Pulmonary VentilationPulmonary VentilationDr. Laila DokhiDr. Laila Dokhi

External respiration can be divided into

4 major functional events1) Ventilation

2) Diffusion

3) Transport of O2 and CO2 in the blood, body fluids, to and from the cells

4) Regulation of ventilation

Mechanics of pulmonary ventilation

Respiratory muscles:Diaphragm – which increase and decrease the vertical diameter of the chest cavity.

Intercostal muscles – affect the anteroposterior diameter of the chest cavity by moving the ribs.

Internal intercostal muscle (downward and backward) lower the ribs and sternum reducing the anteroposterior diameter

External intercostal muscle (downward and forward) raise the ribs and sternum increasing the anteroposterior diameter of the thoracic cavity

Normal quiet breathing

During inspiration: contraction of the diaphragm, pulls the lower surfaces of the lungs downward

During expiration: by relaxation of the diaphragm and elastic recoil of the lungs, chest wall, and abdominal structures compresses the lungs

Accessory muscles of inspiration include neck muscle (pull the upper ribs and sternum upward)

Accessory muscles of expiration include abdominal recti and internal intercostal muscles (pull downward on the sternum and lower rib)

ExpirationExpiration InspirationInspiration

Increased vertical Increased vertical diameterdiameter

Increased A-P Increased A-P diameterdiameter

External External intercostals intercostals contractedcontracted

Internal Internal intercostals intercostals relaxedrelaxed

Abdominals Abdominals contractedcontracted

Elevated Elevated rib cagerib cage

Diaphragmatic Diaphragmatic contractioncontraction

Movement of air in and out of the lungs

The lung is formed of an elastic tissue that collapse like a balloon and inflated and then expel the air out

The lungs are surrounded by a very thin layer of pleural fluid that lubricate the movements of the lungs within the cavity

Continuous suction of excess fluid into lymphatic channels maintain a slight suction between the visceral and parietal pleura

Various pressure in the lungs

Pleural pressure – is the pressure of fluid in the narrow space between the visceral and parietal pleura, normally slightly negative pressure

The normal pleural pressure at the beginning of inspiration is –5cm of H2O (it reach about –7.5cm of H2O due to movement of the chest cage)

The pleural pressure at the beginning of expiration is–7.5cm of H2O to reach –5cm of H2O

Alveolar pressure

Alveolar pressure: – is the pressure inside the lung alveoli

During inspiration: –1cm of H2O (this slight negative pressure is enough to move about 0.5 liter of air into the lungs in the first 2 second of inspiration)

During expiration: it rises to about +1cm of H2O (this forces 0.5 liter of inspired air out of the lungs during the 2 to 3 seconds of expiration

Compliance of the lungs

Definition:

the extent to which the lungs expand for each unit increase in transpulmonary pressure (pleural pressure minus alveolar pressure) ~ 200ml/cm of H2O (each time, the transpulmonary pressure increase by 1cm of H2O, the lungs expand 200ml)

The compliance diagram of the lungs

Which relates lung volume changes to the changes in transpulmonary pressure and it has 2 curves inspiratory and expiratory compliance curve

The compliance diagram are determined by the elastic forces of the lungs, which can be divided into 2 parts:

1-elastic forces of the lung tissue2-elastic force caused by surface tension of the fluid that lines the alveoli

Elastic forces of the lung tissue are determined by the elastin and collagen fibers among the lung tissue (deflated lungs, these fibers contracted and kinked but when the lung expand it becomes stretched and unkinked by elongating)Elastic forces caused by the surface tension accounts for about 2/3rd of the total lung elastic forces and much more complex and it depends on the “surfactant”

Surfactant surface tension and collapse

of the lungs

When water forms surface with air, the water molecules on the surface of water have extra attraction force for each other and contract. Also water surface in the inner surface of the alveoli attempting to contract to force air out of the alveoli through the bronchi which causes the alveoli to collapse (which cause surface tension elastic force) the lungs expanded

Surfactantis a substance produce by type II alveolar epithelial cells (~ 10% of the surface area of the alveoli) which reduce the surface tension of the fluid in the inner surface of the alveoliit is a mixture of phospholipids, proteins, and ions, the most important component is phospholipid dipalmitoyl phosphatidylcholine which is responsible for reducing the surface tension (formed of 2 parts, hydrophilic part dissolves in the water lining the alveoli and hydrophobic part directed toward the air)the alveolar collapse pressure in an average-sized alveolus with radius of about 100µm and lined with surfactant, is about 4cm of H2O, but if it is lined with pure water is about 18cm of H2O important of surfactant in reducing the amount of transpulmonary pressure required to keep

Effect of the thoracic cage on lung expansibility:the thoracic cage has its own elastic and viscous characteristics, similar to the lungs. Muscular effort were required to expand the thoracic cage

Compliance of the thorax and the lungs together:the compliance of the combined lung-thorax system is one half that of the lungs alone 110ml/cm of H2O

The work of breathingthe respiratory muscles perform work to cause inspiration (not expiration)the work of inspiration can be divided into 3 fractions:

The work required to expand the lungs against its elastic forces called compliance work or elastic work.The work required to overcome the viscosity of the lung and chest wall structures called tissue resistance work.The work required to overcome airway resistance called airway resistance work.

Work energy required for respiration:during normal quiet respiration = 2 to 3% of the total work energy ( to 50 fold in exercise, airway resistance).

Pulmonary volumes and capacities

Pulmonary volumes (by using spirometer):

1) Tidal volume – is the volume of air inspired or expired with each normal breath = 500ml in young adult man.

2) Inspiratory reserve volume – is the extra volume of air that can be inspired over and beyond the normal tidal volume = 3000ml.

3) Expiratory reserve volume – is the extra amount of air that can be expired by forceful expiration after the end of a normal tidal expiration ~ 1100ml.

4) Residual volume – is the extra volume of air that still remain in the lungs after the most forceful expiration ~ 1200ml.

The pulmonary capacitiesComprises more than one volume:

1) Inspiratory capacity – is the volume of air inspired by a maximal inspiratory effort after normal expiration = 3500ml = inspiratory reserve volume + tidal volume.

2) The functional residual capacity – is the volume of air remaining in the lungs after normal expiration = 2300ml = expiratory reserve volume + residual volume.

3) The vital capacity – is the volume of air expired by a maximal expiratory effort after maximal inspiration ~ 4600ml = inspiratory reserve volume + tidal volume + expiratory reserve volume.

4) Total lung capacity – is the maximum volume of air that can be accommodated in the lungs ~ 5800ml = vital capacity + residual volume.

5) Minute respiratory volume – is the volume of air breathed in or out of the lungs each minute = respiratory rate x tidal volume = 12 X 500ml = 6000ml/min.

All lung volume and capacity are about 20 to 25% less in women than in men and are greater in athletic persons than in small and asthenic persons.

Forced capacity (FVC & FEV1)

Normal

Obstructive

Restrictive

VCNor

FEVN

)(

1)(

VCN

FEVN

)(

1)(

VCNor

FEVN

)(

1)(

FORCEDFORCEDEXPIRATIONEXPIRATION

NORMALNORMAL

FEVFEV11 = 3.0L = 3.0L

FVC = 4.2LFVC = 4.2LFEVFEV11/FVC = 72%/FVC = 72%

OBSTRUCTIVEOBSTRUCTIVE

FEVFEV11 = 0.9L = 0.9L

FVC = 2.3LFVC = 2.3LFEVFEV11/FVC = 40%/FVC = 40%

RESTRICTIVERESTRICTIVE

FEVFEV11 =1.8L =1.8L

FVC = 2.3LFVC = 2.3LFEVFEV11/FVC = 78%/FVC = 78%

1 SECOND1 SECOND

FEVFEV11

FEVFEV11

FEVFEV11

TIDALTIDALBREATHINGBREATHING

Alveolar ventilation

Movement of air between the lung and atmospheric air, in the gas exchange areas which include the alveoli, the alveolar sacs, the alveolar ducts, and the respiratory bronchiole.

Diffusion: kinetic motion of molecules of gas at high velocity among each others.

Dead space: The respiratory passages where gas exchange does not occur (up to the terminal bronchioles), normal dead space air in the young adult male = 150ml

The rate of alveolar ventilation

Alveolar ventilation per minute is the total volume of new air entering the alveoli and other adjacent gas exchange areas each minute.

Va = Respiratory rate X (Vt – Vd) = Respiratory rate X (Vtidal volume – Vdead space) = 12 X (500 – 150) = 4200ml

Non-respiratory function of the lungs

1) Protection of respiratory tracts.

2) Conversion of angiotensin I to angiotensin II with the help of converting enzymes formed by the lungs.

3) Alpha 1 anti-trypsin is present in the lung secretion which protects the lung from the action of trypsin, proteases and elastase.

4) Humidification.

5) In plays an essential role in the regulation of acid-base balance.

Functions of the respiratory passageways

The trachea, bronchi, and bronchioles:The walls are formed of cartilage and the smooth muscle contraction of the smooth muscle narrowing of the airway.Sympathetic nervous system causes dilatation of the bronchi to supply the central area of the lung, epinephrine and norepinephrine cause dilatation of the bronchial tree.Parasympathetic nerve fibers penetrate the lung parenchyma and secrete acetylcholine that causes mild to moderate constriction of the bronchioles.

Focal factors that cause bronchiolar constriction:1) histamine2) slow reacting substance of anaphylaxis (secreted from the

mast cells in allergic reactions and pollen in the air)

Mucous of the respiratory passageways

Secreted by epithelial cells that lines the respiratory passage:

it moisten the respiratory passages from the nose up to the terminal bronchioles.it traps small particles out of the inspired air – removal of the mucous by movement of the cilia in the ciliated epithelia that line the entire surface of the respiratory passages in the lungs it beat upward while in the nose it beat downward towards the pharynx.

Cough reflex

about 2-5 liter of air is inspired, then epiglottis and vocal cords close tightly to entrap air within the lung.

abdominal muscles contract forcefully against the diaphragm also the intercostal muscles contract forcefully both raise the pressure in the lungs to 100mmHg.

sudden opening of the vocal cords and epiglottis widely so air under pressure in the lung explodes outward carrying with it the foreign body present in the bronchi and trachea.

Respiratory functions of the nose

it warmed the air.

humidification of the air.

filtration of the air (air conditioning function of the upper respiratory passageway) by hair in the nose and by turbinates that cause turbulence of the air).

Vocalization include 2 steps

phonation by larynx articulation by the structures of the mouth

Phonation: mainly by the vocal cords that protrude from the lateral wall of the larynx to the center of the glottis. During normal breathing they are open to allow passage of air and during phonation, the folds close together to cause vibration during passage of air between them. The pitch of vibration is determined by degree of stretch and how tightly the folds are approximated to each other.

Articulation and resonance: needs lips, tongue and soft palate for articulation but resonance need mouth, nose, nasal sinuses, pharynx and chest cavity

Physiological anatomy of the pulmonary circulatory system

Pulmonary artery divided into 2 main branches which divided into very short branches of arteries and arterioles:The pulmonary arterial tree have large compliance because:arteries and arterioles have large diameters.they are very thin and distensible.Allow them to accommodate about 2/3 of the stroke volume of the right ventricle per beat.

Lymphatics:Lymphatics from all lung tissues drain into the right lymphatic duct to prevent lung edema.

Pressure in the pulmonary system

Systolic pressure in the right ventricle is about 25mmHg and the diastolic pressure is about 0 to 1mmHg (1/5th of the left ventricle).Pressures in the pulmonary artery:During systole, the pressure in the pulmonary artery is equal to the pressure of the right ventricle. At the end of systole and after closure of the pulmonary valve, the pressure in the right ventricle falls rapidly while the pressure in the right artery falls slowly due to blood flow through capillaries of the lungs.

Systolic pulmonary arterial pressure is 25mmHg. Diastolic arterial pressure is 8mmHg. Mean pulmonary arterial pressure is 15mmHg. Pulmonary capillary pressure is about 7mmHg.

Left arterial and pulmonary venous pressure:The mean pressure in the left atrium is about 2mmHg (varying from 1mmHg to 5mmHg).

Automatic control of pulmonary blood flow

When the concentration of O2 in the alveoli decrease below normal the adjacent blood vessels constrict and the vascular resistance increases 5 folds (this is opposite to the systemic vessels). This in turn causes most of the blood to flow through other areas of the lung that are better aerated.

The effect of hydrostatic pressure gradients in the lungs on regional pulmonary blood flow:In normal upright adult, the pulmonary arterial pressure in the uppermost portion of the lung is about 15mmHg less than the pulmonary arterial pressure at the level of the heart, but the pressure in the lowest portion of the lungs is about 8mmHg greater than at the heart. So, at rest, in the standing position, there is little flow in the top of the lungs but about 5 times this flow in the lower portion of the lungs.

During exercise the blood flow through the lungs increase from 4 to 7 folds due to:

1) by increasing the number of open capillaries (3 fold)2) by distending all the capillaries and increasing the

rate of flow through each capillary more than 2 fold

These two factors prevent the rise in pulmonary arterial pressure even during maximum exercise, the pulmonary arterial pressure rises very little, this prevent development of pulmonary edema

the alveolar walls are lined with capillaries so the blood flows in the alveolar walls as sheet.

Capillary exchange of fluid in the lungs and pulmonary interstitial fluid dynamics: fluid exchange in the lung capillary is similar qualitatively to the peripheral tissue, but quantitatively there are important differences:

1) Pulmonary capillary pressure is very low ~ 7mmHg, in comparison with the higher capillary pressure in the peripheral tissue ~ 17mmHg.

2) Interstitial fluid pressure in the lung is slightly more negative than in the peripheral subcutaneous tissue, normally measuring 8mmHg.

Pulmonary capillary dynamics

3) The pulmonary capillaries are relatively leaky to protein, so that the colloid osmotic pressure is about 14mmHg in comparison with less than half this in the peripheral tissue.

4) The alveolar walls are extremely thin and weak so that it ruptured by any positive pressure in the interstitial spaces greater than the atmospheric pressure, which allow damping of fluid from the interstitial spaces into the alveoli.

Forces tending to cause movement of fluid Forces tending to cause movement of fluid outward from the capillaries and into the outward from the capillaries and into the pulmonary interstitium:pulmonary interstitium: Capillary pressureCapillary pressure Interstitial fluid colloid osmoticInterstitial fluid colloid osmotic pressurepressure Negative interstitial fluid pressureNegative interstitial fluid pressure TOTAL INWARD FORCETOTAL INWARD FORCE

Forces tending to cause absorption of fluid Forces tending to cause absorption of fluid into the capillaries:into the capillaries: Plasma colloid osmotic pressurePlasma colloid osmotic pressure TOTAL INWARD FORCETOTAL INWARD FORCE

Total outward forceTotal outward forceTotal inward forceTotal inward force NET MEAN FILTRATION PRESSURENET MEAN FILTRATION PRESSURE

77

141488

2929

28282828

+29+29-28-28+1+1

mmHgmmHg

Negative interstitial pressure and mechanism for keeping the alveoli dry:There are small openings between the alveolar epithelial cells through which large protein molecules and large quantities of water and electrolyte can pass. Pulmonary capillaries and the pulmonary lymphatic system maintain a slight negative pressure in the interstitial spaces in which excess fluid is either carried away through the pulmonary lymphatics or is absorbed into the pulmonary capillaries. The alveoli are kept dry except for small amount of fluid that seeps from the epithelium onto the lining surfaces of the alveoli to keep them moist.

Pulmonary edema: any factor that causes the pulmonary interstitial fluid pressure to rise from the negative to positive will cause filling of the pulmonary interstitial spaces and alveoli with large amount of fluid.

1) Left heart failure or mitral valvular disease which causes increase in the pulmonary capillary pressure and flooding of the interstitial spaces and alveoli.

2) Damage to the pulmonary capillary membrane caused by infections e.g., pneumonia or by breathing noxious substances e.g., chlorine gas or sulfur dioxide gas, which causes leakage of both plasma proteins and fluid out of the capillaries.

The most common causes ofpulmonary edema

Acute pulmonary edema occur when the pulmonary capillary pressure rises above the normal level required to maintain negative interstitial pressure, edema occur with 20 to 30 minutes if the capillary pressure rises as much as 25 to 30mmHg above the safe level (acute left heart failure if the pulmonary capillary pressure rises above 50mmHg).

The fluids in the pleural cavity

During the breathing, the lungs expand and contract within the pleural cavity. This movement is facilitated by a thin layer of fluid lies between the parietal and visceral pleurae. The pleural fluid is only few milliliters and the extra amount is pumped to the lymphatic vessels.

Transport of O2 and CO2 between the alveoli and the tissue cells:

Diffusion: movement of O2 from the alveoli into the pulmonary blood and diffusion of CO2 in the opposite direction. Gases dissolved in the fluids and body tissues. Diffusion require energy which is provided by the kinetic motion of the molecules of gas themselves.

The pressure of gas is caused by the constant kinetic movement of gas molecules against the surface. In respiratory physiology, there is a mixture of gases mainly of O2, N2, and CO2. The rate of diffusion of each of these gases is directly proportional with the partial pressure of the gas.

Pressure of gases dissolved in water and tissue:The pressure of gases dissolved in fluid is similar to their pressure in the gaseous phase and they exert their own individual partial pressure.

Partial pressure of gases (in a mixture)

Dissolved gas moleculesDissolved gas molecules

AA BB

Diffusion of gases through fluids pressure difference causes net diffusion:

The net diffusion of gas from the area of high concentration to the area of low concentration = the number of molecules bouncing in the forward direction the number of molecules bouncing in the opposite direction (pressure difference for diffusion).

The solubility of gas, CO2 is more soluble than O2

The relative diffusion rates for different gases:O2 1.0CO2 20.3N2 0.53

The gases of respiratory importance are highly soluble in cell membrane (all are highly soluble in lipids). Also, diffusion of gases through the tissue, including through the respiratory membrane, is equal to the diffusion of gases through water. CO2 diffusion 20 times more rapidly than O2 because of its high solubility in tissue fluids.

Diffusion of gases through tissues

Composition of alveolar air and its relation to atmospheric air:

Alveolar air is partially replaced by atmospheric air with each breath.O2 is constantly absorbed from the alveolar air.CO2 constantly diffuses from the pulmonary blood into the alveoli.The dry atmospheric air enters the respiratory passage is humidified before it reaches the alveoli.

Partial pressures of respiratory gases as they Partial pressures of respiratory gases as they enter and leave the lungs (at sea level)enter and leave the lungs (at sea level)

Atmospheric Air*Atmospheric Air*(mmHg)(mmHg)

Humidified AirHumidified Air(mmHg)(mmHg)

Alveolar AirAlveolar Air(mmHg)(mmHg)

Expired AirExpired Air(mmHg)(mmHg)

597.0 (78.62%)597.0 (78.62%)

563.4 (74.09%)563.4 (74.09%)

569.0 (74.9%)569.0 (74.9%)

566.0 (74.5%)566.0 (74.5%)

159.0 (20.84%)159.0 (20.84%)

149.3 (19.67%)149.3 (19.67%)

104.0 (13.6%)104.0 (13.6%)

120.0 (15.7%)120.0 (15.7%)

0.3 (0.04%)0.3 (0.04%)

0.3 (0.04%)0.3 (0.04%)

40.0 (5.3%)40.0 (5.3%)

27.0 (3.6%)27.0 (3.6%)

3.7 (0.50%)3.7 (0.50%)

47.0 (6.20%)47.0 (6.20%)

47.0 (6.2%)47.0 (6.2%)

47.0 (6.2%)47.0 (6.2%)

NN22 OO22 COCO22 HH22OO

The rate at which alveolar air is renewed by atmospheric air:

The amount of air remaining in the lungs at the end of normal expiration ~ 2300ml (FRC). Only 350ml of air is brought into the alveoli with each breath. Therefore, the amount of alveolar air is replaced by new atmospheric air with each breath is only 1/7th of the total. This slow replacement of alveolar air is important in preventing sudden changes in gaseous concentrations in the blood.

O2 concentration and pressure in the alveoli:

O2 is continuously absorbed into the blood of the lungs and replaced from the atmosphere. So its concentration is lower in the alveoli if its absorbed more rapidly. It’s concentration is higher in the alveoli if new O2 is breathed rapidly.

The solid curve represents O2 absorption at a rate of 250ml/min, and the dotted curve at 1000ml/min. At normal ventilatory rate of 4.2 liters/min and O2 consumption of 250ml/min, the normal operating point is point A. During moderate exercise when O2 is absorbed, each minute 1000ml, the rate of alveolar ventilation is increase 4-fold to maintain the alveolar PO2 at normal value of 104mmHg. Also marked increase in the alveolar ventilation never increase the alveolar PO2 above 149mmHg if the person breathing normal atmospheric air.

CO2 concentration and pressure in the alveoli:CO2 is continuously formed in the body, discharged into the alveoli, then removed by ventilation.

The solid curve represents the normal rate of CO2 excretion of 200ml/min, at normal ventilation of 4.2 liters/min, the operating point for alveolar PCO2 is at point A at 40mmHg. Alveolar PCO2 increases directly in proportion to the rate of CO2 excretion, as represented by the dotted curve for 800ml CO2 excretion/min. Alveolar PCO2 decreases in inverse proportion to alveolar ventilation.

Diffusion of gases through the respiratory membrane

Respiratory unit is composed of respiratory bronchiole, alveolar ducts, atria, and alveoli (about 300 million in the 2 lungs, each alveolus with an average diameter of 0.2 millimeter). The walls of the alveoli, alveolar ducts and other parts of the respiratory unit are extremely thin within, there are interconnecting capillaries which is called the respiratory membrane or pulmonary membrane.

Respiratory membrane

The total surface area of the respiratory membrane is ~ 50 to 100 m2 in normal adult. This large surface area to allow rapid diffusion of gases through the respiratory membrane

Factors that affect the rate of gas diffusion through the respiratory membrane:1. The thickness of the respiratory membrane.

thickness of the respiratory membrane e.g., edema rate of diffusion. The thickness of the respiratory membrane is inversely proportional to the rate of diffusion through the membrane.

2. Surface area of the membrane. Removal of an entire lung decreases the surface area to half normal. In emphysema with dissolution of the alveolar wall S.A. to 5-folds because of loss of the alveolar walls.

Epithelial basement Epithelial basement membranemembrane

Alveolar epitheliumAlveolar epithelium

Interstitial Interstitial spacespace

Capillary basement Capillary basement membranemembrane

Capillary endotheliumCapillary endothelium

Fluid and Fluid and surfactant surfactant layerlayer

Red Red blood blood cellcell

AlveolusAlveolus CapillaryCapillary

DiffusionDiffusion

DiffusionDiffusion CO2CO2

O2O2

3. The diffusion rate of the specific gas. Diffusion coefficient for the transfer of each gas through the respiratory membrane depends on its solubility in the membrane and inversely on the square root of its molecular weight. CO2 diffuses 20 times as rapidly as O2.

4. The pressure difference between the two sides of the membrane (between the alveoli and in the blood). The alveolar pressure represents a measure of the total number of molecules of a particular gas striking a unit area of the alveolar surface of the membrane in unit time. When the pressure of the gas in the alveoli is greater than the pressure of the gas in the blood as for O2, net diffusion from the alveoli into the blood occurs, but when the pressure of the gas in the blood is greater than the pressure in the alveoli as for CO2, net diffusion from the blood into the alveoli occurs

Diffusing capacity: is the volume of a gas that diffuses through the membrane each minute for a pressure difference of 1mmHg.The diffusing capacity for O2: In the average young male adult, the diffusing capacity for O2 under resting conditions averages 21ml/min/mmHg. The mean O2 pressure difference across the respiratory membrane during normal, quiet breathing is ~ mmHg. (11 x 21 = 230 ml) of O2 diffusing through the respiratory membrane each minute equal to the rate at which the body uses O2.

Diffusing capacity of therespiratory membrane

During strenuous exercise or other conditions that increase the pulmonary blood flow and alveolar ventilation, the diffusing capacity for O2 increases to 65ml/min/mmHg (3 times the diffusing capacity under resting conditions). This increase is caused by opening up the dormant pulmonary capillaries to increase the surface area of the blood into which O2 can diffuse.

Changes in O2 diffusing capacityduring exercise

Ventilation-perfusion ratio (V/Q)It is the ratio of alveolar ventilation to pulmonary blood flow per minute. The alveolar ventilation at rest (4.2L/min) and is calculated as:

Alveolar ventilation = respiratory rate x (tidal volume – dead space air).The pulmonary blood flow is equal to right ventricular output per minute (5L/min).

This value is an average value across the lung.At the apex, V/Q ratio = 3.At the base, V/Q ratio = 0.6.So the apex is more ventilated than perfused, and the base is more perfused than ventilated.

During exercise, the V/Q ratio becomes more homogenous among different parts of the lung.

CO2 diffuses through the respiratory membrane so rapidly that the average PCO2 difference between the alveolar and capillary blood is 1mmHg. The diffusion capacity for CO2 is 20 times that of the O2, so we expect that the diffusion capacity for CO2 under resting conditions ~ 400 to 450ml/min/mmHg and during exercise is about 1200 to 1300 ml/min/mmHg.

Diffusing capacity for CO2

The PO2 in the alveolus is 104mmHg and in the venous blood entering the capillary is 40mmHg because large amount of O2 has been removed from this blood as it has passed through the peripheral tissues. The initial pressure difference that causes O2 to diffuse into the pulmonary capillary is 64mmHg (104-40=64mmHg). The rapid rise in blood PO2 as the blood pressure through the capillary, that the PO2 rises to equal that of the alveolar air by the time the blood moved a 1/3rd of the distance through the capillary becoming 104mmHg

Uptake of O2 from the alveoli by the pulmonary blood

Uptake of O2 by the pulmonary blood

during exerciseDuring strenuous exercise, the body requires as much as 20 times the normal amount of O2. Also, because of the increased cardiac output, the time that the blood remains in the capillary may be reduced to less than half normal. Therefore, oxygenation of the blood could suffer. Because of safety factor for diffusion of O2 through the pulmonary membrane, the blood is almost completely saturated with O2 when it leaves the pulmonary capillaries for 2 reasons:

During exercise, the rate of O2 diffusion through the pulmonary membrane increases to 3 fold, due to the number of capillaries.During blood flow through the capillary, the blood becomes almost saturated with O2 by the time it has passed through the 1/3rd of the pulmonary capillary.

The PO2 in the arterial blood reaching the capillary is 95mmHg, the PO2 in the interstitial fluid is 40mmHg and 23mmHg inside the cells. So there is a tremendous initial pressure difference that causes O2 to diffuse very rapidly from the blood into the tissues, so that the capillary PO2 falls to 40mmHg in the interstitium. The blood entering the veins from the tissue capillaries is about 40mmHg.

Diffusion of O2 from the tissuecapillaries into tissue fluid

If the blood flow through the tissue is increased, large quantities of O2 are transported into the tissue in a given period of time, and the tissue PO2 is increased. The upper limit to which the PO2 can rise, even with maximum blood flow is about 95mmHg (because this is the O2 pressure in the arterial blood). Conversely, if the cells utilize more O2 for metabolism than normal, this reduce the interstitial fluid PO2.

Effect of rate of blood flow and tissue metabolism on interstitial

fluid PO2

O2 is used by the cells. Therefore, the intracellular PO2 remains lower than the PO2 in the capillaries. The intracellular PO2 is about 23mmHg (range between 5 to 40mmHg). Because only 1 to 3mmHg of O2 pressure is normally required for full support of the metabolic processes of the cell, so that even with this low PO2 of 2mmHg is more than adequate and safe for the metabolic processes.

Diffusion of O2 from the capillariesto the tissue cells

When O2 is used by the cells, most of it becomes CO2 and this increases the intracellular PCO2. CO2 diffuse from the cells into the tissue capillaries and then carried by the blood to the lungs, when it diffuses from the pulmonary capillaries into the alveoli. CO2 diffuses in opposite direction to the diffusion of O2. CO2 diffuses 20 times as rapidly as O2. Therefore, the pressure differences that cause CO2 diffusion are far less than the pressure differences required to cause O2 diffusion. These pressures are the following:Intracellular PCO2 is about 46mmHg, the interstitial PCO2 is about 45mmHg, there is only a 1mmHg pressure difference.

Diffusion of CO2 from the tissue cells

into the tissue capillaries and from the pulmonary capillaries into the

alveoli

PCO2 of the arterial blood entering the tissues 40mmHg, PCO2 of the venous blood leaving the tissue is about 45mmHg. So that tissue capillary blood is in an equilibrium with the interstitial PCO2 45mmHg.PCO2 of the venous blood entering the pulmonary capillaries in the lungs 45mmHg, PCO2 of the alveolar air is 40mmHg, only 5mmHg pressure difference causes CO2 to diffuse out of the pulmonary capillary into the alveoli.The PCO2 of the pulmonary capillary blood falls exactly to equal the alveolar PCO2 of 40mmHg before it passed more than about 1/3rd the distance through the capillaries

Effect of tissue metabolism and blood flow on interstitial PCO2:Increased tissue metabolism increases the CO2 in the tissue, but increased blood flow carries more CO2 away and decreases its concentration.

About 97% of O2 is transported in chemical combination with haemoglobin and 3% is carried in the dissolved form in the plasma and cells.Under normal conditions O2 carried to the tissues almost entirely by haemoglobin. O2 molecule combines loosely and reversibly with the heme portion of the Hb. When the PO2 is high (as in the pulmonary capillaries) O2 binds with the Hb, but when the PO2 is low (as in the tissue capillaries) O2 is released from the Hb.

Function of haemoglobin totransport O2 in arterial blood

It shows the progressive increase in the percentage saturation of the Hb with the increase in the PO2 in the blood. The PO2 in the arterial blood is about 95mmHg and saturation of Hb with O2 is about 97%. In the venous blood returning from the tissues, the PO2 is about 40mmHg and the saturation of Hb with O2 is about 75%.

The oxygen-haemoglobindissociation curve

In a normal person, 15gm of Hb in each 100ml of blood, each gram of Hb bind with a maximum of about 1.34ml of O2. At 100% saturation, the Hb in 100ml of blood can combine with 20ml of O2.

Maximum amount of O2 than cancombine with the Hb of the blood

In the arterial blood 97/100 x 1.34 x 15gm of Hb = 19.4ml of O2 bound with Hb.In the venous blood 75/100 x 1.34 x 15gm = 14.4ml of O2.So under normal conditions about 5ml of O2 are transported to the tissues by each 100ml of blood.

The amount of O2 released from the

Hb in the tissues

In heavy exercise the muscle cells utilize O2 rapidly, which causes the interstitial fluid PO2 to fall to 15mmHg. Only 4.4ml of O2 remains bound to with Hb in each 100ml of blood (19.4 – 4.4 = 15ml of O2 are transported by each 100ml of blood). Also cardiac output can increase to 7 fold. The amount of O2 transported to the tissue increase to 20 folds (3 x 7 = 21).

Transport of O2 duringstrenuous exercise

3 important conditions1) The pH or (H+ conc),2) the temperature,3) and the concentration of 2,3 diphosphoglycerate

(2,3-DPG). 4) PCO2 concentration (Bohr effect) all shift the

curve to the right.

P50: it is the partial pressure of O2 at which 50% of Hb is saturated with O2. P50 means right shift lower affinity for O2. P50 means left shift higher affinity for O2.

Factors affecting the affinity of Hb for O2

The figure shows the relationship between intracellular PO2 and the rate of O2 usage at different concentrations of ADP. When the rate of ADP concentration is altered, the rate of O2 usage changes in proportion to the change in ADP concentration.

Metabolic use of O2 by the cells

ADP = 1ADP = 1½ normal½ normal

ADP = NADP = Normal resting levelormal resting level

ADP = ADP = ½ normal½ normal

Only 3% of the total O2 is transported in the dissolved state composed with 97% transported by Hb.

In the arterial blood, the PO2 is 95mmHg 0.3ml of O2 is dissolved in dl of blood. In venous blood PO2 is 40mmHg (as in tissue capillaries) 0.12ml of O2 is dissolved in dl of blood.

Transport of O2 in the dissolved state

Tissue consume the O2 directly.It depends on the PO2 (so higher alveolar PO2 will increase the amount of O2 carried in the dissolved state e.g., hyperbaric O2 therapy as in CO poisoning).

Combination of Hb with CO displacement of O2:CO combines with Hb and it displace O2 from Hb. It binds with about 250 times as much tenacity as O2.

The importance of dissolved form

Under normal resting conditions ~ 4ml of CO2 is transported from the tissue to the lungs in each 100ml of blood.

Transport of CO2 in the blood

Chemical forms in which CO2 is transported

1-7% of CO2 is transported in the dissolved state.

2-70% of CO2 is transported in the form HCO3¯. HCO3¯ diffuses out of the RBC with Hb and Cl¯ ions diffuse into the RBC (chloride shift).

3-23% of CO2 is transported in combination with Hb and plasma proteins as carbamino-Hb: CO2 reacts with the amino group of the Hb to form the carbamino-Hb (CO2HHB). This reaction is reversible when CO2 is released into the alveoli.

Change in blood acidity duringCO2 transport

CO2 H+ pH ( acidity of the blood stimulate its release from the blood through the lungs).

The respiratory exchange ratio:

R value changes under different metabolic conditions. If the person is utilizing carbohydrate for body metabolism. R value rises to 1 and it decreases to 0.7 if the person is utilizing fat for metabolism. If the person consume normal diet (CHO, fat and protein), R value is ~ 0.825.

%)80(8.05

4

2

2

uptakeOofrate

outputCOofrateR

Regulation of respiration

1-Neural control of respiration

2-Chemical control of respiration

Neural control of respiration

The respiratory center is composed of groups of neurons located bilaterally in the medulla and pons divided into 3 major collections of neurons:

1) Dorsal respiratory group in the dorsal portion of the medulla and mainly inspiratory neurons.

2) Ventral respiratory group in the ventralateral part of the medulla which contains both expiratory and inspiratory neurons.

3) Pneumotaxic center which is located dorsally in the superior portion of the pons, which helps control both the rate and pattern of breathing.

The dorsal respiratory group

A group of neurons extends in most of the dorsal length of the medulla within the nucleus of the tractus solitarius and it contains the termination of both the vagal and glossopharyngeal nerves from the peripheral chemoreceptors (the baroreceptors). The dorsal neurons discharge rhythmically so it is called the rhythmicity center. The signals begins very weak at first and then increases steadily for 2 seconds and then it ceases to allow expiration. Another inspiratory signal begins for another cycle (the inspiratory signal is a ramp signal).

The pneumotaxic center limits the duration of inspiration and increases the respiratory rate:The pneumotaxic center is located dorsally in the upper pons, it transmits inhibitory signals to the inspiratory area to switch off the inspiratory ramp.

The ventral respiratory group of neurons functions in both inspiration and expiration:Located anteriolateral to the dorsal groups. The ventral group of neurons inactive during normal quiet respiration. Stimulation of the neurons cause some inspiratory or expiratory neurons to be stimulated. The ventral neurons active during increase pulmonary ventilation as in exercise.

The Hering-Breuer inflation reflex

When the lungs are inflated, this causes stimulation of “stretch receptors” in the walls of bronchi and bronchioles which is transmitted through the vagus nerve to the dorsal respiratory groups to “switch off” inspiration.

Chemical control of respiration

Excess CO2 of H+ ions mainly stimulate the respiratory center to increase the strength of both inspiratory and expiratory signals to the respiratory muscles.

Central chemoreceptors

Located on the ventrolateral surfaces of the medulla oblongata (bilaterally). This area is highly sensitive to changes in either blood PCO2 or H+  ion concentration. H+ ions can’t cross the blood-brain barrier (BBB). So CO2 cross the BBB and react with H2O to form carbonic acid and then dissociate into H+ ion and HCO3¯, then the H+ ion which stimulate the chemosensitive area in the brain.

Peripheral chemoreceptorsThese chemical receptors located in several areas outside the brain in the carotid bodies and in the aortic bodies. They are highly sensitive to changes in O2 in the blood, although they respond to changes in CO2 and H+ ion concentration too. Afferent fibers pass from the carotid bodies via the glossopharyngeal nerves and afferent fibers from the aortic bodies pass via the vagal nerves to the dorsal respiratory area to stimulate respiration. So fall in arterial O2 concentration below normal or increase in either CO2 concentration or H+ ion concentration. Fall in blood PO2 excite the chemoreceptor which will cause increase respiration.

Defined as deficient O2 supply to the tissue. In cyanide poisoning, the cytochrome oxidase enzyme is completely blocked by the cyanide to such an extent that the tissue can’t utilize O2 even though plenty is available.

Effects of hypoxia on the body:Severe hypoxia can cause death of the cells, but in less severe cases it results in:

Depressed mental activity and coma. Reduced work capacity of the muscles.

Hypoxia

Treatment of hypoxia

By administration of O2 by:

Placing the patient head in a “tent” of O2.

Allowing the patient to breath either pure or high concentration of O2 from mask.

Administration of O2 through an intranasal tube.

This O2 therapy is effective in case of atmospheric hypoxia, hypoventilation hypoxia and in hypoxia caused by impaired alveolar membrane diffusion.

In hypoxia caused by anemia or abnormal hemoglobin, O2 therapy is less effective because normal O2 is available in the alveoli but the defect is in transporting O2 to the tissues.Also in hypoxia caused by inadequate tissue use of O2, O2 therapy is of no benefit because O2 is available in the alveoli and no abnormality in O2 pickup by the lungs or transport to the tissues but tissue enzyme are incapable of utilizing the O2 that is delivered

HypercapneaMeans excess CO2 in the body fluids. It occurs in association with hypoxia which is caused by hypoventilation or circulatory deficiency. Hypoxia caused by too little O2 in the air, too little Hb, or poisoning of oxidative enzymes, hypercapnea isn’t concomitant of these types of hypoxia. If hypoxia caused by poor diffusion through the pulmonary membrane hypercapnea doesn’t occur because CO2 is 20 times more diffusible than O2 and if it begins to occur it will stimulate pulmonary ventilation to correct the hypercapnea.

In hypoxia cause by hypoventilation, hypercapnea occur with hypoxia because CO2 transfer between the alveoli and the atmosphere is affected. In circulatory deficiency, tissue hypercapnea occur with tissue hypoxia due to diminished CO2 removal from the tissues. When the alveolar PCO2 is above 60-75mmHg, this lead to “air hunger” or called “dyspnea” rapid deep inspiration.

If CO2 rises from 80-100mmHg, the person becomes lethargic and semicomatose.

If PCO2 rises from 120-150mmHg, this lead to death due to depression of the respiratory center.

Cyanosis

Bluish discoloration of the skin and mucus membrane due to more than 5gm/dL of deoxygenated Hb in the blood.

Anaemic person can’t be cyanotic, he hasn’t enough Hb for 5gm to be deoxygenated in 100mL of blood.

In polycythemia, excess Hb that can become deoxygenated can cause cyanosis even under normal conditions.