Introduction To Human Physiology

Respiratory system

Respiratory system Overview 

• Respiratory system is the system responsible for equipment of air to the body tissues.
•  Respiration is a complex process by which living organisms exchange O2 and CO2 between the organism and the environment.
•   Respiration is important in obtaining energy by oxidation of food substances. The obtained energy is stored in form of high energy phosphate compounds like ATP.
•  Respiration includes many processes:

     1- External respiration: exchange of air between the external environment and             pulmonary alveoli.

     2- Exchange of gases between the alveolar air and the blood flowing along the             pulmonary capillaries. 

     3- Transport of gases by the blood.

     4- Exchange of gases between the tissue cells and blood in the tissue                         capillaries.

     5- Internal respiration: consumption of O2 by the cells and production of CO2. 

        Functions of respiratory system:

        

     - In addition to the main function of the respiratory system which is the gas               exchange between the organism and the environment, the respiratory can               perform other non respiratory functions include the following: 

    1- Protective function: respiratory system provides a protection against some                 microorganisms by preventing them from entering the body or by removing             them from the respiratory surface. These are done by:

      Ciliary activity moves the superficial liquid lining layer continuously toward the         pharynx.

      Neutrophils, lymphocytes and alveolar macrophages are present in the alveoli         defense against bacteria and viruses.

      Lungs synthesize immunoglobulin IgA for its own defense. 

      2- Acid –Base balance: respiratory system can alter blood PH by changing                 blood CO2 level so as to keep the blood PH at a level 7.4.This is done                     through the chemoreceptors and respiratory center integrations. 

    3- Olfaction: the sensation of smell occurs when air born molecules are drawn             into the nasal cavity. 

    4- Metabolic functions of the lungs: these functions include:

      Regulation of blood pressure: endothelial cells of the pulmonary capillary                 secrete an enzyme called angiotensin converting enzyme (ACE), which                 converts angiotensin I to active angiotensin II, a potent vasoconstrictor.

      Lungs synthesize hormones like serotonin, histamine, prostaglandin E2, F2             and G2 and release them to the circulation under various circumstances such          as histamine, bradykinin and prostaglandins are released during asthma                 attack .Heparin histamine, serotonin and prostaglandinsE2and F2 are                     released during anaphylactic shock.

      Bradykinin , norepinephrine ,serotonin and prostaglandins are degraded and              removed by the lungs.

Structural considerations 

Respiratory system is composed of the followings: 

1- Respiratory airways. 

2- Two lungs 

3- Chest walls which consist of muscles of respiration such as the diaphragm,             external inter costal muscles, internal intercostal muscles and abdominal                 muscles and the rib cage.

 4- Part CNS concerned with the control of respiratory muscles.

     Respiratory airways 

1- Upper respiratory airways 

     Upper respiratory airways have several physiological functions in addition to             air conduction, such as swallowing, conditioning of air (warming and                         humidification) before its passage to the trachea and defense mechanism. 

     Upper respiratory airways include many parts: the external nose, nasal cavity             and pharynx. 

    - Nose: Mucous membrane of the nose is lined by ciliated columnar epithelium                     containing scattered goblet cells.

     - Pharynx is lined by ciliated columnar epithelium with goblet cells. Oropharynx           is lined by stratified squamous epithelium.

 Structure of respiratory system. 

2- Lower reparatory airways

      The lower respiratory tract consists of larynx, trachea, bronchi and                             bronchioles, alveolar ducts and alveoli in the lungs.

      Larynx: upper part of the larynx and vocal cords are lined by stratified                     squamous epithelium. Lower part is lined by ciliated columnar epithelium.

      Trachea is a tube extends from the larynx to the bifurcation in the                             mediastinum. 

        - It is lined with „C‟ shaped rings of cartilage, which prevent the collapse of the             tube when the air pressure is reduced during inspiration (otherwise                             breathing would be impossible)

.       - The dorsal surface of the trachea has no cartilage, but instead has smooth               muscles, which contract to reduce the size of the trachea, (e.g. during                       coughing or an asthma attack).Smooth muscles relax during swallowing                 (food passing down the esophagus )and also to expand the trachea during             exercise (so air breathed in faster)

 Structure of trachea. a: longitudinal section, b: cross section.

Tracheobronchial Tree 

• Trachea the first generation respiratory passageway is divided into right and left main bronchi, which are the second generation respiratory passageway. 
•  Bronchus in turn is divided into small branches: the bronchioles inside the lung. 
•  Bronchioles are further divided into very small bronchioles: the respiratory bronchioles.
•   There are 20- 25 generations before reaching finally to the alveolar duct and alveoli. 
•  The inner surface of the trachea (bronchi and bronchioles) is lined with mucus secreting goblet cells (the mucus traps foreign particles, e.g. dust and parasites) and ciliated cells carrying the mucus to the nose .
•  Conducting zone extend from the trachea to terminal bronchioles which are ciliated for removal of debris. It is anatomically incapable of gas exchange but they work as a passageway for air movement. It constitutes the anatomical dead space. 
•  Respiratory zone extends from the respiratory bronchioles to the alveoli. It is a site for gas exchange.

Tracheobronchial Tree.

The lungs 

•  Lungs are principle organs of the respiratory system. Each lung is conical shape resting on the diaphragm. 
•  The right lung is larger than the left lung. The right lung has three lobes while the left lung has two lobes .Each lobe is supplied by a lobar bronchus. The lobes are divided into bronchopulmonary segments which are supplied by the segmental bronchi  - Nine bronchopulmonary segments are present in the left lung. - Ten bronchopulmonary segments are present in the right lung. 
•  The lung is surrounded by a double layered serous membrane called pleura: 
• - Parietal pleura is the outer layer of the pleura - Visceral pleura are the inner layer, directly connected to the lung. - Pleural cavity – slit-like potential space filled with 2 ml mucoid pleural fluid, which is secreted by parietal pleura; 
•  Function of the pleural fluid: 

            1- It keeps the two pleura layers together. 

            2- It acts as a lubricant to help the sliding movement between the two                             layers. 

            3- It is essential for the proper expansion and contraction of the lungs.

Pathology note: Pleural effusion: an accumulation of significant quantity of fluid in the pleural cavity .It results from blockage of lymphatics ,increased pulmonary capillary pressure which leads to excessive transudation of fluid into the pleural cavity as in cardiac failure, reduced plasma colloid osmotic pressure in the hyperproteinemia ,and infection or inflammation of the pleura lead to damage the capillary membrane. 

Bronchopulmonary segments. 

Pulmonary ventilation 

Overview 

• Pulmonary ventilation means inflow and outflow of air between the atmosphere and the lung alveoli. 
•  Air moves from the region of a high pressure to one of a lower pressure.
•   A pressure difference is established by the mechanics of pulmonary ventilation: inspiration and expiration.
•   The muscles cause the lungs to expand and contract.
•   Lungs can be expanded and contracted in two ways: 

        - Downward and upward movement of the diaphragm to lengthen or shorten              the chest cavity.

         - Elevation and depression of the ribs to increase and decrease the anterior-              posterior diameter of the chest cavity. 

        - Normal quiet breathing is accomplished by the movement of the diaphragm. 

Inspiration 

• Inspiration is an active process. 
•  The dome shaped diaphragm flattens as it contracts. This increases the   height of the thoracic cavity. 
•  The external intercostal muscles contract to raise the ribs .This increases the circumference of the thoracic cavity
•   During deep or forced inspiration, additional muscles are recruited: scalene,     sternocleidomastoid and pectoralis minor.
•   Intrapleural pressure becomes more negative (-2.5 − -6)mmHg ,due to       increase thoracic volume ,as compare to the atmospheric pressure, therefore   air flows into the lung.

Expiration

•   Quiet expiration in healthy people is a passive process(no muscle     contraction) 
•  Inspiratory muscles relax .
•  Relaxing diaphragm moves superiorly (up).
•   Elastic fibers in lung recoil
•   Volumes of thorax and lungs decrease simultaneously, increasing the pressure to slightly positive so the air flows out of the lungs.
•   Expiration during the exercise or lung diseases becomes active process requiring use of accessory muscles like internal intercostal muscles and abdominal muscles.

 Respiratory muscles action during inspiration and expiration.

Basic concepts of air movement and pressure 

Pulmonary pressure 

• The lungs have tendency to collapse due to their elastic structures, therefore they collapse like a balloon to expel the air through the trachea when there is no force to keep it inflated.
•  The lung floats in the thoracic cavity surrounded by pleural fluid that lubricates movement of the lung in the thoracic cavity.

          Pleural pressure is the pressure of the fluid in the thin space between the                 lung and the chest wall.

         This is slightly negative, and becomes more negative at the beginning of                    the inspiration, reaching to about -6 cm of H2O or even -7.5cm of H2O by              increasing the force that expands the lung. 

        - During inspiration: pleural pressure decreases because thoracic volume                   increases according to the Boyle’s law. 

         - During expiration: pleural pressure increases because thoracic volume                      decreases. 

           Atmospheric pressure is the pressure exerted by the weight of the air in the            atmosphere (760 mmHg at sea level).

          - Alveolar pressure: is the pressure of the air inside the  alveoli. 

          - If the glottis is open, no air moves into or out of the lungs .The pressure in                 all parts of the respiratory tree and all the ways to the alveoli is equal to the              atmospheric pressure (0 cm of H2O).

          - During inspiration the alveolar pressure falls to (-1cm of H2O) as compare                 to the atmospheric pressure. 

           - During expiration, alveolar pressure slightly increases to +1cm of H2O to                 force 0.5 litter of inspired air out of the lung during 2-3 seconds of                             expiration. 

           - Transpulmonary pressure is the differences between the alveolar pressure             and pleural pressure. 

            - Pressure differences between the alveoli and the pressure on the outer                 surface of the lung measures the elastic force of the lung that tends to                     collapse the lung, which is known as recoil pressure.

         - Pulmonary pressures and volumes changes during respiratory cycle                        (inspiration and expiration) are illustrated 

Dalton‟s law: 

The partial The greater the difference in partial pressure

pressure of a gas in a mixture of between 2 points, the greater the rate of gas gases is the percentage of the gas movement.

in the mixture times the total

pressure of the mixture of gas.

Henry‟s law: 

The concentration A small amount of the gases in air dissolves

of a gas dissolved in a liquid is in the fluid lining the alveoli (CO2 is

equal to the partial pressure of 24times more soluble than O2, therefore the gas over the liquid times the CO2exits through the respiratory membrane

solubility coefficient of the gas.       more readily than O2 enters).

Alveolar pressure during inspiration and expiration

Pressures and volumes changes during the respiratory cycle

Work of breathing 

-  Work of breathing is pressure volume work performed in moving air into and out of the lungs. Most of this work is performed during inspiration.

-  Work of breathing must overcome three sources of resistance encountered during inspiration :

1- Airway resistance is generated between air molecules and the walls of conducting airways. 

•      Most of the total airway resistance comes from the large conducting airways, because they are arranged in series and airflow resistances are additive.

•      Small airways provide little resistance because they arranged in parallel and airflow resistance in parallel are added reciprocally.

 Pathophysiology note: Airway diameter can be reduced(and increased  airway resistance)by number of cases e.g., airway diameters are reduced by  smooth muscle contraction and excess inflammatory secretions in

 

 obstructive airway diseases such as asthma and chronic bronchitis .As a  result work caused by airway resistance increases    

 Pharmacology note: Many classes of drugs affect large airway diameter by  affecting bronchial smooth muscles tone .For example β₂ –adrenergic agonists  such as albuterol which stimulates bronchodilation. Other classes of drugs prevent bronchoconstriction or inhibit inflammation e.g., steroids  anticholinergics ,leukotriene receptors antagonists and lipoxygenase   inhibitors .

2-      Compliance work: is the work performed to overcome elastic recoil of the lungs. It accounts for the largest proportion of the total work of breathing. 

 

 Pathology note: In emphysema compliance work is reduced because the  destruction of lung tissues and loss of elastic tissues of the lung, but in  pulmonary fibrosis, compliance work is increased because the fibrotic  tissues require more work to expand.  

2-      Tissues resistance: is generated as the pleural surfaces slide over each other during respiratory cycle .It accounts for a small portion (5%) of the total work of breathing.

 

3-Pulmonary compliance 

-  Pulmonary compliance is a measure of lung dispensability.

-  It is defined as the extent to which the lung will expand for each unit increase in transpulmonary pressure. Compliant lungs are easy to distend.  

 

-  Total lung compliance of both lungs and thorax is 200ml/cm.H₂O, every time transpulmonary pressure increases 1 cm.H₂O lung volume will expand 200 ml.

-  The diagram which shows the relation between lung volume change and change in transpulmonary pressure refers to compliance diagram. (Figure

9.9).     

-  Compliance diagram shows two curves for expiration and inspiration.

Total lung compliance, TLC: total lung capacity, FRC: functional residual capacity, RV: residual volume

Pulmonary surfactant 

-  Surfactant is a surface tension lowering agent present in the alveolus between the alveolar fluid and air.

-  It is a complex mixture of phospholipids (dipalmitoyl phosphocholine), proteins and Ca²⁺.

-  It is secreted by type II alveolar epithelial cells which are 10% of the surface area of the alveoli.

-  Role of surfactant :

-   Surfactant reduces surface tension. The surface tension of normal fluid lining the alveoli without surfactant is 50 dynes/cm, while that for fluid lining the alveoli with normal surfactant is about 5-30dynes/cm.

-            It reduces compliance resistance of the lungs.

-            It maintains alveolar stability .It prevents over distention or collapse (atelectasis) of the alveoli. When there is increase in the diameter of the alveoli, during inspiration, the number of surfactant molecules per unit area decreases and the surface tension increases. 

-  Surfactant production is decreased by the effect of smoking, histamine and hypoxia while its production increases by hormonal effect (insulin, thyroid hormone and glucocorticoid hormone).

Clinical note: Absence of surfactant from the fluid lining the alveoli especially in some newborn babies known as respiratory distress syndrome  of newborn babies (hyaline membrane disease), which is fetal if it is not treated .That is why the  premature babies may be at risk if they are born before the 6 -7 months of gestation.  

Alveolar ventilation 

-  Volume of air moves in and out of the lungs with each normal breath .This represents the tidal volume (V_T).The typical V_T is about 500ml.

-  There are 12-15 breathes per minute  ,therefore the total air volume leaving the lung per minute (minute ventilation ) ,which is measured as in the following equation :  

Minute ventilation=   respiratory rate X V_T 

                                  =   12 breathes /min X 500 ml   

                                  =   6000   ml/min 

Not all the air that passes the lips reaches the alveolar gas compartment ,where the gas exchange occurs, but about 150 ml remains behind in the anatomical dead space .So the alveolar ventilation (air volume entering g the respiratory zone ) is calculated as in the following equation;

  Alveolar ventilation (AV) =12 breathes /min X( 500 ml _150ml )

                                                 = 4.2 Lit/minute  

-  Alveolar ventilation represents the fresh inspired air for gas exchange.

Lung volume and capacities 

Overview 

-  The way to study the pulmonary ventilation is known spirometry, which is done by recording the volume of air moved into and out of the lungs. The device which is used to study the lung volumes is the spirometer, while the record is the spirogram.

-  Lung volumes and capacities are divided into two types

1.      Static lung volumes and capacities  

2.      Dynamic lung volumes and capacities. 

-  There are normal physiological differences in lung volumes and capacities,    e .g; they are less in women than those in men in about 20-25%.They are greater in large and athletic people than in small asthenic people.   

Clinical note:  Lung volumes tend to decease in restrictive lung diseases (e.g., pulmonary fibrosis ) because of limitations of pulmonary expansion and they tend

 to increase in obstructive lung diseases (e.g., emphysema) as a result of increased compliance.  

Static lung volumes and capacities (figure 9.10)  

§  Static lung volumes are not changed with time. They include the following :

1-      The tidal volume (TV): The volume of air inspired or expired with each normal breath (500ml).

2-      The Inspiratory Reserve Volume (IRV): The extra air volume that can be inspired forcefully after inspiration of normal tidal volume.(3000 ml).

3-      The Expiratory Reserve Volume (ERV): The extra amount of air that can be expired forcefully after the end of normal tidal expiration.(1100ml). 

4-      The Residual Volume (RV): Air volume remaining in the lungs after the most forceful expiration. (1200ml).  

Static lungs volumes and capacities.

  Two or more of these volumes together are called: pulmonary capacities.

1-      The Inspiratory Capacity(IC): amount of air that can be breathed beginning at the normal expiratory level and distending the lung to the maximum amount (3500ml). 

 IC=TV+IRV

2-      The functional Residual Capacity (FRC): amount of air remaining in the lungs at the end of normal expiration. (2300ml). 

                                                                        FRC=RV+ERV

3-      Vital Capacity (VC): maximum amount of air that can be expelled from the lung after first filling the lungs to their maximum extent then expiring to the maximum extent. (4600ml).

                                                                    

                                                                    VC=TV+IRV+ERV

                                4-      The Total Lung Capacity (TLC): The maximum                                        volume  which lungs can be expanded with the                                                 greatest possible inspiratory effort.(5800 ml).

                                

                                                                 TLC=TV+IRV+ERV+RV   

                                                                        TLC=VC+RV

 Clinical note: There are two major categories of respiratory diseases, which  can alter the dynamic lung volumes:

 Chronic Obstructive Pulmonary Diseases (COPD): the diseases that interfere  with airflow. They are characterized by increased airway resistance to air flow  caused by excessive secretion or increased contraction of bronchial smooth  muscle. 

 Asthma: is a disease characterized by increased constriction of the bronchi  and bronchioles in response to various stimuli causing air narrowing and  decrease ventilation efficiency. The symptoms include rapid shallow breathing  wheezing, cough and shortness of breath.

 Chronic bronchitis: is the inflammation of the bronchioles causing swelling of  the walls of the bronchioles and bronchi and reducing air passage through  them.

 Emphysema results in damage to the alveoli, so that the walls become less  elastic (taking longer to inflate and deflate). 

 Chronic Restrictive Pulmonary Disease (CRPD): is a chronic disorder that  causes a decrease in lung’s ability to expand. It is characterized by reduced  lung volume. The most common restrictive lung diseases are interstitial lung  fibrosis including sarcoidosis granulomatous disorder and extrapulmonary  restrictive lung diseases including scoiliosis.     

Dynamic lung volumes

 Dynamic lung volumes quantify the time rate of gas flow along the airways.

 They are of a clinical importance in the assessment of airways resistance,

specifically during expiration, therefore they are of interest in patients with

COPD like :asthma ,emphysema ,chronic bronchitis .These are:

1- Forced Vital Capacity (FVC): The maximum air volume which can be

expired forcefully after maximum inspiration.(Figure 9.11 ).

2- Forced Expiratory Volume at the first second of expiration (FEV1):

Maximum air volume which can be expired forcefully at the first second

of expiration after maximal inspiration.

3- FEV1%: Is the ratio of air expired forcefully at the first second related

as a percentage of total amounts of air expired during FVC.

 

FEV1%=FEV1/FVC X 100

 

4- Peak Expiratory Flow (PEF): is the maximal flow rate which is

achieved during force expiration. (Figure 9.11).

5- Maximum Voluntary Ventilation (MVV): is the maximal air volume

which can be expired by breathing deeply and rapidly with maximal voluntary effort for a short time.

6- Forced Expiratory Time (FET): is the time required to expire all air in

the lung by using the force.

7- Estimated Lung Age: is the age when the person pulmonary function is

normal.

  

                                                a: Expiratory flow curve showing PEF

,b: expiratory volume to showing FEV1and FVC

Pathology note: FEV1 and FVC are reduced in lung diseases and the degree of reduction depends on the nature of the diseases. In obstructive diseases the expiratory volumes are reduced because of airway narrowing, therefore FEV1 is reduced more than is FVC and FEV1% is reduced. In restrictive diseases, inspiration is limited by noncompliance of the lung leading to limited expiratory volumes. FVC is reduced more than is FEV1 resulting normal FEV1% or even increased, because the elastic recoil of the lung is preserved.

 

Gas exchange

Overview

 Gas exchange across the respiratory membrane occurs by diffusion.

 Respiratory gases diffuse from area of high partial pressure to area of low

pressure.

 Partial pressure: is the pressure of each gas alone, which is used to express

the concentration of the gas.

- Partial pressure of O2 and CO2 are designed as PO2 and PCO2

respectively

- Partial pressure of a gas is calculated by multiplying its fractional

concentration by the total pressure, for example the percentage of O2 

is 21% of the total pressure 760 mmHg (atmospheric pressure), therefore

thePO2 is 160 mmHg

   Atmospheric air ,alveolar air and expired air have different concentrations of

gases because:

1- Air is humidified before it reaches the alveoli.

2- A constant diffusion of O2 from the alveoli into the blood, while CO2 is

constantly diffusing from the pulmonary blood to the alveoli.

3- The alveolar air is only partially replaced by atmospheric air

Diffusion of gases through the respiratory membrane

 There are about 300 millions alveoli in the two lungs.

 The alveolar walls are thin ,within them is a solid network of

interconnecting capillaries, and blood flows in the alveolar walls as a sheet  Gas exchange occurs through the membrane of all the terminal portions of

the lungs (not only the alveoli).These membranes are known the respiratory membrane or the pulmonary membrane.

 

Respiratory membrane

 The respiratory membrane is composed of the following layers(figure9.12):

1- A layer of fluid lining the alveoli that contains surfactant.

2- The alveolar epithelium

3- An epithelial basement membrane.

4- A thin interstitial space between the alveolar epithelium and the

capillary membrane.

5- A capillary basement membrane that, in many places, fuses with

epithelial basement membrane.

6- The capillary endothelial membrane.

 The membrane is very thin, about 0.6 µm as average, and total surface area

is70 m2 in normal adult .The total amount of blood in the lung capillaries is 60-140 ml, therefore the gas exchange is very rapid.

 The diameter of pulmonary capillaries is 5 µm, so the RBCs must squeeze

through them (RBC touches the membrane) and O2, CO2 dot need to pass

through the plasma.

 

   Factors affecting the rate of diffusion through the respiratory

membrane

1- The thickness of the membrane.

2- The surface area of the membrane.

3- The diffusion coefficient of the gas in the substance of the membrane. 

4- The pressure differences between the two sides of the membrane.

                                                                The respiratory membrane

Diffusing capacity of the respiratory membrane

 Diffusing capacity is the volume of gas that is able to diffuse across the

respiratory membrane in 1 minute with pressure gradient across the membrane of 1 mmHg.

 Exchange of O2 is normally so efficient that is perfusion limited (the

amount of O2 that enters the arterial circulation is limited only by the

amount of blood flow to the lung).

 The diffusing capacity of the lung for CO2 is 20 times greater than that for

O2.At rest the diffusing capacity for O2 is 21ml/min/mmHg, while its 440ml /min/mmHg for CO2.

 All factors that affect diffusion through the respiratory membrane can affect

the diffusing capacity.

 The diffusing capacity for O2 increases during exercise.

 

Perfusion -limited and diffusion-limited gas exchange

 Perfusion -limited gas exchange: diffusion can be increased only       if blood

flow increases, e.g., O2 uptake under normal             condition.

 Diffusion- limited exchange: diffusion continues as long as                 pressure

differences exist across the respiratory membrane, e.g., O2 diffusion during

heavy exercise at high altitude.

 

Pulmonary blood flow

 The pressures in the pulmonary circulation are low compared with those of

systemic circulation.

 In the upright position ,perfusion in the apices of the lung is different from

that of the bases because the effects of gravity, therefore there are three

zones of pulmonary blood flow:

1- Zone 1(top of the lung)

 It has no blood flow because alveolar pressure is greater                 than artery

pressure.

 It can occur when pulmonary artery pressure is decreased

(hemorrhage) and when alveolar pressure is                       increased.