Functions of Respiratory System:

Each part of the resp sys has a unique function

Summarized in the image below

Breathing is the main function we will discuss in detailes!

Breathing is divided into two parts

--> Ventilation

--> Oxygenation

Ventilation

• Defined as the repetitive movement of gas into and out of the lungs.

Into the resp sys --> Inhalation

Out of the resp sys --> Exhalation

Since it is a movement, then the Laws of Motion will apply to it

We will focus here on

The first law:

A body in motion remains in motion

A body at rest remains at rest

UNLESS acted upon by a force

So to create any movement, you need some kind of power, energy, force!

The third law:

For every action

There is a reaction

EQUAL in amount, OPPOSITE in direction!

So whenever movement is created, it will be faced by resistance!

In conclusion,

Ventilation will happen Only if sufficient pressure is applied to

overcome factors opposing its movement

In the resp sys, we have two factors that needs to be overcome

1. Elastic Recoil

To understand it you need to understand --> Volume Pressure Relationship

-->Compliance

2. Viscous Forces

To understand it you need to understand --> Flow Pressure Relationship

--> Resistance

A. Elastic Recoil

What regulates this balance?

1. Pressure-Volume Relationships
2. Compliance

1. Pressure-Volume Relationships

a) The pressures:

• Although it is useful from a conceptual standpoint to discuss the lungs and chest wall as if they were isolated structures, they are, of course, linked together as a single unit.
• Nevertheless, we can still separately evaluate their elastic recoil by having a subject perform a step-wise exhalation following a maximal inspiration.
• At each point, the subject relaxes against an occluded external airway (no air flow) and both the volume change and the pressure gradient across the lungs and chest wall are measured.

The sequence of events reverses during tidal expiration,

• When inspiratory muscles relax, dimensions of the thoracic cage decrease, PPl increases from −8 back to −5 cmH2O and Palv increases one cmH2O above Patm.
• As a result, air flows outside the alveoli following the pressure gradient, Fig. 2b.
• Tidal expiration is therefore a passive process, which needs no further muscle contraction.

During tidal breathing, whether inspiratory or expiratory,

• intra-airways (Paw) pressure is always more than PPl.
• This explains why small airways are always opened, even at the end of tidal expiration.

If inspiration above the tidal limit is required,

• accessory muscles of inspiration must be activated.
• Thoracic cage expands more leading to higher drop in PPl and Palv compared with tidal inspiration
• which explains why more air is delivered to the alveoli compared with tidal inspiration.

Alternatively, expiration below the tidal level is an active process that

• requires contraction of expiratory muscles.
• During forceful expiration, the thoracic cage is compressed to the maximum.
• Both PPl and Palv rise above Patm;
• however, Palv remains more than PPl due to the effect of elastic recoil pressure (Pel) of the alveolar wall.

As demonstrated in Fig. 2c, Paw decreases from the area next to the alveoli upwards.

• This gradual drop in Paw is secondary to simultaneous increase in the airways resistance towards the trachea.
• Taking into consideration the relatively constant PPl around the lung, each small airway can be subdivided into three segments (Fig. 2c):

1. An inflated segment, where PPl is lower than Paw.
2. An equal pressure point, where PPl is equal to Paw.
3. An airflow limiting segment, where PPl is higher than Paw

2. Compliance

The elastic recoil of the lungs, chest wall, and respiratory system can be quantified in a number of ways.

As discussed above, pressure-volume relationships can be plotted by performing sequential measurements during step-wise exhalation.

Although this method provides a great deal of information, it is time-consuming and requires both cooperation and practice on the part of the subject.

In addition, the information obtained cannot easily be converted to numerical form.

Alternatively, a single measurement of pressure and volume can be made.

Although it is rapid and relatively easy to perform, such a measurement provides information about elastic recoil only at a specific lung volume.

A compromise between these approaches is to measure elastic recoil pressure at two volumes.

The difference between these pressures (∆P) and volumes (∆V) can then be used to calculate the compliance (C), where

C = ∆V/∆P.

Note that compliance varies inversely with elastic recoil.

That is, when compliance is low, a given pressure increment produces only a small increase in volume (i.e. the structure is stiff),

whereas

A large increase occurs when the compliance is high.

By measuring the appropriate transmural pressures during relaxation against an occluded airway, the compliance of the lungs (CL), chest wall (CW), and respiratory system (CRS) can be determined from the following equations:

CL = ∆V/∆(Pao - Pes)

CW = ∆V/∆Pes

CRS = ∆V/∆Pao

Note that compliance is simply the slope of the volume-pressure curves shown

What is the origin of Elastic Recoil??? 

Elastic recoil is produced by two factors.

1- Tissue forces  

Result from the deformation of elastic elements in the lung parenchyma (i.e. elastin and collagen) and chest wall (i.e. ribs, muscles, and cartilage) and are easily understood using the analogy of a metal spring.

2- Surface forces, on the other hand,

• Results from the unique elastic properties produced by the alveoli
• Like all air-liquid interfaces, surfactant generates surface tension which tends to reduce alveolar size and increase the pressure required to maintain a given lung volume.
• According to Law of Laplace, all air-liquid interfaces (bubble) generate surface tension which tends to reduce the size and increase the pressure required to maintain a given volume.
• In this sense, alveoli are similar to soap bubbles, in which surface tension acts to both decrease volume and increase internal pressure according to the Laplace equation:

1- Pressure-Flow Relationship

• As gas moves through the airways, pressure is required to overcome both:

* Friction at the airway surface and

* cohesive forces between gas molecules

what are the factors influencing ∆P?

1)- The most important determinant of ∆P is the caliber of the airway,

Since ∆P varies inversely with the 4th or 5th power of the airway radius (depending on whether flow is laminar or turbulent).

This means that viscous forces and the pressure required to overcome them will increase by at least 16 times when airway radius is reduced

by one-half

2- VENTILATION

Partial Pressure of Respiratory Gases 

• In a gas mixture, the pressure exerted by a gas is equal to the product of its fractional concentration (F) and the total pressure of all the gases in the mixture.

Pgas = Ptotal x Fgas

• For example, oxygen comprises about 21% of dry air (i.e. FO2 = 0.21). At sea level at a total barometric pressure (PB) of 760mmHg, the partial pressure of oxygen can be calculated as:

PO2 = PB x FO2

PO2 = 760 x 0.21 = 160 mmHg

• Dry air contains approximately 79% nitrogen (FN2 = 0.79) and only 0.04% CO2 (FCO2 = 0.0004). The partial pressures of these gases in dry air can be calculated in the same way:

PN2 600mmHg

PCO2 0.3mmHg

• When air enters the conducting airways of the lungs, it is heated and humidified.

• The partial pressure of the water vapor (PH2O) is approximately 47mmHg at body temperature.

• This means that the total pressure exerted by dry gas decreases, and the partial pressure of each gas falls. In the airways, gas partial pressure is calculated as:

PIgas = (PB – PH2O) x Fgas where PIgas is the partial pressure of inspired gas.

For example, PIO2 = (760 – 47) x 0.21 = 150mmHg.

• The partial pressure of nitrogen and carbon dioxide are calculated in the same way.

PIN2 563mmHg

PICO2 0.3mmHg

• Once gas enters the alveoli, diffusion occurs leading to a drop in the PO2 and an increase in PCO2.
• The partial pressure of gases in the alveoli cannot be measured, but they can be estimated.
• For practical purposes, we can assume that the mixed alveolar PCO2 (PACO2) is equal to the PCO2 of arterial blood (PaCO2).
• The alveolar air equation is used to calculate the average alveolar PO2 (PAO2) assuming “ideal” conditions, that is, no mismatching of ventilation and perfusion (see lecture on ventilation-perfusion relationships).

PAO2 = (PB – PH2O) FIO2 – PACO2 

R 

• In this equation, R is the respiratory exchange ratio.
• This is the volume of CO2 that enters the alveoli divided by the volume of O2 that diffuses into the pulmonary capillary blood over a given period of time (VCO2/VO2).
• R must also represent the ratio of CO 2 produced to O2 consumed by the tissues.
• For our purposes, R is assumed to be 0.8. That is, there is more O2 leaving the lung than CO2 entering it.
• This means that the P O2 will fall by more than the increase in PACO2.
• It will decrease by PACO2/R.
• The partial pressure of gases in the alveoli are approximately:

PAO2 100mmHg

PACO2 40mmHg

PAN2 573mmHg

• The alveolar air equation is used not only to estimate mixed alveolar PO2 but also to derive an important clinical parameter – the difference between the calculated alveolar and the measured arterial PO2.
• This value is referred to as the PA-aO2 or the A-a gradient and is normally 8-12 mmHg.
• As discussed in subsequent lectures, PA-PaO2 increases in the presence of ventilation-perfusion mismatching, shunt, and diffusion impairment.

Minute Ventilation, Alveolar Ventilation, and Anatomic Dead Space 

• The tidal volume (VT) is the volume of gas that enters the lungs during a single breath.
• It is important to recognize that a significant portion of each tidal breath never reaches the alveoli or participates in gas exchange.
• This portion is named the physiologic dead space and it is divided into two spaces:

The physiologic dead space is divided into two spaces:

1. Anatomic dead space:

• This is the volume of gas that fills the nose, mouth, pharynx, larynx, and conducting airways.
• Since this gas is never in contact with pulmonary capillary blood, it does not participate in gas exchange.
• As expected, the anatomic dead space volume varies with body (and airway) size.
• Although it can be measured, for practical purposes it is often estimated as 1ml per pound of ideal body weight.

2. Alveolar dead space:

• It is the portion of the tidal breath that reaches alveoli that either

--> receive no blood flow or

--> under-perfused relative to the amount of ventilation they receive

• The amount of gas entering the dead space is referred to as the dead space volume (VD).
• The alveolar volume (VA) is the volume of gas that actually reaches the alveoli AND participates in gas exchange during a tidal breath.
• It is, therefore, the difference between tidal volume and dead space volume.

VA = VT – VD

• The total volume of gas that enters or leaves the lungs each minute is referred to as the minute ventilation (VE).
• It is the product of tidal volume and respiratory rate (RR).

VE = VT x RR

• The volume of gas that enters and leaves the physiologic dead space each minute is called the dead space ventilation  

VD = VD x RR

• The alveolar ventilation (VA) is the volume of gas entering and leaving the lungs each minute that participates in gas exchange:

VA = VA x RR

• It is also the difference between minute ventilation and dead space ventilation:

VA = VE – VD

The Influence of Alveolar Ventilation on PACO2 

• The partial pressure of carbon dioxide in the alveolar gas (PACO2) is determined by the rates at which CO2 enters and leaves the alveoli.
• The rate at which CO2 enters the alveoli is proportional to the partial pressure of CO2 in mixed venous blood (PvCO2), which, in turn, depends on the rate of CO2 production by the tissues (VCO2).
• That is,

PACO2 α VCO2

• The rate at which CO2 is removed from the alveoli is directly proportional to alveolar ventilation.
• PACO2 is, therefore, inversely related to VA.

PACO2 α 1 / VA

• Putting these two equations together yields:

PACO2 α VCO2 / VA

or

PACO2 = K x VCO2 / VA

• Since alveolar and arterial PCO2 are essentially equal, we may rewrite this equation as:

PaCO2 = K x VCO2 / VA

• This means that if VCO2 is constant, PaCO2 will double if VA is cut in half.
• If VA is doubled, PaCO2 will be reduced by one-half.

• Since VA = VE – VD, this equation can be rewritten as:

PaCO2 = K x VCO2 / (VE - VD)

or as

PaCO2 = K x VCO2 / VE [1 – (VD / VT)]

• This final equation demonstrates the importance of the dead space to tidal volume ratio.
• As VD/VT rises, VE must increase to maintain the same PaCO2.

The Influence of Alveolar Ventilation on PAO2 

• Unlike PACO2 (and PaCO2), alveolar ventilation does not directly affect PAO2.
• Instead, its effect is indirect and produced by changes in PACO2.
• By examining the alveolar air equation, it is evident that PAO2 and PACO2 must move in opposite directions. That is, if PACO2 (PaCO2) increases, PAO2 will fall.
• The opposite will occur when PCO2 decreases.

Regional Distribution of Alveolar Ventilation:

In normal subjects

• In an upright subject, Pleural pressure progressively increases (becomes less negative) between the top and bottom of the lungs (Although a single value is often used to describe the pressure in the pleural space).

• In a seated or standing subject, the volume of air reaching the alveoli increases from the apex to the base of the lungs (This can be explained by gravity-induced changes in pleural pressure)

• Since the pressure in all alveoli is zero at the end of a passive exhalation, the trans-pulmonary pressure must be higher in the upper lung zones than in the lower zones.

example 10-2=8

10-5=5

4-PERFUSION

• The lungs receive blood flow from two sources: the bronchial circulation and the pulmonary circulation.

1. The bronchial arteries

• Carry oxygenated blood from the left ventricle and originate either directly from the aorta or from intercostal arteries.
• They supply oxygen to several structures in the thorax including the conducting airways, the visceral pleura, and the esophagus.
• A large proportion of the deoxygenated bronchial venous blood drains into the pulmonary veins, thereby producing an anatomic right-to-left shunt.

2. The pulmonary circulation

• Carries the mixed venous blood from all the tissues of the body and provides oxygen to the distal airways and alveoli.
• As compared with the systemic circulation, the pulmonary arteries have

* Thinner walls

* Larger lumens

* Less vascular smooth muscle (there are no muscular vessels analogous to systemic arterioles)

• These histologic features explain three important differences between the pulmonary and systemic circulations.

1. First, pulmonary vascular resistance (PVR) is normally much less than (approximately one-tenth) that of the systemic circulation.
2. Second, pulmonary vascular resistance is fairly evenly distributed between the arteries, capillaries, and veins, whereas arteries and arterioles account for approximately 80 percent of the systemic vascular resistance.
3. Finally, the pulmonary arteries are much more distensible and compressible than their systemic counterparts.

Factors Affecting Pulmonary Vascular Resistance 

Active Factors 

• Pulmonary vascular resistance can be influenced by both neural and humoral factors, which alter vascular smooth muscle tone and vessel caliber.

Neural Factors 

• The pulmonary circulation is supplied with both sympathetic and parasympathetic innervation.
• In general, parasympathetic stimulation causes vascular dilation and a decrease in PVR.
• While increased sympathetic activity leads to vasoconstriction and an increase in PVR.

Humoral Factors 

Pulmonary vasoconstriction is caused by

• Catecholamines, (e.g. dopamine, norepinephrine, and epinephrine)
• Histamine
• PGE2, PGF2α (prostacyclin)
• Thromboxane

Pulmonary vasodilators are

• Acetylcholine
• PGE1 and PGI2 (prostacyclin)

• The most important humoral factor, however, is alveolar hypoxia.
• As PAO2 falls, vasoconstriction occurs in the pre-capillary vessels. The mechanism for this increase in vascular tone is unknown, but the effect is not mediated through the autonomic nervous system.
• Alveolar hypoxia may have a

* Direct effect on vascular smooth muscle or

* It may cause the release of other humoral mediators such as histamine, serotonin, or prostaglandins.

• Vasoconstriction may occur locally (e.g. atelectasis) or diffusely (e.g. hypoventilation, high altitude).
• Hypoxic-induced vasoconstriction is clearly a beneficial response, since it decreases blood flow to regions of the lung that are poorly ventilated.
• Unfortunately, this response is relatively weak due to the lack of vascular smooth muscle.

Passive Factors

• The distensibility, compressibility, relative lack of smooth muscle, and low intra-vascular pressure that characterize the pulmonary circulation cause PVR to be strongly influenced by a variety of extra-vascular or “passive” factors that have no effect on vascular smooth muscle tone.

Lung Volume 

• When discussing the effect of lung volume on PVR, it is important to distinguish between “alveolar” and “extra-alveolar” vessels.

• Alveolar vessels, primarily the pulmonary capillaries, are affected by alveolar volume.
• During inspiration, the increase in alveolar volume causes the capillaries to be compressed and elongated, thereby increasing the resistance of these vessels.
• As lung volume falls below FRC, this process is reversed, and PVR decreases.

• The extra-alveolar vessels are exposed to pleural pressure.
• During a spontaneous inspiration, pleural pressure falls. This increases vascular transmural pressure and vessel diameter and causes vascular resistance to decrease.
• During forced expiration below FRC, pleural pressure rises and resistance increases.
• Since both the alveolar and extra-alveolar vessels contribute significantly to total resistance, a complex relationship exits between lung volume and PVR.
• As shown in Figure 1, PVR is lowest near FRC and progressively rises with both increasing and decreasing lung volume.

•  
• In Zone 1, PA > Pa > Pv.

* Here, no blood flow occurs because the alveolar vessels are completely collapsed.

• In Zone 2, Pa > PA > Pv.

* Here, blood flow occurs, but the pressure gradient driving that flow is Pa – PA, not Pa –

Pv.

• In Zone 3, Pa > Pv > PA.

* Here, blood flow is driven by the difference between pulmonary arterial and venous pressure.

• The extent of each of these zones is dependent

1. On the magnitude of pulmonary vascular and alveolar pressures.

* For example, low intra-vascular pressures (e.g. from hypovolemia) and high alveolar pressure (e.g. forced

expiration, positive pressure ventilation) will create larger Zone 1 and 2 regions.

* On the other hand, low alveolar pressure and/or high intra-vascular pressure will increase Zone 3 regions.

2. Body position also determines the extent and location of the lung zones.

* For example, in an upright subject, Zone 1 (usually minimal or absent) is at the apex, Zone 2 is in the mid-

lung, and Zone 3 is at the base.

* In a supine subject, Zone 1 (if present) will be in the ventral portion of the lungs while Zone 3 will be in the

dorsal regions.

Fluid Flow Across the Pulmonary Capillaries 

• Like all capillaries, the junctions between the endothelial cells of the pulmonary capillaries are permeable to fluids.
• The net movement of fluid across the pulmonary capillaries is described by the Starling equation:

Qf = Kf [(Pc – Pi) – σ(πp – πi)] 

where Qf = net fluid flow;

Kf = filtration coefficient (proportional to capillary permeability);

Pc = capillary hydrostatic pressure; Pi = hydrostatic pressure in the lung interstitium;

σ = reflection coefficient (describes the ability of the capillary to retain solute);

πp = colloid osmotic pressure of the plasma;

πi = colloid osmotic pressure of the lung interstitium.

These factors are illustrated in Figure 4