Chapter 23 Gas Exchange and Transportation
What is air? Mixture of gasses 78.6 % nitrogen 20.9% oxygen 0.04% carbon dioxide 0 4% water vapor depending on temperature and humidity other minor gases argon, neon, helium, methane and ozone Dalton s Law the total atmospheric pressure (i.e. 760 mmhg) is the sum of the contributions of the individual gases
How do we express different concentration of gasses in air? Partial Pressure the separate contribution of each gas in a mixture (at sea level 1 atm. of pressure = 760 mmhg) nitrogen constitutes 78.6% of the atmosphere, thus PN 2 = 78.6% x 760 mm Hg = 597 mm Hg PO 2 = 20.9% x 760 mm Hg = 159 mm Hg PH 2 O = 0.5% x 760 mm Hg = 3.7 mm Hg PCO 2 = 0.04% x 760 mm Hg = 0.3 mm Hg PN 2 + PO 2 + PH 2 O + PCO 2 = 760 mmhg
We are most concerned with oxygen and carbon dioxide. How does the concentration of O2 and CO2 change between the atmosphere and systemic tissues? Oxygen 159 mmhg - atmosphere 105 mmhg - alveolar 100 mmhg - blood arterial 040 mm Hg - systemic tissue 040 mmhg - blood venous Carbon Dioxide.3 mmhg - atmosphere 40 mmhg - alveolar 40 mmhg - blood arterial 45 mmhg - systemic tissue 45 mmhg - blood venous
How is inspired air different than alveolar air? Composition of inspired air and alveolar is different because of three influences 1. air is humidified by contact with moist mucous membranes // alveolar PH 2 O is more than 10 times higher than inhaled air 2. freshly inspired air mixes with residual air left from the previous respiratory cycle // oxygen is diluted and it is enriched with CO 2 3. alveolar air exchanges O 2 and CO 2 with the blood PO 2 of alveolar air is about 65% that of inspired air PCO 2 is more than 130 times higher
How does oxygen and carbon dioxide cross the respiratory membrane? Diffusion allows O 2 and CO 2 to cross the respiratory membrane // movement from high to low concentration air in the alveolus is in contact with a film of water covering the alveolar epithelium /// for oxygen to get into the blood it must dissolve in this water (Henry s Law) pass through the respiratory membrane which separates the air from the bloodstream for carbon dioxide to leave the blood it must pass the other way // diffuse out of the water film into the alveolar air Individual gases diffuse down their own concentration gradients until the partial pressure of each gas in the air is equal to its partial pressure in water
In Alveolar Gas Exchange, What Must Happen Before Gas Molecules Can Cross the Respiratory Membrane? Henry s Law at the air-water interface, for a given temperature, the amount of gas that dissolves in the water is determined by the gass solubility in water and its partial pressure in air the greater the PO 2 in the alveolar air, the more O 2 that can be moved into blood blood arriving at an alveolus has a higher PCO 2 than air /// therefore - releases CO 2 into the lumen of the alveolus
What occurs at the respiratory membrane? Respiratory membrane is the barrier between two simple squamous epithelial cells and their shared basement membrane /// the alveoli and pulmonary capillary unload CO 2 (transported using three mechanisms) load O 2 (must be transported by RBC) Oxygen loading is dependant on how long RBC stays in alveolar capillaries 0.25 sec to load O2 (reach equilibrium) at rest, RBC spends 0.75 sec in alveolar pulmonary capillaries under strenuous exercise, still over alveolus for 0.3 sec adequate if disease destroys respiratory membrane then not enough time to load oxygen!
Pulmonary Capillaries Around Alveolus
Cross Section of Alveolus The Respiratory Membrane
Factors Affecting Gas Exchange Pressure / Solubility / Temperature / ph Respiratory Membrane Thickness / Ventilation VS Perfusion Pressure gradient of the gases PO 2 = 105 mm Hg in alveolar air versus 40 mm Hg in systemic blood PCO 2 = 45 mm Hg in systemic blood arriving versus 40 mm Hg in alveolar air Oxygen 159 mmhg - atmosphere 105 mmhg - alveolar 100 mmhg - blood arterial 040 mm Hg - systemic tissue 040 mmhg - blood venous Carbon Dioxide.3 mmhg - atmosphere 40 mmhg - alveolar 40 mmhg - blood arterial 45 mmhg - systemic tissue 45 mmhg - blood venous
What Physical Factors Affect Gas Exchange? (Pressure & Solubility) Solubility of the gases CO 2 /// 20 times as soluble as O 2 O 2 /// poorly soluble in water (said to be insoluble!)
Ambient Pressure & Concentration Gradients 2,500 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Air in hyperbaric chamber (100% O 2 at 3 atm) Ambient PO 2 (mm Hg) 158 110 Air at sea level (1 atm) Steep gradient, rapid O 2 diffusion Normal gradient and O 2 diffusion Reduced gradient, slower O 2 diffusion 40 Air at 3,000 m (10,000 ft) Atmosphere Pressure gradient of O 2 Venous blood arriving at alveoli
Factors Affecting Gas Exchange membrane thickness / membrane surface area / ventilation-perfusion coupling Membrane thickness only 0.5 m thick presents little obstacle to diffusion pulmonary edema caused by left ventricular failure results in thickening of the respiratory membrane pneumonia also causes thickening of respiratory membrane results = greater distance for gases to travel between blood and air cannot equilibrate fast enough to keep up with blood flow
Factors Affecting Gas Exchange Membrane surface area 100 ml blood in alveolar capillaries, spread thinly over 70 m 2 emphysema, lung cancer, and tuberculosis all decrease surface area for gas exchange these conditions results in hypoxia
Lung Disease Affects Gas Exchange (a) Normal (b) Pneumonia Fluid and blood cells in alveoli Alveolar walls thickened by edema Confluent alveoli (c) Emphysema
Autoregulation to Adjust Blood and Air Within Lungs Ventilation-perfusion coupling the ability to match ventilation and perfusion to each other gas exchange requires both good ventilation of alveolus and good perfusion of the capillaries ventilation-perfusion ratio of 0.8 a flow of 4.2 L of air and 5.5 L of blood per minute at rest
Perfusion Adjustments ( move blood only into areas of lungs with air) Reduced PO 2 in blood vessels Decreased airflow Increased airflow Elevated PO 2 in blood vessels Response to reduced ventilation Result: Blood flow matches airflow Response to increased ventilation Vasoconstriction of pulmonary vessels Vasodilation of pulmonary vessels Decreased blood flow Increased blood flow (a) Perfusion adjusted to changes in ventilation
Ventilation Adjustments (move air only into areas of lung with blood) Reduced PCO 2 in alveoli Decreased blood flow Increased blood flow Elevated PCO 2 in alveoli Constriction of bronchioles Response to reduced perfusion Result: Airflow matches blood flow Response to increased perfusion Dilation of bronchioles Decreased airflow Increased airflow (b) Ventilation adjusted to changes in perfusion
Gas Transport the process of carrying gases from the alveoli to the systemic tissues from the system tissues to the alveoli oxygen transport 98.5% bound to hemoglobin 1.5% dissolved in plasma carbon dioxide transport 70% as bicarbonate ion 23% bound to hemoglobin 7% dissolved in plasma
How are gasses transported in blood?
Oxygen Transport Arterial blood carries about 20 ml of O 2 per deciliter 95% bound to hemoglobin in RBC 1.5% dissolved in plasma
Oxygen Transport Hemoglobin molecule specialized in oxygen transport four protein (globin) portions each with a heme group which binds one O 2 to the ferrous ion (Fe 2+ ) one hemoglobin molecule can carry up to 4 O 2 oxyhemoglobin (HbO 2 ) O 2 bound to hemoglobin deoxyhemoglobin (HHb) hemoglobin with no O 2 100 % saturation Hb with 4 oxygen molecules 50% saturation Hb with 2 oxygen molecules
Carbon Dioxide Transport Carbon dioxide transported in three forms carbonic acid carbamino compounds dissolved in plasma
Carbon Dioxide Transport 70% of CO 2 is hydrated to form carbonic acid CO 2 + H 2 O H 2 CO 3 HCO3 - + H + then dissociates into bicarbonate and hydrogen ions 23% binds to the amino groups of plasma proteins and hemoglobin to form carbamino compounds chiefly carbaminohemoglobin (HbCO 2 ) carbon dioxide does not compete with oxygen they bind to different moieties on the hemoglobin molecule hemoglobin can transport O 2 and CO 2 simultaneously 7% is carried in the blood as dissolved gas
How is oxygen and carbon dioxide load and unload during Systemic Gas Exchange? Unloading of O 2 /// from blood into tissue Loading CO 2 /// from tissue into blood Key event occurs inside RBC // requires carbonic anhydrase CO 2 + H 2 O H 2 CO 3 HCO 3- + H + The Chloride Shift keeps reaction proceeding // exchanges HCO 3- for Cl - H + binds to hemoglobin
How is oxygen unloaded from RBC in the Systemic Gas Exchange? O 2 unloading H + binding to HbO 2 reduces its affinity for O 2 tends to make hemoglobin release oxygen HbO 2 arrives at systemic capillaries 97% saturated, leaves 75% saturated venous reserve oxygen remaining in the blood after it passes through the capillary beds utilization coefficient gives up 22% of its oxygen load
Systemic Gas Exchange Respiring tissue Capillary blood CO 2 7% Dissolved CO 2 gas CO 2 + plasma protein Carbamino compounds CO 2 23% CO 2 + Hb HbCO 2 Chloride shift Cl CO 2 70% CO 2 + H 2 O CAH H 2 CO 3 HCO 3 + H + 98.5% O 2 O 2 + HHb HbO 2 + H + O 2 1.5% Dissolved O 2 gas Key Hb HbCO 2 HbO 2 HHb CAH Hemoglobin Carbaminohemoglobin Oxyhemoglobin Deoxyhemoglobin Carbonic anhydrase
Alveolar Gas Exchange Loading and unloading oxygen and carbon dioxide across respiratory membrane in the lung tissue. The reactions that occur in the lungs are simply the reverse of systemic gas exchange
Alveolar Gas Exchange Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Alveolar air CO 2 Respiratory membrane 7% Dissolved CO 2 gas Capillary blood CO 2 + plasma protein Carbamino compounds CO 2 23% CO 2 + Hb HbCO 2 Chloride shift Cl CO 2 70% CO 2 + H 2 O CAH H 2 CO 3 HCO 3 + H + 98.5% O 2 O 2 + HHb HbO 2 + H + O 2 1.5% Dissolved O 2 gas Key Hb Hemoglobin HbCO 2 Carbaminohemoglobin HbO 2 Oxyhemoglobin HHb Deoxyhemoglobin CAH Carbonic anhydrase
Oxyhemoglobin Dissociation Curve Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 100 20 Percentage O 2 saturation of hemoglobin 80 60 40 20 15 10 5 ml O 2 /dl of blood O 2 unloaded to systemic tissues 0 0 20 40 60 80 100 Systemic tissues Alveoli Partial pressure of O 2 (PO 2 ) in mm Hg relationship between hemoglobin saturation and PO 2
Oxygen Dissociation and Temperature Percentage saturation of hemoglobin 100 90 80 70 60 50 40 30 20 10 0 10 C 20 C 38 C 43 C Normal body temperature 0 20 40 60 80 100 120 140 PO 2 (mm Hg)
100 Oxygen Dissociation and ph Percentage saturation of hemoglobin 90 80 70 60 50 40 30 20 10 0 ph 7.60 ph 7.20 ph 7.40 (normal blood ph) 0 20 40 60 80 100 120 140 PO 2 (mm Hg) Bohr effect: release of O 2 in response to low ph
This Chart Shows Fetal Hb Has a Greater Infinity for O2 Than Maternal Hb
Oxygen Unloading is Adjusted to the Tissue Metabolism Hemoglobin unloads O 2 to match metabolic needs of different states of activity of the tissues Factors that adjust the rate of oxygen unloading ambient PO 2 /// active tissue has PO 2 ; O 2 is released from Hb temperature /// active tissue has temp; promotes O 2 unloading
Adjust the Oxygen Unloading to Metabolism of Tissues Bisphosphoglycerate (BPG) intermediate in glycolisis // as concentration of BPG increases it indicates high level of anarobic metabolism RBCs produce BPG which binds to Hb /// O 2 is unloaded body temp (fever), thyroxine, growth hormone, testosterone, and epinephrine all raise BPG and cause O 2 unloading metabolic rate requires oxygen Haldane effect rate of CO 2 loading is also adjusted to varying needs of the tissues /// low level of oxyhemoglobin enables the blood to transport more CO 2
Blood Gases and the Respiratory Rhythm Rate and depth of breathing adjust to maintain these levels ph 7.35 7.45 PCO 2 40 mm Hg PO 2 95 mm Hg Brainstem respiratory centers receive input from central and peripheral chemoreceptors that monitor these factors Most potent stimulus for breathing is ph (CO 2 ) /// least significant is O 2
Hydrogen Ions (Remember CO2 = H+ ) Pulmonary ventilation is adjusted to maintain the ph within brain central chemoreceptors in the medulla oblongata produce about 75% of the change in respiration induced by ph shift yet H + does not cross the blood-brain barrier very easily CO 2 crosses blood brain barrier rapidly and in CSF reacts with water and produces carbonic acid dissociates into bicarbonate and hydrogen ions /// most H + remains free and greatly stimulates the central chemoreceptors hydrogen ions are also a potent stimulus to the peripheral chemoreceptors which produce about 25% of the respiratory response to ph change
Hydrogen Ions acidosis blood ph lower than 7.35 alkalosis blood ph higher than 7.45 hypocapnia PCO 2 less than 37 mm Hg (normal 37 43 mm Hg) /// most common cause of alkalosis hypercapnia PCO 2 greater than 43 mm Hg /// most common cause of acidosis
How does ventilation affect respiratory rate and ph? Hyperventilation and hypoventilation may change blood ph a metabolic event that changes ph can be corrected by hypoventilaiton (increase acid) or hyperventilation (decrease acid) Hyperventilation is a corrective homeostatic response to metabolic acidosis /// increase ventilation rate - blow off CO 2 faster than body produces CO2 /// remember CO2 is equivalent to free protons acid! this pushes reaction to the left CO 2 (expired) + H 2 O H 2 CO 3 HCO 3- + H + more CO2 is now delivered to the alveolus /// this reduces H + (reduces acid) and raises blood ph towards normal (ph 7.4) Note: excess ventilation then may result in alkalosis /// alkalosis in CNS will result in cesation of breathing
How does hyporventilation affect respiration? Hypoventilation is also a corrective homeostatic response to metabolic alkalosis allows CO 2 to accumulate in the body fluids faster than we exhale it shifts reaction to the right CO 2 + H 2 O H 2 CO 3 HCO 3- + H + raising the H + concentration, lowering ph to normal
Effects of Hydrogen Ions Ketoacidosis acidosis brought about by rapid fat oxidation that releases acidic ketone bodies (as in diabetes mellitus) induces Kussmaul respiration deep rapid respiration /// air hunger hyperventilation cannot remove ketone bodies however, blowing off CO 2 will reduce blood CO 2 concentration and compensates for the ketone bodies to a degree but will not completely correct imbalance
Carbon Dioxide Indirect effects on respiration /// through ph as seen previously Direct effects CO 2 at beginning of exercise may directly stimulate peripheral chemoreceptors Peripheral chemorecptors trigger ventilation more quickly than central chemoreceptors
Why does respiration increase during exercise? As upper motor neurons of brain sends motor commands to the skeletal muscles it also sends collateral signals to the respiratory centers in medulla they increase pulmonary ventilation in anticipation of the needs of the exercising muscles
Why does respiration increase during exercise? Exercise stimulates proprioceptors of the muscles and joints they transmit excitatory signals to the brainstem respiratory centers increase breathing because they are informed that the muscles have been told to move or are actually moving increase in pulmonary ventilation keeps blood gas values at their normal levels in spite of the elevated O 2 consumption and CO 2 generation by the muscles
Control of Ventilation Primary control centers for breathing // Located in the medulla and pons // chemoreceptors Central chemoreceptors // Located in the medulla Peripheral chemoreceptors // Located in the carotid bodies and aortic arch Both chemoreceptors detect changes in carbon dioxide level & hydrogen ions /// stimulates breathing Only peripheral chemoreceptors are stimulated by low oxygen levels // when O2 falls from normal 100 mmhg but still above 50 mmhg - stimulates Severe deficiency of O2 depresses central chemorecptors and DRG // DRG do not respond to any inputs and sends fewer impulses to inhalation muslces // breathing slows O2 drops more starts positive feedback with fatal results!!!
Normal Respiratory Control
Normal Control of Ventilation Hypercapnia Carbon dioxide levels in the blood increase. Carbon dioxide easily diffuses into CSF. Lowers ph and stimulates respiratory center Increased rate and depth of respirations (hyperventilation) Note: Hyperventilation causes respiratory alkalosis // nervous system depression // swimmers do this so they can hold breath longer faint under water danger!
Secondary or Non-Normal Control of Ventilation Hypoxemia // Marked decrease in oxygen Primary stimulus under normal conditions is elevated CO2 however Extended period of high CO2 will cause chemoreceptors not to react to CO2 Chemoreceptors now react to O2 levels important control mechanism in individuals with chronic lung disease This is a move to hypoxic drive
Hypoxic Drive
Respiratory Disorders & Oxygen Imbalances hypoxia a deficiency of oxygen in a tissue or the inability to use oxygen /// a consequence of respiratory diseases hypoxemic hypoxia state of low arterial PO 2 usually due inadequate pulmonary gas exchange oxygen deficiency at high elevations, impaired ventilation drowning, aspiration of a foreign body, respiratory arrest, degenerative lung diseases ischemic hypoxia inadequate circulation of blood /// congestive heart failure anemic hypoxia due to anemia resulting from the inability of the blood to carry adequate oxygen histotoxic hypoxia metabolic poisons such as cyanide prevent the tissues from using oxygen delivered to them
Carbon Monoxide Poisoning Carbon monoxide (CO) - competes for the O 2 binding sites on the hemoglobin molecule colorless, odorless gas in cigarette smoke, engine exhaust, fumes from furnaces and space heaters Carboxyhemoglobin CO binds to ferrous ion of hemoglobin binds 210 times as tightly as oxygen ties up hemoglobin for a long time non-smokers - less than 1.5% of hemoglobin occupied by CO Smokers - CO 10% in heavy smokers atmospheric concentrations of 0.2% CO is quickly lethal