Respiratory Physiology

Dr. T. Simbini
Course Outline
• Anatomy of the Respiratory System
• Ventilation and Lung Mechanics
• Exchange of Gases in Alveoli and Tissues
• Transport of Oxygen in Blood
• Transport of Carbon Dioxide in Blood
• Transport of Hydrogen Ion between Tissues and Blood’
• Control of Respiration
• Hypoxia
• Non-respiratory functions of the lungs
Respiration
• Respiration can have two quite different meanings:
• utilization of oxygen in the metabolism of organic molecules by cells, often termed internal or cellular
respiration,
• the exchange of oxygen and carbon dioxide between an organism and the external environment,
(pulmonary physiology).
• Respiratory System: specialised system to facilitate the exchange of gases between organism
and external environment
• Inhalation and Exhalation - Pulmonary Ventilation
• External Respiration Exchanging Gases Between the Lungs and the Bloodstream
• Internal Respiration Exchanging Gases Between the Bloodstream and Body Tissues 
• Phonation
• Olfaction
• Respiratory system demonstrates the principle of physiology that structure is a determinant
of—and has coevolved with—function. (Vander 13th Ed)
Anatomy of
the
Respiratory
System

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Anatomy of the Respiratory System
• Upper Airway
• Nose, Nasal cavity, Nasopharynx, Larynx
• Filters out large particulates to prevent them from reaching the conducting and alveolar airways
• Serves to warm and humidify air as it enters the body.
• Conducting Pathways
• Begins in the trachea and bifurcates onto bronchi
• Each bronchus continues to bifurcate into 12 generations of smaller bronchi
• 12 to 23 generations become bronchioles (without cartilage)
• Function as an air conduit to and from the lungs, but also provides immunity to foreign substances
• Alveolar Airway
• The last seven generations form the transitional and respiratory zones where gas exchange occurs, are made up
of transitional and respiratory bronchioles, alveolar ducts, and alveoli
• These multiple divisions greatly increase the total cross-sectional area of the airways, from 2.5 cm2 in the
trachea to 11,800 cm2 in the alveoli.
• As a result, the velocity of airflow in the small airways declines to very low values.
Airway Branching
Alveoli
• Lined by two types of cells
• Type I cells: flat cells and are the primary lining cells of the alveoli, covering approximately 95% of the
alveolar epithelial surface area.
• Type II cells are thicker make up only 5% of the surface area, but represent approximately 60% of the
epithelial cells in the alveoli.
• Type II cells are important in alveolar repair as well as production of surfactant
• Surfactant layer plays an important role in maintaining alveolar structure by reducing surface tension, moving
further apart as the alveoli enlarge during inspiration, increasing surface tension, whereas it decreases when
they move closer together during expiration.
• Surrounded by pulmonary capillaries
• Air and blood are separated only by the alveolar epithelium and the capillary endothelium, so they are about
0.5 μm apart
• Also contains macrophages, mast cells and lymphocytes for immunological defence
Functional Zones
• Conducting Zone
• Extends from the top of the trachea to the beginning of the respiratory bronchioles.
• Contains no alveoli and does not exchange gases with the blood.
• Respiratory Zone
• Extends from the respiratory bronchioles down.
• Is the region where gases exchange with the blood.
• Principles of physiology demonstrated
• Physiological processes require the transfer and balance of matter (in this case, oxygen and carbon
dioxide) and energy between compartments,
• Structure (in this case, the thinness of the diffusion barrier and the enormous surface area for gas
exchange) is a determinant of—and has coevolved with—function (the transfer of oxygen and
carbon dioxide between the alveolar air and the blood in the pulmonary capillaries).
Thorax
• Synonymous with chest
• Is a closed compartment bounded at the neck by muscles and connective tissue
• Completely separated from the abdomen by a large, dome-shaped sheet of
skeletal muscle called the diaphragm
• The wall of the thorax is formed by the spinal column, the ribs, the sternum, and
several groups of muscles that run between the ribs - the intercostal muscles.
Respiratory Muscles – Chest Wall
• Movement of the diaphragm accounts for 75% of the change in intrathoracic volume during quiet inspiration.
• The other important inspiratory muscles are the external intercostal muscles, which run obliquely downward
and forward from rib to rib.
• The ribs pivot as if hinged at the back, when the external intercostals contract they elevate the lower ribs,
pushing the sternum outward and increases the anteroposterior diameter of the chest.
• The transverse diameter also increases but to a lesser degree.
• Either the diaphragm or the external intercostal muscles alone can maintain adequate ventilation at rest.
• The muscles in the neck are accessory inspiratory muscles that help elevate the thoracic cage during deep
laboured respiration.
Respiratory Muscles
• Expiratory muscles are the internal intercostals which pass obliquely downward and posteriorly from
rib to rib
• Pull the rib cage downward when they contract.
• Contractions of the muscles of the anterior abdominal wall also aid expiration by pulling the rib cage
downward and inward and by increasing the intra-abdominal pressure, which pushes the diaphragm
upward.
• Lung pleura- completely closed sac around the lung
• Serves as a lubricating fluid/ area
• Parietal pleura: covers the rib cage
• Visceral pleura: covers the lung tissue
• Space between the two pleura contains fluid: intrapleural fluid, this determines the intrapleural
pressure
 Introduction to Respiratory P
hysiology
Anatomy of the lungs

Videos
Alveoli

Thoracic Cavity
Pulmonary Ventilation and Lung Mechanics
• Ventilation is the exchange of air between the atmosphere and alveoli by bulk
flow.
• Flow is proportional to the pressure difference (Δ P) between two points and
inversely proportional to the resistance ( R).
• The relevant pressures are the gas pressure in the alveoli—the alveolar pressure
( Palv)—and the gas pressure at the nose and mouth, normally atmospheric
pressure (Patm) ,
• F (Palv -Patm)/R
• A negative value reflects an inward-directed pressure gradient (inspiration) and a
positive value indicates an outward-directed gradient (expiration).
 • Pressure is inversely proportional to the volume at
constant temperature
• P1V1=P2V2 (at constant temperature)
• the product of pressure and volume is a
constant for a given mass of confined gas and
this holds as long as the temperature is constant
• An increase in the volume of the container
Boyle’s Law decreases the pressure of the gas, whereas a
decrease in the container volume increases the
pressure.
• Alveolar pressure changes are caused by changes in
the dimensions of the chest wall and lungs.
Lung Mechanics
• The lungs are passive elastic structures whose volume depends on a number of factors
1. Transpulmonary pressure: the difference in pressure between the inside and
outside of the lung,
• Transpulmonary pressure Ptp= Palv (alveolar pressure) –Pip(intrapleural
pressure)
2. Stretchability of the lungs
• Transmural pressure is the pressure across a wall
• Convention Ptransmural=Pin - Pout
• Transmural pressure acting on the lungs ( Ptp) is Palv - Pip and, on the chest wall, ( Pcw) is
Pip - Patm.
Pressure changes in Inspiration
• During inspiration the muscles of the chest wall contract and cause the chest wall
to expand
• Simultaneously, the diaphragm contracts downward, further enlarging the
thoracic cavity.
• As the volume of the thoracic cavity expands, Pip decreases.
• Ptp becomes more positive, the lungs expand (volume increases) Palv decreases to
less than Patm
• Hence air flows inside
• Elastic recoil of the lungs drives passive expiration back to the starting point.
 • Patm = Palv= 0
• Ptp is always positive (lungs always have air in
them), therefore the Pip is therefore negative (keeps
the lung open)

At rest when • Pip is maintained negative by the natural elastic

recoil of the lungs
there is no • As the lungs tend to collapse and the thoracic wall
tends to expand, they move away from each other.
breathing • This causes an infinitesimal enlargement of the fluid-
filled intrapleural space between them.
• This equilibrium can be disturbed in a
pneumothorax
Lung mechanics
• In a pneumothorax
• Pip increases from -4mmHg to 0mmHg = Palv=Patm
• Ptp is eliminated and the lungs collapse
• Condition can be caused by trauma to the chest wall or perforation of the alveoli
Mechanics of inspiration
1. Diaphragm and external intercostal muscles contract
• Due to activation by the phrenic nerve
2. Thoracic expansion
• As the thorax enlarges, the thoracic wall moves farther away from the lung surface.
3. Pip decreases, and Ptp increases
• The force acting to expand the lungs—the transpulmonary pressure—is now greater than the
elastic recoil exerted by the lungs, and so the lungs expand further.
4. Lungs expand
5. Palv becomes subatmospheric
6. Air flow into the alveoli
 Mechanics of expiration
1. Diaphragm and inspiration muscles stop contracting
2. Chest wall recoil
3. Pip becomes less negative
4. Ptp decreases
5. Lung recoil
6. Alveolar volume decreases
7. Palv is greater Patm
8. Air flow out of the lungs
• Expiration at rest is passive, depending only upon the relaxation of the inspiratory muscles and the
elastic recoil of the stretched lungs.
• In extreme effort (e.g. exercise) expiration of larger volumes is achieved by contraction of internal
intercostal muscles and the abdominal muscles,
• internal intercostal muscles contraction pulls the chest wall downward and inward, thereby
decreasing thoracic volume.
Video
• Mechanics of Ventilation
• Pulmonary Ventilation (Wendy Riggs)
• Pulmonary Physiology (USMLE)
Lung Volumes
• Tidal Volume (TV):
• The amount of air that moves into the lungs with each inspiration (or the amount that moves out with each
expiration) during quiet breathing.
• About 500ml
• Inspiratory Reserve Volume (IRV):
• The air inspired with a maximal inspiratory effort in excess of the TV
• About 3 L
• Expiratory Reserve Volume:
• The volume expelled by an active expiratory effort after passive expiration
• About 1.2 L
• Residual Volume:
• The air left in the lungs after a maximal expiratory effort
• About 1.2 L
Lung Capacities
• Total Lung Capacity
• Sum of all lung volumes
• About 5 L
• Vital Lung Capacity
• the maximum amount of air expired from the fully inflated lung,
• About 3.5 L (TV + IRV + ERV).
• Inspiratory Capacity
• Is the maximum amount of air inspired from the end-expiratory level
• About 2.5L, (IRV + TV).
• Functional Residual Capacity
• the volume of the air remaining in the lungs after expiration of a normal breath
• About 2.5 L(RV + ERV).
Lung Volumes and
Capacities
Alveolar Ventilation
• Minute ventilation= tidal volume X respiratory rate
• In a typical adult Ventilation = 500ml/breath X 12 breaths/minute = 6000ml/minute
• Not all of this air is available for gaseous exchange
• Conducting air ways have a volume of 150ml (anatomic dead space), subtracted from the TV
• Actual air entering alveoli = 500ml – 150 ml = 350ml
• Alveolar ventilation = (TV- Anatomic dead space)*respiratory rate
• Important in exercises
• Rapid shallow breathes = decreased alveolar ventilation
• Normal breaths = normal alveolar ventilation
• Deep slow breathes = increased alveolar ventilation
External Respiration
Exchange of gases in alveoli and tissues
• Objective: Oxygen must move across the alveolar membranes into the pulmonary capillaries, be
transported by the blood to the tissues, leave the tissue capillaries and enter the extracellular fluid, and
finally cross plasma membranes to gain entry into cells. Carbon dioxide is the reverse
• In a steady state
• Volume of O2 extracted by tissues is in equilibrium with Volume of O2 added by the lungs in the
same time period
• Volume of CO2 added to circulation is in equilibrium with Volume of CO2 extracted from blood by
the lungs
• Respiratory Quotient (RQ)
• Amount of O2 consumed is NOT equal to the amount of CO2 produced
• Depends on the primary source of energy metabolism
• RQ = ratio of CO 2 produced to O 2 consumed
Partial Pressures of Gases
• The total pressure of a mixture of gases is simply the sum of the individual pressures.
• The pressure each gas exerts is independent of the pressure the others exert . (Dalton’s Law)
• Hence each gas pressure is a Partial Pressure of the Total Pressure
• Partial pressure is proportional to the concentration
• Net diffusion occurs from a region of high partial pressure to a region of low partial pressure.
• Diffusion of gases in liquids
• The amount of gas dissolved is directly proportional to the partial pressure of the gas with
which the liquid is in equilibrium. (Henry’s law)
• Diffusion equilibrium is reached only when the partial pressure of a gas in the liquid is equal
to the partial pressure of the gas in the gas phase,
• These principles form the basis of gaseous exchange across alveoli and capillary walls
Alveolar Gas Pressures
• In the atmosphere • Alveolar PO2 is lower than atmospheric
• PO2 = 160 mmHg PO2 because some of the oxygen in the
• PCO2 = 0.3 mmHg air entering the alveoli leaves to enter
• In the alveoli the pulmonary capillaries.
• PO2 = 105 mmHg
• Alveolar PCO2 is higher than
• PCO2 = 40 mmHg
atmospheric PCO2 because carbon
• In the Sa circulation dioxide enters the alveoli from the
• PO2 = 100 mmHg pulmonary capillaries.
• PCO2 = 40 mmHg
• In the Sv circulation
• PO2 = 40 mmHg •
• PCO2 = 46 mmHg
Factors affecting alveoli partial pressures
(PO2/PCO2)
1. PO2 of atmospheric air
• a decrease in the PO2 of the inspired air (high altitude), will decrease alveolar PO2 .
2. The rate of alveolar ventilation
• A decrease in alveolar ventilation will do the same thing
3. The rate of total-body oxygen consumption.
• an increase in the oxygen consumption in the cells (strenuous physical activity), results in a decrease in
the oxygen content of the blood returning to the lungs compared to the resting state.
• This will increase the concentration gradient of oxygen from the lungs to the pulmonary capillaries
resulting in an increase in oxygen diffusion.
• If alveolar ventilation does not change, this will lower alveolar PO2 because a larger fraction of the
oxygen in the entering fresh air will leave the alveoli to enter the blood for use by the tissues.
4. The same applies (but with opposite effects) for CO2 except there is low to zero PCO2 in the atmosphere
 Alveoli Partial Pressures
• At any particular atmospheric PO2 ,it is the ratio of oxygen consumption to alveolar ventilation that
determines alveolar PO2
• the higher the ratio, the lower the alveolar PO2
• Alveolar PCO2 is determined by the ratio of carbon dioxide production to alveolar ventilation
• the higher the ratio, the higher the alveolar PCO2 .
• Hypoventilation exists when there is an increase in the ratio of carbon dioxide production to alveolar
ventilation.
• A person is hypoventilating if the alveolar ventilation cannot keep pace with the carbon dioxide production.
• The result is that alveolar PCO2 increases above the normal value.
• Hyperventilation exists when there is a decrease in the ratio of carbon dioxide production to alveolar
ventilation, that is, when alveolar ventilation is actually too great for the amount of carbon dioxide
being produced.
• The result is that alveolar PCO2 decreases below the normal value.
• “Hyperventilation” is not synonymous with “increased ventilation.” Hyperventilation represents
increased ventilation relative to metabolism.
 Alveolar
Ventilation
and Partial
Pressure

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p+of+alveolar+ventilation+and+partial+pressure.jpg
Gas Exchange Between Alveoli and Blood
• The differences in the partial pressures of oxygen and carbon dioxide on the two sides of the
alveolar-capillary membrane result in the net diffusion of oxygen from alveoli to blood and of
carbon dioxide from blood to alveoli.
• The net diffusion of these gases ceases when the capillary partial pressures become equal to
those in the alveoli.
• The blood that leaves the pulmonary capillaries to return to the heart and be pumped into
the systemic arteries has essentially the same PO2 and PCO2 as alveolar air (not exactly the
same).
• The more capillaries that participate in gas exchange, the more total oxygen and carbon
dioxide are exchanged.
• Many of the pulmonary capillaries at the apex of each lung are normally closed at rest. During exercise,
these capillaries open and receive blood, thereby enhancing gas exchange.
Gas exchange between tissues and blood
• Intracellular PO2<40mmHg, PCO2>46mmHg
• The lowest PO2 of all—less than 5 mmHg—is in the mitochondria, the site of oxygen
utilization.
• Metabolic reactions occurring within cells are constantly consuming oxygen and
producing carbon dioxide.
• A net diffusion of oxygen occurs from blood into cells and, within the cells, into
the mitochondria, and a net diffusion of carbon dioxide occurs from cells into
blood.
Factors affecting gas exchange
• Video
Oxygen in Blood
• Oxygen in blood is in two forms
• dissolved in the plasma and erythrocyte cytosol(3ml)
• reversibly combined with haemoglobin molecules in the erythrocytes. (197ml)
• Henry’s law: the amount of oxygen dissolved in blood is directly proportional to the PO2 of the blood.
• Haemoglobin
• Four haem subunits and four polypeptides (globin)
• Each of the four haem groups in a haemoglobin molecule contains one atom of iron to which molecular oxygen binds.
• Each iron atom can bind one molecule of oxygen, a single haemoglobin molecule can bind four oxygen molecules
• Haemoglobin can exist in one of two forms— deoxyhaemoglobin (Hb ) and oxyhaemoglobin ( HbO2 ).
• The fraction of all the haemoglobin in the form of oxyhaemoglobin is expressed as the percent haemoglobin saturation
• The denominator is the oxygen-carrying capacity of the blood.
Effect of PO2 on Hb Saturation
• Increasing the blood PO2 should increase the
combination of oxygen with haemoglobin.
• Quantitatively this is the oxygen–haemoglobin
dissociation curve.
• Follows the principle of cooperativity
• the binding of one oxygen molecule to
deoxyhaemoglobin increases the affinity of the
remaining sites on the same haemoglobin
molecule,
• the extent to which oxygen combines with
haemoglobin increases very rapidly as the PO2
increases from 10 to 60 mmHg, so that at a
PO2 of 60 mmHg, approximately 90% of the
total haemoglobin is combined with oxygen.
•

https://upload.wikimedia.org/wikipedia/commons/thumb/8/8a/Oxyhaemoglobin_dissociation_curv
e.png/220px-Oxyhaemoglobin_dissociation_curve.png
Oxy-Haem – Dissociation Curve
• Rapid saturation is critical in situations with low PO2 as in high altitude
• Significant limitations of lung function can still allow almost normal oxygen saturation of hemoglobin.
• At sea level, increasing the alveolar (and therefore the arterial) PO2 either by hyperventilating or by breathing
100% oxygen does not appreciably increase the total content of oxygen in the blood.
• The steep portion of the curve from 60 mmHg down to 20 mmHg is ideal for unloading oxygen in the tissues.
• For a small decrease in PO2 due to diffusion of oxygen from the blood to the cells, a large quantity of oxygen
can be unloaded in the peripheral tissue capillary.
• The oxygen bound to haemoglobin does not contribute directly to the PO2 of the blood; only dissolved oxygen
does so.
• oxygen diffusion is governed only by the dissolved portion,
• haemoglobin plays a critical role in determining the total amount of oxygen that will diffuse
 • Sv PO2 = 40mmHg, the Hb saturation is 75%
• Alveolar PO2 = 105mmHg, hence net diffusion
of O2 into pulmonary capillaries
• In erythrocytes, there is increased Hb-O2
association hence increased Hb – O2 saturation
Oxygen to 100%
• Sa PO2 = 100mmHg
delivery to • In tissues, the PO2<40mmHg, net diffusion of
tissues O2 from plasma into interstitial space,
• Increased release of O2 from Hb (as PO2
decreases from 100mmH to 40mmHg)
• Hb is about 75% saturated on leaving the
systemic capillaries (tissues)
• This saturation varies with strenuous activity
Effect of Carbon Monoxide (CO) on Hb-O2
Association
• CO has very high affinity for the oxygen-binding sites in haemoglobin (210 times
higher than O2).
• It reduces the amount of oxygen that combines with haemoglobin in
pulmonary capillaries by competing for these sites.
• Also alters the haemoglobin molecule so as to shift the oxygen–haemoglobin
dissociation curve to the left, thus decreasing the unloading of oxygen from
haemoglobin in the tissues.
• Common cause of death
Factors affecting Hb Saturation
• Increase in Temp, 2,3-DPG, acidity
• Shift the dissociation curve to the
right
• At any given PO2 , haemoglobin
has less affinity for oxygen.
• Decrease
• Shift the dissociation curve to the
left
• At any given PO2 , haemoglobin
has a greater affinity for oxygen.
https://www.researchgate.net/profile/Sitt_Elnissa_Ahmed/publication/316110270/figure/fig1/AS:48407450777
1907@1492423764760/The-oxygen-dissociation-curve-from-Anaesthesia-UK.png
Videos
• Haemoglobin 1
• Haemoglobin 2
• Oxygen transportation
• Haemoglobin Saturation
• Curve Shifts
• Summary
 • Cell/tissue metabolism generates about 200 mL
of carbon dioxide per minute.
• Carbon dioxide is much more soluble in water
than is oxygen, so blood carries more dissolved
Carbon carbon dioxide than dissolved oxygen.
• Carbon Dioxide transport
Dioxide • 70% is converted to carbonic acid
Transportation • 23% is bound to Hb
• 7% is dissolved (this determines the partial
of CO2)
Carbon Dioxide Transport
• Conversion to bicarbonate and proton is catalysed as a fast reaction by carbonic anhydrase in the red blood cell
• Bicarbonate is exchanged for Cl- (Chloride shift) to maintain electroneutrality
• In the pulmonary circulation, Cl- is exchanged for Bicarbonate and CO2 is reformed
• Expelled down its partial pressure gradiant
• Deoxygenated Hb has a higher affinity for CO2 compared to O2.
• Binding produces carbaminohaemoglobin
• Aided by the fact that deoxyhemoglobin, has a greater affinity for carbon dioxide than does oxyhemoglobin.
• Dissolved CO2
• Maintains the partial pressures of CO2
• The last form to be saturated
• Total blood- carbon dioxide is the sum of CO2 as transported by each of these three processes
Transport of H+ Ions in Blood
• H+ ions determines acidity
• Deoxyhemoglobin has a much greater affinity for H+ than does oxyhemoglobin,
• Deoxyhemoglobin becomes converted to oxyhemoglobin hence, releasing the H+ picked
up in the tissues.
• The H+ reacts with bicarboate to produce carbonic acid, which dissociates to form
carbon dioxide and water.
• Increased arterial H + concentration due to carbon dioxide retention (as in
hypoventilation) is termed respiratory acidosis.
• Hyperventilation would decrease arterial PCO2 and H+ concentration, producing
respiratory alkalosis.
Videos
• Carbon Dioxide Transport
• Carbon Dioxide Transport (Wendy Riggs)
• Summary of Systemic Gas Transport
 Control of Respiration
• Neural Control (Medulla)
• Ventral respiratory group (VRG)
• Dorsal respiratory Group
• Pons (Pontine respiratory Group)
• Pneumotaxic Center
• Apneustic center

By OpenStax College - Anatomy & Physiology, Connexions Web site.

http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0,
Medulla Respiratory Group
• Dorsal Respiratory Group
• Provide input to the spinal motor neurons that activate respiratory muscles
involved in inspiration—the diaphragm and inspiratory intercostal muscles.
• Signals transmitted via the phrenic nerve
•
• Ventral Respiratory Group
• Responsible for the rhythmicity of breathing via pacemaker cells that set the
basal respiratory rate
• Contains expiratory neurons that are activated when large ventilation is
required (strenuous exercise)
Pontine Respiratory Group
• Apneustic centre
• Fine tunes the output of the medullary inspiratory neurons
• Forces inspiration
• Pneumotactic center
• helps to smooth the transition between inspiration and expiration.
• Pulmonary stretch receptors
• Lie in the airway smooth muscle layer and are activated by a large lung
inflation.
• Assist in stopping inspiration (Hering–Breuer reflex).
 Control through
chemoreceptors
• Peripheral Chemoreceptors
• Located at the bifurcation of the common carotid
arteries (carotid bodies) and in the thorax on the
arch of the aorta (aortic bodies)
• The carotid bodies, are strategically located to
monitor oxygen supply to the brain.
• Receptors are stimulated mainly by a decrease in
the arterial PO2 (hypoxia) and an increase in the
arterial H+ concentration (metabolic acidosis) and
increased PCO2 (respiratory acidosis)
• They provide excitatory synaptic input to the
medullary inspiratory neurons.
• The carotid body input is the predominant
peripheral chemoreceptor involved in the control of
respiration.
https://www.researchgate.net/figure/Fig-216-
Locations-of-peripheral-chemoreceptors-
22_fig12_306097538
 Control through
chemoreceptors
• Central Chemoreceptors
• are located in the medulla and provide
excitatory synaptic input to the medullary
inspiratory neurons.
• are stimulated by an increase in the H+
concentration of the brain’s extracellular
fluid.

https://www.researchgate.net/figure/Fig-216-
Locations-of-peripheral-chemoreceptors-
22_fig12_306097538
Videos
• Regulation of respiratory system
• More control of respiration
 Changes in PO2
• Low arterial PO2 (<60mmHg) increases
ventilation via peripheral chemoreceptors
• Activating medullary respiratory neurons
• Smaller changes in PO2 do not activate neural
response due to the Oxy-Hb dissociation curve
• peripheral chemoreceptors are not stimulated
in situations in which modest reductions take
place in the oxygen content of the blood
without changes in arterial PO2
• mild to moderate anaemia, in which arterial
PO2 is usually normal, does not activate
peripheral chemoreceptors and does not
stimulate increased ventilation.
http://jeb.biologists.org/content/204/18/3121
 http://www.gedulah.co.uk/e-
learning/durham/respiratory_medici
ne/images/graph_sm.jpg

Changes in PO2
 • Very small increase in arterial PCO2
causes a marked reflex increase in
ventilation.
• The ability of changes in arterial PCO2
to control ventilation reflexively is
largely due to associated changes in
H+ concentration
• The peripheral chemoreceptors are
stimulated by the increased arterial H+
concentration resulting from the
increased PCO2
• The increase in arterial PCO2 causes a
rapid increase in brain extracellular
fluid PCO2
• Increased PCO2 increases brain
http://www.anaesthesia.med.usyd.edu.au/reso extracellular fluid H+ concentration,
urces/lectures/ventilation_clt/ventilation.html which stimulates the central
chemoreceptors.

Changes in PCO2 • Of the two sets of receptors the

central chemoreceptors are the more
important, accounting for about 70%
of the increased ventilation.
 • Metabolic acidosis
• Occurs in diabetes, renal tubular acidosis, severe
diarrhoea/laxative abuse
• Symptoms include: faster respiratory rate
Metabolic • Metabolic alkalosis

changes on • Primary increase in serum bicarbonate

• Excess vomiting, antacids, laxatives, overuse of
arterial H+ diuretics
• controlled primarily by peripheral chemoreceptors
conc • In acidosis, ventilation is reflexively increased
• In alkalosis, ventilation is reflexively depressed
because of decreased peripheral chemoreceptor
output.
Control of Ventilation During Exercise
• The major stimuli to ventilation during exercise, remain unclear.
• PCO2 stimuli
• Only changes in PCOs of systemic venous blood but not for systemic arterial
blood.
• Arterial PCO2 is determined by alveolar PCO2
• Alveolar PCO2 is determined by the ratio of carbon dioxide production to
alveolar ventilation.
• Alveolar ventilation increases in exact proportion to the increased carbon
dioxide production, so alveolar and therefore arterial PCO2 do not change.
Control of Ventilation During Exercise
• PO2 stimuli
• systemic venous PO2 decreases during exercise due to an increase in oxygen consumption in
the tissues, but alveolar PO2 (increased ventilation) and, therefore, systemic arterial PO2
usually remain unchanged
• Ventilation is not the limiting factor in strenuous exercise—cardiac output is.
• H+ Stimuli
• The arterial PCO2 does not change (as explained above), there is no accumulation of excess H
+ resulting from carbon dioxide accumulation.
• In strenuous exercise, there is an increase in arterial H+ concentration due to the generation
and release of lactic acid into the blood. This change in H 1 concentration is responsible, in
part, for stimulating the hyperventilation accompanying strenuous exercise.
 • Sneeze
• Receptors are in the nose or pharynx;
• Cough
Protective • The receptors are in the larynx, trachea, and
bronchi ;
Reflexes • Alcohol inhibits the cough reflex, which may
partially explain the susceptibility of
alcoholics to choking and pneumonia.
Acclimatisation to High Altitude
• At the top of Mt. Everest the atmospheric pressure is 253 mmHg, compared to
760 mmHg at sea level.
• The inspired PO2 is 53 mmHg (21% of atmospheric pressure)
• The alveolar and arterial PO2 must decrease as persons ascend
• Manifested as altitude sickness
• breathlessness, headache, nausea, vomiting, insomnia, fatigue, and
impairment of mental processes.
 • The peripheral chemoreceptors stimulate ventilation.
• Erythropoietin, stimulates erythrocyte synthesis—
resulting in increased erythrocyte and haemoglobin
concentration in blood—and the oxygen-carrying
capacity of blood.
• DPG increases and shifts the oxygen–hemoglobin
Acclimatisation dissociation curve to the right, facilitating oxygen
unloading in the tissues.
to Altitude • Increases in skeletal muscle capillary density, number of
mitochondria, and muscle myoglobin occur, all of which
increase oxygen transfer.
• Plasma volume can be decreased, resulting in an
increased concentration of the erythrocytes and
hemoglobin in the blood.
Video
• Acclimatisation Mount Everest
 • Forms speech sounds (phonation)
• Defends against microbes
Other • Influences arterial concentrations of chemical
functions of messengers by removing some from pulmonary
capillary blood and producing and adding
the respiratory others to this blood

system • Traps and dissolves blood clots arising from

systemic veins such as those in the legs
•