Henley Beach, South Australia

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ANP 1105A&E
Anthony Krantis, PhD
akrantis@uottawa.ca

The Respiratory System

Lecs 3 & 4
These slides contain material to be presented in lecture*.
The information from the lecture should be used in combination with the
relevant chapters of the recommended Text book(s).
Throughout this presentation, there are references to and use of figures
from the text book. In addition, specific animations/videos
are also referenced and can be used by the student for
study purposes, if they wish.
*Slides marked with a STAR will not be covered in the lecture but are
provided as additional learning material
Slides includes material (direct or modified) from 2013 Pearson Education, Inc. Human Anatomy & Physiology, Ninth Edition and material
supplied by Dr J Carnegie and other sources as referenced

Respiratory System
Respiration
Respiration = the series of exchanges that leads to the
uptake of oxygen by the cells, and the release of carbon
dioxide to the lungs
Step 1 = ventilation
Inspiration & expiration

Step 2 = exchange between alveoli (lungs) and pulmonary

capillaries (blood)
Referred to as External Respiration

Step 3 = transport of gases in blood

Step 4 = exchange between blood and cells
Referred to as Internal Respiration

Cellular respiration = use of oxygen in ATP synthesis

Gas Exchanges Between Blood, Lungs, and Tissues

External respirationdiffusion of gases in lungs
Thickness and surface area of respiratory membrane
Partial pressure gradients and gas solubilities
Ventilation-perfusion coupling

Internal respirationdiffusion of gases at body

tissues
Both involve
Physical properties of gases
Composition of alveolar gas

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Ventilation
External Respiration

Internal Respiration

Basic Properties of Gases:

Dalton's Law of Partial Pressures
Total P exerted by mixture of gases
= sum of pressures exerted by each gas
Partial pressure (PP)
Pressure exerted by each gas in
mixture
Directly proportional to its % in
mixture

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Table 22.4 Comparison of Gas Partial Pressures

and Approximate Percentages in the
Atmosphere and in the Alveoli

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Basic Properties of Gases:

Henry's Law
Gas mixtures in contact with liquid
Each gas dissolves in proportion to its PP
At equilibrium, PPs in two phases will be
equal
Amount of each gas that will dissolve
depends on
Solubility: CO2 20x more soluble in
water than O2; little N2 dissolves in
water
Temperature: as T0 rises, solubility
decreases
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Partial Pressure Gradients and Gas Solubilities

Steep PP gradient for O2 in lungs
Venous blood Po2 = 40 mm Hg
Alveolar Po2 = 104 mm Hg
Drives O2 flow to blood
Equilibrium reached across respiratory
membrane in ~0.25 seconds, about 1/3
time a red blood cell is in pulmonary
capillary
Adequate oxygenation even if blood
flow increases 3X

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Figure 22.18 Oxygenation of blood in the pulmonary capillaries at rest.

PO2 (mm Hg)

150

100

PO2 104 mm Hg
50
40
0

Start of
capillary
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0.25

0.50

Time in the
pulmonary capillary (sec)

0.75
End of
capillary

Partial Pressure Gradients and Gas Solubilities

PP gradient for CO2 in lungs less steep
Venous blood Pco2 = 45 mm Hg
Alveolar Pco2 = 40 mm Hg
However CO2 diffuses in equal amounts with
oxygen
CO2 is 20X more soluble in plasma than O2

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Ventilation-Perfusion Coupling
Perfusion- blood flow reaching alveoli
Ventilation- amount of gas reaching alveoli
Ventilation and Perfusion matched
(coupled) for efficient gas exchange
Never balanced for all alveoli due to
Regional variations due to effect of
gravity on blood and air flow
Some alveolar ducts plugged with
mucus

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Ventilation-Perfusion Coupling
Perfusion
Changes in gasses in alveoli cause changes in
diameters of arterioles
Where alveolar O2 is high, arterioles - dilate
Where alveolar O2 is low, arterioles - constrict
Directs most blood where alveolar oxygen high
Where alveolar CO2 is high, bronchioles - dilate
Where alveolar CO2 is low, bronchioles - constrict
Allows elimination of CO2 more rapidly

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Figure 22.19 Ventilation-perfusion coupling

Ventilation less than perfusion

Mismatch of ventilation and perfusion

ventilation and/or perfusion of alveoli
causes local P CO and P O
2

O2 autoregulates
arteriolar diameter

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Ventilation greater than perfusion

Mismatch of ventilation and perfusion

ventilation and/or perfusion of alveoli
causes local P CO and P O
2

O2 autoregulates
arteriolar diameter

Pulmonary arterioles
serving these alveoli
constricts

Pulmonary arterioles
serving these alveoli
dilate

Match of ventilation
and perfusion
ventilation, perfusion

Match of ventilation
and perfusion
ventilation, perfusion

Internal Respiration
Capillary gas exchange in body tissues
Partial pressures and diffusion gradients reversed
compared to external respiration
Tissue Po2 always lower than in systemic
arterial blood O2 from blood to tissues
CO2 from tissues to blood
Venous blood Po2 40 mm Hg and Pco2
45 mm Hg

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Figure 22.17 Partial

pressure gradients
promoting gas
movements in the
body.

Inspired air:
PO 160 mm Hg
2
PCO2 0.3 mm Hg

Alveoli of lungs:
PO2 104 mm Hg
PCO2 40 mm Hg

External
respiration
Pulmonary
arteries

Alveoli

Pulmonary
veins (PO
2
100 mm Hg)

Blood leaving
lungs and
entering tissue
capillaries:
PO2 100 mm Hg
PCO2 40 mm Hg

Blood leaving
tissues and
entering lungs:
PO2 40 mm Hg
PCO2 45 mm Hg

Heart

Systemic
veins

Systemic
arteries

Internal
respiration

Tissues:
PO2 less than 40 mm Hg
PCO2 greater than 45 mm Hg
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O2 Transport in Blood
Molecular O2 carried in blood
1.5% dissolved in plasma
98.5% loosely bound to each Fe of hemoglobin (Hb)
in RBCs
Maximum 4 O2 per Hb = Oxyhemoglobin (HbO2)

Reduced Hb

(has released its O2 )

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O2 and Hemoglobin
Rate of loading and unloading of O2 regulated to
ensure adequate oxygen delivery to cells
Po2
Temperature
Blood pH
Pco2
Concentration of BPG1,3bisphosphoglycerate, metabolite of glycolysis
in RBCs; levels rise when oxygen levels
chronically low promotes the release of the remaining
oxygen molecules bound to the
hemoglobin, thus enhancing the ability of
RBCs to release oxygen near tissues that
need it most.
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Figure 22.20 The amount of oxygen carried by hemoglobin depends on the PO2 (the amount of oxygen) available
locally.

This axis tells you how much

O2 is bound to Hb. At 100%,
each Hb molecule has 4 bound
oxygen molecules.

In the lungs, where PO2 is

high (100 mm Hg), Hb is
almost fully saturated
(98%) with O2.

Hemoglobin

100

Percent O2 saturation of hemoglobin

Oxygen

If more O2 is present,
more O2 is bound.
However, because of
Hbs properties (O2
binding strength
changes with
saturation), this is an
S-shaped curve, not a
straight line.

80

60

40

20

0
0

20

40

60

80

100

PO2 (mm Hg)

This axis tells you the relative

Amount (partial pressure) of
O2 disslolved in the fluid
Surrounding the Hb.

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In the tissues of other organs,

where PO2 is low (40 mm Hg), Hb
is less saturated (75%) with O2.

Influence of Po2 on Hemoglobin Saturation

Arterial blood
Po2 = 100 mm Hg
Contains 20 ml oxygen per 100 ml blood
(20 vol %)
Hb is 98% saturated
Further increases in Po2 (e.g., breathing deeply) produce minimal
increases in O2 binding
Venous blood
Po2 = 40 mm Hg
Contains 15 vol % oxygen
Hb is 75% saturated
Venous reserve
Oxygen remaining in venous blood

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Figure 22.20 The amount of oxygen carried by hemoglobin depends on the PO2 (amount of oxygen) available locally

In the lungs

At sea level, there is lots of O2.

At a PO2 in the lungs of 100 mm Hg,
Hb is 98% saturated.

Percent O2 saturation of hemoglobin

100

98%

80

60

40

20

20

40
60
PO2 (mm Hg)

80

100

At high PO2, large changes in PO2 cause only

small changes in Hb saturation. Notice that the
curve is relatively flat here. Hbs properties
produce a safety margin that ensures that Hb is
almost fully saturated even with a substantial PO2
decrease. As a result, Hb remains saturated even
at high altitude or with lung disease.

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95%
At high altitude, there is less O2.
At a PO2 in the lungs of only 80
mm Hg, Hb is still 95% saturated.

Percent O2 saturation of hemoglobin

100

Figure 22.21 Effect of

temperature, PCO2, and blood pH
on the oxygen-hemoglobin
dissociation curve.

10C
20C

80

38C
43C

60

40

Normal body
temperature

20

Percent O2 saturation of hemoglobin

(a)

100

Decreased carbon dioxide

(PCO2 20 mm Hg) or H+ (pH 7.6)

80
Normal arterial
carbon dioxide
(PCO2 40 mm Hg)
or H+ (pH 7.4)

60

40

Increased carbon dioxide

(PCO2 80 mm Hg)
or H+ (pH 7.2)

20
0

20

40
60
80
PO (mm Hg)
2

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(b)

100

Factors that Increase Release of O2 by Hemoglobin

As cells metabolize glucose and use O2
As Pco2 and H+ increase in capillary blood
Bohr effect - Hb-O2 bond weakens oxygen
unloading where needed most
As Heat production increases directly and
indirectly decreases Hb affinity for O2
increased oxygen unloading to active tissues

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Homeostatic Imbalance
Hypoxia
Inadequate O2 delivery to tissues cyanosis
Anemic hypoxiatoo few RBCs; abnormal or too
little Hb
Ischemic hypoxiaimpaired/blocked circulation
Histotoxic hypoxiacells unable to use O2, as in
metabolic poisons
Hypoxemic hypoxiaabnormal ventilation;
pulmonary disease
Carbon monoxide poisoningespecially from fire;
200X greater affinity for Hb than oxygen

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CO2 Transport in blood

CO2 transported in three forms
7 to 10% dissolved in plasma
20% bound to globin of hemoglobin
(carbaminohemoglobin)
70% transported as bicarbonate ions (HCO3) in
plasma

Occurs primarily in RBCs and is very fast

In plasma this reaction is slow
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Haldane Effect: Property of Hemoglobin(Hb)

De-oxygenation of blood increases its ability to carry CO2
Reduced Hb (less O2 saturation) forms
carbaminohemoglobin and buffers H+ more easily
Lower Po2 and Hb saturation with O2; more CO2
carried in blood
Encourages CO2 exchange in tissues and lungs
As more CO2 enters blood, more O2 dissociates from
hemoglobin (Bohr effect)
As HbO2 releases O2, it more readily forms bonds with
CO2 to form carbaminohemoglobin

Bohr Effect: hemoglobin's oxygen binding affinity is inversely related both

to acidity and to the concentration of carbon dioxide.

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Figure 22.22a Transport and exchange of CO2 and O2.

Tissue cell

Interstitial fluid
(dissolved in plasma)
Slow

Binds to
plasma
proteins

Fast

Chloride
shift
(in) via
transport
protein

Carbonic
anhydrase
(Carbaminohemoglobin)
Red blood cell

(dissolved in plasma)

Oxygen release and carbon dioxide pickup at the tissues

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Blood plasma

Influence of CO2 on Blood pH

Carbonic acidbicarbonate system buffers blood pH
If H+ concentration in blood rises, excess H+ is
removed by combining with HCO3 H2CO3
If H+ concentration begins to drop, H2CO3
dissociates, releasing H+
HCO3 is the alkaline reserve of carbonic acidbicarbonate buffer system

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Influence of CO2 on Blood pH

Respiratory rate & depth affect blood pH
Slow, shallow breathing increased CO2 in
blood drop in pH
Rapid, deep breathing decreased CO2 in
blood rise in pH
Changes in ventilation can adjust pH when
disturbed by metabolic factors

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Influence of CO2 on Blood pH

www.lionden.com

North Glenelg Beach, South Australia

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Control of Respiration
Involves brain centers, chemoreceptors, and other reflexes
Brain control
Reticular formation of Medulla and Pons
Pons neurons Influence and modify activity of VRG neurons
Smooth out transition between inspiration and expiration
Modify and fine-tune breathing rhythms during vocalization,
sleep, exercise
Clustered neurons in medulla important
Ventral respiratory group
Dorsal respiratory group

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Medullary Respiratory Centers

Ventral respiratory group (VRG)
Rhythm-generating & integrative center
Sets eupnea normal breathing (1215 breaths/min)
Its inspiratory neurons excite inspiratory muscles via phrenic
(diaphragm) and intercostal nerves (external intercostals)
Expiratory neurons inhibit inspiratory neurons

Dorsal respiratory group (DRG)

Near root of cranial nerve IX
Integrates input from peripheral stretch
and chemoreceptors; sends information
VRG

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Figure 22.23 Locations of

respiratory centers and their
postulated connections.
Pontine respiratory centers

Pons
Medulla

interact with medullary

respiratory centers to smooth
the respiratory pattern.

Ventral respiratory group (VRG)

contains rhythm generators
whose output drives respiration.
Pons
Medulla
Dorsal respiratory group (DRG)
integrates peripheral sensory
input and modifies the rhythms
generated by the VRG.
To inspiratory
muscles

External
intercostal
muscles
Diaphragm
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Factors influencing Breathing Rate and Depth

Depth = how actively the respiratory center stimulates
respiratory muscles
Rate = duration of inspiratory center activity
Both modified in response to changing body demands
Most important are changing levels of CO2, O2, and H+
Sensed by central and peripheral chemoreceptors
Hyperventilation- depth & rate of breathing that
exceeds body's need to remove CO2
decreases blood CO2 levels (hypocapnia)
cerebral vasoconstriction and cerebral
ischemia dizziness, fainting
Apnea breathing cessation from abnormally low
Pco2
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Chemical Factors
Rising CO2 levels most powerful respiratory stimulant
If blood Pco2 rises (hypercapnia), CO2
accumulates in brain
CO2 in brain hydrated to carbonic acid
dissociates, releasing H+ pH drops
H+ stimulates chemoreceptors of brain stem
Chemoreceptors synapse with respiratory
regulatory centers increased depth and rate
of breathing lower blood Pco2 pH rises

Normally blood Po2 affects breathing only indirectly by influencing

peripheral chemoreceptor sensitivity to changes in Pco2
But when arterial Po2 <60 mm Hg, it becomes major stimulus for
respiration (via peripheral chemoreceptors)

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Chemical Factors
Influence of Po2
Peripheral chemoreceptors in
aortic & carotid bodies sense
arterial O2 level
When stimulated, cause
respiratory centers to increase
ventilation
Declining Po2 normally slight
effect on ventilation
Huge O2 reservoir bound to
Hb
Requires substantial drop in
arterial Po2 (to 60 mm Hg)
to stimulate increased
ventilation

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Chemical Factors
Influence of arterial pH
Can modify respiratory rate & rhythm even if CO2 &
O2 levels normal
Involves peripheral chemoreceptors
Decreased pH may reflect
CO2 retention; accumulation of lactic acid; excess
ketone bodies
Respiratory system controls attempt to raise pH by
increasing respiratory rate and depth

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Inflation Reflex
Hering-Breuer Reflex (inflation reflex)
Stretch receptors in pleurae and airways
stimulated by lung inflation
- Inhibitory signals to medullary respiratory
centers end inhalation and allow expiration
- Acts as protective response more than
normal regulatory mechanism

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Figure 22.24 Neural and chemical influences on brain stem respiratory centers.

Higher brain centers

(cerebral cortexvoluntary
control over breathing)
-breath holding in anger
-gasping with pain
-rise in body temperature

Other receptors (e.g., pain)

and emotional stimuli acting
through the hypothalamus
+

Peripheral
chemoreceptors

Respiratory centers
(medulla and pons)

+
+

Central
chemoreceptors

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Stretch receptors
in lungs

Receptors in
muscles and joints

Irritant
receptors

Respiratory Adjustments: Exercise

Adjustments geared to intensity & duration of exercise
Hyperpnea
Increased ventilation (10 - 20 fold) in response to
metabolic needs
Pco2, Po2, and pH remain surprisingly constant during
exercise
Three neural factors increase ventilation as exercise begins
- Psychological stimuli anticipation of exercise
- Simultaneous cortical motor activation of skeletal muscles
and respiratory centers
Excitatory impulses to respiratory centers from
proprioceptors in moving muscles, tendons, joints

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Respiratory Adjustments: Exercise

Ventilation declines suddenly as exercise ends
because the three neural factors shut off
Gradual decline to baseline because of decline
in CO2 flow after exercise ends
Exercise anaerobic respiration lactic acid
Not from poor respiratory function; from
insufficient cardiac output or skeletal muscle
inability to increase oxygen uptake

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High Altitude
Quick move to > 2400m (8000 ft) acute
mountain sickness (AMS)
Atmos P and Po2 levels lower
Headaches, shortness of breath, nausea,
dizziness
Possible, lethal cerebral & pulmonary
edema

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Acclimatization to High Altitude

Respiratory & hematopoietic adjustments occur
Chemoreceptors more responsive to Pco2 when Po2
declines
Lower Po2 directly stimulates peripheral
chemoreceptors
Ventilation increases to 23 L/min higher than sea
level
Always lower-than-normal Hb saturation levels
Less O2 available
Decline in blood O2 stimulates kidneys to accelerate
production of EPO
RBC numbers increase slowly to provide long-term
compensation

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Chronic Obstructive Pulmonary Disease (COPD)

Exemplified by chronic bronchitis & emphysema
Irreversible decrease in ability to force air out of lungs
Common features
History of smoking in 80% of patients
Dyspnea - labored breathing ("air hunger")
Coughing & frequent pulmonary infections
Most develop respiratory failure (hypoventilation)
accompanied by respiratory acidosis, hypoxemia
Treated with bronchodilators, corticosteroids, oxygen,
sometimes surgery
normal

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emphysema

Figure 22.27 The

pathogenesis of COPD

Tobacco smoke
Air pollution

Continual bronchial
irritation and inflammation

Chronic bronchitis
Excess mucus production
Chronic productive cough

Breakdown of elastin in
connective tissue of lungs

Emphysema
Destruction of alveolar
walls
Loss of lung elasticity

Airway obstruction
or air trapping
Dyspnea
Frequent infections

Hypoventilation
Hypoxemia
Respiratory acidosis
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-1 antitrypsin
deficiency

Asthma: Reversible COPD

Characterized by coughing, dyspnea, wheezing, and
chest tightness
Active inflammation of airways precedes bronchospasms
Inflammation is immune response due to release of
interleukins, production of IgE, and recruitment of
inflammatory cells
Airways thickened with inflammatory exudate magnify
effect of bronchospasms

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Tuberculosis (TB)
Infectious disease caused by bacterium
Mycobacterium tuberculosis
Symptoms-fever, night sweats, weight loss,
racking cough, coughing up blood
Treatment- 12-month course of antibiotics

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Cystic fibrosis
Most common lethal genetic disease in North
America
Abnormal, viscous mucus clogs passageways
bacterial infections
Affects lungs, pancreatic ducts, reproductive
ducts
Causeabnormal gene for Cl- membrane
channel

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