Pulmonary System Notes PDF

Chapter 13 Gas Exchange and Transport 1 Concentration & Partial Pressure of Respired Gases The body’s supply of O2 depends on its concentration and...

Chapter 13 Gas Exchange and Transport 1 Concentration & Partial Pressure of Respired Gases The body’s supply of O2 depends on its concentration and pressure in ambient air. – Ambient air pressure at sea level = 760 mmHg Partial Pressure: percentage of concentration * total pressure of a gas mixture – Dalton’s Law: total pressure = sum of partial pressure of all gases in a mixture 2 Copyright Shawn M. Arent 2024 1  Concentration & Partial Pressure of Respired Gases In Ambient Air (at sea level): O2 = 20.93% = ~ 159mmHg PO2 CO2 = 0.03% = ~ 0.23mmHg PCO2 N2 = 79.04% = ~ 600mmHg PN2 In Tracheal Air: Water vapor reduces the PO2 in the trachea about 10mmHg to 149mmHg In Alveolar Air: Alveolar Air is altered by entry of CO2 from the blood Average Alveolar PO2 = 103mmHg 14.5% O2, 5.5% CO2, 80.0% N2 3 Movement of Gas in Air & Fluids Henry’s Law – gases diffuse from high pressure to low pressure Diffusion rate into a fluid depends upon: 1. Pressure differential – In humans, the pressure difference b/w alveolar and pulmonary blood gases creates the driving force for gas diffusion across the pulmonary membrane. 2. Solubility of the gas in the fluid – CO2 is more soluble (~25x) in fluid than is O2 – this will become useful when loading/unloading the gases. 4 Copyright Shawn M. Arent 2024 2  Gas Exchange in Lungs & Tissues Gas exchange between lungs, the blood, and tissues occurs passively as established by pressure differentials Gas Exchange in the Lungs: – PO2 in alveoli ~ 100mmHg – PO2 in pulmonary capillaries ~ 40mmHg Result – O2 moves into pulmonary capillaries – PCO2 in pulmonary capillaries ~ 46mmHg (vs about 39mmHg in alveoli) Result? Solubility is the main reason this still occurs quickly – Arterial blood leaving the lungs: PO2 = 100mmHg; PCO2 = 40mmHg – These values change little even during vigorous exercise 5 Gas Exchange in Lungs & Tissues Gas exchange in the tissues: – Ultimately, pressure gradients cause diffusion of O2 into and CO2 out of tissues – Since O2 is consumed and CO2 is, essentially, equally produced in the tissues, gas pressures will differ considerably from arterial blood In vigorous exercise, PO2 in a muscle falls toward 0 (from 40 at rest), while PCO2 may approach 90 (from 46 at rest). O2 will leave the blood to enter the cell, while CO2 will flow from the cell into venous blood. Pulmonary Disease implications: – Gas transfer capacity may be impaired by: Thickening of alveolar membrane Reduction in alveolar surface area 6 Copyright Shawn M. Arent 2024 3  7 Transport of O2 in the Blood Two mechanisms exist for O2 transport: 1. Dissolved in plasma 2. Combined with hemoglobin Dissolved in Plasma: – For each 1mmHg pressure,.003mL O2 dissolves into plasma This results in ~ 3mL of O2/liter blood With 5L total blood volume = 15mL dissolved O2 This would really only sustain us for about 4 seconds! – Dissolved O2 establishes the PO2 of the blood 1. Regulates breathing (particularly at altitude) 2. Determines loading/unloading of hemoglobin 8 Copyright Shawn M. Arent 2024 4  Transport of O2 in the Blood Combined w/ Hemoglobin (Hb): – Each of four iron (Fe) atoms associated with hemoglobin combines with one O2 molecule Reaction requires no enzymes – dictated by PO2 in physical solution – Each gram of Hb combines with 1.34mL O2 – Under normal conditions, with normal Hb levels: each dL of blood contains about 20mL O2 Slightly lower in women due to less Hb/dL blood – helps explain slightly lower aerobic capacity of women – Bottom Line: 65-70 times more O2 is carried this way than normally dissolves in plasma 9 Oxygen Extraction & Carrying Capacity Volume percent (vol %) refers to milliliters of oxygen extracted from a 100mL sample of whole blood or packed red blood cells – Human whole blood carries O2 at 14 vol % at altitude – Vol % is higher in animals (& humans) residing at altitude Iron-deficiency anemia reduces O2 carrying capacity considerably – Can affect ability to maintain even moderate-intensity aerobic exercise Hematocrit: percentage of RBC in whole blood 10 Copyright Shawn M. Arent 2024 5  PO2 & Hb Saturation Cooperative Binding: binding of an oxygen molecule to the iron atom in one of the four globin chains in hemoglobin progressively facilitates the binding of subsequent molecules. – Explains hemoglobin’s sigmoidal O2 saturation curve Oxy-hemoglobin dissociation curve illustrates the saturation of Hb with oxygen at various PO2 values Percent saturation = O2 Hb x 100 O2 capacity of Hb Oxygen Transport Cascade: as O2 moves from ambient air at sea level to the mitochondria of maximally active muscle tissue, its partial pressure progressively decreases. 11 PO2 in the Lungs Hb ~ 98% saturated under normal conditions Increased PO2 doesn’t increase saturation In healthy individuals breathing ambient air at sea level, each dL leaving the lungs carries ~20.0 mL of O2 – 19.7 mL bound to Hb, 0.3 mL dissolved in plasma. Hb saturation w/ O2 changes little until PO2 declines to 60 mmHg – provides a “safety buffer” against minor PO2 fluctuations – Even at PO2 of 60, Hb is still 90% saturated! – Rapid drop-off after this though Would breathing pure O2 at sea level do any good? 12 Copyright Shawn M. Arent 2024 6  13 Arteriovenous O2 Difference The a-vO2 difference shows the amount of O2 extracted by tissues – At rest normally averages 4 to 5 mL O2/dL of blood – Keeping a large quantity of O2 on Hb provides an “emergency reserve” in case of sudden increases in metabolic demands During exercise a-vO2 difference increases up to 3 times the resting value as circulating blood gives up its O2 to the working muscle – Particularly pronounced unloading in endurance trained muscle 14 Copyright Shawn M. Arent 2024 7  Bohr Effect Conditions creating the Bohr effect: – Increased PCO2 – Increased Temperature – Increased 2,3 DPG – Decreased pH These will cause a shift to the right of the oxy-hemoglobin dissociation curve – When would these conditions exist? The Bohr Effect describes the reduced effectiveness of Hb to hold O2, particularly in PO2 range b/w 20 & 50 mm Hg – At normal alveolar PO2, the Bohr effect has almost no impact – in other words, it effects Hb unloading not Hb loading. 15 16 Copyright Shawn M. Arent 2024 8  RBC 2,3 Diphosphoglycerate RBC contain no mitochondria – Rely on glycolysis 2,3 DPG is a by-product of glycolysis from RBCs – Binds loosely to Hb reducing its affinity for O2 – Causes greater O2 release to the tissues 2,3 DPG increases with intense exercise and may increase due to training (as well as living at altitude) – Helps deliver O2 to tissues Females have higher 2,3 DPG levels than men of similar fitness status/activity level; may help compensate for the lower Hb 17 Myoglobin, Muscle’s O2 Store Myoglobin is an iron-containing globular protein in skeletal and cardiac muscle – Stores O2 intramuscularly Myoglobin only contains one iron atom Facilitates transfer of O2 to the mitochondria, particularly when exercise begins and during intense exercise when cellular PO2 rapidly declines – Not an S-shaped dissociation curve like Hb – Myoglobin actually binds & retains O2 at low PO2 more readily than Hb No Bohr Effect for myoglobin 18 Copyright Shawn M. Arent 2024 9  19 CO2 Transport Three mechanisms: 1. Dissolved in plasma – ~ 5% CO2 is transported as dissolved CO2 – The dissolved CO2 establishes the PCO2 of the blood 2. Plasma bicarbonate – Carbonic anhydrase facilitates the formation of the bicarbonate (H2CO3) – When HCO3- moves into the plasma, Cl- moves into the RBC to maintain ionic equilibrium (Chloride shift) – 60-80% of total CO2 exists as plasma bicarbonate – Once at the lungs, H+ + HCO3- H2CO3 CO2 + H2O 20 Copyright Shawn M. Arent 2024 10  CO2 Transport 3. Combined w/ Hb in the RBC – CO2 reacts directly with amino acid molecules of blood proteins, including Hb, to form carbamino compounds – Carbamino formation reverses as plasma PCO2 decreases in lungs – causes CO2 to move into solution & enter alveoli – Haldane effect: Hb interaction with O2 reduces its ability to combine with CO2 This aids in releasing CO2 in the lungs 21 Chapter 14 Dynamics of Pulmonary Ventilation 22 Copyright Shawn M. Arent 2024 11  Ventilatory Control: Neural Factors Medulla—contains respiratory center – Controls neurons to activate diaphragm and intercostals A neural center in the hypothalamus integrates input from descending neurons to influence the duration and intensity of respiratory cycle – Ascending neural signals provide peripheral feedback control via the cerebellum Incorporate feedback from chemoreceptors, receptors in the lung, proprioceptors, heat changes, & local blood flow 23 Ventilatory Control: Humoral Factors At rest, chemical state of blood exerts the largest influence on respiration Variations in arterial PO2, PCO2, acidity, & temperature activate neural units in medulla & arterial system Plasma PO2 & Peripheral Chemoreceptors – Peripheral chemoreceptors are located in aorta and carotid arteries to monitor PO2 & initiate ventilation – Ventilation increases if inspired O2 falls below ambient levels – Ventilation also increases during exercise due to: PCO2 increases Temperature increases Decreased pH stimulating peripheral chemoreceptors 24 Copyright Shawn M. Arent 2024 12  Ventilatory Control: Humoral Factors Plasma PCO2 & H+ Concentrations – PCO2 in arterial blood provides the most important respiratory stimulus at rest – Ventilation increases to decrease PCO2 – even in response to small increases in PCO2 – It’s not so much the CO2 that does this, though – it’s the plasma acidity that varies directly w/ blood’s CO2 content – A fall in pH usually reflects CO2 retention (as well as other metabolic causes like lactate accumulation) – Impact of hyperventilation & breath-holding? Hyperventilation moves alveolar air closer to ambient air in PCO2 – urge to breathe can be delayed 25 Regulation of Ventilation During Exercise Chemical Control – Metabolic by-products: CO2 and H+ – Causes an increase in respiration This can actually cause alveolar PO2 to rise above resting Non-Chemical Control – Neurogenic Factors 1. Cortical influence: neural outflow in anticipation 2. Peripheral influence: proprioceptors give feedback – Temperature has little influence on respiratory rate during exercise 26 Copyright Shawn M. Arent 2024 13  Integrated Regulation During Exercise There is really not ONE single mechanism that explains increases in ventilation (hyperpnea) due to exercise – appears to be combined (and maybe simultaneous) effects of several stimuli Phase I (beginning of exercise): neurogenic stimuli from cortex (plus feedback from active limbs) increase respiration Phase II: after about 20 seconds ventilation rises exponentially to reach steady state 1. Central command 2. Peripheral chemoreceptors (e.g., carotid bodies) Phase III: fine tuning of steady-state ventilation through peripheral sensory feedback mechanisms (e.g., CO2, H+) 27 Integrated Regulation In Recovery An abrupt decline in ventilation reflects removal of central command and input from receptors in active muscle Slower recovery phase from gradual metabolic, chemical and thermal adjustments 28 Copyright Shawn M. Arent 2024 14  29 Ventilation & Energy Demands Exercise places the most profound physiologic stress on the respiratory system Ventilation in Steady-Rate Exercise – During light to moderate exercise, ventilation increases linearly with O2 consumption and CO2 production Increases here due mostly to tidal volume – at higher intensities, breathing frequency becomes more important Averages 20-25 L of air for each L of O2 consumed – Ventilatory Equivalent (VE / VO2) Normal values ~ 25 in adults up to about 55% VO2max – 25L air breathed / LO2 consumed Normal values ~ 32 in children Mode of exercise also impacts this (lower ratio in swimming) 30 Copyright Shawn M. Arent 2024 15  Ventilation & Energy Demands Ventilation in Nonsteady-Rate Exercise – VE rises sharply and the ventilatory equivalent rises as high as 35–40 – Ventilatory Threshold – VT The point at which pulmonary ventilation increases disproportionately with O2 consumption during graded exercise – At this point, pulmonary ventilation no longer links tightly w/ O2 demand at cellular level Sodium bicarbonate in the blood buffers almost all of the lactate generated via glycolysis As lactate is buffered, CO2 is regenerated from the bicarbonate which stimulates ventilation and causes R to go above 1.0 – NOT necessarily the anaerobic threshold 31 Ventilation & Energy Demands Ventilation in Nonsteady-Rate Exercise (con’t)… – OBLA Better indicator of “anaerobiosis” Lactate threshold: describes highest O2 consumption or exercise intensity with less than a 1mM per liter increase in blood lactate above resting level OBLA signifies when blood lactate shows a systemic increase (benchmark = 4.0mM but this is debatable) – Specificity of OBLA OBLA differs with exercise mode due to muscle mass being activated OBLA occurs at lower exercise levels (lower VO2) during cycling or arm crank exercise 32 Copyright Shawn M. Arent 2024 16  Lactate (mmol) Speed (km/h) 33 Lactate (mmol) Speed (km/h) 34 Copyright Shawn M. Arent 2024 17  Lactate (mmol) Speed (km/h) 35 Lactate (mmol) Speed (km/h) 36 Copyright Shawn M. Arent 2024 18  Lactate (mmol) Speed (km/h) 37 Some Independence Between OBLA & VO2max Endurance training often improves the exercise intensity for OBLA without a concomitant increase in VO2max Different factors influence OBLA & VO2max Factors influencing ability to sustain a percentage of aerobic capacity without lactate accumulation 1. Muscle fiber type 2. Capillary density 3. Mitochondria size and number 4. Enzyme concentration 38 Copyright Shawn M. Arent 2024 19  Energy Cost of Breathing At rest and during light exercise the O2 cost of breathing is small During maximal exercise, the respiratory muscles require a significant portion of total blood flow (up to 15%) – This limits O2 available to the active locomotor muscles Respiratory Disease: – COPD may triple the O2 cost of breathing at rest This severely limits exercise capacity in COPD patients – Cost of breathing can be 40% of total O2 during exercise Cigarette Smoking: Increased airway resistance Increased rates of asthma and related symptoms Smoking increases reliance on CHO during exercise Smoking blunts HR response to exercise 39 Does Ventilation Limit Aerobic Power & Endurance ? There is less adaptation in pulmonary structure & function than in cardiovascular & neuromuscular systems w/ aerobic exercise Healthy individuals over-breathe at higher levels of O2 consumption – Produces decreased alveolar PCO2 & increased PO2 At max exercise there usually is a breathing reserve – VE at VO2max equals only 60-85% of maximal voluntary ventilation (MVV) Ventilation in healthy individuals is not the limiting factor in exercise 40 Copyright Shawn M. Arent 2024 20  An Important Exception For endurance athletes, the pulmonary system may lag behind the highly developed cardiovascular & aerobic muscular adaptations to training Exercise induced arterial hypoxemia (EIH) may occur in elite endurance athletes – Compromised arterial O2 saturation Potential mechanisms include: 1. Inequalities in ventilation-perfusion ratio w/in the lungs 2. Shunting of blood flow by-passing alveolar capillaries 3. Failure to achieve end-capillary PO2 equilibrium 41 Acid-Base Regulation Buffering: * Acids—dissociate in solution to release H+ * Bases—accept H+ to form hydroxide (OH-) ions * Buffers—minimize changes in pH Alkalosis—increased pH Acidosis—decreased pH Three mechanisms help regulate internal pH 1. Chemical buffers 2. Pulmonary ventilation 3. Renal function 42 Copyright Shawn M. Arent 2024 21  Buffers Chemical buffers: consist of a weak acid and the salt of that acid – Bicarbonate Buffers = a weak acid (carbonic acid) and the salt of the acid (sodium bicarbonate) If H+ is elevated, the weak acid forms; exerts a strong buffering action on lactate; stimulates ventilation to get rid of extra CO2 If H+ decreases (as during hyperventilation), the buffer releases H+ to try to halt CO2 movement out of the system – Phosphate Buffers: consists of phosphoric acid & sodium phosphate Exerts effects in renal tubules and intracellular fluids 43 Buffers – Protein Buffers: Intracellular proteins possess free radicals that when dissociated form OH- that reacts with H+ to form H2O Hb is the most important protein buffer Release of O2 to the tissues makes Hb a weak acid that readily accepts H+ to buffer the system Ventilatory Buffer: – Increase in free H+ stimulates ventilation – Increase ventilation, decrease PCO2 and “blow off” CO2 – Lower plasma CO2 accelerates recombination of H+ + HCO3- lowering H+ concentration – 2x the buffering capacity as the previous 3 chemical buffers 44 Copyright Shawn M. Arent 2024 22  Buffers Renal Buffers: – Kidneys regulate acidity by secreting ammonia and H+ into urine and reabsorbing chloride and bicarbonate – Important long-term defense to maintain the body’s buffer reserve 45 Effects of Short- & Long-Term Exercise During exercise pH decreases as CO2 and lactate production increase Acid-base regulation becomes increasingly more difficult during repeated, acute bouts of all-out exercise that elevate blood lactate to 30mM or higher Low levels of pH are not well tolerated and need to be quickly buffered High levels of acidosis often result in nausea, headache, & dizziness (plus muscle “burn”) 46 Copyright Shawn M. Arent 2024 23