Download 1 Respiratory System

Respiratory
System
For the body to
survive, there must be
a constant supply of
O2 and a constant
disposal of CO2
Respiratory System
Respiratory System - Overview:
Assists in the detection
of odorants
Protects system
(debris / pathogens / dessication)
5
3
4
Produces sound
(vocalization)
Provides surface area for
gas exchange
(between air / blood)
1
2
Moves air to / from gas
exchange surface
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Table 19.1
1
Respiratory System
Functional Anatomy:
Epiglottis
• Conduction of air
Upper Respiratory
System
• Gas exchange
Lower Respiratory
System
• Filters / warms / humidifies
incoming air
1) External nares
2) Nasal cavity
• Resonance chamber
3) Uvula
5) Larynx
4) Pharynx
• Nasopharynx
• Oropharynx
• Laryngopharynx
6) Trachea
7) Bronchial tree
8) Alveoli
• Provide open airway
• channel air / food
• voice production (link)
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.1
Respiratory System
Functional Anatomy:
Trachea
Primary
Bronchus
Naming of pathways:
• > 1 mm diameter = bronchus
• < 1 mm diameter = bronchiole
• < 0.5 mm diameter = terminal bronchiole
Bronchi
bifurcation
(23 orders)
Green = Conducting zone
Purple = Respiratory zone
Bronchiole
Terminal Bronchiole
Respiratory Bronchiole
Alveolus
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9
2
Respiratory System
Functional Anatomy:
Respiratory Mucosa / Submucosa:
Near
trachea
Near
alveoli
Epithelium:
Mucosa:
Mucous membrane
(epithelium / areolar tissue)
Pseudostratified
columnar
Simple
cuboidal
Cilia
No cilia
Lamina Propria (areolar tissue layer):
 smooth
muscle
 smooth
muscle
Mucous
glands
No
mucous
glands
Cartilage:
Plates / none
Rings
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9
Respiratory System
Functional Anatomy:
How are inhaled debris / pathogens cleared from respiratory tract?
Nasal Cavity:
Particles > 10 µm
Conducting Zone:
Particles 5 – 10 µm
Mucus Escalator
Respiratory Zone:
Particles 1 – 5 µm
Macrophages
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.2
3
Respiratory System
Functional Anatomy:
Pseudostratified ciliated
columnar epithelium
Trachea
Goblet cells:
Unicellular mucous
secreting glands
Esophagus
Tough,
flexible tube
15 – 20 tracheal
cartilages
(~ 1” diameter)
• Protect airway
(C-shaped)
• Allow for food passage
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9
Respiratory System
Functional Anatomy:
Right primary bronchus
wider, shorter & steeper
( blockage hazard)
Bronchus
(> 1 mm diameter)
• 1º = Extrapulmonary bronchi
• 2º  = Intrapulmonary bronchi
Bronchitis:
Inflammation of airways
Pseudostratified
ciliated columnar
epithelium
Smooth muscle
Cartilage plate
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9
4
Respiratory System
Mucous glands rare – Why?
Functional Anatomy:
Pseudostratified
ciliated columnar
epithelium
Cartilage
plates?
Thick
smooth muscle
Allergic attack =  Histamine = Bronchoconstriction
Sympathetic stimulation (NE; 2 receptors)
• Leads to bronchodilation
Synthetic drugs (e.g., albuterol)
trigger response
Bronchiole
E (medulla) triggers
response
(< 1 mm diameter)
Alveoli
Parasympathetic stimulation (ACh; muscarinic receptors)
• Leads to bronchoconstriction
(300 million / lung)
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9
Respiratory System
Functional Anatomy:
Surrounded by fine
elastic fibers
Respiratory
bronchiole
Terminal
bronchiole
Alveolar
sac
Type I Pneumocytes:
• Simple squamous; forms wall of alveoli
• Alveolar pores (1 – 6 / alveoli)
Total surface area:
75 - 90 m2 (~1/2 tennis court)
200 m
Type II Pneumocytes:
• Cuboidal / round; secrete surfactant
• Reduces surface tension (stops alveoli collapse)
Alveolar macrophages:
• Clear debris on alveolar surface
Alveolar
pores
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.8
5
Respiratory System
Pneumonia:
Thickening of respiratory membrane
Functional Anatomy:
Gas exchange occurs readily in the alveoli of the lung via
simple diffusion across the respiratory membrane
0.1 – 0.5 m thick
Respiratory Membrane:
1) Type I pneumocytes
2) Endothelial cells of capillaries
3) Fused basement membranes
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.9
Respiratory System
Respiratory Physiology:
Respiration includes:
1
1) Pulmonary ventilation (pumping air in / out of lungs)
2) External respiration (gas exchange @ blood-gas barrier)
2
3) Transport of respiratory gases (blood)
4) Internal respiration (gas exchange @ tissues)
3
4
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19
6
Respiratory System
Pulmonary Ventilation:
Simplified Model:
Trachea
Trachea
Visceral
pleura
Lung
Parietal
pleura
Pleural
cavity
Thoracic
wall
Lung
Pleural
cavity
Thoracic
wall
Diaphragm
Diaphragm
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.12
Respiratory System
Pulmonary Ventilation:
Atmospheric pressure = ~ 760 mm Hg
(Consider Patmospheric = 0 mm Hg)
Pressure relationships in the thoracic cavity:
Intrapulmonary
pressure
(Ppul = 0 mm Hg)
1) Intrapulmonary Pressure (w/in the alveoli):
• Static conditions = 0 mm Hg
• Inhalation (inspiration) = Ppul slightly negative
• Exhalation (expiration) = Ppul slightly positive
2) Intrapleural pressure (w/in pleural cavity):
• Always relatively negative (~ - 4 mm Hg)
• Prevents lungs from collapsing
Diaphragm
Intrapleural pressure
(Pip = - 4 mm Hg)
atmospheric pressure = Patm = 0 mm Hg
7
Respiratory System
Pulmonary Ventilation:
Why is the intrapleural pressure negative?
Answer: Interaction of opposing forces
Forces equilibrate at Pip = - 4 mm Hg
Forces acting to collapse lung:
1) Elasticity of lungs
2) Alveolar surface tension
Force resisting lung collapse:
1) Elasticity of chest wall
Surface tension of
serous fluids keep
lungs “stuck” to
chest wall
Pneumothorax:
(“sucking chest wound”)
Puncture of chest wall;
results in inability to
generate negative pressure
and expand the lungs
Costanzo (Physiology, 4th ed.) – Figure 5.9
Respiratory System
Pulmonary Ventilation:
Pulmonary ventilation is a mechanical process that depends on
thoracic cavity volume changes
Boyle’s Law:
P1V1 = P2V2
P = pressure of gas (mm Hg)
V = volume of gas (mm3)
P1 = initial pressure; V1 = initial volume
P2 = resulting pressure; V2 = resulting volume
Example:
4 mm Hg (2 mm3) = P2 (4 mm3)
P2 = 2 mm Hg
CHANGING THE VOLUME RESULTS IN INVERSE
CHANGE OF PRESSURE
Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.13
8
Respiratory System
Pulmonary Ventilation:
Pulmonary ventilation is a mechanical process that depends on
thoracic cavity volume changes
0 mm Hg
Inspiration:
Muscular expansion of thoracic cavity
- 4 mm Hg
A) Contraction of diaphragm
• Lengthens thorax (pushes liver down)
B) Contraction of external intercostal muscles
• Widens thorax
0 mm Hg
Diaphragm
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13
Respiratory System
Pulmonary Ventilation:
Pulmonary ventilation is a mechanical process that depends on
thoracic cavity volume changes
0 mm Hg
Inspiration:
Muscular expansion of thoracic cavity
- 6 mm Hg
A) Contraction of diaphragm
• Lengthens thorax (pushes liver down)
B) Contraction of external intercostal muscles
• Widens thorax
Results in:
• Reduced intrapleural pressure (Pip)
• Reduced intrapulmonary pressure (Ppul)
- 1 mm Hg
Results in decreased pressure in thoracic
cavity and air enters
Diaphragm
9
Respiratory System
Internal pressure
can reach +100 mm Hg
Pulmonary Ventilation:
(e.g., why you should exhale when lifting weights)
Pulmonary ventilation is a mechanical process that depends on
thoracic cavity volume changes
Expiration:
Retraction of thoracic cavity
Results in increased pressure
in thoracic cavity; air exits
0 mm Hg
- 4 mm Hg
A) Passive Expiration
• Diaphragm / external intercostals relax
• Elastic rebound (lungs rebound)
B) Active (“Forced”) Expiration
• Abdominal muscles contract
• Internal intercostals contract
Eupnea:
Quiet breathing
(active inspiration;
(passive expiration)
+1
0 mm Hg
Hyperpnea:
Forced breathing
(active inspiration;
(active expiration)
Diaphragm
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13
Respiratory System
Pulmonary Ventilation:
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.14
10
Respiratory System
Pulmonary Ventilation:
Several physical factors exist influence pulmonary ventilation
A) Airway resistance
Q = Airflow (L / min)
P = Pressure gradient (mm Hg)
R = Airway resistance (mm Hg / L / sec)
Q = P / R
Airflow is directly proportional to pressure difference between outside air
and alveoli and inversely proportional to resistance of the airway
Resistance determined by
Poiseuille’s Law:
8Lη
Reminder:
r4
Parasympathetic system produces
bronchial constriction
R = Resistance
η = Viscosity of inspired air
Resistance
R =
Why don’t the smallest airways provide
the highest resistance?
Medium-sized
bronchi
Terminal
bronchioles
( diameter =  resistance)
Sympathetic system produces
bronchial dilation
L = Length of airway
r = Radius of airway
( diameter =  resistance)
Bifurcation stage
Respiratory System
Respiratory Distress Syndrome
(e.g., pre-mature babies)
Pulmonary Ventilation:
Several physical factors exist influence pulmonary ventilation
B) Surface tension in alveoli
Surface tension generated as neighboring liquid molecules on the surface
of alveoli are drawn together by attractive forces
Pressure required to
keep alveolus open
Law of Laplace:
2T
P =
r
P = Collapsing pressure on alveolus (dynes / cm2)
T = Surface tension (dynes / cm)
r = Radius of alveolus (cm)
Surfactant
Problem?
Dipalmitoyl
phosphatidylchorine
(DPPC)
Costanzo (Physiology, 4th ed.) – Figure 5.12
11
Respiratory System
Pulmonary Ventilation:
Several physical factors exist influence pulmonary ventilation
C) Lung compliance
Measure of change in lung volume that occurs with a given
transpulmonary pressure
CL =
VL
CL = Lung compliance (cm3 / mm Hg)
VL = Lung volume (cm3)
 (Ppul – Pip)
Ppul = Intrapulmonary pressure (mm Hg)
Ppi = Intrapleural pressure (mm Hg)
(Transmural pressure)
The higher the lung compliance, the easier
it is to expand the lungs at a given pressure
Determined by:
1) Elasticity of lung
Barrel Chest
Emphysema:
Increased lung compliance due
to loss of elastic fibers
Fibrosis:
Decreased lung compliance due
to scar tissue build-up
2) Surface tension
Respiratory System
Tidal Volume:
Amount of air moved into / out of
lung during single respiratory cycle
Pulmonary Ventilation:
Respiratory Volumes / Capacities:
(spirometric reading)
Inspiratory reserve
Volume (IRV)
(~ 3100 ml)
Inspiratory
capacity
(~ 3600 ml)
Increases with:
• Body size
• Gender
• Conditioning
Vital capacity
(~ 4800 ml)
Decreases with:
• Age
Resting Tidal Volume (~ 500 ml)
Expiratory reserve
volume
(~ 1200 ml)
Functional
residual
capacity
Residual volume (~ 1200 ml)
(~ 2400 ml)
Total lung
capacity
(~ 6000 ml)
(Male)
(Female ~ 4200 ml)
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.16
12
Cardiovascular System – Vessels
Pathophysiology:
Forced vital capacity (FVC) is the total volume of
air that can be forcibly expired after maximal inspiration;
this is a useful measure of lung disease
FEV = Forcefully expired volume
FEV1
FVC
< 0.8
> 0.8
0.8
• Both FEV1 and FVC low but
FEV1 decreased more than
FVC
• Both FEV1 and FVC low but
FVC decreased more than
FEV1
Costanzo (Physiology, 4th ed.) – Figure 5.6
Respiratory System
Pulmonary Ventilation:
Physiologic Dead Space:
Anatomic dead space plus any
ventilated alveoli that might not
participate in gas exchange
Not all inhaled air participates in gas exchange; this
volume is referred to as dead space
Anatomic Dead Space:
Volume of air found in the
conducting airways, including
the nose  bronchioles
Rule of Thumb:
Anatomical dead space in a healthy
young adult is equal to 1 ml / pound
of ideal body weight
Costanzo (Physiology, 4th ed.) – Figure 5.3
13
Respiratory System
Pulmonary Ventilation:
Ventilation rate is the volume of air moved into an out of
the lungs per unit time
Minute Volume:
VM = f (breaths / minute) x VT (tidal volume)
= 12 breaths / minute x 500 mL
= 6000 mL / minute
= 6.0 liters / minute
Alveolar Ventilation:
(or physiologic dead space)
VA = f (breaths / minute) x (VT (tidal volume) - VD (anatomic dead space))
= 12 breaths / minute x (500 mL - 150 mL)
= 4200 mL / minute
Available for
gas transfer…
= 4.2 liters / minute
Respiratory System
Respiratory Physiology:
Respiration includes:
1
1) Pulmonary ventilation (pumping air in / out of lungs)
2) External respiration (gas exchange @ blood-gas barrier)
2
3) Transport of respiratory gases (blood)
4) Internal respiration (gas exchange @ tissues)
3
4
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19
14
Respiratory System
Pulmonary Ventilation:
Gas exchange in the respiratory system refers to diffusion of
O2 and CO2 in the lung and in the peripheral tissues
Basic Properties of Gases:
A) Dalton’s Law of Partial Pressures:
The total pressure of a gas is equal to the sum of the pressure of its constituents
For dry gases:
Patmosphere:
760 mm Hg
21%
O2
PX = PB x F
PX = Partial pressure of gas (mm Hg)
PB = Barometric pressure (mm Hg)
F = Fractional concentration of gas
79%
N2
PO2 = 760 x 0.21
PO2 = 160 mm Hg
% Composition of Atmospheric Air
Respiratory System
Gas Exchange:
Gas exchange in the respiratory system refers to diffusion of
O2 and CO2 in the lung and in the peripheral tissues
Basic Properties of Gases:
A) Dalton’s Law of Partial Pressures:
The total pressure of a gas is equal to the sum of the pressure of its constituents
21%
O2
79%
N2
% Composition of Atmospheric Air
Patmosphere:
760 mm Hg
For humidified gases:
PX = (PB – PH2O) x F
PX =
PB =
PH2O
F =
Partial pressure of gas (mm Hg)
Barometric pressure (mm Hg)
= Water vapor pressure at 37C (47 mm Hg)
Fractional concentration of gas
PO2 = (760 – 47) x 0.21
PO2 = 150 mm Hg
15
Note:
At equilibrium, the partial pressure
of a gas in the liquid phase equals
the partial pressure in the gas phase
Respiratory System
Gas Exchange:
(the “bends”)
Gas exchange in the respiratory system refers to diffusion of
O2 and CO2 in the lung and in the peripheral tissues
CO2 >> O2 >> N2
Basic Properties of Gases:
Solubility:
How much of a gas will dissolve in a
liquid at a given partial pressure
B) Henry’s Law:
Gases in a mixture dissolve in a liquid in proportion to their partial pressures
CX = PX x Solubility
CX = Concentration of dissolved gas (mL X / 100 mL blood)
PX = Partial pressure of gas (mm Hg)
Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)
[O2] = PO2 x Solubility
[O2] = 150 x 0.003
[O2] = 0.45 mL / 100 mL blood
Respiratory System
Gas Exchange:
Gas exchange in the respiratory system refers to diffusion of
O2 and CO2 in the lung and in the peripheral tissues
Respiratory
membrane
Basic Properties of Gases:
C) Fick’s Law:
The transfer of a gas across a cell membrane depends on the driving force,
gas solubility, and the surface area available for transport
VX =
VX =
D =
A =
P =
X =
DAP
x
directly proportional
inversely proportional
Volume of gas transferred per unit time
Diffusion coefficient of the gas (includes solubility)
Surface area
Partial pressure difference of the gas
Thickness of the membrane
The driving force for diffusion of a gas is the
partial pressure difference of the gas,
not the concentration difference
60
PO2
in lung
100
40
PO2
in blood
16
Respiratory System
In solution, only dissolved gases
contribute to partial pressures
Gas Exchange:
Unlike alveolar air, where there is only one form of gas,
blood is able to carry gases in addition forms
PX
Bound gas
Dissolved gas
Gases bind directly
to plasma proteins or
to hemoglobin
The higher the solubility
of a gas, the higher the
concentration of the gas
in solution
Chemically
modified gas
Gases react with blood
components to form
new products
Total gas concentration = Dissolved gas + Bound gas + Chemically modified gas
Respiratory System
Gas Exchange:
Gas transport in the lungs:
Costanzo (Physiology, 4th ed.) – Figure 5.16
17
Costanzo (Physiology, 4th ed.) – Figure 5.17
Respiratory System
Gas Exchange:
VX =
Systemic tissues undergo
reversal of pattern observed at lung
Patmosphere:
760 mm Hg
Gas transport in the lungs:
DAP
x
PX = PB x F
Diffusional coefficient 20x greater
for CO2 than for O2
O2 = 21%
CO2 = 0%
O2 = 21%
CO2 = 0%
Lung air modified by gas exchange:
PX = (PB – PH2O) x F
1) O2 into blood; CO2 out of blood
2) Mixture of fresh and residual air
O2 = 14%
CO2 = 6%
PO2 = 60
PX = (PB – PH2O) x F
PCO2 = 6
The amount of O2 / CO2
transferred corresponds to the
needs of the body
Composition reflects
metabolic activity of body
1:1 exchange rate
Due to rapid diffusion
of gases, equilibrium reached
?
Costanzo (Physiology, 4th ed.) – Figure 5.18
Respiratory System
Gas Exchange:
Gas exchange across the alveolar / pulmonary capillary barrier is
described as either diffusion-limited or perfusion-limited
Diffusion-limited:
The total amount of gas transported
across the alveolar / capillary barrier is
limited by the diffusional process
Partial pressure
gradient maintained across
entire length of capillary
(gas does not equilibrate)
Example:
Carbon
monoxide
Perfusion-limited:
The total amount of gas transported
across the alveolar / capillary barrier is
limited by blood flow
Example:
Nitrous
oxide
Partial pressure
gradient not maintained
across length of capillary
(gas equilibrates)
 gas transport =  diffusion rate
 gas transport =  blood flow
18
Respiratory System
Gas Exchange:
Under normal conditions, O2 transport into pulmonary capillaries
is a perfusion-limited process
PO2 (mm Hg)
Exercise
Rest
“wiggle room”
PO2 does not equilibrate until
hemoglobin saturated
Remember:
PO2 only measures free
O2 concentration
Time in pulmonary capillary (s)
Start of
capillary
End of
capillary
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.18
Respiratory System
Pathophysiology:
In certain pathologic conditions, O2 transport
becomes diffusion limited
Lung fibrosis
PO2 equilibrium never
reached
Alveolar wall thickens; slows
down diffusion rate
Outcome:
Decreased PO2 in systemic
arterial blood, especially
during physical activity
VX =
DAP
x
Costanzo (Physiology, 4th ed.) – Figure 5.19
19
Respiratory System
A man climbs to the top of a tall mountain
where the barometric pressure is
measured at 50 mm Hg.
What are the implications to oxygen transport
into pulmonary capillaries for A) PaO2,
B) rate, and C) exercise
Exercise
Rest
“shortness
of breath”
Driving force:
50 – 25 = 25 mm Hg
VX =
DAP
x
Costanzo (Physiology, 4th ed.) – Figure 5.19
Respiratory System
Respiratory Physiology:
Respiration includes:
1
1) Pulmonary ventilation (pumping air in / out of lungs)
2) External respiration (gas exchange @ blood-gas barrier)
2
3) Transport of respiratory gases (blood)
4) Internal respiration (gas exchange @ tissues)
3
4
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19
20
Respiratory System
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
A) Dissolved O2:
Accounts for 2% of total O2 content of blood
Henry’s Law:
Recall:
The concentration of dissolved
O2 is proportional to the partial
pressure of O2
CX = PX x Solubility
CX = Concentration of dissolved gas (mL X / 100 mL blood)
PX = Partial pressure of gas (mm Hg)
Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)
Grossly insufficient to meet the
demands of the tissues
[O2] = PO2 x Solubility
[O2] = 100 x 0.003
At rest, tissues require 250 mL O2 / min
[O2] = 0.30 mL / 100 mL blood
O2 delivery = CO x [dissolved O2]
O2 delivery = 5.0 L / min x 0.3 mL O2 / 100 mL
O2 delivery = 15 mL O2 / min
Respiratory System
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
Accounts for remaining 98% of total O2 content of blood
Globular protein:
2  & 2  subunits each
containing a heme moiety
• 4 O2 / hemoglobin
Iron (ferrous state – Fe2+)
bound to nitrogens
Oxyhemoglobin = O2 bound to hemoglobin
Shouldn’t O2 oxidize iron (ferric state – Fe3+ )?
Deoxyhemoglobin = No O2 present
No – nitrogen bonds prevent this…
Methemoglobin = Iron in ferric
• Does not bind O2
(Fe3+)
state
BUT – if it does happen:
Methemoglobin reductase – reduces Fe3+ to Fe2+
21
Respiratory System
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
Hemoglobin structure demonstrates a developmental shift
Fetal hemoglobin
Adult hemoglobin
(hemoglobin F - HbF)
(hemoglobin A - HbA)
22
2 2
Hemoglobin F has a higher
affinity for O2 than hemoglobin A,
facilitating O2 transfer across
the placenta
Respiratory System
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
Amount of O2 bound to hemoglobin determined by the hemoglobin concentration
and by the O2-binding capacity of that hemoglobin
O2-binding Capacity:
PUTTING IT ALL TOGETHER:
The maximum amount of O2 that can be
bound to hemoglobin per volume of blood
O2 Content:
The actual amount of O2 per unit
volume of blood
(Assumes hemoglobin 100% saturated)
Under normal conditions:
• 1.0 g of hemoglobin can bind 1.34 mL 02
• [hemoglobin A] = 15 g / 100 mL
THUS
O2-binding
capacity
= 15 g / 100 mL x 1.34 mL O2 / g HbA
O2-binding
capacity = 20.1 mL O2 / 100 mL blood
O2
content
= (O2-binding capacity x % saturation) +
dissolved O2
O2 Delivery to tissues:
The actual amount of O2 delivered
to the tissues
O2
= Cardiac output x O2 content of blood
delivery
22
Respiratory System
Oxygen Transport in Blood:
Reminder:
Each hemoglobin as the capacity to
bind 4 O2 molecules
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
The % saturation of hemoglobin is a function of the PO2 of blood
O2-hemoglobin Dissociation Curve:
Describe relationship between percent saturation
of Hb and partial pressure of oxygen
Sigmoid curve
P50
Point at which 50%
of Hb saturated
THE PERCENT SATURATION OF
HEME SITES DOES NOT INCREASE
LINEARLY AS PO2 INCREASES
Change in value is
an indicator for a
change in affinity
of Hb for O2
Sub-unit Cooperativity:
Oxygenation of first heme group facilitates
oxygenation of other heme groups
( P50 =  affinity)
Costanzo (Physiology, 4th ed.) – Figure 5.20
Respiratory System
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
Under normal, resting conditions, arterial blood hemoglobin is 98% saturated
and only ~ 25% of O2 is unloaded at tissues
Small drop in PO2
equates to large
increase in O2
unloading
“wiggle room”
O2 unloaded to
resting tissues
Additional O2
unloaded to
exercising
tissues
~ complete
saturation
Points to Ponder:
1) Hemoglobin is almost completely saturated
at a PO2 of 70 mm Hg
ADAPTIVE SIGNIFICANCE?
2) The unloading of O2 occurs on the steep
portion of the dissociation curve
ADAPTIVE SIGNIFICANCE?
Tissues
Tissues
(exercising) (at rest)
Lungs
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.20
23
Respiratory System
2,3-DPG = 2,3-diphosphoglycerate
• Byproduct of RBC glycolysis
• Binds to  chains of hemoglobin
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
The O2-hemoglobin dissociation curve can shift to the right or the left
depending on local conditions in the blood
Right shift = Decreased Hb affinity for O2
• Facilitates unloading of O2
A)  PCO2
B)  pH
Increased P50
Bohr
effect
C)  temperature
D)  2,3-DPG
‘Adaptive Complex’
Influence Hb saturation by modifying
hemoglobin’s three-dimensional structure
Costanzo (Physiology, 4th ed.) – Figure 5.22
Respiratory System
2,3-DPG = 2,3-diphosphoglycerate
• Byproduct of RBC glycolysis
• Binds to  chains of hemoglobin
Oxygen Transport in Blood:
O2 is carried in two forms in blood: dissolved and bound to hemoglobin
B) O2 bound to hemoglobin:
The O2-hemoglobin dissociation curve can shift to the right or the left
depending on local conditions in the blood
Left shift = Increased Hb affinity for O2
• Hinders unloading of O2
Decreased P50
A)
B)
C)
D)
?
 PCO2
 pH
 temperature
 2,3-DPG
Increased affinity of hemoglobin F (fetus)
due to  2,3-DPG binding
?
Costanzo (Physiology, 4th ed.) – Figure 5.22
24
Respiratory System
Pathophysiology:
Carbon monoxide poisoning is catastrophic
for O2 delivery to tissues
1) CO decreases O2 bound to Hb
Example:
• CO binds to Hb with an affinity that is
250x greater than that of O2
(forms carboxyhemoglobin)
Left shift
“cherry red”
2) CO causes left shift of dissociation curve
• Heme groups not bound to CO have
an increased affinity for O2
Costanzo (Physiology, 4th ed.) – Figure 5.22
Respiratory System
Carbon Dioxide Transport in Blood:
CO2 is carried in three forms in blood: dissolved, bound to
hemoglobin, and as bicarbonate (HCO3-)
A) Dissolved CO2:
Accounts for 5% of total CO2 content of blood
Henry’s Law:
CX = PX x Solubility
CX = Concentration of dissolved gas (mL X / 100 mL blood)
PX = Partial pressure of gas (mm Hg)
Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)
[CO2] = PCO2 x Solubility
[CO2] = 40 x 0.07
(Arterial blood)
[CO2] = 2.80 mL / 100 mL blood
25
Respiratory System
Carbon Dioxide Transport in Blood:
CO2 is carried in three forms in blood: dissolved, bound to
hemoglobin, and as bicarbonate (HCO3-)
B) CO2 bound to hemoglobin:
Accounts for 3% of total CO2 content of blood
• CO2 binds to the terminal
amino groups on globins
Reminder:
The binding of CO2 to hemoglobin
causes a conformational change
reducing the affinity of Hb
for O2 (right shift)
IN TURN
Carbaminohemoglobin = CO2 bound to hemoglobin
When less O2 is bound to Hb,
the affinity of Hb for CO2 increases
(the Haldane effect)
Respiratory System
Carbon Dioxide Transport in Blood:
CO2 is carried in three forms in blood: dissolved, bound to
hemoglobin, and as bicarbonate (HCO3-)
C) CO2 converted to HCO3- :
Accounts for remaining 92% of total CO2 content of blood
Diffuses into
RBCs
CA
CO2 +
REVERSABLE
H20
H2CO3
Plasma
(contributes to
the Bohr effect)
H+
+
HCO3-
1) Carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3)
• Reaction catalyzed by carbonic anhydrase (CA)
2) H2CO3 dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3- )
• HCO3- released into plasma
• H+ buffered in RBC by deoxyhemaglobin
26
Respiratory System
Carbon Dioxide Transport in Blood:
CO2 is carried in three forms in blood: dissolved, bound to
hemoglobin, and as bicarbonate (HCO3-)
C) CO2 converted to HCO3- :
Accounts for remaining 92% of total CO2 content of blood
Chloride shift:
To maintain charge balance in RBCs,
a Cl- is exchanged with a HCO3- as
the HCO3- leaves the cell
• Band three protein functions
as passive transporter
Costanzo (Physiology, 4th ed.) – Figure 5.24
Respiratory System
Gas Transport - Review:
Tissue – Blood Interface:
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10
27
Respiratory System
Note:
Carbonic anhydrase also embedded
in respiratory membrane
Gas Transport:
Lung – Blood Interface:
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10
Respiratory System
Ventilation / Perfusion Relationships:
Recall:
The pulmonary circulation carries blood from
the right ventricle and returns blood
to the left atrium
Pulmonary blood flow is regulated primarily by altering
the resistance of the arterioles
Mechanisms of Regulation:
A) Partial pressure of alveolar O2
Hypoxic
vasoconstriction
 PAO2
B) Vasoactive Chemicals
Reduces pulmonary
flow to poorly
ventilated alveoli
Vasoconstrict
vessel
Mechanism of Action:
• If PAO2 falls below 70 mm Hg, voltage-gated
Ca2+ gates open in vascular smooth muscle,
leading to contraction
Thromboxane A2
Source: Endothelium
Action: Vasoconstriction
Prostacyclin
Source: Endothelium
Action: Vasodilator
Can act locally (blocked alveolus) or globally (high altitude)
28
Respiratory System
Ventilation / Perfusion Relationships:
The distribution of pulmonary blood flow with the lung is uneven
due to the effects of gravity
Zone 1: Apex of lung
Low blood
flow
Gravitational
Effect
Palveoli > Parterial > Pvein
Lower vessel
pressures
• Pulmonary capillaries compressed
by surrounding alveoli
Zone 2: Middle of lung
Parterial > Palveoli > Pvein
Medium blood
flow
• Minimal compression; blood flow driven
by Partial vs. Palveoli difference
Zone 3: Base of lung
Parterial > Pvein > Palveoli
High blood
flow
• The greatest number of capillaries open;
high arterial and venous pressures
Higher vessel
pressures
Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.26
Respiratory System
Control of Breathing:
Breathing is regulated so the lungs can maintain the
PaO2 and PaCO2 within a normal range
Medullary Respiratory Centers:
Amphetamines / Caffeine:
 respiratory center activity
1) Ventral Respiratory Group
• Inspiratory center
PRCs
Oscillating rhythm of neuronal
firing / quiescence
• ‘Pacesetter’ (12 – 15 breaths / min)
2) Dorsal Respiratory Group
• Expiratory center
• Active during forced exhalation
VRG
Barbiturates / Opiates / Alcohol:
 respiratory center activity
DRG
Pontine Respiratory Centers:
1) Apneustic Center
• Triggers prolonged inspiratory gasps
Intercostal
nerves
Phrenic nerve
2) Pneumotaxic Center
• Turns off inspiration
• Limits size of tidal volume
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.23
29
Respiratory System
Control of Breathing:
Depth and rate of breathing can be modified in response
to changing demands on the body
Most important factors regulating
ventilation are chemical
Peripheral
chemoreceptors
• Carotid body (IX)
• Aortic arch (X)
(+)
(CSF)
Central
chemoreceptors
(+)
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24
Respiratory System
Control of Breathing:
Chemical Factors:
Hypercapnia: Increased PCO2 in arterial blood
Hypocapnia: Decreased PCO2 in arterial blood
A) PCO2
• Most potent respiratory stimulant (maintained @  3 mm Hg)
• Mediated via central / peripheral chemoreceptors
Can cross
blood-brain barrier
Can not cross
blood-brain barrier
 CO2 =  ventilation
 CO2 =  ventilation
Ultimately leads to change in
pH of cerebral spinal fluid
Costanzo (Physiology, 4th ed.) – Figure 5.32
30
Respiratory System
Control of Breathing:
Chemical Factors:
A) PCO2
• Most potent respiratory stimulant (maintained @  3 mm Hg)
• Mediated via central / peripheral chemoreceptors
B) PO2
• Minor respiratory stimulant ( O2 =  respiratory rate)
• Mediated via peripheral chemoreceptors
• Stimulated by PO2 < 60 mm Hg in arterial blood
C) Arterial pH
• Independent of changes in arterial PCO2
• Compensatory mechanism for metabolic acidosis
• Mediated by peripheral chemoreceptors (carotid body only)
Issue for individuals
with COPD:
Continual high levels of
PCO2 in system results in
PO2 taking over regulation
IF RESPIRATORY DISTRESS
OCCURS
Respiratory System
Control of Breathing:
Depth and rate of breathing can be modified in response
to changing demands on the body
Addition factors contribute to
ventilation regulation
Hering-Breuer Reflex:
When lung / airways stretched,
inspiratory center inhibited
Lung
stretch
receptors
Peripheral
chemoreceptors
• Carotid body (IX)
• Aortic arch (X)
Function in anticipatory
response to exercise
(+)
(CSF)
Central
chemoreceptors
(+)
(-)
Vagus (X)
nerve
(+)
Joint / muscle
stretch
receptors
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24
31
Respiratory System
Control of Breathing:
Laryngeal
spasm
(e.g., sarin gas)
Depth and rate of breathing can be modified in response
to changing demands on the body
Addition factors contribute to
ventilation regulation
Lung
stretch
receptors
(+)
(CSF)
Central
chemoreceptors
(+)
Nasal cavity = Sneeze
Lower conduction system = Cough
Apnea
(-)
Vagus (X)
nerve
(cessation of breathing)
(-)
(+)
Irritant
receptors
Joint / muscle
stretch
receptors
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24
Epiglottis closes;
thoracic cavity shrinks
Epiglottis opens;
air forcefully released (~ 100 mph)
Respiratory System
Control of Breathing:
Depth and rate of breathing can be modified in response
to changing demands on the body
Higher control centers;
Voluntary control over breathing
Addition factors contribute to
ventilation regulation
Hypoventilation:
Decrease breathing rate / depth
Pain / emotional stimuli
acting through hypothalamus
(+ / -)
Hyperventilation:
Increase breathing rate / depth
(+ / -)
Lung
stretch
receptors
Rate / depth of respiration
exceeds demands for
O2 delivery / CO2 removal
(+)
(CSF)
Central
chemoreceptors
(+)
(-)
Vagus (X)
nerve
(-)
(+)
Joint / muscle
stretch
receptors
Irritant
receptors
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24
32
Respiratory System
formaldehyde
benzene
vinyl chloride
arsenic ammonia
hydrogen cyanide
~ 3,400 deaths / year
contributed to secondhand smoke…
Increase in lung cancer
rates correlated with rise
in smoking among adult
men and women
1900
1956
1978
2004
= Rare…
= 29,000 deaths
= 105,000 deaths
= 160,440 deaths
33