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Respiratory Physiology
Respiration is the process of gas exchange and occurs on two levels:
Internal Respiration
The use of oxygen by the mitochondria to produce ATP by oxidative phosphorylation with
production of carbon dioxide as a waste product.
External Respiration
Exchange of oxygen and carbon dioxide between the atmosphere and body tissues.
External Respiration Involves:
1. Pulmonary ventilation - movement of air in and out of the lungs.
2. Exchange of gases by diffusion between air and blood.
3. Transportation of gases by blood.
4.Exchange of gases by diffusion between blood and tissues.
Forces for Pulmonary Ventilation
Ventilation results from bulk flow of air as the
result of pressure gradients created
between alveoli and atmospheric
pressure.
Pulmonary Pressures
There are four primary pressures associated
with ventilation:
Atmospheric Pressure (Patm)
The pressure of the outside air at sea level
is 760 mm Hg.The remaining lung
pressures are expressed relative to this
pressure.
Intra-Alveolar Pressure (Palv)
) it is less than atmospheric pressure.
During inspiration (
) it is greater than atmospheric pressure.
During expiration (
At
rest
it
is
equal
to
atmospheric
pressure, which is considered to be at 0 mm Hg.
At rest it is - 4 mm Hg.
It varies during ventilation but it is always less than intra-alveolar pressure and is always
negative (that is, less than atmospheric pressure) during normal breathing.
This negative pressure results from elastic forces exerted on the intrapleural space by the
chest wall and the lungs.
I. The chest wall is compressed and the elastic forces are pulling it outward.
II. The lung walls are stretched and the elastic forces are pulling them inward.
III. Hence, the elastic forces are trying to open the intrapleural space. The tension resisting
these elastic forces is surface tension of pleural fluid.
To
maintain this negative intrapleural pressure the pleurae need to be sealed. If it is
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Mechanics of Breathing
When lungs are at rest, the volume of air in lungs is called the functional residual capacity
(FRC). No air is moving into or out of the lungs during this time.
Air flow results from the muscles of respiration creating pressure gradients by changing the
volume of the lungs.
The relationship between pressure and volume is
expressed by Boyle's law (P1V1 = P2V2). When volume
increases, pressure decreases and when volume
decreases, pressure increases.
Inspiration(
)
The
expansion
of
the thoracic cavity during respiration
Expiration (
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Lung Volume
1. Tidal volume (VT) (500ml)
Volume inspired or expired with each normal breath(unforced breath).
2. Inspiratory reserve volume (IRV) (3000ml)
Lung Capacity
1. Inspiratory Capacity (IC) (3500ml)
Maximum volume of air that can be inspired at the end of a resting expiration.
It is sum of tidal volume and inspiratory reserve volume.
2. Vital Capacity(VC) of Forced Vital Capacity (FVC) (4500ml)
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At rest, lung volume is at FRC and the pressure in the airways and lungs is
equal to atmospheric pressure. Under these equilibrium conditions, there is
a collapsing force on the lungs and an expanding force on the chest wall.
As a result of these two opposing forces, intra-pleural pressure is negative
Therefore, at the original FRC, the tendency of the lungs to collapse is less
than the tendency of the chest wall to expand.
Airflow
Is driven by the pressure difference between the mouth (or nose) and
the alveoli.
Airway Resistance
Is described by Poiseuilles law
If airway radius decreases by a factor of 4, then resistance will increase
by factor of 256 (4^4), and airflow will decrease by a factor of 256.
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If the tubes are in series, the total resistance (Rtot) is the sum of the individual resistances:
If the tubes are in parallel (as they are in small airways), the total resistance is the sum of the
inverse of the individual resistances:
Passive forces are due to changes in the transpulmonary pressure during inspiration
and expiration and tractive forces (
) exerted on the airways by the surrounding
tissue.
During inspiration both forces act to decrease resistance while during expiration
increases resistance.
2. Smooth muscles in bronchioles
Carbon dioxide (CO2) affects the radius of bronchioles by causing bronchodilation when
its concentration increases and bronchoconstriction when its concentration
decreases.
3. Secretion of mucous into airways
High lung volumes are associated with greater traction and decreased airway
resistance. Patients with increased airway resistance (e.g., asthma) learn to breathe
at higher lung volumes to offset the high airway resistance associated with their disease.
Low lung volumes are associated with less traction and increased airway resistance,
even to the point of airway collapse.
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II. Restrictive Pulmonary Diseases
Reduce the capacity of lung expansion.
There is a decrease in vital capacity and total lung capacity.
A spirogram displays the volume of gas exhaled against time and provides four major test results:
1. forced vital capacity (FVC)
2. forced expiratory volume in 1 second (FEV1)
3. ratio of FEV1 to FVC (FEV1/FVC)
FEV1 is the volume of air that can be expired in the first second of a forced maximal
expiration.
FEV1 is normally 80% of forced vital capacity, which is expressed as: FEV1 / FVC = 0.8
In obstructive pulmonary disease, such as asthma, FEV1 is reduced more than FVC so that
FEV1/FVC is decreased. (FEV1/FVC < 0.8)
In restrictive pulmonary disease, such as fibrosis, both FEV1 and FVC are reduced and
FEV1/FVC is either normal or is increased. (FEV1/FVC > 0.8)
Lung diseases
1. Asthma
is an obstructive disease in which expiration is impaired.
is characterized by decreased FVC, decreased FEV1 and decreased FEV1/FVC.
Air is not completely expired, leading to air trapping and increased FRC.
increases airway resistance by causing spastic contraction of smooth muscles,
increased mucus secretion and inflammation of bronchioles.
2. COPD
) and emphysema (
).
is a combination of chronic bronchitis (
is an obstructive disease with increased lung compliance in which expiration is impaired.
is characterized by decreased FVC, decreased FEV1, and decreased FEV1/FVC.
Air is not completely expired, leading to air trapping, increased FRC,and barrel-shaped
chest.
increase airway resistance.
3. Fibrosis
is a restrictive disease with decreased lung compliance in which inspiration is impaired.
is characterized by decrease in all lung volumes. Because FEV1 is decreased less than
FVC, FEV1/FVC is increased (or may be normal).
Ventilation
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The process by which air (volume/min) moves in and out of the lung.
Composition of Air
Daltons law of partial pressures
(VCO2 / VO2 )
ratio of 80 CO2 produced (molecules) to 100 O2 consumed (molecules) in tissue. (CO2 / O2 )
the average respiratory quotient is 0.8
Partial pressure of O2 in the alveolus (PAO2) alveolar oxygen equation
PAO2
Dead space
Anatomical dead space
) alveoli.
Refer to those areas of the lung which do not participate in gas exchange.
Includes the conducting airways (anatomical dead space) and any non-perfused alveoli.
Perfusion (Blood flow)
the process by which deoxygenated blood passes through
lung and becomes reoxygenated.
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The Pulmonary Circulation
The driving force of systematic circulation is Pao - Pra = 100-2 = 98
The driving force of pulmonary circulation is Ppa - Pla = 15 - 5 = 10
Pulmonary Vascular Resistance
PVR = 10/6 = 1.67mmHg/L/min
cardiac output flow (QT) = 6L/min
is pulmonary blood flow.
is equal to cardiac output of left
ventricle.
Distribution of pulmonary blood flow
), blood flow is nearly uniform(
When a person is supine(
) through out lung.
When
a person is standing, blood flow is unevenly distributed because of gravity. Blood
flow is lowest at the apex of the lung (zone 1) and highest at the base of the lung (zone 3).
1. Zone 1blood flow is lowest.
Alveolar pressure > arterial pressure > venous pressure. PA > Pa > Pv
Zone 1 likely does not exist in a healthy individual's lungs as pulmonary arterial pressures
exceed alveolar pressure even at the top of the lung apex.
The high alveolar pressure may compress the capillaries
and reduce blood flow in zone 1 and thus creating a zone of
dead space. This situation can occur if arterial blood pressure
is decreased as a result of hemorrhage or if alveolar
pressure is increased because of positive pressure
ventilation.
2. Zone 2blood flow is medium.
arterial pressure > Alveolar pressure > venous pressure. Pa >
PA > Pv
Moving down the lung, arterial pressure progressively
increases because of gravitational effects on hydrostatic
pressure.
Arterial pressure is greater than alveolar pressure in zone 2, and
blood flow is driven by the difference between arterial pressure and alveolar pressure.
3. Zone 3blood flow is highest.
arterial pressure > venous pressure > Alveolar pressure. Pa > Pv > PA
Moving down toward base of the lung, arterial pressure is highest because of gravitational
effects, and venous pressure finally increases to the point where it exceeds alveolar pressure.
In zone 3, blood flow is driven by the difference between arterial and venous pressures, as
in most vascular beds.
Regulation of pulmonary blood flowhypoxic vasoconstriction
(decreased alveolar PO2 < 70 mmHg ) causes vasoconstriction.
In the lungs, hypoxia
This
response
is
the
opposite
in other organs, where hypoxia causes vasodilation.
Physiologically,
is
a
protective
response by shifting blood flow from hypoxic areas to well
perfused areas in an effort to enhance gas exchange.
Low inspired O2 levels can constrict pulmonary vessels and increase PVR.
High levels of inspired O2 can dilate pulmonary vessels and decrease PVR.
9/19
Ventilation-Perfusion ratio ( V / Q )
is the ratio of alveolar ventilation (V) to pulmonary blood flow (Q).
If breathing frequency, tidal volume, and cardiac output are normal,
alveolar ventilation is about 4.0 L/min, whereas pulmonary blood flow
is about 5.0 L/min. the V/Q ratio is approximately 0.8.
This V/Q ratio results in arterial PO2 of 100 mm Hg and arterial PCO2 of
40 mm Hg.
V/Q ratios in different parts of the lung
Ventilation is lower at the apex and higher at the base, but the regional
differences are not as great as for perfusion.
Blood flow is lowest at the apex and highest at the base because of gravitational effects.
Therefore, the V/Q ratio is higher at the apex of the lung and lower at the base of the lung.
As a result of the regional differences in V/Q ratio, there are corresponding differences in the
efficiency of gas exchange and in the resulting pulmonary capillary PO2 and PCO2.
At the apex(higherV/Q), PO2 is highest and PCO2 is lower because gas exchange is more
efficient.
At the base (lower V/Q), PO2 is lowest and PCO2 is higher because gas exchange is less
efficient.
Changes V/Q ratio
1. V/Q ratio in airway obstruction
If the airways is blocked, then ventilation is decreased. If blood flow is
normal, V/Q < 0.8
There is less gas exchange in lung that is perfused but not ventilated.The
blood leaving these capillaries will then have lower PO2 and higher
PCO2
Anatomical shunt
Mixed venous blood bypasses the gas exchange unit and goes
directly into arterial blood
Mix deoxygenated blood with oxygenated blood
Right-Left Shunt
Occur when oxygen-poor blood from right heart flows in the
left heart without passing through functional, ventilated
alveoli.(2% of cardiac output by passes the lungs)
Result in decrease in arterial PO2 because of the mixture of
venous blood with arterial blood.
The magnitude of a right-to-left shunt can be estimated by having
the patient breathe
100% O2 and measuring the degree of dilution of oxygenated
arterial blood by non oxygenated shunted (venous) blood.
10/19
Left-Right Shunt
are more common than right-left shunts because pressures are higher on left side of heart.
cardio abnormalities or traumatic injury.
are caused by congenital
1. Patent ductus arteriosus (PDA) : ductus arteriosus fails to close after birth.
2. Atrial septal defect (ASD) : deficiency of interartrial septum between left and right atrium
3. Atrioventricular septal defect (AVSD) : deficiency of atrioventricular septum between left
ventricle and right atrium
4. Ventricular septal defect (VSD) : deficiency of ventricular septum between left and right
ventricle
arterial
PO2 will be elevated on the right side of the heart because there has been
Gas Exchanges
Dissolved gases
The amount of gas dissolved in a solution (such as blood) is proportional to its partial pressure.
The units of concentration for a dissolved gas are mL gas/100 mL blood.
Henrys Law
11/19
Ficks Law
Rate of diffusion of a gas across a permeable membrane
V'gas = D x A x P/T
Diffusing Capacity
Because these variables are impossible to measure directly (surface area, thickness, and
cofficient), the concept of "Diffusing Capacity" has been developed as measurable factor that
combines the contribution of these variables.
DL = D x A/T
V'gas = DL x P
DL = Vgas / P (Palveolar - Pcapillary)
In order to determine
12/19
Gas Exchange in the Lungs
Partial pressures of O2 and CO2 in the atmosphere are 160 mm
Hg and 0.23 mm Hg.
In the alveoli the pressures of O2 and CO2 are 100 mm Hg and
40 mm Hg.
Deoxygenated blood entering the pulmonary capillaries has a
PO2 of 40 mm Hg and PCO2 of 46 mm Hg. The gases diffuse
down their concentration gradients and leave at the same partial
pressures as the gases in the alveoli (PO2 = 100 mm Hg and
PCO2 = 40 mm Hg).
Oxygen Transport
Hemoglobin
Each subunit contains a heme moiety, which is iron-containing
porphyrin.
The iron is in the ferrous state (Fe2+), which binds O2.
Each subunit has a poly peptide chain. Two of the subunits
have chains and two of the subunits have chains; thus,
normal adult hemoglobin is called 22.
Methemoglobin
Iron is in the Fe3+ state.
Does not bind O2.
Hemoglobin S
causes sickle cell disease.
Two chains are mutated.
In the deoxygenated form, deoxyhemoglobin forms sickle-shaped chain that deform
red blood cells.
O2-binding capacity of blood O2 saturation (SO2)
is the maximum amount of O2 that can be bound to hemoglobin in blood.
is dependent on the hemoglobin concentration in blood.
limits the amount of O2 that can be carried in blood.
is measured at 100% saturation.
O2 content of blood
is the total amount of O2 carried in blood, including bound and dissolved O2.
depends on the hemoglobin concentration, the PO2, and the P50 of hemoglobin.
13/19
At a PO2 of 25mmHg
hemoglobin is 50% saturated.
At 100% saturation 1 gram of hemoglobin carries 1.34 ml of oxygen.
Hemoglobin in blood 12-17gm/dL or an average of 150 gm/L
Oxygen carrying capacity
1.34 ml/gram x 154 grams/liter ~ 200 ml/L
The s-shape of the curve is the result of a change in the affinity of hemoglobin as
each successive O2 molecule binds to a heme site (called positive cooperativity).
Binding of first O2 molecule increases the affinity for the second O2
molecule,and so forth.
The affinity for the fourth O2 molecule is the highest.
This change in affinity facilitates the loading of O2 in the lungs (flat
portion of the curve) and the unloading of O2 at the tissues (steep
portion of the curve).
In the lungs
Alveolar gas has a PO2 of 100mmHg.
Pulmonary capillary blood is oxygenated by the diffusion of O2 from
alveolar gas into blood, so that the PO2 of pulmonary capillary
blood also becomes 100 mm Hg.
The very high affinity of hemoglobin for O2 at a PO2 of 100mm Hg
facilitates the diffusion process. By tightly binding O2, the free O2
concentration and O2 partial pressure are kept low, thus
maintaining partial pressure gradient (that drives the diffusion
of O2).
The curve is almost flat when the PO2 is between 60 and
100mmHg.
In the peripheral tissues
O2 diffuses from arterial blood to the cells.
The gradient for O2 diffusion is maintained because the cells
consume O2 for aerobic metabolism, keeping the tissue PO2 low.
The lower affinity of hemoglobin for O2 in this steep portion of the
curve facilitates the unloading of O2 to the tissues.
The hemoglobin oxygen disassociation curve can shift either to the left or to the right.
When the curve shifts to the right, the affinity of oxygen for hemoglobin decreases and
oxygen can be more easily unloaded.
When the curve shifts to the left, the affinity of oxygen for
hemoglobin increases and oxygen can be more easily loaded.
Factors Affecting Affinity of Hemoglobin for O2
1. Temperature
A higher temperature cause a decrease in affinity of hemoglobin. In
more active tissue with a higher temperature O2 unloads more
easily.
14/19
2. pH (Bohr effect)
[H+] increases (pH decreases) in more active tissue. This decreases
the affinity of hemoglobin : Hb + O2 Hb-O2 + H+
3. PCO2 (carbamino effect)
CO2 binds reversibly with Hb to form carbaminohemoglobin, which has
a lesser affinity for O2 . The increase of CO2 cause decrease in the
affinity of hemoglobin
4. 2,3 - Diphosphoglycerate
2,3 -DPG is produced from glycolysis and decrease affinity of
hemoglobin.
At low [O2], enzyme catalyzes synthesis of 2,3-DPG, decrease in affinity of hemoglobin.
This is helpful during anemia and at high altitudes (chronic hypoxemia) by enhancing
unloading of oxygen by hemoglobin thus results in enhanced oxygen transport to tissues
At high [O2], oxyhemoglobin inhibits enzyme that synthesizes 2,3-DPG and 2,3-DPG levels
decrease.
5. Carbonmonoxide (CO) poisoning
CO competes for O2-binding sites on hemoglobin. The affinity of hemoglobin for CO is 200
times its affinity for O2.
In addition, binding of CO to hemoglobin increases the affinity of remaining sites for O2, causing
a shift of the curve to the left.
Hypoxemia
is decrease in arterial PO2.
The normal Aa gradient is (< 10mmHg). Since O2 normally
equilibrates between alveolar gas and arterial blood, PAO2 is
approximately equal to PaO2.
The Aa gradient is increased (>10mmHg) if O2 does not
equilibrate between alveolar gas and arterial blood (e.g., diffusion
defect, V/Q defect, and right-to-left shunt).
Hypoxia
15/19
Erythropoiesis
Red blood cell production (erythropoiesis) in the bone marrow is controlled by the hormone
erythropoietin, which is synthesized in the kidney by cortical interstitial cells.
Decreased O2 delivery, low Hgb concentration, and low PaO2 stimulate secretion of
erythropoietin. This increases the production of red blood cells.
Chronic renal disease damages the cortical interstitial cells and thereby suppresses their
ability to synthesize erythropoietin. This causes anemia, along with decreased Hgb because
of the lack of erythropoietin. Erythropoietin replacement therapy effectively increases red blood
cell production.
Carbon Dioxide Transport
The carbon dioxide in the blood exists as
Dissolved as CO2: 5-6%
Carbaminohemoglobin : 5-8%
Dissolved as HCO3 - : 86-90%
Role of Carbonic Anhydrase in Carbon Dioxide Transport
Carbonic anhydrase catalyzes the reaction that converts CO2 and H2O to carbonic acid.
Carbonic acid (H2CO3) reversibly disassociates to H+ + bicarbonate.
CO2 + H2O H2CO3 H+ (H+ is buffered by hemoglobin HbH) + HCO3Increase in PCO2 makes the blood more acidic while a decrease in PCO2 does the opposite.
CO2 Exchange and Transport in Systemic Capillaries and Veins
In the tissue
Cell produce CO2 at the rate of 200 ml/minute. As CO2 increases in the
tissues it goes down its concentration gradient from the plasma and into
the erythrocyte.
The pressure gradient favors the diffusion of CO2 from the blood into the
alveoli.
The decrease in CO2 causes the reaction tend to converted into CO2 and
H2O by carbonic anhydrase.
16/19
Effect of Oxygen on Carbon Dioxide Transport(Haldane Effect)
The PO2 affects the ability of the blood to carry CO2.
Output from the dorsal respiratory group travels, via the phrenic
nerve, to the diaphragm and external intercostal muscles
17/19
2. Ventral Respiratory Group
contains two regions of expiratory neurons (nucleus
retrofacialis and the nucleus retroambiguus) and one region
of inspiratory neurons (nucleus paraambiguus)
1. Apneustic center
is located in the lower pons.
Stimulate inspiration by sending stimulatory impulses to
Dorsal Respiratory Group (delay 'switch off' signal from
pneumotaxic center ) activates and prolongs inspiration
(long deep breaths).
2. Pneumotaxic center (a.k.a pontine respiratory group)
18/19
Chemoreceptor Reflexes
Changes in PCO2 are primary stimuli for changes in ventilation
under normal conditions. Both central and peripheral chemoreceptors
are sensitive to changes in pH .
Activation of chemoreceptors cause an increase in ventilation.
2. Pulmonary stretch receptors
Type of mechanoreceptor present in the bronchial smooth
muscle which sense and respond to physical stretching of
airways.
When these receptors are stimulated by distention of lungs,
produce a reflex decrease the respiratory rate by increasing
the length of expiration(HeringBreuer reflex).
3. Irritant receptors
Sensory cells present within respiratory epithelium which can sense and respond to a
variety of chemical irritants.
Initiate coughing and might induce bronchoconstriction in those with asthma.
4. J (juxtacapillary) receptors
to pulmonary
Sensory cells located within in the alveolar walls and are juxtaposed
capillaries
Activated by engorgement of pulmonary capillaries (blood backs into pulmonary
circulation due to left heart failure) or increased pulmonary interstitial volume (pulmonary
edema), then cause rapid, shallow breathing.
5. Joint and muscle receptors
are activated during movement of the limbs.
are involved in the early stimulation of breathing during exercise.
Arterial pH affects the pH of body tissues hence it is necessary to regulate blood pH around
the normal of 7.4.
If the pH < 7.35 it is said to be in a condition of acidosis. causes depression of CNS activity and
leads to coma.
If the pH > 7.45 it is said to be in a condition of alkalosis.causes the nervous system to become
overly excitable and causes uncontrollable muscle seizures and convulsions.
19/19
Role of Respiratory System in Acid-Base Balance
Hemoglobin as a Buffer
Hemoglobin can bind or release H+. Deoxyhemoglobin has a greater affinity for H+ than
oxyhemoglobin as described by the Bohr effect.
In the tissues:
HbO2 O2 + Hb
Hb + H+ Hb-H
This serves as a buffer for the increase in H+ resulting from CO2.
In the lungs:
HbH H+ + Hb
Hb + O2 HbO2
Bicarbonate Ions as a Buffer
When H+ increases in the blood it combines with HCO3- to form CO2.
When CO2 increases this reaction goes in reverse to form HCO3- and H+.
The relationship between CO2 and acidity is described by the Henderson-Hasselbach equation:
The mean values for arterial PO2 and PCO2 do not change during exercise.
Arterial pH does not change during moderate exercise, although it may decrease during
strenuous exercise (lactic acidosis)
Venous PCO2 increases during exercise because the excess CO2 produced by the
exercising muscle is carried to the lungs in venous blood.
Pulmonary blood flow increases because cardiac output increases during exercise. As
a result, more pulmonary capillaries are perfused, and more gas exchange occurs,
resulting decrease the physiologic dead space.
The distribution of V/Q ratios throughout the lung is more during exercise.
B. Adaptation to high altitude
Alveolar PO2 is decreased at high altitude. As a result, arterial PO2 is also decreased
(hypoxemia).