Chapter 23

Gas Exchange and Transportation

What is air?

• Mixture of gasses

– 78.6 % nitrogen– 20.9% oxygen– 0.04% carbon dioxide– 0 – 4% water vapor depending on temperature and

humidity– and minor gases argon, neon, helium, methane and ozone

• Dalton’s Law – the total atmospheric pressure is the sum of the contributions of the individual gases

How do we express different concentration of gasses in air?

– Partial Pressure – the separate contribution of each gas in a mixture (at sea level 1 atm. of pressure = 760 mmHg)

– nitrogen constitutes 78.6% of the atmosphere, thus

• PN2 = 78.6% x 760 mm Hg = 597 mm Hg

• PO2

= 20.9% x 760 mm Hg = 159 mm Hg

• PH2O = 0.5% x 760 mm Hg = 3.7 mm Hg

• PCO2 = 0.04% x 760 mm Hg = 0.3 mm Hg

• PN2

+ PO2

+ PH2O + PCO2

= 760 mmHg

We are most concerned with oxygen and carbon dioxide.

How do these gas concentrations change betweenthe atmosphere and systemic tissues?

159 mmHg - atmosphere105 mmHg - alveolar100 mmHg - blood arterial040 mm Hg - systemic tissue040 mmHg - blood venous

.3 mmHg - atmosphere40 mmHg - alveolar40 mmHg - blood arterial45 mmHg - systemic tissue45 mmHg - blood venous

Carbon DioxideOxygen

How is inspired air different than alveolar air?

• Composition of inspired air and alveolar is different because of three influences

1. air is humidified by contact with moist mucous membranes // alveolar PH2O is more than 10 times higher than inhaled air

2. freshly inspired air mixes with residual air left from the previous respiratory cycle // oxygen is diluted and it is enriched with CO2

3. alveolar air exchanges O2 and CO2 with the blood

• PO2 of alveolar air is about 65% that of inspired air• PCO2 is more than 130 times higher

– The back-and-forth traffic of O2 and CO2 across the respiratory membrane

– air in the alveolus is in contact with a film of water covering the alveolar epithelium /// for oxygen to get into the blood it must dissolve in this water (Henry’s Law)

– pass through the respiratory membrane which separates the air from the bloodstream

– for carbon dioxide to leave the blood it must pass the other way // diffuse out of the water film into the alveolar air

– Individual gases diffuse down their own concentration gradients until the partial pressure of each gas in the air is equal to its partial pressure in water

How is inspired air different than alveolar air?

• Henry’s law – at the air-water interface, for a given temperature, the amount of gas that dissolves in the water is determined by its solubility in water and its partial pressure in air

– the greater the PO2 in the alveolar air, the more O2 that can be moved into blood

– blood arriving at an alveolus has a higher PCO2 than air, it releases CO2 into the lumen of the alveolus

In Alveolar Gas Exchange, What Must Happen Before Gas Molecules Can Cross the Respiratory Membrane?

What happens at the respiratory membrane?

– Respiratory membrane is inter-phase between two simple squamous cell surfaces /// alveoli and capillary

• unload CO2 (transported using three mechanisms)• load O2 (must be transported by RBC)

– Oxygen loading is dependant on how long RBC stays in alveolar capillaries

– 0.25 sec is necessary to load O2 (reach equilibrium)

– at rest, RBC spends 0.75 sec in alveolar capillaries

– strenuous exercise, 0.3, which is still adequate

– If disease destroys respiratory membrane then not enough time to load oxygen!

Pulmonary Capillaries Around Alveolus

Cross Section of AlveolusThe Respiratory Membrane

Factors Affecting Gas Exchange Pressure / Solubility / Temperature / pH

Respiratory Membrane Thickness / Ventilation VS Perfusion

• Pressure gradient of the gases

– PO2

= 105 mm Hg in alveolar air versus 40 mm Hg in blood

– PCO2 = 45 mm Hg in blood arriving

versus 40 mm Hg in alveolar air

159 mmHg - atmosphere105 mmHg - alveolar100 mmHg - blood arterial040 mm Hg - systemic tissue040 mmHg - blood venous

Oxygen

.3 mmHg - atmosphere40 mmHg - alveolar40 mmHg - blood arterial45 mmHg - systemic tissue45 mmHg - blood venous

Carbon Dioxide

• Solubility of the gases

– CO2 /// 20 times as soluble as O2

– O2 /// poorly soluble in water (said to be insoluble!)

What Physical Factors Affect Gas Exchange? (Pressure & Solubility)

Ambient Pressure & Concentration Gradients

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pressure gradient of O2

2,500

158

110

40

Am

bien

t PO

2(m

m H

g)

Air in hyperbaric chamber(100% O2 at 3 atm)

Steep gradient, rapid O2 diffusionNormal gradient and O

2 diffusionReduced gradient, slower O2 diffusion

Air at 3,000 m(10,000 ft)

Air at sea level(1 atm)

Atmosphere Venous bloodarriving atalveoli

Factors Affecting Gas Exchangemembrane thickness / membrane surface area / ventilation-perfusion coupling

• Membrane thickness

– only 0.5 μm thick

– presents little obstacle to diffusion

– pulmonary edema in left side ventricular failure causes edema and thickening of the respiratory membrane

– pneumonia causes thickening of respiratory membrane

– farther to travel between blood and air

– cannot equilibrate fast enough to keep up with blood flow

• Membrane surface area

– 100 ml blood in alveolar capillaries, spread thinly over 70 m2

– emphysema, lung cancer, and tuberculosis decrease surface area for gas exchange

Factors Affecting Gas Exchange

Lung Disease Affects Gas Exchange

(a) Normal

(b) Pneumonia

(c) Emphysema

Fluid andblood cellsin alveoli

Alveolarwallsthickenedby edema

Confluentalveoli

• Ventilation-perfusion coupling

– the ability to match ventilation and perfusion to each other

– gas exchange requires both good ventilation of alveolus and good perfusion of the capillaries

– ventilation-perfusion ratio of 0.8

• a flow of 4.2 L of air

• and 5.5 L of blood per minute at rest

Factors Affecting Gas Exchange

Perfusion AdjustmentsCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

(a) Perfusion adjusted to changesin ventilation

Reduced PO2 inblood vessels

Elevated PO2 inblood vessels

Increasedairflow

Vasoconstriction ofpulmonary vessels

Vasodilation ofpulmonary vessels

Decreasedblood flow

Increasedblood flow

Result:Blood flow

matches airflowResponseto reducedventilation

Responseto increasedventilation

Decreasedairflow

Ventilation Adjustments

Elevated PCO2in alveoli

Reduced PCO2in alveoli

Decreasedblood flow

Result:Airflow matches

blood flow

Responseto increased

perfusionConstriction ofbronchioles

Decreasedairflow

Dilation ofbronchioles

Increasedairflow

Responseto reducedperfusion

(b) Ventilation adjusted to changes in perfusion

Increasedblood flow

Gas Transport

• the process of carrying gases

– from the alveoli to the systemic tissues– from the system tissues to the alveoli

• oxygen transport

– 98.5% bound to hemoglobin– 1.5% dissolved in plasma

• carbon dioxide transport

– 70% as bicarbonate ion – 23% bound to hemoglobin – 7% dissolved in plasma

How are gasses transported in blood?

Oxygen Transport

• Arterial blood carries about 20 mLof O2 per deciliter

– 95% bound to hemoglobin in RBC

– 1.5% dissolved in plasma

Oxygen Transport• Hemoglobin – molecule specialized in oxygen transport

• four protein (globin) portions

• each with a heme group which binds one O2 to the ferrous ion (Fe2+)

• one hemoglobin molecule can carry up to 4 O2

• oxyhemoglobin (HbO2) – O2 bound to hemoglobin

• deoxyhemoglobin (HHb) – hemoglobin with no O2

• 100 % saturation Hb with 4 oxygen molecules

• 50% saturation Hb with 2 oxygen molecules

Carbon Dioxide Transport

• Carbon dioxide transported in three forms

– carbonic acid

– carbamino compounds

– dissolved in plasma

Carbon Dioxide Transport

• 70% of CO2 is hydrated to form carbonic acid

– CO2 + H2O → H2CO3 → HCO3- + H+

– then dissociates into bicarbonate and hydrogen ions

• 23% binds to the amino groups of plasma proteins and hemoglobin to form carbamino compounds – chiefly carbaminohemoglobin (HbCO2)

– carbon dioxide does not compete with oxygen– they bind to different moieties on the hemoglobin

molecule– hemoglobin can transport O2 and CO2 simultaneously

• 7% is carried in the blood as dissolved gas

How do RBC know when to load and unload oxygen?Systemic Gas Exchange

• Unloading of O2 /// from blood into tissue

• Loading CO2 /// from tissue into blood

– Key event occurs inside RBC // requires carbonic anhydrase

• CO2 + H2O → H2CO3 → HCO3- + H+

– The “Chloride Shift”

• keeps reaction proceeding // exchanges HCO3- for Cl-

• H+ binds to hemoglobin

• O2 unloading

– H+ binding to HbO2 reduces its affinity for O2

• tends to make hemoglobin release oxygen

• HbO2 arrives at systemic capillaries 97% saturated, leaves 75% saturated

– venous reserve – oxygen remaining in the blood after it passes through the capillary beds

– utilization coefficient – gives up 22% of its oxygen load

How do RBC know when to load and unload oxygen?Systemic Gas Exchange

Systemic Gas ExchangeCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiring tissue Capillary blood

Dissolved CO2 gas

CO2 + plasma protein

CO2

CO2

O2Dissolved O2 gas

Carbamino compounds

Cl–

7%

23%

70%

98.5%

1.5%

CO2 + Hb

CO2 + H2O

O2 + HHb HbO2+ H+

H2CO3 HCO3– + H+

HbCO2

CAH

Key

Chloride shift

CO2

O2

HbCO2 CarbaminohemoglobinHb Hemoglobin

HHb DeoxyhemoglobinCAH Carbonic anhydrase

HbO2 Oxyhemoglobin

Alveolar Gas Exchange

• The reactions that occur in the lungs are simply the reverse of systemic gas exchange

Alveolar Gas ExchangeCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory membrane Capillary blood

CO2

O2

Alveolar air

Carbamino compounds

7%

23%

70%

98.5%

1.5%

HbCO2

CAH

Key

Cl−Chloride shift

CO2

CO2

O2 Dissolved O2 gas

O2 + HHb HbO2 + H+

HCO3− + H+H2 CO3CO2 + H2O

CO2 + Hb

CO2 + plasma protein

Dissolved CO2 gas

Hb HemoglobinHbCO2 CarbaminohemoglobinHbO2 OxyhemoglobinHHb DeoxyhemoglobinCAH Carbonic anhydrase

Oxyhemoglobin Dissociation Curve

relationship between hemoglobin saturation and PO2

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

100

80

60

40

20

0

20

15

10

5

Systemic tissues Alveoli

Perc

enta

ge O

2sa

tura

tion

of h

emog

lobi

n

mL

O2

/dL

of b

lood

O2 unloadedto systemictissues

Partial pressure of O2 (PO2) in mm Hg

0 20 40 60 80 100

Oxygen Dissociation and Temperature

10°C

38°C43°C

Normal bodytemperature

Perc

enta

ge s

atur

atio

n of

hem

oglo

bin

100

00 20 40 60 80 100 120 140

10°C20°C90

80

70

60

50

40

30

20

10

PO2 (mm Hg)

Oxygen Dissociation and pH

Bohr effect: release of O2 in response to low pH

100

90

80

70

60

50

40

30

20

10

00 20 40 60 80 100 120 140

Perc

enta

ge s

atur

atio

n of

hem

oglo

bin

pH 7.60

pH 7.20

PO2 (mm Hg)

pH 7.40(normal blood pH)

This Chart Shows Fetal Hb Has a Greater Infinity for O2 Than Maternal Hb

Adjustment Oxygen Unloadingto Metabolism of Tissues

• Hemoglobin unloads O2 to match metabolic needs of different states of activity of the tissues

• Factors that adjust the rate of oxygen unloading

– ambient PO2

/// active tissue has ↓ PO2 ; O2 is

released from Hb

– temperature /// active tissue has ↑ temp; promotes O2 unloading

Adjustment of Oxygen Unloadingto Metabolism of Tissues

– Bisphosphoglycerate (BPG) – intermediate in glycolisis // as concentration of BPG increases it indicates high level of anarobicmetabolism

• RBCs produce BPG which binds to Hb /// O2 is unloaded

• ↑ body temp (fever), thyroxine, growth hormone, testosterone, and epinephrine all raise BPG and cause O2 unloading

• ↑ metabolic rate requires ↑ oxygen

• Haldane effect – rate of CO2 loading is also adjusted to varying needs of the tissues /// low level of oxyhemoglobin enables the blood to transport more CO2

Blood Gases and the Respiratory Rhythm

• Rate and depth of breathing adjust to maintain these levels

– pH 7.35 – 7.45– PCO2 40 mm Hg– PO2 95 mm Hg

• Brainstem respiratory centers receive input from central and peripheral chemoreceptors that monitor the

• Composition of blood and CSF /// most potent stimulus for breathing is pH (CO2) /// least significant is O2

Hydrogen Ions (Remember CO2 = H+ )

• Pulmonary ventilation is adjusted to maintain the pH of the brain

– central chemoreceptors in the medulla oblongata produce about 75% of the change in respiration induced by pH shift

– yet H+ does not cross the blood-brain barrier very easily

– CO2 crosses blood brain barrier rapidly and in CSF reacts with water and produces carbonic acid

• dissociates into bicarbonate and hydrogen ions /// most H+

remains free and greatly stimulates the central chemoreceptors

– hydrogen ions are also a potent stimulus to the peripheral chemoreceptors which produce about 25% of the respiratory response to pH change

Hydrogen Ions• acidosis – blood pH lower than 7.35

• alkalosis – blood pH higher than 7.45

• hypocapnia – PCO2 less than 37 mm Hg (normal 37 – 43 mm Hg) /// most common cause of alkalosis

• hypercapnia – PCO2 greater than 43 mm Hg /// most common cause of acidosis

How does hyperventilation affect respiration?

• Respiratory acidosis and respiratory alkalosis /// pH imbalances resulting from a mismatch between the rate of pulmonary ventilation and the rate of CO2 production

• Hyperventilation is a corrective homeostatic response to acidosis /// “blowing off ” CO2 faster than body produces it

– pushes reaction to the left CO2 (expired) + H2O ← H2CO3 ← HCO3

- + ↓ H+

– reduces H+ (reduces acid) and raises blood pH towards normal (pH 7.4)

• Hypoventilation is a corrective homeostatic response to alkalosis

– allows CO2 to accumulate in the body fluids faster than we exhale it

– shifts reaction to the right

– CO2 + H2O → H2CO3 → HCO3- + H+

– raising the H+ concentration, lowering pH to normal

How does hyporventilation affect respiration?

Effects of Hydrogen Ions

• Ketoacidosis – acidosis brought about by rapid fat oxidation that releases acidic ketone bodies (as in diabetes mellitus)

– induces Kussmaul respiration

• Deep rapid respiration /// air hunger

• hyperventilation cannot remove ketone bodies

• however, blowing off CO2 // reduces blood CO2

concentration and compensates for the ketone bodies to some degree

Carbon Dioxide

• Indirect effects on respiration /// through pH as seen previously

• Direct effects

– ↑ CO2 at beginning of exercise may directly stimulate peripheral chemoreceptors

– Peripheral chemorecptors trigger ↑ ventilation more quickly than central chemoreceptors

Why does respiration increase during exercise?

• As upper motor neurons of brain sends motor commands to the skeletal muscles

• it also sends collateral signals to the respiratory centers in medulla

• they increase pulmonary ventilation in anticipation of the needs of the exercising muscles

• Exercise stimulates proprioceptors of the muscles and joints

• they transmit excitatory signals to the brainstem respiratory centers

• increase breathing because they are informed that the muscles have been told to move or are actually moving

• increase in pulmonary ventilation keeps blood gas values at their normal levels in spite of the elevated O2 consumption and CO2 generation by the muscles

Why does respiration increase during exercise?

Control of Ventilation

• Primary control centers for breathing // Located in the medulla and pons

• Chemoreceptors detect changes in carbon dioxide level, hydrogen ion, and oxygen levels in blood or cerebrospinal fluid (CSF)

– Central chemoreceptors // Located in the medulla

– Peripheral chemoreceptors // Located in the carotid bodies and aortic arch

• Carbon dioxide main driver under normal conditions

Respiratory Control

Normal Control of Ventilation

• Hypercapnia

– Carbon dioxide levels in the blood increase.

– Carbon dioxide easily diffuses into CSF.

• Lowers pH and stimulates respiratory center

• Increased rate and depth of respirations (hyperventilation)

• Note: Hyperventilation causes respiratory alkalosis // nervous system depression

Secondary or Non-normal Control of Ventilation

• Hypoxemia // Marked decrease in oxygen

• Primary stimulus under normal conditions is elevated CO2 however

• Extended period of high CO2 will cause chemoreceptors not to react to CO2

• Chemoreceptors now react to O2 levels

• important control mechanism in individuals with chronic lung disease

• This is a move to hypoxic drive

Hypoxic Drive

Respiratory Disorders & Oxygen Imbalances

• hypoxia – a deficiency of oxygen in a tissue or the inability to use oxygen /// a consequence of respiratory diseases

• hypoxemic hypoxia – state of low arterial PO2 – usually due inadequate pulmonary gas exchange– oxygen deficiency at high elevations, impaired ventilation –

drowning, aspiration of a foreign body, respiratory arrest, degenerative lung diseases

• ischemic hypoxia – inadequate circulation of blood /// congestive heart failure

• anemic hypoxia – due to anemia resulting from the inability of the blood to carry adequate oxygen

• histotoxic hypoxia – metabolic poisons such as cyanide prevent the tissues from using oxygen delivered to them

Carbon Monoxide Poisoning

• Carbon monoxide (CO) - competes for the O2 binding sites on the hemoglobin molecule

• colorless, odorless gas in cigarette smoke, engine exhaust, fumes from furnaces and space heaters

• Carboxyhemoglobin – CO binds to ferrous ion of hemoglobin

– binds 210 times as tightly as oxygen

– ties up hemoglobin for a long time

– non-smokers - less than 1.5% of hemoglobin occupied by CO

– Smokers - CO 10% in heavy smokers

– atmospheric concentrations of 0.2% CO is quickly lethal