Lecture 18.pdf

About This Chapter 18.1 Gas Exchange in the Lungs and Tissues 18.2 Gas Transport in the the Blood 18.3 Regulation of Ventilation Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.1 Pulmonary gas exchange and transport Copyright © 2019, 2016, 2013 Pearson Edu...

About This Chapter 18.1 Gas Exchange in the Lungs and Tissues 18.2 Gas Transport in the the Blood 18.3 Regulation of Ventilation Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.1 Pulmonary gas exchange and transport Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Table 18.2 Normal Blood Values in Pulmonary Medicine Blank Arterial Venous PO2 95 mm Hg (85–100) 40 mm Hg PCO2 40 mm Hg (35–45) 46 mm Hg pH 7.4 (7.38–7.42) 7.37 Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved 18.1 Gas Exchange in the Lungs and Tissue • Breathing is bulk flow of air into and out of lungs • Individual gases diffuse along partial pressure gradients until equilibrium – Total pressure of mixed gas = sum of partial pressures of individual gases – Gas exchange between alveoli and blood ▪ PO2 alveolar air  PO2 blood ▪ PCO2 blood  PCO2 alveolar air – Gas exchange between blood and tissues ▪ PO2 blood  PO2 tissue ▪ PCO tissue  PCO blood 2 2 Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.2 Gases diffuse down concentration gradients Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.3(b) Factors Affecting Gas Exchange in the Alveoli (b) Cells form a diffusion barrier between lung and blood. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.3(c) Factors Affecting Gas Exchange in the Alveoli (c) Pathologies that cause hypoxia Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Gas Solubility Affects Diffusion • Movement of gases is directly proportional to 1) pressure gradient of the gas 2) solubility of the gas in liquid 3) temperature constant in mammals Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.4 Gases in solution Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved 18.2 Gas Transport in the Blood • Gas entering into the capillaries first dissolve in the plasma – Dissolved gas accounts for <2% of O2 in blood • Fick equation can be used to estimates oxygen consumption – Oxygen consumption (QO2 ) = CO  (Arterial [O2 ] − Venous[O2 ]) • Hemoglobin binds to oxygen – Hb + O2  HbO2 (oxyhemoglobin) – 4 hemes, so 4 O2 binding-sites • Oxygen binding obeys the law of mass action –  PO shifts reaction to R(Hb + O2 → HbO2 ) 2 –  P shifts reaction to L(Hb + O2  HbO2 ) O2 • Hemoglobin transports most oxygen to the tissues Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Gas Transport in the Blood • PO determines oxygen-Hb binding 2 – PO in the plasma 2 – Available of potential O2-binding sites on Hb ▪ Dependent on amount Hb in RBCs • Oxygen binding is expressed as a percentage – Percent saturation of hemoglobin – Amount of O2 bound / maximum that could be bound • Oxyhemoglobin saturation curves – Relationship between saturation and PO 2 – Demonstrates cooperative effect of each oxygen binding to Hb At normal alveolar and arterial PO2, 98% of Hb bound to oxygen —> as blood passes through lungs under normal conditions, Hb picks up nearly maximum amount of oxygen that it can carry Flat at PO2 levels higher than 100 mm Hg 100% saturated at 650 mm Hg (not possible in life) Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.5 Oxygen transport Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.7 Hemoglobin increases oxygen transport Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Several Factors Affect O2-Hb Binding • Physiological changes in plasma pH, temperature, PCO2 alter O2-binding affinity – Reflected in shape change in the Hb O2 saturation curve ▪ Shift to right: decreased affinity, more O2 released –  pH,  temperature,&  PCO2 – Represents an increase in metabolic activity ▪ Shift to left: increased affinity, less O2 released –  pH,  temperature,&  PCO2 – Represents an decrease in metabolic activity • Bohr effect is a shift in the hemoglobin saturation curve resulting from a pH change • 2,3-bisphosphoglycerate (2,3-BPG) – Shifts saturation curve to right compound made from intermediate of glycolysis pathway Chronic hypoxia triggers increase in its production in RBC which lower the biding affinity of Hb – Chronic hypoxia increases RBC production of 2,3-BPG • Hemoglobin shape also affects O2-binding affinity Fetal Hb has 2 gamma protein chains instead of 2 beta chains found in adult: enhance ability of fetal hemoglobin to bind oxygen in low-oxygen environment of placenta —> at any given placental PO2, oxygen released by maternal Hb is picked up by higher-affinity fetal Hb for delivery to fetus Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.9(a-b) Oxygen-Hemoglobin Binding Curves Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.9(c-f) Oxygen-Hemoglobin Binding Curves Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.10 Arterial oxygen Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Carbon Dioxide Is Transported in Three Ways • Dissolved in plasma (7%) or diffuses into RBCs (93%) with bound to hemoglobin (23%) or converted to HCO3 − (70%) • CO2 and bicarbonate ions – Carbonic anhydrase (CA) concentrated in RBC CO2 —> HCO3- – Chloride shift – exchanges HCO3 − for Cl− to maintain electrical neutrality • Hemoglobin and H+ – Hb + H  HbH – Respiratory acidosis If blood PCO2 is elevated much above normal, the Hb bugger can’t soak up all the H+ procured from the reaction of CO2 + water In those cases, excess H+ accumulates in plasma, causing this condition • Hemoglobin and CO2 – Hb + CO2  HbCO2 (carbaminohemoglobin) both factors decrease Hb binding affinity for oxygen H+ + HCO3- —> CO2 + H2O Decrease in plasma PCO2 allows dissolved CO2 to diffuse out of the RBC and as CO2 levels in RBC decrease, equilibrium of CO2-HCO3- reaction is disturbed, shifting to more CO2 production • CO2 Removal at the lungs – Diffusion of CO2 down PCO2 gradient from blood to alveoli Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.11 Carbon dioxide transport Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.12 Summary of O2 and CO2 exchange and transport The Bohr effect The Haldane effect Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved 18.3 Regulation of Ventilation • Neural networks in the brain stem behaves like a central pattern generator 1. Respiratory neurons in the medulla control inspiratory and expiratory muscles 2. Neurons in the pons integrate sensory information and interact with medullary neurons to influence ventilation 3. Rhythmic pattern of breathing arises from a neural network of spontaneously discharging neurons 4. Ventilation is subject to continuous modulation by chemoreceptor- and mechanoreceptor-linked reflexes and higher brain centers Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.13 The reflex control of ventilation Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Neurons in the Medulla Control Breathing • Dorsal respiratory group – Located in nucleus tractus solitaries (NTS) – To muscles of inspiration – ▪ Phrenic nerve to diaphragm ▪ Intercostal nerves to intercostal muscles Sensory input from chemo- and mechanoreceptors to pons ▪ Vagus nerve and glossopharyngeal nerve • Pontine respiratory groups and other pontine neurones provide tonic input to help coordinate smooth respiratory rhythm • Ventral respiratory group (VRG) – firing neutrons that may act as Pre-Bötzinger complex – basic pacemaker activity spontaneously basic pacemaker for respiratory rhythm – Areas for active expiration or greater-than-normal inspiration vigoureux exercise – keep upper airways open during Innervate muscles of the larynx, pharynx, and tongue tobreathing Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.14 Neural networks in the brain stem control ventilation Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved CO2, Oxygen, and pH Influence Ventilation • Peripheral chemoreceptors – Located in carotid bodies – Sense changes in PO2 , pH, and PCO2 – Specialized glomus cells ▪  PO ,  pH, and  PCO initiate increase in ventilation 2 2 ▪ O2 must fall below 60 mm Hg to trigger reflex • Central chemoreceptors – Located in CNS – Respond to changes in PCO2 – Arterial  PCO , CO2 crosses into brain ECF 2 ▪ CO2 is converted to bicarbonate and H+ ▪ H+ is actually detected Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.16 Carotid Body Cells respond to PO 2 Below 60 mm Hg Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Figure 18.17 Chemoreceptor response Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Protective Reflexes Guard the Lungs • Respond to physical injury or irritation and to over inflation • Bronchoconstriction – Irritant receptors in airway mucosa send signals through sensory neurons • Sneezing • Coughing • Hering-Breuer inflation reflex If tidal volume exceeded a certain volume in anesthetized dogs, stretch receptors in lung signalled brain stem to terminate inspiration —> does not operate during quiet breathing and mild exertion so difficult to demonstrate in humans May play a role in limiting ventilation volumes in human infants Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Higher Brain Centers Affect Patterns of Ventilation • Cerebrum and hypothalamus can change control of brain stem on breath rate and depth – Higher brain center control is not a requirement for ventilation • Limbic system (emotion) can affect breath rater and depth – Can bypass brain stem • Cannot override chemoreceptor reflexes Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Key words Hypoxia, solubility, partial pressure of the gas in solution, mass flow, Fick equation, oxyhemoglobin, Bohr effect, 2,3BPG (2,3-bisphosphoglycerate; previously called 2,3diphosphoglycerate, 2,3-DPG), carbonic anhydrase, carbonic acid, chloride shift, Haldane effect, dorsal respiratory group (DRG), pontine respiratory groups, ventral respiratory group (VRG), peripheral chemoreceptors, carotid bodies, central chemoreceptors, bronchoconstriction, irritant receptors, Hering-Breuer inflation reflex