The Plan Introduction – general concepts Anatomy Mechanics – moving air into the lungs Structures, pressure changes Gas Exchange – moving air from the lungs to blood and tissues Moving O2 in and CO2 out of tissues Control mechanisms Local CNS

Readings - Respiratory McKinley, O’Loughlin, and Bidle, Anatomy and Physiology An integrative Approach, p 883-931. Gas exchange 917-929

Objectives Describe the difference between external and internal respiration. Discuss the roles of Boyle’s, Dalton’s and Henry’s laws with respect to gas exchange in the lungs. Describe the role of partial pressure and diffusion during gas exchange. Discuss the influence of temperature and pH influence gas exchange. Discuss how CO2 and O2 are transported in blood.

Introduction to Gas Exchange How do you get oxygen (O2) from the air into your cells? Principle of diffusion Air is composed of many gases Gases dissolve into liquids Respiratory - Cardiovascular systems interact RBCs (in blood vessels) carry O2 and CO2

Introduction to Gas Exchange Respiration refers to two integrated processes External respiration Includes all processes involved in exchanging O2 and CO2 from the environment Internal respiration Involves the uptake of O2 and production of CO2 associated with individual cells CELLULAR RESPIRATION – use of O2 in the cell’s mitochondria in the electron transport system during metabolism Movement of O2 from air to alveoli to blood (in lungs then system) to interstitium Movement of O2 from interstitium into cells

Blood supply to the Lungs Review Remember: bronchial arteries and veins Air Trachea Pulmonary artery (deoxygenated; from right ventricle; follows bronchial tree) Pulmonary capillaries Pulmonary circulation Pulmonary veins (oxygenated; to left atrium) Artery: deoxygenated blood Systemic circulation Systemic capillaries Target cells like muscle, bone, etc. (a)

Gas Exchange Gas Exchange Occurs between alveolar air and blood across membranes: the blood-air barrier into a liquid – plasma and then into hemoglobin in the RBC Depends on Partial pressures of the gases Diffusion of molecules between gas and liquid Air (nitrogen, oxygen, carbon dioxide, etc enters alveolus and via diffusion moves across the blood-air barrier into a fluid phase – plasma and then into the RBC to attach to hemoglobin. Examine each step … air space

Gas Exchange The Gas Laws Diffusion occurs in response to concentration gradients Rate of diffusion depends on physical principles or gas laws For example, Boyle’s law (Pressure = 1/V) For example, Dalton’s law For example, Henry’s law Movement is: high to low concentration i

Gas Exchange Composition of Air Air in a container – has a pressure Nitrogen (N2) is about 78.6% Oxygen (O2) is about 20.9% Water vapor (H2O) is about 0.5% Carbon dioxide (CO2) is about 0.04% Air in a container – has a pressure All molecules in air contribute to the total pressure each gas has a Partial pressure All partial pressures together add up to 760mm Hg

Gas Exchange Patm = 760 mm Hg = PN2 + PO2 + PH20 + PCO2 Dalton’s Law and Partial Pressures (abbreviated Px) Atmospheric pressure (Patm = 760 mm Hg) Produced by air (gas) molecules bumping into the container wall Each gas contributes to the total pressure In proportion to its number of molecules (Dalton’s law) … (Air: N2 > O2 > CO2) In 760 mm Hg of air … 78.6% = N2; 20.9% = O2; 0.04% = CO2 Patm = 760 mm Hg = PN2 + PO2 + PH20 + PCO2 More bumping = more pressure Dalton:

Gas Exchange Henry’s Law (1803) When gas (O2, CO2 …) under pressure comes in contact with liquid (plasma) Gas dissolves in liquid until equilibrium is reached At a constant temperature Amount of a gas that dissolves in a given type and volume of liquid is directly proportional to partial pressure of that gas in equilibrium with that liquid Gas into liquid More partial pressure more able to dissolve into liquid http://en.wikipedia.org/wiki/Henry's_law

Gas Exchange – gas into a liquid Henry’s Law and the Relationship between Solubility and Pressure. Increased pressure by decreasing vol. Decreased pressure by increasing vol. Copyright 2009 Pearson Education Inc. publishing as Pearson Benjamin Cummings

Gas Exchange Gas Content PCO2 = 40mm Hg PO2 = 104mm Hg PN2 = 573mm Hg The actual amount of a gas in solution (at given partial pressure and temperature) depends on the solubility of that gas in that particular liquid Normal Partial Pressures (Px) -pulmonary vein (oxygenated) PCO2 = 40mm Hg PO2 = 104mm Hg PN2 = 573mm Hg Solubility in Body Fluids (plasma) CO2 is very soluble O2 is less soluble N2 has very low solubility

Blood flow in pulmonary capillary Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Summary diagram Air Space Po2 = 104 mm Hg Air Respiratory membrane Trachea Pco2 = 40 mm Hg Alveolus Pulmonary capillaries CO2 Po2 = 40 mm Hg Pco2 = 45 mm Hg O2 Pulmonary circulation Blood flow in pulmonary capillary Po2 = 104 mm Hg Pco2 = 40 mm Hg Alveolar endothelium Fused basement membranes of the alveolar epithelium and the capillary endothelium Respiratory membrane Capillary endothelium (b) Alveolar gas exchange Systemic capillaries Systemic circulation 104 mm Hg pressure drops to 95mm Hg when blood mixes from pulmonary artery to bronchial artery Blood flow in systemic capillary Po2 = 95 mm Hg CO2 Pco2 = 40 mm Hg Po2 = 40 mm Hg Pco2 = 45 mm Hg Target = muscle cells, etc. (a) Po2 = 40 mm Hg O2 Tissue cells Pco2 = 45 mm Hg Plasma membrane Interstitial fluid Capillary endothelium (c) Systemic gas exchange

Gas Exchange - gas into a liquid (plasma) Diffusion and the Blood-Air Barrier Direction and rate of diffusion of gases across the respiratory membrane is determined by differences in partial pressures and solubilities Alveolus Blood-Air Barrier O2 CO2 Alveolar capillary

Necessities for Gas Exchange Efficiency of Gas Exchange Due to: Substantial differences in partial pressure across the respiratory membrane diffusion gradients required Distances involved in gas exchange are short O2 and CO2 are lipid soluble Total surface area is large more chances for diffusion need more walls – hence more surface area Blood flow and airflow are coordinated blood takes O2 away from alveoli liquid (plasma) gas Copyright 2009 Pearson Education Inc. publishing as Pearson Benjamin Cummings

Problems for Gas Exchange Insufficiencies in Gas Exchange may occur: Substantial differences in partial pressure across the respiratory membrane Skiing in Colorado (lower oxygen levels in mountains) Receiving O2 in the hospital (higher oxygen levels received) Distances involved in gas exchange are short Fibrosis (increased CT = increased wall thickness) O2 and CO2 are lipid soluble always true … Total surface area is large Emphysema – surface area decreased Blood flow and airflow are coordinated Congestive heart failure – slows blood flow Less partial pressure, less oxygen into system (Colorado pressure) Emphysema: lose walls of epithelium

Gas Exchange: alveoli vs blood O2 and CO2 Blood arriving in (to lungs) pulmonary arteries has Low PO2 High PCO2 The concentration gradient causes O2 to enter blood CO2 to leave blood Gas exchange follows the gradients and requires coordination between blood and air flow = deoxygenated blood from the system; right side of heart PO2 is high in alveolar air space PCO2 is low “ “ “ “

Gas exchange: alveoli to blood Blood from pulmonary artery Air Space Type 1 pneumocytes Type 2 secrete surfactant

Gas Exchange: blood to ‘target’ cells Interstitial Fluid blood in systemic capillaries PO2 40 mm Hg = PO2 = 95 mm Hg PCO2 45 mm Hg = PCO2 = 40 mm Hg Concentration gradient in systemic capillaries is opposite of lungs O2 diffuses out of blood – donated to interstitium/cells CO2 diffuses into blood from interstitium/cells

Gas exchange: blood to systemic cells Air Space NOTE: change in PO2 from lung capillaries (104mm) to systemic capillaries (95mm) Blood from lung capillaries **should know this slide Target cells = muscle cells, etc.

Gas Exchange: a problem Gas Pickup and Delivery O2 solubility coefficient is very low in blood plasma. In fact only approximately 2% of the O2 is transported in plasma – thus plasma alone cannot transport enough to meet physiological needs

Gas Transport: Red blood cells Red Blood Cells (RBCs) with hemoglobin O2 and CO2 saturate plasma - this allows gases to diffuse into red blood cells Transport O2 to … and CO2 from … peripheral tissues Blood (cells and plasma) carries O2 1. only 2% dissolved in plasma 2. 98% all O attached to heme groups in RBCs Hb + O2 Hb O2 = oxyhemoglobin

Gas Transport: RBCs Oxygen Transport Hemoglobin Saturation O2 binds to iron ions in hemoglobin (Hb) molecules In a reversible reaction Each RBC has about 280 million Hb molecules Each binds four oxygen molecules Hemoglobin Saturation The percentage of heme units in a hemoglobin molecule that contain bound oxygen If it is not attached to hemoglobin, it is free. If hemoglobin is saturated, oxygen is not free

Oxygen–Hemoglobin Saturation Curve Is a graph relating the saturation of hemoglobin to partial pressure of oxygen Higher PO2 results in greater Hb saturation It’s a curve rather than a straight line Because Hb changes shape each time a molecule of O2 is bound Each O2 bound changes Hb configuration and makes next O2 binding easier This allows Hb to bind O2 when O2 levels are low Steep curve: allows hemoglobin to bind oxygen even when oxygen is low

Oxygen–Hemoglobin Saturation Curve: How to read it *know this slide Lower partial pressure, more free oxygen, less saturated hemoglobin How much O2 is saturated or how much is free?

Gas Transport Oxygen Reserves O2 diffuses from systemic capillaries (high PO2) into interstitial fluid (low PO2) and then eventually to the target cells, eg. muscle cells Amount of O2 released depends on interstitial PO2 Up to 3/4 (75%) may be reserved by RBCs Interstitial fluid: around cells Carbon monoxide takes same sites as oxygen: dangerous

Factors altering Gas Transport Carbon Monoxide CO from burning fuels Binds strongly to hemoglobin on the heme sites May displace O2 and is difficult to dissociate Can result in carbon monoxide poisoning

Factors altering Gas Transport Environmental Factors Affecting Hemoglobin PO2 of blood the higher PO2 = higher saturation Temperature Blood pH Metabolic activity within RBCs

Effects of pH and temp. on Gas Transport The Oxygen–Hemoglobin Saturation Curve Is standardized for normal blood (pH 7.4, 37°C) When pH drops or temperature rises More oxygen is released, less saturation Curve shifts to right When pH rises or temperature drops Less oxygen is released Curve shifts to left

Gas Transport: temp. & pH normal temp. The Effects of pH and Temperature on Hemoglobin Saturation. Increase temperature, more free oxygen (“burns oxygen off”) Decrease pH, more free oxygen Copyright 2009 Pearson Education Inc. publishing as Pearson Benjamin Cummings

Bohr Effect: CO2/pH and O2 Think of muscles undertaking metabolism. They give off CO2. CO2 leaves muscle and enters the systemic capillaries, into the RBCs and enters into the following reaction: CO2 + H2O H2CO3 H+ + HCO3- An increase in CO2 drives the reactions to the right and the pH drops. The pH drops because more H+ is formed. When the ([H+] increases it binds to hemoglobin, alters the configuration of Hb and forces more O2 off of the hemoglobin molecules. The release of O2 from hemoglobin is good because the muscles can use it to undertake more metabolism Bohr Effect = the H+ -induced decrease in affinity of O2 for Hb carbonic anhydrase (enzyme) carbonic acid bicarbonate ion A lot of CO2 drives reaction to right (H ions & bicarbonate) Hydrogen binds to hemoglobin, releases oxygen Low pH (more CO2), oxygen releases so you can use it http://en.wikipedia.org/wiki/Bohr_effect

Decrease in O2 saturation of Hb means more O2 is released Temperature increase = Hb saturation decrease pH decrease = Hb saturation decrease Glucose metabolism increase = Hb saturation decrease CO2 binding to Hb = oxygen release

Gas Transport: Fetal hemoglobin Fetal and Adult Hemoglobin The structure of fetal hemoglobin Differs from that of adult Hb At the same PO2 Fetal Hb binds more O2 than adult Hb Which allows fetus to take O2 from maternal blood Lower partial pressure will travel more oxygen to hemoglobin

Gas Transport A Functional Comparison of Fetal and Adult Hemoglobin.

How is Gas Transported? Carbon Dioxide Transport (CO2) Is generated as a by-product of aerobic metabolism (cellular respiration) CO2 in the bloodstream converted to carbonic acid bound to protein portion of hemoglobin (not heme groups) dissolved in plasma Oxygen Transport (O2) Plasma & hemoglobin

CO2 Transport CO2 in the Bloodstream 70% is transported as carbonic acid (H2CO3) – really HCO3- Which dissociates into H+ and bicarbonate (HCO3-) 23% is bound to amino groups of globular proteins in Hb molecule Forming carbaminohemoglobin 7% is transported as CO2 dissolved in plasma CO2 has a higher solubility coefficient than O2 Copyright 2009 Pearson Education Inc. publishing as Pearson Benjamin Cummings

CO2 – from tissues to alveoli Figure 23.27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Systemic capillary This process occurs as blood moves through systemic capillaries and carbon dioxide (CO2) moves into the blood plasma. Basement membrane Erythrocyte Endothelium 1 CO2 diffuses into an erythrocyte. #3 2 Once inside the RBC, CO2 is joined to H2O to form H2CO3 by carbonic anhydrase. Carbonic acid (H2CO3) splits into bicarbonate (HCO3–) and hydrogen ion (H+). CO2 + H2O H2CO3 HCO3– + H+ Hb H+ 2 3 HCO3–, which is negatively charged, exits from the erythrocyte. Simultaneously chloride ion (Cl–) goes into the erythrocyte to equalize the charges (to prevent development of a negative charge on the outside of the erythrocyte). The movement of HCO3– out of the erythrocyte as Cl– moves into the erythrocyte is called the chloride shift. [Note: H+ attaches (and is buffered) by hemoglobin within erythrocyte.] CO2 + H2O H2CO2 Cl– Carbonic anhydrase HCO3– 1 #2 3 Cl– HCO3– CO2 #1 Plasma Tissue cells (a) Systemic capillaries Pulmonary capillary Erythrocyte Fused basement membranes Hb 2 H+ This process is reversed as blood moves through pulmonary capillaries. 3 CO2 + H2O H2CO3 CO2 Carbonic anhydrase HCO3– moves into the erythrocyte as Cl– moves out. HCO3– 1 1 CI– 2 HCO3– recombines with H+ to form H2CO3, which dissociates into CO2 and H2O. HCO3– 3 CO2 diffuses out of the erythrocyte into the plasma. CO2 then diffuses into an alveolus. Alveolus CI– (b) Pulmonary capillaries

Gas Transport: O2 A Summary of the Primary Gas Transport Mechanisms: Oxygen Transport. 2% O associated with plasma 98% O associated with hg Copyright 2009 Pearson Education Inc. publishing as Pearson Benjamin Cummings

Transport mechanisms: O2 enters and CO2 leaves Red blood cells Cells in peripheral tissues Plasma Alveolar capillary Hb Hb O2 Hb O2 O2 O2 O2 O2 Hb O2 Alveolar air space O2 Systemic capillary O2 pickup O2 delivery Cl HCO3 Alveolar capillary Chloride shift HCO3 Alveolar air space Hb H+ + HCO3 Cl H+ + HCO3 Hb Hb H+ H2CO3 H2CO3 Hb H+ CO2 CO2 H2O CO2 H2O CO2 Hb Hb CO2 Systemic capillary Hb CO2 Hb CO2 CO2 delivery – to air space in lungs CO2 pickup - from tissues

For those who want more: Remember that high concentration of nitrogen (78.6%) in air? Your probably familiar with ‘the bends’ a problem encountered during deep sea diving. You’re diving and as you go deeper and deeper the pressure increases. According to Boyle’s law, the more pressure causes more gas to be dissolved – in this case N2 in the air - is dissolved into plasma. As you come back up to the surface, the pressure decreases and N2 begins to leave the plasma and form bubbles. Since the bubbles can go anywhere, the symptoms may vary – from skin itching, pain in the joints, muscle pain, neurologic problems like disorientation, etc. To minimize this problem, divers have to ascend at a rate – using diving tables - that is slow enough to allow N2 to escape from the blood. This rate allows it to be eliminated from the respiratory system via normal breathing. Alternatively, a diver has to go into a hyperbaric chamber until the N2 is eliminated. A hyperbaric chamber holds the diver in a chamber that has a pressure higher than atmospheric pressure and also has a high O2 concentration. Again the principle is to allow N2 to escape at a slow rate and be eliminated by normal methods. The chamber that has a high oxygen concentration to facilitate the supply of enough oxygen for normal metabolic functions. For more information see the WIKI site below. http://en.wikipedia.org/wiki/Decompression_sickness#Inert_gases