Respiratory system
L5
Faisal I. Mohammed, MD, PhD
Yanal A. Shafagoj MD, PhD
University of Jordan
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Control of Breathing….Introduction
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Q: What the controller system is going to do?
A: Homeostasis of O2, CO2, H+
Q: How?
A: by: Hyperventilation or hypoventilation
Q: What is the feedback system?
A: ↓ PaCO2, ↑PaCO2, ↓ PaO2 (below 60
mmHg), ↓ H+, and finally ↑H+
Note: ↑PaO2 has almost no effect on the controller
system
Regulation of Respiration ….Introduction
•
Sensors
–
•
Central controller
–
•
gather information
integrate signals
Effectors
–
Respiratory muscles
How alveolar ventilation VA affects P O2 and P CO2
A
A
PAO2 depends on :
1. O2 delivery to alveoli (Alveolar Ventilation VA).
2. Rate of O2 absorption to blood (O2 Consumption VO2)
PAO2  (VA/VO2)
HYPERVENTILATION is when alveolar ventilation is
more than CO2 production  decrease PaCO2
HYPOVENTILATION is when alveolar ventilation is
LESS than CO2 production  increase PaCO2
PACO2 = (VO2/VA)* K
K”= constant (= 0.863 mmHg. lit/ml).
If ventilation is doubled then PCO2 is ½
If ventilation is halved then PCO2 is doubled…keeping CO2
production constant.....See the two graphs in the next two slide.
Partial pressure of oxygen in alveoli
160
140
120
Metabolic rate
100
Po2
250 ml/min
80
1000 ml/min
60
40
20
0
0
5
10
15
20
25
30
Alveolar Ventilation
Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
Partial pressure of CO2 in alveoli
200
160
Metabolic rate
120
200 ml/min
Pco2
800 ml/min
80
40
0
2
5
10
15
20
25
30
Alveolar Ventilation
Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
Objectives
Describe the respiratory center
Compare and contrast the effect of carbon dioxide
and oxygen on the chemosensitive area
Explain the role of peripheral chemoreceptors
Describe how rate and depth are controlled
Summarize the process of control of respiration
REGULATION OF PULMONARY
FUNCTION

Respiratory control centers: the main integrators
controlling the nerves that affect the inspiratory and
expiratory muscles are located in the brainstem
 Medullary rhythmicity center: generates the basic
rhythm of the respiratory cycle
 Consists of two interconnected control centers
 Inspiratory center stimulates inspiration
 Expiratory center stimulates expiration
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REGULATION OF PULMONARY
FUNCTION (cont.)

The basic breathing rhythm can be altered by
different inputs to the medullary rhythmicity center
 Input from the apneustic center in the pons
stimulates the inspiratory center to increase the
length and depth of inspiration
 Pneumotaxic center in the pons inhibits the
apneustic center and inspiratory center to prevent
overinflation of the lungs
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A. Location of Respiratory Centers & Control Units
1. Medullary Respiratory Centers
a. Inspiratory Area - DRG - dorsal respiratory group neurons
b. Expiratory Area - VRG - ventral respiratory group neurons
2. Pontine Centers:
a. Pneumotaxic Center - located in upper pons (“off switch”)
b. Apneustic Center - located in lower pons (prevents turn-off)
3. Pulmonary Receptors
a. pulmonary stretch receptors (Hering-Breuer reflex)
b. other receptors??
B. Control of Respiratory Activity
1. Central or Medullary Chemoreceptors
2. Peripheral Chemoreceptors
3. Interaction between Central and Peripheral Chemoreceptors.
4. Cortical Factors
THE RESPIRATORY CENTER

It is a loose collection of inspiratory and
expiratory neurons situated in the medulla
oblongata of the brain stem. Is not a discrete
identifiable center in the strict anatomical
sense. When inspiratory neurons are active,
expiratory neurons are inhibited and vise
versa.
Brain Stem Respiratory Centers
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Neurons in the
reticular formation of
the medulla
oblongata form the
rhythmicity center:
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Controls automatic
breathing.
Consists of interacting
neurons that fire either
during inspiration (I
neurons) or expiration
(E neurons).
Insert fig. 16.25
Respiratory Center
Figure 41-1
Chemoreceptors
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2 groups of chemoreceptors that monitor
changes in blood
PCO2, PO2, and pH.
Central:
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Medulla…chemosensiti
ve area…sensitive to
H+
Peripheral:
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Carotid and aortic
bodies.
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Control breathing
indirectly via sensory
nerve fibers to the
Insert fig. 16.27
Chemoreceptor Control
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Central chemoreceptors:
More sensitive to changes in arterial PC02 through H+
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H20 + CO2
H2C03
H+
H+ cannot cross the blood brain barrier.
C02 can cross the blood brain barrier and
will form H2C03.
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Lowers pH of CSF fasters than it lowers blood
pH
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Directly stimulates central chemoreceptors.
Peripheral Chemoreceptors
nerve impulses
• Carotid body-bifurcation of the carotids
–responds to oxygen (PO2<60 mmHg)
–-responds to carbon dioxide and hydrogen ion…one seventh of
–The central respons but 5 times faster
800
600
400
200
0
0
200
400
600
PO 2
Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
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Brain Stem Respiratory Centers

Neurons in the reticular
formation of the
medulla oblongata form
the rhythmicity center:


Controls automatic
breathing.
Consists of interacting
neurons that fire either
during inspiration (I
neurons) or expiration
(E neurons).
Insert fig. 16.25
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REGULATION OF PULMONARY
FUNCTION (cont.)

Factors that influence breathing: sensors from the nervous system provide
feedback to the medullary rhythmicity center
 Changes in the PO2, PCO2, and pH of arterial blood influence the
medullary rhythmicity area
 PCO2 acts on central chemoreceptors in the medulla—if it increases,
the result is faster breathing; if it decreases, the result is slower
breathing
 A decrease in blood pH stimulates peripheral chemoreceptors in the
carotid and aortic bodies and, even more so, stimulates the central
chemoreceptors (because they are surrounded by unbuffered fluid)
(Figure 24-32)
 Arterial blood PO2 presumably has little influence if it stays above a
certain level
 Low arterial blood PO2 is the main stimulus for breathing in chronic
smokers
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Controls of rate and depth of
respiration
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Arterial PO2
 When PO2 is below 60mmHg, ventilation increases
Arterial PCO2
 It is the most important regulator of ventilation,
small increases in PCO2, greatly increases
ventilation
Arterial pH
 As hydrogen ions increase, alveolar ventilation
increases, but hydrogen ions cannot diffuse into
CSF as well as CO2
Central (medullary) Chemoreceptors (mechanisms) the H+ (CO2)
sensors
blood here
cerebrospinal
fluid between
brain here
H+
Peripheral
Chemoreceptors
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A Summary of
Chemoreceptor
Reflexes
Brain Stem Respiratory Centers
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(continued)
I neurons project to, and stimulate spinal motor
neurons that innervate respiratory muscles.
Expiration is a passive process that occurs when the I
neurons are inhibited.
Activity varies in a reciprocal way.
Rhythmicity Center
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I neurons located primarily in dorsal respiratory group
(DRG):
 Regulate activity of phrenic nerve.
 Project to and stimulate spinal interneurons that
innervate respiratory muscles.
E neurons located in ventral respiratory group (VRG):
 Passive process.
 Controls motor neurons to the internal intercostal
muscles.
Activity of E neurons inhibit I neurons.
 Rhythmicity of I and E neurons may be due to pacemaker
neurons.
Pons Respiratory Centers
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Activities of medullary rhythmicity center is
influenced by pons.
Apneustic center:
 Promotes inspiration by stimulating the I neurons
in the medulla.
Pneumotaxic center:
 Antagonizes the apneustic center.
 Inhibits inspiration.
Chemoreceptors
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2 groups of chemoreceptors that monitor
changes in blood PC0 , P0 ,
and pH.
Central:
2
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2
Medulla.
Peripheral:
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Carotid and aortic bodies.
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Control breathing indirectly
via sensory nerve fibers to the
medulla (X, IX).
Insert fig. 16.27
Effects of Blood PC0 and pH on Ventilation
2
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Chemoreceptor input modifies the rate and depth
of breathing.
 Oxygen content of blood decreases more slowly
because of the large “reservoir” of oxygen
attached to hemoglobin.
 Chemoreceptors are more sensitive to changes
in PC02.
H20 + C02
H2C03
H+ + HC03Rate and depth of ventilation adjusted to maintain
arterial PC02 of 40 mm Hg.
Chemoreceptor Control
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Central chemoreceptors:
 More sensitive to changes in arterial PC02.
H20 + C02
H2C03
H+
H+ cannot cross the blood brain barrier.
C02 can cross the blood brain barrier and will form
H2C03.
 Lowers pH of CSF.
 Directly stimulates central chemoreceptors.
Chemoreceptor Control
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(continued)
Peripheral chemoreceptors:
 Are not stimulated directly by changes in arterial
PC02.
H20 + C02
H2C03
H+ + HCO3Stimulated by rise in [H+] of arterial blood.
 Increased [H+] stimulates peripheral
chemoreceptors.
Chemoreceptor Control of Breathing
Insert fig. 16.29
Effects of Blood P0 on Ventilation
2
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Blood P0 affected by breathing indirectly.
2
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Influences chemoreceptor sensitivity to changes in PC0 .
2
Hypoxic drive:
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Emphysema blunts the chemoreceptor response to PC0 .
Choroid plexus secrete more HC03- into CSF, buffering the
fall in CSF pH.
Abnormally high PC0 enhances sensitivity of carotid bodies
to fall in P0 .
2
2
2
Effects of Pulmonary Receptors on Ventilation
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Lungs contain receptors that influence the brain stem respiratory
control centers via sensory fibers in vagus.
 Unmyelinated C fibers can be stimulated by:
 Capsaicin:
 Produces apnea followed by rapid, shallow breathing.
 Histamine and bradykinin:
 Released in response to noxious agents.
 Irritant receptors are rapidly adaptive receptors.
Hering-Breuer reflex:
 Pulmonary stretch receptors activated during inspiration.
 Inhibits respiratory centers to prevent undue tension on
lungs.
Pulmonary Disorders
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Dyspnea:
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Shortness of breath.
COPD (chronic obstructive pulmonary
disease):
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Asthma:
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Obstructive air flow through bronchioles.
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Caused by inflammation and mucus secretion.
 Inflammation contributes to increased airway
responsiveness to agents that promote bronchial
constriction.
 IgE, exercise.
Pulmonary Disorders (continued)
Emphysema:
 Alveolar tissue is destroyed.
 Chronic progressive condition that reduces surface area for
gas exchange.
 Decreases ability of bronchioles to remain open during
expiration.
 Cigarette smoking stimulates macrophages and
leukocytes to secrete protein digesting enzymes that
destroy tissue.
Pulmonary fibrosis:
 Normal structure of lungs disrupted by accumulation of fibrous
connective tissue proteins.
 Anthracosis.
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Disorders Caused by High Partial Pressures
of Gases
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Nitrogen narcosis:
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At sea level nitrogen is physiologically inert.
Under hyperbaric conditions:
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Nitrogen dissolves slowly.
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Can have deleterious effects.
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Resembles alcohol intoxication.
Decompression sickness:
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Amount of nitrogen dissolved in blood as a diver
ascends decreases due to a decrease in PN .
2
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If occurs rapidly, bubbles of nitrogen gas can form in tissues
and enter the blood.
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Block small blood vessels producing the “bends.”
RESPONSES TO CHANGE IN RESPIRATORY GASES
Hypoxia - O2 deficiency at the tissue level. There could be several causes.
1. Hypoxic-hypoxia (PO2 of arterial blood is reduced). e.g., breathing O2-poor gas or at reduced
atmospheric pressures. When PO2 of inspired air falls to about 60-70 mmHg there is loss of
consciousness (alv. PO2 ~35-40 mm Hg).
At sea level when breathing in an environment with 10% or less O2, you are in trouble.
With altitude, composition of air remains about same but there are pressure changes.
Delayed effects of altitude
Acclimatization
2. Anemic-hypoxia
Essentially low Hb content. Also in CO poisoning, effective Hb content is reduced by HbCO
complexing.
3. Stagnant-hypoxia
Hypoxia due to circulation that is so slow that tissue does not receive its necessary "flow" of
O2. Shock, congestive heart failure (or localized restriction) can lead to damage of important
organs.
4. Histotoxic-hypoxia
Inhibition of tissue oxidative processes by poisons. e.g., Cyanide poisoning - combines with
cytochrome oxidase preventing O2 from serving as the ultimate electron acceptor.
Thank You
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