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Physiology Unit 4 RESPIRATORY PHYSIOLOGY Respira3on • External respira3on – ven3la3on – gas exchange • Internal respira3on – cellular respira3on – gas exchange • Respiratory Cycle – Inspira3on • Moving atmospheric air into the lungs – Expira3on • Moving air out of the lungs Lungs vs. Balloons • A lung is similar to a balloon in that it resists stretch, tending to collapse almost totally unless held inflated by a pressure difference between its inside and outside • Lungs and the chest have elas3c proper3es Lung Compliance • Compliance – Elas3city – Tendency to recoil – Tendency of an elas3c structure to oppose stretching or distor3on * Resists distension • Surface tension * Resists distension - Surfactant • Reduces surface tension • Increases compliance (makes them easier to stretch) Airway Resistance F = ΔP/R • Same variables that affect resistance in blood vessels – Tube length, tube radius, fric3on – Tube radius most important factor • Airway resistance is so small that small pressure differences produce large volumes of air flow – Average atmosphere-‐to-‐alveoli pressure difference is 1 mmHg, but 500 mL of air is moved (%dal volume) – Low pressure and low resistance • Pulmonary 1/10th of systemic vascular resistance Ven3la3on • Exchange of air between atmosphere and alveoli • Atmospheric air pressure is 760 mmHg at sea level • Air moves by bulk flow – F = ΔP/R – F = (Palv – Patm)/R Boyle’s Law • Boyle’s law = (P/V) • Pressure of a given quan3ty of gas is inversely propor3onal to volume • An increase in the volume of the container (lungs) decreases the pressure of the gas (air) Ven3la3on Mechanics • Lung volume depends on: 1. Transpulmonary pressure (Ptp) • Inside to outside of the lung • Ptp = Palv – Pip • The force that keeps the lungs inflated • Transmural pressure – Across the wall 2. How compliant the lungs are Transmural Pressures What Keeps the Lungs Inflated? • Elas3c recoil of the lungs * At rest natural tendency is to collapse • Lungs are held open by the posi3ve Ptp – At rest exactly opposes elas3c recoil • Collapsing force of the lungs is 4 mmHg • Intrapleural pressure is -‐4 mmHg • Elas3c recoil of the chest * At rest natural tendency is to expand Pneumothorax • A pierce in the chest wall allows atmospheric air to rush in causing Pip to go from -‐4 mmHg to 0 mmHg • Transpulmonary pressure ac3ng to hold the lungs open is eliminated • Lung collapses • Chest wall expands Inspira3on/Expira3on • In order for air to • In order for air to move into the lungs, move out of the the pressure in the lungs, the pressure lungs must drop in the lungs must below atmospheric exceed atmospheric pressure pressure • Patm > Palv • Palv > Patm The Respiratory Cycle Par3al Pressure of Gases • Dalton’s Law Pressure of each gas is independent of the pressure of other gases Pressure of the gas is directly propor3onal to its concentra3on Individual gas pressures in air is termed the par3al pressure of a gas Atmospheric air 760 mmHg at sea level • Air is 78% nitrogen – 0.78 ×760 mmHg = 593 mmHg – PN2 = 593 mmHg • Air is 21% oxygen – 0.21 × 760 mmHg = 159 mmHg – PO2 = 159 mmHg – Al3tude and Temperature also affect pressure – – – – Par3al Pressure of O2 and CO2 in Blood Transport of O2 in the Blood • 1 Liter of blood contains 200 mL of oxygen – Dissolved in plasma – Bound to hemoglobin (Hb) • Solubility of O2 is rela3vely low – Only 3 mL of O2 can dissolve in 1 L of blood at arterial PO2 of 100 mmHg (2%) – Remaining 197 mL of oxygen bound Hb (98%) Transport of O2 in the Blood • Hemoglobin – Heme, globin – 280 million Hb per RBC x 4 = >1 billion molecules of oxygen per RBC • States of Hb – Hb • deoxyhemoglobin – O2 + Hb <-‐-‐-‐> HbO2 • Oxyhemoglobin • Oxygen carrying-‐capacity of blood – a % – Amount of HbO2 is 80 % of total Hb, the sample is 80% saturated Oxygen-‐ Hemoglobin Dissocia3on Curve • Sigmoid curve – Each Hb molecule has 4 sub-‐units – Binding coopera3vity • Binding of first O2 increases the affinity for O2 at remaining three heme units • Significance of the shape of the curve – Steep slope between 20-‐60 mmHg • Increased unloading – Plateau • At 60 mmHg, 90% satura3on • Oxygen reserve Shins in the Oxygen-‐Hemoglobin Dissocia3on Curve • Other factors influence the degree of Hb satura3on – 2,3-‐diphosphoglycerate (DPG) – Temperature – pH – PCO2 • A shin to the right decreases the affinity of Hb for O2 – increased unloading in the 3ssues • A shin to the le? increases the affinity of Hb for O2 – increased loading in the lungs Hb Satura3on Effects of DPG Concentra3on • 2,3-‐diphosphoglycerate (DPG) – Always produced by RBCs – Increase in DPG causes a shin to the right • RBCs increase produc3on of DPG when there is a decrease in PO2 PO2 (mmHg) – Higher al3tude – Anemia – Transfer from maternal blood to fetal Hb • Increased unloading in the 3ssues to maintain O2 delivery Hb Satura3on Effects of Temperature PO2 (mmHg) • Higher temperature in 3ssue capillary blood than in arterial blood • The more metabolically ac3ve the 3ssue is, the higher the temperature will be • Increased unloading in the 3ssue – Provides more metabolically ac3ve cells with more O2 Hb Satura3on Effects of pH • Higher [H+] in 3ssue capillary blood than in arterial blood – Elevated PCO2 – Metabolically produced acids such as lac3c acid • The more metabolically ac3ve the 3ssue is, the greater the [H+] – Lower pH – Higher acidity • Increased unloading in the 3ssue – Provides more metabolically ac3ve cells with more O2 Transport of CO2 in Blood • 200 mL CO2/min produced by metabolism • 10% dissolved in plasma • 30% as carbaminohemoglobin (HbCO2) – CO2 + Hb <-‐-‐-‐> HbCO2 • 60% as bicarbonate (HCO3-‐) – CO2 + H2O <-‐-‐-‐> H2CO3 <-‐-‐-‐> HCO3-‐ + H+ – Carbonic anhydrase – Present in RBCs Chloride Shin Tissue Level • Bicarbonate reacCon shins to the right...WHY?? – CO2 + H2O <-‐-‐-‐> H2CO3 <-‐-‐-‐> HCO3-‐ + H+ • Steps: – CO2 diffuses out of the 3ssue cells into the blood – CO2 moved into the red blood cells – CO2 combines with H2O to produce H2CO3 • Carbonic anhydrase makes this reac3on fast – H2CO3 dissociates producing H+ + HCO3-‐ – H+ buffered by hemoglobin, facilita3ng the offloading of O2 • Forms HHb – Cl-‐ moves into the RBC in exchange for HCO3-‐ moving into plasma – Bohr effect • Increased oxygen unloading in 3ssues • Enhanced transport of CO2 Chloride Shin Tissue Level Reverse Chloride Shin Pulmonary Capillaries • Equa3on shins to the len.....WHY?? – CO2 + H2O <-‐-‐-‐> H2CO3 <-‐-‐-‐> HCO3-‐ + H+ • Steps: – Hb oxygenated – Hb decrease in affinity for H+ – Reverse chloride shin as Cl-‐ moves into plasma and HCO3-‐ moves into the RBC – H2CO3 dissociates to CO2 + H2O – CO2 expired out • Remember: – H+ is buffered by Hb in RBC – HCO3-‐ goes into the plasma and buffers incoming H+ Reverse Chloride Shin Pulmonary Capillaries Respiratory Control Centers Rhythmical Breathing • Medulla oblongata – Respiratory Rhythmicity Center • Controls the diaphragm and intercostals • Pons – ApneusCc Center • Terminates inspira3on – Pneumotaxic Center – Modulates ac3vity of apneus3c center – Smoothes the transi3on from inspira3on to expira3on • Cyclic inhibi3on • Pulmonary stretch receptors - Cut off signal for inspira3on to allow expira3on to occur Control of Ven3la3on Monitoring PO2, PCO2, H+ • Respiratory rate and 3dal volume can be altered • Peripheral chemoreceptors – AorCc and CaroCd bodies – Provides afferent input to the medulla via the Vagus Nerve – Sensi3ve to PO2 • Central chemoreceptors – In the Medulla – Highly sensi3ve to PCO2 Control of Ven3la3on Monitoring PO2, PCO2, H+ • Peripheral chemoreceptors – Aor3c and Caro3d Bodies – Sensi3ve to: • Decreased PO2 (hypoxia) • Increased H+ due to the build up of other acids (metabolic acidosis) • Increased H+ due to CO2 reten3on (respiratory acidosis) • Central chemoreceptors – Medulla – Sensi3ve to • Increased H+ in brain extracellular fluid (CSF) – CO2 crosses blood blain barrier to s3mulate receptors Protec3ve Reflexes • Pulmonary irritant reflexes – Reflex constric3on to prevent par3culates from entering lungs – Receptors located between airway epithelial cells – Cough reflex – Sneeze reflex – Cessa3on of breathing reflex – Triggered when noxious agents are inhaled – Chronic smoking causes loss of this reflex