. if someone sits on your chest THESE receptors detect that impediment & would subsequently ↑ the force of breathing

• besides coordinate breathing w/ other behaviors, input from the cortex can temporarily OVERRIDE automatic control of breathing
• the CNS balances ventilation from automatic centers w/ the need to carry out non-respiratory activities such as talking, eating, sniffing, vomiting, breath holding, singing, playing a wind instrument, etc.
• these actions involve voluntary control over respiration but it is not absolute (eg. voluntary breath holding will be overcome by the ventilatory drive from chemoreceptors - their increased firing will overcome voluntary centers & the functions of automatic centers will kick in)