Respiratory protective devices — Human factors — Part 3: Physiological responses and limitations of oxygen and limitations of carbon dioxide in the breathing environment

ISO/TS 16976-3:2011 gives: a description of the factors contributing to the present content of the Earth's atmosphere; a description of the physiology of human respiration; a survey of the current biomedical literature on the effects of carbon dioxide and oxygen on human physiology; examples of environmental circumstances where the partial pressure of oxygen or carbon dioxide can vary from that found at sea level. ISO/TS 16976-3:2011 identifies oxygen and carbon dioxide concentration limit values and the length of time within which they would not be expected to impose physiological distress. To adequately illustrate the effects on human physiology, ISO/TS 16976-3:2011 addresses both high altitude exposures where low partial pressures are encountered, and underwater diving, which involves conditions with high partial pressures. The use of respirators and various work rates during which RPD can be worn are also included.

Appareils de protection respiratoire — Facteurs humains — Partie 3: Réponses physiologiques et limitations en oxygène et en gaz carbonique dans l'environnement respiratoire

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TECHNICAL ISO/TS
SPECIFICATION 16976-3
First edition
2011-08-15

Respiratory protective devices — Human
factors —
Part 3:
Physiological responses and limitations
of oxygen and limitations of carbon
dioxide in the breathing environment
Appareils de protection respiratoire — Facteurs humains —
Partie 3: Réponses physiologiques et limitations en oxygène et en gaz
carbonique dans l'environnement respiratoire




Reference number
ISO/TS 16976-3:2011(E)
©
ISO 2011

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ISO/TS 16976-3:2011(E)

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ii © ISO 2011 – All rights reserved

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ISO/TS 16976-3:2011(E)
Contents Page
Foreword . iv
Introduction . v
1 Scope . 1
2 Terms and definitions, symbols and abbreviated terms . 1
2.1 Terms and definitions . 1
2.2 Symbols and abbreviated terms . 4
3 Oxygen and carbon dioxide in the breathing environment: physiological responses and
limitations . 5
3.1 General . 5
3.2 Oxygen and carbon dioxide gas exchange in the human lung . 5
3.3 Oxygen and carbon dioxide transport in the blood . 6
3.4 Oxygen and carbon dioxide and the control of respiration . 8
3.5 Hyperoxia: physiological effects . 9
3.6 Hypoxia: physiological effects . 10
3.7 Hypercarbia: physiological effects . 13
3.8 Relevance to the use of respiratory protective devices (RPD) . 16
3.9 Interpretation of results . 19
3.10 Significance of results . 20
Bibliography . 21

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ISO/TS 16976-3:2011(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
In other circumstances, particularly when there is an urgent market requirement for such documents, a
technical committee may decide to publish other types of document:
— an ISO Publicly Available Specification (ISO/PAS) represents an agreement between technical experts in
an ISO working group and is accepted for publication if it is approved by more than 50 % of the members
of the parent committee casting a vote;
— an ISO Technical Specification (ISO/TS) represents an agreement between the members of a technical
committee and is accepted for publication if it is approved by 2/3 of the members of the committee casting a
vote.
An ISO/PAS or ISO/TS is reviewed after three years in order to decide whether it will be confirmed for a
further three years, revised to become an International Standard, or withdrawn. If the ISO/PAS or ISO/TS is
confirmed, it is reviewed again after a further three years, at which time it must either be transformed into an
International Standard or be withdrawn.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO/TS 16976-3 was prepared by Technical Committee ISO/TC 94, Personal safety — Protective clothing and
equipment, Subcommittee SC 15, Respiratory protective devices.
ISO/TS 16976 consists of the following parts, under the general title Respiratory protective devices — Human
factors:
 Part 1: Metabolic rates and respiratory flow rates
 Part 2: Anthropometrics
 Part 3: Physiological responses and limitations of oxygen and limitations of carbon dioxide in the
breathing environment
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ISO/TS 16976-3:2011(E)
Introduction
Due to the nature of their occupations, millions of workers worldwide are required to wear respiratory
protective devices (RPD). RPD vary considerably, from filtering devices, supplied breathable gas devices, and
underwater breathing apparatus (UBA), to escape respirators used in emergency situations (self-contained
self-rescuer or SCSR). Many of these devices protect against airborne contaminants without supplying air or
other breathing gas mixtures to the user. Therefore, the user might be protected from particulates or other
airborne toxins but still be exposed to an ambient gas mixture that differs significantly from that which is
normally found at sea level. RPD that supply breathing air to the user, such as an SCBA or UBA, can
malfunction or not adequately remove carbon dioxide from the breathing space, thus exposing the user to an
altered breathing gas environment. In special cases, RPD intentionally expose the wearer to breathing gas
mixtures that significantly differ from the normal atmospheric gas mixture of approximately 79 % nitrogen and
21 % oxygen with additional trace gases. These special circumstances occur in aviation, commercial and
military diving, and in clinical settings.
Breathing gas mixtures that differ from normal atmospheric can have significant effects on most physiological
systems. Many of the physiological responses to exposure to high or low levels of either oxygen or carbon
dioxide can have a profound effect on the ability to work safely, to escape from a dangerous situation, and to
make clear judgements about the environmental dangers. In addition, alteration of the breathing gas
environment can, if severe enough, be dangerous or even fatal. Therefore, monitoring and controlling the
breathing gas, and limiting user exposure to variations in the concentration or partial pressure of oxygen and
carbon dioxide, is crucial to the safety and health of the worker.
This Technical Specification discusses the gas composition of the Earth's atmosphere; the basic physiology of
metabolism as the origin of carbon dioxide in the body, respiratory physiology and the transport of oxygen to
the cells and tissues of the body; and the subsequent transport of carbon dioxide from the tissues to the lungs
for removal from the body. Following the basic physiology of respiration, this Technical Specification
addresses the physiological responses to altered breathing environments (hyperoxia, hypoxia) and to the
effects of excess carbon dioxide in the blood (hypercarbia). Examples are given from the relevant biomedical
literature.
Finally, it deals with the impact of altered partial pressures/concentrations of oxygen and carbon dioxide on
respirator use. The content of this Technical Specification is intended to serve as the basis for advancing
research and development of RPD with the aim of minimizing the changes in the breathing environment, thus
minimizing the physiological impact of RPD use on the wearer. If this can be accomplished, the health and
safety of all workers required by their occupation to wear RPD will be enhanced.

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TECHNICAL SPECIFICATION ISO/TS 16976-3:2011(E)

Respiratory protective devices — Human factors —
Part 3:
Physiological responses and limitations of oxygen and
limitations of carbon dioxide in the breathing environment
1 Scope
This Technical Specification gives:
 a description of the composition of the Earth's atmosphere;
 a description of the physiology of human respiration;
 a survey of the current biomedical literature on the effects of carbon dioxide and oxygen on human
physiology;
 examples of environmental circumstances where the partial pressure of oxygen or carbon dioxide can
vary from that found at sea level.
This Technical Specification identifies oxygen and carbon dioxide concentration limit values and the length of
time within which they would not be expected to impose physiological distress. To adequately illustrate the
effects on human physiology, this Technical Specification addresses both high altitude exposures where low
partial pressures are encountered and underwater diving, which involves conditions with high partial
pressures. The use of respirators and various work rates during which RPD can be worn are also included.
2 Terms and definitions, symbols and abbreviated terms
2.1 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
2.1.1
alveoli
s. alveolus
terminal air sacs of the lungs in which respiratory gas exchange occurs between the alveolar air and the
pulmonary capillary
NOTE The alveoli are the anatomical and functional unit of the lungs.
2.1.2
ambient temperature pressure saturated
ATPS
standard condition for the expression of ventilation parameters related to expired air
NOTE Actual ambient temperature and atmospheric pressure; saturated water pressure.
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ISO/TS 16976-3:2011(E)
2.1.3
body temperature pressure saturated
BTPS
standard condition for the expression of ventilation parameters
NOTE Body temperature (37°C), atmospheric pressure 101,3 kPa (760 mmHg) and water vapour pressure (6,27
kPa) in saturated air.
2.1.4
carbaminohaemoglobin
HbCO
2
haemoglobin that has bound carbon dioxide at the tissue site for transport to the lungs
2.1.5
dead space
‹anatomical› conducting regions of the pulmonary airways that do not contain alveoli and, therefore, where no
gas exchange occurs
NOTE These areas include the nose, mouth, trachea, large bronchia, and the lower branching airways. This volume
is typically 150 ml in a male of average size.
2.1.6
dead space
‹physiological› sum of all anatomical dead space as well as under-perfused (reduced blood flow) alveoli which
are not participating in gas exchange
NOTE The volume of the physiological dead space can vary with the degree of ventilation. Thus, the physiological
dead space is the fraction of the tidal volume that does not participate in gas exchange in the lungs.
2.1.7
dyspnoea
sense of air hunger, difficult or laboured breathing, or a sense of breathlessness
2.1.8
end-tidal carbon dioxide
ET CO
2
volume fraction of carbon dioxide in the breath at the mouth at the end of exhalation
NOTE End-tidal carbon dioxide corresponds closely to alveolar carbon dioxide.
2.1.9
haemoglobin
Hb
specific molecules contained within all red blood cells that bind oxygen or carbon dioxide under normal
physiological states and transport either oxygen or carbon dioxide to or from the tissues of the body
2.1.10
hypercarbia
hypercapnia
excess amount of carbon dioxide in the blood
2.1.11
hyperoxia
volume fraction or partial pressure of oxygen in the breathing environment greater than that which is found in
the Earth's atmosphere at sea level, which contributes to an excess of oxygen in the body
NOTE This can occur when a person is under hyperbaric conditions (i.e. diving), subjected to breathing gas mixtures
with an elevated oxygen fraction, or during certain medical procedures
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ISO/TS 16976-3:2011(E)
2.1.12
hypoxia
volume fraction or partial pressure of oxygen in the breathing environment below that which is found in the
Earth's atmosphere at sea level
NOTE Anaemic hypoxia is due to a reduction of the oxygen carrying capacity of the blood as a result of a decrease in
the total haemoglobin or an alteration in the haemoglobin constituents.
2.1.13
hypocapnia
volume fraction or partial pressure of carbon dioxide in the breathing environment or in the body that is lower
than that which is found in the Earth's atmosphere at sea level
NOTE This usually occurs under hyperventilation conditions (i.e. diving) or in medical settings that contribute to a
reduction of carbon dioxide in the body
2.1.14
inotropic
affecting the force of muscle contraction
NOTE A negative inotropic effect reduces and a positive inotropic effect increases the force of muscular contraction
(e.g. both skeletal and heart muscle).
2.1.15
medulla oblongata, pons
areas of the brain where the respiratory control centre is located
2.1.16
oxyhaemoglobin
HbO
2
haemoglobin that has bound oxygen from the lungs for transport to the body tissues
2.1.17
partial pressure
pressure exerted by each of the components of a gas mixture to form a total pressure
EXAMPLE Air is a mixture of oxygen, nitrogen, carbon dioxide, inert gases (argon, neon), and water vapour. The
volume fraction of oxygen in air is about 20,9 %. At sea level, total atmospheric pressure is 101,3 kPa (760 mmHg). Water
vapour pressure is 6,26 kPa (47 mmHg) (fully saturated in the lungs at a body temperature of approximately 37 °C). To
find partial pressure of oxygen, subtract vapour pressure from total atmospheric pressure and then multiply the oxygen
volume fraction by the dry atmospheric pressure. Thus, 101,3  6,3 = 95,1 kPa (760 mmHg  47 mmHg = 713 mmHg);
0,21  95,1 kPa = 19,9 kPa (= 149 mmHg). If the ambient pressure increases (as in diving), the partial pressure of each
component gas increases. Thus, at 2 atm absolute, the partial pressure of oxygen in dry gas is 101,3  2 = 202,6 kPa
(760 mmHg  2 = 1 520 mmHg); 0,21  202,6 = 42,6 kPa (0,21  1520 mmHg = 319 mmHg) oxygen.
NOTE 1 Partial pressure is dependent on the volume fraction of the component gas.
NOTE 2 The partial pressure of a gas can increase or decrease while its relative volume fraction remains the same.
Partial pressure drives the diffusion of gas across cell membranes and is, therefore, more important than relative volume
fraction of the gas.
2.1.18
respiratory quotient
R
Q
ratio of volume of carbon dioxide exhaled to the volume of oxygen consumed as follows
R VVCO O
Q
22
where
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ISO/TS 16976-3:2011(E)
VCO is the volume of carbon dioxide exhaled;
2
VO is the volume of oxygen consumed
2
NOTE R gives an estimate of the content of substrate utilization during steady-state respiration and metabolism. At
Q
rest, R = 0,82 reflecting a substrate utilization of a combination of carbohydrates and fats as the primary energy source.
Q
2.1.19
respiratory system
tubular and cavernous organs (mouth, trachea, bronchi, lungs, alveoli, etc.) and structures which bring about
pulmonary ventilation and gas exchange between ambient air and blood
2.1.20
standard temperature pressure dry
STPD
standard conditions for expression of oxygen consumption
NOTE Standard temperature (0 °C) and pressure (101,3 kPa, 760 mmHg), dry air (0 % relative humidity).
2.1.21
ventilation (general)
process of exchange of air between the lungs and the ambient environment
2.2 Symbols and abbreviated terms
APR air purifying respirator
2
BSA body surface area, expressed in m
PAPR powered air purifying respirator
SAR supplied air respirator
SCBA self-contained breathing apparatus
UBA underwater breathing apparatus
PCO partial pressure of carbon dioxide
2
P CO alveolar partial pressure of carbon dioxide
A 2
P CO arterial partial pressure of carbon dioxide
a 2
P CO venous partial pressure of carbon dioxide
v 2
PO partial pressure of oxygen
2
P O alveolar partial pressure of oxygen
A 2
P O arterial partial pressure of oxygen
a 2
O partial pressure of inspired oxygen
P
i 2
P O venous partial pressure of oxygen
v 2
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ISO/TS 16976-3:2011(E)
V minute ventilation (expired)
E
total volume expired from the lungs in 1 min, in l/min (BTPS)
V minute ventilation (inspired)
I
total volume of air inspired into the lungs in 1 min, in l/min (BTPS)
VO oxygen consumption
2
volume of oxygen consumed by the human tissues, in l/min, derived from the difference
between the minute volume of inhaled oxygen and the minute volume of exhaled oxygen.
VCO carbon dioxide elimination rate
2
volume of carbon dioxide produced per minute, derived from the product of minute
ventilation and the difference between the fractional concentrations of exhaled and
inhaled carbon dioxide
3 Oxygen and carbon dioxide in the breathing environment: physiological
responses and limitations
3.1 General
The Earth's atmosphere is composed primarily of nitrogen and oxygen along with some trace gases.
Atmospheric carbon dioxide occurs in very low concentrations (approximately 0,03 %). Humans require
oxygen as a primary element in the production of energy during aerobic cellular metabolism. Low atmospheric
oxygen concentrations or partial pressures (such as occur at high altitude) can limit production of metabolic
energy, leading to a compromise in physiological function. On the other hand, low concentrations of carbon
dioxide in the breathing atmosphere do not appear to have any physiological consequence. Carbon dioxide is
produced as a by-product of cellular metabolism and it is this source of carbon dioxide, not the normal
atmospheric concentration, which carries a physiological consequence. However, increased environmental
levels of carbon dioxide, as in the breathing space of respirators or in confined areas, can also have a
profound effect on the respiratory system.
High concentrations of either oxygen or carbon dioxide can have dramatic physiological consequences.
Hyperoxia, especially under ambient pressures greater than one atmosphere (atm), such as occur in diving,
can be toxic and even fatal to humans. High concentrations of carbon dioxide can also have a profound effect
on respiration and metabolism. This overview will address several issues:
 Oxygen and carbon dioxide in normal human physiology;
 Effects of hypoxia and hyperoxia on physiology;
 Effects of hypercarbia on physiology;
 Relevance to respiratory protective devices.
3.2 Oxygen and carbon dioxide gas exchange in the human lung
Normal minute ventilation takes place as a result of neural activity in the respiratory centres in areas of the
brainstem known as the medulla oblongata and the pons. The movement of air in and out of the lungs
facilitates the gas exchange necessary for normal metabolic function.
Gas exchange does not occur in all regions of the pulmonary system. Anatomical dead space (regions where
gas diffusion to the blood does not occur) comprises about 150 ml volume within the pulmonary system.
However, the physiological dead space can add a much larger volume depending on activity level. Inhaled
gas passes through the regions of dead space to the pulmonary alveoli. Gas exchange occurs in the alveoli,
which are in contact with blood capillaries.
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ISO/TS 16976-3:2011(E)
The exchange of oxygen into the blood stream and carbon dioxide out of the blood stream into the alveoli is
driven by simple diffusion down a partial pressure gradient. The partial pressure of oxygen in the alveoli
(P O ) is approximately 13,3 kPa (100 mmHg) whereas the partial pressure of oxygen in the venous blood
A 2
(P O is approximately 5,3 kPa (40 mmHg). Therefore, oxygen will move from the area of higher
v 2)
concentration of oxygen in the alveoli to the area of lower concentration of oxygen in the venous blood.
Oxygen will also be transported into the red blood cells along a similar partial pressure gradient to be bound to
haemoglobin. Conversely, the partial pressure of carbon dioxide in the venous blood (P CO ) is roughly
v 2
6,1 kPa (46 mmHg) and is only 5,3 kPa (40 mmHg) in the alveoli. Therefore, carbon dioxide will move from
the venous blood to the alveoli to be exhaled to the atmosphere.
After this gas exchange has taken place, arterial blood contains a P O of 13,3 kPa (100 mmHg) and a P CO
a 2 a 2
of 5,3 kPa (40 mmHg). The arterial blood arriving at the cells will release oxygen and take up carbon dioxide
based on a similar process of moving along a partial pressure gradient. After oxygen delivery to the cells has
taken place, the red blood cells have a PO of 5,3 kPa (40 mmHg) and a PCO of 6,1 kPa (46 mmHg). Upon
2 2
return to the lungs for another round of gas exchange, each gas again moves along its partial pressure
gradient to repeat the process. Proper oxygen delivery to the cells and carbon dioxide removal from the body
will occur as long as a match exists between ventilation of the lungs and blood perfusion driven by a healthy
circulatory system.
3.3 Oxygen and carbon dioxide transport in the blood
Oxygen has a very low solubility in the blood. Therefore, oxygen is transported to the vital organs, working
muscles, and brain by a special transport mechanism in the blood. When oxygen from the atmosphere
diffuses from the alveoli to the circulation, about 25 % of the oxygen present in the alveoli is rapidly
transported into the red blood cells and binds to haemoglobin to form oxyhaemoglobin. Oxyhaemoglobin in
the red blood cells is carried through the arterial circulation to the capillaries where the oxygen diffuses from
the red blood cells to the cells of the target tissues. The oxygen is then utilized in the aerobic metabolic
processes in the cell mitochondria.
Several factors affect the affinity of oxygen for haemoglobin. For any given ambient PO , an increase in body
2
temperature, blood lactic acid (↓ pH), increased P CO , or an increase in 2,3-diphosphoglycerate (DPG, a
a 2
[4]
product of anaerobic metabolism in red blood cells), can decrease the affinity of oxygen for haemoglobin ).
This phenomenon is known as the Bohr Shift, which makes oxygen delivery easier under acidotic conditions.
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ISO/TS 16976-3:2011(E)

Key
X oxygen partial pressure (torr)
Y haemoglobin saturation (%)
1 decreased P50 (P50 = one half saturation pressure)(increased affinity)
2 increased P50 (decreased affinity)
T temperature
PCO partial pressure of carbon dioxide
2
2,3-DPG 2,3-diphosphoglycerate
pH measure of the acidity or basicity of a solution
NOTE 1 1 torr = 133 Pa.
NOTE 2 See Reference [4].
Figure 1 — Shift of the oxyhaemoglobin dissociation curve by pH, carbon dioxide temperature, and
2,3-diphosphoglycerate (2,3-DPG)
By contrast, carbon dioxide is about 20 to 25 times more soluble in blood than oxygen. Carbon dioxide
produced as a by-product of metabolically active tissues diffuses from the cells of the tissue to the red blood
cells in the circulation along a concentration gradient. Some of the carbon dioxide (approximately 5 to 10 %) is
carried to the lungs in solution in the blood plasma. A portion of the carbon dioxide combines with water to
form carbonic acid according to the equation:
CO + H O  H CO (1)
2 2 2 3
This reaction occurs slowly in the plasma and most of the carbon dioxide remains in solution in the plasma.
However, a small amount of carbonic acid in the plasma dissociates to bicarbonate following the equation:
+
H CO  H + HCO (2)
2 3 3
Whereas the reaction in Equation (2) occurs in very small amounts in the plasma, it occurs to a very large
extent in red blood cells. Red blood cells contain the enzyme carbonic anhydrase (CA), which catalyzes the
6
reversible reaction between carbon dioxide and H O extremely rapidly (approximately 10 reactions per
2
[3]
second) in the following manner:
+
CO + H O H CO  H + HCO (3)
2 2 2 3 3
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ISO/TS 16976-3:2011(E)
Approximately 70 % of the carbon dioxide is transported to the lungs in the form of bicarbonate. In addition,
carbon dioxide combines with haemoglobin to form carbaminohaemoglobin. The affinity of haemoglobin for
carbon dioxide increases as oxygen dissociates from haemoglobin during delivery of oxygen to the tissues
[5]
(see also the Haldane effect ). Approximately 15 % of the carbon dioxide in the blood is transported to the
lungs in the form of carbaminohaemoglobin.
3.4 Oxygen and carbon dioxide and the control of respiration
Human life is strongly dependent on an adequate supply of oxygen to support the metabolic processes that
produce energy. As a result, the ability to sense changes in ambient PO has evolved. In addition, although
2
atmospheric carbon dioxide concentrations are almost negligible, carbon dioxide is produced as a product of
metabolism and has a profound effect on the respiratory system. Thus, mechanisms for sensing PCO in the
2
blood have also evolved. Indeed, changes in PCO are more powerful stimulators of respiration than changes
2
in ambient PO . A detailed discussion of the physiological mechanisms involved in sensing changes in oxygen
2
and carbon dioxide in the atmosphere or the blood is beyond the scope of this Technical Specification.
However, a brief overview of the process is given below.
Chemical sensors (chemoreceptors) are present in both the central nervous system (medulla oblongata in the
brain stem) and the peripheral nervous system integrated with the vascular system (i.e. carotid bodies in the
carotid artery in the neck and chemoreceptors in the aorta) that are capable of sensing changes in P O
2,
a
P CO and pH in the arterial blood. When these areas sense changes in P O and P CO , neural signals are
2 2 2
a a a
integrated into a respiratory response that usually results in a normalization of the P O and/or P CO . Under
2 2
a a
conditions of hypoxia, the decreased P O is sensed primarily by peripheral chemoreceptors in the carotid
2
a
bodies and the aortic bodies. The respiratory response is an increase in ventilation in order to increase the
oxygen uptake to maintain metabolic energy production. However, if the carotid and aortic bodies are
removed or damaged, a decrease in P O can result in a decrease in ventilation because a reduction in brain
2
a
P O can act directly to depress respiratory cells in the brain. Low P O also increases brain blood flow,
2 2
a a
+
thereby lowering P CO and [H ] and decreasing ventilation. Figures 2 and 3 illustrate the basic relationships
2
a
involved in the control of respiration.

Figure 2 — Basic relationships between sensor inputs, processing and outputs from the respiratory
control mechanisms in the central nervous system, and the effectors (respiratory muscles) that
actuate the respiratory process
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ISO/TS 16976-3:2011(E)


a) carbon dioxide response
b) pH response
Key
Key
X1 arterial PCO [mm Hg]
2 X2 arterial pH
Y total ventilation, in l/min
Y total ventilation, in l/min
Figur
...

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