RESPIRATORY

SYSTEM
DR. W. A SAKA
• EXCHANGE OF OXYGEN AND CARBON DIOXIDE
• The exchange of oxygen and carbon dioxide between
alveolar air and pulmonary blood occurs via passive
diffusion.

• This is governed by the behavior of gases as

described by two gas laws, Dalton’s law and Henry’s law.

• Dalton’s law is important for understanding

how gases move down their pressure gradients by diffusion.

• Henry’s law helps explain how the solubility of a gas

relates to its diffusion.
• Dalton’s law states that each gas in a mixture of gases exerts
its own pressure as if no other gases were present.

• The pressure of a specific gas in a mixture is called its partial

pressure (Px); the subscript is the chemical formula of the
gas. The total pressure of the mixture is calculated simply by
adding all of the partial pressures.

• Atmospheric air is a mixture of gases—nitrogen (N2 ), oxygen

(O2 ), argon (Ar), carbon dioxide (CO2 ), variable amounts of
water vapor (H2O), plus other gases present in small
quantities.

• Atmospheric pressure is the sum of the pressures of all of

these gases:
• Atmospheric pressure (760 mmHg)
= PN2 + PO2 + PAr + PH2O + PCO2 + Pother gases

• We can determine the partial pressure exerted by each

component in the mixture by multiplying the percentage of
the gas in the mixture by the total pressure of the mixture.

• Atmospheric air is 78.6% nitrogen, 20.9% oxygen,

0.093% argon, 0.04% carbon dioxide, and 0.06% other
gases; a variable amount of water vapor is also present.

• The amount of water varies from practically 0% over a

desert to 4% over the ocean, to about 0.4% on a cool, dry
day.
• Thus, the partial pressures of the gases in inhaled air are
as follows:
• PN2 = 0.786 × 760 mmHg = 597.4 mmHg
• PO2 = 0.209 × 760 mmHg = 158.8 mmHg
• PAr = 0.0009 × 760 mmHg = 0.7 mmHg
• PH2O = 0.003 × 760 mmHg = 2.3 mmHg
• PCO2 = 0.0004 × 760 mmHg = 0.3 mmHg
• Pother gases = 0.0006 × 760 mmHg = 0.5 mmHg
• Total = 760.0 mmHg
• These partial pressures determine the movement of O2
and CO2 between the atmosphere and lungs, between
the lungs and blood, and between the blood and body
cells.
• Each gas diffuses across a permeable membrane from
the area where its partial pressure is greater to the area
where its partial pressure is less.

• The greater the difference in partial pressure, the

faster the rate of diffusion.

• Compared with inhaled air, alveolar air has less O 2

(13.6% versus 20.9%) and more CO2 (5.2% versus
0.04%) for two reasons.

• First, gas exchange in the alveoli increases the CO 2

content and decreases the O2 content of alveolar air.
• Second, when air is inhaled it becomes humidified as it
passes along the moist mucosal linings.

• As water vapor content of the air increases, the relative

percentage that is O2 decreases.

• In contrast, exhaled air contains more O2 than alveolar air

(16% versus 13.6%) and less CO2 (4.5% versus 5.2%)
because some of the exhaled air was in the anatomic dead
space and did not participate in gas exchange.

• Exhaled air is a mixture of alveolar air and inhaled air

that was in the anatomic dead space.
• Henry’s law states that the quantity of a gas that will
dissolve in a liquid is proportional to the partial pressure of
the gas and its solubility.

• In body fluids, the ability of a gas to stay in solution is

greater when its partial pressure is higher and when it has a
high solubility in water.

• The higher the partial pressure of a gas over a liquid and the
higher the solubility, the more gas will stay in solution.

• In comparison to oxygen, much more CO2 is dissolved in

blood plasma because the solubility of CO2 is 24 times
greater than that of O2.
• Even though the air we breathe contains mostly N 2,
this gas has no known effect on bodily functions,
and at sea level pressure very little of it dissolves in
blood plasma because its solubility is very low.

External and Internal Respiration

• External respiration or pulmonary gas exchange is
the diffusion of O2 from air in the alveoli of the
lungs to blood in pulmonary capillaries and the
diffusion of CO2 in the opposite direction.
• External respiration in the lungs converts deoxygenated
blood (depleted of some O2) coming from the right side
of the heart into oxygenated blood (saturated with O2)
that returns to the left side of the heart.

• As blood flows through the pulmonary capillaries, it

picks up O2 from alveolar air and unloads CO2 into
alveolar air.

• Although this process is commonly called an

“exchange” of gases, each gas diffuses independently
from the area where its partial pressure is higher to the
area where its partial pressure is lower.
• O2 diffuses from alveolar air, where its partial pressure is 105
mmHg, into the blood in pulmonary capillaries, where PO2 is
only 40 mmHg in a resting person.

• If you have been exercising, the PO2 will be even lower

because contracting muscle fibers are using more O2.

• Diffusion continues until the PO2 of pulmonary capillary

blood increases to match the PO2 of alveolar air, 105 mmHg.

• Because blood leaving pulmonary capillaries near alveolar

air spaces mixes with a small volume of blood that has
flowed through conducting portions of the respiratory
system, where gas exchange does not occur.
• Thus, the PO2 of blood in the pulmonary veins is slightly less than
the PO2 in pulmonary capillaries, about 100 mmHg.

• While O2 is diffusing from alveolar air into deoxygenated blood,

CO2 is diffusing in the opposite direction.

• The PCO2 of deoxygenated blood is 46 mmHg in a resting person,

and the PCO2 of alveolar air is 40 mmHg.

• Because of this difference in PCO2, carbon dioxide diffuses from

deoxygenated blood into the alveoli until the PCO 2 of the blood
decreases to 40 mmHg.

• Exhalation keeps alveolar PCO2 at 40 mmHg. Oxygenated blood

returning to the left side of the heart in the pulmonary veins thus has
a PCO2 of 40 mmHg.
• The number of capillaries near alveoli in the lungs is
very large, and blood flows slowly enough through
these capillaries that it picks up a maximal amount
of O2.

• During vigorous exercise, when cardiac output is

increased, blood flows more rapidly through both
the systemic and pulmonary circulations.

• As a result, blood’s transit time in the pulmonary

capillaries is shorter. Still, the PO2 of blood in the
pulmonary veins normally reaches 100 mmHg.
• In diseases that decrease the rate of gas diffusion,
however, the blood may not come into full
equilibrium with alveolar air, especially during
exercise.

• When this happens, the PO2 declines and PCO2 rises

in systemic arterial blood.
• The exchange of O2 and CO2 between systemic capillaries
and tissue cells is called internal respiration or systemic
gas exchange.

• As O2 leaves the bloodstream, oxygenated blood is

converted into deoxygenated blood.

• Unlike external respiration, which occurs only in the lungs,

internal respiration occurs in tissues throughout the body.

• The PO2 of blood pumped into systemic capillaries is

higher (100 mmHg) than the PO 2 in tissue cells (40 mmHg
at rest) because the cells constantly use O 2 to produce ATP.
• Due to this pressure difference, oxygen diffuses out of the
capillaries into tissue cells and blood PO2 drops to 40
mmHg by the time the blood exits systemic capillaries.

• While O2 diffuses from the systemic capillaries into tissue

cells, CO2 diffuses in the opposite direction.

• Because tissue cells are constantly producing CO2, the

PCO2 of cells (45 mmHg at rest) is higher than that of
systemic capillary blood (40 mmHg).

• As a result, CO2 diffuses from tissue cells through

interstitial fluid into systemic capillaries until the PCO 2 in
the blood increases to 45 mmHg.
• The deoxygenated blood then returns to the heart and is
pumped to the lungs for another cycle of external
respiration.

• In a person at rest, tissue cells, on average, need only 25%

of the available O2 in oxygenated blood; despite its name,
deoxygenated blood retains 75% of its O2 content.

• During exercise, more O2 diffuses from the blood into

metabolically active cells, such as contracting skeletal
muscle fibers.

• Active cells use more O2 for ATP production, causing the

O2 content of deoxygenated blood to drop below 75%.
• Factors affecting the rate of pulmonary and systemic
gas exchange include:

1. Partial pressure difference of the gases: Alveolar

PO2 must be higher than blood PO2 for oxygen to
diffuse from alveolar air into the blood.

• The rate of diffusion is faster when the difference

between PO2 in alveolar air and pulmonary capillary
blood is larger; diffusion is slower when the
difference is smaller.
2. Surface area available for gas exchange: the surface area
of the alveoli is huge (about 70 m2 or 750 ft2).

• In addition, many capillaries surround each alveolus, so

many that as much as 900 mL of blood is able to
participate in gas exchange at any instant.

• Any pulmonary disorder that decreases th functional

surface area of the respiratory membranes decreases the
rate of external respiration.

• In emphysema, for example, alveolar walls disintegrate,

so surface area is smaller than normal and pulmonary gas
exchange is slowed.
3. Diffusion distance: the respiratory membrane is
very thin, so diffusion occurs quickly.

• Also, the capillaries are so narrow that the red blood

cells must pass through them in single file, which
minimizes the diffusion distance from an alveolar
air space to hemoglobin inside red blood cells.

• Buildup of interstitial fluid between alveoli, as

occurs in pulmonary edema slows the rate of gas
exchange because it increases diffusion distance
4. Molecular weight and solubility of the gases:
because O2 has a lower molecular weight than CO 2,
it could be expected to diffuse across the respiratory
membrane about 1.2 times faster.

• However, the solubility of CO2 in the fluid portions

of the respiratory membrane is about 24 times
greater than that of O2.

• Taking both of these factors into account, net

outward CO2 diffusion occurs 20 times more rapidly
than net inward O2 diffusion.
TRANSPORT OF RESPIRATORY GASES
TRANSPORT OF OXYGEN
• Oxygen diffuses from the alveoli in to the
pulmonary capillaries along the pressure gradient.

• The gas diffuses into Red blood cells, where it

combines with haemoglobin to form
oxyhaemoglobin.

• Oxygen as dissolved form in the plasma is

negligible and the major form of transport is
oxyhaemoglobin
 REACTIONS BETWEEN HAEMOGLOBIN AND
OXYGEN
• The oxygen enters the haemoglobin and binds to the iron
present in the heme.

• There are 4 haeme in each haemoglobin molecule and each

iron can take one molecule of oxygen.

• When oxygen enters the haemoglobin, there are 4 interactions

between iron and oxygen and the reaction proceed in a
stepwise fashion.

• The hemoglobin, which is partially saturated which oxygen,

will show greater affinity for further oxygen uptake to
become fully saturated.
• The iron stays in a ferrous state, so that the reaction
is an oxygenation, not an oxidation.

• Hb4 + O2 Hb402
 
• Hb4O2 + O2 Hb4O4
 
• Hb4O4 + O2 Hb4O6
 
• Hb4O6 + O2 Hb4 O8
 
• The reaction is rapid, requiring less than 0.01s. The de-
oxygenation (reduction) of Hb4O8 is also very rapid.

• Oxygen affinity is greater for Hemoglobin molecule,

which is partially saturated.

• Hence Oxygen moves towards such Hemoglobin

molecules, rather than binding to a fresh Hemoglobin
molecule.

• This affinity of Hemoglobin for O2 to get fully saturated

at the pulmonary capillaries is responsible for the ‘S’ or
Sigmoid shaped curve of oxygen dissociation curve.
 OXYGEN HEMOGLOBIN DISSOCIATION CURVE
•  The curve relating percentage saturation of the O2 carrying
power of hemoglobin to the PO2 , has a characteristic
sigmoid shape.

• At 60mmhg of P02, the Hemoglobin is already 90%

saturated and thereafter, the curve is flat.

• At 98mmHg, the Hemoglobin is 97% saturated and this

represents the arterial point.

• The curve from 60mmHg t0 98mmHg of P02 is called the

loading part, below 60mmHg of P02 the curve steeply
declines in the % saturation of haemoglobin.
• The declining part of the curve is known as
unloading part of oxygen which occurs in the
tissues. At 40mmHg of P02, the saturation of
Hemoglobin is 70% which is known as venous
point.
• Factors Affecting the Affinity of Hemoglobin for
Oxygen
• Three important conditions affects the O 2.
Hemoglobin dissociation curve: the Ph, the
temperature and the concentration of 2, 3 bi-
phosphoglycerate (2, 3-BPG).
• A rise in temperature or a fall in pH shifts the curve to the
right.

• When the curve is shifted in this direction, a higher PO 2 is

required for Hemoglobin to bind a given amount of O 2.

• Conversely, a fall in temperature or a rise in Ph shifts the

curve to the left, and a lower Po2 is required to bind a
given amount of O2.

• A convenient index of such shifts is the P50, the Po2 at

which Hemoglobin is half saturated with O2. The higher
the P50, the lower the affinity of Hemoglobin for O2.
• The decrease in O2 affinity of haemoglobin when
the pH of blood falls is called Bohr’s effect.

• This is closely associated to the fact that de-

oxygenated haemoglobin binds H+ more actively
than those oxyhaemoglobin.

• The pH of blood falls as its CO2 content increases,

so that when the PCO2 rises, the curve shifts to the
right and the P50 rises.
• 2,3, BPG, is very plentiful in red cells and is formed from 3-
phosphoglyceraldehyde, which is a product of glycolysis.

• An increase in the concentration of 2,3- BPG shifts the reaction to the

right causing more O2 to be liberated.

• Factors affecting concentration of 2, 3-DPG in the red cells include pH,

2, 3- BPG concentration falls when the pH is low because acidosis
inhibits red cell glycolysis.

• Thyroid hormone, growth hormone and androgens increase the

concentration of 2, 3-BPG and the P50.

• Exercise has been reported to produce an increase in 2,3-BPG in 60

minutes, although the rise may not occur in trained athletes.

 
TRANSPORT OF CARBON (IV) OXIDE
• Carbon dioxide is formed in the cell as a result of metabolism.

• Carbon dioxide from tissues diffuses in to the capillaries along

the pressure gradient. In tissues the PCO2 is 46mmHg and in the
capillaries it is 40mmHg.

• This small pressure differences facilitates Carbon dioxide

diffusion for the reasons mentioned earlier.

• Carbon dioxide is transported to lungs by three ways:

1.) Simple physical solution in plasma
2.) Carbamino compounds
3.) Bicarbonate
 
 Transport as Simple Solution:
• Carbon dioxide is freely diffusible in plasma and is 20
times more soluble than oxygen.

• Carbon dioxide on entering the tissue capillaries form

carbonic acid with plasma.
 
• CO2 + H20 → H2CO3
 
• Since the carbonic anhydrase is absent in plasma, the
carbonic acid that is formed can shift the reaction to the
left.

• Hence, this kind of transport occurs for only 5%.

 Transport as carbamino compounds:
• Carbon dioxide combines with NH3 terminal group,
present in the protein molecule and form NH2-COOH.

• The reaction occurs with the plasma proteins and also

in the red blood cells by combining with haemoglobin.

• The transport of Carbon dioxide as carbamino

compounds forms 20% of the total transport of the gas.

 Transport as Bicarbonate: The major form of Carbon

dioxide transport occurs as bicarbonate (75%).
•  
• Carbon dioxide is freely diffusible in red blood cell
membrane and the red cell has carbonic anhydrase
enzyme which catalyses hydration of Carbon
dioxide to form carbonic acid.
 
• C02 +H20 → H2CO3

• CHLORIDE SHIFT: The carbonic acid that is

formed in the red blood cell is a weak acid and
dissociates into H+ and HCO3-.

• The H- is taken up by the deoxygenated hemoglobin

which is a lesser acid and forms HHb.
• The bicarbonate from the red blood cell diffuses into
the plasma in exchange for Cl- ion.

• Since the exit of bicarbonate disturbs Donnan’s

ionic electrochemical equilibrium, another anion Cl -
diffuses into the red cell.

• This is called the chloride shift (Hamberger’s

phenomenon).

• The Carbon dioxide that enters the red cell is

transported as bicarbonate in plasma.
• The red cell in the venous blood is slightly
spherical, due to the entry of water (H 2O), caused by
electrolyte movement into the cell.

• The PH of venous blood (7.38) is also slightly less

compared to the arterial blood (7.40) due to more
Carbon dioxide content.

• HALDANE’S EFFECT: In the lungs, the diffusion

of Oxygen into the pulmonary capillaries leads to
chemical reactions, resulting in the expulsion of
Carbon dioxide.
• This is known as Haldane’s effect. Haldane’s effect helps to reduce
CO2 retention and pH in the venous blood.

• The diffusion O2 in the pulmonary capillaries, releases H + from Hb.

 
HHb + O2 → HbO2 + H+
 
• The free H+ ion in the red cell causes the diffusion of HCO3 - from
plasma.

• This movement occurs in exchange for Cl - ion (reverse chloride

shift).

• HCO3 combines with H+ to form H2CO3 which dissociates into CO2

and H20.
 
 H+ + HCO3- → H2CO3 →

→ CO2 + H2O

• The Carbon dioxide diffuses into the alveoli along

the pressure gradient and expelled in the expired air.
 
EFFECT OF HIGH ALTITUDE ON
RESPIRATION
• In high altitude, the barometric pressure is reduced, but
not the composition of gases in the atmosphere.

• As one climbs the mountains, the partial pressure of

O₂ is increased proportionate to the ascent.

• The reduction in the arterial blood O₂ partial pressure

occurs in hypoxic hypoxia.

• At 1200 feet high, the barometric pressure is reduced

to 38mmHg and alveolar PO₂ decreases to 60mmHg.
• If the exposure to this altitude is sudden as occur in
loss of cabin pressure in an aircraft, acute hypoxia
can result.

• The effect of acute hypoxia is due to hypoxia effects

on the medullary neurons.

• The symptoms like disorientation, euphoric states

similar to alcohol drinking, poor judgement, mental
confusion, headache, palpitation and dyspnea are
observed in the affected subjects.
 
MOUNTAIN SICKNESS
• When a subject goes to high altitude as in mountain
climbing, at 12000ft height, symptoms of mountain
sickness occurs within 24hours.

• It is characterised by nausea, vomiting, headache,

palpitation, dyspnea, and mental confusion.

• At high altitude, if one engages in physical work or

climbing the mountain too rapidly without rest, it
can lead to high altitude pulmonary oedema.
• This is caused by the increased pulmonary capillary
pressure, leading to fluid exit into the pulmonary
interstitial space.

• The symptoms of mountain sickness occur probably

due to cerebral oedema caused by the cerebral dilation
of capillaries and fluid exit, in the presence of hypoxia.

• Administration of large amount of glucocorticoid,

resulted in relief from mountain sickness.

• There are reports that mountain sickness does not

occur if there is diuresis.
• However, use of diuretics does not prevent mountain sickness from
developing.

ACCLIMATIZATION TO HIGH ALTITUDE

• Acclimatization to high altitude (12,000-15,000ft height) occurs
after 4-5 days of exposure.

• In acclimatization, the physiological adaptation to high altitude

occurs. The physiological changes are as follows:

• Stimulation of ventilation from peripheral chemoreceptors

stimulation, caused by the fall in PO₂. The rate and depth of
breathing is increased.

• The respiratory stimulation continues for 4-5 days and thereafter,

normal breathing occurs.
• Increase in the heart rate and cardiac output occur due
to chemoreceptor stimulation by hypoxia and
sympathetic activation.

• Polycythaemia occur due to increased erythropoietin

secretion from the kidney.

• Red cell 2, 3-BPG production increases and the

oxygen dissociation curve shifts to the right, which
raises the P₅₀ value for haemoglobin % saturation.

• The tissues show increase in cytochrome enzymes

content and its activity for greater oxygen utilization.
• The increase in capillary density and mitochondrial
number also helps more oxygen supply and its
utilization.

• The acclimatization changes disappear after a few days,

when an individual comes back to the plains at sea level.

• The acclimatization to high level can be observed up to

18,000ft height. Beyond this level, oxygen has to be
supplied in the respired air, as alveolar PO₂ falls to 35 to
45mmHg.

• This is the critical level of PO₂ in the alveoli, which can

damage the CNS neurons, leading to death.
DYSBARISM
• When a person goes to a high barometric pressure,
nitrogen gas which is inert at atmospheric pressure,
dissolves in the body fluids and form bubbles.

• It also dissolves the fatty tissues like the myelin

sheath of neurons.

• These changes which are observed in high

barometric pressure give the condition called
dysbarism or nitrogen narcosis.
• For every 33ft depth, an atmospheric pressure is
added. If a person goes down to say 30 meters the
pressure exerted would be 4 atmospheres.
 
DECOMPRESSION SICKNESS
• Decompression sickness occur when the subject
rapidly ascends from a high barometric to a low
barometric pressure.

• The condition is prevalent in mine workers, tunnel

workers in sea bed (Caisson’s workers) and in deep
sea divers.
• Rapid ascent to the low barometric pressure from
barometric pressure causes decompression sickness.

• The nitrogen bubbles block the minute capillaries and

form emboli.

• This can lead to chokes (dyspnea), pain in the joints,

sensory disturbances (pins and needles), myocardial
infarction (if emboli are in coronary vessels), strokes and
paralysis (if emboli occurs in cerebral vessel).

• Decompression sickness occurs only if the ascent is rapid.

 
• It can be prevented by wearing decompression suite
or inhaling 100% oxygen with helium (helium has
low solubility in high barometric pressure compared
to nitrogen).

• The decompression sickness can be treated by

recompression followed by decompression.
THE EFFECTS OF EXERCISE ON THE
RESPIRATORY SYSTEM.
• The respiratory and cardiovascular systems make adjustments
in response to both the intensity and duration of exercise.

• Recall that the heart pumps the same amount of blood to the
lungs as to all the rest of the body.

• Thus, as cardiac output rises, the blood flow to the lungs,

termed pulmonary perfusion, increases as well.

• In addition, the O₂ diffusing capacity, a measure of the rate

at which O₂ can diffuse from alveolar air into the blood, may
increase threefold during maximal exercise because more
pulmonary capillaries become maximally perfused.
• As a result, there is a greater surface area available for
diffusion of O₂ into pulmonary blood capillaries.

• When muscles contract during exercise, they consume large

amounts of O₂ and produce large amounts of CO₂.

• During vigorous exercise, O₂ consumption and breathing both

increase dramatically.

• At the onset of exercise, an abrupt increase in breathing is

followed by a more gradual increase.

• With moderate exercise, the increase is due mostly to an

increase in the depth of breathing rather than to increased
breathing rate.
• When exercise is more strenuous, the frequency of breathing
also increases.

• The abrupt increase in breathing at the start of exercise is due

to neural changes that send excitatory impulses to the dorsal
respiratory group (DRG) of the medullary respiratory center
in the medulla.

• These changes include:

(1) anticipation of the activity, which stimulates the limbic
system;
(2) sensory impulses from proprioceptors in muscles, tendons,
and joints;
(3) motor impulses from the primary motor cortex (precentral
gyrus).
• The more gradual increase in breathing during moderate
exercise is due to chemical and physical changes in the
bloodstream, including

(1) slightly decreased PO2, due to increased O₂

consumption;
(2) slightly increased PCO2, due to increased CO₂
production by contracting muscle fibers;
(3) increased temperature, due to liberation of more heat
as more O₂ is utilized.

• During strenuous exercise, HCO3- buffers H+ released by

lactic acid in a reaction that liberates CO2, which further
increases PCO₂.
• At the end of an exercise session, an abrupt decrease
in breathing is followed by a more gradual decline
to the resting level.

• The initial decrease is due mainly to changes in

neural factors when movement stops or slows.

• The more gradual phase reflects the slower return of

blood chemistry levels and temperature to the
resting state.