Chapter 16 Respiratory Physiology Copyright The McGraw-Hill Companies,

Chapter 16 Respiratory Physiology Copyright  The McGraw-Hill Companies,

Chapter 16 Respiratory Physiology Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives Explain how the intrapulmonary and intrapleural pressures vary during ventilation and relate these pressure changes to Boyles law. Define the terms compliance and elasticity, and explain now these lung properties affect ventilation. Discuss the significance of surface tension in lung mechanics, explain how the law of Laplace applies to lung function and describe the role of pulmonary surfactant. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives

(continued) Explain how inspiration and expiration are accomplished in unforced breathing and describe the accessory respiratory muscles used in forced breathing. Describe the roles of the medulla, pons, and cerebral cortex in the regulation of breathing. Explain how chemoreceptors in the medulla and the peripheral chemoreceptors in the aortic and carotid bodies respond to changes in PC02, pH, and P02. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives (continued)

Describe the loading and unloading reactions and explain how the extent of these reactions is influenced by the P0 and affinity of HB for 02. Explain how oxygen transport is influenced by changes in blood pH, temperature, and explain the effect and physiological significance of 2,3-DPG on oxygen transport. Describe the hyperpnea of exercise and explain how the anaerobic threshold is affected by endurance training. 2 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Respiration Includes 3 separate functions: Ventilation:

Gas exchange: Breathing. Between air and capillaries in the lungs. Between systemic capillaries and tissues of the body. 02 utilization: Cellular respiration. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ventilation

Mechanical process that moves air in and out of the lungs. [O2] of air is higher in the lungs than in the blood, O2 diffuses from air to the blood. C02 moves from the blood to the air by diffusing down its concentration gradient. Gas exchange occurs entirely by diffusion. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Alveoli ~ 300 million air sacs (alveoli). Large surface area (6080 m2).

Each alveolus is 1 cell layer thick. 2 types of cells: Alveolar type I: Structural cells. Alveolar type II: Secrete surfactant. Figure 16.1 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Respiratory Zone

Region of gas exchange between air and blood. Includes respiratory bronchioles and alveolar sacs. Must contain alveoli. Figure 16.4 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Conducting Zone All the structures air passes through before reaching the

respiratory zone. Warms and humidifies inspired air. Filters and cleans: Insert fig. 16.5 Mucus secreted to trap particles in the inspired air. Mucus moved by cilia to be expectorated. Figure 16.5 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Physical Properties of the Lungs Compliance:

Distensibility (stretchability): 100 x more distensible than a balloon. Ease with which the lungs can expand. Compliance is reduced by factors that produce resistance to distension. Elasticity: Tendency to return to initial size after distension. High content of elastin proteins. Very elastic and resist distension.

Recoil ability. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Surface Tension Force exerted by fluid in alveoli to resist distension. Lungs secrete and absorb fluid, leaving a very thin film of fluid. This film of fluid causes surface tension. H20 molecules at the surface are attracted to other H20 molecules by attractive forces. Force is directed inward, raising pressure in alveoli.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Law of Laplace Pressure in alveoli is directly proportional to surface tension; and inversely proportional to radius of alveoli. Insert fig. 16.11 Pressure in smaller alveolus greater. Figure 16.11 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Surfactant

Phospholipid produced by alveolar type II cells. Lowers surface tension. Insert fig. 16.12 Reduces attractive forces of hydrogen bonding by becoming interspersed between H20 molecules. As alveoli radius decreases, surfactants ability to lower surface tension increases. Figure 16.12 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Boyles Law Changes in intrapulmonary pressure occur as a result of changes in lung volume. Increase in lung volume decreases intrapulmonary pressure. Pressure of gas is inversely proportional to its volume. Air goes in. Decrease in lung volume, raises intrapulmonary pressure above atmosphere. Air goes out.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lung Pressures Intrapulmonary pressure: Intrapleural pressure: Intra-alveolar pressure (pressure in the alveoli). Pressure in the intrapleural space. Pressure is negative, due to lack of air in the intrapleural space. Transpulmonary pressure: Pressure difference across the wall of the lung. Intrapulmonary pressure intrapleural

pressure. Keeps the lungs against the chest wall. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Quiet Inspiration Active process: Contraction of diaphragm, increases thoracic volume vertically. Contraction of parasternal and internal intercostals, increases thoracic volume laterally. Increase in lung volume decreases pressure in alveoli, and air rushes in.

Pressure changes: Alveolar changes from 0 to 3 mm Hg. Intrapleural changes from 4 to 6 mm Hg. Transpulmonary pressure = +3 mm Hg. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Expiration Quiet expiration is a passive process. After being stretched, lungs recoil. Decrease in lung volume raises the pressure within alveoli above atmosphere, and pushes air out. Pressure changes:

Intrapulmonary pressure changes from 3 to +3 mm Hg. Intrapleural pressure changes from 6 to 3 mm Hg. Transpulmonary pressure = +6 mm Hg. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pulmonary Ventilation Insert fig. 16.15 Figure 16.15 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pulmonary Function Tests Assessed by spirometry. Subject breathes into a closed system in which air is trapped within a bell floating in H20.

The bell moves up when the subject exhales and down when the subject inhales. Insert fig. 16.16 Figure 16.16 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Terms Used to Describe Lung Volumes and Capacities Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anatomical Dead Space Not all of the inspired air reached the alveoli. As fresh air is inhaled it is mixed with air in anatomical dead space.

Conducting zone and alveoli where [02] is lower than normal and [C02] is higher than normal. Alveolar ventilation = F x (TV- DS). F = frequency (breaths/min.). TV = tidal volume. DS = dead space. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Restrictive and Obstructive Disorders Restrictive disorder:

Vital capacity is reduced. FVC is normal. Obstructive disorder: VC is normal. FEV1 is < 80%. Figure 16.17 Insert fig. 16.17 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pulmonary Disorders Dyspnea: Shortness of breath.

COPD (chronic obstructive pulmonary disease): Asthma: Obstructive air flow through bronchioles. Caused by inflammation and mucus secretion. Inflammation contributes to increased airway responsiveness to agents that promote bronchial constriction. IgE, exercise. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pulmonary Disorders Emphysema:

Alveolar tissue is destroyed. Chronic progressive condition that reduces surface area for gas exchange. (continued) Decreases ability of bronchioles to remain open during expiration. Cigarette smoking stimulates macrophages and leukocytes to secrete protein digesting enzymes that destroy tissue. Pulmonary fibrosis: Normal structure of lungs disrupted by accumulation of fibrous connective tissue proteins. Anthracosis. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gas Exchange in the Lungs Partial pressure: The pressure that an particular gas exerts independently. PATM = PN + P0 + PC0 + PH 0= 760 mm Hg. 02 is humidified = 105 mm Hg. 2 2 2 2

H20 contributes to partial pressure (47 mm Hg). P0 (sea level) = 150 mm Hg. 2 PC0 = 40 mm Hg. 2 Figure 16.20 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Significance of Blood P0 and PC0 Measurements 2 2

At normal P02 arterial blood = 100 mm Hg. P02 level in the systemic veins is = 40 mm Hg; PC02 = 46 mm Hg. Provides a good index of lung function. Figure 16.23 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pulmonary Circulation Rate of blood flow through the pulmonary circulation is = flow rate through the systemic circulation.

Pulmonary vascular resistance is low. Driving pressure is about 10 mm Hg. Low pressure pathway produces less net filtration than produced in the systemic capillaries. Autoregulation: Pulmonary arterioles constrict when alveolar P0 decreases. Matches ventilation/perfusion ratio. 2 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lung Ventilation/Perfusion

Ratios Functionally: Alveoli at apex are underperfused (overventilated). Alveoli at the base are underventilated (overperfused). Insert fig. 16.24 Figure 16.24 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Brain Stem Respiratory Centers

Rhythmicity center: Controls automatic breathing. Iinteracting neurons that fire either during inspiration (I neurons) or expiration (E neurons). Insert fig. 16.25 Figure 16.25 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Rhythmicity Center I neurons located primarily in dorsal

respiratory group (DRG): E neurons located in ventral respiratory group (VRG): Regulate activity of phrenic nerve. Passive process. Activity of E neurons inhibit I neurons. Rhythmicity of I and E neurons may be due to pacemaker neurons. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pons Respiratory Centers

Medullary rhythmicity center influenced by pons. Apneustic center: Promotes inspiration by stimulating the I neurons in the medulla. Pneumotaxic center: Antagonizes the apneustic center. Inhibits inspiration. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemoreceptors Monitor changes in blood PC0 , P0 , and pH. Central:

2 2 Insert fig. 16.27 Medulla. Peripheral: Carotid and aortic bodies. Control breathing indirectly. Figure 16.27 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Central Chemoreceptors More sensitive to changes in arterial PC0 . H2C03 H+ H20 + C02 2 H+ cannot cross the blood brain barrier. C02 can cross the blood brain barrier and will form H2C03. Lowers pH of CSF. Directly stimulates central chemoreceptors. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Peripheral Chemoreceptors Are not stimulated directly by changes in arterial PC0 . H20 + C02 H2C03 H+ 2 Stimulated by rise in [H+] of arterial blood. Increased [H+] stimulates peripheral chemoreceptors. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemoreceptor Control of Breathing Insert fig. 16.29

Figure 16.20 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Effects of Pulmonary Receptors on Ventilation Lungs contain receptors that influence the brain stem respiratory control centers via sensory fibers in vagus. Unmyelinated C fibers can be stimulated by: Capsaicin: Histamine and bradykinin:

Produces apnea followed by rapid, shallow breathing. Released in response to noxious agents. Irritant receptors are rapidly adaptive receptors. Hering-Breuer reflex: Pulmonary stretch receptors activated during inspiration. Inhibits respiratory centers to prevent undue tension on lungs. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hemoglobin 280 million hemoglobin/RBC. Each hemoglobin

has 4 polypeptide chains and 4 hemes. In the center of each heme group is 1 atom of iron that can combine with 1 molecule 02. Insert fig. 16.32 Figure 16.32 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hemoglobin Methemoglobin: Lacks electrons and cannot bind with 02.

(continued) Blood normally contains a small amount. Carboxyhemoglobin: The bond with carbon monoxide is 210 times stronger than the bond with oxygen. Transport of 02 to tissues is impaired. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hemoglobin Oxygen-carrying capacity of blood determined by its [hemoglobin]. Anemia:

[Hemoglobin] below normal. Polycythemia: [Hemoglobin] above normal. Hemoglobin production controlled by erythropoietin. (continued) Production stimulated by PC0 delivery to kidneys. 2 Loading/unloading depends: P0 of environment. Affinity between hemoglobin and 0 . 2 2

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Oxyhemoglobin Dissociation Curve Graphic illustration of the % oxyhemoglobin saturation at different values of P02. Loading and unloading of 02. Steep portion of the sigmoidal curve, small changes in P02 produce large differences in % saturation (unload more 02). Decreased pH, increased temperature, and increased 2,3 DPG:

Affinity of hemoglobin for 02 decreases. Greater unloading of 02: Shift to the curve to the right. Figure 16.34 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Effects of pH and Temperature Affinity is decreased when pH is decreased. Increased temperature and 2,3-DPG: Shift the curve to the

right. Insert fig. 16.35 Figure 16.35 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. C02 Transport C02 transported in the blood: HC03- (70%). Dissolved C02 (10%). Carbaminohemoglobin (20%). H20 + C02ca H2C03 High PC0

2 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chloride Shift at Systemic Capillaries H20 + C02 At the tissues, C02 diffuses into the RBC; shifts the reaction to the right. HC03- diffuses into the blood. RBC becomes more +. Cl- attracted in (Cl- shift).

H+ released buffered by combining with deoxyhemoglobin. HbC02 formed. H+ + HC03- Increased [HC03-] produced in RBC: H2C03 Unloading of 02. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbon Dioxide Transport and Chloride Shift Insert fig. 16.38 Figure 16.38 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

At Pulmonary Capillaries H20 + C02 H2C03 H+ + HC03At the alveoli, C02 diffuses into the alveoli; reaction shifts to the left. Decreased [HC03-] in RBC, HC03- diffuses into the RBC. RBC becomes more -. Deoxyhemoglobin converted to oxyhemoglobin. Cl- diffuses out (reverse Cl- shift).

Has weak affinity for H+. Gives off HbC02. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reverse Chloride Shift in Lungs Insert fig. 16.39 Figure 16.39 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ventilation During Exercise During exercise, breathing becomes deeper and more rapid.

Produce > total minute volume. Neurogenic mechanism: Sensory nerve activity from exercising muscles stimulates the respiratory muscles. Cerebral cortex input may stimulate brain stem centers. Humoral mechanism: PC0 and pH may be different at chemoreceptors. Cyclic variations in the values that cannot be detected by blood samples. Figure 16.41 2 Insert fig. 16.41 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lactate Threshold and Endurance Training Maximum rate of oxygen consumption that can be obtained before blood lactic acid levels rise as a result of anaerobic respiration. 50-70% maximum 02 uptake has been reached. Endurance trained athletes have higher lactate threshold, because of higher cardiac output. Have higher rate of oxygen delivery to muscles. Have increased content of mitochondria in skeletal muscles. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acclimatization to High

Altitude Adjustments in respiratory function when moving to an area with higher altitude: Changes in ventilation: Hypoxic ventilatory response produces hyperventilation. Affinity of hemoglobin for 02: Increases total minute volume. Increased tidal volume. Action of 2,3-DPG decreases affinity of hemoglobin for 02.

Increased hemoglobin production: Kidneys secrete erythropoietin.

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