Transcript Supplement 1_Typical lecture_E S Prakash

Manuscript: Explicit Constructivism: a missing
link in ineffective lectures?
Author: E.S.Prakash
Supplement 1: Typical Lecture
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Chemical and neural regulation of
respiration
E.S.Prakash, School of Medicine, AIMST University, Malaysia
E-mail: [email protected]
How much do we already know?
Just write the answers with the question number on a sheet of paper
1.
2.
3.
4.
5.
At sea level, barometric pressure is:
mmHg
Barometric pressure is the same as atmospheric
pressure. T/F
In the upright position, ventilation-perfusion ratio is
highest in the upper lung zones. T/F
The maximum volume of air that you can expel
after a maximal inspiration is called:
The amount of air that remains in the lungs after a
tidal expiration is called:
6.
If you breathe 500 ml per breath 12 times a
minute and your dead space is 150 ml, then,
what is the amount of fresh gas supplied to your
alveoli per minute?
Organization of content in these lectures:
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Neural control of breathing
Neural control systems: functional organization
Chemoreceptors: functional organization
Classification of chemoreceptors
Ventilatory responses:
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to changes in acid-base balance
To CO2 excess
To oxygen lack
Interaction of hypoxia and CO2
Content outline continued:
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Nonchemical influences on respiration
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Responses mediated by airway receptors
Responses mediated by receptors in the lung
parenchyma
Coughing & sneezing
Regulation of respiration during sleep
Abnormal respiratory patterns
Neural control of breathing
There are 2 systems:
 One for voluntary control
 One for spontaneous breathing
System for voluntary control of breathing:
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Regulator neurons located in cerebral cortex
When does this system work?
When we control our breathing voluntarily
Example: when you hold your breath
Example: when you hyperventilate
Pathway: From cerebral cortex to motor neurons
in the spinal cord which supply muscles of
respiration (diaphragm & intercostal muscles)
System for spontaneous control of breathing:
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Breathing is mostly spontaneous
Breathing is rhythmic (rate as well as depth)
We are not aware that we are breathing
Location of respiratory center: medulla
Please see schematic on next slide
Mechanism of spontaneous breathing
Pons
Medullary
chemoreceptors
Medulla
Afferents from
carotid bodies
terminate here
Pre-Botzinger
complex; preBOTC
(Pacemaker)
I neurons
Diaphragm &
intercostal
muscles
Spinal
cord
Phrenic neurons
Component
Details
Central
chemoreceptor
neurons
(sensory)
Project to Pre-Botzinger complex of
neurons
Pre-BOTC
Discharge spontaneously; pacemaker
neurons for breathing (like SA node in
heart); entrained by input from
chemoreceptors
I neurons
Fire during inspiration; thus the name;
project to lower motor neurons (e.g.
phrenic n.) that drive muscles of
inspiration
Feedback to the respiratory center from
lungs:

During inspiration,
 lungs expand, and lung parenchyma is stretched;
 stretch receptors are present here;
 these are activated and convey information to the
brain via sensory branches of vagus nerve
Role of pons in respiration:
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There is an area called pneumotaxic center in the
pons;
If this area is damaged, then, depth of inspiration
is increased (see next slide)
So, this center may serve to switch breathing from
inspiration to expiration
This switch works to inhibit I neurons during
expiration
Effect of vagotomy on breathing rate and
depth; note the increase in depth
Normal
After
vagotomy
Effect of damage to the pneumotaxic
center in vagotomized animals:
normal
After
vagotomy
apneusis
Functional organization of
chemoreceptors:

A rise in PCO2, a fall in pH or PO2 of arterial blood
increases respiratory neuron activity in the medulla.

Stimulus: a change in blood chemistry …
Sensed by: receptors called chemoreceptors
Response: change in minute ventilation
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Functional organization of
chemoreceptors (contd.)
Location of chemoreceptors:
 Central chemoreceptors (in
medulla); also called
medullary chemoreceptors
 Arterial chemoreceptors (in
carotid & aortic bodies);
sometimes called peripheral
chemoreceptors
Functional organization of
chemoreceptors (contd.)

Innervation of peripheral (systemic arterial
chemoreceptors);
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Figure at Link: http://www.medicine.mcgill.ca/physio/resp-web/Figures/Figtt20.jpg

Note carotid body is supplied by branch of IX nerve and
aortic bodies are supplied by branch of X nerve.
Some facts about systemic arterial
chemoreceptors:
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There are 2 types of cells in the carotid body;
Type I glomus cells contain oxygen sensitive K
channels (these are the chemoreceptors)
Type II cells are supporting cells
They have a very high blood flow
In carotid bodies, blood flow rate: 2000 ml/100 g
tissue/min
For example, the brain gets 50 ml/100 g/min
Stimuli that activate peripheral
chemoreceptors:
1.
Low PaO2 (hypoxemia)
2.
Drop in arterial pH (acidosis)
3.
Rise in PaCO2 (hypercapnia)
4.
Low blood flow through the receptors; i.e., when
cardiac output and BP are low

Note: these receptors are very sensitive to drop in
PaO2 (hypoxemia) compared to rise in PaCO2
(hypercapnia)
So what are the normal values of each?
Arterial Blood Gases & pH
Normal range
Arterial pH
7.35 – 7.45
Arterial PO2
81 – 100 mm Hg
Arterial PCO2
35 – 45 mm Hg
Central chemoreceptors
(medullary chemoreceptors)

Location: brain stem, ventral surface of medulla
http://www.lib.mcg.edu/edu/eshuphysio/program/section4/4ch6/4ch6img/page21.jpg
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They are located near I neurons
They project to respiratory neurons
Central chemoreceptors and respiratory neurons are
distinct
They are mainly sensitive to changes in PaCO2
A rise in PaCO2 effectively stimulates central
chemoreceptors
A rise in PaCO2 lowers CSF pH which
is sensed by medullary chemoreceptors
CO2 crosses the blood brain barrier (BBB)
CO2
blood
brain ISF
CO2 + H2O
H2CO3
H+ + HCO3
Carbonic anhydrase
Drop in CSF pH
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Central chemoreceptor neurons monitor the H+
ion concentration of brain ISF;
Greater the PaCO2, > the minute ventilation;
If you lower PaCO2, minute ventilation is lowered
Effect of addition of metabolic acid
(e.g., lactic acid, on ventilation)
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Example: lactic acidosis (metabolic acidosis)
Arterial pH is low (< 7.35);
Breathing is rapid and deep (Kussmaul’s
respiration) and CO2 is blown off
This response is mediated by carotid bodies
(peripheral chemoreceptors) and is lost if they are
removed.
Effect of a rise in blood pH on minute
ventilation
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Example: metabolic alkalosis due to vomiting;
i.e., loss of HCl;
Arterial pH is high (> 7.45)
Respiration is slowed; i.e., decrease in minute
ventilation)
As a result PaCO2 gradually rises
What happens if more CO2 is produced as
a result of metabolism?
More CO2 in blood as a result of ↑metabolism
Transient rise in PaCO2
Fall in CSF pH
Respiration is stimulated effectively
Steady state PaCO2 is normal
Ventilatory response to CO2 lack or excess
200
Minute
ventilation
(l/min)
100
0
0
40
50
75
Alveolar PCO2 (mm Hg)
100
Ventilatory response to oxygen lack:
200
Minute
ventilation
(l/min)
100
0
0
25
50
75
PO2 (mm Hg)
100
Ventilatory response to hypoxia, hypercapnia, severe exercise
and maximal voluntary ventilation (MVV) compared
200
Minute
ventilation
(l/min)
100
MVV: 125-175 l/min
Max. ventilation during exercise
Response to hypercapnia
Response to hypoxia
0
0
50
100
Alveolar PO2 or PCO2 (mm Hg)
Comments:
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Normally, minute ventilation is about 5 l/min
MVV = 125-175 l/min (higher in males cf. females)
Thus, there is a great ventilatory reserve;
But MVV can be sustained only for a short time
Hypoxia and hypercapnia alone are not as potent
as severe exercise in stimulating ventilation
So, other factors also drive ventilation during
exercise.
Interaction of ventilatory responses to
CO2 and O2 (all partial pressures in mm Hg)
100
PAO2 = 40
PAO2 = 55
75
Ventilation
(l/min)
PAO2 = 100
50
25
0
40
PACO2
50
Conclusion:

Conclusion: Hypoxia makes an individual more
sensitive to CO2 excess
Ventilation at high altitudes:
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Barometric (atmospheric) pressure is lower;
When PaO2 is < 60 mm Hg, min. ventilation ↑
What happens to PaCO2?
It is lowered as a result of hyperventilation
What happens to pH of arterial blood?
pH increases slightly say from 7.4 to 7.45
Arterial blood gases: Hypoxemia (low PaO2);
hypocapnia (PaCO2 < 35 mm Hg); respiratory
alkalosis (pH > 7.45 because of hypocapnia)
Some working definitions for you:
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Normocapnia: PaCO2 between 35 and 45 mm Hg
Hypocapnia: PaCO2 < 35 mm Hg
Hypercapnia: PaCO2 > 45 mm Hg
Hypoxemia: PaO2 < 80 mm Hg
Note: significant activation of carotid bodies
occurs only when PaO2 < 60 mm Hg
Effects of breath holding:
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Respiration can be voluntarily inhibited for some time
Eventually, voluntary control is overridden (breaking
point)
What is breaking due to?
Rise in PaCO2 (acute hypercapnia)
Fall in PaO2
Individuals can hold their breath longer after removal
of carotid bodies;
Psychologic factors also contribute
Effects of hyperventilation:
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Overbreathing to exhaustion;
Eventually there is a “breaking point”
Note a period of apnea following
hyperventilation;
What is breaking here due to?
apnea
CO2 lack
Overbreathing
Effects of chronic hypercapnia:
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When does chronic hypercapnia occur?
What is the basic cause of chronic hypercapnia?
Failure to eliminate CO2; (respiratory failure)
Reason: reduction in alveolar ventilation
Note:
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acute hypercapnia stimulates breathing
chronic hypercapnia depresses the respiratory center
Nonchemical influences on respiration:
Stimulus
Response
Excessive
Inhibition of
lung inflation inflation; lung
deflation
Excessive
Inhibition of
lung deflation deflation; lung
inflation
Lung
inflation
Further
inflation
Name of
reflex
Hering
Breuer
inflation
reflex
Receptor
Hering
Breuer
deflation
reflex
Vagal
afferents
from
airways
Head’s
paradoxical
reflex
?
Vagal
afferents
from
airways
Nonchemical influences on respiration (contd.):
Stimulus
Response
Lung
hyperinflation;
increase in
pulmonary
interstitial fluid
pressure; or
intravenous
injection of
capsaicin
Injection of
histamine
Apnea followed by
tachypnea;
bradycardia;
hypotension; skeletal
muscle weakness
Cough,
bronchoconstriction,
mucus secretion
Name of
reflex
J reflex
Cough
reflex
Receptor
Juxtacapillary
receptors (C
vagal fiber
endings)
Irritant
receptor;
among airway
epithelial cells
Mechanism and significance of cough:
Deep inspiration
Forced expiration against a closed glottis
Intrathoracic pressure increases to 100 mm Hg or more
Glottis opened by explosive outflow of air
Airways are cleared of irritants
Ondine’s curse:
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Spontaneous control of breathing is disrupted;
Voluntary control is intact;
One could stay alive only by remembering to
breathe;
Clinical analog:
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bulbar poliomyelitis affecting respiratory neurons in
the brain stem;
disease processes compressing the medulla
Regulation of respiration during sleep:
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Respiration is less rigorously controlled during
sleep;
Brief periods of apnea occur even in normal
people;
Ventilatory response to hypoxia varies;
Sensitivity of brain stem mechanisms reduced?
Abnormal breathing patterns:
Periodic breathing
(Cheyne-Stokes respiration)
Normal
Cheyne-Stokes respiration:
Periods of apnea punctuated by periods of
hyperpnea
It occurs in:
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1.
2.
congestive heart failure
brain stem disease affecting respiratory centers
Mechanisms postulated to explain this:
Prolonged lung-to-brain circulation time
Changes in sensitivity of medullary respiratory
neurons
Activity:
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Hyperventilate to exhaustion
Then, note your pattern of breathing
Explain your observations
hyperventilation
Periodic breathing
normal
Following
hyperventilation
Outline of the explanation:
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Hyperventilation eliminates CO2;
Apnea is due to lack of CO2
During apnea, PaO2 falls & stimulates breathing
Few breaths eliminate hypoxia
Now there is no stimulus for breathing
So there is apnea again
Normal breathing resumes only when PaCO2 is
40 mm Hg
Conclusion: normal breathing pattern is entrained
by PaCO2 not PaO2
Some items for self-study:
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How is breathing regulated during exercise?
What is the mechanism of hiccups?
What is the mechanism of yawning?
What is the mechanism of sneezing?
What happens when you sigh?
POST-TEST
You should also be able to answer these
questions:
1.
2.
3.
Describe with the help of schematic diagram,
the neural mechanism of spontaneous breathing
Describe with the help of schematic diagram,
the neural mechanism of voluntary control of
respiration
Describe with the help of schematic diagram,
the role of systemic arterial chemoreceptors in
the regulation of alveolar ventilation
4.
5.
6.
7.
Describe with the help of schematic diagrams
the functional organization and functions of
medullary chemoreceptors.
How does CO2 stimulate breathing?
What is the relationship between PaCO2 and
minute ventilation?
Describe the mechanism responsible for periodic
breathing following voluntary hyperventilation
8.
9.
10.
Explain the factors that affect breath holding
time.
Briefly explain the effect of damage to the
pneumotaxic center on the pattern of breathing
Briefly explain the effect of vagotomy on the
pattern of breathing in experimental animals.
11.
12.
13.
14.
15.
What is the difference between the effect of
acute hypercapnia and chronic hypercapnia on
minute ventilation?
What is Kussmaul’s respiration? When does it
occur? What is the mechanism involved?
What is periodic breathing? When does it
occur? What is Cheyne-Stokes respiration?
What are the Hering Breuer reflexes?
What is Head’s paradoxical reflex?
Required Reading:

Chapter 36. Regulation of respiration. Ganong
WF. Review of Medical Physiology, Mc Graw
Hill Co, 2005