Lecture 2 MECHANICS OF PULMONARY VENTILATION

Lung and chest wall compliance

Zuheir A Hasan

Professor of physiology

College of Medicine

HU

3/26/2021 1

Lecture Objectives

• Describe the pressure–volume characteristics of the lung and the chest wall,

• Define Lung and chest wall compliance and understand methods of measurements lung compliance

• Predict changes in the compliance of the lung and the chest wall in different physiologic and pathologic conditions.

• Describe the effects of surface tension on lung compliance

• Describe the chemical composition of lung surfactant

• Understand the roles of pulmonary surfactant in the recoil and expansion of the lung

• Understand the pathophysiology of infant respiratory distress syndrome and adult respiratory distress syndrome

• Describe the laboratory assessment of alpha 1 antitrypsin and its clinical significance

• List the non respiratory functions of the lungs and air ways

3/26/2021 2

Intra-alveolar and intrapleural pressure changes throughout the respiratory cycle

Movement of Air in and Out of Lungs During Tidal Breathing

Changes in pressure

• Pleural Pressures• Resting -5 cm

H20• Inspiration -8 cm

H20

• Alveolar Pressure• Resting 0 cm

H20• Inspiration

-1 cm H20• Expiration 1 cm

H20

Volume pressure curves

33/26/2021

Duration of inspiration = 2 secLength of expiration 3 sec

Lung compliance(distensibility of the lungs)

• Compliance describes the distensibility of the respiratory system . ( lungs and the chest wall ) • Lung compliance is the inverse of lung elasticity • Reflects the distensibility of the lung

• Lung compliance describes the change in lung volume for a given change in pressure.

• it is the extent to which the lungs will expand for each unit increase in transpulmonary pressure

• The total compliance of both lungs together in the normal adult human averages about 200 milliliters of air per centimeter of water transpulmonary pressure.

• That is, every time the transpulmonary pressure increases 1 centimeter of water, the lung volume, after 10 to 20 seconds, will expand 200 milliliters

3/26/2021 4

Lung compliance

• The compliance of the lungs and chest wall is inversely correlated with their elastic properties or elastance.

• The greater the amount of elastic tissue, the greater the tendency to “snap back,” and the greater the elastic recoil force, but the lower the compliance

• Lung compliance of both chest wall and lung is 100 ml/cm H20

3/26/2021 5

Pressure volume curve and lung complianceMeasurement of the pressure-volume curve of excised lung. The lung

is held at each pressure for a few seconds while its volume is measured.

3/26/2021 6

The curves nonlinear and becomes flatter at high expanding pressures. Note that the inflation and deflation curves are not the same; this is called hysteresis

Measurement of lung volumes and lung compliance with a body plethysmograph (body box) uses Boyle's gas law, which states that pressure multiplied by volume is constant (at a constant temperature)..

3/26/2021 7

where P1 and P2 are mouth pressures and V is FRC

Body plethysmograph

3/26/2021 8

3/27/2021 9

Pressure volume curves and calculations of lung compliance

3/26/2021 10

Compliance is higher at higher lung volume Compare the two slopesin the diagram

Pressure–Volume Curve (compliance of the lung) showing inspiratory and expiratory compliance curves Compliance diagram in a healthy person. This diagram shows changes in lung volume during changes in transpulmonarypressure (alveolar pressure minus pleural pressure).

3/26/2021 11

Lungs with high compliance have a steep slope on their pressure–volume curves

That is , a small change in distending pressure will cause a large change in volume. Lung CmplinacwAn unusual feature of the pressure-volume loop for the air-filled lung is that the slopes of the relationships for inspiration and expiration are different, a phenomenon called hysteresis

Properties of the volume pressure curve

• Increase in transpulmonary pressure cause an increases, lung volume

• This relationship is not a straight line: the lung is composed of living tissue,

• The lung distends easily at low lung volumes ( has higher compliance)

• At high lung volumes the distensible components of alveolar walls have already been stretched, and large increases in transpulmonary pressure yield only small increases in volume. ( low compliance )

• The lung also is difficult to distend at very low lung volumes (Below residua volume), because some alveoli may be collapsed and extra energy is necessary to reopen them

3/26/2021 12

Hysteresis

• Hysteresis An unusual feature of the pressure-volume loop for the air-filled lung is that the slopes of the relationships for inspiration and expiration are different

• Usually, compliance is measured on the expiration limb of the pressure-volume loop because the inspiration limb is complicated by the decrease in compliance at maximal expanding pressures.

• Hysteresis could be explained by the higher density of surfactant on the lung surface during expiration when compared to inspiration

3/26/2021 13

COMPLIANCE OF LUNGS

• Determined by elastic forces

• Elastic forces

• lung tissue

• surface tension

3/26/2021 14

Comparison of pressure-volume curves of air-filled and saline-filled lungs alveolar pressure is maintained at atmospheric pressure (0 cm H2O) and pleural pressure is changed in order to change the transpulmonary pressure

3/27/2021 15

Note that the saline filled lung has a higher compliance and also much less hysteresis than the air-filled lung.

Lung compliance is determined by elastic forces

• Elastic forces of Lung tissue (elastin and collagen fibers) (⅓ of total lung elasticity)

• Surface tension of the fluid that lines the inside walls of the alveoli and other lung air spaces. (⅔ of total lung elasticity))

Elastic forces and lung compliance

• The elastic forces of the lung tissue are determined by elastin and collagen fibers interwoven among the lung parenchyma.

• In deflated lungs, these fibers are in an elastically contracted and kinked state;

• when the lungs expand, the fibers become stretched and unkinked, thereby elongating and exerting even more elastic force

• about one third of the total lung elasticity is due to elastic properties of the lung , whereas the fluid-air surface tension forces in the alveoli represent about two thirds.

• The fluid-air surface tension elastic forces of the lungs is decreased by surfactant

• The fluid-air surface tension elastic forces of the lungs also increase tremendously when surfactant is not present in the alveolar fluid.

• This situation causes the condition called respiratory distress syndrome of the newborn. It is fatal if not treated with strong measures by application of continuous positive pressure breathing

3/26/2021 16

Pressure

Volu

me

Normal

Fibrosis

Emphysema

Representative static pulmonary compliance curve for normal lungs , low compliance for example, lungs with fibrosis; and lungs with high compliance, for example, lungs

with emphysema

3/26/2021 17

Compliance of the Thorax and the Lungs Together

• The compliance of the entire pulmonary system (the lungs and thoracic cage together) is measured while expanding the lungs of a totally relaxed subject.

• To measure compliance, air is forced into the lungs a little at a time while recording lung pressures and volumes.

• For this, the subject inspires or expires from a spirometer and then relaxes the respiratory muscles while the airway pressure is measured (“relaxation pressure”).

• To inflate this total pulmonary system, almost twice as much pressure as is required to inflate the same lungs after removal from the chest cage is necessary

• Therefore, the compliance of the combined lung-thorax system is almost exactly one half that of the lungs alone—110 milliliters of volume per centimeter of water pressure for the combined system, compared with 200 ml/cm for the lungs alone.

• Furthermore, when the lungs are expanded to high volumes or compressed to low volumes, the limitations of the chest become extreme.

• When near these limits, the compliance of the combined lung-thorax system can be less than one fifth that of the lungs alone.

3/26/2021 18

Relaxation pressure-volume curve of the lung, chest wall, and respiratory system. The curve for the respiratory system is the sum of the individual curves

3/26/2021 19

At FRC the collapsing force on the lungs is exactly equal to the expanding force onthechest wall, The combined lung and chest-wall system neither has a tendency to collapse nor to expand.Volume less than FRC the collapsing force on the lungs is smaller than the expanding force on the chest wall and that airway pressure for the combined system is negative; thus the combined system tends to expand, as air flows into the lungs down the pressure gradient.

Relaxation pressure-volume curve of the lung, chest wall, and respiratory system. The curve for the respiratory system is the sum of the individual curves

3/27/2021 20

Volume is greater than FRC. the collapsing (elastic) force of the lungs is greater. The expanding force on the chest wall is smaller, however, and the combined lung and chest-wall system “wants” to collapse. And airway pressure for the combined system is positive; thus the overallsystem tends to collapse, as air flows out of the lungs down the pressure gradient.) At highest lung volumes, both the lungs and the chest wall “want” to collapse[notice that the chest wall curve has crossed the vertical axis at high volumes], and there is a large collapsing force on the combined system.)

3/27/2021 21

Pulmonary Surfactant

• Surfactant is a complex mixture of several phospholipids, proteins, and ions.

• Components are the phospholipid dipalmitoyl phosphatidylcholine, surfactant apoproteins, and calcium ions

• . The major phospholipid is phosphatidylcholine, approximately 75% of which is present as dipalmitoyl phosphatidylcholine (DPPC). DPPC is the major surface-active component in surfactant, and it decreases surface tension.

• The second most abundant phospholipid is phosphatidylglycerol (PG), which accounts for 1% to 10% of total surfactant.

• These lipids are important in formation of the monolayer on the alveolar-air interface, and PG is important in the spreading of surfactant over a large surface area.

• Secreted by type II alveolar epithelial cells in the lungs and lines the alveoli.

• Reduces surface tension at the alveolar – air interface with hydrogen-bonding between H2O molecules

3/27/2021 22

Synthesis and removal of surfactant

• Pulmonary surfactant appears to be continuously produced in the lung

• is also continuously cleared from the lung.• Some pulmonary surfactant is taken back into the type

II cells (reuptake), where it is recycled and secreted again,

• it is degraded and used to synthesize other phospholipids.

• Surfactant is also cleared from the alveoli by alveolar macrophages

• Absorption into the lymphatics, or migration up to the small airways and the mucociliary escalator

3/27/2021 23

What is the effects of reducing surface tension by surfactants

• prevents small alveoli from collapsing thus stabilization of alveoli

• increases compliance.

• reduces the pulmonary capillary filtration as it makes pulmonary interstitial pressure lessnegative.

• Thus it helps prevent pulmonary edema, which interferes with gas exchange.

3/26/2021 24

Compliance of

Surface tension

• Attraction of water molecules at air-water interface

• Increase will result in collapse of alveoli

• Prevented by surfactant

3/26/2021 25

Effect of alveolar size and surfactant on collapsing pressure.

3/26/2021 26

Schematic representation of two alveoli ofdifferent sizes connected to a common airway. surface Tension and

Laplace law equationsNo surfactant

3/26/2021 27

Schematic representation of two alveoli ofdifferent sizes connected to a common airway. surface tension with

surfactant

3/26/2021 28

Stability of alveoli 1. Role of surfactant 2. Alveolar Interdependence

• In addition to surfactant , a second factor tending to stabilize the alveoli is their mechanical interdependence,

• Alveoli do not hang from the airways like a “bunch of grapes” (the translation of the Latin word “acinus”, and they are not spheres.

• They are mechanically interdependent polygons with flat walls shared by adjacent alveoli.

• Alveoli are normally held open by the chest wall pulling on the outer surface of the lung,

• . If an alveolus were to begin to collapse, it would increase the stresses on

• the walls of the adjacent alveoli, which would tend to hold it open. This process would oppose a tendency for isolated alveoli with a relative lack of pulmonary surfactant to collapse spontaneously.

• Conversely, if a whole subdivision of the lung (such as a lobule) has collapsed, as soon as the first alveolus is reinflated, it helps to pull other alveoli open by its mechanical interdependence with them.

• Thus, both pulmonary surfactant and the mechanical interdependence of the alveoli help stabilize the alveoli and oppose alveolar collapse (atelectasis

3/26/2021 29

Alveolar Interdependence

3/26/2021 30

Clinical consequences of a lack of pulmonary surfactant

• Neonatal respiratory distress syndrome (Infant respiratory distress syndrome )

• Adult respiratory distress syndrome or “shock lung syndrome)

3/26/2021 31

Neonatal respiratory distress syndrome(hyaline membrane disease),

• Surfactant may be present as early as gestational week wee 24 and almost always present by 35 week

• Generally, a lecithin:sphingomyelin ratio greater than2:1 in amniotic fluid reflects mature levels of surfactant

• Prematurely born infants who do not have functional pulmonary surfactant experience great difficulty in inflating their lungs, especially on their first breaths.

• Even if their alveoli are inflated for them with positive-pressure ventilation, the tendency toward spontaneous collapse is great because their alveoli are much less stable without pulmonary surfactant.

• The infant exhibits atelectasis (lungs collapse), difficulty reinflating the lungs (as a result of decreased compliance as well as Pulmonary edema, and hemorrhage

• RDS that is characterized by impaired gas exchange , V/q mismatch and hypoxemia

3/26/2021 32

Neonatal respiratory distress syndrome• During fetal life, Cl– is secreted with fluid by the pulmonary epithelial cells.

• At birth, there is a shift to Na+ absorption by these cells via the epithelial Na+ channels (ENaCs), and fluid is absorbed with the

• Na+. Prolonged immaturity of the ENaCs contributes to the pulmonary abnormalities in IRDS

3/26/2021 33

Acute respiratory distress syndrome (also known as adult respiratory distress syndrome or “shock lung syndrome”

• Alveolar hypoxia or hypoxemia (low oxygen in the arterial blood), or bot due to surgery or

trauma h, may lead to a decrease in surfactant production or an increase in surfactant destruction.

• One approach to maintain patients with acute or infant respiratory distress syndrome is to ventilate their lungs with positive-pressure ventilators and to keep their alveolar pressure above atmospheric pressure during expiration known as positive end-expiratory pressure [PEEP].

• This process opposes the increased elastic recoil of the alveoli and the tendency for spontaneous atelectasis to occur because of a lack of pulmonary surfactant.

•

3/26/2021 34

Patchy atelectasis is also associated with surfactant deficiency

• in patients who have undergone cardiac surgery involving use of a pump oxygenator and interruption of the pulmonary circulation.

• In addition, surfactant deficiency may play a role in some of the abnormalities that develop following occlusion of a main bronchus, occlusion of one pulmonary artery, or long-term inhalation of 100% O2.

• Cigarette smoking also decreases lung surfactant.

3/26/2021 35

Laboratory testing Alpha-1-Antitrypsin measurements in serum

• Workup of individuals with suspected disorders such as familial chronic obstructive lung disease

• Diagnosis of alpha-1-antitrypsin deficiency

• Alpha-1-antitrypsin (A1A) is the most abundant serum protease inhibitor and inhibits trypsin and elastin, as well as several other proteases.

• The release of proteolytic enzymes from plasma onto organ surfaces and into tissue spaces results in tissue damage unless inhibitors are present.

• Congenital deficiency of A1A is associated with the development of emphysema at an unusually early age and with an increased incidence of neonatal hepatitis, usually progressing to cirrhosis.

3/26/2021 36

Noe respiratory functions of the lung

• It is a route for water loss and heat elimination.

• Moistening of inspired air is essential to prevent the alveolar linings from drying out.

• It enhances venous return “respiratory pump,”

• acid–base balance

• Phonation It enables speech, singing, and other vocalization.

• Defenses against inhaled particulate matter and infections

▪ Metabolic functions synthesis , storage and removal of substances

Synthesis of surfactants and activation of Angiotensin IEntrapping and removal of blood clots when present in

pulmonary circulation

373/26/2021

Defenses of the Respiratory System against inhaled particulate matter

• Filtration of Inspired Air :

• airborne particles (10–15 μm) are filtered out in diameter. Red out of the inhaled air by hair or vibrissae

• Particles larger than particles greater than 10 μm in diameter are removed on impact in the large surface area of the nasal septum and turbinates

• Lymphoid tissues, the tonsils and adenoids, provide immunological protection against inhaled pathogens

383/26/2021

Mucociliary escalator:

• A pseudo-stratified ciliated columnar epithelium lines the upper airway from the posterior two-thirds of the nose to the respiratory bronchioles.

• Covered by a ‘mucous blanket’

• Mucus is secreted by goblet cells in the epithelium and mucous cells of the submucosal glands,

• a low-viscosity serous fluid layer secreted by the bronchial glands.

• This ‘mucous blanket’ forms the first line of defense against inhaled particle .

3/26/2021 39

Importance mucociliary escalator

• important mechanism for the removal of inhaled particles that come to rest in the airways.

• Material trapped in the mucus is continuously moved upward toward the pharynx.

• This movement can be greatly increased during a cough

• Mucus that reaches the pharynx is usually swallowed, expectorated, or removed by blowing one’s nose.

• Patients who cannot clear their tracheobronchial secretions (e.g., an intubated patient or a patient who cannot cough adequately) continue to produce secretions.

• If the secretions are not removed from the patient by suction or other means, airway obstruction may develop.

3/26/2021 40

Factors affecting muco-ciliary function

• Secretions of goblet cells are stimulated by inhaled irritant gases and inflammatory mediators.

• Bronchial gland secretions is mediated by the parasympathetic nervous system via the vagusnerve and Ach

• Muco-ciliary motility is impaired:

• Dehydration,

• Smoking

• Drugs: inhaled and local anesthetics , atropine.

• dry inspired gases, extremes of temperature.

413/26/2021

cough and sneeze

• Filtered or aspirated material trapped in the mucus that lines the respiratory tract can be removed in several ways.

• Mucociliary escalator

• Mechanical or chemical stimulation of receptors in the nose, trachea, larynx, or elsewhere in the respiratory tract may produce bronchoconstriction to prevent deeper penetration of the irritant into the airways

• May also produce cough or sneeze

• Sneeze results from stimulation of receptors in the nose or nasopharynx; a cough results stimulation of receptors in the trachea

3/26/2021 42

cough and sneeze

• In either case, a deep inspiration is followed by a forced expiration against a closed glottis.

• Pressure in the chest surrounding the lungs (intrapleural pressure) may rise to more than 100 mm Hg during this phase of the reflex.

• The glottis opens suddenly, and pressure in the airways decreases rapidly, resulting in compression of the airways and an explosive expiration, with linear airflow velocities said to approach the speed of sound

3/27/2021 43

• Coughs can be initiated by many causes, including postnasal drip from allergies or viral infections, asthma, gastroesophageal reflux,

• Adverse effect of the by the drug angiotensin-converting enzyme inhibitors

• Mucus production from chronic bronchitis, infections, and other airway disorders.

3/26/2021 44

Immune mediators in the respiratory system • The airway epithelial cells secrete a variety of

substance

• Mucins, defensins, lysozyme, lactoferrin, and nitric oxide, which non-specifically shield the lung from microbial attack

• . Immunoglobulins• mainly IgA, present in the bronchial secretions resist

infections and help maintain the integrity of the respiratory mucosa

453/26/2021

Functions of alveolar macrophages

• Macrophages scavenge within the air sacs

• Engulf the particles that reach the alveoli and deposit them via pores of Kohn on the muco-ciliary escalator or remove them via blood or lymph

• secrete many enzymes, arachidonic acid metabolites, immune response components, growth factors, cytokines, and other mediators that modulate the function of other cells, such as lymphocytes.

3/26/2021 46

Filtering and removal of small blood thrombi the circulation before they can reach the brain or other

vital organs

• Pulmonary capillaries release substances that break down blood clots.

• Pulmonary endothelium is a rich source of fibrinolysin activator, which converts plasminogen present in plasma to fibrinolysin

• Fibrinolysin breaks down fibrin-to-fibrin degradation products.

• The lung is rich source of heparin (which inhibits coagulation)

• In addition , removal of (fat or air) emboli

3/26/2021 47

Metabolic functions of the lung : Biologically active substances metabolized by the lungs.

• Synthesized and used in the lungs• Surfactant

• Partially removed from the blood• Prostaglandins• Bradykinin• Adenine nucleotides• Serotonin• Norepinephrine• Acetylcholine

• Activated in the lungs• Angiotensin I → angiotensin II

483/26/2021

Substances synthesized and released by endothelia cells of pulmonary

circulation• Synthesis and release of prostaglandins, Histamine,

lysosomal enzymes leukotrienes, platelet Activating factor and serotonin

• These substances are leased during acute lung injury in response to conditions such as pulmonary , anaphylaxis , toxicity, fat embolism• May cause bronchoconstriction

• May cause immune or inflammatory responses

• May initiate cardiopulmonary reflexes

• May cause vasoconstriction

3/26/2021 49

3/26/2021 50