Control of Respiration Flashcards
Starting at the periphery, how does that signal control breathing?
Peripheral receptors sense a change –> Vagus nerve (X) mechanoreceptor afferent and Glossopharyngeal nerve (IX) chemoreceptor afferent –> Dorsal respiratory group (DRG) in the NTS –> Efferents (Phrenic, Thoracic, Abdominal, Cranial) Motorneurons cross midline to control breathing behavior
Ventral respiratory group (VRG)
Expiration
Anatomical location in medulla oblongata: retrofacial nucleus (RFN) = Botzinger complex (BotC), nucleus ambiguus (NA), nucleus retro-ambigualis (NRA)
Inspiratory and expiratory neurons from NRA provide rhythmical drive to phrenic and thoracic motorneurons (E, I, E)
Neurons from preBotC generate rhythm
preBotzinger complex (preBotC)
Within VRG, below RFN and above NA in the VRG
Cluster of neurons generates rhythm
Motor efferents coming out of brainstem
Phrenic motorneurons: for diaphragm
Thoracic motorneurons: for intercostal muscles
Abdominal motorneurons: for abdominal muscles
Cranial motorneurons: for larynx and pharynx
Dorsal respiratory group (DRG)
Inspiration
Anatomical location in medulla oblongata: near 4th ventricle, ventro-lateral nucleus of the tractur solitarius (vl-NTS)
Afferent fibers from mechanoreceptors (vagus nerve X) and chemoreceptors (glossopharyngeal nerve IX): lung stretch receptors (SAR)
Efferent fibers cross midline and synapse with phrenic motorneurons
Pontine respiratory group (PRG)
Shaping breathing pattern (switch from Insp to Exp)
Anatomic location in pons: nucleus parabrachialis medialis (NPBM), Kolliker-Fuse nucleus (KF)
Apneustic center is in lower pons: vigorous inspiration
Pneumotaxic center is in upper pons: signals termination of inspiration (and expiration, so you don’t injure lung?)
Suprapontine (CNS) input
Influences on DRG, VRG, PRG that are higher up (deeper in brain, CNS)
These inputs will stimulate ventilation MORE than is needed for metabolic exchange of O2 and CO2, so will lead to alveolar hyperventilation, hypocapnia and respiratory alkalosis
Cerebral cortex (volitional), limbic system (distress?), hypothalamus (affective behaviour), descending reticular formation
What happens if you ventilate MORE than is needed for metabolic exchange of O2 and CO2?
Alveolar hyperventilation
Hypocapnia (low PCO2)
Respiratory alkalosis
Two spinal pathways that output signal to breathing muscles
Automatic: ventrolateral columns
Voluntary: dorsolateral cord (corticospinal tract)
Note: if autonomic pathway partially damaged, will get primary alveolar hypoventilation (PCO2 increased, “Ondine’s curse”)
Reflexes of the upper airway
Nose: dive reflex, sneeze reflex
Pharynx: reflex swallowing
Larynx: cough, apnea
Pulmonary vagal mechanoreceptors
These exert effects on breathing pattern:
SAR: slowly adapting (stretch) receptors
RAR: rapidly adapting (irritant) receptors
J: juxtapulmonary capillary receptors
Bronchial C fibers
Slowly adapting (stretch) receptors (SAR)
Activated by lung inflation to cause inspiration to stop (Hering-Breuer reflex)
In parenchyma of lung and smaller airway smooth muscle
Myelinated afferent fibers signal to vagus nerve which goes to NTS
Hering-Breuer not that important in humans, but helps animals limit inspiration and helps them keep breathing (increase respiratory frequency)
Rapidly adapting (irritant) receptors (RAR)
Stimulated by inhalation of irritant materials and by local mechanical distortion –> cause hyperpnea, cough, bronchoconstriction
Located in epithelium larger airway and larynx
Myelinated afferent fibers signal to vagus nerve which ends bilaterally at NTS
Note: inflate lungs faster, then get faster firing of these RARs
Juxtapulmonary capillary (J) receptors
Stimulated by interstitial distortion, congestion, pulmonary emboli and cause tachypnea
Located in alveolar-capillary interstitial space
Non-myelinated free nerve endings signal to vagus nerve which terminates bilaterally in NTS and area postrema
Bronchial C-fibers, RAR, and cough mechanism
Cough is due to activation of sensory receptors in larynx/lower respiratory tract that send impulses to brain stem
Cough reflex is interaction between C-fiber receptors and RAR
Tachykinins released from C-fibers and diffuse to RARs
Stimulation of C-fibers can cause inhibition of cough
Stimuli: dust, irritant gases, casaicin, PE, pulmonary congestion
Mediators: ACh, histamine, serotonin, prostaglandins, bradykinin, substance P
ACE inhibitors and cough
ACE inhibitors cause accumulation of angiotensin I in the lung, and accumulation of bradykinin and other mediators activate cough mechanism
(ACE inactivates bradykinin, so ACE inhibitors lead to accumulation of bradykinin)
ACE inhibitors: lisinopril and captopril
Chest wall mechanoreceptors
Coordinate breathing during changes of posture and speech
Muscle spindles
Golgi tendon organs
Muscle spindles
Respond to muscle stretching and cause stimulation of respiratory motorneurons
Located on intrafusal muscle fibers of intercostal muscles (and a little on diaphragm)
Golgi tendon organs
Respond to muscle tension (pressure) and cause inhibition of respiratory motor neurons
Located on diaphragm
Peripheral sensory afferents that ALL stimulate ventilation
Muscle spindles (in limb muscles)
Articular proprioceptors (in limb joints)
Pain afferents
Autonomic regulation of airways
NE and EPI at beta receptors cause bronchodilation
ACh at muscarinic receptors causes bronchoconstriction
Vasoactive intestinal peptide and NO act through non-adrenergic non-cholinergic (NANC) system and cause bronchodilation
Peripheral chemoreceptors
Located in carotid bodies in carotid bifurcation (aortic arch not that important)
Sense low PaO2, high PaCO2, high [H+] and increase ventilation
Only respond when PaO2 is BELOW 60 mmHg
Hypoxia (lack of O2) potentiates response to PaCO2, and high PaCO2 potentiates response to low O2
Central chemoreceptors
Located as regions of chemosensitivity bilaterally on ventrolateral surface of medulla (RTN, d-NTS, near vagus and glossopharyngeal) in ECF and exposed to CSF
Sense high PaCO2 (strictly speaking), and high [H+] of CSF and increase ventilation
Even though BBB impermeable to ions, CO2 diffuses easily and turns into H+ and HCO3- so central chemoreceptors can indirectly respond to [H+]
How does carotid body communicate with the brain?
Carotid body –> carotid sinus nerve –> glossopharyngeal nerve –> DRG
Do the peripheral or central chemoreceptors respond to hypoxia (PaO2)?
Peripheral chemoreceptors (carotid bodies)
Only respond to hypoxia when PaCO2 less than 60 mmHg (makes sense bcause this is when hemoglobin actually gets less saturated!)
Do the peripheral or central chemoreceptors respond to hypercapnia (PaCO2)?
Central responsible or 70-80% of response
Peripheral responsible for 20-30% of response
Note: in low O2 situations, carotid bodies help increase ventilation more; in high O2 situations, carotid bodies don’t do anything
Do the peripheral or central chemoreceptors respond to metabolic acidosis (increased [H+])?
Carotid bodies only (peripheral), UNLESS cerebral anaerobiosis happens in the brain and that can trigger central chemoreceptors
Acidosis –> left shift –> any given PaCO2 gives higher ventilation
Alkalosis –> right shift –> any given PaCO2 gives lower ventilation
Dejor’s Test
Breathing 100% O2 decreases ventilation (carotid bodies turned off!) and increases end tidal CO2
Primary and secondary (2-3 days later) ventilatory response to altitude
Primary: Hypoxia –> increased ventilation via carotid bodies –> increased PAO2 and decreased PACO2 –> as PaCO2 decreased (pH is increased–respiratory alkalosis), less stimulation via central chemoreceptor response to low PaCO2 –> decrease breathing (bad!)
Secondary: After 2-3 days, kidneys excrete HCO3- to compensate so that pH decreases again –> increased [H+] in CSF increases ventilation via central chemoreceptors, and still have carotid body stimulation
Summary: peripheral stimulation to increase ventilation blunted by central stimulation, then kidneys correct pH back to more acidic and central chemoreceptors increase ventilation again
Note: can give acetazolamide (carbonic anhydrase inhibitor) before going to altitude to help acclimatization (you’ll still hyperventlate, but won’t get as much of an increase in CSF pH because you’re operating at minor metabolic acidosis already)
Adaptations to chronic hypoxia
Polycythemia: kidneys secrete erythropoietin –> increase RBCs –> increased O2 content for given PaO2
Increased 2,3-DPG: shifts Hb-O2 curve right –> more O2 unloaded at tissues (but can impair O2 loading in lung)
Pulmonary hypertension: hypoxic pulmonary vasoconstriction –> increased vascular resistance –> increased pulmonary artery pressure –> can cause right side heart failure (BAD!)
Why is ventilation decreased during sleep?
Reduced metabolic rate
Diminished cortical and reticular activating system activity
Respiratory muscle relaxation during REM sleep
