Patterns of Respiration BY AHMAD YOUNES PROFESSOR OF

Patterns of Respiration BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINE Mansoura faculty of medicine

The central pattern generator is composed of predominately three neuronal groups 1 - Dorsal respiratory group 2 - Ventral respiratory group 3 - Pontine respiratory group. – The dorsal respiratory group is in the ventrolateral subnucleus of the nucleus tractus solitarius. This neuronal group is primarily active during inspiration receiving input from pulmonary vagal afferents. Many of these neurons excite lower motor cranial nerves that dilate the upper airway prior to excitation of the contralateral phrenic and intercostal neurons in the spinal cord. This coordinated output must occur in the correct timed sequence to permit the movement of air through a patent airway.

Ventral respiratory group • The ventral respiratory group is located in the ventral lateral medulla from the top of the cervical cord to the level of the facial nerve. • This group contains the Botzinger complex, the pre. Botzinger neurons, the rostral portion of nucleus ambiguous, and nucleus retroambigualis. • The Botzinger complex contains neurons that are active during expiration and inhibit inspiration. • The pre. Botzinger complex contains propriobulbar neurons that participate in generating the rhythm of respiration. • The caudal portion of this group is primarily composed of expiratory neurons that project to intercostal, abdominal, and external sphincter motor neurons.

Ventilatory control • The medullary centers respond to direct influences from the upper airways, intra-arterial chemoreceptors, and lung afferents by the 5 th, 9 th, and 10 th cranial nerves, respectively. • The dorsal respiratory group seems to be active primarily during inspiration. • The ventral respiratory group, contains both inspiratory and expiratory neurons. Ventral respiratory group output increases in response to the need forced expiration occurring during exercise or with increased airways resistance. • Respiratory effector muscles are innervated from the ventral respiratory group by phrenic, intercostal, and abdominal motoneurons.

Pontine respiratory centers • The pneumotaxic center in the rostral pons consists of the nucleus parabrachialis and the Kolliker-Fuse nucleus. • This area seems primarily to influence the duration of inspiration and provide tonic input to respiratory pattern generators. • The apneustic center, located in the lower pons, functions to provide signals that terminate smoothly inspiratory efforts. • The pontine input serves to fine tune respiratory patterns and may additionally modulate responses to hypercapnia, hypoxia, and lung inflation. • The automatic central control of respiration may be influenced and temporarily overridden by volitional control from the cerebral cortex (motor area , area 4, 6) for a variety of activities, such as speech, singing, laughing, intentional and psychogenic alterations of respiration, and breath holding.

Descending motoneurons include two anatomically separate groups: • The corticospinal and corticobulbar tracts for the volitional control of respiration and • The reticulospinal tracts for the automatic control of respiration. • volitional respiratory act is associated with a suppression of the background spontaneous breathing (automatic respiratory rhythm). Such an inhibition is obvious in specific respiratory acts such as breath holding, during speech, and when playing a wind instrument. • These voluntary modifications of breathing pattern (both in term of amplitude and frequency) can be made for long periods of time without any superimposed automatic rhythmic activity at least as long as Pa. CO 2 does not rise.

Central chemoreceptors • Central chemoreceptors, located primarily within the ventrolateral surface of medulla, respond to changes in brain extracellular fluid [H 1] concentration. • Other receptors have been recently identified in the brainstem, hypothalamus, and the cerebellum. • These receptors are effectively CO 2 receptors because central [H 1] concentrations are directly dependent on central PCO 2 levels. • Central [H 1] may differ significantly from arterial [H 1] because the blood-brain barrier prevents polar solute diffusion into the cerebrospinal fluid. This isolation results in an indirect central response to most peripheral acidbase disturbances mediated through changes in Pa. CO 2. • Central responses to changes in PCO 2 levels are also slightly delayed for a few minutes by the location of receptors in the brain only, rather than in peripheral vascular tissues.

Peripheral chemoreceptors • Peripheral chemoreceptors include the carotid bodies and the aortic bodies. • The carotid bodies, located bilaterally at the bifurcation of the internal and external carotid arteries, are the primary peripheral monitors. • They are highly vascular structures that monitor the status of blood about to be delivered to the brain and provide afferent input to the medulla through the 9 th cranial nerve. • The carotid bodies respond mainly to Pa. O 2, but also to changes in Pa. CO 2 and p. H. • They do not respond to lowered oxygen content from anemia or carbon monoxide toxicity.

Other afferent pathways • Pulmonary stretch receptors are located in proximal airway smooth muscles, and respond to inflation, especially in the setting of hyperinflation. Pulmonary stretch receptors mediate a shortened inspiratory and prolonged expiratory duration. • Additional input is also provided by rapidly adapting receptors that sense flow and irritation. J receptors are located in the juxtacapillary area and seem to mediate dyspnea in the setting of pulmonary vascular congestion. • Bronchial c-fibers also affect bronchomotor tone and respond to pulmonary inflammation.

Other afferent pathways • Afferent activity from chest wall and respiratory muscles additionally influences central controller activity. • Feedback information regarding muscle stretch, loading, and fatigue may impact both regulatory and somato-sensory responses. • Upper airway receptors promote airway patency by activation of local muscles including the genioglossus.

During sleep • During sleep, the metabolic rate falls (hence, decreased CO 2 production), but this is offset by a proportionately greater fall in minute ventilation with the result that the Pa. CO 2 increases slightly. • The fall in ventilation is due to increased upper airway resistance and decreased chemosensitivity as well as the loss of the wakefulness stimulus to breathe. • The result is that the Pa. CO 2 rises and the Pa. O 2 falls slightly

Because of the normal position on the flat portion of the O 2 Hb dissociation curve, there is little change in the Sa. O 2 as a result of the fall in PO 2 associated with sleep. If the baseline awake Pa. O 2 is lower, the fall in Sa. O 2 will be greater for the same drop in Pa. O 2. • In patients with lung disease and a lower awake PO 2, even a normal sleep-related drop in PO 2 will be associated with a larger decrease in the Sa. O 2. • The change in ventilation with sleep is due to a fall in Vt with minimal change in the RR. • During the transition from wake to stage N 1 and early stage N 2, the ventilation can be slightly irregular. However, in stable stage N 2 and stage N 3, the Vt and RR are nearly constant. • During REM sleep, ventilation is irregular with periods of decreased Vt associated with bursts of eye movements. • The FRC decreases from wake to sleep.

• During sleep, the hypercapnic ventilatory response and hypoxic ventilatory response are reduced during NREM compared with wake and decreased in REM sleep compared with NREM sleep. • Both hypoxia and hypercapnea may trigger arousals from sleep, resulting in a return to the more tightly regulated ventilatory control associated with wakefulness. • Arousal thresholds for hypercapnia range between 65 and 66 mm. Hg and do not vary consistently among the different sleep stages. • The threshold for arousal in response to hypoxia is more variable and seems less reliable. Severe oxygen desaturations in some individuals do not uniformly result in arousals.

Alveolar hypoventilation • Alveolar hypoventilation during wakefulness is defined as an Pa. CO 2 of 45 mm Hg or higher. • If the sleeping Pa. CO 2 is ≥ 10 mm Hg above the awake value, Sleep hypoventilation is said to be present. Hypoxemia is defined as a low arterial partial pressure of oxygen (Pa. O 2) relative to predicted values. A Pa. O 2 < 55 mm Hg while breathing room air is considered severe and an indication for chronic 24 -hour supplemental oxygen therapy. Milder degree of hypoxemia can be identified by comparing a Pa. O 2 with a predicted value for age. • A simple estimate of a normal predicted Pa. O 2 Pao 2=105 – 1/2 age (yr).

Normal respiration • Eupnea: Normal breathing at a rate of 12 -20 bpm e g. normal physiology • Normal respiration at rest for healthy subjects: - inhalation is 1. 5 -2 s - exhalation is 1. 5 -2 s - automatic pause of almost no breathing is 2 s - tidal volume (the depth of inhalation) is 500 -600 ml - breathing frequency is 10 -12 breaths/min.

Abnormal respiration • Bradypnea: Slow respiratory rate <12 bpm. e g. normal during sleep, brain tumors, diabetic coma, drugs (alcohol, narcotics), increased intracranial pressure, metabolic acidosis, uremia • Tachypnea: Increased respiratory rate >20 bpm, regular rhythm e g. anxiety , asthmatic, atelectasis, brain lesions, drugs (aspirin), exercise, fever, hypercapnia, hypoxemia, metabolic acidosis, pain • Hypopnea: decreased depth with normal rate and rhythm e g. normal during sleep , circulatory failure, meningitis, unconsciousness • Hyperpnea: increased depth, normal rate and rhythm e g. exertion, fever, pain.

Bradypnea • Bradypnea (Greek from bradys, slow + pnoia, breath; British English spelling bradypnoea) refers to an abnormally slow breathing rate. • The rate at which bradypnea is diagnosed depends upon the age of the patient. Age ranges and bradypnea • Age 0– 1 year < 30 breaths per minute • Age 1– 3 years < 25 breaths per minute • Age 3– 12 years < 20 breaths per minute • Age 12– 50 years < 12 breaths per minute • Age 50 and up < 13 breaths per minute

Causes: • • • Normal during sleep, Brain tumors Diabetic coma Drugs (alcohol, narcotics ↑ICP, metabolic alkalosis Hypothyroidism

Tachypnea • Tachypnea (or "tachypnoea") (Greek: "rapid breathing") is the condition of rapid breathing. • In adult humans at rest, any rate between 12 -20 breaths per minute is normal and tachypnea is indicated by a respiratory rate >20 breaths per minute.

Hyperventilation • Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, (hyperpnoea)[causing falling Paco 2 below normal (35– 45 mm. Hg). • Stress or anxiety commonly are causes of hyperventilation; as a consequence of various lung diseases, head injury, or stroke (central neurogenic hyperventilation, apneustic respirations, ataxic respiration, Cheyne–Stokes respiration or Biot's respiration) and metabolic acidosis, In the setting of diabetic ketoacidosis, this is known as Kussmaul breathing – characterized by long, deep breaths.

Hypoventilation • Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate to perform needed gas exchange. • It causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. • Hypoventilation during wakefulness is defined as an Pa. CO 2 equal to or greater than 45 mm Hg. During sleep, Score hypoventilation during sleep if there is a ≥ 10 mm Hg increase in Pa. CO 2 during sleep in comparison with an awake supine value.

Kussmaul breathing • Kussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis but also renal failure. • In metabolic acidosis, breathing is first rapid and shallow but as acidosis worsens, breathing gradually becomes deep, labored and gasping. It is this latter type of breathing pattern that is referred to as Kussmaul breathing.

Kussmaul breathing

Apneustic Respiration • The apneustic center of the lower pons appears to promote inspiration by stimulation of the Inspiratory neurons in the medulla oblongata providing a constant stimulus. • The apneustic center of pons sends signals to the dorsal respiratory center in the medulla to delay the 'switch off' signal of the inspiratory ramp provided by the pneumotaxic center of pons. It controls the intensity of breathing. • The apneustic center is inhibited by pulmonary stretch receptors. However, it gives positive impulses to the inspiratory neurons.

Apneustic Respiration • Apneustic respiration is an abnormal pattern of breathing characterized by deep, gasping inspiration with a pause at full inspiration followed by a brief, insufficient release, with an increase in the ratio of inspiratory to expiratory time. • It is caused by damage to the pons or upper medulla caused by strokes or trauma. • Specifically, concurrent removal of input from the vagus nerve and the pneumotaxic center causes this pattern of breathing. • It can also be temporarily caused by some drugs, such as ketamine. • It is an ominous sign, with a generally poor prognosis. Apneustic respiration in patients with achondroplasia ( congenital small foramen magnum which compress the distal medulla and upper cervical cord )

Apneustic respiration during wakfullness. .

• Apneustic respiration during NREM N 1 and N 2.

Ataxic Breathing • This type of breathing is characterized by clusters of cyclic irregular breathing followed by recurrent periods of apnea. • The apnea length is greater than the ventilatory phase. • Ataxic breathing is often noted in medullary lesions. Biot’s breathing is a special type of cluster breathing (ataxic breathing) characterized by breaths of nearly equal volume separated by long periods of apnea. • This is really a variant of ataxic or cluster breathing and may be found in patients with medullary lesions.

Ataxic Respiration • As the breathing pattern deteriorates, it merges with agonal respirations. • It is caused by damage to the medulla oblongata due to strokes or trauma. It generally indicates a poor prognosis, and usually progresses to complete apnea. • The term is sometimes used interchangeably with Biot's Respirations, but technically, Biot's respirations refers to groups of similar-sized breaths alternating with regular periods of apnea.

Agonal Respiration • • • Agonal respiration is an abnormal pattern of breathing characterized by gasping, labored breathing, accompanied by strange vocalizations and myoclonus. Possible causes include cerebral ischemia, extreme hypoxia or even anoxia. Agonal breathing is an extremely serious medical sign requiring immediate medical attention, as the condition generally progresses to complete apnea and heralds death. The term is sometimes (inaccurately) used to refer to labored, gasping breathing patterns accompanying organ failure (e. g. liver failure and renal failure), SIRS, septic shock, and metabolic acidosis (see Kussmaul breathing, or in general any labored breathing, including Biot's respirations and ataxic respirations. Correct usage would restrict the term to the last breaths before death.

Myoclonus • • • Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. Contractions are called positive myoclonus; relaxations are called negative myoclonus. The most common time for people to encounter them is while falling asleep (hypnic jerk), but myoclonic jerks are also a sign of a number of neurological disorders. Hiccups are also a kind of myoclonic jerk specifically affecting the diaphragm. Most often, myoclonus is one of several signs in a wide variety of nervous system disorders such as multiple sclerosis, Parkinson's disease, some forms of epilepsy, and occasionally in intracranial hypotension.

Agonal Respirations • Agonal respirations are also commonly seen in cases of cardiogenic shock or cardiac arrest where agonal respirations may persist for several minutes after cessation of heartbeat. • The presence of agonal respirations in these cases indicates a more favorable prognosis than in cases of cardiac arrest without agonal respirations. • In an unresponsive, pulseless patient in cardiac arrest, agonal gasps are not effective breaths. • Agonal respiration is not the same as, and is unrelated to, the phenomenon of death rattle.

Death Rattle • A death rattle is a medical term that describes the sound produced by someone who is near death when saliva accumulates in the throat. • Those who are dying may lose their ability to swallow, resulting in such an accumulation. • Related symptoms can include shortness of breath and rapid chest movement. • While death rattle is a strong indication that someone is near death. it can also be produced by other problems that cause interference with the swallowing reflex, such as the case with brain injuries. • It is sometimes misinterpreted as the sound of the person choking to death. • In palliative care, drugs such as atropine may be used for their anticholinergic effects to reduce secretions and minimize this effect.

Cheyne-Stokes and Cheyne-Stokes Variant Patterns of Breathing • Cheyne-Stokes breathing (CSB) is a special type of central apnea manifested as cyclic changes in breathing with a crescendodecrescendo sequence separated by central apneas. • The Cheyne-Stokes variant pattern of breathing is distinguished by the substitution of hypopneas for apneas. • AASM scoring CSB if there at least 3 consecutive cycles of cyclical crescendo-decrescendo change in breathing amplitude accompanied by at least one of the following: 1 - five or more central apneas and hypopneas per hour of sleep; and 2 - a cyclic crescendodecrescendo change in breathing amplitude and duration of at least 10 consecutive minutes. • The cycle length is most commonly in the range of 60 seconds but must be at least 45 seconds in duration. • The arousals typically occur in the middle of the hyperventilation cycle. • This breathing pattern is most prominently seen in NREM sleep, particularly stages 1 and 2, and attenuates or disappears during REM sleep.

Cheyne-Stokes and Cheyne-Stokes Variant Patterns of Breathing • In neurologic disorders, the Cheyne-Stokes type of breathing is mostly noted in bilateral cerebral hemispheric lesions and it worsens during sleep, whereas Cheyne-Stokes variant patterns of breathing may also be noted in brain stem lesions, in addition to bilateral cerebral hemispheric disease. • This pattern of breathing is noted in patients with severe congestive cardiac failure.

Dysrhythmic Breathing • Dysrhythmic breathing is characterized by nonrhythmic respiration of irregular rate, rhythm, and amplitude during wakefulness with or without O 2 desaturation that becomes worse during sleep • Dysrhythmic breathing may result from an abnormality in the automatic respiratory pattern generator in the brain stem.

Inspiratory Gasp • Inspiratory gasp is characterized by a short inspiration time and a relatively prolonged expiration (reduced inspiratory-expiratory time ratio). • Gasping or irregular breathing has been noted after lesion in the medulla.

Apraxia • Apraxia (from the Greek root word praxis, for an act, or preceded by a privative a, meaning without) is characterized by loss of the ability to execute or carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements. • It is a disorder of motor planning, which may be acquired or developmental, but is not caused by incoordination, sensory loss, or failure to comprehend simple commands (which can be tested by asking the person to recognize the correct movement from a series).

Apraxia • It is caused by damage to specific areas of the cerebrum. • Apraxia should not be confused with ataxia, a lack of coordination of movements; aphasia, an inability to produce and/or comprehend language; abulia, the lack of desire to carry out an action; or allochiria, in which patients perceive stimuli to one side of the body as occurring on the other.

Apraxia • Apraxia is neurological condition characterized by loss of the ability to perform activities that a person is physically able and willing to do. • Apraxia is caused by brain damage related to conditions such as head injury, stroke, brain tumor, and Alzheimer's disease. • The damage affects the brain's ability to correctly signal instructions to the body. Forms of apraxia include the inability to say some words or make gestures.

Causes and symptoms • Apraxia is caused by conditions that affect parts of the brain that control movements. • Apraxia is a result of damage to the brain's cerebral hemispheres. These are the two halves of the cerebrum and are the location of brain activities such as voluntary movements. • Apraxia causes a lapse in carrying out movements that a person knows how to do, is physically able to perform, and wants to do. • A person may be willing and able to do something like bathe. However, the brain does not send the signals that allow the person to perform the necessary sequence of activities to do this correctly.

Types of apraxia • Buccofacial or orofacial apraxia is the inability of a person to follow through on commands involving face and lip motions. These activities include coughing, licking the lips, whistling, and winking. It is the most common form of apraxia. • Limb-kinetic apraxia is the inability to make precise movements with an arm or leg. • Ideomotor apraxia is the inability to make the proper movement in response to a command to pantomime an activity like waving. • Constructional apraxia is the inability to copy, draw, or build simple figures. • Ideational apraxia is the inability to do an activity that involves performing a series of movements in a sequence. A person with this condition could have trouble dressing, eating, or bathing. It is also known as conceptual apraxia. • Oculomotor apraxia is characterized by difficulty moving the eyes. • Verbal apraxia is a condition involving difficulty coordinating mouth and speech movements. It is referred to as apraxia of speech

Respiratory apraxia • Respiratory apraxia is defined as failure to perform voluntary respiratory movement on command with the lack of pyramidal defect.

SLEEP-RELATED RESPIRATORY DYSRHYTHMIA Sleep Apnea • Three types of sleep apnea have been noted: central, upper airway obstructive, and mixed. • Normal individuals may experience a few episodes of sleep apnea, particularly central apnea, at the onset of NREM sleep and during REM sleep. • To be of pathologic significance, the sleep apnea should last at least 10 seconds and the apnea index (number of apneas per hour of sleep) should be at least 5. • In addition to a duration of 10 seconds , apnea is scored when the peak amplitude drops by 90% or more of the baseline, and this amplitude reduction must last for at least 90% of the event’s duration.

Sleep Apnea • Cessation of airflow with no respiratory effort constitutes central apnea. During this period there is no diaphragmatic and intercostal muscle activity or air exchange through the nose or mouth. • Upper airway obstructive sleep apnea (OSA) is manifested by absence of air exchange through the nose or mouth but persistence of diaphragmatic and intercostal muscle activity. • During mixed apnea, initially airflow ceases, as does respiratory effort (central apnea); this is followed by a period of upper airway OSA. • On rare occasions this pattern may be reversed, resulting in an initial period of OSA followed by central apnea

Sleep-Related Hypopnea • Reduction of nasal pressure signal excursion (or that of the alternative airflow sensor) by 30% or more of the baseline amplitude lasting for a period of at least 10 seconds and accompanied by a 4% or more desaturation from the pre-event baseline. Furthermore, at least 90% of the event’s duration must meet the amplitude reduction criteria for hypopnea. • An alternative is a reduction of the amplitude excursion in the nasal pressure signal (or that of the alternative airflow sensor) by 50% or more of the baseline lasting for at least 10 seconds and accompanied by oxygen desaturation of 3% or more from the pre-event baseline, or the event is associated with an arousal. This amplitude reduction must be present for at least 90% of the event’s duration.

Sleep-Related Hypopnea • Sleep-related apneas and hypopneas in neurologic diseases are secondary sleep apnea syndromes, in contrast to primary OSA syndrome, in which no cause except for minor deviations of the upper airway anatomic configuration is found to account for the appearance of apnea. • The neurologic illness may be aggravated by the secondary sleep apnea because of the adverse effects of sleep induced hypoxemia and hypercapnia, and repeated arousals with sleep fragmentation. Paradoxical Breathing • The thorax and abdomen move in opposite directions during paradoxical breathing, indicating increased upper airway resistance. • In upper airway resistance syndrome, this may be noted without any change in oronasal airflow; • In OSA, paradoxical breathing is accompanied by reduction or absence of oronasal airflow.

Sleep-Related Hypoventilation • sleep-related hypoventilation, a type of respiratory dysrhythmia without any apnea or hypopnea, is seen commonly in neuromuscular and intrinsic pulmonary and thoracic restrictive disorders, and sometimes in brain stem lesions. • Sleep-related hypoventilation is characterized by an increase in the partial pressure of Pa. CO 2 of 10 mm Hg above the supine awake values during sleep. This abnormal rise in Pa. CO 2 is accompanied by severe sleep-related hypoxemia that is not due to apnea or hypopnea

Documentation of an increased partial pressure of carbon dioxide (PCO 2) during sleep. Note the alveolar plateaus (black circles). PCO 2 = exhaled PCO 2 waveform tracing; PETCO 2 = end-tidal reading; Sp. O 2 = pulse oximetry.

Catathrenia • Catathrenia (respiratory dysrhythmia with bradypnea and groaning), characterized by prolonged expiration with the characteristic groaning noise. • This may be mistaken for a central apnea but is really not an apnea , and there is no oxygen desaturation during the episode. • It is considered a parasomnia, and the etiology and mechanism are at present unknown.

Catathrenia: a rare parasomnia which may mimic central sleep apnea on polysomnogram. Note prolonged expiration in the flow and effort channels followed by arousals without oxygen desaturation in stage 2 NREM sleep.

Other Abnormal Breathing Patterns • Nocturnal stridor causing severe inspiratory breathing difficulty • Prolonged periods of central apnea accompanied by mild O 2 desaturation in relaxed wakefulness, as if the respiratory centers “forgot” to breathe. • Transient occlusion of the upper airway or transient uncoupling of intercostal and diaphragmatic muscle activity, • Transient sudden respiratory arrest