Transcript Respiratory System

Topics to Review
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pH
Buffers
Diffusion
Law of mass action (chemistry)
Functions of the Respiratory System
• Provides a way to exchange O2 and CO2 between the
atmosphere and the blood
– oxygen is used by the cells of the body solely for
the process of aerobic respiration
– carbon dioxide is a waste product of aerobic
respiration and must be removed from the body
• Regulation of body pH
• Protection from inhaled pathogens and irritating
substances
• Vocalization
The Respiratory System
• Together, the respiratory system and the circulatory
system deliver O2 to cells and remove CO2 from the
body through 3 processes
– Pulmonary ventilation (breathing)
• movement of air into and out of the lungs
• Inspiration/inhalation and expiration/expiration
– Gas Exchange
• O2 and CO2 are exchanged between the air in
the lungs and the blood
• O2 and CO2 are exchanged between the blood
and the cells
– Transport
• movement of O2 and CO2 between the lungs and
cells
Organization of the Respiratory System
• Anatomically, the respiratory system includes the:
– upper respiratory tract (mouth, nasal cavity, pharynx
and larynx)
– lower respiratory tract (the trachea, 2 primary
bronchi, the branches of the primary bronchi and
the lungs)
• Functionally, the respiratory system includes the:
– the conducting zone (semi-rigid airways) lead from
the external environment of the body to the
exchange surface of the lungs
– the exchange surface (respiratory zone) consists of
the alveoli which are a series of interconnected
sacs (surrounded by pulmonary capillaries) which
expand and collapse during ventilation and allows
oxygen and carbon dioxide to be exchanged
between the air in the lungs and the blood
The Thorax and Respiratory Muscles
• The bones of the spine and ribs and their associated
skeletal muscles form the thoracic cage
• Contraction and relaxation of these muscles alter the
dimensions of the thoracic cage which promotes
ventilation
– 2 sets of intercostal muscles connect the 12 pairs of
ribs
– additional muscles (sternocleidomastoid and
scalenes) connect the head and neck to the
sternum and the first 2 ribs
– a dome-shaped sheet of skeletal muscle called the
diaphragm forms the floor
– the abdominal muscles also participate in
ventilation
The Pleural Membranes and Fluid
• Within the thorax are 2 double layered pleural sacs
surrounding each of the 2 lungs
• Parietal pleura
– lines the interior of the thoracic wall and the
superior face of the diaphragm
• Visceral pleura
– covers the external surface of the lungs (alveoli)
• A narrow intrapleural space between the pleura is
filled with 25 mL of pleural fluid which holds the 2
layers together by the cohesive property of water
– serves to lubricate the area between the thorax and
the outer lung surface
– holds the lungs tight against the thoracic wall
• prevents lungs from completely emptying even
after a forceful expiration
Proximal Respiratory Tract
• Air enters the upper respiratory tract through either the
mouth or nose and passes through the pharynx
– warms and humidifies (adds H2O) inspired air
– hair in the nose filters inspired air of any dust
• Air then passes through the larynx or “voice box”
– contains the vocal cords (bands of connective
tissue) which tighten and vibrate to produce sound
• Air continues into the lower respiratory tract through
the trachea which is a semi-flexible tube held open by
C-shaped rings of cartilage
• The distal end of the trachea splits into 2 primary
bronchi which lead to the 2 lungs branch repeatedly
into progressively smaller bronchi
– the walls of the bronchi are supported by cartilage
Trachea (Cross Section)
• The inner (mucosal) surface of the trachea and
bronchi consists of epithelial tissue that functions as
the mucocilliary escalator to trap and eliminate debris
• Goblet cells
–secrete mucus to trap debris in inspired air
• Pseudostratified ciliated columnar epithelium
–move debris trapped in mucus up towards the
mouth for expectoration/swallowing
Middle and Distal Respiratory Tract
• Bronchi send air into the bronchioles
– these airways are supported by smooth muscle only
• contraction causes bronchoconstriction which
decreases the airway diameter and makes
ventilation more difficult
–increases airway resistance to decrease flow
• relaxation causes bronchodilation increases the
airway diameter which makes ventilation easier
–decreases airway resistance to increase flow
• branch into respiratory bronchioles which begins the
• Bronchioles move air into the blind sacs called alveoli
where gas exchange occurs (respiratory zone)
– approximately 150 – 300 million per lung
Anatomy of Alveoli
• Composed of very thin (simple) epithelial tissue
consisting of 2 predominant alveolar cell types
– Type I (squamous) alveolar cells
• allows for very rapid exchange of O2 and CO2
– Type II or great (cuboidal) alveolar cells
• secrete surfactant into the alveolar lumen
• Exterior surface is surrounded by large numbers of
blood capillaries for gas exchange and large numbers
of elastic fibers to aid in lung recoil during exhalation
• White blood cells (macrophages) within the lumen of
the alveoli protect against inhaled pathogens
• Alveoli represents an enormous surface area for gas
exchange (2800 square feet or half of a football field)
Properties of Alveoli
• Compliant
– ability to be easily stretched or deformed
– allows lungs to fill up with air during inspiration
– attributed by the very thin Type I alveolar cells
• Elastic
– ability to resist being stretched or deformed
– allows lungs recoil (deflate) during expiration
– attributed by:
• interior (luminal) surface covered with a thin film
of water which creates surface tension at the airfluid interface (surface) of the alveoli
• the elastic fibers surrounding the alveoli
Alveolar Surface Tension and Elasticity
• During inhalation the alveoli expand and adjacent
water molecules on the luminal surface are pulled
apart from one another causing the H-bonds between
them to be stretched (like a spring) creating tension
• During exhalation the tension within the H-bonds is
released which returns the water molecules to their
original spacing pulling the alveoli inward allowing
them to recoil
Surfactant
• Type II alveolar cells secrete surfactant (“surface
active agent”) which is a fluid consisting of amphiphilic
molecules into the lumen of the alveoli
• These molecules disrupt the cohesive forces between
water molecules by inserting themselves between
some of the water molecules preventing H-bonds from
forming and thus decreases the surface tension of the
water on the luminal surface
• Reducing surface tension simultaneously increases
compliance and reduces elasticity of the alveoli
which greatly decreases the amount of effort needed
to inflate the lungs while retaining the ability to deflate
the lungs
• Without surfactant, the muscles of respiration cannot
contract with enough force to overcome the alveolar
surface tension resulting in the inability to breathe
Pulmonary Ventilation
• The movement of air into and out of the airways
occurs as a result of increasing and decreasing the
dimensions of the thoracic cavity through the
contraction and relaxation of the skeletal muscles of
respiration
• Since the alveoli are “stuck” to the interior surface of
the thorax via the pleura, dimensional changes in the
thoracic cavity result in the same dimensional changes
in the alveoli
• Dimensional changes in the alveoli create air pressure
changes in the alveoli as expressed by Boyle’s Law
Boyle’s Law
• The mathematical inverse relationship that describes
what happens to the pressure of a gas or fluid in a
container following a change in the volume
(dimensions) of the container
– If the volume of a container increases, then
pressure within the container must decrease
– If volume of a container decreases, then pressure
within the container must increase
V1 x P1 = V2 x P2
V = volume of a container
P = pressure within the container
• force of collisions between molecules within the
container and the wall of the container
• determined by the “concentration” of
molecules within the container
Pulmonary Ventilation
• Changes in the pressure in alveolar air (alv) create air
pressure gradients between the air in the alveoli and
the atmospheric air that surrounds our bodies (atm)
which drive air flow into and out of the lungs
• Air always flows from an area of higher pressure to an
area of lower pressure
– When alv < atm inspiration occurs
• air flows into the lungs
– When alv > atm expiration occurs
• air flows out of the lungs
– When alv = atm no air flow occurs
• at transition between inspiration and expiration
Inspiration
• Before inspiration (at end of previous expiration), the
alv (0 mm Hg) = atm (0 mm Hg) (no air movement)
• Expansion of the thoracic cavity (by the contraction of
the diaphragm, the external intercostals, the scalenes
and the sternocleidomastoid) pulls the alveoli open
which increases their volume and decreases their
pressure (-1 mm Hg)
– the alveolar pressure decreases below
atmospheric pressure, creating a pressure gradient
resulting in inspiration
• As the alveoli fill with air (more molecules), the alv
pressure increases until it equals atm pressure
• Inspiration ends when alv (0 mm Hg) = atm (0 mm Hg)
Expiration
• Expiration is a passive process that does not require
muscle contraction to occur
• Before expiration, (at end of previous inspiration), the
alv (0 mm Hg) = atm (0 mm Hg) (no air movement)
• Expiration begins as action potentials along the nerves
that innervate the muscles of inspiration cease
allowing these muscles to relax returning the
diaphragm and ribcage to their relaxed positions
– allows the alveoli to collapse which decreases their
volume and increases their pressure (1 mm Hg)
• the alveolar pressure increases above
atmospheric pressure, creating a pressure
gradient resulting in quiet (passive) expiration
• As the alveoli empty with air, the alv pressure
decreases until it equals atm pressure
• Expiration ends when alv (0 mm Hg) = atm (0 mm Hg)
Control of Ventilation
• Ventilation occurs automatically
whereby the contraction of the
skeletal muscles of respiration
are controlled by a
spontaneously firing network of
neurons in the brainstem but
can be controlled voluntarily up
to an extent
Respiratory Centers of the Medulla
• The dorsal respiratory group (DRG) is the pacesetter
for ventilation where in a person at rest initiates bursts
of action potentials every 5 seconds setting a quiet
ventilation rate of 12 breaths/minute
– action potentials travel down the phrenic nerve
stimulating the diaphragm and the intercostal
nerves stimulating the external intercostals
– periods of time between these bursts action
potentials allow for expiration as the muscles relax
Receptors of Respiration
• Various chemoreceptors (monitoring changes in H+,
CO2 or O2) initiate reflexes which alter the firing of
action potentials by the DRG promoting different
ventilation patterns
• An increase in either CO2 (hypercapnia) or H+ will
stimulate the DRG and result in an increase in
respiration rate and depth (hyperventilation)
• A decrease in either CO2 or H+ will inhibit the DRG
and result in a decrease in respiration rate and
depth (hypoventilation)
• Only a substantial decrease in systemic arterial O2
(<60 mm Hg) will stimulate the DRG and result in
hyperventilation
– an increase in O2 will inhibit the DRG and result in
hypoventilation
Respiratory Centers of the Medulla
• The ventral respiratory group (VRG), or expiratory
center is a group of neurons that fire action potentials
only during forced expiration
– forced expiration requires an additional decrease in
thoracic and lung volume over what passive
expiration can provide
– stimulates the contraction of the internal intercostals
(pull ribs inward) and the abdominals (decrease
abdominal volume and displace the liver and
intestines upward)
• further decreases the thoracic cavity volume
allowing the lungs to collapse to a greater extent
increases the amount of air that exits the lungs
Respiratory Centers of the Pons
• Pneumotaxic center
– sends action potentials every 5 seconds to the DRG
which inhibits the DRG from firing action potentials
to the diaphragm and external intercostals
• ending inspiration
• providing a smooth transition between inspiration
and expiration
• The amount (volume) of air that enters or exits the
lungs during either quiet or forced breathing can be
plotted on a graph called a spirogram
Lung Volumes
• Tidal volume (TV)
– volume of air that moves into and out of the lungs
with each breath during quiet ventilation (500 ml)
• Inspiratory reserve volume (IRV)
– additional volume of air that can be inspired forcibly
into the lungs after a tidal inspiration
• Expiratory reserve volume (ERV)
– additional volume of air that can be expired forcibly
from the lungs after a tidal expiration
• Residual volume (RV)
– volume of air left in the lungs after forced expiration
– this air can NEVER be expired
Lung Capacities
• The addition of 2 or more specific lung volumes is
referred to as a capacity
• Inspiratory capacity (IC)
– total amount of air that can be inspired after a tidal
expiration (IRV + TV)
• Functional residual capacity (FRC)
– amount of air remaining in the lungs after a tidal
expiration (RV + ERV)
• Vital capacity (VC)
– the total amount air capable of entering/exiting the
airways (TV + IRV + ERV) (4600 ml)
• Total lung capacity (TLC)
– sum of all lung volumes (5800 ml)
Gas Exchange and Dalton’s Law
• The exchange of O2and CO2 between alveolar air and
capillary blood and between capillary blood and body
cells occur simultaneously by diffusion where each
gas moves down its respective concentration gradient
• The concentration of a gas can be expressed in terms
of pressure (or as a partial pressure), typically in units
of mmHg (millimeters of mercury)
• Air found within the alveoli (at sea level) is a mixture
of gasses and has a total pressure of 760 mmHg
– 13.2% of the molecules in alveolar air are O2, and
therefore provides only 13.2% of 760 mmHg, or 100
mmHg, which is its partial pressure (PO2)
– 5.2% of the molecules in alveolar air are CO2, and
therefore provides only 5.2% of 760 mmHg, or 40
mmHg, which is its partial pressure (PCO2)
Simultaneous Gas Exchange
• ALVEOLI of the lungs
– Inhaled O2 diffuses out of the alveoli into the blood
• the amount of O2 in the blood increases
• the O2 is pumped by the heart to the cells of body
– CO2 diffuses out the blood into the alveoli to be
subsequently exhaled
• the amount of CO2 in the blood decreases
• CELLS of the body
– O2 diffuses out of the blood and into the cells
• the amount of O2 in the blood decreases
• the O2 is used by the cells for aerobic cellular
respiration
– The CO2 produced as a product of aerobic cellular
respiration diffuses out the cells and into the blood
• the amount of CO2 in the blood increases
• the CO2 is pumped by the heart to the lungs
Gas Exchange
Alveolar Gas Exchange
• Blood that is flowing towards the lungs is:
– low in O2 (PO2 = 40 mmHg)
– high in CO2 (PCO2 = 46 mmHg)
• O2 diffuses from the alveoli into the blood because:
– the PO2 in the alveolus is greater (100 mmHg) than
the PO2 in the blood (40 mmHg)
• CO2 diffuses from the blood into the alveoli because:
– the PCO2 in the blood is greater (46 mmHg) than the
PCO2 in the alveolus (40 mmHg)
• Each gas diffuses until they reach equilibrium with
the pressures in the alveoli which DO NOT CHANGE
since ventilation continuously adds O2 and removes
CO2
• After gas exchange at the lungs has been completed,
the blood leaving the lungs has a PO2 of 100 mm Hg
and a PCO2 of 40 mm Hg
Systemic Gas Exchange
• Blood that is delivered to all the cells of the body is:
– high in O2 (100 mmHg)
– low in CO2 (40 mmHg)
• O2 diffuses from the blood into the interstitial fluid
– PO2 in the blood is greater (100 mmHg) than the
PO2 in the interstitial fluid (40 mmHg)
• CO2 diffuses from the interstitial fluid to the blood
– PCO2 in the interstitial fluid is greater (46 mmHg)
than the PCO2 in the blood (40 mmHg)
• Each gas diffuses until they reach equilibrium with
the pressures in the cell which DO NOT CHANGE
since cell respiration continuously uses O2 and
produces CO2
• After gas exchange at the cells has been completed,
the blood leaving the cells has a PO2 of 40 mm Hg and
a PCO2 of 46 mm Hg
Gas Transport in Blood
• The law of mass action plays an important role in how
O2 and CO2 are transported
• As O2 and CO2 are added to or removed from the
blood their respective concentration changes in blood
disturb the equilibrium of reactions, shifting the
balance between reactants and products
Oxygen Transport in Blood
• The vast majority of O2 (98%) in blood is found within
erythrocytes (red blood cells (RBCs)) bound to the
protein hemoglobin (Hb)
– in pulmonary capillaries when plasma PO2 increases
as O2 diffuses in from alveoli, O2 attaches to Hb
• Hb + O2 HbO2
– at cells where O2 is being used and plasma PO2
decreases, O2 detaches from Hb and enters the cell
• HbO2 → Hb + O2
• Overall the binding of oxygen to hemoglobin is
reversible and is expressed as Hb + O2 ↔ HbO2
– if O2 increases, then reaction shifts to the right
– if O2 decreases, then reaction shifts to the left
• Plasma (fluid portion of blood) cannot hold much O2
(2%) since it is only slightly soluble in water
Hemoglobin (Hb)
• Protein made of 4 polypeptide chains (subunits) each
containing a heme group
– each heme group contains one atom of iron (Fe)
(makes RBCs/blood red) in the center which is
capable of binding to one molecule of O2
• A single molecule of hemoglobin can load, carry and
drop off up to 4 O2 between the alveoli of the lungs
and respiring tissues of the body
• Each RBC is filled with 280 million molecules of Hb
– can carry 1.12 billion molecules of O2
• Since there are 25 trillion RBCs in circulation
– the blood can theoretically transport up to
28,000,000,000,000,000,000,000 molecules of O2
Oxygen Transport vs. Oxygen Consumption
• In a person at rest, 1000 mL of O2 per minute is
delivered to respiring tissues
– plasma can carry 15 mL of O2 per minute
– RBCs can carry 985 mL of O2 per minute
• In a person at rest, respiring tissues use only 250 mL
of O2 per minute and accordingly the blood drops off
only what the cells need, or 25% of its “payload”
– the remaining oxygen circulates back to the lungs
• The remaining 75% of the oxygen that remains in
blood is regarded as a reservoir which is available to
respiring cells when their use of oxygen increases
such as during exercise
Factors that Influence O2 and Hb Binding
• 5 parameters influence both the loading of O2 onto
and unloading of O2 off from Hb which determines the
the number of O2 molecules that are bound to a single
Hb either at the lungs or at respiring tissues
– the PO2 of the blood
• 100 mmHg at the lungs
• 40 mmHg at the respiring tissues
– the PCO2 of the blood
• 46 mmHg at the respiring tissues
• 40 mmHg at the lungs
– the temperature of the blood
– the [H+] (pH) of the blood
– the [2,3-DPG] in red blood cells
• carbohydrate intermediate of glycolysis
• changes as metabolic rate changes
Influence of PO2 on Hemoglobin Saturation
• An oxygen-hemoglobin association (or dissociation)
curve relates the amount of oxygen that is bound to
hemoglobin (expressed as % hemoglobin saturation
with O2) at a particular PO2 in the blood
– the greater the PO2 in the blood, the more O2 is
bound to Hb
• The Hb at the lungs (PO2 = 100) is 100% saturated
(bound to 4 O2)
• In a person who is at rest the Hb at the cells (PO2 =
40) is 75% saturated (bound to 3 O2)
– one molecule of O2 moves off of Hb and enters the
cells of the respiring tissues
• If the cells of the respiring tissues use more O2, the
blood PO2 at the cells will decrease below 40 mmHg
promoting more O2 to be unloaded off of Hb
Other Factors Influencing Hemoglobin Saturation
• Blood temperature, blood [H+], blood PCO2 and
concentrations of 2,3-DPG in RBCs each influence the
binding (affinity/attractiveness) of O2 to Hb
• An increase in any of these factors in the blood at
respiring cells will decrease the affinity of Hb for O2 at
respiring tissues
– increase O2 unloading at respiring tissues
– “right shift” of the O2 -Hb dissociation curve
• A decrease in any of these factors in the blood at
respiring cells will increase the affinity of Hb for O2 at
respiring tissues
– decrease O2 unloading at respiring tissues
– “left shift” of the O2 -Hb dissociation curve
Carbon Dioxide Transport
• CO2 that diffuses out of a respiring cell is transported
in the blood in 3 forms:
– as bicarbonate ion (HCO3–) in plasma (70%)
• CO2 can be converted into bicarbonate ions and
bicarbonate ions can be converted into CO2
through the reversible chemical reaction
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3which obeys the laws of mass action
– as carbaminohemoglobin
• bound to amino acids (not heme) of Hb (23%)
– as dissolved gas in plasma (7%)
• CO2 is 20 times more soluble in plasma than O2
therefore more can be carried by plasma
Conversion of CO2 to HCO3–
CO2 + H2O → H2CO3 → H+ + HCO3• CO2 diffuses out of a respiring systemic tissue cell and
enters a RBC, which increases the amount of CO2 in
the RBC
– inside the RBC, carbonic anhydrase combines
CO2 and H2O forming carbonic acid (H2CO3)
• H2CO3 quickly dissociates into hydrogen ions
(H+) and bicarbonate ions (HCO3-) in the RBC
–creates a high [HCO3-] in the RBC
–creates a high [H+] in the RBC
• Hb (which just dropped off some of its O2)
acts as a buffer by binding to the H+
produced in order to prevent a decrease in
the pH of the RBC
Respiratory Acidosis
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
• An increase in the PCO2 of the body will drive the
above reaction to the right resulting in the synthesis of
excessive amounts of H+ causing the body pH to
decrease (acidic)
– respiratory acidosis (pH < 7.4) can denature
proteins and depress the CNS
• Chemoreceptors will stimulate the DRG to increase
the ventilation rate and depth (hyperventilation)
– removes CO2 from the body faster resulting in a
decrease in CO2 levels
– causes the above reaction to proceed to the left
decreasing the amount of H+
• increasing the pH of the body back to 7.4
Respiratory Alkalosis
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
• A decrease in the PCO2 of the body will drive the above
reaction to the left resulting in a decrease in the
amount of H+ causing the body pH to increase basic
(alkaline)
– respiratory alkalosis (pH > 7.4) can denature
proteins and depress the CNS
• Chemoreceptors will inhibit the DRG to decrease the
ventilation rate and depth (hypoventilation)
– removes CO2 from the body more slowly resulting in
an increase in CO2 levels
– causes the reaction to proceed to the right
increasing the amount of H+
• decreasing the pH of the body back to 7.4
Transport of CO2 as HCO3–
• The high [HCO3-] in the RBC promotes the diffusion of
HCO3- out of the RBC into blood plasma
– HCO3- is more soluble than CO2 therefore more can
be carried
– the volume of plasma is greater than the collective
volume of the cytosol of the RBCs and thus has a
greater capacity to carry HCO3- (CO2)
– Cl- diffuses from the plasma into the RBC to
electrically counterbalance the diffusion of HCO3out of the RBC (chloride shift)
• HCO3- circulates back to the lungs in the plasma
Conversion of HCO3– to CO2
H+ + HCO3- → H2CO3 → CO2 + H2O
• As the blood flows through the pulmonary capillaries,
CO2 diffuses out of the plasma and RBCs and enters
the alveoli, which decreases the amount of CO2 in the
RBC
• HCO3- diffuses from the plasma into the RBCs which
increases the amount of HCO3- in the RBC
– Cl- diffuses out of the RBC (reverse chloride shift)
• In the RBC, H+ and HCO3- combines to form H2CO3
– H2CO3 is then converted by carbonic anhydrase to
CO2 and H2O
• CO2 diffuses out of the RBC and into the alveoli
and removed from the body on the next
expiration