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PHYSIOLOGY LECTURE OUTLINE:

RESPIRATORY PHYSIOLOGY

The Primary Functions of the Respiratory System

1. Ventilation (Inspiration - Expiration) to exchange air with the body and environment.

2. To exchange gases, oxygen and carbon dioxide, between lungs and blood.

3. To homeostatically maintain pH of body fluids.4. For vocalization and sound production.

Respiratory System

The Respiratory System includes structures involved in ventilation and gas exchange. The respiratorysystem divided into upper and lower tracts as well as conduction and respiratory portions. Below is a

basic outline of the anatomical structures:

Upper tract

Nose, nasal cavity, mouth, pharynx (throat) and larynx (voice box).

Lower tractTrachea (wind pipe), left and right primary bronchi, secondary and tertiary bronchi, bronchioles, terminal

and respiratory bronchioles, alveolar duct, alveolar sac and alveoli - the end where gas is exchanged).

The conducting portion consists of the airways from environment that lead to the exchange surface of

lungs (from nose to terminal bronchioles). The respiratory portion is from the respiratory bronchioles to

the alveoli (the surface area for gas exchange). The diameter of airways get progressively smaller, buttotal cross-sectional surface area increases. Velocity of air flow is therefore highest in trachea, lowest in

terminal bronchioles.

Air moves down its pressure gradient caused by the changes in volume of the thoracic cavity. The lungs

are located in the thoracic cavity and as the volume of the thoracic cavity increases, the pressure insidethis cavity (and thus in the lungs) decreases. As the volume of the thoracic cavity decreases, the pressure

increases. Thus, movement of thorax creates alternating conditions of high and low pressure within lungs.This creates air exchange in response to pressure gradients.

The relationship between the pressure and volume of a gas is described by Boyle's Law (P1 V1 = P2 V2).As volume decreases, pressure increases and vice versa. Changes in volume of chest cavity during

ventilation cause pressure gradients. Increase chest volume - decrease pressure - air moves in from

atmosphere. Decrease chest volume - increase pressure - air moves out from body.

The Bones and Muscles of the Thorax Surround the Lungs

The thoracic cage is created by the bones and muscles bounding the thorax: The ribs and spine; chestwall; and the diaphragm, a dome-shaped skeletal muscle forming thoracic floor.

The internal and external intercostal muscles connect the 12 rib pairs. The sternocleidomastoids and

scalenes connect the head and neck to the first 2 ribs.

Because the muscles of the thorax are skeletal muscles, they are innervated by somatic motor neurons.

Control of those neurons originates in a network of respiratory neurons in the medulla oblongata. The

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thorax is functionally a sealed cavity with 3 membranous bags. The pericardial sac contains the heart and

there are 2 pleural, each sac containing one lung.

Pleural Sacs Enclose the Lungs

Lungs are light, spongy tissue mostly occupied by air-filled spaces.. The narrow apex of each lung is at

the top of the thoracic cavity, under the upper ribs and clavicle. The bronchi connect lungs to trachea tothe atmosphere. Each lung is divided into lobes: the right lung into three lobes, and the left lung into two

(tri before you bi). Because of the space occupied by the heart, the left lung is smaller than the right. Each

lung is contained in double-walled pleural sac. It is like an air-filled balloon surrounded by a water-filledballoon. The pleura contains elastic connective tissue and capillaries. The pleural fluid holds opposingpleural layers together, creating a slippery surface allowing movement of membranes as lungs move. It

holds lungs tight and stretched against thoracic wall due to fluid's cohesiveness.

The Alveoli are the Site of Gas Exchange

An alveolus has a single layer of thin exchange epithelium and is the site of gas exchange.

There are 3 types of cells in alveoli:

1. Type I alveolar cells: Very thin, allowing gas exchange.

2. Type II alveolar cells: Thicker, secrete surfactant to ease lung expansion.

3. Alveolar macrophages: Protect and defend

Alveoli do not contain muscle fibers and cannot contract. There are elastin fibers between alveoli and

these do contribute to elastic recoil when lung tissue is stretched. Capillaries cover 80-90% of alveolarsurface forming an almost continuous blood-air contact. Gas exchange occurs by simple diffusion. The

single endothelial cell of the capillary and the single squamous epithelium of the alveoli have a fused

basement membrane in between them, this arrangement allows for a rapid diffusion of gases.

The Pulmonary Circulation is a High-Flow, Low-Pressure System

At rest, the pulmonary circulation of the cardiovascular system contains about 0.5 L of blood (10% of

total blood volume) with 75 ml in capillaries for gas exchange. The conducting portions of the respiratorytract that are not involved in gas exchange receive oxygenated arterial blood from the systemic

circulation. But the deoxygenated venous blood leaving these regions does not return to the systemiccirculation and the vena cava. Instead, it flows into the pulmonary veins along with freshly oxygenated

blood from the alveoli. The addition of deoxygenated blood slightly lowers the oxygen content of the

blood before it ever reaches the left side of the heart.

The rate of blood flow through the lungs is greater than that of other tissues. The lungs receive the entire

volume of right ventricle cardiac output (5 L/min). The pulmonary circulation has low pressure in, with anaverage pressure = 25/8 mm Hg compared to 120/80 mm Hg systemic blood pressure. This is correlated

with low pulmonary resistance.

The pulmonary arteries are much more compliant (distensibile, easier to stretch) than the aorta andsystemic arteries. Also, the total length of pulmonary blood vessels is shorter. As we already know, this

means that the right ventricle doesn't have to pump as hard to overcome peripheral resistance. This allows

for low pulmonary blood pressure. In turn, there is low net hydrostatic pressure, yielding low fluid flowinto interstitial space. Lymphatic system removes filtered fluid, a small volume of interstitial fluid, less

than 0.5 L/day of fluid is lost from the pulmonary capillaries, compared to the loss of 3 L/day from the

systemic capillaries.

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GAS LAWS

Air flow is similar to blood flow in that the driving force for air flow is a pressure gradient and it is

opposed by resistance.

Air Flow = P/R

Air is a Mixture of GasesThe atmosphere is mixture of gases and water vapor. In many parts of the world, pollutant gases such asozone, sulfur dioxide, and carbon monoxide are also present in varying trace amounts.

Dalton's Law

The total pressure of a gaseous mixture is the sum of individual gas (partial) pressures. Individual gases

move down partial pressure gradients. The sum of all partial pressures gives the total pressure for a

mixture of gases (Dalton's Law). This is how individualgas exchange occurs: gases move from areas ofhigher partial pressures to areas of lower partial pressures.

Partial pressures = Patm x % of gas in atmosphere. Partial pressures vary with amount of water vapor.

e.g., air is a mixture of gases.

N2 = 79%

O2 = 21%CO2 = 0.03%

If atmospheric pressure of air at sea level is 760 mmHg (a standard value, see section below) and air is amixture of the above gases (N2, O2 and CO2), then we can calculate the partial pressure exerted by each

gas in this mixture. The partial pressure of N2 is symbolized by PN2 and partial pressure of O2 is PO2, etc.

Calculating Partial Pressures of gases in air at sea level:

1) PN2 = 760 mm Hg x % of gas in mixture (79%, = 0.79)

= 760 mm Hg x 0.79

= 600 mm Hg

2) PO2 = 760 mm Hg x % of gas in mixture (21%, = 0.21)

= 760 mm Hg x 0.21

= 160 mm Hg

3) PCO2 = 760 mm Hg x % of gas in mixture (0.03%, = 0.003)

= 760 mm Hg x 0.003

= 0.24 mm Hg (which is negligible)

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Boyle's Law Describes Pressure-Volume Relationship of Gases

Gas pressure in a sealed container is created by the collision of gas molecules with the walls of thecontainer and each other. The smaller the container, the more frequent the collisions, resulting in higher

pressures. Boyle's Law states: P1 V1 = P2 V2. As volume decreases, pressure increases and vice versa.

Changes in volume of chest cavity during ventilation cause pressure gradients, which create air flow. Anincrease in chest volume causes a decrease in pressure - air moves in from atmosphere. A decrease inchestvolume causes an increase in pressure - air moves out from body.

The Solubility of a Gas in Liquid Depends on Pressure, Solubility and Temperature

Where air and water meet, a particular gas flows from the medium with higher partial pressure to medium

with lower partial pressure. Movement of a gas into a liquid is directly proportional to 3 factors:

1. The Partial Pressure gradient of that gas.

The greater the partial pressure gradient, the more soluble the gas in liquid.

2. Temperature of liquid and surroundings.The warmer the liquid, the less soluble the gas in it! Think of the soda can example.

3. Solubility of the gas in that liquid.Gases have different solubilities in liquids depending on their molecular chemistry.

Solubility: The more soluble a gas is, the less partial pressure needed to force it into solution. Poorersolubility requires higher partial pressures to move even small amounts of gas. Oxygen is about 20 times

less soluble in water than carbon dioxide is. This is why there is such a large partial pressure gradient for

O2 (60 mm Hg) compared to the more soluble CO2 (6 mm Hg).

Gases move between phases until equilibrium is reached. Partial pressure for a gas in the air phase atequilibrium = Partial pressure of that gas in liquid phase. This does not mean that concentrations are

equal! Concentrations depend on solubility. Thus O2 needs oxygen-carrying compounds in blood, such ashemoglobin (Hb).

VENTILATION

Ventilation = Movement of air between environment and lungs, the first exchange.

The Airways Warm, Humidify, and Filter Inspired Air

The upper airways condition inspired air before it reaches alveoli in three main ways:

1. Warm air to body temperature (37 C) to avoid alveolar damage.2. Humidify to 100% to keep exchange epithelium moist.

3. Filter out foreign material, to protect delicate lung tissue.

Most of this conditioning is done in the nasal cavity, that is why breathing through your nose has adifferent effect than breathing through your mouth. Heat and water from the mucosal lining of airways

warms and humidifies the inspired air. Filtration occurs in the nasal cavity, trachea and bronchi. These

areas are lined with ciliated epithelium that secrete mucus and dilute saline, which traps inhaled particleslarger than 2 mm and has immunoglobulins to disable microorganisms.

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The cilia of the epithelial lining is referred to as the mucus escalator. The mucus is continuously moved

toward pharynx, then swallowed or spat out! The stomach acids will further destroy microorganisms.Secretion of the watery saline layer beneath the mucus is a critical step in mucus escalator. Cilia would be

trapped in mucus without it. Cystic fibrosis is a genetic disorder wherein there are defective Cl - channels

which inhibit saline production, so the mucus is thick and hampers cilia movement.

During Ventilation, Air Flows Because of Pressure Gradients

The lungs are held to the thoracic cage by pleural fluid and contraction of thoracic muscles creates thepumping action and the pressure gradients. Air moves in response to pressure gradients. The primarymuscles involved in quiet breathing (eupnea) are: the diaphragm, intercostals and scalenes.

Forced breathing is termed hypereupnea (e.g., exercise, wind instrument, blowing up a balloon): Otherchest and abdomen muscles assist.

Air flow in respiratory system obeys the same rules as blood flow: Air flow = P/R. Flow increases as the

pressure gradient increases and decreases as resistance (R) increases.

Various Respiratory Pressures

1. Atmospheric pressure is the weight of the column of air above you. This remains relatively constant, Atsea level, this value is 760 mmHg. The pressure in the lungs must be higher or lower than atmospheric

pressure for air flow to be created.

2. Intra-alveolar pressure (PA): The pressure inside the alveoli, where gas is exchanged.

3. Intra-pleural pressure: The pressure within the pleural fluid, which is always less than intra-alveolar.

Inspiration Occurs When Alveolar Pressure Decreases

Inspiration: Somatic motor neurons trigger contraction of diaphragm, inspiratory muscles. Diaphragmcontraction - compression of dome shape, drops toward abdomen, causing 60-75% change of thoracic

cavity volume. External intercostal and scalene contraction to move rib cage upwards and out, causing 25-40% change of thoracic cavity volume. As thoracic cavity volume increases, pressure decreases and air

moves into lungs.

Typically, very small changes in alveolar pressure are required for ventilation. When thoracic cavity

volume increase, inter-alveolar pressure drops about 2 mm Hg below atmospheric (to about 758 mm Hg)and air begins to flow into alveoli. Air flow continues until pressure inside lungs equals atmospheric

pressure (760 mm Hg). At the end of inspiration, the somatic motor neurons to the diaphragm and

external intercostals stop firing, causing relaxation. This allows for passive expiration, due to elastic recoilof lungs, not muscle contraction. Expiration occurs when intra-alveolar pressure exceeds atmospheric

pressure (reaches about 762 mm Hg).

Active expiration happens during exercise or forced heavy breathing. This occurs during voluntaryexhalations and when ventilation exceeds 30-40 breaths/min. Uses internal intercostals and abdominals

muscles, expiratory muscles. Diseases afflicting skeletal muscle can adversely affect ventilation.

Myasthenia gravis is a disease in which ACh receptors on motor end plates are destroyed. Also, polio iscaused by a virus that can paralyze respiratory muscles.

Intrapleural Pressure Changes during Ventilation

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The lungs are "stuck" to the thoracic cage by pleural fluid and this aids in lung expansion and contraction.

Intrapleural pressure is sub-atmospheric and sub-intra-alveolar (usually ranging from 754 to 758 mmHg). Puncturing the pleural cavity leads to pneumothorax - a loss of the pressure gradient that keeps

lungs in their stretched state. The afflicted lung will collapse under elastic recoil. Air must be removed

from the intra-pleural space and puncture sealed to correct pneumothorax.

Lung Compliance and Elastance May Change in Disease States

Compliance is the ability of the lungs to stretch. High-compliance lungs are easily stretched. Low-

compliance lungs require more force to stretch lungs (more work, which means more energy)

Pulmonary Elastance = Elasticity. High compliance doesn't necessarily mean high elastance.

Pulmonary Elasticity vs. ComplianceElasticity (elastance, elastic recoil) means that something is able to return to its original shape after the

force stretching it has been removed. Compliant simply means that a substance can be stretched. In

physiology, the normal lung is both compliant and elastic.

Pulmonary elasticity is generated by 2 things:

1) Elastic Fibers

These fibers are an integral part of lung tissue and the natural tendency of these fibers to recoil facilitatespassive expiration.

2) Surface TensionThe alveolar surface has a thin layer of water on it. The water molecules create surface tension between

the air-fluid boundaries in the alveoli. Surface tension arises due to the strong attractive force that water

has for itself. If we remember from the beginning of semester, one of the key properties of water iscohesion (water is said to have a high affinity for itself). The polarity of the water molecule means that it

can form hydrogen bonds with itself, creating a cohesive layer of water, generating tension on the surface

of the alveoli. Surface tension tends to make the bag-shaped alveoli collapse, the smaller it is, the closerwater can be to itself and that suits the chemical nature of water. This assist elastic recoil but also

increases the work needed to stretch the air-filled lung.

Surfactant Decreases the Work of Breathing

Molecules that disrupt the cohesive forces between water molecules will reduce the surface tension

generated by water and decrease the work load of breathing. Surfactant is a phospholipoprotein made and

released by alveolar type II cells. Surfactant molecules positions themselves in between water molecules,thereby reducing surface tension, creating more compliant lungs.

Law of La PlaceThe law of La Place describes the force (pressure) that is created by a fluid sphere or bubble. The pressure

(P) depends on surface tension (T) and radius (r).

La Place's Law: P = 2 T/r

Alveoli are analogous to spheres and behave much like balloons. If two alveoli have different diameters

but are lined by fluids with the same surface tension, according to La Place's law, the pressure inside thesmaller alveolus will be greater. This would force the smaller alveoli to collapse into the larger ones. If

this were to happen, much of the convoluted surface area of the alveoli would be lost. Surfactants reduce

surface tension and prevent all alveoli from collapsing, but is more concentrated in smaller alveoli,making surface tension is less than in the larger alveoli. This acts to equalize the pressures among the

different sized alveoli.

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Newborn Respiratory Distress Syndrome (NRDS) typically occurs in premature babies, whose alveolartype II cells are not fully developed. Thus, they do not make adequate surfactant to prevent alveoli from

collapsing, giving them low-compliance lungs and collapsing alveoli. Coupled with under developed

respiratory muscles, the newborn babies have a very difficult time breathing normally and must expend agreat deal of energy to re-inflate the collapsed alveoli.

The condition known as adult respiratory distress syndrome (ARDS) is not related to surfactantproduction. ARDS is caused by pulmonary edema that occurs when pulmonary capillaries become leakyto plasma proteins as a result of infection or autoimmune disease.

Emphysema is a condition in which elastin fibers are destroyed. These lungs have high compliance andlow elastance. They exhibit poor recoil during expiration. With the changes of emphysema, the lung

becomes even more compliant but less elastic, resulting in a hyper-inflated lung and the "barrel-chest"

associated with chronic emphysema.

Restrictive lung diseases show reduced compliance. More work must be expended to stretch a stiff lung.

Possible causes: Inelastic scar tissue, insufficient surfactant production

Airway Diameter is the Primary Determinant of Airway Resistance

Resistance to air flow also influences work of breathing Poiseuille's Law: Length (L), viscosity (), and

radius (r) affect resistance (R)

The radius of the airways becomes a primary determinant of resistance. The length and viscosity arevirtually constant in respiratory system (as in the cardiovascular system). About 90% of airway resistance

is due to trachea and bronchi, but the cartilage maintains a constant diameter.

Control of Airway Resistance

The diameter of bronchiole is adjustable (they do not have cartilage and do have smooth muscle).Bronchoconstriction increases resistance and decreases amount of fresh air to alveoli. These chnages are

under nervous, hormonal, and paracrine control. If there is an increase in CO2, this leads tobronchodilation (increased air flow). If histamine is released from mast cells this causes

bronchoconstriction (decreased air flow).

Stimulation of the parasympathetic division of the ANS causes bronchoconstriction. Stimulation of the

sympathetic division causes bronchodilation.

Asthma is an allergic inflammatory condition characterized by significant bronchoconstriction. This

significantly increases resistance to air flow, particularly inhibiting passive expiration. Although

histamine release is a central trigger in the bronchoconstriction of asthma and anaphylactic shock, we nowknow that a variety of other chemical signals are also responsible. Leukotrienes are lipid-likebronchoconstrictors secreted by mast cells, macrophages, and eosinophils during the inflammatory

response. Some of the newest drugs for treating asthma are the leukotriene receptor antagonists such as

Pranlukast (Accolade).

For instance, without medical treatment, the massive bronchoconstriction of an asthma attack or allergic

reaction can be fatal. The quick administration of an epinephrine injection or a beta-agonist inhaler suchas ephedrine or isoproterenol induces bronchodilation that relieves the problem.

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Question: During anaphylactic shock and severe allergic reactions, the release of histamine causesbronchoconstriction. Why doesn't the stress of the attack cause the release of epinephrine and

bronchodilation?

Answer: It probably does, but not in amounts high enough to overcome the effects of the massive

amounts of histamine being released. A typical subcutaneous injection for anaphylactic shock contains

0.3-0.5 mg of epinephrine, a pharmacological dose.

Pulmonary Function Tests Measure Lung Volumes During Ventilation

Spirometers are used to measure volume of moving air with each breath. Obstructive lung diseasesinvolve diminished air flow during expiration due to narrowing of bronchioles.

Lung Volumes

Air moved during breathing is divided into four lung volumes:

1. Tidal volume (VT): Air volume moving in a single normal inspiration or expiration.

2. Inspiratory reserve volume (IRV): Additional volume inspired above tidal volume.

3. Expiratory reserve volume (ERV): Air exhaled beyond the end of normal expiration.

4. Residual volume (RV): Air in respiratory system after maximal exhalation (not measured directly).

Residual volume is measured by having the subject breathe helium, then calculating the dilution of thehelium upon re-breathing room air.

Lung Capacities

Lung capacities are the sums of 2 or more lung volumes (are calculated volumes).

1. IRV + ERV + VT = Vital capacity (VC). Maximum volume of air voluntarily moved throughrespiratory system

2. VC + RV = Total lung capacity (TLC)

3. VT + IRV = Inspiratory capacity

4. ERV + RV = Functional residual capacity

Patients with restrictive lung disease such as fibrosis have a decreased inspiratory capacity. Emphysemapatients who have lost elastic recoil cannot expel as much air during passive expiration and have anincreased functional residual capacity.

Auscultation of Breath Sounds

Breath sounds have wide range of normal variation and are important to use as diagnostic tools, like heart

sound auscultation. For example, air whistling through constricted airways produces the characteristic

wheezingthat accompanies an asthmatic attack.

Rate and Depth of Breathing Determine the Efficiency of Breathing

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Total pulmonary ventilation = Volume of air moved into/out of lungs each minute. Ventilation rate x tidal

volume = Total pulmonary ventilation 2. Measures effectiveness of ventilation. Normal adult rate = 12-20breaths/min - Total pulmonary ventilation of 6 L/min. Anatomic dead space = Conducting airways not

exchanging gas.

In some pathologies, there may also be alveolar dead space, that is, alveoli that are being ventilated but

not being perfused. This might occur with low blood pressure, when the capillaries in the apex of the lung

are collapsed. The combination of alveolar dead space and anatomic dead space is called physiologic deadspace.

Alveolar ventilation is more accurate indicator of ventilation efficiency. Alveolar ventilation = Ventilation

rate x (tidal volume - dead space volume). At 12 breaths/min, alveolar ventilation rate under sameconditions before = 4.2 L/min (vs. 6 L/min).

Gas Composition in the Alveoli Varies Little During Normal Breathing

PO2 and PCO2 vary during hypo- and hyperventilation. Hyperventilation: PO2 increases and PCO2 decreases.

Hypoventilation: PO2 decreases and PCO2 increases. During normal breathing, partial pressures remain

fairly constant. PO2 = 100 mm Hg. PCO2 = 40 mm Hg. Why?

Oxygen entering alveoli approximately equals oxygen entering blood Fresh air entering lungs is only

about 10% of total lung volume.

Ventilation and perfusion are matched to ensure efficient exchange and delivery of gases. Oxygentransport in the blood is largely due to hemoglobin (Hb). Hemoglobin (Hb)-oxygen binding affinity is

affected by: pH, CO2, temperature, and 2,3-DPG. These changes are reflected in the oxygen-Hb

dissociation curve.

Most CO2 is converted into H+ and HCO3- by carbonic anhydrase inside RBCs. The reaction is: CO 2 +H2O H

+ + HCO3. Therefore, body pH is related to PCO2 and ventilation. Respiration is under the

control of a central pattern generator in the medulla oblongata and the pons. Chemical factors such as P O2,PCO2, and H

+ of body fluids affect ventilation via central and peripheral chemoreceptors. We can also exert

conscious control over breathing, but not past the point of chemoreceptor response.

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