CONTROL OF RESPIRATION

Spontaneous respiration is produced by rhythmic discharge of motor neurons

that innervate the respiratory muscles.

HISTORY

 Galen(200 AD) - recognised that section of the highest level of spinal

cord resulted in immediate death by respiratory arrest

 Legallois (1812) - demonstrated that breathing depended on integrity of a

small region in medulla

 Flourens (1854) - destruction of the vital knots in the floor of the IV

th
ventricle causes respiratory arrest

Respiration is controlled:

 Neural

 Chemical

NEURAL CONTROL

 Voluntary (cortex)

 Automatic (pons,medulla)

AUTOMATIC CONTROL

 Medullary :

Respiration is initiated by a small group of synaptically coupled

pacemaker cells in pre-Botzinger complex on either sides of medulla

Also contact with hypoglossal nuclei and so tongue is involved in

regulating airway resistance

Centres

 Dorsal respiratory group

 Ventral respiratory group

DRG
  Located near nucleus of tractus solitarius

 Mainly inspiratory cells

 Primary site of rhythm generation

 Receives afferents from Proprioceptors of respiratory muscles and chest

wall

Sensors of upper airway, lungs and peripheral chemoreceptors

Axons descends in the contralateral spinal cord to the anterior horn cells that
innervate diapraghm and inspiratory intercostals

VRG

 Located close to nucleus ambigus and retroambigualis

 Contains both inspiratory and expiratory cells

 No inherent rhythmicity

 No sensory input from peripheral or central chemoreceptors

 Efferents to contralateral anterior horn cells to intercostals, abdominal

and accessory muscles

 Inactive during quiet breathing

 Provides powerful expiratory signals to abdominal muscles during forced

b

 reathing

PONTINE CENTRES

 Pneumotaxic

 Apneustic

PNEUMOTAXIC

 Dorsolateral part of reticular formation

  Neurons form nucleus parabrachialis

 Influence timing of inspiratory cut-off

 Modulate respiratory response to hypoxia hypercapnia and lung inflation

 Indirectly increase respiratory rate by reducing duration of inspiration

APNEUSTIC

 Caudal to PNC near pontomedullary border

 Prolongs inspiratory activity

 Accelerates depth of inspiration by acting directly on DRG

CHEMICAL CONTROL

 Respiratory chemoreceptors (peripheral)

 Medullary chemoreceptors(central)

PERIPHERAL CHEMORECEPTORS

 Carotid and aortic body

 Type 1 cells (glomus)

 Assoc with cup like endings

 Contain catecholamines released upon exposure to hypoxia

 Transmitter is dopamine

 Type 2 cells

 Glia like cells

 Surrounds about 4-6 type 1 cells, Sustentacular function

CAROTID BODY

 In internal carotid artery near bifurcation of common carotid

 Afferents through IXthCN

 Reduction in Po2 is the potent stimulus

 Mildly sensitive to increase in Pco2 & pH

 Hypoxia,hypercapnia& acidosis results in increased ventilation

 Stimulation also causes increase in bronchomotor tone, blood pressure,

catecholamine secretion and pulmonary vascular resistance

 Blood flow -0.04ml/mt (2mg)

 2000ml/100gtissue/min

 Not stimulated in anemia,CO poisoning

 Stimulated in cyanide poisoning

AORTIC BODY

 Situated on arch of aorta

 Chemoreceptors in aortic body are supplied by aortic nerve, a branch of

Xth cranial nerve

CENTRAL CHEMORECEPTORS

 In medulla,close to dorsal group of neurons

 Receptors also in solitary tract nuclei ,locus ceruleus,hypothalamus

 Send stimulatory impulses to medullary centers causing increased rate

and force of breathing

 Responds to changes in CSF and extracellular pH

 Hypercapnic acidosis is a more potent stimulus than metabolc acidosis

RECEPTORS IN RESPIRATORY TRACT &LUNGS

(NONCHEMICAL)

 Irritant receptors

 Stretch receptors

 ‘J’ receptors

 Others
 IRRITANT

 Rapidly adapting

 Densely located around carina

 Mechanical stimuli:- hyperinflation of lungs

 Chemical stimuli:-cigarette smoke, ammonia, sulfurdioxide and CO2

 Stimulation- cough,increased mucus production and rapid shallow

breathing by shortening expiration

 Implicated in bronchoconstriction in asthma and in alterations of

breathing pattern in CO

STRETCH RECEPTORS

 Slowly adapting

 Situated within airway smooth muscle

 Responsible for Hering-Breuer Reflex

 Concentrated in trachea and large airways

 Inspiration- stretches the lung- receptors stimulated- inhibit inspiratory

centers

 Also causes bronchodilatation,tachycardia, hyperpnea

J RECEPTORS

 Non myelinated

 Slowly conducting C type fibers

 Mainly in periphery of lungs

 Stimulated during

 Pulmonary congesion

 Pulmonary edema
 Pneumonia

Hyper inflation

Microembolism

Produce apnea followed by rapid shallow

breathing,laryngealconstriction,hypotension and bradycardia

AFFERENTS FROM HIGHER CENTRES

 Pain and emotional stimuli affect respiration.

 Afferents from the limbic system and hypothalamus to the respiratory

neurons in the brain stem

RESPIRATORY MUSCLE AFFERENTS.

 Muscle spindles

 Slowly adapting mechanoreceptors

 Mainly in intercostal muscles

 Can provide added respiratory load compensation

Golgi tendon organs

Mechanoreceptors

Mainly in diaphragm

Responds to change in position of body

Stimulated during muscular exercise

OTHERS

 Baroreceptors

 Thermoreceptors
  Pain receptors

 Cough reflex

 Sneezing reflex

 Deglutition reflex

CLINICAL ASPECTS
1.EXERCISE

 O2consumption &CO2 production increase 20 times

 4 phases

 Phase1 -Abrupt increase in ventilation coincides with start of exercise,

prior to alterations in gas tensions , neurogenic component,muscle
spindles important

 Phase 2–Hypercapnic response to exercise begins 10 or 15 seconds

following onset,coincident with alterations in blood gas tensions
  Phase 3- steady state response to exercise, linked to CO2 production

 Phase 4- further increase in ventilation with metabolic production

of lactic acid, lactic acidosis induced hyperpnea is mediated by peripheral
chemoreceptor also relate to increased body temperature and arterial Po2

2.SLEEP

 In wakefulness, automatic and voluntary control acts

 During sleep, automatic control predominate at least during slow wave

sleep

 Absence of automatic control results in Ondine’s curse

ABNORMAL PATTERNS

 Abnormal respiratory patterns are a common consequence of stroke.

 Seen in 60 percent of patients with acute neurologic disorders including

acute stroke.

CHEYNE STOKE

 Recurrent central apnea alternating with a crescendo-decrescendo pattern

of tidal volume.

 Most commonly recognized abnormal respiratory pattern after stroke, but

in approximately 90 percent of patients it reflects underlying
cardiopulmonary disease

 Unilateral hemispheric and brainstem infarcts

 Has little prognostic value

 Hypocapnia is almost always present and may exacerbate the underlying

neurologic condition.

 Hypoxemia is frequently present due to concomitant heart and lung

disease.
 Heart failure, Uremia, Some brain diseases, During sleep in some normal
individuals

PERIODIC BREATHING

 Characterized by regular, recurrent cycles of changing tidal volumes in

which the lowest tidal volume is less than half the maximal tidal volume
in that cycle

 It is the most frequent abnormal respiratory pattern directly related to

stroke

 More common among patients with subarachnoid hemorrhage

ATAXIC BREATHING

 Rare respiratory pattern

 Characterized by an erratic rate and depth of breathing, alternating with

interspersed episodes of apnea

 Only respiratory pattern with true localizing value and is indicative of a

medullary lesion.

 Occur in patients with neurodegenerative disorders ( Shy-Drager

syndrome).

 Caused by dysfunction of the dorsal respiratory neurons in the medulla

that control the rhythmicity of breathing.

APNEUSTIC BREATHING

 Characterized by sustained deep inspiration lasting several seconds

followed by a rapid exhalation and a brief post-expiratory phase.

 Dysfunction of the inspiratory cut-off mechanism localized in the

inferomedial posterior region of the pons

 The pattern is rarely observed because patients usually have severe bulbar
dysfunction and require mechanical ventilation

 Weaning from mechanical ventilation is often difficult, and long-term

ventilation via tracheostomy is often necessary.
 HYPOVENTILATION

 Alveolar hypoventilation exists when actual Pco2> 37-43mm Hg

 In clinically significant case it rises above 45mmHg

 Underlying mechanism involves defect in either sensors or integrating

neurons, of metabolic respiratory control system or in effector organ of
breathing

 The cerebral acid base status, abnormalities in blood gases are not sensed.

 Patients fail to breath normally in response to metabolic respiratory

stimuli but as voluntary control , motor pathway and ventilatory
apparatus are intact, they are capable of voluntarily ^ respiration

 So they have impaired response and often hypo ventilate mainly during
sleep, as ventilation mainly depends on metabolic parameters during
sleep

 OBESITY HYPOVENTILATION SYNDROME

 Body mass index over 30 kg/m2

 Arterial carbon dioxide level over 45 mmHg or 6.0 kPa as determined by

ABG measurement

 No alternative explanation for hypoventilation, such as use of narcotics

 Combination of obesity, hypoxia during sleep and hypercapnia

 This is the result of hypoventilation during sleep

 Obstructive sleep apnea is often but not necessarily present

 2 TYPES

 First is OHS in the context of obstructive sleep apnea; this is confirmed

by the occurrence of 5 or more episodes of apnea, hypopnea or
respiratory-related arousals per hour ( high AHI )during sleep

 . The second is OHS primarily due to "sleep hypoventilation syndrome";

this requires a rise of CO2 levels by 10 mmHg (1.3 kPa) after sleep
 compared to awake measurements and overnight drops in oxygen levels
without simultaneous apnea or hypopnea.

 In many patients, both phenomena are present

 RX - Weight reduction, Exercise , CPAP, Bariatric surgery,

Tracheostomy

CHRONIC HYPOVENTILATION

 Results from defect in effector elements of respiratory system,

 Disorders of chemoreceptorsbrain stem sp cord , ph nerve , respmuscle

chest wall structures lung and airway

 Regardless of cause – main disturbance is reduction of alveolar

ventilation leading to ^ PCO2 causing obligatory < PO2 causing
hypoxemia

 Chronic disturbance leads to 20 physiologic response leading to clinical

features of chronic hypoventilation

PRIMARY ALVEOLAR HYPOVENTILATION

 Characterized by chronic hypercapnia& hypoxemia in absence of

identifiable neurologic, respiratory muscle weakness or mechanical
ventilatory defect

 Occur due to failure in metabolic control system

 As voluntary system is intact patient can hyperventilate & reduce arterial

PCO2 levels

 Failure of chemoreceptors of medullary neuronal network

 Important role for genetic and metabolic factors

  Structural abnormalities of carotid body chemoreceptor have been
demonstrated

 Occurs in all age groups ( mainly males- 20-50- yrs )

 Symptoms are insidious

 Dyspnea is uncommon, & arterial PCO2 may be normal when awake

 1st suspected when patient develops severe respiratory depression after

conventional doses of anaesthesia

 ABG- Hypercapnia, Hypoxemia, Chronic respiratory acidosisIn absence

of respiratory muscle weakness & mechanical ventilatory defects

 RX Caution on sedatives, Methylxanthines, Analeptics, Progesterone

Acetazolamide, LTOT, NIV

HYPERVENTILATION

 ^ rate of alveolar ventilation that is excessive for rate of metabolic CO2

production resulting in arterial pCO2 below nml (37-43mmHg)

 Hyperventilation is often associated with dyspnea

PATHOGENESIS

Arises from excessive ventilatory drive, Hypoxemia, Pulmonary disorders

CVS disorders,

C/F

Respiratory alkalosis, Hypokalemia, Hypophosphatemia, Hypocalcemia

CVS - cardiac arrythmias,ischemia

CNS - syncope (every 1mmHg < PCO2 cerebral blood flow < by 2%)

RX

Treat the underlying cause

Alkalemia causing tetany ,cardiac ischemia – low conc: CO2

Psychogenic -- reassurance