Respiratory System III PDF

11/10/2023 Overview/Learning Outcomes Understand major components of lung anatomy and physiological function of the respiratory system • Anatomy and physiology of breathing • Alveoli and respiratory epithelial cells • Respiratory muscles • Respiratory control (of breathing and respiratory rate) Th...

11/10/2023 Overview/Learning Outcomes Understand major components of lung anatomy and physiological function of the respiratory system • Anatomy and physiology of breathing • Alveoli and respiratory epithelial cells • Respiratory muscles • Respiratory control (of breathing and respiratory rate) The Respiratory System III • The Mechanics of Breathing and its Control • Respiratory volumes by spirometry • Respiratory Diseases 6H4Z1020 Physiological Systems • Gas exchange & Gas Transport • Partial pressure gradients • Oxygen-haemoglobin dissociation curves Dr Virginia Hawkins [email protected] Key Reference: Pocock Human Physiology 5e Fundamentals of Anatomy & Physiology (Martini 2018: 11e pg857 -905) 1 2 Respiratory System – Gas Transport Dr M Hayes: Physiological Systems (6H4Z1020) & Systems Physiology (324Z0041 / 6H4Z1019) • Role of haemoglobin in the transport of O2 and CO2 in blood • Gas exchange across respiratory surfaces and in tissues Recommended reading: Kay & Evans Chapter 6 – The respiratory system Kay & Evans Resources (eg MCQs) – Moodle link Pocock: Chapter 25 – The Properties of Blood Chapter 32 – Intro to the respiratory system Chapter 33 – The Mechanics of breathing Chapter 34 – Alveolar ventilation & blood gas exchange Chapter 35 – Control of Respiration Pocock Resources (eg MCQs) – Moodle link Respiratory Gases & Gas Transport Other links on moodle 4 Metabolic rate and glucose oxidation Gas transport • The circulatory system delivers 02 to tissues and removes C02 from tissues • Breathing provides oxygen (O2 ) for metabolism (ATP synthesis) • Metabolic rate is the rate cells use O2 to release energy ~ energy release is about 20 k joules / litre of 02 used ~ at rest = 300 k joules / hour or 4.2 k joules / hour / kg ~ can increase during activity by more than 10x • Oxidation of glucose releases CO2, metabolic H20 and ATP: ~ C6H1206 + 602 → 6C02 + 6H20 + 36 ATP molecules (glycolysis + Citric acid cycle + oxidative phosphorylation) • Metabolism is normally aerobic but during exercise it can be anaerobic which produces lactic acid and much less ATP: ~ glucose → pyruvate + 2 ATP → lactic acid ~ the liver converts lactic acid back to pyruvate • Pulmonary (lung) circulation absorbs 02 from air and removes C02 from the body • Systemic (body) circulation delivers 02 to tissues and removes C02 from tissues • The gases diffuse down partial pressure gradients: P02 • Metabolism forms ATP 5 5 / PC02 Head & Neck C02 → Venous Return carrying CO2 3 4 Body Pulmonary blood flow 5 l / min at rest → 02 Cardiac Output carrying 02 ATP ← Tissue Metabolism  Pocock: Chapter 27 Fig 27.1; pg 412 6 6 1 11/10/2023 Pulmonary Blood Flow Gradients Partial Pressure Gradients and Gas Exchange • Partial pressure gradients across epithelial cell membranes in the alveoli cause O2 to be absorbed and CO2 to be expired • Partial pressures (P) are calculated from the total air pressure and the amount of gas in a mixture: ~ sea level air pressure at is 760 mmHg (less at altitude) ~ O2 in air is about 20.9% but CO2 is only 0.03% ~ partial pressure of O2 is 20.9% of 760 PO2 = 159 mmHg ~ partial pressure of CO2 is 0.03% of 760 PCO2 = 0.3 mmHg • Partial pressures of alveolar / expired air are typically: ~ alveolar PO2 = 104 mmHg & expired air PO2 = 130 mmHg ~ alveolar PCO2 = 40 mmHg & expired air PCO2 = 27 mmHg 7 • Blood flow through the upright lung is greatest at the base and least at the apex due to low pulmonary BP and gravity ~ pulmonary blood pressures are 25 / 8 mmHg (systolic/diastolic) ~ this effect does not occur when lying down (asleep)  Pocock: Chapter 34 Fig 34.4; pg 530 7 8 8 Oxygen absorption and transport Key steps in Gas transport • O2 and CO2 are small uncharged gas molecules that diffuse: • Oxygen diffusion is driven by partial pressure gradients: ~ between air and blood in the lungs ~ high blood flow maintains the pressure gradients for O2 to diffuse into red blood cells (RBCs) and tissues ~ between blood and cells in the tissues ~ haemoglobin is essential for efficient transport of O2 and CO2 ~ environmental air pressure is 760 mmHg ~ Po2 in environmental air is 160 mmHg (21% of 760) ~ Po2 in alveolar air is 100 mmHg (13% of 760) ~ Po2 in venous blood & tissues is 40 mmHg (5% of 760) ~ tissue Po2 falls below 40 mmHg during exercise • Haemoglobin rapidly becomes 100% saturated with O2 See Figure 23-12: Anatomy & Physiology (2011; 9/e) Martini. pg 830 9 9  Pocock: Chapter 32 Table 32.1; pg 506 • Carbon Monoxide (CO) is a poisonous gas that displaces O2 from haemoglobin binding sites 10 Gas Diffusion through Respiratory Epithelia Oxygen pick up and delivery to tissues • O2 molecules bind to all four iron atoms in haemoglobin molecules in red blood cells and are carried to the tissues • Due to the large surface area and high blood flow gas exchanges across alveolar membranes is very fast • O2 and CO2 diffuse rapidly down their partial pressure gradients • Epithelial and endothelial cells are very thin (1-2 m) Respiratory medium (air) Mucous: Absorptive epithelial cell: Extracellular fluid: Capillary endothelial cells: Red blood cells: • O2 molecules rapidly dissociate from haemoglobin in the tissues 11 O2 CO2 12 12 2 11/10/2023 Oxygen-haemoglobin Dissociation Curve at pH 7.4 Red blood cells and haemoglobin • Red blood cells (RBCs) contain haemoglobin that carries oxygen bound to an iron atom in a heam / heme group • Adult haemoglobin has 4 protein subunits: ~ 2 a subunits and 2 β subunits in adults (2 γ in a foetus) ~ each subunit has a haem (heme) / iron binding site for O2 O2 pick-up in Lungs a-subunits O2 Release to Cells ß-subunits  Pocock: Chapter 25 Fig 25.7(b); pg 372 & Biology (2008; 8/e) Campbell Ch 42; pg 924 13 14 14 Bohr Shift at low pH & Myoglobin Bohr shift releases more O2 • Increased metabolism causes blood pH to falls towards 7.2 due to increased CO2 / [H+] • Low pH causes the Bohr shift in Hb / O2 dissociation to release more oxygen to active tissues • Myoglobin is an oxygen binding protein in skeletal / heart muscle 15  Pocock: Chapter 25 Fig 25.11); pg 372  Pocock: Chapter 25 Fig 25.12 & 13; pg 374 • Myoglobin has a very high affinity for O2 and stores O2 for muscle use during anaerobic metabolism due to hypoxia 15 O2 dissociation from haemoglobin in pregnancy • A foetus forms foetal (2a2γ) 100 haemoglobin which has a Fetus higher affinity for O2 than its 80 mothers haemoglobin (Hb) Mother • Maternal Hb can unload O2 to 60 the foetus via the placenta 40 • After birth the foetal 2a2γ Hb is rapidly broken down and 20 replaced by adult 2a2β Hb 0 • Rapid breakdown of foetal Hb 0 20 40 60 80 100 can cause neonatal jaundice and a risk of brain damage P (mm Hg) O2 saturation of hemoglobin (%) 13 • During normal metabolism blood is about pH 7.4 • O2 partial pressure (PO2) in the lungs is 100 mmHg and Hb saturation is 96-100% ~ O2 pick-up by RBCs • O2 partial pressure (PO2) in tissues is < 40 mmHg and Hb saturation is < 75% ~ O2 release to cells • O2 saturation can reduce to < 20% during exercise ~ more O2 released  Campbell Biology (2011; 9/e) pg 974: O2 16 16 CO2 absorption and transport • CO2 is eliminated to prevent acidosis (low pH) • CO2 diffusion is driven by partial pressure gradients: ~ Pco2 in venous blood is 45 mmHg (6% of 760) CO2 Pick up and delivery to the lungs • Some CO2 binds haemoglobin forming carbamino-haemoglobin and is carried to the lungs in RBCs where release occurs • Most CO2 forms carbonic acid and then HCO3- and H+ • H+ reversibly binds to haemoglobin to be carried to the lungs ~ Pco2 in alveolar air is 40 mmHg (5% of 760) ~ Pco2 in fresh air is 0.23 mmHg (0.03% of 760)  Pocock: Chapter 32 Table 32.1; pg 506 17 • CO2 enters RBCs and is carried to the lungs Amerman Human Anatomy & Physiology 18 3 11/10/2023 Summary of Gas Exchange • O2 and CO2 are taken up by RBCs according to the partial pressure gradients Summary • Lung structure is specialised for its function with a large surface area available for gas exchange • Alveoli are surrounded by a capillary network • Inspiration is active, expiration is passive • Breathing is controlled by the autonomic nervous system (pons and medulla) sensing and responding to changes in blood CO2 and O2 levels Amerman Human Anatomy & Physiology 19 20 Content header • Bullet point • Bullet point 21 4