PHYSICAL PRINCIPLES OF GAS EXCHANGE; DIFFUSION OF OXYGEN AND Diffusion of Gases in Liquids

CARBON DIOXIDE THROUGH THE RESPIRATORY MEMBRANE

RESPIRATORY SYSTEM “From gas phase to liquid phase”
Dr. Paloma
When a liquid is exposed to air containing a particular gas, molecules of that
gas will enter the liquid & dissolve in it

Henry’s law
 the amount of gas dissolved will be directly proportional to the
partial pressure of the gas with which the liquid is in equilibrium

 at equilibrium, the partial pressures of the gas molecules in the

liquid & gaseous phases must be identical

 gas exchanges between gas & liquid phases obey the law of
diffusion (high to low until equilibrium is reached)

 The amount of dissolved gas molecules at equilibrium is also

determined by the solubility coefficient of the gas

 Partial pressure = Concentration of dissolved gasSolubility

RESPIRATORY SYSTEM – GAS EXCHANGE coefficient

Physics of Gas Diffusion & Gas Partial Pressures  If the concentration of the dissolved gas is increased, its partial
pressure will also increase & vice versa
Dalton’s law
  in a mixture of gases, each gas exerts its own individual  If the solubility coefficient of the gas is increased, its partial
pressure, the so called partial pressure. pressure will decrease & vice versa
 the partial pressure of a gas is directly proportional to its
concentration  partial pressures of dissolved gasses are also denoted by a P in
  net diffusion of a gas occurs from a region where its partial front of the symbol for the gas. e.g. PO2, PCO2
pressure is high to a region where it is low
 usually expressed in mmHg units

partial pressures are denoted by a P in front of the symbol for the gas. e.g.  different gasses have different solubilities
PO2, PCO2
 The more soluble a gas is the more of this gas is needed to
 atmospheric or barometric pressure is the sum of all the partial pressures produce a given partial pressure that can be exerted by a less
of the gases in the air (760 mmHg at sea level). soluble gas

 air is about 79% nitrogen & 21% oxygen, w/ very small amount of CO2,  The amount of CO2 needed to produce the same P exerted by
water vapor & inert gases O2 is about 20 times that of O2 (diagram below)
PO2 = 760 x 0.21 ≈160 mmHg (sea level)
PN2 =760 x 0.79 ≈ 600 mmHg (sea level)
Partial Pressures of Respiratory Gases as They Ender & Leave the Lungs
(1) thickness of the membrane,

(2) surface area of the membrane

(3) diffusion coefficient of the gas in the substance of the membrane

(4) partial pressure difference of the gas between two sides of the
membrane

Diffusion rate formula

Layers of the Respiratory Membrane

1. Layer of fluid lining the alveolus containing surfactant

D – diffusion rate
2. Alveolar epithelium com-posed of thin epithelial cells ΔP – difference between the partial pressures
A – cross-sectional area for diffusion
3. Epithelial basement membrane S – solubility of the gas
d – distance of diffusion
4. A thin interstitial space between alveolar epithelium & capillary membrane MW – molecular weight of the gas

5. Capillary basement

6. Capillary endothelial membrane

RESPIRATORY MEMBRANE
Thickness = 0.6μM
Total Surface area = 70 M2 (25 ft x 30 ft)
Total amount of blood contained in this area = 100 ml

Factors That Affect the Rate of Gas Diffusion Through the Respiratory Effects of Various Conditions on Alveolar Gas Ventilation
Membrane CONDITION Alveolar Po2 Alveolar Pco2
  Normal gas exchange requires that ventilation and perfusion of
Breathing air with Decreases No change the alveoli are correctly matched with each other
low PO2
 If an alveolus is well ventilated it must be also well perfused. If it is
Alveolar Increases Decreases poorly ventilated, the blood flowing in it should also be reduced
ventilation & accordingly, else there is ventilation-perfusion inequality
unchanged
metabolism  Is expressed as VA/Q

Alveolar Decreases Increases

ventilation &
unchanged
metabolism

Metabolism & Increase Decreas

unchanged e
alveolar
ventilation

Alveolar Decreas Increase

ventilation & e
unchanged
metabolism

Proportional No change No change Zero V/Q Infinity

increase in
metabolism and
alveolar
ventilation In between these 2 extremes
 If V/Q is less than normal (poor ventilation) = physiologic shunt
 The alveolar PO2 increases as alveolar ventilation increases up to
a ceiling of 149 mmHg  If V/Q is greater than normal (poor perfusion) = physiologic
dead space (wasted ventilation)
 The alveolar PCO2 increases directly in proportion to the rate of
carbon dioxide excretion

 Second, the alveolar PCO2 decreases in inverse proportion to

alveolar ventilation

TRANSPORT OF OXYGEN AND CARBON DIOXIDE IN BLOOD AND TISSUE

FLUIDS
Concept of Ventilation-Perfusion Ratio
Transport of Oxygen from the Lungs to the Body Tissues

Diffusion of O2 from Alveoli to Pulmonary Capillary Blood’

Diffusion of oxygen from a tissue capillary to the cells. (PO2 in interstitial

fluid = 40 mm Hg, and in tissue cells = 23 mm Hg.)

Effect of blood flow and rate of oxygen consumption on tissue PO2

 SAFETY FACTOR 
EQUILIBRIUM

Uptake of oxygen by the pulmonary capillary blood (Resting condition)

During Exercise
the time that the blood remains in the pulmonary capillary may be reduced
to less than ½ the normal

Not a problem because:

Diffusing capacity for O2 increases almost 3x during exercise

nonexercising conditions - the blood becomes almost saturated with O2 by

the time it has passed through 1/3 of the pulmonary capillary (allowance for  Increased rate of blood flow increases interstitial fluid PO2.
exercise or diseases) (NOTED BY SAFETY FACTOR @ DIAGRAM)  Increased rate of tissue metabolism decreases interstitial fluid
PO2
Arterial blood has lower PO2 than pulmonary capillary and pulmonary
veins blood
Diffusion of Carbon Dioxide from the Peripheral Tissue Cells into the
effect of “venous admixture.”(a combination of fully oxygenated blood and Capillaries and from the Pulmonary Capillaries into the Alveoli
venous blood) (noted by the short plateau @ Diagram)

98% of blood that enters the left atrium passed through the alveolar
capillaries w/ a Po2 of 104 mm Hg.
2% of the blood passed from the aorta thru the bronchial circulation, w/c
supplies the deep tissues of the lungs & is not exposed to lung air

 Intracellular Pco2, 46 mm Hg;

 Interstitial Pco2, 45 mm Hg.

 Pco2 of the arterial blood entering tissues, 40 mm Hg;

 Pco2 of the venous blood leaving the tissues, 45 mm Hg.

Changes in PO2 in the pulmonary capillary blood, systemic arterial blood, and
systemic capillary blood, demonstrating the effect of “venous admixture.”
 Role of Hemoglobin in Oxygen Transport

EQUILIBRIUM

O2-Hgb Dissociation curve

 97% of the O2 transported from the lungs to the tissues carried in

combination with hemoglobin in the red blood cells.
 Pco2 of the blood entering the pulmonary capillaries at the
arterial end, 45 mm Hg;  3% is transported in the dissolved state in the water of the plasma
and blood cells
 Pco2 of the alveolar air, 40 mm Hg.

Maximum Amount of Oxygen That Can Combine with the Hemoglobin of

the Blood
Effect of Rate of Tissue Metabolism and Tissue Blood Flow on Interstitial
PCO2
Normal Values
Hemoglobin (Hgb) = 15 grams per 100ml of blood
 A decrease in blood flow increases peripheral tissue Pco2 & vice
1 gram of Hgb can bind 1.34ml of O2
versa
15 x 1.34 = 20.1 – means that
At 100% saturation, arterial blood carries 20 ml of O2 per 100ml of blood
 Increase in tissue metabolic rate greatly elevates the interstitial
This is usually expressed as 20 volumes percent.
fluid Pco2 & vice versa
 Venous blood is 75% saturated and can be expressed as 15

volumes %
 So normally
our tissues
receive 5
volumes%
of O2
(5 ml of O2
per 100ml
of passing
blood)
OXYGEN TRANSPORT

FACTORS THAT SHIFT THE OXYGEN DICUSSIATION CURVE

Under normal operating conditions, the rate of oxygen usage by the cells is
controlled ultimately by the rate of energy expenditure within the cells—
that is, by the rate at which ADP is formed from ATP.

Shift to right:

(1) Increased hydrogen ions (Bohr Effect)

(2) Increased CO2
(3) Increased temperature
(4) Increased 2,3-BPG
(5) Decreased pH

Shift to left:
(Opposite to the above)
(1) Decreased hydrogen ions (Bohr Effect)
(2) Decreased CO2
(3) Decreased temperature
(4) Decreased 2,3-BPG
(5) Increased pH

Shift to the right means decreased affinity for O2

Shift to the left means increased affinity for O2
Combination of Hemoglobin with Carbon Monoxide—Displacement Transport of Carbon Dioxide in the Blood
of Oxygen
Chemical Forms in Which Carbon Dioxide Is Transported
1. Transport of carbon dioxide in the dissolved state (7%)

2. Transport of carbon dioxide in combination with hemoglobin & plasma

proteins-carbaminohemoglobin (23%)

3. Transport of carbon dioxide in the form of bicarbonate ion (70%)

 CO – a poison

 Lethal at 0.6 mHg (a volume concentration of less than one part

per thousand in air) or .001% Note: Role of carbonic anhydrase
Chloride shift (bicarbonate-chloride carrier protein in the red cell
Treatment: membrane
 100% O2 and 5% CO2
 w/ oxygen and carbon dioxide therapy, CO can be removed from
the blood as much as 10 times faster as without therapy
 Hgb has a greater affinity (205x more) for CO than O2

CO2 TRANSPORT
Expiration of CO2 is by bulk flow, whereas all movements of CO2 across
membranes are by diffusion. Arrows reflect relative proportions of the fates
of the CO2. About two-thirds of the CO2 entering the blood in the tissues
ultimately is converted to HCO3 in the erythrocytes where carbonic
anhydrase is located, most of the HCO3 then moves out of the erythrocytes
into the plasma in exchange for chloride ions ( "chloride shift")
 REGULATION OF RESPIRATION

RESPIRATORY CENTER

(1) dorsal respiratory group

dorsal portion of the medulla
mainly causes inspiration
(2) ventral respiratory group
ventrolateral part of the medulla
mainly causes expiration
(3) pneumotaxic center
dorsally in superior portion of pons
mainly controls rate & depth of breathing.

 Binding of H+ by hemoglobin (buffering effect of Hgb)

 Deoxyhemoglobin has a greater affinity for H+ than does
oxyhemoglobin

HALDANE EFFECT
O2 binding by Hgb promotes release of CO2

Combination of O2 w/ Hgb in the lungs makes Hgb a stronger acid &

displaces CO2 from the blood & into the alveoli in 2 ways:

(1) Acidic Hgb has less tendency to combine w/ CO2 to form

carbaminohemoglobin, displacing much of the CO2 that is present in the
carbamino form

(2) Acidic Hgb releases H+, & these bind w/ HCO3- ions to form H2CO3;
dissociates into H2O & CO2 & the CO2 is released from the blood into the
alveoli & into the air.

dorsal respiratory group plays the most fundamental role in the control of
respiration

Dorsal Respiratory Group

Rhythmical inspiratory discharges from the dorsal respiratory group

The inspiratory signal is a ramp signal (steady increase in signal strength)

One respiratory cycle activity

On for 2 seconds (ramp manner)
Off for 3 seconds (abrupt onset)

1 complete breath
2 seconds for inspiration
3 seconds for expiration

5 seconds for 1 breath so 12 cycles in 1 minute (normal respiratory rate)

Portions of the CO2 dissociation curve when the PO2 is 100 mm Hg or 40 mm

Hg.

The arrow represents the Haldane effect on the transport of CO2

Haldane effect doubles the amount of CO2 released from the blood in the
lungs and approximately doubles the pickup of CO2 in the tissues.
 Chemosensitive Area of the Respiratory Center (central chemoreceptors)
Control of Inspiratory Ramp  Inspiratory area is stimulated by signals from chemosensitive
area
1.Control of the rate of increase of the ramp signal (for rapid filling of  chemosensitive area (located beneath ventral medullary surface.
lungs)  Excitation of chemosensitive neurons by H+ is primary stimulus
 CO2 in the blood indirectly stimulates the chemosensitive
2.Control of the limiting point at which the ramp suddenly ceases. neurons by forming H+
This is the usual method for controlling the rate of respiration  Blood CO2 more potent than blood H+ because BB barrier is
early cessation = increased rate (illustrated below) permeable to CO2 but not to H+
delayed cessation = decreased rate  CO2 has a potent acute effect on controlling respiratory drive
but only a weak chronic effect

A Pneumotaxic Center
limits the duration of inspiration and increases the respiratory rate VRG of
Neurons
inactive during normal quiet respiration
activated by signals that spill over from the dorsal respiratory area
contribute to both inspiration and expiration
Chemical Control of Respiration
provides powerful expiratory signals to the abdominal muscles during  marked increase in ventilation caused by an increase in Pco2 in
very heavy expiration. the normal range between 35 & 75 mm Hg
Hering- Breuer inflation reflex  relative low potency of effect of [H+]
mediated by pulmonary stretch receptors
cuts short inspiration when TV > 1.5 L
prevents over-inflation of lungs

Peripheral Chemoreceptor System

 High PaCO2 stimulates:

 peripheral chemoreceptors when it increased [H+] in blood

 central chemoreceptors by increasing [H+] in the brain ECF

 sensitive to changes in arterial Po2 in the range of 60 down to 30

mm Hg

 Increase in discharge when arterial PO2 drops

 Increase in ventilation when arterial PO2 drops (starting from 60

mmHg)

Low PaO2 & non-carbonic acids stimulate peripheral chemoreceptors Effect of exercise on oxygen consumption and ventilatory rate
 Cheyne-Stokes breathing, showing changing PCO2 in the pulmonary blood
(red line) and delayed changes in the PCO2 of the fluids of the respiratory
center (blue line)

 Note the initial drop of PaCO2 following increase in ventilation

(TOP 2nd figure)

 Note the increase in alveolar ventilation even when PaCO2 is still

normal(BOTTOM 2nd figure)
These indicate that the increase in ventilation during exercise is
not due to PCO2, or pH changes

Changes in alveolar ventilation (bottom curve) & arterial PCO2 (top curve)
during a 1-minute period of exercise & also after termination of exercise.

Other Factors That Affect Respiration

 Voluntary Control of Respiration
 Irritant Receptors in the Airways
 Brain Edema
 Anesthesia

Cheyne-Stokes Breathing (a form of periodic breathing)

Obstructive Sleep Apnea

 caused by blockage of the upper airway

 loud snoring & labored breathing

 interrupted by periods of apnea

 low PO2 & high PCO2

 fragmented, restless sleep

 excessive daytime drowsiness

 CPAP