Respiratory Physiology I PDF

FFFJ1023: Anatomy, Physiology & Biochemistry II RESPIRATORY PHYSIOLOGY I DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] www.ukm.my/fper ...

FFFJ1023: Anatomy, Physiology & Biochemistry II RESPIRATORY PHYSIOLOGY I DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] www.ukm.my/fper  LEARNING OBJECTIVES At the end of the lecture, students should be able to: explain the general functions of the respiratory system. explain the mechanics of breathing in relations to intrapleural and alveolar pressure. explain pulmonary compliance and factors affecting it. explain the role of surfactant and factors influencing it. describe the work of breathing. www.ukm.my/fper OBJECTIVE 1 Explain the general functions of the respiratory system. www.ukm.my/fper  External Respiration RESPIRATION Respiration encompasses three related functions: ✓ pulmonary ventilation (breathing). ✓ gas (O2 and CO2) exchange (i) between alveoli and blood between air and blood in the lungs; and (ii) between blood and other tissues. ✓ oxygen utilization by the tissues in the energy- liberating reactions of cell respiration. Ventilation and the exchange of gases between the air and blood are collectively called external respiration. Gas exchange between the blood and other tissues Internal Respiration and oxygen utilization by the tissues are collectively known as internal respiration. The intracellular metabolic processes that utilize O2 and produce CO2 during the production of ATP are termed cellular respiration. Gas exchange is passive via diffusion  THE RESPIRATORY SYSTEM Structurally, the respiratory system consists of two parts: ✓ The upper respiratory system includes the nose, nasal cavity, pharynx, and associated structures; ✓ The lower respiratory system includes the larynx, trachea, bronchi, and lungs.  STRUCTURE OF RESPIRATORY AIRWAYS The air passages of the respiratory system are divided into two functional zones: 1) Conducting zone Respiratory airways that carry air to the region where gas exchange occurs. It consists of airway from the beginning of trachea to the beginning bronchioles. Functions: ✓ Warms and moistens inspired air. ✓ Filters and cleans inspired air: – Conducting zone is lined with mucus-secreting and ciliated cells. – Mucus secreted to trap particles in the inspired air. – Mucus moved by cilia to be expectorated. – Defense mechanism: cilia, mucus, phagocytes. ✓ Conducts the sound during speech.  RESPIRATORY AIRWAYS 2) Respiratory zone The region where gas exchange occurs. It includes the respiratory bronchioles, the alveolar ducts, and the alveolar sacs. Functions: ✓ Exchange of gases - the presence of alveoli RESPIRATORY AIRWAYS  FUNCTIONS OF THE RESPIRATORY SYSTEM Gas exchange (main function). ✓ Gas exchange occurs in respiratory bronchioles and alveoli (respiratory zone). Lung defense mechanisms. ✓ Filters unwanted materials for circulation. e.g.: alveolar macrophages ingest inhaled foreign matter (bacteria and small particles); Regulation of acid–base balance and blood pH by changing blood CO2 level. Enables speech, singing, and other vocalization. Smells. Synthesize and metabolize different compounds: ✓ Type II alveolar cells produce surfactant that facilitates lung expansion. ✓ The lungs produce an enzyme called angiotensin-converting enzyme (ACE). ACE converts angiotensin I to angiotensin II, which is part of the renin–angiotensin–aldosterone hormonal pathway that plays a role in regulating Na+ level in the ECF. *Angiotensin is a peptide hormone that causes vasoconstriction and increase in BP.  Test Your Understanding! The term “cellular respiration” is applied to: A. Exchange of gases in the lungs B. Ventilation of the lungs (breathing) C. Exchange of gases in the body tissues D. The production of ATP in the cells Answer: D  Test Your Understanding! What term refers to the exchange of gases between alveolar air and blood in the pulmonary capillaries? A. Inhalation B. Internal respiration C. Ventilation D. External respiration Answer: D  Test Your Understanding! What is the function of ciliated cells in the lungs? A. They form part of the respiratory membrane B. To move mucus out of the bronchial tree C. To secrete surfactant onto the lining of the alveoli D. To phagocytose inhaled bacteria Answer: B OBJECTIVE 2 Explain the mechanics of breathing in relations to intrapleural and alveolar pressure. ✓ Explain the major events in inspiration and expiration. ✓ Relate Boyle’s law to events of inspiration and expiration. ✓ Explain how intrapleural and intrapulmonary pressures change during breathing. www.ukm.my/fper  Mechanics of Breathing (Pulmonary Ventilation) Pulmonary Ventilation : The physical movement of air into and out of the lungs. Pulmonary ventilation consist of two phases: (1) inspiration (inhalation) and expiration (exhalation), is a mechanical process that depends on volume changes in the thoracic cavity. Inspiration Expiration Mechanics of Breathing (Pulmonary Ventilation) Major Events in Inspiration: 1) The diaphragm contracts. 2) The external intercostal muscle contract. Inspiration 3) The thoracic cavity expands, 4) The alveolar pressure (Palv) drop below atmosphere pressure (Patm). 5) Air flows into the lungs and the lung volume expands. ❖ During deep inhalation, the scalene and sternocleidomastoid muscle expand thoracic cavity further, thereby creating a greater drop in Palv. Mechanics of Breathing (Pulmonary Ventilation) Major Events in Expiration: 1) The diaphragm relaxes. 2) The external intercostal muscle relaxes. 3) The chest and lungs recoil, and thoracic Expiration cavity contracts, 4) The alveolar pressure (Palv) increases above atmosphere pressure (Patm). 5) Air flows out of lungs and the lung volume decreases. ❖ During forced exhalation, internal intercostal and abdominal muscles contract, thereby reducing the size of thoracic cavity further, and creating a greater increase in Palv. Mechanics of Breathing (Pulmonary Ventilation)  Pressure And Volume 1) For inspiration to occur, the lungs must expand, Inspiration Expiration which increases lung volume and thus decreases the pressure in the lungs to below atmospheric pressure, and subsequently air moves into the lungs. 1) 2) Air will flow from a region of  pressure to the one of  pressure. Volume depends on the movement of diaphragm & ribs A rule to keep in mind is: ✓ Changes in volume cause pressure changes. 2) During expiration, as lung volume decreases, pressure ✓ Pressure changes lead to the flow of gases to inside the lungs exceeds atmospheric pressure, equalize the pressure. causing air to move out from the lungs.  Boyle’s Law The inverse relationship between volume and pressure, called Boyle’s law. At constant temperature, the pressure of a gas varies inversely with its volume. That is, 1 P= 𝑉 *where P is the pressure of the gas, and V is its volume. Thus, Boyle’s law states that, in a container, such as the thoracic cavity or an alveolus, as volume increases, pressure decreases; as volume decreases, pressure increases. By analogy: In a large container, the pressure decreases because the gas molecules have more space to move around, reducing the frequency of collisions with each other and the container walls. If the volume of the container is reduced, the gas molecules collide more frequently, and the pressure will rise.  Pressure Changes During Breathing Three pressures that are important in ventilation: 1) Atmospheric pressure (Patm) ✓ The atmospheric air pressure outside the body. At sea level, atmospheric pressure is 760 mm Hg. ✓ Patm is always assigned a value of zero. ✓ Respiratory pressures are measured in reference to Patm − Negative respiratory pressure: less than Patm − Positive respiratory pressure: greater than Patm − Zero respiratory pressure: equal to Patm  Pressure Changes During Breathing 2) Intra-alveolar pressure (Palv) or intrapulmonary pressure (Ppul) ✓ the pressure within the alveoli. ✓ Palv rises and falls with the phases of breathing, but it always equalizes with the atmospheric pressure eventually.  Intra-alveolar Pressure changes During inspiration and expiration PB = Patm 1) At the end of expiration, Palv is equal to Patm 2) During inspiration, increased thoracic volume and there is no air movement. results in increased alveolar Volume and decreased Palv. Patm > Palv, thus air moves into the lungs.  Intra-alveolar Pressure changes During inspiration and expiration 3) At the end of inspiration, Palv is equal to Patm 4) During expiration, decreased thoracic volume and there is no air movement. results in decreased alveolar Volume and increased Palv. Palv > P atm, thus air moves out of the lungs.  Pressure Changes During Breathing 3) Intrapleural pressure (Pip) ✓ the pressure within the pleural sac. It is the pressure exerted outside the lungs within the thoracic cavity. ✓ Pip < Patm (subatmospheric). Just before inhalation, it is about 4 mmHg less than the atmospheric pressure, or about 756 mmHg at an atmospheric pressure of 760 mmHg. ✓ Pip does not equilibrate Patm or Palv because the pleural sac is a closed sac with no openings, so air cannot enter or leave despite any pressure gradients that might exist between the pleural cavity and the atmosphere or lungs. Pleura Parietal pleura covers the thoracic wall and superior surface of the diaphragm. Visceral pleura cover the external lung surface The pleurae produce pleural fluid, which fills the slitlike pleural cavity between them Summary: Pressure Changes During Breathing Clinical Relevance Pneumothorax occurs when air enters the pleural cavity, typically due to a puncture in the thoracic wall. During inspiration, air is drawn through the wound into the pleural cavity, transforming the potential space into an air-filled cavity. Pip = Patm results in the lungs recoiling and collapsing.  Test Your Understanding! Which of the following is true during inspiration? A. Intrapleural pressure is positive B. Alveolar pressure equals atmospheric pressure C. Alveolar pressure is higher than atmospheric pressure D. Intrapleural pressure is more negative than it is during expiration Answer: D  Test Your Understanding! When the diaphragm and external intercostals muscles contract, which of the following actions does NOT occur? A. Air moves into the lung B. The intrapleural pressure increases C. The diaphragm moves downward D. The intra-alveolar pressure decreases Answer: B  Test Your Understanding! When we inhale A. alveolar pressure decreases and intrapleural pressure increases B. both alveolar pressure and intrapleural pressure increase C. both alveolar pressure and intrapleural pressure decrease D. alveolar pressure increases and intrapleural pressure decreases Answer: C  Test Your Understanding! During internal and external respiration, gases move by A. osmosis B. active transport C. diffusion D. endocytosis Answer: C  Test Your Understanding! According to Boyle’s law, the pressure in a fixed amount of gas will increase as its volume decreases. Which one of the statements that follow is consistent with Boyle’s law? A. When the diaphragm contracts, pressure in the lungs increases. B. When the chest recoils during exhalation, the air in the lungs is at a negative pressure. C. When the chest recoils during exhalation, the air in the lungs increases in volume. D. When the diaphragm contracts, pressure in the lungs decreases. Answer: D  OBJECTIVE 3 Explain pulmonary compliance and factors affecting it. ✓ Define pulmonary compliance. ✓ Explain how pulmonary compliance, elasticity and surface tension affect breathing. ✓ Factors that affect the compliance of lungs. www.ukm.my/fper  Physical Properties of the Lungs In order for inspiration to occur, the lungs must be able to expand when stretched; they must have high compliance. For expiration to occur, the lungs must get smaller when this tension is released: they must have elasticity. The tendency to get smaller is also aided by surface tension forces within the alveoli.  Pulmonary/Lung Compliance Lung compliance refers to distensibility of the lung and chest wall (how easily lung expands with pressure). ✓ High compliance means that the lungs and chest wall expand easily. ✓ Low compliance means that they resist expansion. By analogy, a thin balloon that is easy to inflate has high compliance, and a heavy and stiff balloon that takes a lot of effort to inflate has low compliance. Lung compliance can be defined as the change in lung volume per change in transpulmonary pressure, ∆V C= (a slope of the pressure-volume curve) ∆P ∆P = transpulmonary pressure (Palv – Pip) Compliance is an important indicator of lung health and function. In the lungs, compliance is related to two principal factors: elasticity and surface tension.  Factors That Affect Lung Compliance Lung compliance is reduced Lung compliance is increased The deposition of inelastic fibers in lung Pulmonary emphysema tissue (pulmonary fibrosis). ✓ The destruction of alveolar septal The atelectasis (collapse) of the alveoli tissue rich with elastic fibers without (infant respiratory distress syndrome and replacement pulmonary edema). ✓ Increased alveolar size – increased Increased resistance to airflow caused by compliance airway obstruction (asthma, bronchitis, and ✓ smoking leads to destruction of elastic lung cancer). fibers in the lungs and is the prime Deformities of the thoracic wall that cause of emphysema reduce its ability to expand. Lung size ✓ Large lung size → increase compliance ✓ Small lung size → reduce compliance Factors That Reduce Compliance Pulmonary fibrosis stiffens the lungs through deposits of scar tissue, decreasing low compliance and making it more difficult for the lungs to inflate and deflate. Factors That Increase Compliance In emphysema, the inner walls of the lungs’ air sacs (alveoli) are damaged, causing them to eventually rupture. This creates one larger air space instead of many small ones, and reduce the surface area available for gas exchange.  Elasticity (elastic recoil) The term elastic recoil refers to how readily the lungs rebound after having been stretched. It is responsible for the lungs returning to their pre-inspiratory volume when the inspiratory muscles relax at the end of inspiration. Pulmonary elastic behavior depends mainly on two factors: ✓ Elastic fibres of the lungs ✓ alveolar surface tension. OBJECTIVE 4 Explain the role of surfactant and factors influencing it. www.ukm.my/fper  Alveolar Surface Tension A thin layer of alveolar fluid coats the luminal surface of alveoli and exerts a force known as surface tension, which promotes alveolar collapse inward and resists distension. Surface tension arises from the attraction between water molecules, causing them to draw closer together. This attraction results in the formation of droplets. Since water molecules in alveolar fluid are also attracted to the surface of the alveoli, the formation of droplets causes the alveoli to collapse. Alveolar surface Water droplet  Surfactant Consists of phospholipids secreted by Type II alveolar cells. Lowers surface tension by getting between H2O molecules, reducing their ability to attract each other via hydrogen bonds. Alveolar surface  Function of Surfactant ↓ surface tension during expiration ✓ Prevents alveoli collapse – Laplace law Prevents lungs edema ✓ Without surfactant, ↑ surface tension will lead to fluid transudation Prevents alveoli collapse after expansion in the newborn baby. ✓ Deficiency in the newborn baby – hyaline membrane disease/ Infant respiratory distress syndrome (IRDS) - ↑ surface tension, atelectasis, dyspnea, hypoventilation. Alveolar surface Law of Laplace The pressure created by surface tension should be greater in the smaller alveolus than in the larger alveolus. This implies that without surfactant, smaller alveoli would collapse and empty their air into larger alveoli.  Test Your Understanding! Pulmonary surfactant A. increases the surface tension of the alveolar lining liquid. B. is secreted by type I alveolar epithelial cells. C. is a protein. D. increases the work required to expand the lung. E. helps to prevent transudation of fluid from the capillaries into the alveolar spaces. Answer: E  Test Your Understanding! A. The presence of sufficient surfactant in the alveoli is to prevent alveoli collapse by A. humidifying the air before it enters. B. warming the air before it enters. C. reducing the surface tension of alveolar fluid. D. protecting the alveolar surface from dehydration. Answer: C  Airway Resistance The rate of airflow through the airways depends on both the pressure difference and the resistance: Airflow = Palv − Patm resistance  Airway Resistance Three factors influencing airway resistance. 1) Diameter of the bronchioles. ✓ Bronchodilation—increase in the diameter of a bronchus or bronchiole. – Epinephrine and sympathetic stimulation stimulate bronchodilation and increase airflow. ✓ Bronchoconstriction—decrease in the diameter of a bronchus or bronchiole. – Histamine, parasympathetic nerves, cold air, and chemical irritants stimulate bronchoconstriction. – Extreme bronchoconstriction can lead to suffocation, as seen in conditions like anaphylactic shock and asthma (narrowed airways due to mucosal inflammation and smooth muscle hypertrophy). 2) Lung compliance ✓ Compliance reduced by degenerative lung diseases in which the lungs are stiffened by scar tissue. 3) Surface tension of the alveoli and distal bronchioles ✓ Infant respiratory distress syndrome (IRDS) Airway Resistance OBJECTIVE 5 Describe the work of breathing. www.ukm.my/fper  The Work Of Breathing Muscular effort (O2 and energy) required for ventilation. During normal quiet breathing, the respiratory muscles must work during inspiration to expand the lungs against their elastic forces, to overcome airway resistance and non-elastic tissue, whereas expiration is passive. Normally, the lungs are highly compliant and airway resistance is low, so only about 3% of the total energy expended by the body is used for quiet breathing.  The Work Of Breathing The work of breathing may be increased (marked increase in O2 consumption and metabolic demand) in four different situations: 1) When pulmonary compliance is decreased, such as with pulmonary fibrosis, more work is required to expand the lungs. 2) When airway resistance is increased, such as with COPD, more work is required to achieve the greater pressure gradients necessary to overcome the resistance so that adequate airflow can occur. 3) When elastic recoil is decreased, as with emphysema, passive expiration may be inadequate to expel the volume of air normally exhaled during quiet breathing. Thus, the abdominal muscles must work to aid in emptying the lungs, even when the person is at rest. 4) When there is a need for increased ventilation, such as during exercise, more work is required to accomplish both a greater depth of breathing (a larger volume of air moving in and out with each breath) and a faster rate of breathing (more breaths per minute). How can the work of breathing be reduced? THANK YOU  FFFJ1023: Anatomy, Physiology & Biochemistry II RESPIRATORY PHYSIOLOGY II DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] www.ukm.my/fper www.ukm.my/fper  Learning Objectives At the end of the lecture, students should be able to: define ventilation and perfusion. explain dead space and alveolar ventilation. explain pulmonary blood circulation and its regulation. define the gravitational effects on ventilation perfusion inequality. discuss ventilation perfusion mismatch. OBJECTIVE 1 Define ventilation and perfusion www.ukm.my/fper 1) Ventilation (V) ✓ The process of moving air in and out of the lungs, specifically the exchange of gases (O2 and CO2) between the lungs and the external environment. During ventilation, inhalation brings O2-rich air into the lungs, while exhalation removes CO2 from the body by expelling it from the lungs. 2) Perfusion (Q) ✓ The circulation of blood through the pulmonary capillaries in the lungs. It involves the delivery of blood to the alveoli for gas exchange.  Modes of Breathing Respiratory movements can be classified: ✓ Based on pattern of muscle activity ✓ Based on quiet breathing and forced breathing Normal pattern of quiet breathing is called eupnea. Eupnea consists of shallow, deep, or combined shallow and deep breathing. ✓ A pattern of shallow (chest) breathing, called costal breathing, consists of an upward and outward movement of the chest due to contraction of the external intercostal muscles. ✓ A pattern of deep (abdominal) breathing, called diaphragmatic breathing consists of the outward movement of the abdomen due to the contraction and descent of the diaphragm. In forced breathing (hyperpnea) ✓ Forced inspiration and expiration are aided by contraction of the accessory respiratory muscles. ✓ Eg. During deep, forced inhalation, the scalene and sternocleidomastoid muscle expand thoracic cavity. While deep, forced exhalation, internal intercostal and abdominal muscles contract.  Respiratory Rate (RR) Number of breath per minute ✓ Normal adult: 12 – 18 breath/min ✓ Normal children: 18 – 30 breath/min Respiratory system can adapt to meet O2 demands of the body by varying: ✓ The number of breaths per minute (RR) ✓ Amount of air moved per breath (tidal volume)  Variation in Breathing Rhythms Eupnea: relaxed, quiet breathing. Normal RR & tidal volume 500 mL Apnea: temporary cessation of breathing Hyperpnoea: increased ventilation; RR can be increased or normal Dyspnea: labored, gasping breathing; shortness of breath Orthopnea: dyspnea that occurs when person is lying down Tachypnoea: increased RR; rapid & shallow breathing Respiratory arrest: permanent cessation of breathing Hyperventilation: increased pulmonary ventilation in excess of metabolic demand Hypoventilation: reduced pulmonary ventilation Kussmaul respiration: deep, rapid breathing often induced by acidosis Orthopnea: dyspnea that occurs when person is lying down OBJECTIVE 2 Explain dead space and alveolar ventilation Define dead space. Explain the factors affecting dead space. Respiratory Minute Volume and alveolar ventilation rate. Explain and compare the various lung volumes and capacities. www.ukm.my/fper  Dead Space (ventilation without gas exchange)  Dead Space (ventilation without gas exchange) Anatomical dead space (VD) ✓ The conducting airways where gas exchange does not take place. ✓ Normal volume = 150 ml (increases slightly with age). Physiological dead space (VP) ✓ Anatomical dead space + alveolar dead space (regions of the lung that are ventilated but no perfusion).  Dead Space (ventilation without gas exchange) Factors affecting VD Factors affecting VP Body size: increased size → increased VD Affected by changes in alveolar ventilation Body posture: standing ↑, lying ↓ & perfusion Age: loss of elastic tissues → increased VD ✓ Reduced pulmonary perfusion Gender: male has higher VD – Pulmonary embolism, pulmonary Tracheostomy: decreases VD congestion Exercise: ↑ VD ✓ Emphysema Chemicals: – Decreased O2 diffusion due to ✓ Epinephrine causes bronchodilation → reduced surface area for gas increases VD exchange ✓ Histamine/Ach cause bronchoconstriction → decreases VD  Alveolar Ventilation The volume of air available for gas exchange per minute is called alveolar ventilation (VA), VA = f(VT − VD) where VA is alveolar ventilation (milliliters per minute), f is respiratory rate - RR (frequency; breaths per minute), VT is tidal volume (milliliters per respiration), and VD is dead space (milliliters per respiration). The VA takes into account the volume of air wasted in the dead space and measures the flow of fresh gases in and out of the alveoli during a particular time interval. Eg.: A person inhales 500 mL of air, and 150 mL stays in anatomical dead space, then 350 mL reaches alveoli. VA = 12 bpm x ( 500 mL - 150 mL)= 4,200 mL/min Alveolar Ventilation Respiratory Minute Volume vs. Alveolar Ventilation Rate Respiratory Minute Volume Alveolar ventilation rate It measures pulmonary ventilation = the total Rate of alveolar ventilation = total volume of volume of gas that flows into or out of the new air entering the alveoli per minute respiratory tract per minute RR x VT VA = RR(VT – VD) E.g.: E.g.: = 12(500 – 150) = 12 x 500 ml = 4200 ml/min = 6000 ml/min.  Spirometry (The Measurement of Pulmonary Ventilation) Assessed clinically by spirometry, a method that measures volumes of air moved during inspiration and expiration. In this procedure, a subject breathes in a closed system in which air is trapped within a light plastic bell floating in water. The bell moves up when the subject exhales and down when the subject inhales. The movements of the bell cause corresponding movements of a pen, which traces a record of the breathing called a spirogram.  Spirometry (The Measurement of Pulmonary Ventilation) Tidal volume is amount of air expired/breath in quiet breathing Vital capacity is amount of air that can be forcefully exhaled after a maximum inhalation = sum of inspiratory reserve, tidal volume, and expiratory reserve  Lung Volumes and Capacities (TV) (IRV) (ERV ) (RV ) (TLC ) (IRV + TV + ERV + RV) (VC ) (IRV + TV + ERV) (IC ) (IRV + TV) (FRC ) (ERV + RV) Two general categories of respiratory dysfunction yield abnormal results during spirometry: 1) obstructive lung disease (difficulty in emptying the lungs): Because a patient with obstructive lung disease experiences more difficulty emptying the lungs than filling them, the TLC is essentially normal, but the FRC and RV are elevated as a result of the additional air trapped in the lungs following expiration. Because the RV is increased, the VC is reduced. With more air remaining in the lungs, less of the TLC is available to be used in exchanging air with the atmosphere. Another common finding is a markedly reduced FEV1 because the airflow rate is reduced by the airway obstruction. Even though both the VC and the FEV1 are reduced, the FEV1 is reduced more markedly than the VC is. As a result, the FEV1/VC% is much lower than the normal 80%— that is, much less than 80% of the reduced VC can be blown out during the first second. Breathing: fast & deep, barrel shaped chest Energy for expiration > inspiration ✓ eg: bronchiole asthma 2) restrictive lung disease (difficulty in filling the lungs) In restrictive lung disease, the lungs are less compliant than normal. Total lung capacity, inspiratory capacity, and VC are reduced because the lungs cannot be expanded as normal The percentage of the VC that can be exhaled within one second is the normal 80% or an even higher percentage because air can flow freely in the airways. Therefore, the FEV1/VC% is particularly useful in distinguishing between obstructive and restrictive lung disease. Also, in contrast to obstructive lung disease, the RV is usually normal in restrictive lung disease. Breathing: normal & shallow, peak expiratory flow (PEF) ↓ ✓ eg: kyphosis, scoliosis, kyphoscoliosis Use the graphs to explain why vital capacity is reduced in obstructive lung disease and in restrictive lung disease compared to normal as shown in previous slide?  Importance of RV and FRC To provide air between inspiration and expiration, so that PaO2 and PaCO2 will not change that much between those phases. RV  when there is a loss of elasticity. 𝑅𝑉 Eg.: Chronic bronchial asthma: > 25%. 𝑇𝑉 𝑅𝑉 In old man, > 25% due to loss of elastic tissues. 𝑇𝑉 Pulmonary fibrosis, tuberculosis → RV  and FRC . ✓  lung compliance Obstructive disease → RV  and FRC . ✓ Airway closure → additional air trapped in the lungs following expiration.  OBJECTIVE 3 Explain pulmonary blood circulation and its regulation www.ukm.my/fper Blood Circulation Gas exchange at the lungs and in the body cells moves O2 into cells and CO2 out. O2 and CO2 Exchange by DIFFUSION  Perfusion 1) Pulmonary Circulation ✓ This is the flow of blood from the heart's right ventricle through the pulmonary artery to the lungs. ✓ Pressure in various parts of the lung varies 2) Bronchial Circulation ✓ This circulation provides blood to the bronchi (airways), connective tissues, septa then to pulmonary vein  Factors Contributing To Uneven Pulmonary Perfusion 1) Gravity ✓ Blood flow at Apex of the lung < Base of the lung. 2) Intrapleural (Pip) and intra-alveolar (Palv) pressures during breathing During inspiration, Pip is more -ve ✓ Pulmonary arteries and veins distended – *central venous Pressure drops * pressure in the great veins at the entrance of right atrium ✓ Diaphragm contracts − Intra-abdominal pressure increased – inferior vena cava compressed – squeezes blood toward the heart ✓  Venous Return (VR) →  Stroke Volume (SV) →  Cardiac Output (CO)→ increases lung perfusion  Factors Contributing To Uneven Pulmonary Perfusion During expiration ✓Pip is less –ve ✓Palv increased − Thoracic veins are compressed ✓increases central venous pressure − Diaphragm relax – low intra-abdominal pressure ✓  VR →  SV →  CO → decreases lung perfusion  Regulation Of Pulmonary Perfusion The role of sympathetic nervous system in pulmonary perfusion is relatively limited compared to its involvement in systemic circulation (reduces blood flow by 30%). Influence by local factors; PAO2 & PACO2 ✓ Eg. bronchus or bronchiole obstruction ✓  PAO2 /  PACO2 – pulmonary vasoconstriction ✓ shunting blood away from low ventilated area PAO2: Partial pressure of O2 in alveoli Regulation Of Pulmonary Perfusion  Regulation Of Pulmonary Perfusion Low perfusion to certain lung areas: ✓ PACO2 - bronchoconstriction ✓Shift ventilation away from poorly perfused area Circulating humoral agents that regulate vascular tone: ✓ Pulmonary vasodilator: − Eg. NO, bradykinin, prostaglandin, prostacyclin, ANP ✓ Pulmonary vasoconstrictor − Eg. thromboxane, serotonin, Angiotensin II, etc. Ventilation-Perfusion Coupling OBJECTIVE 4 Define the gravitational effects on ventilation perfusion inequality www.ukm.my/fper  Distribution Of Perfusion In An Upright Position The heart pumps against gravity to perfuse the lung Blood pressure in the apex < base. When a person is standing upright, ventilation and perfusion are both less at the top of the lung and greater at the bottom of the lung, but gravity exerts a more marked effect on blood flow than on airflow. Therefore, the ventilation– perfusion (V:Q) ratio decreases from the top to the bottom of the lung ✓ Increased pressure will increase perfusion ✓ So, the base of the lung is better perfused compared to the apex  Distribution of Ventilation (V) & Perfusion (Q) in an upright position The lung is divided into 3 zones based on pulmonary arterial pressure (Pa), the alveolar pressure (PA), and the pulmonary venous pressure (PV). Pulmonary capillary bed is surrounded by air-filled alveoli; perfusion is affected by alveolar pressure 1) Zone I (apex): PA > Pa > Pv Pip is more –ve → greater transpulmonary P → larger alveoli Area is higher than heart level → Pa Capillary bed collapses; decreased perfusion 2) Zone II (middle): Pa > PA > Pv Intermittent perfusion (increased during systole, decreased during diastole) 3) Zone III (base): Pa > Pv > PA Small alveoli Blood flow is determined by arterial-venous pressure difference Good perfusion OBJECTIVE 5 Discuss ventilation perfusion mismatch www.ukm.my/fper  Ratio of ventilation (V) to perfusion (Q) The ventilation rate (V) refers to the volume of gas inhaled and exhaled from the lungs in a given time period (minute). Tidal volume X Respiratory rate (volume of air inhaled and exhaled in single breath) In an average man, the ventilation rate is roughly 6L/min. The perfusion (Q) of the lungs refers to the total volume of blood reaching the pulmonary capillaries in a given time period.  V & Q Mismatch Both V and Q is better at the base, however they are not perfectly matched at any zones. ✓ at the base, Q exceeds V → low V:Q ✓ at the apex, V exceeds Q → high V:Q Normal V:Q = 0.8 [4.2 Lmin-1 ventilation / 5.5Lmin-1 blood flow] Inadequate ventilation → Less V:Q ratio → impaired gas exchange → decrease PO2 and increase PCO2. A mismatch in ventilation and perfusion can arise due to either reduced ventilation of part of the lung or reduced perfusion  Effects of V:Q on PACO2 and PAO2 1) V : Q < 1 Blood passing through with no oxygenation or CO2 removal PO2 = 40 PCO2 = 45 PO2 = 104 PaO2 = 40, PaCO2 = 45 PCO2 = 40 PO2 = 149 Causes: alveoli PCO2 = 0 ✓ Pulmonary congestion – pneumonia, oedema ✓ Pulmonary collapse – atelectasis 1 2 2) V : Q = 1 (normal) 3 An "ideal" lung unit with perfectly matched V Pulmonary and Q capillary PO2 = 104; PCO2 = 40 3) V : Q > 1 and infinity Alveolar dead space with ventilated lung units that receive no blood supply Causes: ✓ Poor perfusion – low cardiac output ✓ COPD ✓ Emphysema causing non-perfused Dead space pockets of lung  Hypoventilation Hyperventilation Inadequate alveolar Alveolar ventilation exceeds ventilation in relation to metabolic demands. metabolic demands. Lung removes CO2 at faster CO2 removal does not keep up rate than it is produced with CO2 production causing resulting in hypocapnia (PaCO2 hypercapnia (PaCO2 > 44 < 36 mmHg). mmHg). Both hypoventilation & Results in hypoxemia. hyperventilation can be determined by ABG analysis.  Clinical Relevance 1) Reduced Ventilation of the Lungs HYPOXIA ✓ Primarily reduced ventilation affects oxygen levels, as carbon dioxide is more soluble and continues to diffuse despite the impairment. ✓ Eg.: Pneumonia, asthma, COPD 2) Reduced Perfusion of the Lungs REDUCE blood flow to alveoli ✓ Blood has to be redirected to other areas of the lung. ✓ Eg.: Pulmonary embolism THANK YOU  FFFJ1023: Anatomy, Physiology & Biochemistry II RESPIRATORY PHYSIOLOGY III DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] www.ukm.my/fper  Learning Objectives At the end of the lecture, students should be able to:  explain partial pressure of gases  explain diffusion capacities of gases and the factors influencing them  describe the transportation and release of oxygen  explain the significance of the oxygen-haemoglobin saturation curve and factors affecting it  describe transportation of carbon dioxide in the blood OBJECTIVE 1 Explain partial pressure of gases www.ukm.my/fper  Partial pressure of gases  The pressure of a specific gas in a mixture is called its partial pressure.  Henry’s law regarding the amount of gas dissolved in fluid depends on its: 1. Solubility of the gas in the fluid 2. Partial pressure of the gas 3. Temperature of the fluid constant  The higher the partial pressure of a gas over a liquid and the higher the solubility, the more gas will stay in solution.  As blood flows through the pulmonary capillaries, it picks up O2 from alveolar air and unloads CO2 into alveolar air.  Each gas diffuses independently from the area where its partial pressure is higher to the area where its partial pressure is lower. OBJECTIVE 2 Explain diffusion capacities of gases and the factors influencing them www.ukm.my/fper  Law of Diffusion Fick’s law: 𝐴 Vgas = x *D (P1 – P2) 𝑇 Sol *D = √MW  Rate of diffusion of a gas (Vgas) is proportional to: 1. Membrane surface area (A) 2. Partial pressure difference (P1 – P2) 3. Solubility of gas (sol)  Rate of diffusion of gases is inversely proportional to: 1. Membrane thickness (T) 2. Square root of molecular weight (MW) Gas Exchange  Gas exchange at the lungs and in the body cells moves O2 into cells and CO2 out.  O2 and CO2 Exchange by DIFFUSION  Gas Exchange (Across Blood-Gas Barrier)  Respiratory membrane is composed of several layers: 1. Fluid lining the alveolus that contains surfactant 2. Alveolar epithelium 3. Epithelial basement membrane 4. Interstitial space 5. Capillary basement membrane 6. Capillary endothelium 7. Overall thickness is < 0.5 µm  Diffusing Capacity Of The Lung For Gas  Defined as volume of a gas diffuses through the membrane each minute for a pressure difference of 1 mmHg.  CO2 (440 ml/min/mmHg ) is 20 times greater than that of O2 (21 ml/min/mmHg).  This is due to high solubility of CO2 in lipids membrane.  Factors limiting O2 diffusion  Pulmonary fibrosis  presence of fibrous tissue (scar) increases membrane thickness limit O2  low solubility of O2 in lipid membrane limit O2  Emphysema Pulmonary fibrosis  destruction of the walls of the alveoli reduce surface area for gas diffusion limit O2 diffusion shortness of breath Emphysema OBJECTIVE 3 Describe the transportation and release of oxygen www.ukm.my/fper  O2 Transport In The Blood 1. Dissolved in plasma (obeys Henry’s law) – 3%  creates partial pressure of O2 1. Solubility of the gas in the fluid 2. Temperature of the fluid 3. Partial pressure of the gas 2. Mainly bound to Hb (97%)  depends on Hb concentration in blood  1 Hb molecule binds 4 molecules of O2  increases O2 carrying capacity 70-folds O2 Transport In The Blood  Amount of O2 in the blood determined by Amount of dissolved O2 Amount of Hb in blood Affinity of Hb for O2 Changes In PO2 and PCO2 In Blood What causes oxygen to enter pulmonary capillaries from alveoli and to enter tissue cells from systemic capillaries? OBJECTIVE 4 Explain the significance of the oxygen-haemoglobin saturation curve and factors affecting it www.ukm.my/fper  Loading & Unloading Reaction lung deoxyHb + O2 tissues HbO2 Depends on PO2 of the environment – High PO2 favors the loading reaction Affinity (bond strength) of Hb for O2 The Oxyhemoglobin (O2-Hb) Dissociation Curve How to understand this O2-Hb dissociation curve? (O2 content)  The Oxyhemoglobin (O2-Hb) Dissociation Curve As PO2 increases, more O2 combines with hemoglobin.  Between 20 and 40  When the PO2 is between 60 Oxygenated blood in mmHg, large amounts of O2-Hb saturation = 30%. systemic arteries. - 100 mmHg, O2-Hb O2 are released from Hb Deoxygenated blood O2-Hb saturation = 70%. At PO2 = 100 mmHg, saturation = >90%. in response to only small (contracting skeletal Deoxygenated blood in O2-Hb saturation = 97%. muscle)  Thus, blood picks up a nearly systemic veins (average decreases in PO2. full load of O2 from the lungs at rest)  In active tissues such as even when the PO2 of contracting muscles, PO2 alveolar air is as low as 60 may drop well below 40 mmHg. mmHg.  Then, a large % of the O2 S-shaped curve is released from Hb, or sigmoidal providing more O2 to metabolically active tissues. What point on the curve represents blood in your pulmonary veins if you were jogging?  O2-Hb Dissociation Curve To summarize the O2-Hb dissociation curve,  The curve showed the difference between the arterial and venous PO2 and the % oxyhemoglobin saturation at rest.  The relationship between %Hb saturation and PO2 is depicted by an S-shaped curve with a plateau region between a blood PO2 of 60 and 100 mm Hg and a steep portion between 0 and 60 mm Hg.  The volume % of O2 in blood represents the effect of blood PO2 on the amount of O2 bound with Hb.  The PO2 is the primary factor determining the % Hb saturation.  when the PO2 is high, Hb binds with large amounts of O2 and is almost 100% saturated.  When PO2 is low, Hb is only partially saturated.  O2-Hb Dissociation Curve  When we're resting, there's a lot of oxyhemoglobin left in our blood, acting as a backup oxygen supply.  If someone stops breathing, this reserve can keep the brain and heart functioning for about 4 to 5 minutes without CPR.  This reserve oxygen can also be used when the body needs more oxygen, like during exercise.  O2-Hb Dissociation Curve  Convenient index is P50  PO2 where Hb is half-saturated (50%) with O2  A common point of reference on O2 dissociation curve.  The higher P50, the lower the affinity of Hb for O2, therefore,  The curve is shifted to the right  Higher PO2 is required to maintain 50% O2 saturation (for Hb to bind O2).  The lower P50, the higher the affinity of Hb for O2  The curve is shifted to the left  Factors affecting affinity of Hb for O2 Several other factors influence the tightness or affinity with which hemoglobin binds O2. 1) Blood pH   PCO2  pH (acidic) lower the affinity (Bohr effect)  unloading of O2 from Hb shifting the curve to the right.  The main acids produced by metabolically active tissues are lactic acid and carbonic acid. When  pH, the entire O2–Hb dissociation curve shifts to the right; at any given PO2, Hb is less saturated with O2.  deoxyHb binds H+ more actively than does HbO2 2) Blood temperature   temperature lower the affinity  unloading of O2 from Hb shifting the curve to the right.  Body temperature is often raised by the heat.  Heat is produced by contracting muscle fibers and as a by- product of the cell metabolism. Metabolically active cells require more O2 to liberate more heat. The heat in turn promote release of O2 from oxyhemoglobin.  Factors affecting affinity of Hb for O2 3) PCO2  CO2 also can bind to Hb.   PCO2 Hb releases O2 more readily.  shifting the curve to the right.  PCO2 and pH are related factors because low blood pH (acidity) results from high PCO2. As CO2 enters the blood, much of it is temporarily converted to carbonic acid (H2CO3), a reaction catalyzed by an enzyme in RBC called carbonic anhydrase (CA):  The carbonic acid thus formed in RBCs dissociates into H+ and HCO3-.   H+ concentration  pH. Thus, an  PCO2 produces a more acidic environment, which helps release O2 from Hb.   PCO2 ( pH) shifts the curve to the left.  Factors affecting affinity of Hb for O2 4) [2,3-BPG] aka 2,3-diphosphoglycerate (2,3-DPG)   2,3-BPG lower the affinity  unloading of O2 from Hb shifting the curve to the right.  Product of glycolysis in RBC HbO2 + 2,3-BPG Hb-2,3BPG + O2  Factors that affect [2,3-BPG]  Chronic hypoxia – at high altitude, chronic lung disease  Anaemia  Hormones – TH, GH, androgens  Rise in temperature – during exercise  Acidosis – inhibit glycolysis How 2,3-DPG promotes the unloading of oxygen to the tissues?  Hb Saturation During Exercise  During exercise,   PO2 in capillaries active muscle   PCO2   pH due to acidic metabolites   Temperature in active muscle  These factors lead to,  lower the affinity (Bohr effect)   unloading of O2 from Hb  shifting the curve to the right.  CO and O2 compete for the same binding sites on Hb, but Hb’s affinity for CO is >200 times that of its affinity for O2.  The combination of CO and Hb is known as carboxyhemoglobin (HbCO).  OBJECTIVE 5 Describe transportation of carbon dioxide in the blood www.ukm.my/fper  CO2 transport 1. Dissolved in plasma – 7% of CO2 transport 2. As bicarbonate ion (70%) CO2 + H2O H2CO3 H+ + HCO3- – The first reaction is very slow in plasma but fast in RBC due to presence of carbonic anhydrase (CA) – The second reaction is fast, without an enzyme 3. 23% combined with proteins (in plasma and Hb) – CO2 combines with terminal amine groups to form carbamino compounds (mainly globin of Hb)  Chloride shift  70% HCO3- diffuses from RBC into plasma in exchange with Cl- prevents excessive drop of blood pH  More HCO3- diffuse into plasma, RBC gain more positive charge.  Cl- moves into RBC to retain electrical neutrality of RBC.  bicarbonate-chloride carrier protein in the RBC membrane shuttles (passive diffusion) these HCO3- and Cl- ions in opposite direction at high rate.  RBC membrane is relatively impermeable to H+.  venous blood contains higher Cl- than arterial blood.  H+ is buffered by Hb.  Binding of Hb to H+ promotes unloading of O2 to tissues.  Bohr effect (promoting O2 transport)  A shift of O2-Hb curve in response to changes in CO2 & H+   CO2  H+ CO2 + H2O H2CO3 H+ + HCO3-  At the lung, low PCO2 and H+ the curve shift to the left – increases Hb affinity for O2  Increases O2 transport  At tissue, CO2 enters the blood, increased H+ - shift the curve to the right – Hb unload O2 to tissues  Hb buffers H+ released by H2CO3  Improves the ability to transport CO2  Haldane effect (promoting CO2 transport)  In the lung, binding of O2 to Hb will displace CO2 from the blood.  Hb becomes stronger acid.  less tendency to combine with CO2.  Hb releases H+ which will combine with HCO3- to form H2CO3.  More CO2 is released to the alveoli.  HbO2 has a reduced capacity for CO2 transport.  Increasing O2 saturation reduces CO2 contents & shift the CO2 dissociation curve to right.   formation of carbamino compound.  Release H+ from Hb and HCO3- in lungs.  In the tissues, Haldane effect causes increased CO2 transport.  Clinical Relevance  Metabolic acidosis  pH of the blood falls below 7.35  An excess of H+ production or a reduction in the HCO3- buffer  Diabetic ketoacidosis THANK YOU  FFFJ1023: Anatomy, Physiology & Biochemistry II RESPIRATORY PHYSIOLOGY IV DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] www.ukm.my/fper  Learning Objectives At the end of the lecture, students should be able to: Describe the neural and chemical control of respiration. Describe the influence of various reflexes on the activities of respiratory centre. Describe different conditions affecting ventilation. Explain the different types of hypoxia and their effects on ventilation. OBJECTIVE 1 Describe the neural and chemical control of respiration www.ukm.my/fper  Neural Control (Regulation) of Respiration The activity of respiratory muscles, including the diaphragm and external intercostal muscles, is regulated by the phrenic nerves and intercostal nerves. The respiratory centre in the brain stem, can be divided into two principal areas on the basis of location and function: 1) the medullary respiratory center in the medulla oblongata 2) the pontine respiratory group in the pons  Respiratory Centre The medullary respiratory center consists of two neuronal clusters known as: 1) the dorsal respiratory group (DRG) ✓ Forms inspiratory neurons ✓ Generate inspiratory action potentials to stimulate phrenic nerve to the diaphragm ✓ Responsible for basic rhythm of respiration (automatic breathing) ✓ Receive input from peripheral chemoreceptor and from other receptor in the lung to regulate ventilation  Respiratory Centre The medullary respiratory center consists of two neuronal clusters known as: 2) the ventral respiratory group (VRG) ✓ contain both inspiratory and expiratory neurons, both of which remain inactive during normal quiet breathing. ✓ The VRG becomes activated when forceful breathing is required, Eg. during exercise, when playing a wind instrument, or at high altitudes. ✓ Inspiratory neurons stimulate spinal interneurons → activate spinal motoneurons of respiration ✓ expiratory neurons inhibit motoneurons of phrenic nerve during expiration Respiratory Centre  Respiratory Centre The pontine respiratory group in the pons exert “fine- tuning” influences over the medullary center to help produce normal, smooth inspirations and expirations. It consists of: 1) Pneumotaxic centre ✓ sends impulses to the DRG that help “switch off” the inspiratory neurons, limiting the duration of inspiration ✓ helps to control the rate and pattern of breathing → increases respiratory rate ✓ antagonise apneustic centre and inhibit inspiration 2) Apneustic centre ✓ stimulate inspiration neuron in VRG *This two centres modify the inspiratory depth & rate established by medullary centres.  Respiratory Centre The pontine respiratory group in the ponsexert “fine- tuning” influences over the medullary center to help produce normal, smooth inspirations and expirations. It consists of: 1) Pneumotaxic centre ✓ sends impulses to the DRG that help “switch off” the inspiratory neurons, limiting the duration of inspiration ✓ helps to control the rate and pattern of breathing → increases respiratory rate ✓ antagonise apneustic centre and inhibit inspiration 2) Apneustic centre ✓ stimulate inspiration neuron in VRG *This two centres modify the inspiratory depth & rate established by medullary centres. Neural Mechanism- Summary  Chemoreceptor Regulation of Breathing Chemoreceptors - responsive to chemicals. Chemoreceptors detect the levels of CO2 in the blood by monitoring the concentrations of H+ in the blood. Chemoreceptors, are found in two major body locations: 1) Central chemoreceptors They are located throughout the brain stem, including the ventrolateral medulla oblongata. Stimulated by high [H+] in CSF and brain interstitial fluid. ✓ Blood-brain barrier is impermeable to plasma H+. ✓ Blood CO2 can easily cross BBB CO2 + H2O → H2CO3 → H+ + HCO3- They can be desensitized over time from chronic hypoxia (O2 deficiency) and increased CO2  Chemoreceptor Regulation of Breathing 2) Peripheral chemoreceptors. They are found in: ✓ the aortic arch which detects changes in blood O2 and CO2; ✓ the carotid arteries which detects changes in blood O2, CO2 and pH. Receive enormous blood supply and have high metabolic rate They respond to: ✓ hypotension / reduced blood flow ✓ hypoventilation – reduced O2 content in the blood Stimulated by ✓ increased PaCO2 and [H+] ✓ decreased PaO2 < 60 mmHg ✓ cyanide ✓ K+ – increased during exercise & induces hyperpnoea not stimulated in ✓ anaemia ✓ CO poisoning.  Effects of Blood PO2 on Ventilation Low blood PO2 (hypoxemia) has little effect on ventilation. ✓ It influences chemoreceptor sensitivity to PCO2 ✓ PO2 has to fall to about half normal before ventilation is significantly affected ✓ Emphysema reduces chemoreceptor response to PCO2 – ventilation is stimulated by hypoxic drive rather than PCO2  Effects of Blood PCO2 on Ventilation Chemoreceptors modify ventilation to maintain normal CO2, O2, and pH levels. ✓ PCO2 is most crucial because of its effects on blood pH. H2O + CO2  H2CO3  H+ + HCO3- Hyperventilation causes low CO2 (hypocapnia). Hypoventilation causes high CO2 (hypercapnia). Brain chemoreceptors are responsible for greatest effects on ventilation. ✓ H+ can't cross BBB but CO2 can, which is why it is monitored and has greatest effects. ✓ Rate and depth of ventilation adjusted to maintain arterial PCO2 of ~40 mmHg. Effects of Blood PCO2 and pH on Ventilation Changes in PCO2 regulate ventilation by a negative feedback mechanism  Modification of Ventilation Cerebral And Limbic System Chemical Control Respiration can be CO2 is major regulator voluntarily controlled and ✓ Increase or decrease in pH can modified by emotions stimulate chemo sensitive area, causing a greater rate and depth of respiration O2 levels in blood affect respiration when a 50% or greater decrease from normal levels exists Other Factors Control of Respiration Neural and chemical influences on brain stem respiratory centers. Excitatory influences (+) increase the frequency of impulses sent to the muscles of respiration and recruit additional motor units, resulting in deeper, faster breathing. Inhibitory influences (−) have the reverse effect. In some cases, the influences may be excitatory or inhibitory (+/-), depending on which receptors or brain regions are activated. The cerebral cortex also directly innervates respiratory muscle motor neurons (not shown).  Other Factors Control of Respiration 1) Pulmonary stretch receptors present in smooth muscles of the airways (bronchi & bronchioles) involved in Hering-Breuer reflex ✓ prevents over-inflation of the lung – when tidal volume increases >3x normal ✓ signal from receptors sent via vagus to DRG to “switch off” inspiration 2) Irritant receptors stimulated by noxious gases, cigarette smoke dusts, cold air results in bronchoconstriction and hyperpnoea 3) J receptors (juxtapulmonary capillary receptors) endings of nonmyelinated C fibres in alveolar walls close to capillaries results in rapid shallow breathing & dyspnoea e.g. left heart failure, interstitial lung disease 4) Bronchial C fibres response to chemicals in bronchial circulation reflex response - rapid shallow breathing, bronchoconstriction and mucus secretion  Other Factors Control of Respiration 5) Nose and upper airway receptors respond to mechanical & chemical stimulation results in reflex response – sneezing, coughing bronchoconstriction 6) Joint and muscle receptors impulses from limbs stimulate ventilation during exercise 7) Gamma system in airway obstruction (e.g. asthma), large respiratory effort required to move the lung and chest wall muscle spindles in intercostal muscles and diaphragm are stimulated reflex control on the strength of contraction 8) Arterial baroreceptors An increase in arterial BP can cause reflex hypoventilation and apnea A decrease in arterial BP results in hyperventilation (through unknown pathways) 9) Receptors for pain and temperature Pain often causes a period of apnea followed by hyperventilation Heating the skin may also result in hyperventilation OBJECTIVE 2 Describe the influence of various reflexes on the activities of respiratory centre www.ukm.my/fper  Reflex Control 1) Herring-Breuer Reflex Due to stimulation of stretch receptor in the lung during inspiration → inspiration stop. Limits the degree of inspiration and prevents overinflation of the lungs ✓ Infants – Reflex plays a role in regulating basic rhythm of breathing and preventing overinflation of lungs ✓ Adults – Reflex important only when tidal volume large as in exercise 2) Straining, vomiting–glottis closure -inhibit respiration 3) Impulse from proprioceptors in muscle and joints –ventilation ↑ 4) Cough/sneezing – deep inspiration → glottis closed → contraction of abdominal muscle → expiratory muscle contract → intrapleural pressure increase → 100 mmHg or more → when glottis open – forced expiration at 600miles/hr. 5) Yawning – Deep inspiration, to open alveoli, to prevents atelectasis. OBJECTIVE 3 Describe different conditions affecting ventilation www.ukm.my/fper  Ventilation In Exercise Ventilation increases abruptly ✓ At onset of exercise ✓ Movement of limbs has strong influence ✓ Learned component Ventilation increases gradually ✓ After immediate increase, gradual increase occurs (4-6 minutes) ✓ Anaerobic threshold is highest level of exercise without causing significant change in blood pH – If exceeded, lactic acid produced by skeletal muscles  Effect of Aging on Ventilation Vital capacity and maximum minute ventilation decrease. Residual volume and dead space  Mucociliary clearance increase. Lung compliance . Lung elasticity . Ability to remove mucus from  Residual volume and dead space respiratory passageways decreases. Gas exchange across respiratory membrane is reduced. OBJECTIVE 4 Explain the different types of hypoxia and their effects on ventilation www.ukm.my/fper  Hypoxia (=Anoxia) The deficiency of O2 supply to the tissue levels Reduced O2 1) Hypoxic hypoxia in the lungs (Eg.: high altitude) PaO2 is significantly reduced Causes: O2 ✓ Physiologic – high altitude ✓ Pathologic Hb – Hypoventilation: COPD, myasthenia gravis, poliomyelitis – Abnormal V:Q matching – Airway obstruction, pulmonary embolism: Impaired gas diffusion – Pulmonary oedema: Right-left shunt – Congenital heart disease  Hypoxia (=Anoxia) The deficiency of O2 supply to the tissue levels 2) Stagnant (ischemic) hypoxia Results of low blood flow →  Tissue perfusion O2 Normal Hb and PaO2 e.g. heart failure Hb ✓ Reduced O2 supply to tissues STAGNANT HYPOXIA  Hypoxia (=Anoxia) The deficiency of O2 supply to the tissue levels 3) Cytotoxic hypoxia Normal PAO2 & PaO2 but tissues unable to use O2 O2 Mainly due to poisoning of oxidative enzymes of the cells e.g. cyanide poisoning Hb Venous PO2 is abnormally high Inability of the tissues to use oxygen due to inhibition of the oxidative enzyme activity. CYTOTOXIC HYPOXIA  Hypoxia (=Anoxia) The deficiency of O2 supply to the tissue levels 4) Anemic hypoxia [Hb] is significantly reduced ✓ Reduced O2 content in the blood O2 Causes ✓ Large amount of blood loss Hb ✓ Reduced Hb synthesis: vitamin B12  Hb and folate deficiencies ✓ Abnormal Hb synthesis due to genetic defect: sickle cell anaemia ✓ CO poisoning: CO prevents binding of O2 to Hb ANEMIC HYPOXIA THANK YOU