Transcript Pulmonary Ventilation

Pulmonary Ventilation
Dr. Laila Dokhi
External respiration can be divided into
4 major functional events
1) Ventilation
2) Diffusion
3) Transport of O2 and CO2 in the
blood, body fluids, to and from
the cells
4) Regulation of ventilation
Mechanics of pulmonary ventilation
Respiratory muscles:
Diaphragm – which increase and decrease the vertical
diameter of the chest cavity.
Intercostal muscles – affect the anteroposterior
diameter of the chest cavity by moving the ribs.
Internal intercostal muscle (downward and backward)
 lower the ribs and sternum  reducing the
anteroposterior diameter
External intercostal muscle (downward and forward) 
raise the ribs and sternum  increasing the
anteroposterior diameter of the thoracic cavity
Normal quiet breathing
During inspiration: contraction of the diaphragm, pulls
the lower surfaces of the lungs downward
During expiration: by relaxation of the diaphragm and
elastic recoil of the lungs, chest wall, and abdominal
structures compresses the lungs
Accessory muscles of inspiration include neck muscle
(pull the upper ribs and sternum upward)
Accessory muscles of expiration include abdominal
recti and internal intercostal muscles (pull downward
on the sternum and lower rib)
Expiration
Inspiration
Increased vertical
diameter
Increased A-P
diameter
External
intercostals
contracted
Elevated
rib cage
Internal
intercostals
relaxed
Diaphragmatic
contraction
Abdominals
contracted
Movement of air in and out of the lungs
The lung is formed of an elastic tissue that collapse
like a balloon and inflated and then expel the air out
The lungs are surrounded by a very thin layer of pleural
fluid that lubricate the movements of the lungs within
the cavity
Continuous suction of excess fluid into lymphatic
channels maintain a slight suction between the visceral
and parietal pleura
Various pressure in the lungs
Pleural pressure – is the pressure of fluid in the narrow
space between the visceral and parietal pleura,
normally slightly negative pressure
The normal pleural pressure at the beginning of
inspiration is –5cm of H2O (it reach about –7.5cm of
H2O due to movement of the chest cage)
The pleural pressure at the beginning of expiration is
–7.5cm of H2O to reach –5cm of H2O
Alveolar pressure
Alveolar pressure: – is the pressure inside the lung
alveoli
During inspiration:  –1cm of H2O (this slight
negative pressure is enough to move about 0.5 liter
of air into the lungs in the first 2 second of
inspiration)
During expiration: it rises to about +1cm of H2O (this
forces 0.5 liter of inspired air out of the lungs during
the 2 to 3 seconds of expiration
Compliance of the lungs
Definition:
the extent to which the lungs expand for
each unit increase in transpulmonary
pressure (pleural pressure minus
alveolar pressure) ~ 200ml/cm of H2O
(each time, the transpulmonary pressure
increase by 1cm of H2O, the lungs
expand 200ml)
The compliance diagram of the lungs
Which relates lung volume changes to the changes in
transpulmonary pressure and it has 2 curves inspiratory and
expiratory compliance curve
The compliance diagram are determined by the elastic forces of the
lungs, which can be divided into 2 parts:
1-elastic forces of the lung tissue
2-elastic force caused by surface tension of the fluid that lines
the alveoli
Elastic forces of the lung tissue are determined by the elastin and
collagen fibers among the lung tissue (deflated lungs, these fibers
contracted and kinked but when the lung expand it becomes
stretched and unkinked by elongating)
Elastic forces caused by the surface tension accounts for about
2/3rd of the total lung elastic forces and much more complex and it
depends on the “surfactant”
Surfactant surface tension and collapse
of the lungs
When water forms surface with air, the water
molecules on the surface of water have extra
attraction force for each other and contract.
Also water surface in the inner surface of the
alveoli attempting to contract to force air out of
the alveoli through the bronchi which causes
the alveoli to collapse (which cause surface
tension elastic force) the lungs expanded
Surfactant
is a substance produce by type II alveolar epithelial cells
(~ 10% of the surface area of the alveoli) which reduce
the surface tension of the fluid in the inner surface of the
alveoli
it is a mixture of phospholipids, proteins, and ions, the
most important component is phospholipid dipalmitoyl
phosphatidylcholine which is responsible for reducing the
surface tension (formed of 2 parts, hydrophilic part
dissolves in the water lining the alveoli and hydrophobic
part directed toward the air)
the alveolar collapse pressure in an average-sized
alveolus with radius of about 100µm and lined with
surfactant, is about 4cm of H2O, but if it is lined with pure
water is about 18cm of H2O  important of surfactant in
reducing the amount of transpulmonary pressure required
to keep
Effect of the thoracic cage on lung
expansibility:
the thoracic cage has its own elastic and viscous
characteristics, similar to the lungs. Muscular effort
were required to expand the thoracic cage
Compliance of the thorax and the lungs
together:
the compliance of the combined lung-thorax system
is one half that of the lungs alone 110ml/cm of H2O
The work of breathing
the respiratory muscles perform work to cause
inspiration (not expiration)
the work of inspiration can be divided into 3
fractions:
The work required to expand the lungs against its
elastic forces called compliance work or elastic work.
The work required to overcome the viscosity of the
lung and chest wall structures called tissue
resistance work.
The work required to overcome airway resistance
called airway resistance work.
Work energy required for respiration:
during normal quiet respiration = 2 to 3% of the total
work energy ( to 50 fold in exercise,  airway
resistance).
Pulmonary volumes and capacities
Pulmonary volumes (by using spirometer):
1) Tidal volume – is the volume of air inspired or expired with
each normal breath = 500ml in young adult man.
2) Inspiratory reserve volume – is the extra volume of air
that can be inspired over and beyond the normal tidal volume
= 3000ml.
3) Expiratory reserve volume – is the extra amount of air
that can be expired by forceful expiration after the end of a
normal tidal expiration ~ 1100ml.
4) Residual volume – is the extra volume of air that still
remain in the lungs after the most forceful expiration ~
1200ml.
The pulmonary capacities
Comprises more than one volume:
1)
Inspiratory capacity – is the volume of air inspired by a maximal
inspiratory effort after normal expiration = 3500ml = inspiratory reserve
volume + tidal volume.
2)
The functional residual capacity – is the volume of air remaining in the
lungs after normal expiration = 2300ml = expiratory reserve volume +
residual volume.
3)
The vital capacity – is the volume of air expired by a maximal expiratory
effort after maximal inspiration ~ 4600ml = inspiratory reserve volume +
tidal volume + expiratory reserve volume.
4)
Total lung capacity – is the maximum volume of air that can be
accommodated in the lungs ~ 5800ml = vital capacity + residual volume.
5)
Minute respiratory volume – is the volume of air breathed in or out of the
lungs each minute = respiratory rate x tidal volume = 12 X 500ml =
6000ml/min.
All lung volume and capacity are about 20 to 25% less in women than in men
and are greater in athletic persons than in small and asthenic persons.
Forced capacity (FVC & FEV1)
Normal
( N ) FEV1
( N ) VC
Obstructive  ( N ) FEV1
 or ( N ) VC
Restrictive
 ( N ) FEV1
 or ( N ) VC
TIDAL
BREATHING
FORCED
EXPIRATION
NORMAL
FEV1
FEV1
FEV1 = 3.0L
FVC = 4.2L
FEV1/FVC = 72%
OBSTRUCTIVE
FEV1 = 0.9L
FVC = 2.3L
FEV1/FVC = 40%
RESTRICTIVE
FEV1
1 SECOND
FEV1 =1.8L
FVC = 2.3L
FEV1/FVC = 78%
Alveolar ventilation
Movement of air between the lung and atmospheric air,
in the gas exchange areas which include the alveoli,
the alveolar sacs, the alveolar ducts, and the
respiratory bronchiole.
Diffusion: kinetic motion of molecules of gas at high
velocity among each others.
Dead space: The respiratory passages where gas
exchange does not occur (up to the terminal
bronchioles), normal dead space air in the young adult
male = 150ml
The rate of alveolar ventilation
Alveolar ventilation per minute is the total volume of
new air entering the alveoli and other adjacent gas
exchange areas each minute.
Va = Respiratory rate X (Vt – Vd)
= Respiratory rate X (Vtidal volume – Vdead space)
= 12 X (500 – 150) = 4200ml
Non-respiratory function of the lungs
1) Protection of respiratory tracts.
2) Conversion of angiotensin I to
angiotensin II with the help of
converting enzymes formed by the
lungs.
3) Alpha 1 anti-trypsin is present in the
lung secretion which protects the
lung from the action of trypsin,
proteases and elastase.
4) Humidification.
5) In plays an essential role in the
regulation of acid-base balance.
Functions of the respiratory passageways
The trachea, bronchi, and bronchioles:
The walls are formed of cartilage and the smooth muscle
 contraction of the smooth muscle  narrowing of the
airway.
Sympathetic nervous system causes dilatation of the
bronchi to supply the central area of the lung, epinephrine
and norepinephrine cause dilatation of the bronchial tree.
Parasympathetic nerve fibers penetrate the lung
parenchyma and secrete acetylcholine that causes mild to
moderate constriction of the bronchioles.
Focal factors that cause bronchiolar constriction:
1) histamine
2) slow reacting substance of anaphylaxis (secreted from the
mast cells in allergic reactions and pollen in the air)
Mucous of the respiratory passageways
Secreted by epithelial cells that lines the
respiratory passage:
it moisten the respiratory passages from the nose
up to the terminal bronchioles.
it traps small particles out of the inspired air –
removal of the mucous by movement of the cilia in
the ciliated epithelia that line the entire surface of
the respiratory passages in the lungs it beat upward
while in the nose it beat downward towards the
pharynx.
Cough reflex
about 2-5 liter of air is inspired, then epiglottis
and vocal cords close tightly to entrap air within
the lung.
abdominal muscles contract forcefully against
the diaphragm also the intercostal muscles
contract forcefully both raise the pressure in the
lungs to 100mmHg.
sudden opening of the vocal cords and
epiglottis widely so air under pressure in the
lung explodes outward carrying with it the
foreign body present in the bronchi and trachea.
Respiratory functions of the nose
it warmed the air.
humidification of the air.
filtration of the air (air conditioning
function of the upper respiratory
passageway) by hair in the nose
and by turbinates that cause
turbulence of the air).
Vocalization include 2 steps
phonation by larynx
articulation by the structures of the mouth
Phonation: mainly by the vocal cords that protrude from the
lateral wall of the larynx to the center of the glottis.
During normal breathing they are open to allow passage of air
and during phonation, the folds close together to cause vibration
during passage of air between them. The pitch of vibration is
determined by degree of stretch and how tightly the folds are
approximated to each other.
Articulation and resonance: needs lips, tongue and soft
palate for articulation but resonance need mouth, nose, nasal
sinuses, pharynx and chest cavity
Physiological anatomy of the pulmonary
circulatory system
Pulmonary artery divided into 2 main branches which
divided into very short branches of arteries and
arterioles:
The pulmonary arterial tree have large compliance
because:
arteries and arterioles have large diameters.
they are very thin and distensible.
Allow them to accommodate about 2/3 of the stroke
volume of the right ventricle per beat.
Lymphatics:
Lymphatics from all lung tissues drain into the right
lymphatic duct to prevent lung edema.
Pressure in the pulmonary system
Systolic pressure in the right ventricle is about 25mmHg and the
diastolic pressure is about 0 to 1mmHg (1/5th of the left
ventricle).
Pressures in the pulmonary artery:
During systole, the pressure in the pulmonary artery is equal to
the pressure of the right ventricle. At the end of systole and after
closure of the pulmonary valve, the pressure in the right ventricle
falls rapidly while the pressure in the right artery falls slowly due
to blood flow through capillaries of the lungs.
Systolic pulmonary arterial pressure is 25mmHg.
Diastolic arterial pressure is 8mmHg.
Mean pulmonary arterial pressure is 15mmHg.
Pulmonary capillary pressure is about 7mmHg.
Left arterial and pulmonary venous pressure:
The mean pressure in the left atrium is about 2mmHg (varying
from 1mmHg to 5mmHg).
Automatic control of pulmonary blood flow
When the concentration of O2 in the alveoli decrease below
normal the adjacent blood vessels constrict and the vascular
resistance increases 5 folds (this is opposite to the systemic
vessels). This in turn causes most of the blood to flow through
other areas of the lung that are better aerated.
The effect of hydrostatic pressure gradients in the
lungs on regional pulmonary blood flow:
In normal upright adult, the pulmonary arterial pressure in the
uppermost portion of the lung is about 15mmHg less than the
pulmonary arterial pressure at the level of the heart, but the
pressure in the lowest portion of the lungs is about 8mmHg
greater than at the heart. So, at rest, in the standing position,
there is little flow in the top of the lungs but about 5 times this
flow in the lower portion of the lungs.
During exercise the blood flow through
the lungs increase from 4 to 7 folds
due to:
1) by increasing the number of open capillaries (3 fold)
2) by distending all the capillaries and increasing the
rate of flow through each capillary more than 2 fold
These two factors prevent the rise in
pulmonary arterial pressure even during
maximum exercise, the pulmonary arterial
pressure rises very little, this prevent
development of pulmonary edema
Pulmonary capillary dynamics
the alveolar walls are lined with capillaries so the blood
flows in the alveolar walls as sheet.
Capillary exchange of fluid in the lungs and pulmonary
interstitial fluid dynamics: fluid exchange in the lung
capillary is similar qualitatively to the peripheral
tissue, but quantitatively there are important
differences:
1) Pulmonary capillary pressure is very low ~ 7mmHg, in
comparison with the higher capillary pressure in the
peripheral tissue ~ 17mmHg.
2) Interstitial fluid pressure in the lung is slightly more
negative than in the peripheral subcutaneous tissue,
normally measuring 8mmHg.
3) The pulmonary capillaries are relatively leaky to protein,
so that the colloid osmotic pressure is about 14mmHg in
comparison with less than half this in the peripheral
tissue.
4) The alveolar walls are extremely thin and weak so that it
ruptured by any positive pressure in the interstitial
spaces greater than the atmospheric pressure, which
allow damping of fluid from the interstitial spaces into
the alveoli.
mmHg
Forces tending to cause movement of fluid
outward from the capillaries and into the
pulmonary interstitium:
Capillary pressure
Interstitial fluid colloid osmotic
pressure
Negative interstitial fluid pressure
TOTAL INWARD FORCE
14
8
29
Forces tending to cause absorption of fluid
into the capillaries:
Plasma colloid osmotic pressure
TOTAL INWARD FORCE
28
28
Total outward force
Total inward force
NET MEAN FILTRATION PRESSURE
7
+29
-28
+1
Negative interstitial pressure and mechanism
for keeping the alveoli dry:
There are small openings between the alveolar epithelial cells
through which large protein molecules and large quantities of
water and electrolyte can pass. Pulmonary capillaries and the
pulmonary lymphatic system maintain a slight negative pressure
in the interstitial spaces in which excess fluid is either carried
away through the pulmonary lymphatics or is absorbed into the
pulmonary capillaries. The alveoli are kept dry except for small
amount of fluid that seeps from the epithelium onto the lining
surfaces of the alveoli to keep them moist.
Pulmonary edema: any factor that causes the pulmonary
interstitial fluid pressure to rise from the negative to positive will
cause filling of the pulmonary interstitial spaces and alveoli with
large amount of fluid.
The most common causes of
pulmonary edema
1) Left heart failure or mitral valvular disease which
causes increase in the pulmonary capillary
pressure and flooding of the interstitial spaces
and alveoli.
2) Damage to the pulmonary capillary membrane
caused by infections e.g., pneumonia or by
breathing noxious substances e.g., chlorine gas
or sulfur dioxide gas, which causes leakage of
both plasma proteins and fluid out of the
capillaries.
Acute pulmonary edema occur when the
pulmonary capillary pressure rises above the
normal level required to maintain negative
interstitial pressure, edema occur with 20 to
30 minutes if the capillary pressure rises as
much as 25 to 30mmHg above the safe level
(acute left heart failure if the pulmonary
capillary pressure rises above 50mmHg).
The fluids in the pleural cavity
During the breathing, the lungs
expand and contract within the
pleural cavity. This movement is
facilitated by a thin layer of fluid
lies between the parietal and
visceral pleurae. The pleural fluid
is only few milliliters and the extra
amount is pumped to the
lymphatic vessels.
Transport of O2 and CO2 between the
alveoli and the tissue cells:
Diffusion: movement of O2 from the alveoli
into the pulmonary blood and diffusion of CO2
in the opposite direction. Gases dissolved in
the fluids and body tissues. Diffusion require
energy which is provided by the kinetic
motion of the molecules of gas themselves.
Partial pressure of gases (in a mixture)
The pressure of gas is caused by the constant
kinetic movement of gas molecules against the
surface. In respiratory physiology, there is a
mixture of gases mainly of O2, N2, and CO2. The
rate of diffusion of each of these gases is directly
proportional with the partial pressure of the gas.
Pressure of gases dissolved in water and tissue:
The pressure of gases dissolved in fluid is similar
to their pressure in the gaseous phase and they
exert their own individual partial pressure.
Dissolved gas molecules
A
B
Diffusion of gases through fluids pressure
difference causes net diffusion:
The net diffusion of gas from the area of high
concentration to the area of low concentration = the
number of molecules bouncing in the forward direction
 the number of molecules bouncing in the opposite
direction (pressure difference for diffusion).
The solubility of gas, CO2 is more soluble than O2
The relative diffusion rates for different gases:
O2
1.0
CO2
20.3
N2
0.53
Diffusion of gases through tissues
The gases of respiratory importance are
highly soluble in cell membrane (all are
highly soluble in lipids). Also, diffusion of
gases through the tissue, including through
the respiratory membrane, is equal to the
diffusion of gases through water. CO2
diffusion 20 times more rapidly than O2
because of its high solubility in tissue fluids.
Composition of alveolar air and its
relation to atmospheric air:
Alveolar air is partially replaced by
atmospheric air with each breath.
O2 is constantly absorbed from the
alveolar air.
CO2 constantly diffuses from the
pulmonary blood into the alveoli.
The dry atmospheric air enters the
respiratory passage is humidified
before it reaches the alveoli.
Partial pressures of respiratory gases as they
enter and leave the lungs (at sea level)
N2
O2
CO2
H2O
Atmospheric Air*
(mmHg)
597.0 (78.62%) 159.0 (20.84%)
0.3 (0.04%)
3.7 (0.50%)
Humidified Air
(mmHg)
563.4 (74.09%) 149.3 (19.67%)
0.3 (0.04%)
47.0 (6.20%)
Alveolar Air
(mmHg)
569.0 (74.9%)
104.0 (13.6%)
40.0 (5.3%)
47.0 (6.2%)
Expired Air
(mmHg)
566.0 (74.5%)
120.0 (15.7%)
27.0 (3.6%)
47.0 (6.2%)
The rate at which alveolar air is
renewed by atmospheric air:
The amount of air remaining in the lungs at
the end of normal expiration ~ 2300ml (FRC).
Only 350ml of air is brought into the alveoli
with each breath. Therefore, the amount of
alveolar air is replaced by new atmospheric
air with each breath is only 1/7th of the total.
This slow replacement of alveolar air is
important in preventing sudden changes in
gaseous concentrations in the blood.
O2 concentration and pressure in the
alveoli:
O2 is continuously absorbed into the blood of
the lungs and replaced from the atmosphere.
So its concentration is lower in the alveoli if
its absorbed more rapidly. It’s concentration
is higher in the alveoli if new O2 is breathed
rapidly.
The solid curve represents O2 absorption at a
rate of 250ml/min, and the dotted curve at
1000ml/min. At normal ventilatory rate of 4.2
liters/min and O2 consumption of 250ml/min,
the normal operating point is point A. During
moderate exercise when O2 is absorbed, each
minute 1000ml, the rate of alveolar ventilation
is increase 4-fold to maintain the alveolar PO2
at normal value of 104mmHg. Also marked
increase in the alveolar ventilation never
increase the alveolar PO2 above 149mmHg if
the person breathing normal atmospheric air.
CO2 concentration and pressure in the
alveoli:
CO2 is continuously formed in the body,
discharged into the alveoli, then removed by
ventilation.
The solid curve represents the normal rate of CO2
excretion of 200ml/min, at normal ventilation of 4.2
liters/min, the operating point for alveolar PCO2 is
at point A at 40mmHg. Alveolar PCO2 increases
directly in proportion to the rate of CO2 excretion,
as represented by the dotted curve for 800ml CO2
excretion/min. Alveolar PCO2 decreases in inverse
proportion to alveolar ventilation.
Diffusion of gases through the
respiratory membrane
Respiratory unit is composed of respiratory
bronchiole, alveolar ducts, atria, and alveoli
(about 300 million in the 2 lungs, each
alveolus with an average diameter of 0.2
millimeter). The walls of the alveoli, alveolar
ducts and other parts of the respiratory unit
are extremely thin within, there are
interconnecting capillaries which is called
the respiratory membrane or pulmonary
membrane.
Respiratory membrane
The total surface area of the
respiratory membrane is ~ 50 to
100 m2 in normal adult. This
large surface area to allow rapid
diffusion of gases through the
respiratory membrane
Factors that affect the rate of gas diffusion
through the respiratory membrane:
1. The thickness of the respiratory membrane.
 thickness of the respiratory membrane e.g.,
edema   rate of diffusion. The thickness
of the respiratory membrane is inversely
proportional to the rate of diffusion through
the membrane.
2. Surface area of the membrane. Removal of
an entire lung decreases the surface area to
half normal. In emphysema with dissolution
of the alveolar wall   S.A. to 5-folds
because of loss of the alveolar walls.
Epithelial basement
membrane
Interstitial
space
Capillary basement
membrane
Capillary endothelium
Alveolar epithelium
Red
blood
cell
Fluid and
surfactant
layer
Alveolus
Diffusion
Diffusion
Capillary
O2
CO2
3. The diffusion rate of the specific gas.
Diffusion coefficient for the transfer of
each gas through the respiratory
membrane depends on its solubility in the
membrane and inversely on the square
root of its molecular weight. CO2 diffuses
20 times as rapidly as O2.
4. The pressure difference between the two
sides of the membrane (between the alveoli
and in the blood). The alveolar pressure
represents a measure of the total number of
molecules of a particular gas striking a unit
area of the alveolar surface of the membrane
in unit time. When the pressure of the gas in
the alveoli is greater than the pressure of the
gas in the blood as for O2, net diffusion from
the alveoli into the blood occurs, but when the
pressure of the gas in the blood is greater
than the pressure in the alveoli as for CO2, net
diffusion from the blood into the alveoli
occurs
Diffusing capacity of the
respiratory membrane
Diffusing capacity: is the volume of a gas that
diffuses through the membrane each minute for
a pressure difference of 1mmHg.
The diffusing capacity for O2: In the average
young male adult, the diffusing capacity for O2
under resting conditions averages
21ml/min/mmHg. The mean O2 pressure
difference across the respiratory membrane
during normal, quiet breathing is ~ mmHg. (11 x
21 = 230 ml) of O2 diffusing through the
respiratory membrane each minute equal to the
rate at which the body uses O2.
Changes in O2 diffusing capacity
during exercise
During strenuous exercise or other
conditions that increase the pulmonary
blood flow and alveolar ventilation, the
diffusing capacity for O2 increases to
65ml/min/mmHg (3 times the diffusing
capacity under resting conditions). This
increase is caused by opening up the
dormant pulmonary capillaries to
increase the surface area of the blood
into which O2 can diffuse.
Ventilation-perfusion ratio (V/Q)
It is the ratio of alveolar ventilation to
pulmonary blood flow per minute. The alveolar
ventilation at rest (4.2L/min) and is calculated
as:
Alveolar ventilation = respiratory rate x (tidal volume – dead
space air).
The pulmonary blood flow is equal to right ventricular output
per minute (5L/min).
This value is an average value across the lung.
At the apex, V/Q ratio = 3.
At the base, V/Q ratio = 0.6.
So the apex is more ventilated than perfused, and the base is
more perfused than ventilated.
During exercise, the V/Q ratio becomes more
homogenous among different parts of the
lung.
Diffusing capacity for CO2
CO2 diffuses through the respiratory
membrane so rapidly that the average PCO2
difference between the alveolar and capillary
blood is 1mmHg. The diffusion capacity for
CO2 is 20 times that of the O2, so we expect
that the diffusion capacity for CO2 under
resting conditions ~ 400 to 450ml/min/mmHg
and during exercise is about 1200 to 1300
ml/min/mmHg.
Uptake of O2 from the alveoli by the
pulmonary blood
The PO2 in the alveolus is 104mmHg and in the
venous blood entering the capillary is 40mmHg
because large amount of O2 has been removed
from this blood as it has passed through the
peripheral tissues. The initial pressure
difference that causes O2 to diffuse into the
pulmonary capillary is 64mmHg (10440=64mmHg). The rapid rise in blood PO2 as the
blood pressure through the capillary, that the
PO2 rises to equal that of the alveolar air by the
time the blood moved a 1/3rd of the distance
through the capillary becoming 104mmHg
Uptake of O2 by the pulmonary blood
during exercise
During strenuous exercise, the body requires as much as
20 times the normal amount of O2. Also, because of the
increased cardiac output, the time that the blood remains
in the capillary may be reduced to less than half normal.
Therefore, oxygenation of the blood could suffer.
Because of safety factor for diffusion of O2 through the
pulmonary membrane, the blood is almost completely
saturated with O2 when it leaves the pulmonary capillaries
for 2 reasons:
During exercise, the rate of O2 diffusion through the pulmonary
membrane increases to 3 fold, due to the number of capillaries.
During blood flow through the capillary, the blood becomes
almost saturated with O2 by the time it has passed through the
1/3rd of the pulmonary capillary.
Diffusion of O2 from the tissue
capillaries into tissue fluid
The PO2 in the arterial blood reaching the
capillary is 95mmHg, the PO2 in the interstitial
fluid is 40mmHg and 23mmHg inside the
cells. So there is a tremendous initial
pressure difference that causes O2 to diffuse
very rapidly from the blood into the tissues,
so that the capillary PO2 falls to 40mmHg in
the interstitium. The blood entering the veins
from the tissue capillaries is about 40mmHg.
Effect of rate of blood flow and tissue
metabolism on interstitial fluid PO2
If the blood flow through the tissue is
increased, large quantities of O2 are
transported into the tissue in a given period
of time, and the tissue PO2 is increased. The
upper limit to which the PO2 can rise, even
with maximum blood flow is about 95mmHg
(because this is the O2 pressure in the
arterial blood). Conversely, if the cells utilize
more O2 for metabolism than normal, this
reduce the interstitial fluid PO2.
Diffusion of O2 from the capillaries
to the tissue cells
O2 is used by the cells. Therefore, the
intracellular PO2 remains lower than the PO2
in the capillaries. The intracellular PO2 is
about 23mmHg (range between 5 to
40mmHg). Because only 1 to 3mmHg of O2
pressure is normally required for full support
of the metabolic processes of the cell, so
that even with this low PO2 of 2mmHg is
more than adequate and safe for the
metabolic processes.
Diffusion of CO2 from the tissue cells
into the tissue capillaries and from the
pulmonary capillaries into the alveoli
When O2 is used by the cells, most of it becomes CO2 and
this increases the intracellular PCO2. CO2 diffuse from the
cells into the tissue capillaries and then carried by the blood
to the lungs, when it diffuses from the pulmonary capillaries
into the alveoli. CO2 diffuses in opposite direction to the
diffusion of O2. CO2 diffuses 20 times as rapidly as O2.
Therefore, the pressure differences that cause CO2
diffusion are far less than the pressure differences required
to cause O2 diffusion. These pressures are the following:
Intracellular PCO2 is about 46mmHg, the interstitial PCO2 is
about 45mmHg, there is only a 1mmHg pressure difference.
PCO2 of the arterial blood entering the tissues 40mmHg,
PCO2 of the venous blood leaving the tissue is about
45mmHg. So that tissue capillary blood is in an equilibrium
with the interstitial PCO2 45mmHg.
PCO2 of the venous blood entering the pulmonary capillaries
in the lungs 45mmHg, PCO2 of the alveolar air is 40mmHg,
only 5mmHg pressure difference causes CO2 to diffuse out of
the pulmonary capillary into the alveoli.
The PCO2 of the pulmonary capillary blood falls exactly to
equal the alveolar PCO2 of 40mmHg before it passed more
than about 1/3rd the distance through the capillaries
Effect of tissue metabolism and blood flow on interstitial PCO2:
Increased tissue metabolism increases the CO2 in the tissue,
but increased blood flow carries more CO2 away and
decreases its concentration.
Function of haemoglobin to
transport O2 in arterial blood
About 97% of O2 is transported in chemical
combination with haemoglobin and 3% is carried
in the dissolved form in the plasma and cells.
Under normal conditions O2 carried to the
tissues almost entirely by haemoglobin. O2
molecule combines loosely and reversibly with
the heme portion of the Hb. When the PO2 is
high (as in the pulmonary capillaries) O2 binds
with the Hb, but when the PO2 is low (as in the
tissue capillaries) O2 is released from the Hb.
The oxygen-haemoglobin
dissociation curve
It shows the progressive increase in the
percentage saturation of the Hb with the
increase in the PO2 in the blood. The
PO2 in the arterial blood is about
95mmHg and saturation of Hb with O2 is
about 97%. In the venous blood
returning from the tissues, the PO2 is
about 40mmHg and the saturation of Hb
with O2 is about 75%.
Maximum amount of O2 than can
combine with the Hb of the blood
In a normal person, 15gm of Hb in
each 100ml of blood, each gram of
Hb bind with a maximum of about
1.34ml of O2. At 100% saturation,
the Hb in 100ml of blood can
combine with 20ml of O2.
The amount of O2 released from the
Hb in the tissues
In the arterial blood 97/100 x 1.34 x
15gm of Hb = 19.4ml of O2 bound with
Hb.
In the venous blood 75/100 x 1.34 x
15gm = 14.4ml of O2.
So under normal conditions about 5ml
of O2 are transported to the tissues by
each 100ml of blood.
Transport of O2 during
strenuous exercise
In heavy exercise the muscle cells utilize
O2 rapidly, which causes the interstitial
fluid PO2 to fall to 15mmHg. Only 4.4ml
of O2 remains bound to with Hb in each
100ml of blood (19.4 – 4.4 = 15ml of O2
are transported by each 100ml of blood).
Also cardiac output can increase to 7
fold. The amount of O2 transported to
the tissue increase to 20 folds (3 x 7 =
21).
Factors affecting the affinity of Hb for O2
3 important conditions
1) The  pH or (H+ conc),
2) the  temperature,
3) and the  concentration of 2,3 diphosphoglycerate
(2,3-DPG).
4)  PCO2 concentration (Bohr effect)  all shift the
curve to the right.
P50: it is the partial pressure of O2 at which 50%
of Hb is saturated with O2.
 P50 means right shift  lower affinity for O2.
 P50 means left shift  higher affinity for O2.
Metabolic use of O2 by the cells
The figure shows the relationship
between intracellular PO2 and the
rate of O2 usage at different
concentrations of ADP. When the
rate of ADP concentration is altered,
the rate of O2 usage changes in
proportion to the change in ADP
concentration.
ADP = 1½ normal
ADP = Normal resting level
ADP = ½ normal
Transport of O2 in the dissolved state
Only 3% of the total O2 is transported
in the dissolved state composed with
97% transported by Hb.
In the arterial blood, the PO2 is
95mmHg  0.3ml of O2 is dissolved in
dl of blood. In venous blood PO2 is
40mmHg (as in tissue capillaries) 
0.12ml of O2 is dissolved in dl of
blood.
The importance of dissolved form
Tissue consume the O2 directly.
It depends on the PO2 (so higher alveolar
PO2 will increase the amount of O2 carried
in the dissolved state e.g., hyperbaric O2
therapy as in CO poisoning).
Combination of Hb with CO
displacement of O2:
CO combines with Hb and it displace O2
from Hb. It binds with about 250 times as
much tenacity as O2.
Transport of CO2 in the blood
Under normal resting conditions
~ 4ml of CO2 is transported from
the tissue to the lungs in each
100ml of blood.
Chemical forms in which CO2 is transported
1-7% of CO2 is transported in the dissolved
state.
2-70% of CO2 is transported in the form
HCO3¯. HCO3¯ diffuses out of the RBC
with Hb and Cl¯ ions diffuse into the RBC
(chloride shift).
3-23% of CO2 is transported in
combination with Hb and plasma proteins
as carbamino-Hb: CO2 reacts with the
amino group of the Hb to form the
carbamino-Hb (CO2HHB). This reaction is
reversible when CO2 is released into the
alveoli.
Change in blood acidity during
CO2 transport
 CO2   H+   pH ( acidity of the blood 
stimulate its release from the blood through the
lungs).
The respiratory exchange ratio:
rate of CO2 output 4
R
  0.8 (80%)
rate of O 2 uptake 5
R value changes under different metabolic conditions. If
the person is utilizing carbohydrate for body metabolism.
R value rises to 1 and it decreases to 0.7 if the person is
utilizing fat for metabolism. If the person consume normal
diet (CHO, fat and protein), R value is ~ 0.825.
Regulation of respiration
1-Neural control of respiration
2-Chemical control of respiration
Neural control of respiration
The respiratory center is composed of
groups of neurons located bilaterally in the
medulla and pons divided into 3 major
collections of neurons:
1) Dorsal respiratory group in the dorsal portion of
the medulla and mainly inspiratory neurons.
2) Ventral respiratory group in the ventralateral
part of the medulla which contains both
expiratory and inspiratory neurons.
3) Pneumotaxic center which is located dorsally in
the superior portion of the pons, which helps
control both the rate and pattern of breathing.
The dorsal respiratory group
A group of neurons extends in most of the
dorsal length of the medulla within the nucleus
of the tractus solitarius and it contains the
termination of both the vagal and
glossopharyngeal nerves from the peripheral
chemoreceptors (the baroreceptors). The
dorsal neurons discharge rhythmically so it is
called the rhythmicity center. The signals
begins very weak at first and then increases
steadily for 2 seconds and then it ceases to
allow expiration. Another inspiratory signal
begins for another cycle (the inspiratory signal
is a ramp signal).
The pneumotaxic center limits the duration of
inspiration and increases the respiratory rate:
The pneumotaxic center is located dorsally in the
upper pons, it transmits inhibitory signals to the
inspiratory area to switch off the inspiratory ramp.
The ventral respiratory group of neurons
functions in both inspiration and expiration:
Located anteriolateral to the dorsal groups. The
ventral group of neurons inactive during normal quiet
respiration. Stimulation of the neurons cause some
inspiratory or expiratory neurons to be stimulated.
The ventral neurons active during increase
pulmonary ventilation as in exercise.
The Hering-Breuer inflation reflex
When the lungs are inflated, this
causes stimulation of “stretch
receptors” in the walls of bronchi
and bronchioles which is
transmitted through the vagus
nerve to the dorsal respiratory
groups to “switch off” inspiration.
Chemical control of respiration
Excess CO2 of  H+ ions mainly
stimulate the respiratory center to
increase the strength of both
inspiratory and expiratory signals
to the respiratory muscles.
Central chemoreceptors
Located on the ventrolateral surfaces
of the medulla oblongata (bilaterally).
This area is highly sensitive to
changes in either blood PCO2 or
H+ ion concentration. H+ ions can’t
cross the blood-brain barrier (BBB).
So CO2 cross the BBB and react with
H2O to form carbonic acid and then
dissociate into H+ ion and HCO3¯,
then the H+ ion which stimulate the
chemosensitive area in the brain.
Peripheral chemoreceptors
These chemical receptors located in several
areas outside the brain in the carotid bodies and
in the aortic bodies. They are highly sensitive to
changes in O2 in the blood, although they respond
to changes in CO2 and H+ ion concentration too.
Afferent fibers pass from the carotid bodies via
the glossopharyngeal nerves and afferent fibers
from the aortic bodies pass via the vagal nerves
to the dorsal respiratory area to stimulate
respiration. So fall in arterial O2 concentration
below normal or increase in either CO2
concentration or H+ ion concentration. Fall in
blood PO2 excite the chemoreceptor which will
cause increase respiration.
Hypoxia
Defined as deficient O2 supply to the tissue.
In cyanide poisoning, the cytochrome
oxidase enzyme is completely blocked by the
cyanide to such an extent that the tissue
can’t utilize O2 even though plenty is
available.
Effects of hypoxia on the body:
Severe hypoxia can cause death of the cells,
but in less severe cases it results in:
Depressed mental activity and coma.
Reduced work capacity of the muscles.
Treatment of hypoxia
By administration of O2 by:
Placing the patient head in a “tent” of O2.
Allowing the patient to breath either pure or
high concentration of O2 from mask.
Administration of O2 through an intranasal
tube.
This O2 therapy is effective in case of
atmospheric hypoxia, hypoventilation
hypoxia and in hypoxia caused by impaired
alveolar membrane diffusion.
In hypoxia caused by anemia or abnormal
hemoglobin, O2 therapy is less effective
because normal O2 is available in the
alveoli but the defect is in transporting O2
to the tissues.
Also in hypoxia caused by inadequate
tissue use of O2, O2 therapy is of no benefit
because O2 is available in the alveoli and
no abnormality in O2 pickup by the lungs
or transport to the tissues but tissue
enzyme are incapable of utilizing the O2
that is delivered
Hypercapnea
Means excess CO2 in the body fluids. It
occurs in association with hypoxia which is
caused by hypoventilation or circulatory
deficiency. Hypoxia caused by too little O2 in
the air, too little Hb, or poisoning of oxidative
enzymes, hypercapnea isn’t concomitant of
these types of hypoxia. If hypoxia caused by
poor diffusion through the pulmonary
membrane hypercapnea doesn’t occur
because CO2 is 20 times more diffusible than
O2 and if it begins to occur it will stimulate
pulmonary ventilation to correct the
hypercapnea.
In hypoxia cause by hypoventilation,
hypercapnea occur with hypoxia because CO2
transfer between the alveoli and the
atmosphere is affected. In circulatory
deficiency, tissue hypercapnea occur with
tissue hypoxia due to diminished CO2 removal
from the tissues. When the alveolar PCO2 is
above 60-75mmHg, this lead to “air hunger” or
called “dyspnea” rapid deep inspiration.
If CO2 rises from 80-100mmHg, the person
becomes lethargic and semicomatose.
If PCO2 rises from 120-150mmHg, this lead to
death due to depression of the respiratory
center.
Cyanosis
Bluish discoloration of the skin and
mucus membrane due to more than
5gm/dL of deoxygenated Hb in the
blood.
Anaemic person can’t be cyanotic, he
hasn’t enough Hb for 5gm to be
deoxygenated in 100mL of blood.
In polycythemia, excess Hb that can
become deoxygenated can cause
cyanosis even under normal
conditions.