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Respiratory System

Part 2: Respiratory Physiology

Respiration

• Exchange of gases between air and body

cells

• Three steps

1. Ventilation

2. External respiration

3. Internal respiration

Ventilation

• Pulmonary ventilation consists of two phases

1. Inspiration: gases flow into the lungs

2. Expiration: gases exit the lungs

• Relies on pressure gradients

– Atmosphere and alveoli

• Negative pressure breathing

– Thoracic pressures

– Atmospheric pressure

Boyle’s Law

• The relationship between the pressure and

volume of a fixed quantity of gas in a closed

container

• Pressure (P) varies inversely with volume (V):

P1V1 = P2V2

While one increases the other decreases

Ventilation

• Intrapleural pressure is subatmospheric

– Inward elastic recoil of lung tissue

– Outward elastic recoil of chest wallResting lung volume

Ventilation

• Atmospheric pressure (Patm)

– Pressure exerted by the air surrounding the body

– 760 mm Hg at sea level

• Thoracic pressures are described relative to Patm

– Negative respiratory pressure is less than Patm

– Positive respiratory pressure is greater than Patm

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Figure 22.12

Atmospheric pressure

Intrapleural

pressure

756 mm Hg

(–4 mm Hg)

Transpulmonary

pressure

760 mm Hg

–756 mm Hg

= 4 mm Hg

Thoracic wall

Diaphragm

LungIntrapulmonary

pressure 760 mm Hg

(0 mm Hg)

Parietal pleura

Pleural cavity

Visceral pleura

756

760

Ventilation

• Intrapulmonary (intra-alveolar) pressure (Ppul)

– Pressure in the alveoli

– Fluctuates with breathing

– Always eventually equalizes with Patm

Ventilation

• Intrapleural pressure (Pip):

– Pressure in the pleural cavity

– Fluctuates with breathing

– Always a negative pressure (<Patm and <Ppul)

Ventilation

• Negative Pip is caused by opposing forces

– Two inward forces promote lung collapse

• Elastic recoil of lungs decreases lung size

• Surface tension of alveolar fluid reduces alveolar size

– One outward force tends to enlarge the lungs

• Elasticity of the chest wall pulls the thorax outward

Pulmonary Ventilation

• Inspiration and expiration

• Mechanical processes that depend on volume changes in the

thoracic cavity

– Volume changes → pressure changes

– Pressure changes → pressure gradient → gases flow to

equalize pressure

Inspiration

• An active process

– Inspiratory muscles contract

• Thoracic volume increases

• Lungs are stretched and intrapulmonary volume

increases

– Intrapulmonary pressure drops

– Air flows into the lungs, down its pressure gradient

» Ppul = Patm

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Figure 22.13 (1 of 2)

Sequence of events

Changes in anterior-posterior and superior-

inferior dimensions

Changes in lateraldimensions

(superior view)

Ribs are elevatedand sternum flares

as external

intercostalscontract.

Diaphragmmoves inferiorly

during contraction.

Externalintercostalscontract.

Inspiratory muscles contract (diaphragm descends; rib cage rises).

2

1

Thoracic cavity volume increases.

3 Lungs are stretched; intrapulmonary volume increases.

4 Intrapulmonary pressure drops (to –1 mm Hg).

5 Air (gases) flows into lungs down its pressure gradient until intrapulmonary pressure is equal to atmospheric pressure

Question

• What part of the lung tissue expands during

inspiration?

Expiration

• Quiet expiration is normally a passive process

– Inspiratory muscles relax

• Thoracic cavity volume decreases

• Elastic lungs recoil and intrapulmonary volume decreases

– Ppul rises

• Air flows out of the lungs down its pressure gradient until Ppul = 0

Figure 22.13 (2 of 2)

Sequenceof events

Changes in anterior-posterior and superior-

inferior dimensions

Changes inlateral dimensions

(superior view)

Ribs and sternumare depressed

as external

intercostalsrelax.

Externalintercostalsrelax.

Diaphragmmovessuperiorly

as it relaxes.

1 Inspiratory muscles relax (diaphragm rises; rib cage descends due to recoil of costal cartilages).

2 Thoracic cavity volume decreases.

3 Elastic lungs recoil passively; intrapulmonary volume decreases.

4 Intrapulmonary pres-sure rises (to +1 mm Hg).

5 Air (gases) flows out of lungs down its pressure gradient until intra-pulmonary pressure is 0.

Figure 22.14

5 seconds elapsed

Volume of breath

Intrapulmonarypressure

Expiration

Intrapleuralpressure

Trans-pulmonarypressure

InspirationIntrapulmonary pressure. Pressure inside lung decreases as lung volume increases during inspiration; pressure increases during expiration.

Intrapleural pressure.Pleural cavity pressure becomes more negative as chest wall expands during inspiration. Returns to initial value as chest wall recoils.

Volume of breath.During each breath, the pressure gradients move 0.5 liter of air into and out of the lungs.

Air Flow

• Physical factors influencing efficiency of air flow

– Inspiratory muscles overcome three factors that hinder

air passage and pulmonary ventilation

1. Airway resistance

2. Alveolar surface tension

3. Lung compliance

NOTE: Study guide, Respiratory pg 10

6b. Friction is inversely proportional to airway diameter

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Air Flow

• Broncoconstriction

– Smooth muscle contracts

– Reduced air flow

Lung Compliance

• Measure of lung’s ability to stretch and expand

• Diminished by

– Nonelastic scar tissue (fibrosis)

– Reduced production of surfactant

– Decreased flexibility of the thoracic cage

• Emphysema/COPD is associated with increased

compliance

– Due to diminished elastic recoil – patient has no trouble filling lungs with air, but great effort is required for exhalation

Gas Laws

• Dalton’s Law of Partial Pressure

– Describes how a gas behaves when it is part of a mixture

• Partial pressure = pressure exerted by a single gas in the mixture = proportional to the percentage of gas in a mixture

• Total pressure exerted by a mixture of gases is the sum of the pressures exerted by each gas

Gas Laws

• Dalton’s Law of Partial Pressure

– Example:

• Air contains 20.9% O2

• Atmospheric Pressure = 760 mmHg

0.209 P o2 x 760 mmHg = 160 mmHg

= partial pressure of oxygen in the atmosphere

Gas Laws

• Fick’s Law of Diffusion– Gives the rate of diffusion for a given gas across a

membrane

– CO2 has a high diffusion coefficient and diffuses 20 times more rapidly across a membrane than O2

Vg = (A) (P1-P2) (D)

(T)

• A = membrane surface area

• P1-P2 = difference in partial pressures

• D = diffusion coefficient

• T = thickness of membrane

Gas Laws

• Diseases related to gas diffusion– Pulmonary edema

– COPD

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Gas Exchange

• External respiration

– Pulmonary gas exchange

• Internal respiration

– Gas exchange between blood capillaries and

tissues

External Respiration

• Exchange of O2 and CO2 across the respiratory

membrane

– Between lung and blood

Thought Question

• Can you think of some factors that might

influence the exchange of gases between the

lungs and the blood? Hint: remember Fick’s

Law?

External Respiration

• Respiratory membrane

– Site of gas exchange between lung and blood

• Not actually a membrane, but a collection of

associated structures

– Membrane of lung epithelium

– Pulmonary capillary membrane

– Surfactant

– Connective tissue

Figure 22.9c

Capillary

Type II (surfactant-

secreting) cell

Type I cell

of alveolar wall

Endothelial cell nucleus

Macrophage

Alveoli (gas-filled

air spaces)

Red blood cell

in capillary

Alveolar pores

Capillary

endothelium

Fused basement

membranes of the

alveolar epithelium

and the capillary

endothelium

Alveolar

epithelium

Respiratory

membrane

Red blood

cell

O2

Alveolus

CO2

Capillary

Alveolus

Nucleus of type I

(squamous

epithelial) cell

(c) Detailed anatomy of the respiratory membrane

External Respiration

• Partial pressure gradient for O2 in the lungs is

steep

– Venous blood pO2 = 40 mm Hg

– Alveolar pO2 = 104 mm Hg

Oxygen readily diffuses from alveoli to lung

capillaries

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External Respiration

• Partial pressure gradient for CO2 in the lungs

– Venous blood pCO2 = 45 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!

Figure 22.19

Inspired air:

P 160 mm Hg

P 0.3 mm Hg

Blood leaving

lungs and

entering tissue

capillaries:

P 100 mm Hg

P 40 mm Hg

Alveoli of lungs:

P 104 mm Hg

P 40 mm HgO2

Heart

Blood leaving

tissues and

entering lungs:

P 40 mm Hg

P 45 mm Hg

Systemic

veins

Systemic

arteries

Tissues:

P less than 40 mm Hg

P greater than 45 mm Hg

Internal

respiration

External

respiration

Pulmonary

veins (P

100 mm Hg)

Pulmonary

arteries

CO2

O2

CO2

O2

CO2O2

CO2

O2

CO2

O2

Partial

pressure of

O2 in inspired

air is greater

than that of

blood

entering the

lungs

O2 flows out

of alveoli and

into

bloodstream

EXTERNAL

RESPIRATION

Figure 22.19

Inspired air:

P 160 mm Hg

P 0.3 mm Hg

Blood leaving

lungs and

entering tissue

capillaries:

P 100 mm Hg

P 40 mm Hg

Alveoli of lungs:

P 104 mm Hg

P 40 mm HgO2

Heart

Blood leaving

tissues and

entering lungs:

P 40 mm Hg

P 45 mm Hg

Systemic

veins

Systemic

arteries

Tissues:

P less than 40 mm Hg

P greater than 45 mm Hg

Internal

respiration

External

respiration

Pulmonary

veins (P

100 mm Hg)

Pulmonary

arteries

CO2

O2

CO2

O2

CO2O2

CO2

O2

CO2

O2

Partial

pressure of

CO2 in

inspired air is

less than that

of blood

entering the

lungs

CO2 flows out

of

bloodstream

and into

alveoli,

where it is

exhaled

EXTERNAL

RESPIRATION Factors Affecting External Respiration

Anatomical adaptations

• Moist surfaces

• Thickness and surface area

• Narrow capillaries = RBC’s single file

Physiological and physical factors

• Pulmonary disease

• Affect of drugs on minute volume

• Partial pressure changes with altitude

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

– pCO2 in tissue is higher than in systemic arterial

blood

Figure 22.19

Inspired air:

P 160 mm Hg

P 0.3 mm Hg

Blood leaving

lungs and

entering tissue

capillaries:

P 100 mm Hg

P 40 mm Hg

Alveoli of lungs:

P 104 mm Hg

P 40 mm HgO2

Heart

Blood leaving

tissues and

entering lungs:

P 40 mm Hg

P 45 mm Hg

Systemic

veins

Systemic

arteries

Tissues:

P less than 40 mm Hg

P greater than 45 mm Hg

Internal

respiration

External

respiration

Pulmonary

veins (P

100 mm Hg)

Pulmonary

arteries

CO2

O2

CO2

O2

CO2O2

CO2

O2

CO2

O2

Partial

pressure of

O2 in

oxygenated

blood is

greater than

that of

tissues

O2 flows out

of

bloodstream

and into

tissues

INTERNAL

RESPIRATION

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Figure 22.19

Inspired air:

P 160 mm Hg

P 0.3 mm Hg

Blood leaving

lungs and

entering tissue

capillaries:

P 100 mm Hg

P 40 mm Hg

Alveoli of lungs:

P 104 mm Hg

P 40 mm HgO2

Heart

Blood leaving

tissues and

entering lungs:

P 40 mm Hg

P 45 mm Hg

Systemic

veins

Systemic

arteries

Tissues:

P less than 40 mm Hg

P greater than 45 mm Hg

Internal

respiration

External

respiration

Pulmonary

veins (P

100 mm Hg)

Pulmonary

arteries

CO2

O2

CO2

O2

CO2O2

CO2

O2

CO2

O2

Partial

pressure of

CO2 in

oxygenated

blood is less

than that of

tissues

CO2 flows out

of tissues

and into

bloodstream

INTERNAL

RESPIRATION Gas Transport (page 12)

• Oxygen (O2) transport

• Carbon dioxide (CO2) transport

O2 Transport

�Molecular O2 is carried in the blood

� Solubility in plasma low

� Few O2 = partial pressure

� Only 1.5% dissolved in plasma

� paO2 does not include O2 bound to hemoglobin

� Poor measure of total O2

O2 Transport

• Hemoglobin

– Bound O2 does not contribute to partial pressure

• Maintaining partial pressure gradient → diffusion

– 98.5% loosely bound to each Fe of hemoglobin

(Hb) in RBCs

• (4) O2 per hemoglobin

O2 Transport

• Oxyhemoglobin (HbO2)

– Hemoglobin-O2 combination

• Reduced hemoglobin (HHb)

– Hemoglobin that has released O2

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O2 Transport

• Loading and unloading of O2 is facilitated by

change in shape of Hb

– As O2 binds, Hb affinity for O2 increases

• 4 heme groups bound to O2

– Saturated

• 1, 2 or 3 heme groups bound to O2

– Partially saturated

• Measure of oxygen saturation = SO2

O2 Transport

• Rate of loading and unloading of O2 is

regulated by

– pO2

– Temperature

– Blood pH

– pCO2

– Products of metabolism

Modify hemoglobin shape

O2 Transport

• Factors that promote oxyhemoglobin formation

– ↑ pO2

– ↓ pCO2

Conditions found in the lungs promote O2

binding to Hb

O2 Transport

• Factors that promote oxyhemoglobin dissociation

– ↓ pO2

– ↑ temperature

– ↑ pCO2

– ↑ products of metabolism

Conditions found in the tissues promote O2

unloading

Oxyhemoglobin Dissociation

• Influence of pO2 on hemoglobin saturation

– Arterial blood

• paO2 = 100 mm Hg

• Hb is 97-100% saturated

– SO2 100%

– Venous blood (resting tissues)

• pO2 = 40 mm Hg

• Hb is 75% saturated

– Venous blood still contains oxyhemoglobin!

Figure 22.20

Difference in partial

pressures = some O2

unloaded to resting

tissues

LungsExercising

tissues

Resting

tissues

Greater difference

in partial pressures

= Additional O2

unloaded to

exercising tissues

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Oxyhemoglobin Dissociation

– Utilization coefficient

• Difference between arterial and venous SO2

– Example: arterial SO2 = 100%; venous SO2 = 75%

– Utilization coefficient 25%

– ↑ metabolism = ↓ paO2 = larger partial pressure

difference

Oxyhemoglobin Dissociation

• Only 20–25% of bound O2 is unloaded during

one systemic circulation (at rest)

• If O2 levels in tissues drop:

– More oxygen dissociates from hemoglobin and is

used by cells

• Blood flow and heart rate need not increase!

Oxyhemoglobin Dissociation

• Other factors influencing hemoglobin

saturation

• ↑ temperature and ↑ H+

– Conditions found at cells enhance O2 unloading

– Shift the O2-hemoglobin dissociation curve to the

right

Figure 22.21

O2P (mm Hg)

Normal body

temperature

10°C

20°C38°C

43°C

Normal arterial

carbon dioxide

(P 40 mm Hg)

or H+ (pH 7.4)

CO2

Increased carbon dioxide

(P 80 mm Hg)

or H+ (pH 7.2)CO2

Decreased carbon dioxide

(P 20 mm Hg) or H+ (pH 7.6)CO2

(a)

(b)

Factors promoting Oxyhemoglobin dissociation shift curve to the right

CO2 Transport

• CO2 is transported in the blood in three forms

– 7-10% dissolved in plasma

– 20% bound to globin of hemoglobin

• carbaminohemoglobin or HbCO2

– 70% transported as bicarbonate ions (HCO3–) in

plasma

CO2 Transport

H2O + CO2 ↔ H2CO3 ↔ HCO3- + H+

CA

Key

H2O = water

CO2 = carbon dioxide

H2CO3 = carbonic acid

HCO3- = bicarbonate ion

H+ = hydrogen ion

CA = carbonic anhydrase

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CO2 Transport

H2O + CO2 ↔ H2CO3 ↔ HCO3- + H+

CA

• Reaction happens in plasma but is 1,000X faster in the RBC because of CA

• H+ ions = acid = decrease pH = improved O2 unloading from hemoglobin

• HCO3- diffuses out, replaced by Cl- to maintain equilibrium = Chloride Shift

Cl-

Figure 22.22a

Red blood cell

Blood plasma

Slow

Tissue cell Interstitial fluid

Carbonic

anhydrase

CO2

CO2

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

CO2 (dissolved in plasma)

CO2 + H2O H2CO3 HCO3– + H+

FastCO2 + H2O H2CO3

O2 (dissolved in plasma)

CO2 + Hb HbCO2

HbO2 O2 + Hb

(Carbamino-

hemoglobin)

HCO3– + H+

HCO3–

Cl–

Cl–

HHb

Binds to

plasma

proteins

Chloride

shift

(in) via

transport

protein

CO2

CO2

CO2

CO2

CO2

O2

O2

In the tissues

CO2 Transport

• In pulmonary capillaries reaction is reversed

– 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

H2O + CO2 ↔ H2CO3 ↔ HCO3- + H+

CA

Figure 22.22b

Blood plasma

Alveolus Fused basement membranes

CO2

CO2

CO2

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

CO2

O2

O2 O2 (dissolved in plasma)

Cl–

Slow

CO2 (dissolved in plasma)

CO2 + H2O H2CO3 HCO3– + H+

Red blood cell

Carbonic

anhydrase

FastCO2 + H2O H2CO3

CO2 + Hb HbCO2

O2 + HHb HbO2 + H+

(Carbamino-

hemoglobin)

HCO3– + H+

HCO3–

Cl–

Chloride

shift

(out) via

transport

protein

In the lungs