Lesson 1 Chapter 11 – The Respiratory System [Part 1]

Lesson 1 Chapter 11 – The Respiratory System [Part 1] 1 Unit 9 Study Guide The Respiratory System brings oxygen in from the atmosphere, and the cardiovascular system transports it to the cells. Simultaneously, carbon dioxide waste produced by cells is carried by the blood to the respiratory system, and is eliminated to the environment. The respiratory system is concerned with gas exchange, or external respiration, which is different from internal (or cellular) respiration. If either the respiratory or cardiovascular systems malfunction, the results are the same: homeostatic disruption, cell death from lack of oxygen, and a drastic increase in carbon dioxide in the body. The origin of the lung is mesoderm. External respiration or breathing (pulmonary ventilation) is a process of inhaling the air into the lungs and expelling the air that contains more carbon-dioxide from the lungs to the outer environment. Exchange of gases in and out of the blood also takes place simultaneously. External respiration is a physical process in which oxygen is taken up by capillaries of lung alveoli and carbon-dioxide is released from blood. Internal respiration or cellular respiration/tissue respiration is a metabolic process during which oxygen is released to tissues and carbon dioxide is absorbed by the blood. Once inside the cell the oxygen is utilized for production of energy in the form of ATP (adenosine triphosphate). Lesson 1 Chapter 11 – The Respiratory System [Part 1] 2 Pulmonary ventilation Pulmonary ventilation is commonly referred to as breathing. It is the process of air flowing into the lungs during inspiration (inhalation) and out of the lungs during expiration (exhalation). Air flows because of pressure differences between the atmosphere and the gases inside the lungs. Mechanics of Inspiration: Quiet inspiration: To explain the mechanics of inspiration, compare the thoracic cavity to a box, which has a single entrance at the top. This entrance corresponds to the trachea. The capacity of the box can be increased by increasing all its diameters. Thus the pressure within the box will reduce and the air from atmosphere will rush into it. Forced inspiration: In deep forced inspiration, maximum increase in the capacity of thoracic cavity occurs. In this process, every muscle that can raise the rib is brought into action. If the upper limbs can be supported by grasping a chair back or table, the sternal origin of the pectoralis major can also assist in the process. Mechanics of Expiration: Quiet expiration: It is largely a passive phenomenon and is brought about by elastic recoil of the lungs, relaxation of intercostals muscles and diaphragm and increased tone in muscles of abdominal wall, which force the relaxing diaphragm upwards. Forced expiration: It is an active process brought about by forced contraction of muscles of anterior abdominal wall, which are assisted by other muscles. The quadratus lumborum muscle contracts and pulls the twelfth rib downwards. Now if some of the intercostals muscles contract, they will pull the ribs together towards the 12th rib and the volume of thoracic cavity will decrease. Serratus posterior inferior and latissimus dorsi also play a minor role. Boyle’s Law A law stating that the pressure of a given mass of an ideal gas is inversely proportional to its volume at a constant temperature. Lesson 1 Chapter 11 – The Respiratory System [Part 1] The Pleural Space • Pleural sac – Double-walled, closed sac that separates each lung from the thoracic wall – Pleural cavity – interior of plural sac – Intrapleural fluid • Secreted by surfaces of the pleura • Lubricates pleural surfaces 3 Lesson 1 Chapter 11 – The Respiratory System [Part 1] 4 There are four different pressure considerations important in ventilation – Atmospheric (barometric) pressure • – Alveolar pressure (aka intrapulmonary pressure) • – the pressure in the alveoli of the lungs Pleural pressure (aka intrapleural pressure) • – the pressure exerted by the atmosphere the pressure between the visceral pleura and the thoracic pleura in the pleural cavity. Called also intrathoracic pressure Transpulmonary pressure (aka transmural pressure) • The pressure difference across the lungs; the difference between the pressure at the airway opening and the pressure on the visceral pleural surface (i.e., pressure at the airway opening - pleural pressure). Atmospheric sea level pressure = 760mmHg Intralveolar pressure = 760mmHg [at rest] During inhalation = 758-759mmHg [negative] Exhalation = 761-762mmHg [positive] Intrapleural pressure = 756 (-4) mmHg Transmural pressure = Palv - Pip Note: Quiet respiration factors +/- of 1, whereas forced deep respiration factors +/- 2 mmHg. Also: Intrapleural pressure is less than the intrapulmonary (alveolar) pressure to prevent lung collapse. Lesson 1 Chapter 11 – The Respiratory System [Part 1] 5 Pneumothorax (a) Traumatic pneumothorax. A puncture in the chest wall permits air from the atmosphere to flow down its pressure gradient and enter the pleural cavity, abolishing the transmural pressure gradient. (b) Collapsed lung. When the transmural pressure gradient is abolished, the lung collapses to its unstretched size, and the chest wall springs outward. (c) Spontaneous pneumothorax. A hole in the lung wall permits air to move down its pressure gradient and enter the pleural cavity from the lungs, abolishing the transmural pressure gradient. As with traumatic pneumothorax, the lung collapses to its unstretched size. Lesson 1 Chapter 11 – The Respiratory System [Part 1] Alveolar pressure decreases & air rushes in Alveolar pressure increases & air rushes out Factors Affecting Pulmonary Ventilation The intrapleural and intrapulmonary pressures vary during ventilation. A. The intrapleural pressure is always less than the intrapulmonary pressure. B. The intrapulmonary pressure is subatmospheric (lesser) during inspiration and greater than the atmospheric pressure during expiration. C. Pressure changes in the lungs are produced by variations in lung volume, in accordance with the inverse relationship between the volume and pressure of a gas described by Boyle’s law. The mechanics of ventilation are influenced by the physical properties of the lungs. • 1. Pulmonary compliance The compliance of the lungs, or the ease with which they expand, refers specifically to the change in lung volume per change in transpulmonary pressure (the difference between intrapulmonary pressure and intrapleural pressure). • 2. Elastic recoil The elasticity of the lungs refers to their tendency to recoil after distension. • • Elastic tissue • Alveolar surface tension (pulmonary surfactant) The surface tension of the fluid in the alveoli exerts a force directed inward, which acts to resist distension. 3. Airway resistance Mechanics of ventilation: Continued Compliance • Refers to how much effort is required to stretch or distend the lungs • The less compliant the lungs are, the more work is required to produce a given degree of inflation • Decreased by factors such as pulmonary fibrosis 6 Lesson 1 Chapter 11 – The Respiratory System [Part 1] 7 Elastic Recoil  Refers to how readily the lungs rebound after having been stretched  Responsible for lungs returning to their preinspiratory volume when inspiratory muscles relax at end of inspiration  Depends on two factors o Highly elastic connective tissue in the lungs o Alveolar surface tension  Thin liquid film lines each alveolus  Reduces tendency of alveoli to recoil Pulmonary Surfactant   Lipoprotein molecules secreted by type II alveolar cells Counter the surface tension – lowering the surface tension o Helps maintain lung stability  Newborn respiratory distress syndrome Airway Resistance • Primary determinant of resistance to airflow is the radius of the conducting airway • Autonomic nervous system controls contraction of smooth muscle in walls of bronchioles (changes the radii) • Dilation by the adrenergic system  – Directly by release of norepinephrine which activates receptors on bronchial smooth muscles – Indirectly by adrenal medulla releasing epinephrine Chronic obstructive pulmonary disease abnormally increases airway resistance o Expiration is more difficult than inspiration o Diseases  COPD (any disorder marked by persistent obstruction of bronchial air flow.)  Chronic bronchitis (a progressive lung disorder, caused by blockage of the airways, which inhibits the breathing process) Lesson 1 Chapter 11 – The Respiratory System [Part 1]   - 8 Emphysema (is a chronic respiratory disease where there is over-inflation of the air sacs (alveoli) in the lungs, causing a decrease in lung function, and often, breathlessness.) Asthma (Asthma is a chronic (long-lasting) inflammatory disease of the airways.) Sympathetic motorneurons  bronchodilation  lower Air Resistance  high air flow [Epinephrine] Parasympathetic motorneurons  bronchoconstrict.  higher A.R  lower air flow [Histamine] [Nicotine] Air flow rate (F) depends on the pressure gradient P (the difference between atmospheric and intra-alveolar pressure), and on the resistance of airways to airflow (R): P F R Pulmonary volumes and capacities Lung volume changes with different respiratory efforts. Recorded by a spirometer Lesson 1 Chapter 11 – The Respiratory System [Part 1] TV = Tidal volume (500ml) IRV = Inspiratory reserve volume (3,000 ml) IC = Inspiratory capacity (3,500 ml) ERV = Expiratory reserve volume (1,000 ml) RV = Residual volume (1,200 ml) FRC = Functional residual capacity (2,200 ml) VC = Vital capacity (4,500 ml) TLC = Total lung capacity (5,700 ml) 9 Lesson 1 Chapter 11 – The Respiratory System [Part 1] 10 (L ) 5 4 3 2 1 In s p ira to ry re se rv e v o lu m e I n s p ir a t o r y c a p a c ity V ita l c a p a c ity T id a l v o l. E x p ir a to r y re se rv e v o lu m e R e s id u a l v o lu m e F u n c tio n a l r e s id u a l c a p a c ity T o ta l lu n g c a p a c ity R e s id u a l v o lu m e Inspiratory reserve volume: the maximal volume that can be inhaled from the end-inspiratory level Tidal volume: that volume of air moved into or out of the lungs during quiet breathing (VT indicates a subdivision of the lung; when tidal volume is precisely measured, as in gas exchange calculation, the symbol VT or VT is used.) Residual volume: the volume of air remaining in the lungs after a maximal exhalation Expiratory reserve volume: the maximal volume of air that can be exhaled from the endexpiratory position Inspiratory capacity: the sum of IRV and TV Inspiratory vital capacity: the maximum volume of air inhaled from the point of maximum expiration Vital capacity: the volume of air breathed out after the deepest inhalation. Chronic obstructive lung disease (COPD) describes a group of lung conditions (diseases) that make it difficult to empty the air out of the lungs. This difficulty can lead to shortness of breath (also called breathlessness) or the feeling of being tired. COPD is a word that can be used to describe a person with chronic bronchitis, emphysema or a combination of these. COPD is a different condition from asthma, but it can be difficult to distinguish between COPD and chronic asthma. Lesson 1 Chapter 11 – The Respiratory System [Part 1] 11 What is chronic bronchitis? Chronic bronchitis is a constant swelling and irritability of the breathing tubes (bronchi or bronchioles) and results in increased mucus (phlegm) production. Chronic bronchitis is diagnosed when a person reports cough and mucus on most days for 3 months during 2 consecutive years when other lung conditions have been eliminated as a cause. This means that other conditions (and there are many) that may cause sputum production or cough are not the cause. Airway obstruction occurs in chronic bronchitis because the swelling and excessive mucus production cause the inside of the breathing tubes to be narrower than normal. The narrowing of the airways prevents the normal amount of air from reaching the lungs. The amount of narrowing is measured with a breathing test called spirometry. What is emphysema? Emphysema is a disease that involves the alveoli (air sacs) of the lung. Normally there are over 300 million alveoli in the lung. These alveoli are stretchy and springy, like little balloons. Like a balloon, it takes effort to blow-up a normal alveoli, however, it takes no energy to empty the air sac because the alveoli spring back to their original size. In emphysema, the walls of some of the alveoli have been ruined. When this happens the alveoli become stretchy and act more like paper bags. A paper bag is easy to blow-up, but you need to squeeze the bag to get the air out. So, instead of just needing effort to get air into the lungs, it also takes energy to squeeze the air out. As it is difficult to push all of the air out of the lungs, they do not empty efficiently and therefore contain more air than normal. This is called hyperinflation or air trapping. The combination of constantly having extra air in the lungs and the extra effort needed to breathe, results in the feeling of shortness of breath. The "obstruction" in emphysema is because the breathing tubes tend to collapse on exhalation, preventing you from getting the normal amount of air out of your lungs. This is a result of the loss of stable alveolar walls, which normally hold the breathing tubes open as your exhale. Airway obstruction is measured with spirometry (a breathing test). Several other tests can be performed that can tell your provider if it is likely that you have a lot of emphysema causing your COPD. Gas Exchange in the Lungs I. According to Dalton’s law, the total pressure of a gas mixture is equal to the sum of the pressures that each gas in the mixture would exert independently. A. The partial pressure of a gas in a dry gas mixture is thus equal to the total pressure times the percent composition of that gas in the mixture. Lesson 1 Chapter 11 – The Respiratory System [Part 1] 12 B. Since the total pressure of a gas mixture decreases with altitude above sea level, the partial pressures of the constituent gases likewise decrease with altitude. C. When the partial pressure of a gas in a wet gas mixture is calculated, the water vapor pressure must be taken into account. II. According to Henry’s law, the amount of gas that can be dissolved in a fluid is directly proportional to the partial pressure of that gas in contact with the fluid. A. The concentrations of oxygen and carbon dioxide that are dissolved in plasma are proportional to an electric current generated by special electrodes that react with these gases. B. Normal arterial blood has a PO2 of 100 mm Hg, indicating a concentration of dissolved oxygen of 0.3 ml per 100 ml of blood; the oxygen contained in red blood cells (about 19.7 mil per 100 ml of blood) does not affect the P O2 measurement. Pulmonary and Alveolar Ventilation • Minute ventilation is the volume of air breathed in and out in one minute – • Pulmonary ventilation (ml/min) = tidal volume (ml/breath) x respiratory frequency (breaths/min) Alveolar ventilation is more important than pulmonary ventilation – Volume of air exchanged between the atmosphere and the alveoli per minute – Less than pulmonary ventilation due to anatomic dead space • Volume of air in conducting airways that is useless for exchange • Averages about 150 ml in adults o Alveolar ventilation = (tidal volume – dead space) x respiratory rate = (500 – 150) X 12 breaths/min = 350 X 12 = 4200ml/min Lesson 1 Chapter 11 – The Respiratory System [Part 1] • 13 Pulmonary ventilation = Tidal volume X Respiratory Rate = 500 ml/breath X 12 breaths /min = 6000 ml/min Anatomic Dead Space • The volume of air in the conducting airways • Air not used for gas exchange = 150 ml • Alveolar ventilation is less than pulmonary ventilation because of dead space Hemoglobin and Oxygen Transport I. Hemoglobin is composed of two alpha and two beta polypeptide chains and four heme groups, each containing a central atom of iron. o When the iron is in the reduced form and not attached to oxygen, the hemoglobin is called deoxyhemoglobin, or reduced hemoglobin; when it is attached to oxygen, it is called oxyhemoglobin. o If the iron is attached to carbon monoxide, the hemoglobin is called carboxyhemoglobin. When the iron is in an oxidized state and unable to transport any gas, the hemoglobin is called methemoglobin. o Deoxyhemoglobin combines with oxygen in the lungs (the loading reaction) and breaks its bonds with oxygen in the tissue capillaries (the unloading reaction). The extent of each reaction is determined by the PO2 and the affinity of hemoglobin for oxygen. II. A graph of percent oxyhemoglobin is saturation at different values of PO2 is called an oxyhemoglobin dissociation curve. o At rest, the difference between arterial and venous oxyhemoglobin saturations indicates that about 22% of the oxyhemoglobin unloads its oxygen to the tissues. o During exercise, the venous PO2 and percent oxyhemoglobin saturation are decreased, indicating a higher percent of the oxyhemoglobin unloaded its oxygen to the tissues. Lesson 1 Chapter 11 – The Respiratory System [Part 1] 14 III. The pH and temperature of the blood influence the affinity of hemoglobin for oxygen and thus the extent of loading and unloading. o A fall in pH decreases the affinity of hemoglobin for oxygen, and a rise in pH increases the affinity. This is called the Bohr effect. o A rise in temperature decreases the affinity of hemoglobin for oxygen. o When the affinity is decreased, the oxyhemoglobin dissociation curve is shifted to the right. This indicates a greater percentage unloading of oxygen to the tissues. IV. The affinity of hemoglobin for oxygen is also decreased by an organic molecule in the red blood cells called 2,3-diphosphoglyceric acid (2,3-DPG). o Since oxyhemoglobin inhibits 2,3-DPG production, 2,3-DPG concentrations will be higher when anemia or low PO2 (as in high altitude) causes a decrease in oxyhemoglobin. o If a person is anemic, the lowered hemoglobin concentration is partially compensated for because a higher percent of the oxyhemoglobin will unload its oxygen as a result of the effect of 2,3-DPG. o Fetal hemoglobin cannot bind to 2,3-DPG, and thus it has a higher affinity for oxygen than the mother’s hemoglobin. This facilitates the transfer of oxygen to the fetus. V. Inherited defects in the amino acid composition of hemoglobin are responsible for such diseases as sickle-cell anemia and thalassemia. VI. Striated muscles have myoglobin, a pigment related to hemoglobin, which can combine with oxygen and deliver it to the muscle cell mitochondria at low P O2values. Fick’s law • Factors influencing the rate of net diffusion of a substance across the membrane depends on: – concentration gradient/partial pressure difference – permeability / solubility and molecular weight of the gas – surface area of membrane – distance/thickness of the membrane Lesson 1 Chapter 11 – The Respiratory System [Part 1] T y p e II a lv e o la r c e ll P u lm o n a ry c a p illa ry A lv e o la r m ac ro p h a g e 0 .1  m Type I a lv e o la r c e ll Type I cells: Flattened cells represent gas exchange Type II cells: It responds to damage of the vulnerable type I cell by dividing and acting as a progenitor cell for both type I and type II cells. In addition, it synthesises, stores and releases pulmonary surfactant A lv e o lu s E ry th ro c y te 15 S u rfa c ta n t Inadequate Gas Exchange • Inadequate gas exchange can occur when the thickness of the barrier separating the air and blood is pathologically increased • As thickness increases, the rate of gas transfer decreases – Pulmonary oedema – Pulmonary fibrosis – Pneumonia Carbon Dioxide Transport and Acid-Base Balance I. Red blood cells contain an enzyme called carbonic anhydrase, which catalyzes the reversible reaction whereby carbon dioxide and water are used to form carbonic acid. o This reaction is favored by the high PCO2 in the tissue capillaries, and as a result, carbon dioxide produced by the tissues is converted into carbonic acid in the red blood cells. o Carbonic acid then ionizes to form H+ and HCO3- (bicarbonate). o Since much of the H+ is buffered by hemoglobin, but more bicarbonate is free to diffuse outward, an electrical gradient is established that draws Cl- into the red blood cells. This is called the chloride shift. Lesson 1 Chapter 11 – The Respiratory System [Part 1] 16 o A reverse chloride shift occurs in the lungs. In this process, the low P CO2 favors the conversion of carbonic acid to carbon dioxide, which can be exhaled. II. By adjusting the blood concentration of carbon dioxide and thus of carbonic acid, the process of ventilation helps to maintain proper acid-base balance of the blood. o Normal arterial blood pH is 7.40; a pH less than 7.35 is termed acidosis, and a pH greater than 7.45 is termed alkalosis. o Hyperventilation causes respiratory alkalosis, and hypoventilation causes respiratory acidosis. o Metabolic acidosis stimulates hyperventilation, which can cause a respiratory alkalosis as a partial compensation. o Production CO2 in tissue generates H+ ions: CO2 + H2O  H2CO3  H+ + HCO3o Reduced pH shifts dissociation curve to the right (Bohr shift), decreasing affinity and causing an additional amount of O2 to be unloaded without further decreases in PO2. The higher C02, there will be more acid (production of hydrogen ion. C02 is very soluble in water, so whenever C02 is released in our blood plasma, it reacts with water (look at equation above) H2C03 can be dissociated in both directions. Law of Mass Action, It depends on which substrate is greater. - In this case, the substrate are H+ and C02 - If there is too much H+, then H+ will react with HC03-, and create C02, H20, and H2C03 Lesson 1 Chapter 11 – The Respiratory System [Part 1] 17 - If the substrate C02 is higher, then that is the determiner which will dissociate into the right hand side (H+ and HC03-) VERY IMPORTANT Relationship between the acidity and shifting of the curve Whenever there is more acid, then the curve will be shifted to the right; CALLED BOHR SHIFT In a shift effect, it means that b/c of the acid situation, hemoglobin will be doing oxygen unloading with further decreases in p02 Conditions: Hypoxia - Deficiency of O2 at cellular (tissue) level Types of hypoxia: o Hypoxic Hypoxia--low pO2 in arterial blood  high altitude, fluid in lungs & obstructions, low ventilation o Anemic Hypoxia--too little Hb  hemorrhage or anemia - Ischemic hypoxia--blood flow is too low o Formation of emboli - block the blood flow to specific areas - Histotoxic hypoxia--cyanide poisoning o blocks metabolic stages & O2 uptake o cells are unable to use the oxygen available to them. o cyanide combines with cytochrome oxidase and inhibits cellular respiration. Bohr and Haldane Effect ** (Work in synchrony) The Haldane effect describes how oxygen concentrations determine hemoglobin's affinity for carbon dioxide. For example, high oxygen concentrations enhance the unloading of carbon dioxide. The converse is also true: low oxygen concentations promote loading of carbon dioxide onto hemoglobin. In both situations, it is oxygen that causes the change in carbon dioxide levels. The Bohr effect, on the other hand, describes how carbon dioxide and H+ affect the affinity of hemoglobin for oxygen. High CO2 and H+ concentrations cause decreases in affinity for oxygen, while low concentrations cause high affinity for oxygen. Lesson 1 Chapter 11 – The Respiratory System [Part 1] - - 18 To further illustrate the difference, it might help to look at specific examples. In the lungs, when hemoglobin loaded with carbon dioxide is exposed to high oxygen levels, hemoglobin's affinity for carbon dioxide decreases. This is an example of the Haldane effect. In active muscles, carbon dioxide and H+ levels are high. Oxygenated blood that flows past is affected by these conditions, and the affinity of hemoglobin for oxygen is decreased, allowing oxygen to be transferred to the tissues. Because we are looking at the situation from the perpsective of carbon dioxide changing oxygen affinity, this is an example of the Bohr effect.