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Advance physiology
Respiratory system physiology
Assist. Prof. Dr. Majida Al-Qayim
Department of physiology and pharmacology
Ganongg;s Review of Medical Physiology. 23rd edition
Respiratory System
The respiratory system is made up of
 gas-exchanging organ (the lungs)
a"pump" that ventilates the lungs. The pump
consists of the chest wall; the respiratory
muscles, which increase and decrease the size of
the thoracic cavity
and the areas in the brain that control the
muscles; and the tracts and nerves that connect
the brain to the muscles.
Lungs are cone-shaped organs situated in the thoracic cavity. The left lung
is divided by an oblique fissure into superior and inferior lobes. The right
lung is divided by oblique and horizontal fissures into superior, middle
and inferior lobes. Each lobe receives a secondary (lobar) bronchus from
the primary bronchi. Inside the lungs, the secondary bronchi give rise to
smaller bronchi called 'tertiary (segmental) bronchi', which in turn divide
into smaller tubes called 'bronchioles'. Bronchioles branch repeatedly to
form the terminal bronchioles that divide into respiratory bronchioles.
Air passages
Between the trachea and the alveolar sacs, the airways
divide 23 times.
The first 16 generations of passages form the
conducting zone of the airways that transports gas
from and to the exterior. They are made up of
bronchi, bronchioles, and terminal bronchioles.
Volume of conducting zone is about 150 ml
The remaining seven generations form the respiratory
zones where gas exchange occurs; they are made up
of respiratory bronchioles, alveolar ducts, and
alveoli. volume of respiratory zone is 3 litters
Components of Respiratory zone
a. Respiratory bronchioles
b. Alveolar ducts
i. Smooth muscle
ii. Elastic and collagen fibers
iii. Alveoli
iv. Terminate into clusters of alveolialveolar sacs
c. Alveolar sacs
i. Groups of alveoli
d. Alveoli
Air ways crosssectional area
These multiple divisions greatly
increase the total crosssectional area of the airways,
from 2.5 cm2 in the trachea to
11,800 cm2 in the alveoli .
Consequently, the velocity of air
flow in the small airways
declines to very low values . As a
result, forward velocity of gas
during inspiration falls to a very
low level in this zone because of
the extremely rapid increase in
total cross-sectional area in the
respiratory zone.
Respiratory membraneA layer of fluid lining the alveolus and
(Blood-Gas barrier) containing
surfactant that reduces the surface
tension of the
alveolar fluid
2. The alveolar epithelium composed
of thin
epithelial cells
3. An epithelial basement membrane
4. A thin interstitial space between
the alveolar
epithelium and the capillary
5. A capillary basement membrane .�
that in many
places fuses with the alveolar epithelia
6. The capillary endothelial membrane
Alveolar wall
The alveoli are lined by two types of epithelial cells.
Type I cells are flat cells with large cytoplasmic extensions and
are the primary lining cells of the alveoli, covering
approximately 95% of the alveolar epithelial surface area.
Type II cells (granular pneumocytes) are thicker and contain
numerous lamellar inclusion bodies. A primary function of
these cells is to secrete surfactant; however, they are also
important in alveolar repair as well as other cellular
physiology. Although these cells make up approximately 5% of
the surface area, they represent approximately 60% of the
epithelial cells in the alveoli.
The alveoli also contain other specialized cells, including
pulmonary alveolar macrophages (PAMs, or AMs),
lymphocytes, plasma cells, neuroendocrine cells, and mast
cells. The mast cells contain heparin, various lipids, histamine,
and various proteases that participate in allergic reactions
Airway’s cellular types
Cells within airway
Pulmonary epithelial cells
Goblet cells
Clara cells
Fibroblast cells
Smooth muscle cells
Structure of the mucociliary
Mechanics of Breathing
The aim of the breathing is to ventilate the lung . So the pulmonary
ventilation is the physical movement of air into and out from the
lung . Ventilation results from bulk flow of air as the result of
pressure gradients which created between alveoli and atmospheric
pressure as a result of volume changes.
Boyle's law :-This law states that the pressure of gas in any container
is inversely related to the volume of the container. In other words,
when volume increases, pressure decreases and when volume
decreases, pressure increases.
P1V1 = P2V2
P = pressure of a gas in mm Hg
V = volume of a gas in cubic millimeters
Alveolar volume and pressure
changes In respiratory cycle
During inspiration, alveolar volume
increases and intra-alveolar pressure
falls causing air molecules to enter
down the pressure gradient created by
the inspiration. The air flow stops
when pressure is equal to atmospheric
pressure (0 mm Hg). During
expiration, alveolar volume decreases
and intra-alveolar pressure increases
causing air molecules to leave down a
pressure gradient in the reverse
direction until the pressure returns to
0 mm Hg. The movement of air into
and out of the alveoli is due to the
changes in the volume of the thoracic
cavity produced by the muscles of
Mechanics of respiration
As the external intercostals & diaphragm
contract, the lungs expand. The
expansion of the lungs causes the
pressure in the lungs (and alveoli) to
become slightly negative relative to
atmospheric pressure. As a result, air
moves from an area of higher pressure
(the air) to an area of lower pressure
(our lungs & alveoli). During expiration,
the respiration muscles relax & lung
volume decreases. This causes pressure
in the lungs (and alveoli) to become
slight positive relative to atmospheric
pressure. As a result, air leaves the lungs.
Elastic Recoil of lung and chest
A negative force is always required on the outside of the lungs to keep the
lungs expanded. This is provided by negative pressure in the normal
pleural space. The basic cause of this negative pressure is pumping of
fluid from the space by the lymphatics. Because the normal collapse
tendency of the lungs is about –4 mm Hg, the pleural fluid pressure
must always be at least as negative as –4 mm Hg to keep the lungs
expanded. The pumping forces results from the elastic forces exerted
on the intrapleural space by the chest wall and the lungs. The chest wall
is compressed and the elastic forces are pulling it outward. The lung
walls are stretched and the elastic forces are pulling them inward
Pressure – volume curve
(lung Compliance )
This curve explain the relation ship between the lung volume
with intrapleural pressure . The more –ve intrapleural the
greatest lung volume.
Charcterized by
 It is non linear
 Hysteresis behavior
 Volume changes to constant transpolmunary pressure
 Animal species
Lung compliance
Lung Compliance:- C= ∆ v∕∆ p
The ease with which lungs can be expanded Specifically,
the measure of the change in lung volume that occurs
with a given change in intrapleural pressure
Determined by three main factors
1- elastic recoil of lung and chest, the lung tissue and
surrounding thoracic cage collagen fiber and elastine in
alveoli wall
2- Lung surface tension
3- Airway resistance
Pressure – volume curve
(lung Compliance )in
normal and disease
Increased in age, emphysema, reduced elastic
Decreased in lung congestion, fibrosis, atalactasis(
un ventilated area)
Factors That Diminish Lung Compliance
Scar tissue or fibrosis that reduces the natural
resilience of the lungs
• Blockage of the smaller respiratory passages
with mucus or fluid
• Reduced production of surfactant
• Decreased flexibility of the thoracic cage or its
decreased ability to expand
Physiological dead space
Anatomical dead space + Alveolar dead space
Definition - It is the volume of the respiratory tract that does not participate in
gas exchange. It is approximately 300 ml in normal lungs. It is important to
distinguish between the anatomic dead space (respiratory system volume
exclusive of alveoli) and the total (physiologic) dead space (volume of gas not
equilibrating with blood; ie, wasted ventilation).
Alveolar ventilation (VA) is the volume of air reached the alveoli in per minute
that (1) reaches the alveoli and (2) takes part in gas exchange. Alveolar
ventilation is often misunderstood as representing only the volume of air that
reaches the alveoli. Physiologically, VA is the volume of alveolar air/minute that
takes part in gas exchange (transfer of oxygen and carbon dioxide) with the
pulmonary capillaries.
Factors influencing alveolar dead space:-Low cardiac output can increase
alveolar dead space (increasing West's zone 1)
Pulmonary embolism
600 mL
200 mL
Tidal volume
(600 – 150) x (200 – 150) x Alveolar
10 = 4500 mL 30 = 1500 mL ventilation
Regional differences for alveolar ventilation
The upper part are less ventilated because streach of the lung in the lower are much graeter
because: In rest compartments in the top will be more expanded greater volume V) than basal
lung compartments because the intrapleural pressure in the upper part is more negative than
the lower . As the pressure-volume curve for the same change in pleural pressure during
inspiration the volume change (ΔV) will be greatest in basal parts of the lung, and progressively
smaller towards the top. Due to this gravitational effect on the lung the ratio ΔV/V, an index of
alveolar ventilation, is smallest in upper lung regions. This differences in the intrapleural -ve
pressure between upper and lower due to the gravity and the lung mass.
This situation changed with position
Note the extremely rapid increase in total cross-sectional area and reduced resistance of airways in the
respiratory zone. As a result, forward velocity of gas flow during inspiration falls to a very low level in the base
with better ventilation and gas exchange .A unit with increased resistance, increased compliance, or both will
take longer to fill and longer to empty . In normal adults, the respiratory rate is ~12 breaths per minute, with an
inspiratory time of approximately 2 seconds and an expiratory time of about 3 seconds. In normal individuals,
this is sufficient time to almost reach equilibrium in the alveolar pressure . However, in the presence of an
increased resistance (or an increased compliance), equilibrium is not reached. This contributes to the air
trapping seen in diseases associated with increased resistance (e.g., chronic bronchitis) or increased
compliance (e.g., emphysema).
Lung Blood Flow( circulation)
• The pulmonary circulation In the pulmonary circulation,
almost all the blood in the body passes via the pulmonary
artery to the pulmonary capillary bed, where it is
oxygenated and returned to the left atrium via the
pulmonary veins . They form capillaries, which drain into
bronchial veins or anastomose with pulmonary capillaries
or veins . The bronchial veins drain into the azygos vein.
• The bronchial circulation includes the bronchial arteries
that come from systemic arteries, it nourishes the trachea
down to the terminal bronchioles and also supplies the
pleura and hilar lymph nodes. It should be noted that
lymphatic channels are more abundant in the lungs than in
any other organ.
Lung perfusion
(Pulmonary blood flow)
The term “perfusion” refers to the amount of
blood flowing through an organ in a given period
of time, usually one minute, the lungs receive
Cardiac Output (about 5 L per minute).This is
because the right and left sides of the heart have
to output the same volume of blood. So, the same
volume passing through systemic circulation also
has to pass through the lungs.
Therefore, you have a numerical value for perfusion,
5 L / min
Regional differences for alveolar perfusion
(Un even perfusion )
Lung mass
Random variations in the resistance of
blood vessels. Some evidence that proximal
regions of an acinus receive more blood
flow than distal regions. In some animals
some regions of the lung have an
intrinsically higher vascular resistance.
 Three pressures control the capillary blood
Pa: arterial pressure
Pv: venous pressure
PA: alveolar pressure
Ventilation- perfusion ratio
Gas exchange is only optimal when individual
regions are ventilated in proportion to their
capillary blood flow. Well ventilated regions ideally
have high capillary blood flows. Poorly ventilated
regions ideally have little capillary blood flow. Three
regions or 3 zones in standing position and 2 zones
in laying and animals
Extreme alterations of V/Q
• An area with no ventilation (and thus a V/Q of zero) is termed "shunt."
• An area with no perfusion (and thus a V/Q undefined though approaching infinity) is termed dead
space.The V/Q ratio in normal person, equals approximately to 1 and V/Q’s above 1 are termed
hyperventilation disorders. Those below 1 are termed hypoventilation disorders.
• A lower V/Q ratio (with respect to the expected value for a particular lung area in a defined position)
impairs pulmonary gas exchange and is a cause of low arterial partial pressure of oxygen (paO2). Excretion
of carbon dioxide is also impaired but a rise in arterial partial pressure of carbon dioxide (paCO2) is very
uncommon because this leads to respiratory stimulation and the resultant increase in alveolar ventilation
returns paCO2 to within the normal range. These abnormal phenomena are usually seen in chronic
bronchitis, asthma and acute pulmonary edema.
• A high V/Q ratio increases paO2 and decreases paCO2. This finding is typically associated with pulmonary
embolism (where blood circulation is impaired by an embolus). Ventilation is wasted, as it fails to
oxygenate any blood. A high V/Q can also be observed in COPD as a maladaptive ventilatory overwork of
the undamaged lung parenchyma.
Gases diffusion
Importance's of a thin
blood gas barier
• Diffusion of any gas is judged by the Fick’s law of diffusion
, in which transfer of any gas ( v• )through a sheet of tissue
is proportional to tissue surface area (A) and the
difference in gas partial pressure (P1- P2) between the
two sides of the tissue , and inversely to thickness of the
tissue(T )
Lung is big A( 50-100 m2 ) and Low T( microne)
D :- diffusion coaffeciant of any gas it depends on :a. property of tissue
b. molecular of gas
c. solubility of gas
Gas Exchange in the Lungs and
tissues is derived by the partial
pressures gradient
There must be a pressure gradient
for gases to be exchange between air
in the alveoli and blood in the
capillary in lung and between blood in
capillary and tissues. This results from
the different partial pressure for
gases in aire, blood, and tissue. Partial
pressure of any gas is the pressure of
that gas if it alone occupied
the volume of the mixture at the
same temperature
Oxygen Transport
Dissolved oxygen
This obeys Henry’s law , that is , the amount dissolved isoproportional to the partial pressure of the
gas . For each mmHg there is 0. 003 ml O2 per 100 ml of blood so for adult man at PO2 100 mmHg
contains 0.3 ml of oxygen per 100 mi blood , which is inadequate , and must be another method for
the sopply of oxygen.
Reaction of Hemoglobin & Oxygen
The dynamics of the reaction of hemoglobin with O2 make it a particularly suitable O2 carrier.
Hemoglobin is a protein made up of four subunits, each of which contains a heme moiety attached
to a polypeptide chain. In normal adults, most of the hemoglobin molecules contain two and two
chains. Heme is a porphyrin ring complex that includes one atom of ferrous iron. Each of the four
iron atoms in hemoglobin can reversibly bind one O2 molecule. The iron stays in the ferrous state,
so that the reaction is oxygenation, not oxidation. It has been customary to write the reaction of
hemoglobin with O2 as Hb + O2 ¨Æ HbO2
The reaction is rapid, requiring less than 0.01 s. The deoxygenation (reduction) of Hb4O8 is also very
rapid. The quaternary structure of hemoglobin determines its affinity for O2. In deoxyhemoglobin,
the globin units are tightly bound in a tense (T) configuration, which reduces the affinity of the
molecule for O2. When O2 is first bound, the bonds holding the globin units are released, producing
a relaxed (R) configuration, which exposes more O2 binding sites. The net result is a 500-fold
increase in O2 affinity. In tissue, these reactions are reversed, releasing O2. The transition from one
state to another has been calculated to occur about 108 times in the life of a red blood cell.
The Oxygen-Hemoglobin Curve
association and dissociation
• This curve explain the
relationship between
the percentage of
hemoglobin saturation
with O2 and the partial
pressure of O2 in the
lung capillary
Factors Affecting the Affinity of Hemoglobin for Oxygen
Three important conditions affect the oxygen–
hemoglobin dissociation curve:
 pH,
 temperature
 concentration of 2,3-biphosphoglycerate
(BPG; 2,3-BPG). A rise in temperature or a
fall in pH shifts the curve to the right.
When the curve is shifted in this direction,
a higher PO2 is required for hemoglobin to
bind a given amount of O2. Conversely, a
fall in temperature or a rise in pH shifts
the curve to the left, and a lower PO2 is
required to bind a given amount of O2. A
convenient index for comparison of such
shifts is the P50, the PO2 at which
hemoglobin is half saturated with O2. The
higher the P50, the lower the affinity of
hemoglobin for O2.
Carbon Dioxide transporting:The solubility of CO2 in blood is about 20 times that of O2; therefore, considerably
more CO2 than O2 is present in simple solution at equal partial pressures. The CO2 that
diffuses into red blood cells is rapidly hydrated to H2CO3 because of the presence of
carbonic anhydrase. The H2CO3 dissociates to H+ and HCO3–, and the H+ is buffered,
primarily by hemoglobin, while the HCO3– enters the plasma. Some of the CO2 in the red
cells reacts with the amino groups of hemoglobin and other proteins (R), forming
carbamino compounds:
Because deoxyhemoglobin binds more H+ than oxyhemoglobin does and forms
carbamino compounds more readily, binding of O2 to hemoglobin reduces its affinity for
CO2(Haldane effect). Consequently, venous blood carries more CO2 than arterial blood,
CO2 uptake is facilitated in the tissues, and CO2 release is facilitated in the lungs. About
11% of the CO2 added to the blood in the systemic capillaries is carried to the lungs as
 Fate of CO2 in the blood
 In plasma
1. Dissolved
2. Formation of carbamino compounds with plasma protein
3. Hydration, H buffered, HCO3 in plasma
 In red blood cells
1. Dissolved
2. Formation of carbamino-Hb
3. Hydration, H buffered, 70% of HCO3 enters the plasma
4. Cl shifts into cells
Chloride shift
Because the rise in the HCO3– content of red cells is much greater than
that in plasma as the blood passes through the capillaries, about 70% of
the HCO3– formed in the red cells enters the plasma. The excess HCO3–
leaves the red cells in exchange for Cl– (Figure 36–6). This process is
mediated by anion exchanger 1 (AE1; formerly called Band 3), a major
membrane protein in the red blood cell. Because of this chloride shift, the
Cl– content of the red cells in venous blood is significantly greater than that
in arterial blood. The chloride shift occurs rapidly and is essentially
complete within 1 s.
Diffusion &Perfusion limitation for
gases:. Whether or not substances passing from the alveoli to the
capillary blood reach equilibrium in the 0.75 s that blood
takes to traverse the pulmonary capillaries at rest depends
on their reaction with substances in the blood. Thus, for
example, the anesthetic gas nitrous oxide (N2O) does not
react and reaches equilibrium in about 0.1 s. In this
situation, the amount of N2O taken up is not limited by
diffusion but by the amount of blood flowing through the
pulmonary capillaries; that is, it is flow-limited. On the
other hand, carbon monoxide (CO) is taken up by
hemoglobin in the red blood cells at such a high rate that
the partial pressure of CO in the capillaries stays very low
and equilibrium is not reached in the 0.75 s the blood is in
the pulmonary capillaries. Therefore, the transfer of CO is
not limited by perfusion at rest and instead is diffusionlimited. O2 is intermediate between N2O and CO; it is taken
up by hemoglobin, but much less avidly than CO, and it
reaches equilibrium with capillary blood in about 0.3 s.
Thus, its uptake is perfusion-limited. The diffusing capacity
for CO (DLCO) is measured as an index of diffusing capacity
because its uptake is diffusion-limited. DLCO is
proportionate to the amount of CO entering the blood
(VCO) divided by the partial pressure of CO in the alveoli
minus the partial pressure of CO in the blood entering the
pulmonary capillaries. Except in habitual cigarette smokers,
this latter term is close to zero, so it can be ignored and the
equation becomes:
Innervations of air ways
As with most organ systems, the CNS and PNS work in cohort to maintain homeostasis . There are four
distinct components of the autonomic nervous system:
parasympathetic originates from the medulla in the brainstem (cranial nerve X, the vagus) innervating
smooth muscle cells, blood vessels, and bronchial epithelial cells (including goblet cells and submucosal
glands), Two types of fibers:
1- excitatory motor neurons (cholinergic) Acetylcholine and substance P are neurotransmitters of
2- inhibitory (nonadrenergic) motor neurons. dynorphin andvasoactive intestinal peptide are
neurotransmitters of inhibitory motor neurons
Parasympathetic stimulation through the vagus nerve is responsible for:
- the slightly constricted smooth muscle tone in the normal resting lung.
- increase the synthesis of mucus glycoprotein, which raises the viscosity of mucus.
- blood vessel dilation
Parasympathetic innervation is greater in the larger airways, and it diminishes toward the smaller conducting airways in the
Sympathetic innervation of the bronchi
originate from about T1 to T5,
Stimulation of the sympathetic system causes:airway relaxation,
blood vessel constriction,
inhibition of glandular secretion (causing a watary secretion )
nonadrenergic noncholinergic inhibitory (relaxation) innervation of the bronchioles that produces
bronchodilation mediated by dynorphin and vasoactive intestinal peptide are neurotransmitters of
inhibitory motor neurons.
nonadrenergic noncholinergic stimulatory(constriction). Acetylcholine and substance P are
neurotransmitters of excitatory motor
There is no voluntary motor innervation in the lung, nor are there pain fibers. Pain fibers are found only
in the pleura.
Neural control of Respiration
The chief function of the lung is
to exchange O2 and CO2
between blood and gas , thus
maintain normal PO2 and
PCO2 in arterial blood . This
control is under the three
basic elements :
1. Sensors (Receptors )
2. Central controller :Voluntary(in
the cerebral cortex ) and
Involutary(in the pons and
medullary oblongata)
3.Effectors (Respiratory muscle)
Central Controller:
Medullary center
Pacemaker for ventilation (Rythmicity center Controls automatic breathing ,
consist of interacting of tow groups of cells
a-dorsal group :mainly inspiratory ( I ) neurons,control the descending spinal cord
pathways to stimulate motor neurons that innervate muscles of inspiration to bring
about inspiration
b- ventral group : both inspiratory (I)and expiratory (E) neurons, which inhibit I neurons
and control the descending spinal cord pathways to the motor neurons that innervating
muscles of expiration to bring about expiration
Apneustic center located in the pons stimulate I neurons ,to promote inspiration
Apneuses: inspiratory arrest :prolonged inspiratory gasps interrupted by transient
expiratory efforts.
Pneumotaxic center located in the pons inhibit I neurons by inhibition of apneustic center
aid in establishing the normal respiratory rhythm
Reticular activating system (RAS)
located in the reticular system of the brain stem activity associated the awake or conscious
Other neural structures
1- Hypothalamus :change in respiration associated with temperature regulation
2-Limbic system :respiratory changes in motion
3-Cerebral cortex :voluntary control
Periphral Chemoreceptors
Located in the carotid bodies at the bifurcation of the common carotid arteries and in
the aortic bodies above and bellow aortic arch . They contains islands of these glomus
cells surrounded by supportive cells and innervated with unmyelinated endings of gloss
pharyngeal nerve fibers that carry signals to the respiratory centers in the medulla .They
are sensitive to : -arise in the CO2 pressure , -a decrease in O2 pressur, - an increase in H+
They account for approximately 20% of ventilatory response
Central Chemreceptors
Located in the ventral surface of the medulla
They moniter the H+ concentration in the cerebrospinal fluid (CSF) and the brain interstitium
. They are the major chemical control of respiration under normal conditions . They
account for 70-80 % of the ventilatory response toincrease in PaCO2 .
CO2 readily penetrates the blood –brain –barrier and the blood –CSF barrier ,and hydrated
into H+ and HCO3¯
B-Nonchemical Receptors
In the airways & lungs receptors
 Stretch receptors :They are vagal myelinated nerv endings located among airway smooth muscle
,they stimulated by inflation of the lung . The response are : - Inspiratory time shortening - HeringBreuer inflation and deflation reflexes -Bronchodilatio -Tachycardia
 Irritant receptors : they are vagal myelinated nerv endings under and between the epithelial cells of
airways and lungs .They respond to inhaled irritating substances ,like histamine, prostaglandins. The
responses are :-Hyperpnea
-Mucus secretions
J receptors(juxtacapillary):located at the alveolar wall close to pulmonary capillaries .They respond to
: -increase of interstitial fluid volume
-engorgement of capillaries
-exogenous and endogenous sub.(eg.bradykinin,serotonin) The responses are :-Apnea,
followed by rapid breathing
-Mucus secretion
 Out the airways & lungs receptors
 Respiratory muscle spindle receptors ; joint receptors; proprioceptors and tendons stimulate the
inspiratory neurons ,contribute to respiratory drive during exercise
 Baroreceptors (in carotid sinuses; aortic arch; atria;and ventricles)inhibit respiration
 Higher centers afferent from limbic system and hypothalamus during pain and emotional stimuli.
 Visceral reflexes: during vomiting ;swallowing and sneezing by inhibition of respiration and closure
of the glottis during these activities.