chapter 17 respiratory

8/12/2019 Chapter 17 Respiratory

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Chapter 17 - Respiratory System: Gas Exchange and Regulation of Breathing

Pulmonary Circulation

The cells of the body consume an average !" ml of oxygen per minuteand produceabout "" ml of car#on dioxide per minute. The ratio of the carbon dioxide produced

over the oxygen consumed is called the respiratory $uotient% Hence, the averagerespiratory quotient is "%&.

The figure below illustrates the movements of oxygen and carbon dioxide into and out

of the lungs and tissue under resting conditions.


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The figure above illustrates how oxygen and carbon dioxide goes between alveolar air

and blood across the respiratory mem#ranecomposed oftype ' epithelial cells of thealveolar walls, endothelial cellsof capillariesand the #asement

mem#ranessandwiched between them.

(iffusion of Gases

Partial Pressure of Gases

The partial pressure of a gas is the proportion of pressurecontributed by an

individual gas to the total pressure of a mixture of gases. Partial pressure is found by

multiplying:

1. )ractional concentration of a gas in a mixture by,

. *otal pressure exerted by a gas mixture.

The total pressure of air can be described as the sum of the ma!or gases found in air

Pair " Pnitrogen # Poxygen # Pwater

$n a molar basis air is 7+, nitrogenand 1, oxygen assuming %ero humidity. &ny

humidity 'water vapor( su#tractsfrom the proportions of nitrogen and oxygen.

Car#on dioxideaccounts for only "%",of the air molecules.


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&t .ero humidityand at sea le/elin air:

Pnitrogen " ).*+ x*) mm

Hg"

)) mm

Hg

Poxygen " ).1 x*) mm

Hg"

1) mm

Hg

Pcarbon dioxide " ).)))- x *) mmHg

" ).- mmHg

&t 1"", humiditythe partial pressure of H$ is 07 mm g. This causes partial

pressures to be:

Pnitrogen " - mm Hg

Poxygen " 1) mm Hg

Pcarbon dioxide " ).1 mm Hg

Solu#ility of Gases in 2i$uids /as molecules dissolved in water have a certain partial pressure. 0hen a liquid andgas come into contact, the concentration of gas molecules in the liquid is proportionalto

the partial pressure of the gas. &t a given partial pressure the relative concentration of

different dissolved gases will differ based on there different solu#ilityin the liquid. orexample carbon dioxide is " timesmore soluble in blood than oxygen.

enry3s la4describes this relationship with :

c " 2P

0here:

c " 3olar concentration of gas

P " Partial pressure of gas in atmosphere

2 "Henry4s law constant 'based on gas andtemperature(

0hen containers of water are exposed to 1)) mm Hg of pure oxygen or carbondioxide, overtime the gas in the air e$uili#rates with the gas dissolved in the liquid till

they are both at 1)) mm Hg. However, because carbon dioxide dissol/es more readilyin

water, the concentration of the gas in the water is much higherfor carbon dioxide than

for oxygen. This becomes clear when the calculations are made:


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Pressure at 7oC Concentration in 5irConcentration in

6ater

$xygen 1)) mm Hg . mmole5liter ).1 mmole5liter

6arbondioxide

1)) mm Hg . mmole5liter -.) mmole5liter

Exchange of xygen and Car#on (ioxide

/ases will diffuse down their partial pressure gradients%

Gas Exchange in the 2ungs

&lthough partial pressures of oxygen and carbon dioxide in the atmosphere are 18"mm gand "% mm g, respectively, in the alveoli the pressures are 1"" mm gforoxygen and 0" mm gfor carbon dioxide. This is because:

1. Exchangesof gas between alveoli and capillaries.

. 9ixingof atmospheric air with air of anatomic dead spaces.

-. Saturationof alveoli air with 4ater /apor.


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7eoxygenated blood entering the pulmonary capillaries has a P$of 0" mm g and

P6$of 08 mm g. The gases diffuse down their concentration gradients and leave at the

same partial pressures as the gases in the alveoli 'P$ " 1"" mm gand P6$ " 0" mm

g(.


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(iffusionis a very rapid process ta2ing about "%! secondsor within the first ,of

the capillary length in the alveoli. The rapidness of the rate of diffusion is due to the

relative thinness of the respiratory membrane.

Gas Exchange in Respiring *issue

0hen oxygenated blood enters the tissue the P$is 1"" mm gand that of P6$is 0"

mm g. The tissues have a lower partial pressure of oxygen because of oxygen

utili%ation and a higher carbon dioxide concentration because of carbon dioxideproduction.

The amount of P$ and P6$ in the venous blood depends on the meta#olic acti/ityof

the tissue with the greater activity resulting in lower P$ and higher P6$.

The venous blood from all parts of the body returns to the right side of the heart andmixes. The venous blood in the right atrium is therefore calledmixed /enous #lood% &t

rest, the typical values are a P$of 0" mm g and P6$of 08 mm g.

(eterminants of 5l/eolar Pand PC &lveolar P$and P6$are determined by:

1. P$ and P6$of inspired air.

. 3inute alveolar /entilation%

-. 8ates of oxygen consumptionand carbon dioxide production.

9ormally P$and P6$of inspired air remains constant and the alveolar partial

pressures depend on the last two factors. This is reflected by the fact that:

1. 0hen alveolar /entilation increasesrelative to oxygen consumptionalveolarP$increasesand P6$decreases.

. 0hen alveolar /entilation decreasesrelative to oxygen consumptionalveolar

P$decreasesand P6$ increases.

9ormal alveolar ventilation is ad!usted to meet tissue demands. This appropriate

increase in ventilation is referred to as hyperpnea% ypo/entilation occurs when

alveolar ventilation is insufficientto meet tissue demand. &s a consequence P6$ risesand P$ decreases.yper/entilation occurs when alveolar ventilation exceedsthe


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demands of the tissue so that P$ increases and P6$ decreases.

*ransport of Gases in Blood

xygen *ransport #y emoglo#in

&pproximately 1%!, of the oxygen transported in the blood is dissolved in plasma or

the cytosol of red blood cells while the remaining +.; is bound to hemoglo#in. The

oxygen bound to hemoglobin is in equilibrium with the oxygen dissolved in plasmawhich is related to P$. The oxygen is transported bound to the hemeportions of the

hemoglobin molecule. The binding of oxygen to hemoglobin depends upon the P$in the

surrounding fluid. The higher the P$the greater the binding.


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The math:

Hemoglobin in blood 1=1*gm5d> or an average of 1) gm5>

$xygen carrying capacity

1.-? ml5gram x 1? grams5liter @ )) ml5>

6ardiac output liter5minute

Alood supplies

liter5minute x )) ml $5> " 1""" ml min.

Tissues need !" ml min. Therefore, under resting conditions venous blood is

still 7!,saturated.

5nemia is a decrease in $carrying capacity of the blood. 0ith anemia, tissues may

not be supplied with the oxygen they need and fatigue occurs more readily.

emoglo#in xygen (isassociation Cur/e

The curve that shows percent saturation of hemoglobin as a function of P$is s-shaped'sigmoidal(. The s=shaped nature of the curve can be explained in the following way:

&t low partial pressures the affinity of hemoglobin for $is lo4% &n increase inP$results in only a small increase in percent saturation.

&s the P$increases the hemoglobin molecule acquires at least one molecule of $ . The

binding of one molecule of $to hemoglobin causes a conformational change in the

hemoglobin that increases the affinityof the remaining subunits for oxygen. This iscalled positi/e cooperati/ity% The positive cooperativity causes the steep part of the curve as

the P$goes from 1 mm Hg to ) mm Hg.

rom ) mm Hg to ) mm Hg the slope of the curve decreases because as the $binds tohemoglobin fe4er #inding sitesbecome available. &bove a P$of ) mm Hg the slope of the

curve becomes nearly flat.

&t the P$of the systemic arteries of 1)) mm Hg the hemoglobin is +&, saturated. &t the

P$of the systemic veins the hemoglobin is 7!, saturated. &t rest the tissue ta2es onlyabout !,of the $ transported in the blood.


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The hemoglobin oxygen disassociation curve can shift either to the left or to the right.

0hen the curve shifts to the right; the affinity of oxygen for hemoglobin decreases and

oxygen can be more easily unloaded% 0hen the curve shifts to the left; the affinity of oxygenfor hemoglobin increasesand oxygen can be more easily loaded%


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)actors 5ffecting 5ffinity of emoglo#in for actors that affect the affinity of hemoglobin for oxygen include:

1% *emperature

& higher temperature cause a decreasein affinity. Bn more active tissue with a higher

temperature $unloads more easily.

% p

Hydrogen ion increases'pH decreases( in more active tissue. This decreasesthe affinity

of hemoglobin by the Bohr effect which can be expressed in this equation

Hb # $==C

Hb=$ # H#

D==

Bn more active tissue pH decreasesand $is more easily unloaded.

% PC 6$binds reversibly with Hb to form car#aminohemoglo#in a molecule which has alesser affinity for $. This decreasein the affinity of Hb for oxygen in the presence of

6$is called the car#amino effect%

These first three factors wor2 together to promote $unloading in respiring tissues and$loading in the lungs.

0% ; - (iphosphoglycerate

,- =7P/ is produced from an intermediate compound in glycolysis and decreasestheaffinity of hemoglobin for oxygen. &t low oxygen levels an en%yme cataly%es the synthesis

of ,-=7P/. Hence, ,-=7P/ concentration increases, the affinity of Hb for

oxygen decreases% This is helpful for unloadingoxygen during anemia and at highaltitudes. &t high oxygen levels, oxyhemoglobin inhibits the en%yme that synthesi%es ,-=

7P/ and ,-=7P/ levels decrease.

Car#on (ioxide *ransport in Blood

The carbon dioxide in the blood exists as


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7issolved as carbon

dioxide: =;

6arbaminohemoglobin : =;

7issolved as H6$-= : =+);

Role of Car#onic 5nhydrase in Car#on (ioxide *ransport

Car#onic anhydrase cataly%es the reaction that converts 6$and H$ to carbonic

acid. 6arbonic acid reversibly disassociates to H## bicarbonate. The equation is:

6$ # H$==C

H6$-==C

H# # H6$-=

D== D==

Hence, an increasein P6$ma2es the blood more acidicwhile a decrease in P6$ does the

opposite. This reaction is important in the transport and exchange of Cand plays animportant role in maintaining acid-#ase #alance.

CExchange and *ransport in Systemic Capillaries and


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Bn the lungs, the pressure gradient favors the diffusion of 6$from the blood into thealveoli. The decrease in 6$causes bicarbonate in the erythrocyte to bind with H

#to

form carbonic acid which in turn is converted into 6$and H$ by carbonic anhydrase.

0hile bicarbonate in the erythrocyte decreases more bicarbonate is brought into the

erythrocyte in exchange for 6l=.

Effect of xygen on Car#on (ioxide *ransport

The P$affects the ability of the blood to carry 6$. The binding of $to hemoglobin

decreases the affinity of Hb for 6$. 6onversely, a decrease in P$increases the binding of

6$to hemoglobin. This phenomenon is called the aldane Effect%


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7uring $uiet #reathing the breathing cycle consists in the contraction of the inspiratory

muscles followed by relaxation of the same muscle during expiration. 7uring more acti/e

#reathingthe expiratory muscles contractduring the expiration phase. This is reflected bythe activity of the motor neurons innervating the respective muscles.

Generation of Breathing Rhythm in the Brainstem

Respiratory control regions are present in the medullaand ponsof the brainstem.There are two general classes of neurons located here:

'nspiratory neurons which generate action potentials during inspiration.

Expiratory neurons which generate action potentials during expiration.

Respiratory Centers of the 9edulla

Two respiratory centers in the medulla include:

1% (orsal Respiratory Group contains primarily inspiratory neurons%The

inspiratory neurons show a ramp increasein activity during inspiration followed by

an a#rupt termination.


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%


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increases, as during exercise, the inspiratory neurons contribute to enhanced

inspiration and the expiratory neurons stimulate the muscles that increase the force

of expiration.

Respiratory Center of Pons

This center contains #oth inspiratoryand expiratory neurons and mixed

neuronsthat control #othinspiratory and expiratory neurons. This center may facilitatethe transitionbetween inspiration and expiration.

Central Pattern Generator

The central pattern generator is a networ2 of neurons that generates a regular, repeatingpattern of neural activity called the respiratory rhythm.

9odel of Respiratory Control (uring >uiet Breathing

The figure above shows a simplified model to describe how the breathing rhythm is

generated by the central pattern generator and modified by other centers of the central nervoussystem. 9ote that the central control region resides in the medulla but other portions of the brain

including the pons; cere#ral cortex; cere#ellum; lim#ic system;

hypothalamus and medullary cardio/ascular areasprovide input that can modify thisrhythm.

Peripheral 'nput to Respiratory Centers

The central pattern generator is reflexively controlled by various types of receptorsthat include:

1% Chemoreceptors = Peripheral'in systemic arteries( and central 'in brain(

monitor conditions in arterial #loodand in cere#rospinal fluid. 8egulate

ventilation under resting conditions.% Pulmonary stretch receptors in smooth muscles of airways.

% 'rritant receptorslining the respiratory tract.

0% Proprioceptors in muscles and !oints.

Control of


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Peripheral chemoreceptors are located in the carotid #odiesnear the carotid sinus.


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These are speciali%ed cells in direct contact with arterial blood that communicate with

afferent neurons that pro!ect to the respiratory control regions. These cells respond to

changes in arterial P, PCorp. The primary stimulusfor chemoreceptors is pH.The main cause of decreases in pH is an increase in P6$. Peripheral chemoreceptors also

respond to arterial P$but only when arterial P$drops #elo4 8" mm g. This is an

extreme drop that usually does not occur. Central chemoreceptors are neurons in the medullathat respond directly to changes

in hydrogen ion concentrationin the cere#rospinal fluid. H ions do not cross the

blood=brain barrier but carbon dioxide does. 6arbon dioxide is converted to H ion andbicarbonate ion by car#onic anhydrasein the 6


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the central chemoreceptors are not exposed to H#from sources other than 6$because of

the blood=brain barrier. $nly theperipheral receptors are sensitive to when it

drops #elo4 8" mm g. &ctivation of chemoreceptors cause an increase in ventilation.The figure below shows this reflex operating during hyperventilation and

hypoventilation.

2ocal Regulation of


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Bn lung diseases that cause obstruction of airways such as emphysema and bronchitis,

the airflow to certain alveoli decreases and the blood flow in the capillaries of thesealveoli will have less gas exchange. The blood leaving these capillaries will then have

a lo4erP$and a higher P6$and a ventilation=perfusion ratio of less than 1.


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0hen pulmonary capillaries are bloc2ed, blood flow to the alveoli decreases and the

capillaries less affected by the bloc2age and still flowing through the alveoli will have

a greater gas exchange. &s a result the blood and air in these alveoli will havea higher P$and a lo4erP6$. The ventilation=perfusion ratio will be greater than 1.

2ocal Control of


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xygenacts primarily on pulmonary arterioles with

a lo4P$causing /asoconstrictionwith decreased flow and car#on dioxideacts primarily on

the #ronchioles with a highP6$causing #ronchodilationand increased ventilation. Therefore,when E5F is highthe increase in P$causes/asodilationand the decrease in

P6$causes #ronchoconstrictionand the ratio returns towards 1. 0hen E5F is lo4the decrease

in P$causes/asoconstriction and the increase in P6$ causes #ronchodilation. 9ote that the

effect of oxygen and carbon dioxide on pulmonary arterioles is the opposite of the effects ofthese gases on systemic arterioles.

*he Respiratory System in 5cid-Base omeostasis

5cid-Base (istur#ances in Blood


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6hanges in the pH of the body has serious consequences because it changes the shape of

protein molecules. &rterial pH affects the pH of body tissues hence it is necessary to regulate

blood pH within narrow limits around the normal of 7%0. Bf the pH drops #elo4 7%!it is said tobe in a condition of acidosis% Bf the pH increases to greaterthan 7%0!it is said to be in a

condition of al?alosis%

chapter 17 respiratory

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