Human Anatomy and

Physiology II

Respiratory Physiology
Suggested Readings
McKinley Text
Chapter 23 – Respiratory system
• Sections 23.5 – 23.9

Tortora Text
Chapter 23 – Respiratory system
• Sectio s 23.4 - 23.9
Functions of the Respiratory
System
Gas Exchange
Acid-Base balance
Thermoregulation
Immune function
Vocalization
Enhances venous return
Air Passages
Mouth / Nose
Pharynx
Larynx
Trachea
Bronchi
Bronchioles
alveoli
 Bronchioles
Bronchoconstrict or dilate
Control air flow
Smooth muscle

Alveoli
Alveolar duct

Respiratory Alveolar duct

bronchioles
Terminal Alveolar
bronchiole sac

(a)
 Alveoli
Site of Gas Exchange
Thin-walled
Large surface area for diffusion (75 m2)
Terminal bronchiole
Respiratory bronchiole

Smooth
muscle
Elastic
fibres
Alveolus

Capillaries
Alveoli
contain fine elastic fibres
Pores of Kohn connect adjacent alveoli
Helps equalize air pressure
Red blood
cell

Alveolar pores
Capillary
O2 Capillary
Type I cell CO2
Macrophage Alveolus
Alveolus Endothelial cell
Alveolar
epithelium

Respiratory
capillary membrane
Alveoli Type II cell Capillary
endothelium
Alveoli
Type I Alveolar cells
Make up the wall
Type II cells
Secrete surfactant
• ↓ surface tension
Macrophages
Immune function
Respiration
Ventilation
External Respiration
Gas exchange between alveoli and blood
Gas Transport
Internal Respiration
Gas exchange between blood and tissues
Mechanics of Breathing
Two phases
Inspiration
• gases flow into the lungs
Expiration
• gases exit the lungs

Dependent on pressure differences

 Pressure Relationships in the
Thoracic Cavity
Atmospheric (air) pressure (Patm)
760 mm Hg at sea level

Respiratory pressures
are relative to Patm
Alveolar pressure
Pleural pressure
 Respiratory mechanics:
Pressures:
• Atmospheric pressure
• air
• Intra-alveolar pressure
• in alveoli
• Intra-pleural pressure
• Pleural space
• Transpulmonary pressure
• difference

13
 Pulmonary Ventilation
Mechanical processes depend on volume
changes in the thoracic cavity
Volume changes  pressure changes
Pressure changes  gases flow to equalize
pressure
Respiratory Mechanics
Boyle’s law :
the pressure exerted by a gas varies inversely with the volume of a gas (if volume ↑, then
pressure ↓)

Boyle’s Law
 Respiratory mechanics:
Demonstration of recoil forces of lung and chest wall:
Pneumothorax

16
Anatomy of the Respiratory
Muscles
 Quiet Inspiration

Inspiratory muscles contract

Diaphragm and external intercostals
Thoracic volume ↑
Lungs stretch
Intrapulmonary pressure ↓
Air flows into the lungs
• down its pressure gradient, until Ppul = Patm
Respiratory Muscle Activity During Inspiration
Forced Inspiration
Recruit Scalenus and sternocleidomastoid
Greater ↑ in thoracic volume
Larger ↓ in thoracic pressure

Larger pressure gradient

More air flow in
Quiet Expiration
Passive process
Inspiratory muscles relax
Thoracic cavity volume decreases
• Elastic lungs recoil
increase in alveolar pressure
Air flows out of the lungs
Respiratory Muscle Activity During Expiration
Forced Expiration
Recruit Abdominals and
internal intercostals
Larger decrease in thoracic
volume
• Larger increase in thoracic
pressure
Larger gradient
• More air flow out
Control of Ventilation
Involves
Chemoreceptors
monitoring blood gases

Inputs to neurons in the

reticular formation of
the medulla and pons
Control of Ventilation
Respiratory centres in brain stem establish a rhythmic
breathing pattern

Medullary respiratory centre

• Dorsal respiratory group (DRG)
 Mostly inspiratory neurons
• Ventral respiratory group (VRG)
 Inspiratory neurons
 Expiratory neurons
• Receive input from
chemoreceptors
Control of Ventilation
Pre-Bötzinger complex
• Generates respiratory rhythm
Apneustic centre
• Prevents inspiratory neurons from
being switched off
 Provides extra boost to inspiratory
drive
Pneumotaxic centre
• Sends impulses to DRG that help
“switch off” inspiratory neurons
 Dominates over apneustic centre
Peripheral Chemoreceptors
Carotid bodies are located in the carotid sinus
Aortic bodies are located in the aortic arch

Monitors blood
Respond to
↑ H, ↑ CO2, or
↓↓↓ O2
Carbon Dioxide and H+
CO2 and water combine in the body to
make carbonic acid
If CO2 increases, so does H+
Affect pH of the body
Central Chemoreceptors
In Medulla (respiratory centre)
Monitors cerebrospinal fluid
Sensitive to changes in ↑ H+, via ↑ CO2
 Arterial PCO2

P CO2 decreases pH in
brain extracellular
fluid (ECF)

Central chemoreceptors Peripheral chemoreceptors

in medulla respond to H+ in carotid and aortic bodies
in brain ECF (mediate 70% (mediate 30% of the CO2
of the CO2 response) response)
Afferent impulses

Medullary
respiratory centres
Efferent impulses
Respiratory muscle

Ventilation
(more CO2 exhaled)
Initial stimulus
Physiological response Arterial P CO2 and pH
Result return to normal

Figure 22.25
Trigger for Inspiration
↑ metabolism leads to ↑ CO2 and ↓ O2
↑ CO2 converts to ↑ H+
CO2 and H+ in blood triggers peripheral chemoreceptors
CO2 crosses blood-brain barrier and converts to H+, which
triggers central chemoreceptors

Input goes to Respiratory Centre

Triggers inspiratory neurons
Inspiratory muscles contract for inspiration

31
Role of Oxygen

O2 is NOT a significant
factor in normal control
of breathing

BUT - if O2 levels drop

below 60 mmHg – then
it does become a factor
Eg. High altitude
Depth and Rate of Breathing
Hyperventilation
increased depth and rate of breathing
High removal of CO2
Causes CO2 levels to decline (hypocapnia)
• Lose “trigger” for inspiration
 Longer breath holds possible
• May cause cerebral vasoconstriction and cerebral
ischemia
Summary of Chemical Factors
↑ CO2 is the most powerful respiratory
stimulant
If arterial Po2 < 60 mm Hg, it becomes the
major stimulus
Eg. High altitude
↑ arterial H+ (eg. Lactic acid) also act as a
respiratory stimulant
Influence of Higher Brain centres
Hypothalamus / limbic system
modify rate and depth of respiration
Example: breath holding that occurs in anger or
gasping with pain

↑ body temperature acts to ↑ respiratory rate

Cortical controls bypass medullary controls

Example: voluntary breath holding
Control of Respiration - Reflexes
Hering-Breuer reflex
Stretch receptors triggered to prevent overinflation of the lungs
• Signals the end of inhalation and allow expiration to occur
• Protective response
Pulmonary Irritant Reflex
Receptors in the bronchioles respond to irritants
• Reflex constriction of air passages
• eg. Asthma, allergies
Receptors in the larger airways mediate the cough and sneeze
reflexes
Nonrespiratory Air Movements
Most result from reflex action
Examples include:
Cough
Sneeze
Crying
Laughing
Hiccups
yawns
 Higher brain centres
(cerebral cortex—voluntary
control over breathing)
Other receptors (e.g., pain) +
and emotional stimuli acting –
through the hypothalamus
+
Respiratory centres
–
(medulla and pons)

Peripheral
+
chemoreceptors
O2 , CO2 , H+ + – Stretch receptors
in lungs
Central
Chemoreceptors –
CO2 , H+ + Irritant
receptors
Receptors in
muscles and joints

Figure 22.24
Respiratory Adjustments: Exercise
Increased CO2 production and O2 consumption
Larger gradients for gas exchange
Faster / greater diffusion

Other factors that contribute to higher breathing

Psychological - anticipation of exercise
• Cortical activation of muscles and respiratory centre
Sensory feedback from muscles
Higher body temperature
Higher blood lactic acid and CO2 levels
Higher epinephrine
 Physical Factors Influencing
Pulmonary Ventilation
Four factors
Airway resistance
Alveolar surface tension
Lung compliance
Elastic Recoil
Airway Resistance
Relationship between flow (F), pressure (P), and
resistance (R):
F = P
R

 Radius of bronchioles is the biggest determinant

 P - pressure gradient between atmosphere and

alveoli
Airway Resistance

Asthma
Severe constriction or
obstruction of bronchioles
• Prevents ventilation

Epinephrine dilates bronchioles and reduces

air resistance
Eg. exercise
Eg. Epi pen with allergy response
Alveolar Surface Tension
Surface tension
Attracts liquid molecules to one another at a
gas-liquid interface
Resists any force that tends to increase the
surface area of the liquid
Alveolar Surface Tension
Surfactant
Detergent-like lipid and protein complex produced
by type II alveolar cells
↓ surface tension of alveolar fluid
• discourages alveolar collapse

Premature infants
• ↓ surfactant
• respiratory distress
Lung Compliance
Expandability of the lungs
change in lung volume with a given change in
pressure
Relates to effort required to distend the lungs

Normally high due to

Distensibility of the lung tissue (connective tissue)
Alveolar surface surfactant
Lung Compliance
Diminished by
Nonelastic scar tissue (fibrosis)
Reduced production of surfactant
Decreased flexibility of the thoracic cage
• eg. Paralysis of respiratory muscles
Elastic Recoil
How the lungs rebound after being stretched
Help lungs return to their pre-inspiratory volume
Depends on two factors
Connective tissue in the lungs
• Elastin / Collagen
Alveolar surface tension
• Increases tendency of alveoli to recoil
Respiratory Volumes
Used to assess a person’s respiratory status
Lung Volumes and Capacities
Description Average
Value
Tidal volume (TV) Volume of air entering or leaving lungs 500 ml
during a single breath
Inspiratory reserve Extra volume of air that can be maximally 3000 ml
volume (IRV) inspired over and above the typical resting
tidal volume

Inspiratory capacity Maximum volume of air that can be 3500 ml

(IC) inspired at the end of a normal quiet
expiration (IC =IRV + IV)

Expiratory reserve Extra volume of air that can be actively 1000 ml

volume (ERV) expired by maximal contraction beyond the
normal volume of air after a resting tidal
volume
Residual volume Minimum volume of air remaining in the 1200 ml
(RV) lungs even after a maximal expiration

Chapter 13 The Respiratory System

Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Lung Volumes and Capacities
Description Average Value

Functional residual Volume of air in lungs at end of 2200 ml

capacity (FRC) normal passive expiration
(FRC = ERV + RV)

Vital capacity (VC) Maximum volume of air that can be 4500 ml

moved out during a single breath
following a maximal inspiration (VC
= IRV + TV + ERV)
Total lung capacity (TLC) Maximum volume of air that the 5700 ml
lungs can hold (TLC = VC + RV)

Forced expiratory Volume of air that can be expired

volume in one second during the first second of expiration
(FEV1) in a VC determination

Chapter 13 The Respiratory System

Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Spirogram
Lung Volumes to remember
Tidal Volume – air moved on a quiet breath
Usually about 500 mL
Vital Capacity
Maximum air you can move - ~ 5 or 6 L
Reserve volumes – extra air that can be added to
either inspiration or expiration if the breath is
deeper
• Inspiratory – 3L, Expiratory – 1 L
Residual Volume – air left in lungs - ~1200 mL
Dead Space
inspired air that doesn’t contribute to gas
exchange

Anatomical dead space

volume of air passageways (~150 ml)
Alveolar dead space
alveoli with no gas exchange due to collapse or
obstruction
 Pulmonary Function Tests
Minute ventilation
total amount of gas flow into or out of
the respiratory tract in one minute
Forced vital capacity (FVC)
gas forcibly expelled after taking a deep
breath
Forced expiratory volume (FEV)
the amount of gas expelled during
specific time intervals of the FVC
Obstructive Disease
High compliance
Low recoil
Difficult to breathe out
• Less “fresh air” each breath
Easier to breathe in

Eg. Emphysema, Asthma

Chronic bronchitis
Emphysema
Primarily caused by
smoking

Break-down of collagen/elastin in septal walls

Loss of lung recoil
Harder to breath out (over-inflated)
Increased tar and mucous production
Decreased surface area for gas exchange
Greater diffusion distance – less O2 exchange
Patients are bluish, fatigued, out of breath
Emphysema
Emphysema
Chronic Bronchitis
Response to chronic irritants
Smoking or pollutants

Inflamed airways
High production of mucous
Decreases airway diameter
Harder to move air
Irritants trigger cough reflex and bronchoconstriction
 • Tobacco smoke -1 antitrypsin
• Air pollution deficiency

Continual bronchial Breakdown of elastin in

irritation and inflammation connective tissue of lungs

Chronic bronchitis Emphysema

Bronchial edema, Destruction of alveolar
chronic productive cough, walls, loss of lung
bronchospasm elasticity, air trapping

• Airway obstruction
or air trapping
• Dyspnea
• Frequent infections

• Abnormal ventilation-
perfusion ratio
• Hypoxemia
• Hypoventilation

Figure 22.27
Restrictive Disease
Low compliance, high recoil
Eg, Fibrosis - Increased fibroids
Hard to breathe in, easy to breathe out
Hard to hold air in long enough for gas
exchange
Restrictive Disease
Eg. Asbestos exposure
Increased fibroids
More collagen
Lungs become stiffer
Inflammation and scarring

Can also lead to mesothelioma

Gas exchange
• Exchange oxygen and CO2 between the
alveolar air and blood and tissues
•External respiration (alveoli to blood)
•Internal respiration (blood to tissues)

•Gas exchange is by simple diffusion

•Need a concentration (partial pressure) gradient
•gas will move from higher partial pressure
lower partial pressure
Basic Properties of Gases:
Dalton’s Law of Partial Pressures
The partial pressure of each gas is directly
proportional to its percentage in the mixture
Partial Pressures
•Fraction of a gas in an atmosphere x the
atmospheric pressure (or barometric pressure).

•Fraction of oxygen in air = 21%

•Fraction of nitrogen in air = 79%
•Carbon dioxide and other gases are less than 1%
of the air
Gas exchange

If atmospheric pressure at sea level is 760 mmHg then:

Partial pressure of oxygen is

0.21 x 760 = 160 mm Hg in dry air

Partial pressure of nitrogen is

0.79 x 760 = 600 mm Hg in dry air

Since 0.03% of air is CO2, partial pressure of CO2 =

0.23 mmHg in dry air
Gas exchange
•Fraction of O2, CO2, and N2 is the same in air at any
altitude .
•In Calgary, 21% of air is oxygen and at the top of Mt.
Everest it is also 21%

•Partial pressure of O2 is different at these locales

because the atmospheric pressure is much different:
•In Vancouver(sea level), bp = 760 mm Hg x 0.21 = 160 mm
Hg in dry air
•In Calgary(1,048 m), bp = 670 mm Hg x 0.21 = 140 mm Hg
in dry air
•At top of Everest (8,848 m) the bp = 253 mm Hg x 0.21 = 53
mm Hg in dry air
Composition of Alveolar Gas
Alveoli contain more CO2 and water vapour
than atmospheric air, due to
Gas exchanges in the lungs
Humidification of air
Mixing of alveolar gas that occurs with each breath
• Tidal volume is 500 mL
• Residual volume is 1200 mL
Table 22.4
Oxygen and Carbon Dioxide Exchange Across Pulmonary and Systemic
Capillaries Caused by Partial Pressure Gradients
External Respiration
Exchange of O2 and CO2 across the
respiratory membrane
Influenced by
Partial pressure gradients and gas solubilities
Ventilation-perfusion coupling
Structural characteristics of the respiratory
membrane
Diffusion
Depends on
Concentration gradient
Diffusion distance
Solubility
Surface area
• alveoli
 Gas exchange process:
Rate of gas transfer across the alveoli is governed by
Fick’s law of diffusion:

Where: K = diffusion coefficient (constant) for a gas, A =

surface area available for exchange, D = thickness of barrier,
P2-P1 = partial pressure gradient for gas
Thickness and Surface Area of
the Respiratory Membrane
Respiratory membranes
0.5 to 1 m thick
Large total surface area (40 X that of skin)
Thicken if lungs become waterlogged
(edema), and gas exchange ↓
↓ surface area with emphysema
walls of adjacent alveoli break down
Partial Pressure Gradients
Partial pressure gradient for O2 in lungs is steep
Venous blood Po2 = 40 mm Hg
Alveolar Po2 = 104 mm Hg
• O2 partial pressures reach equilibrium of 104 mm Hg in
~0.25 seconds, about 1/3 the time a red blood cell is in a
pulmonary capillary

P 104 mm Hg
O2

Time in the
Start of pulmonary capillary (s) End of
capillary capillary
Partial Pressure Gradients and
Gas Solubilities
Partial pressure gradient for CO2 in the lungs
is less steep:
Venous blood Pco2 = 46 mm Hg
Alveolar Pco2 = 40 mm Hg
BUT CO2 is 20 times more soluble in
plasma than oxygen
CO2 diffuses in equal amounts with oxygen
Internal Respiration
Capillary gas exchange in body tissues
Partial pressures and diffusion gradients are
reversed compared to external respiration
Po2 in tissue is always lower than in systemic
arterial blood
Po2 of venous blood is 40 mm Hg and Pco2 is
45 mm Hg
Oxygen and Carbon Dioxide Exchange Across Pulmonary and Systemic
Capillaries Caused by Partial Pressure Gradients
Ventilation-Perfusion Coupling
Ventilation: amount of gas reaching the
alveoli
Perfusion: blood flow reaching the alveoli
Ventilation and perfusion must be matched
(coupled) for efficient gas exchange
 Mismatch of ventilation and O2
Pulmonary arterioles Match of ventilation
perfusion ventilation and/or autoregulates
serving these alveoli and perfusion
perfusion of alveoli causes local arteriole ventilation, perfusion
CO2 P O2and P constrict
diameter

(a)

Mismatch of ventilation and O2

Pulmonary arterioles Match of ventilation
perfusion ventilation and/or autoregulates
serving these alveoli and perfusion
perfusion of alveoli causes local arteriole ventilation, perfusion
CO2 P O2and P dilate
diameter

(b)

Figure 22.19
Ventilation-Perfusion Coupling
Carbon Dioxide - Bronchioles
↑ CO2 causes bronchiole dilation
↓ CO2 causes bronchoconstriction

Oxygen – Alveoli
↑ O2 causes vasodilation
↓ O2 causes vasoconstriction
Ventilation/perfusion matching:

83
Ventilation/perfusion matching:

84
O2 Transport in Blood
Molecular O2 is carried in the blood
1.5% dissolved in plasma
98.5% loosely bound to each Fe of hemoglobin
(Hb) in RBCs
4 O2 per Hb
 Gas Transport
Most oxygen in the blood is transported
bound to hemoglobin.
Hb + O2 ↔ HbO2
(reduced hemoglobin or (oxyhemoglobin)

deoxyhemoglobin)
Gas Transport: oxygen
At level of gas exchange surface (where the PO2 is 100 mmHg) –
Hb quickly becomes saturated with oxygen -

87
Gas Transport: oxygen
At the level of the tissue (where the PO2 is 30-40 mmHg) – Hb
unloads 25-30% of its oxygen – which diffuses into tissue:

88
O2 and Hemoglobin
Rate of loading and unloading of O 2 is
regulated by
Po2
Temperature
Blood pH
Pco2
Concentration of DPG (*)
Factors Affecting the Affinity of
Hb for O2
Eg. Exercise

Copyright © 2014 John Wiley & Sons, Inc.

All rights reserved.
Factors Affecting the Affinity of
Hb for O2

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
Factors Affecting the Affinity of
Hb for O2

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
Hypoxia
Inadequate O2 delivery to tissues
Due to a variety of causes
• Not enough oxygen (eg. High altitude)
• Too few RBCs
• Abnormal or too little Hb
• Blocked or poor circulation
• Metabolic poisons
• Pulmonary disease
• Carbon monoxide
Carbon Monoxide Poisoning
CO has 200x the affinity for Hb
Binds Hb and doesn’t let go
Blocks sites from oxygen
CO2 Transport
CO2 is transported in the blood in three
forms
7 to 10% dissolved in plasma
20% bound to globin of hemoglobin
(carbaminohemoglobin)
70% transported as bicarbonate ions (HCO3–) in
plasma
 Transport and Exchange of CO2
CO2 combines with water to form carbonic
acid (H2CO3), which quickly dissociates:
CO2 + H2O  H2CO3  H+ + HCO3–

Carbon Water Carbonic Hydrogen Bicarbonate ion

dioxide acid ion
 Tissue cell Interstitial fluid
CO2 CO2 (dissolved in plasma)
Binds to
Slow plasma
CO2 CO2 + H2O H2CO3 HCO3– + H+
CO2 HCO3– proteins
Chloride
Fast Cl–
CO2 CO2 + H2O H2CO3 HCO3– + H+ shift
Carbonic Cl– (in) via
CO2
anhydrase HHb transport
CO2 CO2 + Hb HbCO2 (Carbamino- protein
hemoglobin)
Red blood cell HbO2 O2 + Hb

CO2
O2

O2 O2 (dissolved in plasma) Blood plasma

(a) Oxygen release and carbon dioxide pickup at the tissues

Figure 22.22a
Transport and Exchange of CO2
In systemic capillaries
HCO3– quickly diffuses from RBCs into the
plasma
The chloride shift occurs: outrush of HCO3–
from the RBCs is balanced as Cl– moves in
from the plasma
 Alveolus Fused basement membranes
CO2 CO2 (dissolved in plasma)
Slow
CO2 CO2 + H2O H2CO3 HCO3– + H+
HCO3–
Chloride
Fast Cl–
CO2 CO2 + H2O H2CO3 HCO3 + H
– +
shift
Carbonic Cl–
(out) via
anhydrase
transport
CO2 CO2 + Hb HbCO2 (Carbamino-
protein
hemoglobin)
Red blood cell O2 + HHb HbO2 + H+

O2
O2 O2 (dissolved in plasma) Blood plasma

(b) Oxygen pickup and carbon dioxide release in the lungs

Figure 22.22b
Transport and Exchange of CO2
In pulmonary capillaries
HCO3– moves into the RBCs and binds with H+
to form H2CO3
H2CO3 is split by carbonic anhydrase into CO2
and water
CO2 diffuses into the alveoli
Acid-Base Conditions
Respiratory Acidosis
If ventilation is hindered (e.g. emphysema),
CO2 may build-up
• CO2 combines with water (carbonic acid equation)
H+ will also build up
This will drop pH

If breathing can’t be corrected, the kidney will

actively work to correct H+ levels
Acid-Base Conditions
Respiratory Alkalosis
E.g. Hyperventilation

Fast breathing will cause excessive loss of CO2

• Also loss of H+
This will cause the body to be alkalotic

Seen in high altitude conditions as well

Acid-Base Conditions
Metabolic Acidosis
Eg. High acid (low pH) due to exercise or a kidney or buffer
problem
Will trigger faster breathing to help reduce CO2
• Will reduce H+
Metabolic Alkalosis
Low H+
Breathing will slow down to try and build H+ and CO 2 levels

More in Urinary system – stay tuned!

 Respiratory Conditions

Upper respiratory infections

Colds and flu
• Caused by viruses
• Antibiotics not effective

Pneumonia: infection of the lungs

• May be caused by bacteria or viruses
• High mortality rate in seniors
• Treatment depends on cause

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 Respiratory Conditions
Tuberculosis
bacterial infection that scars the lungs
• May be active with symptoms, or dormant and will
reactivate later
• Treatment: antibiotics
Botulism: poisoning by bacterial toxin
• Toxin consumed in improperly preserved foods
• Causes paralysis of skeletal muscles including intercostals
and diaphragm
• Respiratory failure

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 Lung Cancer
Uncontrolled growth of abnormal cells
Impairs air flow, gas exchange, blood flow
One-third of all U.S. cancer deaths
Causes
90% of cases associated with smoking
Radon gas
Workplace chemicals such as asbestos

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