RESPIRATORY PHYSIOLOGY

Mahan Josiah Mallo

Department of Physiology, Bingham University, Karu
Functions of the Respiratory System
• The four primary functions of the respiratory system are:
1. Exchange of gases between the atmosphere and the blood. The body
brings in O₂ for distribution to the tissues and eliminates Co₂ waste
produced by metabolism
2. Homeostatic regulation of body pH. The lungs can alter body pH by
selectively retaining or excreting Co₂
3. Protection from inhaled pathogens and irritating substances. The
respiratory epithelium is well supplied with mechanisms that trap and
destroy potentially harmful substances before they can enter the body
4. Vocalization: Air moving across the vocal cords creates vibrations
used for speech, singing and other forms of communication
5. Metabolic and endocrine functions:
i. type II alveoler cells secrete the surfactant for local use
ii. Secretion of some protaglandins, histamins and kallikrein
iii. Removal of some subtstances from the blood e.g serotonin, bradykinin,
Ach
iv. The lungs contains the fibrinolytic system that lyses blood clot in the
pulmonary system
v. Angiotension I is converted to angiotensin II in the lungs by ACE
vi. Vasoactive intestinal peptide is secreted in the lungs
 Introduction
• Respiration is divided into two:
• Cellular Respiration: Which is the intracellular reaction
of oxygen with organic molecules to produce Co₂, H₂O
and energy in form of ATP.
• External Respiration: Which is the movement of gases
between the environment and the body’s cells.
 External Respiration
• It is Divided into four Integrated processes:
1. The exchange of air between the atmosphere and the lungs.
This process is known as ventilation or breathing. Inspiration
(Inhalation) is the movement of air into the lungs. Expiration
(exhalation) is the movement of air out of the lungs.
2. The exchange of O₂ and CO₂ between the lungs and the
blood
3. The transport of O₂ and CO₂ by the blood
4. The exchange of gases between blood and the cells.
 External Respiration…
• External respiration requires the coordinated functioning of the
respiratory and cardiovascular systems. The respiratory system
consist of structures involved in ventilation and gas exchange:
1. The conducting systems of passages or airways, that lead from the
external environment to the exchange surface of the lungs
2. The alveoli (singular alveolus) which is a series of interconnected
sacs that collectively form the exchange surface, where O₂ moves
from inhaled air to the blood, and CO₂ moves from the blood to air
that is about to be exhaled
3. The bones and muscles of the thorax (chest cavity) and abdomen
that assist in ventilation.
 Nasal cavity
Oral cavity (mouth)
Pharynx
(throat) Larynx (voice box)

Trachea (windpipe)
Bronchus
Lungs

Diaphragm

Alveolar
capillaries

Respiratory
Alveolus bronchiole

Terminal
bronchioles
 Bifurcation Larynx
of trachea Trachea
Upper lobe Upper lobe
of right of left lung
lung
Alveoli
Main
bronchi
Bronchioles
Middle
lobe
Lower
Lower lobe of
lobe of left lung
right lung

Alveoli
fig. 20-2; pg. 632
 Gas Exchange in the Lungs and
Tissues
• The gas law state that individual gases flow from regions of
higher partial pressure to regions of lower pressure
(concentration gradient).
• This rule also governs the exchange of gases and carbon
dioxide in the lungs and tissues.
• The Lungs are contained in a space with a volume of
approximately 4L, but they have a surface area for gas
exchange that is the size of a tennis court. The lungs weighs
about 1Kg.
 Gas Exchange in the Lungs and
Tissues…
• Normal alveolar Po₂ is about 100 mmHg.
• The Po₂ of systemic venous blood arriving at the lungs is 40 mmHg.
• O₂ therefore moves down its partial pressure (concentration) gradient
from the alveoli into the capillaries.
• Diffusion goes to equilibrium, and the Po₂ of arterial blood leaving the
lungs is the same as in the alveoli i.e 100 mmHg.
• When arterial blood reaches tissue capillaries, the gradient is
reversed. Cells are continuously using oxygen for oxidative
phosphorylation.
 Alveolar
space Alveolar
epithelium
O2 CO2
Alveolar
capillary Interstitial
membrane fluid

Capillary
Capillary endothelium
Red cell

(c) 2003 Brooks/Cole – Thomson Learning

fig. 20-5; pg. 634

 Gas Exchange in the Lungs and
Tissues…
• In the cells of a person at rest, intracellular Po₂ averages 40
mmHg.
• Arterial blood arriving at the cells, oxygen diffuses down its
partial pressure gradient from plasma into cells
• Once again, diffusion goes to equilibrium, and as a result
venous blood has the same Po₂ as the cells it just passed
• Conversely, Pco₂ is higher in tissues than in systemic capillary
blood because of Co₂ production during metabolism.
• Cellular Pco₂ in a person at rest is about 46 mmHg, compared
to an arterial plasma Pco₂ of 40 mmHg.
 Gas Exchange in the Lungs and
Tissues…
• The gradient causes Co₂ to diffuse out of cells into the
capillaries. Diffusion goes to equilibrium, and systemic venous
blood averages a Pco₂ of 46 mmHg.
• At the pulmonary capillaries, the process reverses. Venous
blood bringing waste Co₂ from the cells has a Pco₂ of 46
mmHg. Alveolar Pco₂ is 40mmHg. Because Pco₂ is higher in
the plasma, Co₂ moves from the capillaries into the alveoli. By
the time blood leaves the alveoli, it has a Pco₂ of 40 mmHg,
identical to the Pco₂ of the alveoli.
Copyright © 2007 Lippincott Williams & McArdle, Katch, and Katch: Exercise Physiology: Energy,
Wilkins. Nutrition, and Human Performance, Sixth Edition
 Oxygen Transport
• Blood
• Blood is an 'aqueous body fluid'. In other words it is water containing a
whole range of substances. It is contained in a complex network called
the vascular system and is pumped around the body by the heart.
• Blood has two main functions. It:
i. provides defence against disease
ii. transports compounds, ions, and some elements to and from other
tissues and cells
• Oxygen is one of the substances transported with the assistance of red
blood cells.
 Oxygen Transport
• Oxygen is transported in two ways in the blood:
i. Bound to hemoglobin in a reversible reaction and
ii Dissolved in the plasma
• The red blood cells contain a pigment called hemoglobin, each
molecule of which binds four oxygen molecules.
Oxyhemoglobin forms.
• The oxygen molecules are carried to individual cells in the body
tissue where they are released. The binding of oxygen is
a reversible reaction Hb + 4O₂ ↔ Hb.4O₂
 Oxy-Hemoglobin Dissociation Curve
• At high oxygen concentrations oxyhemoglobin forms, but at low
oxygen concentrations oxyhemoglobin dissociates to hemoglobin and
oxygen.
• The balance can be shown by an oxygen dissociation curve for
oxyhemoglobin.
 Oxygen Dissociation Curve
• The curve shows that:
• at relatively low oxygen concentrations there is uncombined
hemoglobin in the blood and little or no oxyhemoglobin, e.g. in body
tissue
• at relatively high oxygen concentrations there is little or no
uncombined hemoglobin in the blood; it is in the form of
oxyhemoglobin, e.g. in the lungs.
 Factors that Affects the Oxy-
Hemoglobin Dissociation Curve
• Any factor that changes the conformation of the hemoglobin
protein may affect its ability to bind oxygen.
• Physiological changes in plasma temperature, Pco₂ and pH
alter the oxygen binding affinity of hemoglobin.
• ↑ temperature and Pco₂ will decrease the affinity of hemoglobin
for oxygen and shift the curve to the right.
• ↓ pH will decrease the affinity of hemoglobin for oxygen and
shift the curve to the right. (the Bohr effect).
Factors that Affects the Oxy-
Hemoglobin Dissociation Curve…
• ↑ in 2,3-DPG production in red blood cells lower the binding
affinity of hemoglobin and shifts the curve to the right. 2, 3-
diphosphoglycerate is a compound made from an intermediate
of the glycolysis pathway.
• Chronic hypoxia triggers an increase in 2,3-DPG production in
RBC. Increased levels of 2,3-DPG lower the affinity of Hb and
shift the HbO2 dissociation curve to the right. Ascent to high
altitude and anemia are two situations that increase 2,3-DPG
production
Factors that Affects the Oxy-
Hemoglobin Dissociation Curve…
• Fetal hemoglobin (HbF) shifts the curve to the left: Changes in
Hb structure also change its oxygen binding affinity, e.g fetal
hemoglobin has gamma chain isoforms for two of its subunit.
• The presence of gamma chains enhances the ability of fetal
hemoglobin to bind oxygen in the low oxygen environment of
plasma
 Oxyhemoglobin dissociation curve
• Right
Left shift increased HB
shiftdecreased HBaffinity
affinityforforOO
2 (
2 (
release
releaseofofOO
2 to
2 to
tissues)
• Acidosis
Alkalosis
• Hyperthermia
Hypothermia
• 2,3
2,3 DPG
• COHB
 Carbon dioxide Transport
• Co₂ is a by product of cellular respiration. It is more soluble in
body fluids than O₂ . But the cells produce far more Co₂ than
can dissolve in the plasma.
• Only about 7% of the Co₂ carried by venous blood is dissolved
in the blood
• 93% diffuses into RBC, where 70% is converted to bicarbonate
ion (HCO₃) and then 23% binds to Hb.
• Elevated Co₂ in the body (hypercapnia) results into a pH
disturbance called acidosis. So Co₂ must be removed by the
lungs for proper functioning of the body.
 Carbon dioxide Transport
• 70% of Co₂ that enters the blood is transported to the lungs as
bicarbonate ions (HCO₃) dissolved in the plasma
• The conversion of Co₂ to HCO₃ is important because:
i. It provides an additional means by which Co₂ can be
transported from cells to lungs and
ii. HCO₃ is available to act as a buffer for metabolic acids,
thereby helping to stabilize the body’s pH. HCO₃ is the most
important buffer in the body.
 Carbon dioxide Transport
• The conversion of Co₂ to HCO₃ depends on the presence of an
enzyme found concentrated in the RBC called carbonic
anhydrase.
• Dissolved Co₂ in the plasma diffuses into RBC where it may
react with water in the presence of carbonic anhydrase to form
carbonic acid. Carbonic acid then dissociates into hydrogen ion
and a bicarbonate ion.
carbonic anhydrase
Co₂ + H₂O ↔ H₂Co3 ↔ H + HCO₃
 Hypoxia
• Hypoxia is a condition of the body in which the tissues are
starved of oxygen or the reduction of oxygen supply to the
tissues or below physiological levels.
• There are four types of hypoxia:
1. Hypoxic hypoxia
2. Anemic hypoxia
3. Ischemic hypoxia
4. Histotoxic hypoxia
 Different Types of Hypoxia
• Hypoxic hypoxia: Low arterial Po₂; it can be caused by deficiency of
O₂ in the atmosphere e.g in high altitude, alveolar hypoventilation e.g
in neuromuscular disorders and decreased lung diffusion capacity.
• Anemic hypoxia: Inadequate O₂ transport to the tissues by the blood.
Decreased total amount of O₂ bound to hemoglobin, It can be
caused by blood loss, anemia (low Hb or altered Hbo₂ binding),
carbon monoxide poisoning.
• Normally, oxygen would bind to hemoglobin in the lungs and be
released in areas with low oxygen partial pressure. When carbon
monoxide binds to hemoglobin, it cannot be released as easily as
oxygen.
 Different Types of Hypoxia…
• The slow release rate of carbon monoxide causes an accumulation
of CO-bound hemoglobin molecules as exposure to carbon
monoxide continues. Because of this, fewer hemoglobin particles
are available to bind and deliver oxygen, thus causing the gradual
suffocation associated with carbon monoxide poisoning.
• Carbon monoxide has 210 times greater affinity for hemoglobin
than oxygen. A small environmental concentration will thus cause
toxic levels of carboxyhemoglobin. After the carbon monoxide has
selectively bound to hemoglobin the oxygen-hemoglobin
dissociation curve shifts to the left, reducing oxygen release
 Different Types of Hypoxia…
• Carbon monoxide poisoning is caused by inhaling combustion
fumes. Depending on the degree and length of exposure, carbon
monoxide poisoning can cause:
• Headache.
• Dizziness.
• Nausea
• Permanent brain damage
• Damage to your heart, possibly leading to life-threatening cardiac
complications
• Death
 Different Types of Hypoxia…
• Ischemic hypoxia: Reduced blood flow. It can be caused by
heart failure (whole body hypoxia), shock (peripheral hypoxia)
and thrombosis (hypoxia in a single organ)
• Histotoxic hypoxia: Failure of cells to use O₂ because cells
have been poisoned. It can be caused by cyanide poisoning,
vitamin deficiency and other factors.
• Cyanide poisoning is poisoning that results from exposure to a
number of forms of cyanide. Early symptoms include headache,
dizziness, fast heart rate, shortness of breath, and vomiting.
 Different Types of Hypoxia…
• This may then be followed by seizures, slow heart rate, low blood
pressure, loss of consciousness, and cardiac arrest. Onset of
symptoms is usually within a few minutes. If a person survives, there
may be long-term neurological problems.
• cyanide prevents cells from using oxygen to make energy molecules.
Hydrogen cyanide binds to hemoglobin in place of O2. The
hemoglobin bound cyanide is transported throughout the body and
released to the cells where it enters the mitochondria binding
to cytochrome c oxidase preventing the electron transport to O2.
• In doing so, cyanide stops oxidative phosphorylation depriving the cells
of ATP. Cyanide binds to hemoglobin in place of O2, so you suffocate.
 Effects of Hypoxia in the body
• Hypoxia, if severe enough can cause death of cells throughout the
body, but in less severe degrees it causes principally:
I. Depressed mental activity, sometimes culminating in coma, and
II. Reduced work capacity of the muscles.
• If O₂ delivery stops for 5-10 min to the brain, permanent brain
damage results. Neurons of the brain have a very high rate of O₂
consumption and are unable to meet their metabolic need for ATP by
using anaerobic pathways, which have low yields of ATP/glucose.
Because of the brains sensitivity to hypoxia, homeostatic controls do
everything possible to maintain cerebral blood flow, even if it means
depriving other cells of O₂
 Effects of Hypoxia in the body…
• Hypoxia is the primary problems that people experience when
ascending to high altitude. High altitude is considered anything
above 1500 m (5000 ft), but most pathological responses to
altitude occur above 2500 m.
• In most people arriving at high altitude, normal physiological
responses kick in to help acclimatize the body to chronic
hypoxia. Within two hours of arrival, hypoxia triggers the release
of erythropoietin from the kidneys and liver. This hormone
stimulates RBC production and as a result, new erythrocytes
appear in the blood within four days.
 Acclimatization
• Reduced atmospheric PO2 leads to a decrease in alveolar
partial pressures of oxygen, this leads to an initial reduction in
oxygen delivery PO2.
• Acclimatization is the process by which the body responds to
this challenge.
• Traditional belief is that this adaptation is achieved by
increasing PO2 through respiratory, hematological, and cardiac
changes.
 Acclimatization
• It is the process or result of becoming accustomed to a new climate or
to new conditions.
• the most important feature of acclimatization to high altitude is an
increase in the rate and depth of breathing
• Although most people gradually recover as they adapt to the
low atmospheric pressure of high altitude, some persons experience a
reaction that can be severe and, unless they return to low altitude,
possibly fatal.
• Acclimatization shows wide inter-individual variability; some individuals
acclimatize quicker, more effectively, or both than others and are,
therefore, relatively less susceptible to acute high-altitude illness
 Altitude Sickness
• Altitude sickness, also called mountain sickness, it is an
acute reaction to a change from sea level or other low-
altitude environments to altitudes above 8,000 feet (2,400
metres).
• Altitude sickness was recognized as early as the 16th century.
In 1878 French physiologist Paul Bert demonstrated that the
symptoms of altitude sickness are the result of a deficiency
of oxygen in the tissues of the body.
• Mountain climbers, pilots, and persons living at high altitudes
are the most likely to be affected.
 Altitude Sickness…
• At higher altitudes, the air becomes thinner and the amount of breathable
oxygen decreases.
• The lower barometric pressures of high altitudes lead to a lower partial
pressure of oxygen in the alveoli, or air sacs in the lungs, which in turn
decreases the amount of oxygen absorbed from the alveoli by red blood
cells for transport to the body’s tissues.
• The resulting insufficiency of oxygen in the arterial blood supply causes the
characteristic symptoms of altitude sickness.
• The main protection against altitude sickness in aircraft is the use of
pressurized air in cabins.
• Mountain climbers often use a mixture of pure oxygen and air to relieve
altitude sickness while climbing high mountains.
 Altitude Sickness…
• Acute high-altitude illness describes the neurological or pulmonary syndromes
experienced when unacclimatized individuals ascend too rapidly. The symptoms
of acute altitude sickness fall into four main categories:
• (1) respiratory symptoms such as shortness of breath upon exertion, and
deeper and more rapid breathing;
• (2) mental or muscular symptoms such as weakness, fatigue,
dizziness, headache, sleeplessness, decreased mental acuity, decreased
muscular coordination, and impaired sight and hearing;
• (3) cardiac symptoms such as pain in the chest, palpitations, and irregular
heartbeat; and
• (4) gastrointestinal symptoms such as nausea and vomiting. The symptoms
usually occur within six hours to four days after arrival at high altitude and
disappear within two to five days as acclimatization occurs.
 Deep Sea Diving
• Deep sea diving is an act of descending into deep water, generally with
some form of breathing apparatus, and remaining there for an
extended period.
• It is used in fishing for sponges, coral, and pearls; in work on the
underwater parts of bridges, docks, and other structures; in examining
and repairing the underwater parts of ships; in recovering valuables
from sunken ships; in raising sunken ships to the surface; and in
certain military operations.
• Decompression sickness is caused by a reduction in ambient
pressure that results in the formation of bubbles of inert gases within
tissues of the body. It may happen when leaving a high-pressure
environment, ascending from depth
Deep Sea Diving
• Under the normal atmospheric pressure at the sea level (760mmHg), the
body contains about 1L of N2 dissolved in the body fluids and the tissues, and
its partial pressure in the blood equals that in the alveolar air i.e about
573mmHg N2 is an inert gas it is neither utilized nor produced by the body,
and its function is only to dilute the atmospheric oxygen and to keep the
alveoli distended.
• One of the major problems that face divers is the high pressure of water ( 1
atmosphere for every 10 meters of depth in sea water) which compresses the
chest and makes breathing difficult.
• They had to breathe air under a high pressure to resist the high water
pressure
• Users of SCUBA also breathe air from tanks under a high pressure for the
same reason.
• In all compressed air equipments, the pressure of the inspired air is matched
to that of the surroundings.
Deep Sea Diving
• During diving, breathing air (20% oxygen) is preferred to 100% oxygen to
avoid oxygen toxicity, and CO2 is routinely removed from the breathe air
to prevent its accumulation in the body
• The Po₂ and PN₂ increase in the breath air in proportion to its total
pressure, and this increases the dissolved amounts of these gases in the
body tissues and fluids.
• The dissolved o₂ is used by the tissues while N2 remains dissolved in
adipose tissues.
• This dissolved N2 may produce problems to the divers both during
descending in deep water (N2 narcosis) as well as during ascending from
this water (decompression)
• Nitrogen and the trace gases (argon, krypton, neon, xenon and helium)
are physiologically inert at the normal atmospheric pressure.
• Under high pressures these inert gases exert anaesthetic effects
Nitrogen narcosis
• The condition occurs when breathing air (which contains 80% N2) at
a pressure of 4-5 atmospheres (i.e at the depths of 30-40m under
sea water.
• The increased PN2 in the blood produces euphoria ( a sense of
pleasant excitement and well being that is called rapture of the deep).
• At greater depths, symptoms similar to those of alcohol intoxication
appear and the intellectual functions are impaired while the manual
skills are maintained.
• At still greater depths, the manual skills are also lost (leading to
incoordination of movements) and narcosis (tendency to sleep)
occurs which eventually terminates to comma.
High pressure nervous syndrome (HPNS)

• This syndrome is the risk of helium toxicity. It usually occurs

when breathing mixtures of O2 and helium at depths exceeding
70m ( at which the pressure is about 8 atmospheres).
• Its symptoms include tremors, drowsiness and the depression
of the α activity in the EEG.
• Unlike nitrogen narcosis, the intellectual functions are not
severely affected while the manual skills are impaired
Avoidance of Nitrogen narcosis

• Nitrogen narcosis can be avoided by breathing mixtures of O2

and helium, and deeper dives can also be made.
• Helium is one half soluble as N2 (so it is less dissolved in the
body fluids) and has smaller molecular weight than N 2 (so it
diffuses out from the tissues more easier than N 2
 Decompression Sickness
• Too rapid ascent from great depths causes the diver to
suffer decompression sickness.
• Decompression sickness (DCS) also known as divers disease
or caisson disease) describes a condition arising from dissolved
gases coming out of solution into bubbles inside the body on
depressurization. DCS is best known as a diving disorder that affects
divers having breathed gas that is at a higher pressure than the
surface pressure, owing to the pressure of the surrounding water.
• To prevent this, deep-sea divers either use an all-steel, armored
diving suit or breathe a special mixture of nine gases developed by
the Swiss mathematician Hannes Keller.
Symptoms of decompression sickness
• The symptoms of decompression sickness commonly appear 10-
30minutes after returning to the surface then progress. They include the
following:
i. Severe pains, paraesthesia and itching
ii. The nitrogen bubbles that enter the blood stream can obstruct any
artery resulting in one or more of the following symptoms:
a. Neurological symptoms due to blocking of the spinal and cerebral
arteries. E.g. dizziness, impaired vision, confusion, unsteadiness,
extreme muscle fatigue or paralysis as well as collapse and
unconsciuosness
b. Feeling of shortness of breath (dyspnea) that is called chokes by the
divers, due to excitation of the pulmonary irritant receptors secondary
to blocking of the pulmonary vessels
c. Angina pectoris, due to myocardial ischemia caused by blocking of the
Treatment of decompression sickness
• The risk of decompression sickness can be decreased by:
• Breathing oxygen-helium gas during the dives
• Slow ascend to the surface
• If its symptoms appear, the condition can be treated by
recompression in a pressure chamber followed by slow
decompression
• This is frequently life saving and recovery is often complete
(however, some neurological symptoms may persist due the
irreversable damage to the nervous system).
Respiratory responses to exercise
During muscular exercise, ventilation is markedly increased (up to 120
litres/minute or more) in order to:
• Supply excess oxygen
• Eliminate excess carbon dioxide
• Allow more heat loss through the respiratory system
 Control of Respiration
• Body must maintain homeostatic balance
between blood PO2, PCO2, pH

• This requires coordination between respiratory

and cardiovascular systems

• Coordination occurs via involuntary regulation of

pulmonary ventilation
 Control of Respiration
• Need for chemical regulatory mechanism:
• Maintenance of alveolar pCO2 at constant level
• Combat the effect of excess H+ in the body
• Raising pO2 if it falls to potentially lethal level
 Control of Respiration
• The control of respiration is divided into two
• (1) Chemical control: The chemical regulation of
respiration concerns the hydrogen ion content of
the respiratory neurons which in turn is dependent upon the
carbon dioxide tension of the blood and the rate of flow of blood
through the medulla, and
• (2) Neural control: These are inspiratory and expiratory centers
in the medulla oblongata which are responsible for establishing
the rate and depth of breathing via signals to respiratory muscles
Chemical Control of Respiration
• Chemical regulation of breathing is part of the involuntary (autonomic)
control of breathing.
• This mechanism is part of the bodies homeostasis to maintain an
appropriate balance and concentration of CO2, O2, HCO2- and pH.
• There are two types of respiratory chemoreceptors that react strongly to a
change in the blood gases: central and peripheral chemoreceptors.
• Chemoreceptors: detects arterial pCO2 and pH
• increase in alveolar PCO2 causes an increase in breathing rate
• PO2 normally stimulates ventilation when it falls below 60 mmHg, and when
the fall is accompanied by an increase in PCO2, the increase in ventilation
is greater
 Central Chemoreceptors
• Central chemoreceptors are located on the ventrolateral surface of
the medulla oblongata.
• They respond indirectly to blood pCO2 but not to pO2. CO2 diffuses across
the blood-brain barrier from blood to cerebrospinal fluid (CSF) while H+ and
HCO3- are unable to cross.
• As the blood CO2 readily passes the blood-brain barrier into the CSF it will
react with H2O to make H2CO3, that will split into HCO3- and H+.
• CO2 + H2O → HCO3- + H+
• An increase in H+ concentration will directly stimulate the chemoreceptor
neurons in the medulla oblongata. They will relay this information and
cause an increase in ventilation which will lead to a decrease in CO2.
 Central Chemoreceptors…
• Central chemoreceptors: Stimulated by ↑ CO 2 in cerebrospinal
fluid ↑ Rate and depth of breathing, remove excess CO 2 from
body

• The central chemoreceptors are responsible for ~80% of the

response to CO2 concentration.
 Peripheral Chemoreceptors
• Peripheral chemoreceptors are located in carotid and aortic
bodies, it was discovered by Heymans C and Neil E in 1930.
Carotid body is near the carotid bifurcation on each side, and
usually two or more aortic bodies are found near the arch of the
aorta. These chemoreceptors increase their firing rate in
response to increased arterial PCO2, or decreased arterial pH,
and especially to a decreased arterial PO2,
• The peripheral chemoreceptors are responsible for ~20% of the
response to an increase in pCO2.
 Chemical Control of Respiration…
• Stimulus for activation of peripheral receptors is Hypoxia-
decrease in arterial pO2, Vascular stasis- amount of O2
delivered to receptors is decreased, Asphyxia- lack of O2 plus
CO2 excess, and Drugs- cyanide poisoning.
• Central chemoreceptor. Also known as medullary
chemoreceptor Located on the ventral surface of medulla.
Stimulated by the H+ concentration of CSF and brain interstitial
fluid. Magnitude of stimulation is directly proportional to H+
concentration, which increases linearly with arterial pCO2.
Chemical Control of Respiration…
• The resultant accumulation of CO2 in the body (hypercapnia)
depresses the central nervous system, including the respiratory
center, and produces headache, confusion, and eventually coma
(CO2 narcosis). CO2 primarily acts on central chemoreceptors.
• Effect of H+ concentration on respiration: H+ normally cannot act
through modification of central chemoreceptors.
• Acidosis (increase H+ concentration in blood) produces marked
respiratory stimulation causing hyperventilation.
• Alkalosis (decrease H+ concentration in blood) depresses
respiratory center and causes hypoventilation
 Neural Control of Respiration
• The neural control of respiration refers to functional interactions
between networks of neurons that regulate movements of the
lungs, airways and chest wall and abdomen, in order to
accomplish
• (i) effective organismal uptake of oxygen and expulsion of
carbon dioxide, airway liquids and irritants,
• (ii) regulation of blood pH.
 Neural Control of Respiration…
• Breathing is special in several respects: it is the only function you
can perform consciously as well as unconsciously, and it can be a
completely voluntary act or a completely involuntary act, as it is
controlled by two sets of nerves, one belonging to
the voluntary nervous system, the other to the involuntary
• The medulla oblongata is the primary respiratory control center. Its
main function is to send signals to the muscles that control
respiration to cause breathing to occur.
• There are two regions in the medulla that control respiration: The
ventral respiratory group stimulates expiratory movements and the
dorsal respiratory group that stimulates inspiratory movements.
Neural Control of Respiration…
• Respiration is controlled by spontaneous neural discharge from
the brain to nerves that innervate respiratory muscles.
• The most important muscle to breathing is the diaphragm. The
diaphragm has its own nerve supply and can operate as
a voluntary muscle or involuntary muscle, thus allowing us to
hold our breath or slow our breathing if we wish to.
• The involuntary act of breathing is driven by carbon dioxide
sensors in the body.
 Control of Respiration…
• Although we can temporarily alter our respiratory performance,
we cannot override the chemoreceptor reflexes.
• For example, you can hold your breath voluntarily only until
elevated PCO2 in the blood and cerebrospinal fluid activates
the chemoreceptors reflex, forcing you to inhale.
• Small children sometimes attempt to manipulate their parents
by threatening to hold their breath until they die. However, the
chemoreceptor reflexes make it impossible for the children to
carry out that threat.