RESPIRATORY pdf - Proff. Amjad Fawzi

ESPIRATORY

YSTEM

RESPIRATORY PHYSIOLOGY ……… Proff.Amjad Fawzi

Respiratory System Functions

1.  Gas exchanger
2.  Regulation of blood pH
3.  Voice production
4.  Olfaction
5.  Protection

Respiration includes 2 processes:

6. External respiration: uptake of O2 and removal of CO2 between lungs and

environment.

7. Internal respiration: uptake of O2 and removal of CO2 between cells and

their fluid medium.

The respiratory system is made up of a gas exchanging organ(the lungs) and a
pump that ventilate the lungs. This pump is made up of:

1. Chest wall muscles which increase and decrease the size of thoracic cavity.
2. least resistance to air flow is in the very small bronchiols and terminal

bronchiols because of their large cross-sectional area.Alveoli are lined
mostly by thin layer of squamous epithelium.

3. Brain centers which control the respiratory muscles.
4. Nerves which connect the brain with respiratory muscles.

Respiratory Airways:

1. Anatomical classification: nose, pharynx (upper respiratory tract),larynx,

trachea, bronchi, bronchioles, terminal bronchioles, respiratory bronchioles,
alveolar ducts, alveolar sacs, and alveoli(lower respiratory tract).

2. Physiological classification: nose, pharynx, larynx, trachea, bronchi,

bronchioles,  terminal  bronchioles(conducting  zone-divided  16  times),
respiratory  bronchioles,  alveolar  ducts,  alveolar  sacs,  and  alveoli(respiratory
zone-divided  7  times).These  23  divisions  greatly  increase  the  total  cross
sectional area thus much reducing air flow through small airways.

To keep the trachea from collapsing multiple cartilage rings extend about five sixth
of the way around the trachea which become less and less extensive and then they
are  completely  gone  in  the  bronchioles  which  by  now  are  not  prevented  from
collapsing  by  any  rigidity  of  their  walls.  Instead,  they  are  expanded  by  the  same
transpulmonary  pressures  that  expand  the  alveoli.  In  all  areas  of  the  trachea  and
bronchi not occupied by cartilage plates, the walls are composed mainly of smooth
muscles. The walls of the bronchioles are almost entirely smooth muscles, with the
exception of the respiratory bronchioles that has only a few smooth muscle fibers.
The  chief  site  of  airway  resistance  in  the  airway  passages  is  at  the  medium-sized
segmantal  bronchi,  where  the  radius  of  the  individual  bronchi  is  decreased.  The
typeI) alveolar cells and few thick (type II) surfactant secreting cells in addition to
the alveolar macrophages which engulph small particles reaching the alveoli. Mast
cells  also  present  which  contains  histamine  responsible  for  allergic
reactions(bronchial asthma).

ESPIRATORY

YSTEM

Respiratory functions of the nose:

[1] Warming the airby the extensive surfaces of the conchae and septum.
[2] The air is almost completely humidified.
[3] The air is filtered.

When a person breathes air through atube directly into the trachea (as through a

tracheostomy), the cooling and especially the drying effect in the lower lung can lead
to serious lung crusting and infection. The nasal filtration of air for removing particles
from air is so effective that almost no particles larger than 4 to 6 microns in diameter
enter the lung through the nose. Of the remaining particles, many of smaller size settle
out  in  the  smaller  bronchioles  as  a  result  of  gravitational  precipitation.  Some  of  the
particles smaller than 1 micron in diameter diffuse against the walls of the alveoli and
adhere  to  the  alveolar  fluid.  But  many  particles  smaller  that  0.5  micron  in  diameter
remain suspended in the alveolar air and are later expelled by expiration. For instance,
the particles of cigarette smoke have a particle size of about 0.3 micron. Almost none
of these are precipitated in the respiratory passageways before they reach the alveoli.
However, up to one third of them do precipitate in the alveoli by the diffusion process,
and  the  remaining  suspended  and  expelled  in  the  expired  air.  Particles  that  become
entrapped  in  the  alveoli  are  removed  mainly  byalveolar  macrophages.  An  excess  of
particles  causes  growth  of  fibrous  tissue  in  the  alveolar  septa,  leading  to  permanent
debility.

All the respiratory passages are kept moist by a layer of mucus that coats the

entire surface which is secreted by goblet cells in the epithelial lining of the passages
and  by  small  submucous  glands.  Themucus  also  traps  small  particles  out  of  the
inspired  air  and  keeps  most  of  these  from  ever  reaching  the  alveoli.  Then  the  mucus
itself is removed from the passages by the continual beating of the cilia, which cover
the  entire  surface  of  the  respiratory  passages.  The  cilia  in  the  lower  respiratory
passages beat upward while those in the nose beat downward. This continual beating
causes the coat of mucus to flow slowly toward the pharynx. Then the mucus and its
entrapped particles are either swallowed or coughed to the exterior.

[A]

Nervous control of the bronchioles:

The only important nervous control to

the bronchioles is by way of parasympathetic vagus nerves fibers. These nerves secrete
acetylcholine  and  when  activated  cause  mild  to  moderate  constriction  of  the
bronchioles.  Irritants  entering  the  airways,  such  as  smoke,  dust,  sulfur  dioxide,  and
some  of  the  acidic  elements  in  smog,  can  all  initiate  local  reactions  that  cause
obstructive constriction of the bronchioles mediated through a parasympathetic reflex.

[B]

Humoral control of the bronchioles:

several different humoral substances

are often quite active in causing bronchiolar constriction. Two of the most important of
these are histamine and the substance called slow reactive substance of anaphylaxis
(SRA). Both of these are released in the lung tissues by mast cells during allergic
reactions. Therefore, they play key roles in causing the airway obstruction that occurs

ESPIRATORY

YSTEM

in allergic asthma. In addition, the airway smooth muscle is highly responsive to CO

high blood CO

producing bronchodilataion and low

bronchoconstriction. In

contrast to the humoral substances that constrict the bronchioles, two other hormones,
epinephrine and norepinephrine, both of which are secreted by the adrenal glands in
response to sympathetic stimulation relax the bronchioles (by activation of
β

receptors). Therefore, activation of the sympathetic nervous system is often valuable

in relaxing the airways and preventing obstruction.

Factor

Effect

Parasympathetic stimulation

Bronchoconstriction

Histamine and SRA

Bronchoconstriction

Low blood PCO2

Bronchoconstriction

High blood PCO2

Bronchodilatation

Sympathetic stimulation to the adrenal glands
(epinephrine and norepinephrine)

Bronchodilatation

The process of respiration can be divided into four major
events:

[1] Pulmonary ventilation which means the inflow and outflow of air between the
atmosphere and the lung alveoli.
[2] Pulmonary diffusion (gas exchange in the lung).
[3] Transport of oxygen and carbon dioxide in the blood and body fluids to and from
the cells.
[4] Regulation of ventilation.

(I)

Pulmonary Ventilation

Which includes inspiration and expiration.

[A]Inspiration: Normal inspiration is an active process. The lungs can expand in two
ways:

[1]By  downward  and  upward  movement  of  the  muscles  of  diaphragm  (supplied
by phrenic nerves). The downward movement of diaphragm accounts for 75% of
the  change  in  intrathoracic  volume  during  quiet  inspiration.  In  inspiration,
contraction of the diaphragm pulls the lower surfaces of the lungs downward.
[2]By  raising  the  rib  cage.  In  natural  resting  position,  the  ribs  are  extended
forward  and  downward,  thus  allowing  the  sternum  to  fall  backward  toward  the
spinal column. But when the rib cage is elevated, the ribs project directly forward
so  that  the  sternum  now  also  moves  forward  away  from  the  spine,  making  the
anterioposterior  thickness  of  the  chest  greater  during  maximum  inspiration.  The
foreword  movement  of sternum  accounts for 25% of  the  change in  intrathoracic
volume during quiet inspiration. The muscles for raising the rib cage (muscle of
inspiration) are external intercostals, sternocleidomastoid ,and scalene. At rest,

ESPIRATORY

YSTEM

adequate ventilation can be maintained by diaphragm or external intercostals
muscle alone.

[B]Expiration: Normal expiration is a passive process. The lungs can be shrinked or
contracted by two

ways:
[1]Relaxation of diaphragm and the inspiratory muscles which cause compression
on  the  lungs.  In  contrast,  during  heavy  breathing,  however,  the  compression
forces  are  not  powerful  enough  to  cause  the  necessary  rapid  expiration,  so  that
abdominal  muscles  (abdominal  recti)and  the  muscles  that  pull  the  rib  cage
downward  (internal  intercostals),  i.e.  muscles  of  expiration  are  contracted  and
added to the force needed for rapid expiration.
[2]Elastic recoil tendency of the lung.

Maximal  expiratory  pressure  is  achieved  by  fully  contracting  the  expiratory  muscles
with the lungs fully inflated and the glottis- or airway closed. Forced expiration against
a  closed  airway  is  termed  a  valsalva  maneuverand  is  commonly  performed  when
lifting  heavy  objects  or  when  defecating.  Normally,  the  maximal  expiratory  pressure
that  can  be  achieved  is  100-150  cm  H20  greater  than  atmospheric  pressure.  As  lung
volume decreases, the maximal achievable expiratory pressure decreases as well.

Elastic recoil tendency of the lungs:

The lungs have a continual elastic tendency

to  collapse  and  therefore  to  pull  away  from  the  chest  wall.  This  is  called  the  elastic
recoil tendency of the lungs and it is caused by two different factors:
[A]The  presence  of  elastic  fibers  throughout  the  lungs  which  are  stretched  by  lung
inflation  and  therefore  attempt  to  shorten.  They  account  for  about  one  third  of  the
recoil tendency.
[B]The  surface  tension  of  the  fluid  lining  the  alveoli  which  is  more  important,
accounts  for  about  two  third  of  the  recoil  tendency,and  causes  a  continual  elastic
tendency  for  the  alveoli  to  collapse.  The  surface  tension  is  caused  by  intermolecular
attraction  between  the  surface  molecules  of  the  alveolar  fluid  that  is  each  molecule
pulls on the next one.

Intrapleural(intrathoracic) pressure

:The negative(subatmospheric) pleural

pressure in the pleural space required to prevent collapse of the lungs is called the
pleural pressure (or intrathoracic pressure) which is about – 2.5 mm Hg at the end of
expiration and -12 to -18 mm Hg at the end of inspiration.

Pressure changes during inspiration and expiration:

A thin layer

of fluid normally present between visceral and parietal pleurae. This fluid
helps the lung to slide easily on the chest wall(lubricant) but resist being
pulled awayfrom it(sealant) in the same way that 2 moist pieces of glass
slide on each other but resist separation.
The lungs are stretched when expanded at birth

. At end of quiet expiration,their

tendency to recoil from the chest wall is just balanced by the tendency of the chest
wall to recoil in the opposite direction (neutral point).If the chest wall is opened, the
lungs collapse(pleural pressure becomes atmospheric) and if the lungs lose their

ESPIRATORY

YSTEM

elasticity the chest expands and becomes barrel- shaped(eg: emphysema).Inspiration is
an active process.The contraction of the inspiratory muscles increases the intrathoracic
volume.During quiet breathing, the intrapleuralpressure ,which is about -2.5 mmHg
(relative to atmospheric)at the start of inspiration, decreases to about -6mmHgm and
lungs become more expanded. The pressure in the airway becomes slightly negative,
and air flows into the lungs. At the end of inspiration, the lung recoil pulls the chest
back to the expiratory position, where the recoil pressure of the lungs and chest wall
balance. The pressure in the airway becomes slightly positive, and air flows out of the
lungs. Expiration during quiet breathing is passive since it does not involve expiratory
muscle contraction(depends on lung recoil).Strong inspiratory effort during exercise
reduces pleural pressure to as low as -30 mmHg and correspondingly graeter lung
expansion. Adequate deflation is achieved by contraction of
expiratotymuscles(expiration here is active).

The role of surfactant:

A substance known as surfactant, which is a

lipoprotein  secreted  from  type  II  alveolar  epithelial  cells  and  has  many  important
functions:
[1]Itreduces  the  surface  tension  of  the  fluid  lining  the  alveoli  by  decreasing  the
forces between the surface molecules of the alveolar fluid, and therefore, allowing the
lungs to expand. In the absence of surfactant, -20 to -30 mm Hg intrapleural pressure
required  to  overcome  the  collapse  tendency  of  the  alveoli  as  it  occur  in  some
premature  babies  who  do  not  secrete  adequate  quantities  of  surfactant  a  condition
known as hyaline membrane disease or respiratory distress syndrome.
[2]Surfactant also plays an important role in stabilizing the sizes of the alveoli. When
the  alveolus  becomes  smaller  and  the  surfactant  becomes  more  concentrated  at  the
surface  of  the  alveolar  lining  fluid,  the  surface  tension  becomes  progressively  more
reduced. On the other hand, as an alveolus becomes larger and the surfactant becomes
less concentrated at the surface of the alveolar lining fluid, the surface tension becomes
much greater. Thus, this special characteristic of surfactant helps to stabilize the sizes
of  the  alveoli,  causing  the  larger  alveoli  to  contract  more  and  the  smaller  ones  to
contract less. This effect helps to ensure that the alveoli in any one area of the lung all
remain approximately the same size.
[3]Surfactant is also playing a role in preventing accumulation of edema fluid in the
alveoli. This can be explained as follow; the surface tension of the fluid in the alveoli
not  only  tends  to  cause  collapse  of  the  alveoli, but  it  also  tends  to  pull  fluid  into  the
alveoli from the alveolar wall. In the normal lung, when there is adequate amounts of
surfactant,  still  the  surface  tension  can  pull  fluid  from  the  wall  with  an  average
pressure  of  -3  mm  Hg  into  the  alveoli  which  can  reabsorb  to  interstitium  with  an
average pressure of-9 mm Hg. This is what keeps the alveoli dry. On the other hand, in
the absence of surfactant, the average surface tension force may becomes as great as -
10 to -20 mm Hg which tends to pull fluid into the alveoli causing massive filtration of
fluid  out  of  the  capillaries  wall  into  the  alveoli,  thus  filling  the  alveoli  with  fluid
causing sever pulmonary edema.

ESPIRATORY

YSTEM

Expansibility of the lungs and thorax( Compliance):

defined as the volume

increase in the lungs for each unit increase in alveolar pressure.It indicates how easily
a structure can be stretched or inflated. Compliance = [V2-V1] / [P2-P1].
The  compliance  and  elasticity  (elastance)  are  inversely  related,i.e.,  Compliance  =
1/elastance.
The  Compliance  of  the  normal  lungs  and  thorax  combined  (total  pulmonary
Compliance)  is  120-130  ml  /  cm  H

O. That is, every time the alveolar pressure is

increased or intrapelural pressure decreased by 1 cm of water, the lungs expand 130
ml.Any condition that restrict expansion of the lungs (restrictive lung diseases') causes
abnormal low compliance such as:

[1]fibrotic or edematouslung.
[2] Any abnormality that reduces the expansibility of the thoracic cage like
neuromuscular or musculoskeletal diseases such as deformities of the chest cage (as
kyphosis, sever scoliosis).

Increased compliance is produced by the pathological processes that occur in

emphysema and also result of the aging process. In both condition, there is a decrease
in the retractive force in the lungs with consequent increase in compliance.

The Work Of Breathing:

During normal quiet respiration, respiratory muscle

contraction  occurs  only  during  inspiration,  whereas  expiration  is  entirely  a  passive
process  caused  by  elastic  recoil  of  the  lung  and  chest  cage  structures.  Thus,  the
respiratory muscles normally perform work only to cause inspiration and not at all to
cause  expiration.  During  normal  quiet  breathing  most  of  the  work  performed  by  the
respiratory muscles is used to expand the lungs against its elastic forces (compliance
work).  A  small  amount  of  only  few  per  cent  of  the  total  work  is  used  to  overcome
tissue  resistance  (tissue  resistance  work)  which  is  due  to  the  viscosity  of  the  lungs
and  chest  wall  structures  and  somewhat  more  is  used  to  overcome  airway  resistance
(airway resistance work).

The work required to expand the lungs is greater in adults than in children

because greater volumes of gas have to be shifted in adults than in children.

Compliance work and tissue resistance works are especially increased by diseases

that cause fibrosis of the lungs. On the other hand, airway resistance work is increased
in heavy breathing and in obstructive airway diseases in which air must flow through
the respiratory passageways at a very high velocity and greater proportion of the work
is then used to overcome airway resistance. During normal quiet respiration (at a basal
level of total energy production by the body) or even during heavy exercise (at a high
level  of  total  energy  production  by  the  body),  only  2-3%  of  the  total  energy  (total
O2consumption)  expended  by  the  body  is  required  to  energize  the  pulmonary
ventilatory  process.  On  the  other  hand,  pulmonary  diseases  that  decrease  the
pulmonary  compliance,  or  that  increases  airway  resistance,  or  that  increase  the
viscosity  of  the  lung  or  chest  wall  can  at  times  increase  the  work  of  breathing  up  to

ESPIRATORY

YSTEM

30% or more of the total energy expended by the body is for respiration alone which
may in certain circumstances lead to death.

The dead space

It is the space in which the gas exchange is not taking place.

Some of the air that a person breathes never reaches the gas exchange areas but instead
goes to fill the respiratory passages. The respiratory passages where no gas exchange
takes  place  is  called  the  anatomical  dead  space  (which  consist  of  nose,  pharynx,
larynx,  trachea,  bronchi,  bronchioles).  The  normal  anatomical  dead  space  air  in  the
young adult is about 150 ml. This increases slightly with age. It also increases by more
than  half  during  a  maximal  inspiration  because  the  trachea  and  bronchi  expand
markedly  as  the  lungs  expand.  There  is  another  type  of  dead  space  and  is  called
physiological  dead space.  This  is  due  to  some  alveoli  are  not functional  or  are only
partially functional because of absent or poor blood flow through adjacent pulmonary
capillaries.  Therefore,  from  a  functional  point  of  view,  these  alveoli  must  also  be
considered to be dead space. In the normal person, all the alveoli are functional in the
normal lung. Therefore, the volume of physiological dead space is equal to zero.
Total dead space = anatomical D.S. + physiological D.S.
= 150 + 0 = 150 ml. i.e. equal to anatomical dead space.

In person with partially functional or nonfunctional alveoli in some part of lungs,

the physiologic dead space is sometimes as much as ten times the anatomical dead
space. If the tidal volume is 500 ml, a normal dead space of 150 ml, and a respiratory
rate of 12 times per minute, alveolar ventilation equals 12 x (500 - 150) = 4200ml /
min.

Ventilation — Perfusion Ratio (VA/Q):

[1]If some areas of the lungs are well ventilated but have no
or almost no blood flow, VA/Q = infinity. Therefore, the
alveolar air has the same composition and concentration of
the humidified inspired air (pO

= 149 mm Hg, PCO

0.3mm

Hg). In normal person in the upright position, both

blood  flow  and  alveolarventilation  are  considerably  less in
the upper part of the lung than in the lower part. However,
blood flow is decreased considerably more than ventilation
because the low-pressure pulmonary capillaries at the lung
apices  are  compressed  by  the  higher-pressure  lung  alveoli.
Therefore, at the top of the lung, VA/Q is as much as three
times  as  great  as the ideal value, which  causes  a  moderate
degree of  physiologic  dead space in this area  of  the  lung.
VA/Q  equal  to  infinity  does  not  occur  in  the  normal  lung
but instead occurs only in abnormal conditions such as in some lung diseases, a fall in
arterial  pressure  (following  haemorrhage)  or  breathing  against  a  high  pressure  as
occurs  when  a  person  is  blowing  on  a  musical  instrument.  Breathing  against  a  high
pressure  causes  a  compression  of  the  pulmonary  capillaries  by  the  high  alveolar

ESPIRATORY

YSTEM

pressure. In some chronic obstructive lung diseases such as emphysema, some areas of
the lungs exhibit very serious physiologic shunt and other areas very serious
physiologic dead space. Both of these tremendously decrease the effectiveness of the
lungs as gas exchange organ.

[2]If some areas of the lung have excellent blood flow but little or no ventilation,
VA/Q = zero. Therefore, the alveolar air comes to equilibrium with the venous blood
gases (PO

= 40 mm Hg, PCO

= 45 mm Hg) without further gases exchange because

there is no new gas coming from the exterior air to the alveoli. Whenever VA/Q is
below normal (i.e. low ventilation and normal perfusion), the ventilation is not enough
to provide the O

needed to oxygenate the blood flowing through the alveolar

capillaries  and  consequently  leads  to  hypoxemia.  Therefore,  a  certain  fraction  of  the
venous blood passing through the pulmonary capillaries does not become oxygenated.
This  fraction  is  called  shunted  bloodas  it  occurs  normally  in  the  bottom  of  the  lung
with  VA/Q  as  low  as  0.6  times  the  ideal  value.  Also,  some  additional  blood  flows
through  the  bronchial  vessels  rather  than  through  the  alveolar  capillaries,  normally
about 2% of the cardiac output, this too is unoxygenated, i.e. shunted blood. The total
quantitative amount of shunted blood per minute is called the physiologic shunt

At a ratio of either zero(shunt) or infinity(dead space), there will be no proper

exchange  of  gases  through  the  respiratory  membranes  of  the  affected  alveoli.When
alveolar  ventilation  is  normal  for  a  given  alveolus  and  blood  flow  is  also  normal  for
the  same  alveolus,  the  VA/Q  is  also  said  to  be  normal(0.8).Therefore,  PCO

(40 mm

Hg) and PO

(104 mm Hg) in the alveoli lie somewhere between that of the inspired air

and that of venous blood.

Compensatory Mechanisms For Matching The Ventilation And
Perfusion:

For proper blood oxygenation, the right proportion of air and capillary blood should be
available to each alveolus, local changes in the tone of smooth muscles of bronchioles
and pulmonary vessels help to maintain this equilibrium through two mechanisms:

[1] Local blood PCO

.if an alveolus is receiving too much air for its blood supply,

the blood CO

will be washed out and the concentration of CO

in the blood and in the

surrounding tissue will be low. Consequently the airways supplying the alveolus are
exposed to this low tissue CO

concentration and become constricted and vice versa.

By this local mechanism, ventilation can be matched to blood supply.

[2] Local blood PO

if an alveolus is receiving too little air for its blood supply,

the blood and tissue O2 will be decreased. A decreased O

concentration in the

pulmonary vessel causes a constriction to these vessels and vice versa (the opposite
effect that exerted on systemic arteries). By this local mechanism, perfusion can match
ventilation.

(II)

Pulmonary Diffusion (Gas Exchange in the Lungs):

ESPIRATORY

YSTEM

After the alveoli are ventilated with fresh air, the next step is diffusion of oxygen from
the alveoli into the pulmonary blood and diffusion of CO

in the opposite direction,

from the pulmonary blood into the alveoli.At rest, during each minute, body cells
consume about 200ml of oxygen and produce about the same amount of CO

.The

relative amounts of these two gases depend primarily upon what nutrients are being
used for energy; e.g., when glucose is utilized, one molecule of CO

is produced for

every molecule of oxygen consumed. The ration of CO

produced / O

consumed is

known as the respiratory quotient (RQ);accordingly for glucose RQ = 1.When fat is
utilized, only 7 molecules of CO

are produced for every 10molecules of O

consumed,

and RQ = 0.7.On mixed diet, the RQ is between these values.

Composition of alveolar air:

Alveolar air does not have the same concentrations

of gases as atmospheric air and there are several reasons for this difference:
[1]The alveolar air is only partially replaced by atmospheric air with each breath. This
is because that the amount of alveolar air replaced by new atmospheric air with each
breath (tidal volume  - dead space) is only one several of functional residual capacity.
So  that  many  breaths  are  required  to  exchange  most  of  the  alveolar  air.  This  slow
replacement of alveolar air is of particular importance in preventing sudden changes in
gaseous  concentrations  in  the  blood.  This  makes  the  respiratory  control  mechanism
much  more  stable  and  helps  to  prevent  excessive  increases  and  decreases  in  tissue
oxygenation, tissue CO

concentration, and tissue pH when respiration is temporarily

interrupted.
[2]O

is constantly being absorbed from the alveolar air into the blood of the lungs,

and new O

is continually entering the alveoli from the atmosphere. Therefore, O

concentration in the alveoli, and therefore, its partial pressure as well, is controlled by:
[a]- the rate of absorption of O

into the blood, [b]-the rate of entry of new O

into the

lungs by ventilatory process.
[3]CO

is constantly diffusing from the pulmonary blood into the alveoli. The two

factors that determine alveolar concentration of CO

and also its partial pressure are (a)

the rate of excretion of CO

from the blood into the alveoli and (b)the rate at which

are removed from the alveoli out by alveolar ventilation.

[4]Dry atmospheric air that enters the respiratory passage is humidified even before it
reaches the alveoli. This water vapor

simply dilutes all the

other gases in the inspired air as

shown in the table.

Composition

Atmospheric air
(mm Hg)

Humidified air
(mm Hg)

Alveolar air
(mm Hg)

Expired air
(mm Hg)

567

563.7

569

566

159

149

104

120

0.3

Total

760

ESPIRATORY

YSTEM

The Respiratory Unit:

It is composed of a respiratory bronchiole, alveolar

ducts,  alveolar  sacs,  and  alveoli  (about  300  million  in  the  two  lungs).  Each  alveolus
having an average diameter of about 0.2 mm. the alveolar gases are in close proximity
to the blood of the capillaries. The gaseous exchange between the alveolar air and the
pulmonary  blood  occurs  through  the  membrane  of  all  the  terminal  portions  of  the
lungs. These membranes are collectively called the respiratory membrane (pulmonary
membrane)which consist of the following layers:
[1] Alayer of fluid lining the alveolus and containingsurfactant.
[2] The alveolar epithelium.
[3] The epithelial basement membrane.
[4] Avery thin interstitial space.
[5]  Acapillary  basement  membrane  that  in  many  placesfuses  with  the  epithelial
basement membrane and
obliterating the interstitial space.
[6] The capillary endothelial membrane.

The average thickness of these layers is about 0.63 micron. The total surface area

of the respiratory membrane is estimated to be about 160 square meters, over which a
quantity  of  blood of about  60-140  ml  only  (the  quantity  of  blood  in the  capillaries  if
the  lung  at  any  given  instant)  is  spread,  which  explain  the  rapidity  of  respiratory
exchange  of  gases.  In  addition,  the  diameter  of  the  pulmonary  capillaries  is  about  8
microns which is about the same diameter of RBC, therefore, RBC as it pass through
these capillaries are in fact in close contact with the endothelial membrane. This also
help in making the gas exchange rapid because the gases can pass directly from RBC
to the alveoli without passing through significant plasma.

Factors That Affect Rate Of Gas Diffusion Through The
Respiratory Membrane:

[1]

The thickness of the membrane:

any factor that increases the thickness to

more  than  two  or  three  times  the  normal  can  decrease  significantly  the  rate  of  gases
diffusion.  This  can  occur  in  edema  of  the  interstitial  space  of  the  membrane,  and  in
some fibrotic diseases of the lung.
[2]

The surface area of respiratory membrane:

when the total surface area is

decreased to about one third to one fourth normal, exchange of gases through the
membrane is impeded to a significant degree even under resting conditions. This can
occur in emphysema of the lung in which many alveoli coalesce with dissolution of
many alveolar walls.

[3] The diffusion coefficient:

depends proportionally on the solubility of the gas

in the membrane and inversely on the square root of its molecular weight. Therefore,
for a given pressuredifference, CO

diffuse through the membrane about

times as

rapidly as O

. Oxygenin turn diffuses about two times as rapidly as nitrogen.

ESPIRATORY

YSTEM

[4] The pressure difference

between the two sides of the membrane, which tends

to move the gas from area of higher partial pressure to an area of low partial pressure.

(III)

Transport of oxygen and carbon dioxide in the blood
and body fluids

Blood transports O2 and CO2 between the lungs and other body
tissues.Gases are transported in different forms:

1.  Dissolved in plasma
2.  Chemical combination with Hb
3.  Converted into different molecule.

It is important to understand the difference between the partial pressure of a gas
and the gas content of a liquid. The partial pressure of the gas represents the
pressure it would exert in the gas phase. The gas content represents the volume of
the gas per unit volume of liquid that is present. Liquids must be exposed to a gas
tension for a finite time for the gases to dissolve in the liquid phase. If the
exposure time is long enough, the gas tension in the liquid will become equal to
that of the gas phase and an equilibrium will exist between the gases and the
liquid phases. Gases can move from one point to another by diffusion, which is
driven by the pressure difference between the two points. Thus, O

diffuses from

the alveoli (PO

= 104 mm Hg) into the pulmonary capillary blood (PO

= 40 mm

Hg) where it combines with Hb. Then from the systemic capillaries (PO

= 95

mm Hg) O

diffuses to and equilibrate with interstitial fluid of 40 mm Hg and

then diffuses to the cells (PO

= 23 mm Hg). Therefore, PO

of the blood leaving

the tissues capillaries and entering the veins is about 40 mm Hg. Conversely,
when O

is metabolized in the cells, the PCO

rises to a high value (PCO

= 46

mm Hg), which causes CO

to diffuse into the interstitial fluid with PCO

of 45

mm Hg and then it diffuses to and equilibrate with CO

of blood in tissue

capillaries (PCO

= 40 mm Hg) and combines with chemical substances in the

blood that increase CO

transport. Therefore, PCO

of the blood leaving the tissue

capillaries and entering the veins is about 45 mm Hg. Similarly, it diffuses out of
the blood into the alveoli because the PCO

in the alveoli (40 mm Hg) is lower

than that in the pulmonary capillary blood (45 mm Hg).
About 98% of the blood that enters the left atrium from the lungs passes through
the alveolar capillaries and becomes fully oxygenated (PO

= 104 mm Hg) and

2% passes through the bronchial circulation (dead space), which represents the
shunted blood by passing the gas exchange areas and has a PO

about the same of

the normal venous blood (PO

= 40 mm Hg). This blood combines in the

pulmonary veins with the oxygenated blood from the alveolar capillaries. This
mixing of the blood is called venous admixture of blood, and it causes the PO

the blood pumped by the left heart into the aorta to fall to about 95 mm Hg.

The PO

in the interstitial fluids is affected by:

ESPIRATORY

YSTEM

1- The blood flow: As the blood flow increases, the O

delivery to the tissues

increases.

2- Tissue metabolism; if the cells utilize more O

for metabolism than normally,

this tends to reduce the interstitial fluid PO

3- Hb concentration; because about 97% of the O

transported in the blood is

carried by Hb, a decrease in Hb concentration reduces the O

delivery to the

interstitial fluid causing a reduction in PO

in the interstitial fluid.

Since only 3 mm Hg of O

pressure is normally required for full support of the

metabolic processes of the cell, one can see that even this low cellular PO

, 23 mm Hg,

is more than adequate and actually provides a considerable safety factor.

The PCO

in the interstitial fluid can be affected by:

1- the decrease in blood flow which causes an increase in the PCO

2- increase in metabolic rate greatly elevates the PCO

at all levels of blood flow.

Oxygen Transport

Each RBC molecule contains about 250 million Hb molecules.Each Hb
molecule consists of:

1. globin portion(4 polypeptide chains)
2. Four iron containing pigmets(heme groups)

Each iron atom binds one oxygen molecule thus Hb molecule can bind up
to 4 oxygen molecules(100% saturated) or fewer o2 molecules(partially
saturated).

ESPIRATORY

YSTEM

Oxygen binding occurs in response to the high PO2 in the lungs
forming oxyhemoglobin.

Once O2 binds to Hb,other molecules binds more readily because Hb
affinity for O2 increases as its saturation increases(co-operative binding).

The formation of oxyHb is the reversable reaction(Hb +O2 = Hb02)
depending on concentration of reactants and products of reaction.

In the lungs, when PO2 is high the reaction procedes to the right forming
HbO2(O2 loading).

In the tissuess, when PO2 is high the reaction procedes to the left ;0xyHb
is dissociated releasing O2 (O2 unloading).

This is a curve which correlates between partial pressure of oxygen and
hemoglobin saturation with oxygen.

The degree of Hb saturation deppends on PO2. In the lungs,the PO2 is
about 100 mmHg,Hb has high affinity for O2 and it is 98% saturated with
O2.In the tissues,PO2 is 40 mmHg, Hb has lower affinity for O2 and it is
75% saturated with O2 when leaving the tissues.

The curve is "S" shaped with flat slope at higher PO2s (80-
100mmHg)and steep slope at lower PO2(10-60 mmHg).

At see level,PO2 in the lungs=100mmHg and Hb is 98% saturated.

ESPIRATORY

YSTEM

At higher altitude or cardiopulmonary diseases PO2 decreases by 20%
(PO2=80%) but Hb is still highly saturated(95%).

In the tissues where PO2= 40 mmHg, Hb has a lower affinity for O2 and
it  is  only  75%  saturated.During  vigorus  exercise,PO2  decreases(20
mmHg) because muscles use more O2 and Hb is 35% saturated.As PO2
decreases, Hb releases much more O2 to the tissues. This allows the body
to  math  closely  between  O2  delivery  by  Hb  and  the  O2  utilization  by
tissues.

In addition to PO2,Hb saturation is altered by four other factors:

1.  pH
2.  temperature
3.  PCO2
4.  BPG(Biphosphoglycerate)

Any of these factors or all of them togetherplay a role during exercise.

During vigorous exercise,contracting muscle produce more metabolic
acids like lactic acid which lowers pH,more temperature and more

ESPIRATORY

YSTEM

CO2..In addition, high temp and lower PO2 increase BPG production by
RBC which decreases Hb affinity for O2 thus releasing more O2 to active
cells.When pH decreases, the curve shifts to right(increased O2
unloading).A similar shift occurs in response to high temp,high
POC2,high BPG.

At decreased temperatures,the Hb affinity for O2 is higher(less O2 is
released);the curve shifts to left.Similar shift occurs in response to high
pH,low PCO2,low BPG.

The role of 2,3 — PPG:

It is highly charged anion that binds to the Bchains of

deoxygenated Hb but not to those of oxyHb as follow: HbO

+ 2,3-DPG→ Hb-2,3-

DPG + O

. In this equilibrium, an increase in the concentration of 2,3-DPG shifts the

reaction to the right, causing more O

to be liberated.

The normal 2,3-DPG in the RBC keeps the O

-Hb dissociation curve shifted slightly to

the  right  all  the  time.  In  hypoxic  conditions  that  last  longer  than  a  few  hours,  the
quantity  of  2,3-DPG  in  the  RBC increases  considerably, thus  shifting  the  curve  even
farther  to  the  right.This  mechanism  might  be  important  for  adaptation  to  hypoxia.
However,  the  presence  of  the  excess  2,3-DPG  also  makes  it  difficult  for  the  Hb  to
combine with O

in the lungs when the alveolar PO

is reduced, thereby often creating

as much harm as good. Thyroid hormones, growth hormone, and androgens increase
the concentration of 2,3-DPG in the RBC and hence P

. 2,3-DPG is very plentiful in

RBC.

The role of Hb-F:

The greater affinity of Hb-F than Hb-A for O

facilitates the

movement of O

from the mother to the fetus. The cause of this greater affinity is the

poor binding of 2,3-DPG by the y polypeptide chains that replace Bchains in Hb-F.

Transport of O

in the dissolved state

: 0.17 ml of O

is normally transported in

the dissolved state to the tissues by each 100 ml of blood (3% of the total transported
O

). If a person breathsO

in high concentration ( very high alveolar PO

), the amount

then transported in the dissolved state can become very high.

Myoglobin:

It is an iron-containing pigment found in skeletal muscle. It resembles

Hb but binds one rather 4 mol of O

per mol. Its dissociation curve is a rectangular

rather than a sigmoid curve. Because its curve is to the left of the Hb curve, it takes up
O

from Hb in the blood. It releases O

only at low PO2 values, but the PO

exercising muscle is close to zero. The muscle blood supply is compressed during
contractions, and myoglobin may provide O

when blood flow is cut off.

Combination of Hb with CO:

CO has affinity of 230 times to combine with Hb

than O

do and form carboxyHb. A patient poisoned with CO can be treated by

ESPIRATORY

YSTEM

administration pure O

, for O

at high alveolar pressure displaces CO from its

combination with Hb far more rapidly than can O

at the low pressure of atmospheric

. The patient can also be benefited by simultaneous administration of a few per cent

because this strongly stimulates the respiratory center. This increases alveolar

ventilation and reduces the alveolar CO concentration, which allows increased CO
release from the blood.

CO2 Transport:

7% dissolved in plasma and 93% carried by RBC(23% combined with
Hb forming carbamino-Hb, 70% converted into bicarbonate ions).

Carbamino-Hb

: CO2 combines reversibly with the globin

portion of Hb forming carbamino-Hb.

a. In the tissues where PCO2 is high, Hb-CO2 is formed.
b. In the lungs where PCO2 is low, Hb-CO2 is dissociated and

CO2 is exhaled.

Bicarbonate ions

: 70% of CO2 is converted into bicarbonate

ions (faster than CO2) within the RBC in a sequence of reversible
reactions then tranported in plasma:

a. In the tissues( regions with high PCO2) CO2 enters RBC

combines  with  water  to  form  carbonic  acid.This  reaction  is
catalyzed  by  carbonic  anhydrase  enzyme.  Similar  reaction  occurs
in  plasma  but  without  enzyme  it  is  very  slow.Carbonic  acid
dissociates  into  H+  and  bicarbonate.Hydrogen  ions  is  buffered  by
Hb  forming(H-HB).To  maintain  electrical  neutrality,bicarbonate
ions  diffuse  out  of  RBC  in  exchange  with  chloride  ions(chloride

ESPIRATORY

YSTEM

shift).Within the plasma,bicarbonate ions act as pHbuffer. .

b. In the lungs, CO2 diffuses out of the plasma into the

alveoli.This  lowers  PCO2in  the  blood  causing  the  chemical
reactions to reverse.Bicarbonate ions diffuse back into RBC and
chloride ions diffuse out(chloride shift).Hydrogen ions combine
with  bicarbonate  ions  to  form  carbonic  acid.  Carbonic  acid
breaksdown  into  CO2  and  H2O.This  reverse  reaction  is  also

ESPIRATORY

YSTEM

catalyzed

carbonic

anhydrase

enzyme.

During  external  respiration,small  amounts  of  O2  remains
dissolved  in  plasma  with  the  majority  in  combination  with  Hb
forming  oxy-hemoglobin(Hb-O2).when  Hb  is  saturated  with
O2,its  affinity  for  CO2  decreases.Any  CO2  combined  with  Hb

ESPIRATORY

YSTEM

,dissociates and diffuses out of RBC through plasma and then to
alveoli.The  H+  ions  released  from  Hb  is  combined  with
bicarbonate  ions  which  diffuses  into  RBC  from  plasma  in
exchange  for  chloride(chloride  shift).Then  reaction  between
H+and  bicarbonate  to  form  carbonic  acid  which  breaks  down
into CO2 and H2O.This CO2  plus small amounts transported in
the dissolved form diffuse into alveoli.

In other wards,O2 loading facilitates CO2 unloading from

Hb.This is called

Haldane effect

During internal respiration,small amounts of CO2 remains dissolved in
plasma with the majourity within RBC reacting with water to form carbonic
acid which dissociates into H+ and Bicarbonate ions.within RBC, H+ ions
are buffered by Hb forming H-Hb.

When Hb is bound to H+ it has lower affinity

for O2 thus O2 dissociates from Hb and diffuses out of RBC to the tissue.The
interaction between H+ binding and Hb affinity for O2 is called

Bohr effect.By

forming H+ ions,CO2 loading facilitates O2 unloading.Small amounts of
O2 transported in dissolved state also diffuses out into tissue cells.DeoxyHb
has high affinity to CO2

ESPIRATORY

YSTEM

The Response of Respiratory System to Exercise and
Stress:

During exercise or other stressful conditions, the body may require as much

times of the normal amount of O

The increased cardiac output causes blood to

stay half normal time in the pulmonary capillary. Yet, the blood is still almost
completely saturated with O

when it leaves the pulmonary capillaries due to an

increase in the diffusing capacity of the respiratory membrane for O

about threefolds

during exercise, the reasons for this are:

[A] The average RBC spends approximately 0.75 sec in the pulmonary capillary.
If O

equilibration occurs in 0.25 sec, then there is normally no increase in the

content for the last 0.50 sec of transit through the pulmonary capillary. This

time provides a safety margin that ensures an adequate O

uptake during periods

of stress.
[B] The opening up a number of previously dormant pulmonary capillaries, and
dilatation of already functioning pulmonary capillaries thereby increases the
surface area of blood into which the oxygen can diffuse.
[C] Increased alveolar ventilation.
[D] More ideal ventilation-perfusion ratio in the upper part of the lungs.
[E] During exercise, there is a considerable shift of the Hb-O

dissociation curve

to the right (i.e. decrease in the affinity of Hb to combine with O

) in the muscle

capillary blood due to the release of large amounts of CO

, acids, and phosphate

compounds, in addition to high temperature of the muscles. Then in the lungs, the
events are reversed, thus, the shift occurs in the opposite direction (i.e. to the left,
which means an increase in the affinity of Hb to combine with O

), thus allowing

pickup of extra amounts of O

from the alveoli.

(IV)Regulation of Respiration

The respiratory centre

The respiratory cycle (inspiration and expiration) is

regulated by the respiratory center in the brain which is composed of three major
groups of neurons located bilaterally in the medulla oblongata and pons and these are:

[1] The dorsal group of neurons:

This group of neurons is located in the medulla

within the nucleus of the tractussolitorius which is also the sensory termination of both
the  vagal  and  glossopharyngeal  nerves  transmitting  sensory  signals  into  the
respiratory  center  from  the  peripheral  chemoreceptors,  baroreceptors  and  several
different  types  of  receptors  in  the  lung.  They  are  responsible  for  the  basic  rhythm  of
respiration by autonomous repetitive bursts of inspiratory action potentials. The nerve
signal that is transmitted to the inspiratory muscles (through contralateral phrenic and
intercostal  motoneurons  and  to  the  ventral  respiratory  group)  begins  very  weakly  at
first and increase steadily in a ramp fashion for about 2-sec. Then it abruptly ceases for
approximately the next 3 sec, and then begins again for still another cycle, and again

ESPIRATORY

YSTEM

and again. The advantage of this is that it causes a steady increase in the volume of the
lungs during inspiration, rather than inspiratory gasps.

[2] The pneumotaxic group:

This group of neurons is located within the pons in

the  nucleus  parabrachialis  and  they  transmit  impulses  continuously  to  the  dorsal
respiratory  group  of neurons. The  primary  effect  of  these  is to  control  the  switch  off
point  of  the  inspiratory  ramp, thus  controlling the duration  of  the  filling  phase of the
lung cycle.

[3] The ventral group:

These neurons are located in the nucleus ambiguus and

nucleus retroambiguus and is comprised of the upper motor neurons of the vagus and
the  nerves  to  accessory  muscles  of  respiration.These  neurons  contribute  to  both
inspiration  and  expiration,  however,  they  are  especially  important  inproviding  the
powerful expiratory forces during expiration. Thus, this area operates more or less as
an overdrive mechanism when high levels of pulmonary ventilation are required.

Control Of Respiration:

The respiratory centers and consequently the

ventilation can be controlled by the following chemical and neural factors:

1. Chemical control: mediated through changes in PCO

, [H

], and PO

2. Neural control:

a.  Higher brain centers and peripheral proprioceptors control of respiration.
b.  Motor cortex control ofrespiration.
c.  Vasomotor center control of respiration.
d.  Body temperature control of respiration.

1. Chemical control of respiration:

A: Central chemoreceptors:

Surplus of CO

or H

affected respiration mainly by

excitatory effects on the respiratory center itself, causing greatly increased strength of
both the inspiratory and expiratory signals to the respiratory muscles. The resulting
increase in ventilation (4-fold increase caused by decreasing the blood pH or 11-fold
increase caused by increasing PCO

) increases the elimination of CO

from the blood,

this also removes H

from the blood because decreased CO

also decreases the blood

carbonic acid. It is believed that the blood CO

and H

do-not affect the respiratory

centers  directly.  Instead,  achemosensitive  area  located  bilaterally  only  a  few  microns
beneath  the  surface  of  themedulla  ventral  to  the  entry  of  the  glossopharyngeal  and
vagal  nerves  into  the  medulla,  this  area  is  highly  sensitive  to  changes  in  H  ion
concentration, and it in turn excites the other portions of the respiratory center. It has
especially potent effects on increasing the degree of activity of the inspiratory center,
increasing both the rate of rise of the inspiratory ramp signals and also the intensity of
the signal. However, H

do not easily cross either the blood-brain barrier or the blood-

cerebrospinal fluid barrier. For this reason, changes in H

concentration in the blood

actually have considerably less effect in stimulating the chemosensitive neurons than
do changes in CO

. This is because CO

passes through blood-brain barrier and blood-

cerebrospinal fluid barrier very easily. Consequently, whenever the blood CO

concentration increases, the PCO

in both the interstitial fluid of the medulla and in the

ESPIRATORY

YSTEM

cerebrospinal fluid also increase. In both of these fluids the CO

immediately reacts

with the water to form carbonic acid which dissociates into H

and bicarbonates. Thus,

paradoxically, more H

are released into the respiratory chemosensitive sensory area

when the blood CO

concentration increases than when the blood H

concentration

increases. For this reason, respiratory center activity is affected considerably more by
changes in blood CO

than by changes in blood H

The stimulatory effect of increased CO

on respiration reaches its peak within a

few minutes after an increase in blood PCO

. Thereafter, the stimulation gradually

declines for the next one to two days to as little as one-fifth the initial effect due to
adaptation of the receptors. Therefore, A change in blood CO

concentration has a

very potent acute effect on controlling respiration but only a weak chronic effect after
a few days' adaptation.

: Arterial PO

does not have a significant direct effect on the respiratory center of

the brain in controlling respiration. Instead, it acts almost entirely on peripheral
chemoreceptors located in the carotid and aortic bodies, and these in turn transmit
appropriate nervous signals to the respiratory center for control of respiration.

B: Peripheral chemoreceptors(carotid and aortic bodies):

Carotid

bodiesare  located  bilaterally  in  the  bifurcations  of  the  common  carotid  arteries,  and
their afferent never fibers pass to the glossopharyngeal nerves and thence to the dorsal
respiratory area of the medulla. Aortic bodies  are located along the arch of the aorta,
and their afferent  fibers pass through the vagito the dorsal respiratory area.

The blood flow through the carotid and aortic bodies is extremely high. Because
of this, arteriovenousoxygen difference is very small, which means that the
venous blood leaving these bodies still has a PO

nearly equal to that of the

arterial blood. It also means that PO

of the tissues in these bodies remains atall

ESPIRATORY

YSTEM

times almost equal to that of the arterial blood. Thesebodies are more influenced
by :

(a)arterial PO

which is determined by the amount of dissolved O

ratherthan by

arterial oxygen content.Hence, they are not influenced by a low Hb level.When
the arterial PO

falls below normal (especially PO

in the range between 60 and 30

mm Hg), or when the blood pressure sufficiently low causing a low blood flow
(even though constituents of blood do not change), the chemoreceptors become
strongly stimulated.

(b)increase in CO

or H

concentration: also excites the chemoreceptors and in

this way indirectly increases respiratory activity. However, the direct effects of
both these factors in the respiratoiy center itself are so much powerful.

The cause of the poor effect of low PO

on respiratory control in comparison to

those of CO

and H

concentration can be explained as follow: The increase in

ventilation that does occur when the PO

falls blows off the respiratory stimulants

(CO

and consequently H+). However, overseveral days, the respiratory center

gradually becomes adapted to the diminished CO

and alveolar ventilation then

rises to as high as five to seven times normal. This is part of the acclimatization
that  occurs  as  a  person  slowly  ascends  a  mountain.  Yet,  under  some  abnormal
conditions,  as  occurs  in  pneumonia,  emphysema    in  which  gas  exchange  is
impaired,  the  PCO

and H

concentrations increase at the same time that the

arterial PO

decrease. Under these conditions, all three of the feedback

mechanisms work together, and the PO

mechanism then exerts its full share of

respiratory stimulation, sometimes becoming even more potent as a controller of
respiration than the PCO

and H

mechanisms.

ESPIRATORY

YSTEM

2.Neural control:

A: Peripheral receptors



Stretch receptors:

in the wall of the bronchi and bronchiole transmit signals

through  the  vagi  into  the  dorsal  respiratory  group  of  neurons  when  the  lungs
become  overstretched(the  tidal  volume  increases  to  greater  than  approximately
1.5  liters).  Therefore,  when  the  lungs  become  overly  inflated,  the  stretch
receptors  activate  an  appropriate  feedback  response  that  switches  off  the
inspiratory  ramp  and  thus  limits  further  inspiration.  This  is  called  the  Hering-
Breuer inflation reflex,this reflex appears to be mainly a protective mechanism
for  preventing  excess  lung  inflation  rather  than  important  ingredient  in  the
normal control of ventilation.



J receptors:

These receptors are located in the pulmonary interstitium at the

level  of  the  pulmonary  capillaries  and  are  stimulated  by  distension  of  the
pulmonary  vessels  (e.g.,  as  caused  by  left  ventricular  failure,  pulmonary
embolization, and  certain  chemicals  or drugs). These  receptors  initiate  reflexes
causing rapid, shallow breathing (tachypnea).



Chest wall receptors:

which can detect the force generated by the respiratory

muscle  during  breathing.  If  the  force  required  to  distend  the  lungs  becomes
excessive  (either  as  a  result  of  high  airway  resistance  or  low  compliance),  the
information  from  these  receptors  gives  rise  to  the  sensation  of  dyspnea
(difficulty in breathing).



Irritant receptors:located in the large airways and are stimulated by smoke,

noxious gases, and particulates in the inspired air. These receptors initiate
reflexes that cause coughing, bronchconstriction, mucus secretion, and breath
holding (i.e., apnea).



Joint proprioceptors During exercise, the body movements, especially of the

limbs, are believed to increase pulmonary ventilation by exciting that then
transmit excitatory impulses to the respiratory center.

ESPIRATORY

YSTEM

Motor cortex:

Respiration can be controlled voluntarily, and that one can

hyperventilated or hyporventilated to such an extent that serious derangements in
PCO

, pH and PO

can occur in the blood. This is mediated by the nervous pathway for

voluntary control passes directly from the motor cortex and other higher centers
downward through the corticospinal tract to the spinal neurons that drive the
respiratory muscles.

Vasomotor center:

The

vasomotor

center

that

control

peripheral

vasoconstriction and heart activity is closely related to respiratory center in the
medulla. A moderate degree of spillover of nerve signals occurs between the two
centers. Therefore, almost any factor that increase the activity of the vasomotor center
also has at least a moderate effect on increasing respiration.

Body temperature:

An increase in body temperature increases the rate of

respiration directly by increasing respiratory center activity and indirectly by
increasing the cellular metabolism and eventually enhances the chemical stimuli for
increased respiration.

In strenuous exercise, O

utilization and CO

formation can increase as much as

twentyfold associated with increase in alveolar ventilation. This increase in alveolar
ventilation is not mainly due to change in blood PO

, PCO

,and H

concentration

which all remain almost exactly normal, There are at least two different effects seem to
be predominantly concerned :

[A] The brain, on transmitting impulses to the contracting muscles, is believed to

transmit  collateral  impulses  into  the  brain  stem  to  excite  the  respiratory  center  .But,
occasionally, the nervous signals are either too strong or two weak in their stimulation
of  the  respiratory  center,  then  the  chemical  factors  play  a  very  significant  role  in
bringing  about  the  final  adjustment  in  respiration  required  to  keep  the  CO

and H

concentrations of the body fluids as nearly normal as possible.

[B]Joint proporioceptors transmit excitatory impulses to the respiratory center.

Pulmonary Blood Flow:

The pulmonary circulation is basically low-pressure,

low-resistance, highly compliant system. Pressure in the pulmonary artery is about 25
mmHg systolic and 8 mmHg diastolic (a mean of about 14 mmHg). Pressure in the left
atrium is about 5 mmHg, resulting in pressure drop across the pulmonary circulation of
about 9 mmHg. Pulmonary vascular resistance is 1.8 mmHg/L/min which is about
10% of the systemic vascular rersistance(18 mmHg/L/min).

Abnormalities Of Respiratory Control:

1.Respiratory center depression:the activity of respiratory center may be depressed
or even totally inactivated by cerebrovascular disease, acute brain edema, anesthesia
and overdose of narcotics.

ESPIRATORY

YSTEM

2.Periodic breathing:The most common type of periodic breathing is called  cheyne-
stokes  breathing  which  is  characterized  by  slowly  waxing  and  waning  respiration
separated by periods of apnea and can seen in heart failure or brain stem lesions.
3.Kussmaul's  respirationwhich  is  a  rapid,  deep  breathing  often  seen  in  patients
suffering  from  diabetic  ketoacidosis.  It  occurs  as  the  body  tries  to  compensate  for
metabolic acidosis by increasing the rate of CO

excretion.

Hypoxia:

Hypoxia is cellular deficiency of

. Traditionally hypoxia has been

divided into 4 types:

[1] Hypoxic hypoxia:

In which the PO

of the arterial blood is reduced due to low

atmospheric O2, inadequate ventilation of the alveoli or insufficient diffusion of O

through the respiratory membrane.

[2] Anaemic hypoxia:

In which the arterial PO

is normal but the amount of Hb

available to carry O

is reduced.

[3] Ischaemic hypoxia:

In which the blood flow to a tissue is so low that adequate

is not delivered to it despite a normal PO

and Hb concentration.

[4] Histotoxic hypoxia:

because of the action of certain toxic agents, the tissue

cells cannot make use of the O

supplied to them such as in cyanide poisoning, in

which the action of cytochrome oxidase(respiratory chain enzyme in the mitochondria)
is completely blocked.Also, deficiency of oxidative enzymes such as vitamin B
deficiency (Beriberi).

Cyanosis:

It is a dusky bluish discoloration of the tissues and appears when the

reduced  Hb  concentration  of  the  blood  in  the  capillaries  is  more  than  5  gm/dl.
Cyanosis is easily seen in mucus membrane and  thin skin areas like lips, fingers, ear
lobes, also nail bed.  In polycythaemia, cyanosis is very common because of the large
amount of Hb in the blood whereas in anaemia, cyanosis is rare because it is difficult
for  there  to  be  enough  deoxygenated  Hb  to  produce  the  cyanotic  color.  Cyanosis
divided into 2 types:

[1]

Central cyanosis: In which there is Hb-undersaturation or an abnormal Hb

derivative, and the mucous membranes and skin are both affected.

[2]

Peripheral cyanosis: Which is due to a slowing of blood flow to an area and

abnormally great extraction of O

from normally saturated arterial blood. It result

from  vasoconstriction  and  diminished  peripheral  blood  flow,  such  as  occurs  in
moderate  cold  exposure,  shock,  heart  failure,  and  peripheral  vascular  disease.
Often,  in  these  conditions,  the  mucous  membranes  of  the  oral  cavity  may  be

ESPIRATORY

YSTEM

spared. In very cold weather cyanosis does not developed, because the drop in
skin temperature inhibits the dissociation of oxy Hb and the O

consumption of

the cold tissues is decreased. Cyanosis does not occur in anaemic or histotoxic
hypoxia. In CO poisoning, the color of reduced Hb is obscured by the cherry red
color of carboxyHb. A discoloration of the skin and mucous membranes similar
to cyanosis is produced by high circulating levels of met Hb.

Hypercapnia:

It means excess CO

in the body fluids. Hypercapnia is association

with hypoxia when hypoxia is caused by hypoventilation or by circulatory deficiency.
Hypoxia resulting from poor diffusion through pulmonary membrane, serious
hypercapnia usually does not occur because CO

diffuses 20 times as rapidly as O

Therapy

: In hypoxia, O

therapy is of great value, especially in certain types of

hypoxia (such as law atmospheric O2, hypoventilation hypoxia, diffusional hypoxia")
and of slight value in hypoxia due to other causes. inchronic hypoxia,O

lack becomes

a far more powerful stimulus to respiration than usual, sometimes increasing the
ventilation as much 5-7 times. Therefore, during O

therapy, relief of the hypoxia

occasionally causes the level of pulmonary ventilation to decrease so low that lethal
levels of hypercapnia develop. For this reason, O

therapy in hypoxia is sometimes

contraindicated.

Toxicity:

Administration of 100% O

has been demonstrated to exert toxic

effects. The toxicity seems to be due to the production of the superoxide anion (O

)

and H

. When 80-100% O

administered for periods of 8 hours or more the

respiratory passages become irritated, causing substernal distress, nasal congestion,
sore throat and coughing. Exposure for 24-48 hours causes lung damage as well. The
reason O

produce the irritation is probably due to inhibition the ability of lung

macrophages to kill bacteria, and surfactant production is reduced.

ESPIRATORY

YSTEM

Lung Volumes And Capacities

Pulmonary ventilation can be recorded by using the spirometer and the process called
spirometry by which volume of air that is moved in and out of the lung can be
recorded. The volumes and capacities of lungs are:
[1] The tidal volume (TV):Is the volume of air inspired or expired with each normal
breath and it is about 500

in average young adult man.

[2]

The inspiratory reserve volume (IRV):

Is the extra volume of air that can be inspired

over and beyond tidal volume and it is about 3000 ml.

[3]

The expiratory reserve volume (ERV):

Is the amount of air that can be expired after the

normal tidal expiration, which is about 1100 ml.

[4]

The residual volume (RV):

Is the volume of air still remaining in the lungs after the most

forceful expiration, which is about 1200 ml.This is important because it provides air in the alveoli to
aerate the blood even between breaths which otherwise the concentration of oxygen and carbon
dioxide in the blood would rise and fall markedly with each respiration, which would certainly be
disadvantageous to the respiratory process.

This volume cannot be measured directly by spirometer. Therefore, an indirect method must be

used usually the helium dilution method. Once the functional residual capacity (FRC) has been
determined, the residual volume can then be determined by subtracting the expiratory reserve volume
from the functional residual capacity, i.e. RV = FRC - ERV.

The other way for determination of lung RV is by using body plethysmogrph.

[5]The inspiratory capacity (IC)

= TV +IRV = 500 +3000 = 3500

ml.

This is the amount of

air that a person cans breath beginning at the normal expiratory level and distending the lungs to the
maximum amount.

[6] The functional residual capacity (FRC)

ERV + RV = 1100 + 1200 = 2300

ml.

This is the amount of air remaining in the lungs at the end of normal expiration.
[7] The vital capacity (VC)= IRV + TV + ERV = 3000 + 500 + 1100 = 4600

ml.

This is the maximum amount of air that a person can expel from the lungs after filling
the lungs first to their maximum extent, and then expiring to the maximum extent.

Vital capacity can be decreased markedly in restrictive lung diseases (paralysis of

the  respiratory  muscles,  tuberculosis,  lung  cancer,  fibrotic  pleurisy,  pulmonary
vascular  congestion  and  edema  as  in  left  sided  heart  failure)  and  may  be  normal  in
obstructive  lung  diseases  (asthma,  chronic  bronchitis,  emphysema).  When  the  vital
capacity is reduced to about 40% of normal, the patient can no longer perform even the
simplest movements without becoming breathless.
[8] The total lung capacity (TLC)= VC + RV = 4600 + 1200 = 5800 ml

This is the

maximum volume to which the lungs can be expanded with the greatest possible
inspiratory effort.

All pulmonary volumes and capacities are about 20-25% less in women than

men, and they are greater in large athletic persons than in small and asthenic persons.
Pulmonary volumes and capacities change with the position of the body, most of them
decreasing when the person lies down and increasing on standing, this change with
position is caused by two factors:

ESPIRATORY

YSTEM

[A] - a tendency for the abdominal contents to press upward against the diaphragm in
the lying position.
[B]-an increases in the pulmonary blood volume in the lying position, which
correspondingly
decreases

the

space available
for

pulmonary

air.

Lung Function Tests

1.Forced  vital  capacity  (FVC):  It  is  the  maximum  volume  of  air
expired  forcefully  following  maximum  inspiration,  a  normal
subject this is accomplished in 3-4 sec.
2.Timed vital capacity (forced expiratory volume-1 sec, FEV1):
It  is  the  volume  of  air  expired  during  the  first  second  of  forceful
expiration.
3.Percent vital capacity (FEV1%): [FEV1/VC] x 100. In normal
subject, the FEV1% is at least  80%. However, in  obstructive  lung
diseases like asthma, FEV1% is markedly reduced while normal in
restrictive lung diseases.

ESPIRATORY

YSTEM

4.Peak expiratory flow (PEF):It is the maximum airflow obtained
during  maximum  expiratory  effort  after  maximum  inspiration.
When  a  person expires  with  great  force  through  Wright  peak  flow
meter,  the  expiratory  airflow  reaches  a  maximum  flow  beyond
which  the  flow  cannot  be  increased  even  with  greatly  increased
additional  force.  This  is  because  the  pressure  that  force  the  air
outside also tends to collapse the bronchioles at the same time, thus
greatly  increasing  the  airway  resistance  and  opposing  the
movement of the air to the exterior. The maximum expiratory flow
is much greater when the lungs are filled with a large volume of air
than  when  they  are  almost  empty.  The  curve  recorded  for
maximum expiratory flow was achieved by asking the subject first
to  inhale  as  much  air  as  possible  and  then  expires  with  maximum
expiratory  effort  until  he  can  expire  no  more.  A  normal  subject
cans  quickly  reaches  a  maximum  expiratory  airflow  over  400
liters/min.Maximum  expiratory  flow  is  reduced  in  cases  of
restrictive  (constrictive)  lung  diseases  like  fibrotic  diseases  of
lungs, kyphosis, scoliosis, fibrotic pleurisy, and in obstructive lung
diseases  like  asthma,  and  emphysema.  In  restrictive  lung  diseases
there  is  a  reduction  in  the  compliance  of  the  lungs  and
consequently there is a reduction in total lung capacity. Therefore,
the maximal expiratory flow cannot rise to equal that of the normal
curve.

In  obstructive  lung  diseases,  there  is  much  more  difficulty  in
expiration than on inspiration, because the closing tendency of the
airways is greatly increased by positive pressure in the chest during
expiration,  while  negative  pleural  pressure  of  inspiration  actually
pulls the airway open at the same time that it expands the alveoli.
Therefore,  because  of  the  obstruction  of  the  airways  and  its
tendency  to  collapse  easily  during  expiration,  the  maximum
expiratory flow is greatly reduced.

5.TheForced Expiratory Flow

25%–75%

(FEF

25%–75%

): The FEF

25%–

75%

is the average ﬂow rate that occurs during the middle 50 percent

ESPIRATORY

YSTEM

of an FVC measurement. This average measurement reﬂects the
condition of medium- to small-sized airways. The average FEF

25%–

75%

for normal healthy men aged 20 to 30 years is about 4.5 L/sec

(270 L/min), and for women of the same age, about 3.5 L/sec (210
L/min). The FEF

25%–75%

decreases with age and in obstructive lung

disease. In obstructive lung disease, ﬂow rates as low as 0.3 L/sec
18 L/min) have been reported. The FEF

25%–75%

is also decreased in

patients  with  restrictive  lung  disorders,  primarily  because  of  the
low  vital  capacity  associated  with  restrictive  lung  disorders.
Although  the  FEF

25%–75%

has no value in distinguishing between

obstructive  and  restrictive  disease,  it  is  helpful  in  further
conﬁrming—or  ruling  out—an  obstructive  pulmonary  disease  in
patients with borderline low FEV1%.
6.The  minute  respiratory  volume  (the  minute  ventilation):The
minute  respiratory  volume  is  the  total  amount  of  new  air  moved
into  the  respiratory  passages  each  minute  and  this  is  equal  to  TV
(500  ml)  x  respiratory  rate  (about  12  breaths  /  min)  =  6000  ml.
Respiratory rate is between 14-34 breaths / min between 2-4 years
of  age,  20-25  breaths/min  between  5-14  years  of  life,  and  10-18
breaths/min in adult subject.

7.Test  For  Lung  Diffusing  Capacity:  The  ability  of  the
respiratory  membrane  to  exchange  a  gas  between  the  alveoli  and
the pulmonary blood  can be  expressed  in  quantitative terms by its
diffusing  capacity  ,which  defined  as  the  volume  of  a  gas  that
diffuses  through  the  membrane  each  minute  for  a  pressure
difference of 1 mm Hg.

Gas dilution method ( Helium and CO mixture in low

concentrations)  is  used  to  test  lung  diffusing  capacity(DLCO-
single  breath  test).  In  average  young  male  adult,  the  diffusing
capacity  for  oxygen  under  resting  conditions  average  21-25
ml/min/mm Hg. Since the diffusion coefficient of CO

is 20 times

that of O

, one would expect a diffusing capacity for CO

under

resting conditions of about 400-450 ml/min/mm Hg and during

ESPIRATORY

YSTEM

exercise of about 1200-1300 ml/min/mm Hg. The importance of
this high diffusing capacity for CO

is that: when the respiratory

membrane becomes progressively damaged, its capacity for
transmitting O

into the blood is often impaired enough to cause

death of the person while CO

diffusion can still occur in adequate

amounts. However, the patient's life can be maintained by intensive
O

therapy that overcomes the reduction in O

diffusing capacity.