This document discusses the control of breathing and the neural mechanisms that regulate respiration. There are two main mechanisms - voluntary control located in the cerebral cortex, and automatic control driven by pacemaker cells in the medulla. The medulla contains respiratory centers that generate the rhythmic pattern of breathing through inspiratory and expiratory motor neurons. Breathing is regulated by chemical and non-chemical stimuli that act on central and peripheral chemoreceptors to modulate the respiratory centers. Abnormalities in the respiratory rhythm can occur due to lesions or diseases that disrupt the control centers.

1. DR.SASWAT SUBHANKAR
CONTROL OF BREATHING

2. INTRODUCTION
 SPONTANEOUS RESPIRATION IS PRODUCED BY
RYTHMIC DISCHARGES OF MOTOR NEURONS
THAT INNERVATE RESPIRATORY MUSCLES.
 2 SEPARATE NEURAL MECHANISMS REGULATE
RESPIRATION:
1. VOLUNTARY: a.LOCATED IN CEREBRAL
CORTEX.
b.SENDS IMPULSES TO
RESPIRATORY MOTOR NEURONS
VIA CORTICOSPINAL TRACTS.

3. 2. AUTOMATIC: a. RUN BY PACEMAKER CELLS
IN MEDULLA.
b. ACTIVATES MOTOR
NEURONS IN CERVICAL &
THORACIC SPINAL CORD.
 PHENOMENON OF RECIPROCAL INHIBITION IS
SEEN IN INSPIRATORY AND EXPIRATORY
MUSCLES DUE TO ACTIVITY IN DESCENDING
PATHWAYS.

4. COMPONENTS OF AUTOMATIC
RESPIRATION
CENTRAL
CONTROLLER
EFFECTORSSENSORS
INPUT OUTPUT

5. STIMULI AFFECTING RESPIRATORY CENTRE
 CHEMICAL: 1. CO2 (VIA CSF,BRAIN
INTERSTITIAL FLUID H+ CONC.)
2. O2
3.H+
VIA CAROTID AND
AORTIC BODIES.

6.  NON CHEMICAL: 1. VAGAL AFFERENTS FROM
RECEPTORS IN AIRWAYS AND LUNGS.
2. AFFERENTS FROM
PONS,HYPOTHALAMUS,LIMBIC SYSTEM.
3. AFFERENTS FROM PROPRIOCEPTORS.
4. AFFERENTS FROM BARORECEPTORS:
ARTERIAL,ATRIAL,VENTRICULAR,PULMONARY.

7. CENTRAL CONTROLLER

8. MEDULLARY SYSTEM
 MAIN COMPONENT OF AUTOMATIC
RESPIRATION OR RESPIRATORY CONTROL
PATTERN GENERATOR IS LOCATED IN
MEDULLA.
 RYTHMIC RESPIRATION IS GENERATED BY A
SMALL GROUP OF SYNAPTICALLY COUPLED
PACEMAKER CELLS IN THE PRE-BOTZINGER
COMPLEX(pre-BOTC) ON EITHER SIDE OF
MEDULLA BETWEEN NUCLEUS AMBIGUUS
AND LATERAL RETICULAR NUCLEUS.

9. LOCATION OF
pre- BOTC.

10.  NEURONS CONTAIN NK1 AND µ-OPIOID
RECEPTORS.
 DORSAL AND VENTRAL RESPIRATORY
GROUPS:
- DORSAL RESPIRATORY GROUP(DRG) IS MAINLY
A/W INSPIRATION;VENTRAL RESPIRATORY
GROUP(VRG) WITH EXPIRATION.
- POSSESS THE PROPERTY OF INTRINSIC
PERIODIC FIRING AND ARE RESPONSIBLE FOR
BASIC RYTHMS OF VENTILATIONS.

11. PONTINE INFLUENCES.
 PNEUMOTAXIC CENTRE: - LOCATED IN
UPPER PONS.
- SWITCH OFF CENTRE OR INHIBITS
INSPIRATION AND THUS REGULATES
INSPIRATION VOLUME.
 APNEUSTIC CENTRE: - LOCATED IN LOWER
PONS.
- IMPULSES FROM THIS CENTRE HAVE AN
EXCITATORY EFFECT ON THE INSPIRATORY
AREA .

13. CENTRAL CHEMORECEPTORS.
 LOCATED ON THE VENTRAL SURFACE OF
MEDULLA.
 MEDIATE THE HYPERVENTILATION PRODUCED
BY INCREASING ARTERIAL PCO2.
 MONITOR THE H+ CONC. OF CSF,INCLUDING
THE BRAIN INTERSTITIAL FLUID.
 CO2 PENETRATES BBB
H2CO3 H+ + HCO3-

15. LOCATION OF THE
CENTRAL
CHEMORECEPTORS.

16. CENTRAL NEURAL MECHANISM
 A 3-PART RHYTHM IS SEEN:
1. INSPIRATION.
2. POST-INSPIRATORY ACTIVITY.
3. EXPIRATION.

17. 1.INSPIRATION: - INSPIRATORY NEURONS THAT
ARE PRE-MOTOR TO THE PHRENIC AND
INTERCOSTAL MOTOR NUCLEI DISPLAY AN
AUGMENTING DISCHARGE.
- THE NEURONS RECEIVE INCREASING
EXCITATORY POST-SYNAPTIC ACTIVITY DURING
INSPIRATION.
- AT THE END OF INSPIRATION, DISCHARGE FROM
INSPIRATORY NEURONS ARE EXTINGUISHED BY
AN INHIBITORY ACTIVITY FROM OTHER
NEURONS.

18. 2. POST INSPIRATORY ACTIVITY: -
INSPIRATORY NEURONS RECEIVE BOTH
EXCITATORY AND INHIBITORY POST-SYNAPTIC
POTENTIALS.
- A/W ACTIVE BRAKING OF AIRFLOW AT THE
BEGINNING OF EXPIRATION.
- DURATION OF THIS PHASE IS AN IMPORTANT
DETERMINANT OF TOTAL DURATION OF
EXPIRATION.

19. 3. EXPIRATION: - INSPIRATORY NEURONS
RECEIVE INHIBITORY POST-SYNAPTIC
POTENTIALS IN AN AUGMENTING MANNER.
- THROUGHOUT EXPIRATION THERE IS A
DECREASING INHIBITION OF THE FOLLOWING
INSPIRATION-EARLY IN EXPIRATION, LARGE
STIMULI ARE NEEDED TO TRIGGER THE ONSET
OF INSPIRATION THAN LATE EXPIRATION.

21. PERIPHERAL CHEMORECEPTORS.

22. CAROTID AND AORTIC BODIES
 CAROTID BODY IS PRESENT NEAR CAROTID
BIFURCATION.
 2 OR MORE AORTIC BODIES ARE PRESENT
NEAR ARCH OF AORTA.
 CAROTID BODY:-COMPOSED OF 2 TYPES OF
CELLS.
- TYPE I CELLS/GLOMUS CELLS:RESEMBLE
ADRENAL CHROMAFFIN CELLS-CONTAIN
DENSE CORE GRANULES CONTAINING
CATECHOLAMINES THAT ARE RELEASED ON
EXPOSURE TO HYPOXIA,CYANIDE.

23. O2 SENSITIVE K+ CHANNELS.
DECREASED K+ EFFLUX DEPOLARISING THE CELL
AND CAUSING Ca2+ INFLUX
TRIGGERS AP AND NEUROTRANSMITTER RELEASE.
EXCITATION OF AFFERENT NERVE FIBRE

24. -TYPE II CELLS/GLIAL CELLS: EACH CELL
SURROUNDS 4-6 TYPE I CELLS.
FUNCTION IS PROBABLY SUSTENTACULAR.
- BLOOD FLOW IS ABOUT 2000ml/100g/min.
- O2 NEEDS OF THE CELLS ARE MET BY
DISSOLVED O2 ALONE-RECEPTORS ARE NOT
STIMULATED BY ANEMIA/CO POISONING BUT
IN CONDITIONS WHEN ARTERIAL PO2 IS LOW.

25.  AFFERENTS FROM CAROTID BODIES ASCEND
TO MEDULLA VIA GLOSSOPHARYNGEAL
NERVES.
 FIBRES FROM AORTIC BODIES ASCEND IN THE
VAGI.
 THE PERIPHERAL CHEMORECEPTORS ARE
RESPONSIBLE FOR ALL THE INCREASE OF
VENTILATION A/W ARTERIAL HYPOXEMIA.

27.  COMPLETE LOSS OF HYPOXIC VENTILATORY
DRIVE HAS BEEN SEEN IN PATIENTS OF B/L
CAROTID BODY RESECTION.
 RESPONSE OF PERIPHERAL CHEMORECEPTORS
TO ARTERIAL PCO2 IS LESS IMPORTANT THAN
THAT OF CENTRAL CHEMORECEPTORS.
 IN HUMANS,THE CAROTID AND NOT THE
AORTIC BODIES RESPOND TO INCREASED H+
CONCENTRATION.

28. NON-LINEAR RESPONSE OF
CAROTID BODIES TO ARTERIAL
PO2.
•SENSITIVITY OF
CAROTID BODIES
TO ARTERIAL PO2
BEGINS AT
AROUND 500mm
Hg.
•RELATIVELY
LITTLE
RESPONSE
OCCURS UNTIL
THE ARTERIAL
PO2 DROPS
BELOW 100mm
Hg.

29. LUNG RECEPTORS.
 PULMONARY STRETCH RECEPTORS:
- SLOWLY ADAPTING PULMONARY STRETCH
RECEPTORS.
- PRESENT WITHIN AIRWAY SMOOTH MUSCLE.
- DISCHARGE IN RESPONSE TO DISTENSION OF
THE LUNG.
- IMPULSES TRAVEL VIA LARGE MYELINATED
FIBRES IN VAGUS N.

30. - HERING-BREUER REFLEX:
STIMULATION OF PULMONARY STRETCH
RECEPTORS
INHIBITION OF APNEUSTIC CENTRE AND
INSPIRATORY AREA
EXPIRATION.

31. - THE OPPOSITE RESPONSE IS ALSO SEEN; i.e.
DEFLATION OF THE LUNGS TENDS TO INITIATE
INSPIRATORY ACTIVITY.
- BILATERAL VAGOTOMY CAUSES SLOW,DEEP
BREATHING IN MOST ANIMAL MODELS.

32.  IRRITANT RECEPTORS:- LIE BETWEEN AIRWAY
EPITHELIAL CELLS.
- RAPIDLY ADAPTING.
- STIMULATED BY NOXIOUS GASES, CIGARETTE
SMOKE, DUSTS AND COLD AIR.
- IMPULSES TRAVEL UP THE VAGUS IN MYELINATED
FIBRES.
- REFLEX INCLUDES HYPERPNEA AND
BRONCHOCONSTRICTION.

33.  J RECEPTORS:- ENDINGS OF UNMYELINATED C
FIBRES.
- IMPULSES PASS UP THE VAGUS N IN SLOWLY
CONDUCTING UNMYELINATED FIBRES.
- RESULTS IN RAPID,SHALLOW BREATHING.
- ENGORGEMENT OF PULMONARY CAPILLARIES AND
INCREASE IN INTERSTITIAL FLUID VOLUME OF
ALVEOLAR WALL CAN ACTIVATE THESE
RECEPTORS.

34.  BRONCHIAL C FIBRES: - RESPOND TO
CHEMICALS INJECTED INTO BRONCHIAL
CIRCULATION.
- REFLEXES INCLUDE RAPID SHALLOW
BREATHING, BRONCHOCONSTRICTION AND
MUCUS SECRETION.

35. OTHER RECEPTORS
 NOSE AND UPPER AIRWAY RECEPTORS:
- RESPOND TO MECHANICAL AND CHEMICAL
STIMULI.
- REFLEXES INCLUDE SNEEZING,COUGHING
AND BRONCHOCONSTRICTION.
 JOINT AND MUSCLE RECEPTORS: - ACTIVE
DURING EXERCISE,ESPECIALLY IN EARLY
STAGES.

36.  GAMMA SYSTEM: - MOST MUSCLES CONTAIN
MUSCLE SPINDLES THAT SENSE ELONGATION
OF MUSCLE.
- INVOLVED IN THE SENSATION OF DYSPNEA
THAT OCCURS WHEN UNUSUALLY LARGE
RESPIRATORY EFFORTS ARE REQUIRED TO
MOVE THE LUNG AND CHEST WALL e.g.
AIRWAY OBSTRUCTION.

37.  ARTERIAL BARORECEPTORS: - AN INCREASE
IN ARTERIAL B.P. CAN CAUSE REFLEX
HYPOVENTILATION THROUGH STIMULATION OF
AORTIC AND CAROTID SINUS RECEPTORS.
- A DECREASE IN B.P. CAN CAUSE
HYPOVENTILATION.
 PAIN AND TEMPERATURE:- PAIN OFTEN
CAUSES A PERIOD OF APNEA FOLLOWED BY
HYPERVENTILATION.
- HEATING OF SKIN MAY CAUSE
HYPERVENTILATION.

39. INTEGRATED RESPONSES.

40. RESPONSE TO CO2
 ARTERIAL PCO2 IS THE MOST IMPORTANT
STIMULUS TO VENTILATION UNDER MOST
CONDITIONS.
 ARTERIAL PCO2 IS NORMALLY MAINTAINED AT
40mm Hg. WHEN PCO2 RISES,VENTILATION IS
STIMULATED AND THE RATE OF PULMONARY
EXCRETION OF CO2 INCREASES.
 MOST OF THE STIMULUS COMES FROM CENTRAL
CHEMORECEPTORS.
 RESPONSE IS MAGNIFIED IF ARTERIAL PO2 IS
LOWERED.

41. RELATIVELY
LINEAR
RESPONSE OF
VENTILATION
WITH
INCREASING
PCO2 IS DUE TO
INCREASE IN
BOTH RATE AND
DEPTH OF
VENTILATION.

42. RESPONSE TO O2
 WHEN O2 CONTENT OF INSPIRED AIR
DECREASES, RMV INCREASES.
 MARKED STIMULATION OCCURS WHEN PO2
FALLS <100mm Hg.
 ROLE OF THIS HYPOXIC STIMULUS IN DAY-TO-
DAY CONTROL OF VENTILATION IS SMALL. IT IS
USEFUL DURING ASCENT TO HIGH ALTITUDES.

43. AT PCO2 35.8,
ALMOST NO
INCREASE OF
VENTILATION
OCCURS UNTIL PO2
IS REDUCED TO
ABOUT 50mm Hg.

44.  PTS. WITH SEVERE LUNG DISEASE HAVE
CHRONIC CO2 RETENTION AND THE pH OF
BRAIN ECF HAS RETURNED TO NEAR NORMAL
IN SPITE OF A RAISED PCO2.UNDER THESE
CONDITIONS ARTERIAL HYPOXEMIA BECOMES
THE CHIEF STIMULUS TO VENTILATION.
IF SUCH A PT. IS GIVEN A HIGH O2 MIXTURE
TO BREATHE, VENTILATION MAY BECOME
GROSSLY DEPRESSED.

45. RESPONSE TO pH.
 A REDUCTION IN ARTERIAL BLOOD pH
STIMULATES VENTILATION.
 CHIEF SITE OF ACTION IS THE PERIPHERAL
CHEMORECEPTORS.
 CENTRAL CHEMORECEPTORS OR THE
RESPIRATORY CENTRE ITSELF CAN BE
AFFECTED BY A CHANGE IN BLOOD pH IF IT IS
LARGE ENOUGH-IN THIS CASE,BBB BECOMES
PARTLY PERMEABLE TO H+ IONS.

46. RESPONSE TO EXERCISE
 INITIAL RAPID RESPONSE THAT IS NEURALLY
MEDIATED FOLLOWED BY A SLOWER
EXPONENTIAL RESPONSE THAT PLATEAUS.
 IN SEVERE EXERCISE,ACCUMULATION OF LA
LEADS TO FURTHER INCREASE.
 AN ADDITIONAL STIMULUS IS THOUGHT TO
ACT DURING EXERCISE WHICH INCREASES
VENTILATION SUFFICIENTLY SO THAT THERE
IS LITTLE CHANGE IN PCO2 DESPITE THE RISE
IN METABOLIC RATE.

47.  ROLE OF CAROTID BODY IS DISPUTED-ONE
HYPOTHESIS SUGGESTS THAT OSCILLATIONS
IN PO2 AND PCO2 MAY STIMULATE THE
PERIPHERAL CHEMORECEPTORS.

48. ABNORMALITIES OF RESPIRATORY
RHYTHM.

49. TRANSECTION AT VARIOUS LEVELS

50.  CHEYNE-STOKES BREATHING:
- PERIODIC BREATHING CHARACTERISED BY A
CYCLIC RISE AND FALL IN VENTILATION WITH
PERIODS OF APNEA OR NEAR APNEA.
- CAUSES: CCF,UREMIA,DRUGS(SEDATIVES,
OPIATES), CNS TUMORS.
- IN CARDIAC DISEASE, THERE IS PROLONGATION
OF LUNG-TO-BRAIN CIRCULATION SO THAT IT
TAKES LONGER FOR CHANGES IN ARTERIAL GAS
TENSIONS TO AFFECT THE RESPIRATORY AREA IN
MEDULLA.

51. CHEYNE-
STOKES
BREATHING.

52.  SLEEP APNEA: - CAUSES MAY BE
CENTRAL(FAILURE OF DISCHARGE IN NEURONS)
OR OBSTRUCTIVE.
- DUE TO RELAXATION OF PHARYNGEAL MUSCLES
OR IN SOME CASES DUE TO FAILURE OF
GENIOGLOSSUS MUSCLE TO CONTRACT DURING
INSPIRATION.
- COMMON IN REM SLEEP.
- SEEN IN PREMATURE INFANTS,ADULT MALES AND
POST-MENOPAUSAL WOMEN.

53.  BIOTS BREATHING: -
- PERIODS, OR "CLUSTERS", OF FAIRLY RAPID
RESPIRATIONS OF CLOSE TO EQUAL DEPTH
FOLLOWED BY REGULAR PERIODS OF APNEA THAT
CAN LAST BETWEEN 15 SECONDS TO 120 SECONDS.
- CAUSES: DAMAGE TO THE MEDULLA OBLONGATA
BY STROKE (CVA) OR TRAUMA, OR PRESSURE ON
THE MEDULLA DUE TO UNCAL OR TENORIAL
HERNIATION, PROLONGED OPIOID ABUSE.

54. BIOTS
BREATHING