Respiratory systemChapter # 3

Respiration

Act of breathing resulting in exchange ofoxygen & CO2 b/w body tissues andatmosphere

Divisions

◦ 4 main divisions

Pulmonary ventilation

Inflow & outflow of air b/w atmosphere & lungalveoli

Diffusion

Of oxygen & CO2 b/w alveoli & blood

Transport

Of oxygen & CO2 in blood and body fluids to& from cells

Regulation

Of ventilation & other acts of respiration

Functions of respiration◦ Supply of oxygen to tissues & removal of CO2

from blood

◦ Helps in regulating acid base balance byadjusting CO2 elimination from body

◦ Helps in keeping constant condition of water inbody through elimination of excess water vapors

◦ Eliminates certain harmful volatile substancesfrom body e.g. ammonia, alcohol etc

Mechanics of respiration

Lungs can be expanded & contracted in2 ways;◦ By downward & upward movement of

diaphragm to lengthen or shorten chestcavity

◦ By elevation & depression of ribs to increase& decrease anteroposterior diameter of chestcavity

Inspiration & muscles of inspiration◦ During inspiration (in normal quiet breathing); main role is played by contraction of diaphragm that

pulls lower surfaces of lungs downward

Other muscles;◦ External intercostal (main muscle)

◦ Sternocleidomastoid muscles

◦ Anterior serrati

◦ Scaleni

Expiration & muscles of expiration◦ During expiration, diaphragm simply relaxes

& elastic recoils of lungs, chest wall &abdominal structures compresses lungs

Muscles helping in expiration;◦ Abdominal recti (main muscle)

◦ Internal intercostals

Lungs pressure

Pleural pressure◦ Pressure in narrow space b/w lung pleura &

chest wall pleura

◦ Negative pressure which prevents collapse oflungs

◦ Also called lung recoil pressure

◦ Value; 5 cm of H2O

Alveolar pressure◦ Pressure inside lung alveoli

◦ Different during inspiration & expiration

◦ Inspiration – alveolar pressure becomes -1 cm ofH2O which causes air to move into lungs

◦ Expiration – alveolar pressure rises to about+1 cm of H2O this forces inspired air out of lungs

Transpulmonary pressure◦ Difference b/w alveolar pressure & pleural

pressure

◦ Pressure difference b/w alveoli & outersurface of lungs

◦ Actually it is measure of recoil pressure

Recoil pressure◦ Elastic forces in lungs that tend to collapse

lungs at each point of expansion

Pulmonary volumes

Tidal volume

◦ Volume of air inspired or expired with

each normal breath

◦ Value: 500 ml

Inspiratory reserve volume

◦ Extra volume of air that can be inspired in

after normal tidal volume

◦ Value: 3000 ml

Expiratory reserve volume

◦ Extra amount of air that can be expired by

forceful expiration after end of normal tidal

expiration

◦ Value: 1100 ml

Residual volume

◦ Volume of air still remaining in lungs after

most forceful expiration

◦ Value: 1200 ml

Pulmonary capacities

Combination of two or more pulmonaryvolumes

Inspiratory capacity

Combination of tidal volume & inspiratoryreserve volume

Formula: I.C = T.V + IRV

Significance

This is the amount of air that a person canbreath;◦ beginning at normal expiratory level & ending at

maximum lung distension

Value: 3500 ml

Functional residual capacity Combination of expiratory volume &

residual volume Formula: FRC = ERV + RV Significance This is amount of air remaining in lungs

at end of normal expiration Value: 2300 ml

Vital capacity Combination of inspiratory reserve

volume, tidal volume & expiratoryreserve volume

Formula: VC = IRV + TV + ERV

Maximum amount of air that a personcan expel from lungs;◦ after first filling lungs to their maximum extent

& then expiring to maximum limit

Total lung capacity Combination of vital capacity & residual

volume Formula: TLC = VC + RV Significance Maximum volume to which lungs can be

expanded with greatest possibleinspiratory effort

Value: 5800 ml

Composition of inspired,

expired & alveolar air Lungs can never be completely emptied of air b/c

of residual volume

The Relative Composition (% by Volume) ofInspired, Expired & Alveolar Air

GasInspired air

%

Expired air

%

Alveolar air

%

Oxygen 20.71 14.6 13.2

Carbon

dioxide0.04 3.8 5.0

Water

vapour1.25 6.2 6.2

Nitrogen 78.0 75.4 75.6

Inspired air contains approximately 21% by

volume of oxygen gas

As this fresh air is drawn into alveoli;

◦ it mixes with air already present (residual

volume)

Residual volume dilutes fresh air, so

oxygen content falls

CO2 content of alveolar air increases

significantly as gas exchange proceeds

◦ & CO2 diffuses from blood into alveoli

Oxygen content of expired air is higher than

that in alveoli

◦ This is explained by fact that expired air from

alveoli mixes with dead space air whose oxygen

content is same as that of atmosphere

CO2 content in expired air is less than that

of alveolar air

◦ explained by fact that expired air from alveoli

mixes with dead space air containing very low

levels of carbon dioxide

Water vapour content of expired air issignificantly higher than that of inspired air◦ as air is breathed into alveoli, water from lining of

alveoli evaporates into alveolar air such thatexpired air is greater in volume than inspired air

Nitrogen gas is neither used or produced bybody and actual amounts of nitrogen ininspired an expired air do not change◦ slightly larger volume of expired air means that

nitrogen forms part of larger volume duringexpiration and so its % by volume decreases

There are several reasons for alveolar air

differences

◦ First, alveolar air is only partially replaced by

atmospheric air with each breath

◦ Second, oxygen is constantly being absorbed

into pulmonary blood from alveolar air

◦ Third, carbon dioxide is constantly diffusing from

pulmonary blood into alveoli

◦ Fourth, dry atmospheric air that enters

respiratory passages is humidified even before it

reaches alveoli

Transport of O2 & CO2 in Blood

& body fluids O2 is transported in combination with Hb to tissue

capillaries

CO2 also combines with chemical substances inblood that increases its transport to lungs

Whole transport of O2 in blood can be dividedinto following steps;

1. Diffusion of O2 from alveolus intopulmonary blood

Partial pressure of gaseous O2 in alveolus is104 mmHg

◦ while PO2 in venous blood entering capillary is only40 mmHg

Thus, due to pressure difference of 64

mmHg;

◦ O2 diffuses from alveolus into pulmonary

blood

In exercise

◦ During strenuous exercise body require as

much as 20 times normal amount of oxygen;

◦ This increase in O2 demand is met by;

Diffusing capacity for oxygen increases three folds

during exercise

Increased number of capillaries open in exercise

Dilatation of alveoli & capillaries

2. Transport of oxygen in arterial blood

About 98% of blood coming from lung

has partial pressure of O2 about 104

mmHg

◦ while remaining 2% of blood, which comes

from bronchial vessels, comprises of venous

blood;

has PO2 of 40 mmHg (equal to that of normal

venous blood)

◦ Mixing of these two bloods in left atrium

makes final partial pressure of O2 about 95

mmHg

◦ This blood is then pumped by aorta into

systemic circulation as oxygenated blood

3. Diffusion of O2 from capillaries intointerstitial fluid

PO2 in interstitial fluid is 40 mmHg;◦ while oxygenated blood has PO2 of about 95 mmHg

◦ This difference in O2 conc. causes diffusion of O2from capillaries into interstitial fluid

Depends upon 2 factors◦ Rate of tissue blood flow

◦ Rate of tissue metabolism

4. Diffusion of O2 from interstitial spaces intocells

Normal intracellular PO2 – approx. 23 mmHg;◦ b/c only 1-3 mmHg of O2 is normally required by cells

◦ Thus pressure difference causes O2 to diffuse intocells

5. Diffusion of CO2 from cells into

interstitial fluid

PCO2 inside cell is 46 mmHg;

◦ while in interstitial is 45 mmHg

◦ Pressure difference causes CO2 to diffuse out

from cells into interstitial fluid

6. Diffusion of CO2 from interstitial fluid

into capillaries

PCO2 in interstitial fluid is 45 mmHg;

◦ while in arterial end of capillary PCO2 is 40

mmHg

◦ Due to this pressure difference in PCO2, CO2

diffuses from interstitial fluid into capillaries

7. Diffusion of CO2 from pulmonary blood

into alveolus

PCO2 of venous blood entering pulmonary

capillaries is 45 mmHg;

◦ while PCO2 of alveolar air is only 40 mmHg;

◦ Thus, only 5 mmHg pressure difference causes

all required CO2 diffusion out of pulmonary

capillaries into alveoli

◦ Finally CO2 from alveolus is exchanged

TRANSPORT OF O2 IN BLOOD

About 97% of O2 transported from lungs to tissues

is carried in combination with Hb in RBCs

Remaining 3% of O2 is carried in dissolved state in

water of plasma & cells

Oxygen-hemoglobin dissociation curve

When PO2 is high (lungs) O2 binds with Hb

But when PO2 is low (tissues) O2 is released from

Hb

◦ This relationship b/w PO2 & amount of oxygenation and de-

oxygenation of Hb is called Oxygen-Hb dissociation curve

Oxygen-hemoglobin dissociation curve

Value of O2-Hb combinations◦ Normal conc. of Hb – 15 gm/100ml of blood

◦ Normal amount of O2 carried by 1 gm of Hb –1.34 ml of O2

◦ Max. amount of O2 carried by 100 ml of blood– 20 ml of O2

Percentage of Hb bound with O2 –known as percent saturation of Hb

Amount of O2 released by Hb During normal conditions about 5 ml of

O2 is carried to tissues in each 100 ml ofblood

Amount of O2 released by Hb duringexercise

During strenuous exercise three times asmuch O2 is transported in each 100 ml ofblood◦ i.e. 15 ml O2 / 100 ml blood

Utilization coefficient Percentage of blood that gives up O2 as

it passes through tissue capillaries

◦ Normally 25% of blood, gives up its O2 totissues

◦ During strenuous exercise – 75-85% or allblood can give up its O2

Physiological significance of O2-Hbdissociation curve

Sigmoid shape of curve is of great physiologicalsignificance◦ b/c it ensures that oxygenation & de-oxygenation of

Hb takes place in most optimum way

In lungs

At PO2 of 104 mmHg in alveolar air – more than97% of Hb becomes saturated with O2

Even at PO2 of 60 mmHg – percent saturation ofHb is 89%

So in any condition associated with fall inalveolar PO2;◦ appreciable amount of Hb can still be saturated

In tissues

A drop of PO2 from 100 to 50 mmHg wouldrelease only 18% of O2

◦ while drop from 50 to 0 mmHg – release 75-85% ofO2

Significance of this phenomenon is supply ofmore O2 to tissues during exercise where PO2 ismuch lowered

Metabolic use of O2 by cells

Depends on following factors◦ Intracellular PO2

◦ Distance of cells from capillaries

◦ Blood flow of tissues

Combination of Hb & CO

CO combines with Hb at same point as

does O2 – but 250 times more rapidly than

O2

The condition in which CO binds with Hb &

displaces O2 – termed as CO poisoning

Shift of O2-Hb dissociation curve

Shifting of curve to right

Indicates that Hb has decreased affinity foroxygen

This makes it more difficult for Hb to bind tooxygen◦ requiring higher PO2 to achieve same oxygen

saturation

Rightward shift – increases PO2 in tissueswhen it is most needed;◦ such as during exercise

Causes◦ Increase H+ conc. or decreased pH

◦ Increased CO2 conc.

◦ Increased temp.

◦ Increased diphosphoglycerate

◦ Increased metabolism of tissues

Shifting of curve to left

Left shift of curve is sign of hemoglobin's

increased affinity for oxygen

◦ e.g. at the lungs

Causes

◦ Decrease H+ conc. or decreased pH

◦ Decreased CO2 conc.

◦ Decreased temp.

◦ Decreased diphosphoglycerate

◦ CO poisoning

◦ Decreased metabolism

TRANSPORT OF CO2 IN BLOOD

Under normal resting condition;◦ an avg; of 4 ml of CO2 is transported from tissue

to lungs in each 100 ml of blood

Forms of CO2 transport

1. Transport of CO2 in dissolved state

About 7% of CO2 – transported as dissolveCO2

◦ Arterial blood content – 2.4 ml of CO2 / 100 ml

◦ Venous blood content – 2.7 ml of CO2 / 100 ml

◦ Thus 0.3 ml – transported in dissolved state ineach 100 ml of blood

2. Transport of CO2 as carbamino compounds

30% of CO2 – transported in combination withHb & plasma proteins

Comprises transport of 1.5 ml of CO2 / 100 mlof blood

CO2 combines with NH2 groups of bloodproteins to form unstable carbaminocompounds

Mostly CO2 combines with Hb formingcarbamino-Hb◦ Since de-oxygenated Hb has more affinity for

CO2;

◦ so in tissues when Hb is reduced – deoxy Hb isformed, which facilitates CO2 to lungs

3. Transport of CO2 as bicarbonate ions

70% of CO2 is carried as bicarbonate ions

HCO3 ions are formed in RBCs & to lesserextent in plasma

This transport comprises 2.2 ml of CO2 / 100ml of blood

Chloride shift

Bicarbonate ions formed in RBCs diffuse outinto plasma

To maintain electrical neutrality of RBCs;◦ an equal number of chloride ions diffuse into

cells from plasma

◦ This is known as chloride shift

CO2 dissociation curve This curve predicts relationship b/w

quantity of CO2 present in blood in allforms & PCO2

◦ i.e. dependence of total blood CO2 on Pco2

Haldane effect An increase in CO2 in blood will cause

O2 to be displaced from Hb◦ This phenomenon is known as Haldane

effect

Respiratory exchange ratio Ratio of CO2 output to O2 uptake◦ R = rate of CO2 output / rate of O2 uptake

Regulation of respiration

Respiratory center

Composed of several widely spread groupsof neurons in brain

Located in medulla oblongata & pons

Divisions◦ 4 major parts

1. Dorsal respiratory group

Location◦ In dorsal portion of medulla within nucleus of

tractus solitarius

Connections◦ Nucleus of tractus solitarius receive sensory

signals via vagus & glassopharyngeal fromperipheral chemoreceptors & baroreceptors

FunctionsResponsible for generating repetitive bursts

of inspiratory action potential

Generate inspiratory Ramp signals During inspiration – signals for contraction of

inspiration begins very weakly at first

Then increases steadily in ramp fashion for about 2sec

Abruptly ceases in next 3 sec & then begins again

This inspiratory signal is known as ramp signal

2. Pneumataxic center Location◦ Dorsally in nucleus parabrachialis of upper

pons

Connections◦ Serves as input source for inspiratory area

FunctionsTransmits impulses continuously to

inspiratory area to control switch off point ofinspiratory ramp

Thus controls duration of inspiration

Can increase heart rate (up to 30-40 breathsper min)

3. Ventral respiratory group

Location◦ In ventral medulla found in nucleus ambigus &

nucleus retroambigus

FunctionsWorks when more than normal ventilation is

required – thus it activates to increase respiratoryrate

Some part of it may also cause inspiration

Provides powerful expiratory signals toabdominal muscles during expiration

4. Apneustic center

Location◦ In lower pons

Connections◦ Serves as input drive to dorsal respiratory group

FunctionsSends signals to dorsal respiratory group of

neurons to prevent Switch-off of inspiratory rampsignal

Controls depth of respiration

Hering breuer inflation reflex◦ This reflex is started when lungs become

overstretched

◦ Stretch receptors located in walls of bronchi &bronchioles transmit signals via vagi into dorsalrespiratory group

◦ This switches off inspiratory ramp, stops furtherinspiration & thus increases rate of inspiration

Control of respiration◦ Overall control divided into;

A. Chemical regulation

B. Nervous regulation

A. Chemical regulation

Respiration – maintain proper conc. of O2, CO2 &H+ ions in tissues◦ so highly responsive to changes in these, i.e.,

◦ excess of CO2

◦ change in H+

◦ lack of O2

Chemosensitive area

Location◦ Lies bilaterally beneath ventral structure of medulla

Functions◦ Highly sensitive to changes in blood CO2 & H+

ion conc.

◦ Increases rate & depth of respiration byincreasing intensity of inspiratory ramp signals

Excess of CO2

◦ Changes of CO2 in blood

◦ Excess of CO2 – most important factor b/c it cancross blood brain barrier It does this by reacting with water of tissues to form

carbonic acid

This in turn dissociates into H & bicarbonate ions

◦ H+ ions have potent direct stimulatory effect onchemosensitive area to increase rate & depth ofrespiration

◦ Changes in CSF PCO2

◦ Changing PCO2 in CSF itself has more rapidexcitation of chemosensitive area b/c CSF has very little protein & acid base buffers

◦ Therefore H+ ion conc. increases almost instantlywhen CO2 enters CSF from brain vessels

B. Nervous regulation of respiration

Various mechanisms of regulation;1. Chemoreceptors

2. Hering Breuer Reflex

3. Impulses from higher centers

4. Impulses from vasomotor center

5. Effect of temp

1. Chemoreceptors

Nature◦ Special type of nervous chemical receptors

Location◦ Located in;

Carotid bodies

Aortic bodies

Other arteries of thorax & abdomen

◦ Carotid bodies

◦ Located bilaterally in bifurcation of commoncarotid arteries

◦ Their afferent nerve fibers pass through Hering’snerves to glassopharyngeal nerves

◦ & then to dorsal respiratory area

◦ Aortic bodies

◦ Located along arch of aorta

◦ Their afferent nerve fibers pass through vagito dorsal respiratory area

◦ Note; chemoreceptors are exposed at alltimes to arterial blood, not venous blood

◦ Their partial pressure of O2 is same as PO2

of arterial blood

◦ Basic mechanism Chemoreceptors are important for detecting

changes in O2, CO2 & H+ in blood

Have glandular cells – act as chemoreceptors &stimulate nerve endings

Chemoreceptors – stimulated by changes inarterial PO2 range of 60 & 30 mmHg

Effect of CO2 & H+ on chemoreceptors◦ Increase in CO2 & H+ - excites chemoreceptors

◦ But their direct effect on respiratory center stimulationis more powerful then their effect mediated throughchemoreceptors

2. Hering Breuer Reflex◦ Control rhythm & depth of respiration

◦ Stretch receptors present in tracheo-bronchial treeprobably at point of bronchial branching

◦ As lung expand during act of respiration impulses are carried to apneustic center which inhibits

discharge of inspiratory center

So act of inspiration ceases & expiration follows“Hering-Breuer Inflation Reflex”

◦ During forced deflation of lungs – respiration maybe stimulated “Hering Breuer Deflation reflex”

3. Impulses from higher centers◦ Emotional activities modify breathing;

◦ e.g., fear, anxiety, rage stimulates breathing

◦ In Shock – respiration depressed

4. Afferent impulses from sensoryreceptors◦ Painful stimuli stimulate respiratory center

◦ Newborn child doesn’t breath usually, but startsbreathing after slap

◦ Bucket full of water thrown on man causes gasp& stimulated breathing is found

5. Impulses from vasomotor center & effectof BP on breathing

◦ Vasomotor center directly excites respiratorycenter This effect brought about by baroreceptors located in

carotid & aortic arch which are very sensitive to changesin BP

◦ Baroreceptors – stimulated when there is rise inBP

◦ They sends impulses to cardiac center,vasomotor center & respiratory center These impulses are inhibitory in nature

◦ Thus as BP rise, heart slows down (Marey’sreflex) & respiration depressed

◦ So rise in BP will depress breathing & vice versa

6. Effect of temp

◦ Increase in temp increases rate of respiration

◦ Hypothalamus initiates cascade of neurogenic

reactions;

to decrease body temp by increasing rate of respiration

◦ This facilitates loss of heat from body through

water vapours in expired air

Regulation of respiration during exercise

In strenuous exercise, O2 consumption & CO2formation can increase as much as 20 folds

During exercise arterial PO2, PCO2 & pH allremain almost normal

Following factors increases respiration duringexercise

Brain, on sending impulses to exercising musclesalso transmits collateral impulses to brain stem toexcite respiratory center according to need of body

During exercises body movements are believed toincrease pulmonary ventilation; by exciting joint proprioceptors which in turn excite

respiratory center in brain

Hypoxia developing in muscles during exercise

elicits afferent nerve signals to respiratory center

to excite respiration

Many experiments suggest that brains ability to

increase ventilatory response during exercise is

mainly “learned response”

Specific pulmonary

abnormalities Emphysema◦ An increase in size of alveoli, either due to

dilatation or destruction of their walls

Pneumonia◦ Any inflammatory condition of lung in which

some or all of alveoli are filled with fluid & bloodcells

◦ Results in two pulmonary abnormalities; Reduction in total available surface area of respiratory

membrane

Decreased ventilation-perfusion ratio

◦ Causes Bacteria or viruses

Asthma◦ Spastic condition of bronchiolar smooth muscle,

causing extreme difficulty in breathing

◦ Cause

◦ Usual cause is hypersensitivity of bronchioles toforeign substances in air

◦ Mechanism

◦ Allergic person has tendency to form largeamount of IgE antibodies which attach to mastcells

◦ On exposure to antigen IgE antibodies react withit & mast cell granules rupture, releasingsubstances

◦ These substances cause bronchospasm