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