Control of Breathing

Respiratory Block

Physiology 439 team work

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@Physiology_439
•Gray: extra information
•Textbook: Guyton + Linda
Objectives :

01
Understand the role of the medulla oblongata in
determining the basic pattern of respiratory activity.

List some factors that can modify the basic breathing

pattern like e.g.
• A- The Hering-Breuer reflexes,

02 B- The proprioceptor reflexes, C- the protective reflexes,

like the irritant, and the J-receptors.

03 Compare and contrast metabolic and respiratory acidosis

, PCO central chemoreceptors. and metabolic and respiratory
alkalosis.
 The overall process of external respiration

The last mechanism of External Breathing will be Discussed in this lecture

Take an idea about the lecture with this helpful video
* A small increase in PCO2
will greatly increase
ventilation
Pco2‫ﻻن أي زﯾﺎدة ﺣﺘﻰ ﻟﻮ ﺑﺴﯿﻄﮫ ﻓﻲ ال‬
‫ ف ﻻزم ﻧﺘﻔﺎدى ھﺬا‬PH‫راح ﯾﺄﺛﺮ ﻓﻲ ال‬
‫اﻟﺸﻲ‬ When PO2 is
Arterial VERY low
PO2: (Hypoxia)

Control of The most

rate and Arterial important regulator
ventilation increases
depth of PCO2: of ventilation is
PCO2*
respiration

As hydrogen
Arterial
pH: ions increase
(acidosis)
Medullary Pontine
Respiratory Respiratory
centers centers

Chemical control
CONTROL OF mechanism
Nervous control VENTILATION
mechanism. Several mechanisms are involved
which can be grouped into two
main categories which are closely
integrated Peripheral Central
chemoreceptors chemoreceptors.
 Nervous control
mechanism.

RESPIRATORY NEURONAL
CENTER

1-Composed of several groups

of neurons.
2-Located in the entire length
of the medulla and pons.

Can be divided into four

major groups of neurons:

3-Ventral 2-The
4-The apneustic 1-Dorsal
respiratory pneumotaxic
center. respiratory group
group. center.
 Determines basic rhythm
of breathing
(rhythmicity center)
Medullary Respiratory centers

1-Higher brain centers

The rhythmicity center 2-Centers in the brain
receives impulses from: stem (medulla and pons)
3-Special receptors
1. Inspiratory area (respiratory reflexes)
(Dorsal Respiratory
Group)-DRG:

Causes contraction of
The medullary respiratory diaphragm and
center stimulates basic external intercostals
DRG
inspiration for about 2 ‫ طﯾب ﻛﯾف؟‬Rhythm ‫ﯾﺣﺎﻓظ ﻋﻠﻰ اﻟـ‬
seconds and then basic ‫اﻹﺷﺎرات ﺗﺑدا ﺑﺷﻛل ﺧﻔﯾف ﺑﻌدﯾن ﺗﻘوى‬
The rhythmicity center
expiration for about 3 Diaphragm ‫اﻛﺛر وﯾﺻﯾر ﺗﻘﻠص ل‬
sends excitatory impulses ‫ﺑﻌدﯾن اﻹﺷﺎرات ﺗوﻗف وﯾرﺟﻊ ال‬
seconds (5sec/ breath = via the intercostal and ‫ ﻟوﺿﻌﮫ اﻟطﺑﯾﻌﻲ‬Diaphragm
12breaths/min). phrenic nerves to the ‫ﺑﻣﻌﻧﻰ ان اﻹﺷﺎرات ﺗﺑدأ ﺑﺎﻟﺗدرﯾﺞ وﺗوﻗف‬
external intercostal muscles
and diaphragm
Count:
Medullary Respiratory centers

Although it contains both inspiratory and expiratory

neurons, It is inactive during normal quiet breathing

2. Expiratory area
(Ventral Respiratory Activated by inspiratory area during forceful
Group)-VRG: breathing.

Causes contraction of the internal intercostals

and abdominal muscles ( mainly expiratory).

DRG CONTROL normal (rest) inspiration & expiration

While VRG control forced inspiration & expiration
 2. Pneumotaxic area:
It transmits inhibitory impulses
to the apneustic center and to
the inspiratory area to switch
1. Apneustic area:
off inspiration.(so increase
Stimulates inspiratory area of
respiratory rate)
Pontine medulla to prolong
Therefore, breathing is more inhalation.(so decrease
Respiratory
rapid when pneumotaxic area is respiratory rate)
active. centers
Therefore slow respiration and
Transition
prolonged respiratory cycles will
between inhalation
result if it is stimulated. It
and exhalation is
receives inhibitory impulses from
controlled by:
the sensory vagal fibers and
inhibitory impulses from
the pneumotaxic center.

In summary we have 4 centers that control breathing, 2 in the medulla and 2 in the pons
In medulla we have DRG (responsible for basic Rhythm) and VRD(responsible for forced breathing)
DRG is controlled by Apneustic and Pneumotaxic located in the pons which receive input from the Peripheral nervous system
about PO2 and Pco2 and respond to it by Apneustic —> prolong breathing and decrease RR
and Pneumotaxic —> inhibit DRG and increases RR
Hering-Breuer inflation reflex This reflex appears to be mainly a
“Protection reflex” By stretching receptors protective mechanism for
preventing excess lung inflation

Switches off inspiratory

signals and
thus stops further
inspiration .

01 02 03

When the lung becomes

overstretched (tidal volume is increases the rate of
about 1.5 L)stretch receptors respiration as does the
located in the wall of bronchi and pneumotaxic
bronchioles transmit signals
center.
through vagus nerve to DRG
producing effect similar to
pneumotaxic center stimulation.
 Chemical Control Of Ventilation
The rhythmicity center (Dorsal respiratory group) is affected by chemical
changes in the blood via
two types of chemoreceptors :

Peripheral chemoreceptors Central chemoreceptors.

Peripheral chemoreceptors Respiratory control by peripheral
chemoreceptors in carotid and aortic
bodies

Peripheral chemoreceptors sends signals

which are either excitatory or inhibitory.
These signals depend on pH, CO2, and O2. • At Normal PO2, PCO2 and pH, low
grade of tonic activity in the
nerves.(At these circumstances the
signals will be at a normally low
•Located mainly in the carotid and aortic rate).
bodies, but may be found anywhere in the
• ↓ PCO2 and ↑pH causes low tonic
circulatory system.
activity which causes a decrease in
• When stimulated, send excitatory ventilation.
impulses to the rhythmicity center (via • In metabolic acidosis:
glossopharyngeal and vagus nerves). ↓ pH causes an increase in
• Highly sensitive to changes in arterial ventilation to wash out CO2 and to
bring pH to normal.
PO2and to a lesser extent to PCO2 and pH
• In metabolic alkalosis:
( ‫ اﻋﻠﻰ‬O2‫)ﺣﺴﺎﺳﯿﺘﮫ ﻟﻞ‬
↑ pH(due to low amount of C02)
• ↓ of PO2,↑ in PCO2and ↓ of pH, causes decrease ventilation, the CO2
stimulate the chemoreceptors to increase is kept in the blood to compensate
the drop in CO2 levels.
ventilation.
Peripheral Chemoreceptor System Activity
Role of Oxygen in Respiratory Control

Most of the chemoreceptors are in the carotid bodies

However, a few are also in the aortic bodies.

When oxygen concentration in the

arterial blood falls below normal, the
chemoreceptors become strongly
stimulated.

Impulse rate is particularly sensitive

to changes in arterial Po2 in the
range of 60 down to 30 mm Hg.

Under these conditions, low arterial

Po2 obviously drives the ventilatory
process quite strongly.
Central chemoreceptors Effect of CO2 on central
chemoreceptors

•Most probably located on the

ventrolateral surface ( ‫)اﻟﺠﺰء اﻷﻣﺎﻣﻲ اﻟﺠﺎﻧﺒﻲ‬ Although carbon dioxide has
of medulla oblongata (which is bathed little direct effect in stimulating
“surrounded with” cerebrospinal fluid). the neurons in the chemosensitive area, it does
have a potent indirect effect. It does this by reacting
• Highly sensitive to the hydrogen ion with the water of the tissues to form carbonic acid,
concentration of the CSF(cerebrospinal which dissociates into hydrogen and bicarbonate ions;
fluid). the hydrogen ions then have a potent direct
stimulatory effect on respiration.
• Evoked “triggered” by arterial PCO2
(CO2 can freely cross the blood brain
barrier(BBB) into CSF, while BBB is
relatively impermeable to H and HCO-3
ions)
 Why does CO2 have a more potent effect in
stimulating chemosensitive neurons than do blood
H ions?
• Blood brain barrier is nearly impermeable to H+ ions,
but CO2 passes this barrier very easily. When the blood
PCO2 increases, so does the PCO2 of both the interstitial
fluid of the medulla and the CSF.

• In these fluids, the CO2 reacts with the water to form

new H+ ions More H+ ions are released into the
respiratory chemosensitive sensory area of the medulla
when the blood CO2 concentration increases than when
the blood H+ ion increases.

• For this reason, respiratory center activity is increased

very strongly by changes in blood CO2.
From Guyton
The figure shows quantitatively the approximate effects of
blood PCO2 and blood pH (which is an inverse logarithmic
measure of hydrogen ion concentration) on alveolar
From 438 Physiology team ventilation. Note especially the marked increase in
comparing between ↑CO2 and↑ hydrogen, who’s affecting more? The CO2 ventilation caused by an increase in PCO2 in the normal
why? ↑CO2 in the blood will cause more↑ventilation than increase in blood H+ and that’s will NOT affect the CNS range between 35 and 75 mm Hg, which demonstrates the
tremendous effect that CO2 changes have in controlling
(medullary response center) since it does not cross the BBB. On the other hand, CO2 can cross the BBB and it respiration. By contrast, the change in respiration in the
indirectly gives off H+ there from its reaction with H2O (acid/base equation). So, the Cerebrospinal fluid and the normal blood pH range, which is between 7.3 and 7.5, is less
interstitial fluid of the medulla the hydrogen ion will stimulate the chemoreceptors directly. than one tenth as great.
 A change in CO2 concentration has a potent acute effect on controlling
respiratory drive, but only a weak chronic effect after a few days’ adaptation.

This means that:

• Excitation of the respiratory center by CO2 is great after the blood CO2 first increases, but it
gradually declines over the next 1 to 2 days. (‫)اﻟﺠﺴﻢ ﯾﺘﻌﻮد ﻋﻠﯿﮫ‬

How does the body adapt to increased CO2?

• Part of this decline results • The kidneys increasing the • Over a period of hours, the
from renal readjustment of blood HCO3, which binds HCO3 ions slowly diffuse
the H+ ion concentration with H+ ions in the blood through the BBB– CSF
in the circulating blood and CSF to reduce their barriers and combine directly
back toward normal after concentrations with the H+ ions adjacent to
the CO2 first increases. the respiratory neurons as well,
thus reducing the H+ ions
back to near normal.
From Linda
Commands from the cerebral cortex can temporarily override the automatic brain
stem centers. For example, a person can voluntarily hyperventilate (i.e., increase
breathing frequency and volume). The consequence of hyperventilation is a
decrease in PaCO2, which causes arterial pH to increase. Hyperventilation is
self-limiting, however, because the decrease in PaCO2 will produce
unconsciousness and the person will revert to a normal breathing pattern.
Although more difficult, a person may voluntarily hypoventilate (i.e.,
breath-holding). Hypoventilation causes a decrease in PaO2 and an increase in
PaCO2, both of which are strong drives for ventilation. A period of prior
hyperventilation can prolong the duration of breath-holding.
Notes:

● If a person has chronic hypercapnia and hypoxia, the body’s adaptation to increased CO2 allows the low
O2 (hypoxia) to be the main drive/stimulus for respiratory regulation.

● PO2 becomes the main stimulus, not PCO2.

● If this patient is present to the ER with a respiratory problem, he is immediately given oxygen to correct the
hypoxia

● Returning O2 levels back to normal causes a sharp respiratory rate decline

● This results in shut down or respiratory failure because the hypoxia became the main drive for respiratory
regulation.

● For this reason, patients with chronic hypercapnia and hypoxia should be given oxygen, but NOT until it
reaches normal levels.
 Effect of CO2 and H ion concentration on
Chemoreceptors Activity

● An increase in either carbon dioxide concentration or hydrogen ion concentration also excites the
chemoreceptors and, in this
way, indirectly increases respiratory activity.
difference between the peripheral and central effects of carbon dioxide:
● the stimulation by way of the peripheral chemoreceptors occurs as much as five times as rapidly as central stimulation
● so that the peripheral chemoreceptors might be especially important in increasing the rapidity of response to carbon
dioxide at the onset of exercise.

Summary of chemoreceptor control of breathing:

The lower the arterial PO2, the greater the impulse of a

nerve from the carotid body to increase respiration and
return PO2 levels back to normal.
 Other factors influencing respiration

irritant receptors in the lung J receptors

airways

The epithelium in the few receptors in the wall of

trachea, bronchi, and the alveoli in juxta position
bronchioles is supplied by to the pulmonary
irritant receptors that are capillaries. They are
stimulated by irritants that stimulated especially when
enters the respiratory the pulmonary capillary
airways causing coughing, becomes engorged by
sneezing and blood or when pulmonary
bronchoconstriction in edema occurs e.g. in CHF,
bronchial asthma and their stimulation cause the
emphysema. patient feels dyspnea.
Helpful summary followed by Quiz

Summary of factors affecting respiration

● Stimulus for peripheral chemoreceptors: O2, CO2,

PH, H+
Types of receptors that influence respiration: ● Stimulus for central chemoreceptors: H+ “direct”
● Central chemoreceptors
● Peripheral chemoreceptors
Co2” indirect” , why is that? co2 enter the BBB and
● Lung stretch receptors dissolve in CSF into H+ and bicarbonate than H
● Lung J receptors stimulate the central chemoreceptors which is mean
● Irritant receptors
● Muscle & joint receptors
the Co2 itself not the main stimulus
 Respiratory Acidosis Respiratory Alkalosis

• Hypoventilation. • Hyperventilation.
• Accumulation of CO2 in the tissues. • Excessive loss of CO2

–PCO2 increases –PCO2 decreases ( 35 mmHg).

– pH decreases. – pH increases.

Metabolic Acidosis Metabolic Alkalosis

• Ingestion, infusion, or production of a fixed acid. • Excessive loss of fixed acids from the body
• Decreased renal excretion of hydrogen ions. • Ingestion, infusion, or excessive renal reabsorption
• Loss of bicarbonate or other bases from the of bases such as bicarbonate
extracellular compartment. • pH increases.
• Metabolic disorders as diabetic ketoacidosis.

The respiratory system can compensate for metabolic acidosis or alkalosis by altering
alveolar ventilation
 Another helpful Quiz

Quiz 3.When the respiratory drive for increased pulmonary

ventilation becomes greater than normal, a special set
of respiratory neurons that are inactive during normal
1.The basic rhythm of respiration is generated by quiet breathing then becomes active, contributing to
neurons located in the medulla. What limits the the respiratory drive. These neurons are located in which
duration of inspiration and increases respiratory rate? structure?
A) Apneustic center
A.Apneustic center B) Dorsal respiratory group
B.DRG C) Nucleus of the tractus solitarius
C.VRG D) Pneumotaxic center
D.Pneumotaxic center E) Ventral respiratory group

4.The afferent (sensory) endings for the Hering-Breuer reflex

are mechanoreceptors located in the?
A) Carotid arteries
2.What is the most important pathway for the respiratory B) Alveoli
response to systemic arterial CO2 (PCO2)? C) External intercostals
A) CO2 activation of the carotid bodies D) Bronchi and bronchioles
B) Hydrogen ion (H+) activation of the carotid bodies
C) CO2 activation of the chemosensitive area of the
medulla
D) H+ activation of the chemosensitive area of the 5.Which of the following is stimulated first during metabolic
medulla acidosis?
E) CO2 activation of receptors in the lungs A) Central chemoreceptors
B) Peripheral chemoreceptors
C) Lung J receptors
D) Lung stretch receptors

1) 2)D 3)E 4)D 5)B

 SAQs

1.List the type of receptors that are able to inhibit respiration?

2.Why does CO2 have a more potent effect in stimulating chemosensitive neurons than do blood
H ions?

1.Higher brain centers(cortex),stretch receptors, irritant receptors,receptors in hypothalamus and pneumotaxic center.

2.Since H ions cannot cross the BBB, it needs to be in CO2 form to cross. That's why Respiratory center activity is
increased very strongly by changes in blood CO2.
 Team leaders : TeiF Almutiri Abdulaziz Alkraida

Team Members
▷ Mishal Althunayan ▷ Renad Alhomaidi
▷ Basel Fakeeha
▷ Ibrahim altamimi
▷
▷
Aseel alshehri
Noura abdulaziz
Reviewed by
▷ Abdulaziz Alsuhaim ▷ Yasmin Al Qarni - Ghadah alouthman
▷ Mohammad Alkatheri ▷ Alaa Alsulmi - homoud Algadheb
▷ Basam alasmari ▷ Farah Albakr
▷ Morshed Alharbi ▷ Muneerah alsadhan
▷ Ahmad Al Khayat ▷ Sarah alobaid
▷
▷
Mohammod alghedan
Nawaf alghamdi
▷ Farrah alsaid Contact us
▷ Noura almsaud
▷ Raed alntaifi ▷ Hessah alalyan
▷ Homoud alghadeb ▷ Rema alhdleg
▷ Mishal alhamed ▷ Raghad alsweed
▷ Musab alamri ▷ Raghad asiari
▷ Fayez AlTabbaa ▷ Ghadah alouthman
▷ Khalid Al Tuwejri ▷ Haya alanazi
▷ Mohammed alsalman ▷ Asma alamri
▷ Rania Almutiri
The Sub leader:
▷ Yara alasmari Sarah alQhtani
▷ Asma alamri