MBChB I Respiratory Lectures 2024 PDF

MBChB I Respiratory Lectures 2024 Pressure and volume Prof. Faadiel Essop Room 3027, BMRI Email: [email protected]  Respiratory mechanics: gas laws (Dalton’s Law) Atmosphere is a mixture of gases (nitrogen [78%]; oxygen [21%]) and water vapor (1%) Ga...

MBChB I Respiratory Lectures 2024 Pressure and volume Prof. Faadiel Essop Room 3027, BMRI Email: [email protected]  Respiratory mechanics: gas laws (Dalton’s Law) Atmosphere is a mixture of gases (nitrogen [78%]; oxygen [21%]) and water vapor (1%) Gases move down pressure gradients Air is a mixture of gases Dalton’s law Total pressure = sum of partial pressures of individual gases Pressure of individual gas in a mixture is known as the partial pressure (Pgas) Atmospheric pressure (Patm) = 760 mmHg (sea level) Oxygen levels = 21% of the atmosphere What is the partial pressure of oxygen (PO2)? Partial pressure of gas (Pgas) = Patm x % gas in atmosphere PO2 = 760 x 0.21 = 160 mmHg (sea level, dry air) John Dalton 1766-1844  Respiratory mechanics: gas laws (Dalton’s Law) In humid air, water vapor “dilutes” the contribution of other gases to the total pressure Partial Pressures (Pgas) of atmospheric gases at 760 mm Hg Pgas in 25 °C air, 100% Pgas in 37 °C air, 100% Gas and its percentage in air Pgas in dry 25 °C air humidity humidity O2, 21% 160 mm Hg 155 mm Hg 150 mm Hg CO2, 0.03% 0.25 mm Hg 0.24 mm Hg 0.235 mm Hg Water vapor 0 mm Hg 24 mm Hg 47 mm Hg To calculate the partial pressure of a gas in humid air, you must first subtract the water vapor pressure from the total pressure. At 100% humidity and 25 °C, water vapor pressure = 24 mm Hg: Pgas inhumid air =(Patm − PH2O )  %of gas PO2 = (760 − 24)  21% = 155mmHg  Respiratory mechanics: gas laws (Boyle’s Law) Boyle’s Law expresses the inverse relationship between pressure and volume P1V1 = P2 V2 For example, the container on the left is 1 L (V1) and has a pressure of 100 mm Hg (P1). What happens to the pressure when the volume decreases to 0.5 L? 100mmHg 1L =P2 × 0.5L 200mmHg =P2 Hence the pressure has increased 2-fold  Respiratory mechanics: gas laws (Boyle’s Law) Robert Boyle 1627-1691 Graph shows data from Boyle’s original 1662 experiment, which shows that pressure and volume are inversely related. No units are given as he used arbitrary units in his experiments. https://courses.lumenlearning.com/wm-biology2/chapter/the-mechanics-of-human-breathing/  Respiratory mechanics: gas laws (Boyle’s Law) As the volume of the gas increases, the pressure decreases proportionately (in diagram you go from A to B to C) Conversely, the pressure increases proportionately as the volume decreases (in diagram you go from C to B to A) Note: same number of gas molecules present in all three containers Sherwood, CH13, p452 Boyle’s law: at any constant temperature, the pressure exerted by a gas varies inversely with the volume of the gas  Respiratory mechanics: gas laws (Charles’ Law) Gas volume (V) is directly proportional to temperature (T) when the pressure is constant: V1/T1 = V2/T2 The gas volume (V1) at its initial temperature (T1) will increase to V2 as its temperature increases to T2 Likewise, the gas will reduce in volume if its temperature is lowered On a cold day, as air is warmed in the conducting part of the respiratory system, it will increase in volume Jacques Charles 1746-1823  Respiratory mechanics: definitions Pulmonary ventilation: -commonly referred to as breathing -process of air flowing into the lungs during inspiration (inhalation) & out of the lungs during expiration (exhalation) Alveolar ventilation: -exchange of gas between alveoli & external environment Respiratory cycle: -consists of one breath in (inhalation; inspiration) & one breath out (exhalation; expiration) Air moves into & out of lungs (during breathing) from a region of higher pressure to a region of lower pressure – down a pressure gradient Ventilation from ventilatio (from ventus) Latin: ‘’wind’’  Respiratory mechanics: pressures Pressures important in ventilation: Atmospheric pressure: -pressure exerted by weight of air in the atmosphere on objects on earth’s surface (760 mmHg at sea level) Intra-alveolar pressure: -pressure within alveoli -anytime it differs from atmospheric pressure, incoming airflow equilibrates these two pressures Intrapleural pressure: -pressure within pleural sac -usually less than atmospheric pressure (756 mmHg) Sherwood, CH13, p451 -does not equilibrate with atmospheric and intra- alveolar pressures as enclosed in a sac  Respiratory mechanics: pressures Why is the intrapleural pressure subatmospheric? Elasticity of the lungs means they tend to pull inwards towards collapse Surface tension (alveoli) also tends to pull inwards to collapse Elasticity of the chest wall tends to pull outwards Thus, competing ‘’pulls’’ lead to slight expansion of the pleural cavity – increased volume Boyle’s law means the pressure now lowered (typically by 4 mmHg) Sherwood, CH13, p451  Respiratory mechanics: lung region ventilation & compliance Gravity & posture the reasons for regional differences in intrapleural pressures in the lung apex versus base In upright position, gravity pulls lungs downward & away from the apex of the thoracic cage This creates lower intrapleural pressure at apex Gravity also pushes lungs into the thoracic cavity & increases pleural pressure Boron & Boulpaep, CH27, p631 (2nd ed)  Respiratory mechanics: inspiration For air to move, pressure inside lungs must become lower than atmospheric pressure With inspiration, thoracic volume increases – due to skeletal muscles (rib cage) & diaphragm contracting Diaphragm contraction and flattening causes 60-75% of inspiratory volume change (quiet breathing) Rib cage movement provides remainder of volume change (25-40%) Intercostal and scalene muscles pull ribs upward and outward Boyle’s law: as thoracic volume increases, pressure decreases & air flows into the lungs Silverthorn, CH17, p581  Respiratory mechanics: inspiration Lungs can be expanded in two ways i.e. downward and upward movement of diaphragm & elevation of ribs Muscles that raise the rib cage = inspiratory muscles Inspiratory muscles include: External intercostals, sternocleidomastoid muscles, anterior serrati & scalenes Silverthorn, CH17, p571  Respiratory mechanics: inspiration Inspiratory muscles do not act directly on lung, but change volume of thoracic cavity Before inspiration, muscles are relaxed & no air flowing Onset of inspiration the phrenic nerve stimulates diaphragm to contract, descend downwards; abdominal muscles bulge outward Intercostal nerves stimulate external intercostal muscles to contract – ribs & sternum upwards and outwards Intra-alveolar pressure (759 mmHg) and intrapleural (754 mmHg) pressure decrease to allow airflow into the lungs Intercostal and scalene muscles pull ribs upward and outward Sherwood, CH13, p453 Transmural pressure gradient ensures lungs stretched to fill expanded thoracic cavity  Respiratory mechanics: inspiration Quiet breathing Sherwood, CH13, p454 Sherwood, CH13, p453 Deeper inspirations: contract diaphragm & external intercostals more forcefully & the accessory inspiratory muscles (sternocleidomastoid & scalene)  Respiratory mechanics: inspiration Single inspiration: -at time zero (brief pause between breaths) alveolar pressure (PA1) is equal to atmospheric pressure -at time 0-2 sec inspiration takes place -increased thoracic volume, lowered alveolar pressure (A2) by 1 mmHg -air flows into alveoli (refer black, bottom graph: C1 to C2) -as thoracic volume changes faster than air can flow, PA reaches lowest value through inspiration (refer A2) -air flow continues until pressure equalizes between PA and atmospheric pressure (refer A3) -end of inspiration, lung volume at its maximum (C2) -intrapleural pressure also decreases due to pleural Silverthorn, CH17, p582 cavity expansion Note: atmospheric pressure in this example set as 0 mmHg (vs. 760 mmHg) to allow for easy comparisons without altitude considerations)  Respiratory mechanics: expiration Expiration is a passive process during quiet breathing Inspiratory muscles relax at end of inspiration Diaphragm returns to dome-shaped position Elevated rib cage falls due to gravity (following muscle relaxation) Chest wall and stretched lungs recoil Lung comprises elastin fibers that possess natural recoil tendency Sherwood, CH13, p454 Normal, resting ventilation rate: 12-20 breaths/min (adult)  Respiratory mechanics: pneumothorax (collapsed lung) Knife thrust between ribs punctures pleural membrane Atmospheric air flows down pressure gradient into pleural cavity Intrapleural and intra-alveolar pressures now = atmospheric pressure Transmural pressure gradient no longer exists across lung and chest walls Thus no force to stretch the lung & it collapses to its unstretched state; thoracic wall extends outwards due to unrestricted dimensions Silverthorn, CH17, p583 How correct this? a) remove as much air from pleural cavity Pneumothorax: ‘’presence of air in the pleural cavity’’ with suction pump b) sealing hole to present air entering  Respiratory mechanics: expiration Expiration is a passive process during quiet breathing Inspiratory muscles relax at end of inspiration Diaphragm returns to dome-shaped position Elevated rib cage falls due to gravity (following muscle relaxation) Chest wall and stretched lungs recoil Lung volumes decreases & PA increases (Boyle’s law) Air flows from higher PA to relatively lower atmospheric pressure Air flow ceases when PA = atmospheric Sherwood, CH13, p454 pressure Normal, resting ventilation rate: PA: alveolar pressure 12-20 breaths/min (adult)  Respiratory mechanics: active expiration Exercise or forced heavy breathing, then active respiration occurs Intercostal (internal) and abdominal muscles (expiratory muscles) contract to further increase intra-alveolar pressure versus atmospheric Abdominal contraction exerts upward force on diaphragm, up into thoracic cavity Intercostal muscles pull ribs downward and inward to flatten chest wall and decrease thoracic cavity size Intrapleural pressure also increases but lungs do not collapse due to transmural pressure gradient Sherwood, CH13, p454 Active respiration occurs when ventilation rate 30-40 breaths/min (adult)  Respiratory mechanics: expiration Single expiration: -at time 2-4 sec expiration takes place -lung & thoracic volumes decrease -air pressure in lungs increases (refer A4) -intrapleural pressure also higher (refer B3) -alveolar pressure now relatively higher versus atmospheric pressure & hence air flows out of lungs -When PA = atmospheric pressure (refer A5), air flow ceases (refer C3) -respiratory cycle ended now & ready to begin with the next breath PA: alveolar pressure Silverthorn, CH17, p582 Note: atmospheric pressure in this example set as 0 mmHg (vs. 760 mmHg) to allow for easy comparisons without altitude considerations)  Respiratory mechanics: ventilation types Type Characteristics Apnea Stops briefly & completely (e.g. during sleep) Bradypnea Slower than normal (e.g. poisons, injury) Dyspnea Short of breath, labored Eupnea Normal breathing Hyperpnea Breathing more deeply (e.g. exercise) Hyperventilation Deep & fast, letting more air out (CO2) vs. intake Hypopnea Partial blockage of air (e.g. when sleeping) Tachypnea Rapid shallow breathing (e.g. pneumonia) Pnea: from ancient Greek: ‘’breathing’’  Respiratory mechanics: lung compliance & elastance Pulmonary elasticity Compliance Elastic recoil (elastance) How much effort to stretch lungs: ΔV/ΔP -lung volume change (stretch) due to given change in transmural pressure gradient -low compliance thus requires larger transmural pressure gradient (more force) with inspiration -greater expansion by thorax via vigorous contraction of inspiratory muscles (more work) Sherwood, CH13, p451 -high compliance means it stretches easily  Respiratory mechanics: lung compliance & elastance Pulmonary elasticity Compliance Elastic recoil (elastance) How much effort to stretch lungs: ΔV/ΔP -lung volume change (stretch) due to given change in transmural pressure gradient -low compliance thus requires larger transmural pressure gradient (more force) with inspiration -greater expansion by thorax via vigorous contraction of inspiratory muscles (more work) Sherwood, CH13, p451 -high compliance means it stretches easily  Respiratory mechanics: lung compliance & elastance Restrictive lung diseases – decreased compliance Respiratory muscles need to work harder to stretch stiff lung Example: pulmonary fibrosis -long-term exposure to pollution and/or toxins (e.g. asbestos, silicon) -triggers inflammatory response -alveolar macrophages secrete factors -stimulate fibroblasts to synthesize https://www.mayoclinic.org/diseases-conditions/pulmonary- inelastic collagen fibers fibrosis/symptoms-causes/syc-20353690 - can lead to pulmonary hypertension, right-sided heart failure  Respiratory mechanics: lung compliance & elastance Pulmonary elasticity Compliance Elastic recoil (elastance) Elastic connective Alveolar surface tissue tension Elastance: ability to return to resting volume when stretching force is released High compliance lung (stretches easily) probably lost elastic tissue & wont return to resting volume when stretching force released  Respiratory mechanics: lung compliance & elastance Mice exposed to 6 months of cigarette smoke vs. controls Emphysema: alveoli wall damage & rupture, decreases lung surface area Example: smokers -alveolar macrophages activated to counter-act inhaled irritants -macrophages secrete elastase enzyme -elastase breaks down elastin fibers & alveoli lose elastic recoil abilities -thus expiration becomes a conscious effort -individuals have more difficulty exhaling vs. inhaling  Respiratory mechanics: lung compliance & elastance Pulmonary elasticity Compliance Elastic recoil (elastance) Elastic connective Alveolar surface tissue tension -major factor  Respiratory mechanics: lung compliance & elastance Alveolar surface tension: -H2O mols more attracted to other H2O mols vs. air at interface -hydrogen bonding responsible for surface tension of H2O -such unequal attraction creates a force (surface tension) at the surface of this liquid -hydrogen bonding leads to increased cohesiveness of H2O (‘’clinging’’ together) & makes it difficult to stretch and deform -it resists any force that increases its surface area & opposes alveolus expansion -thus the greater the surface tension, the less lung compliance -as H2O mols try get as close to each other as possible, the liquid surface areas tends to shrink as small as possible -such surface tension tends to reduce alveolar size squeezing in on air inside (promotes lung collapse) Sherwood, CH13, p449 Alveolar surface tension also helps with elastic recoil after inspiration  Respiratory mechanics: lung compliance & elastance Emphysema: alveoli wall damage & rupture, decreases lung surface area Example: smokers -alveolar macrophages activated to counter-act inhaled irritants -macrophages secrete elastase enzyme -elastase breaks down elastin fibers & alveoli lose elastic recoil abilities -thus expiration becomes a conscious effort -individuals have more difficulty exhaling vs. inhaling -breakdown of alveolar walls leads to decreased alveolar surface tension – lowered elastic recoil  Respiratory mechanics: lung compliance & elastance Silverthorn, CH17, p585 Pierre-Simon Laplace 1749-1827 Alveolar surface tension similar to tension existing in spherical bubble -alveoli not perfect spheres -thin film of fluid creates surface tension directed towards center -creates pressure within interior of bubble -Law of LaPlace is an expression of this pressure -note P = inward directed collapsing pressure -this law means that more work needed to expand smaller alveoli  Respiratory mechanics: lung compliance & elastance Silverthorn, CH17, p585 -cohesive force between H2O mols so strong that if alveoli lined with H2O only, surface tension so great causing lung collapse -lungs would also be poorly compliant & need exhausting muscular efforts to achieve stretching and inflation of alveoli -lungs secrete surfactant (surface active agents) that lowers surface tension -disrupt cohesive forces by H2O mols by substituting itself for H2O at the surface -thus pulmonary surfactant decreases the resistance of the lungs to stretch -pulmonary surfactant decreases surface tension to greater degree in small alveoli  Respiratory mechanics: lung compliance & elastance Sodium stearate – anionic surfactant common in most soaps http://www.bristol.ac.uk/chemistry/research/ eastoe/what-are-surfactants/ Liu et al. EDIS 2013 (11). https://doi.org/10.32473/edis-hs1230-2013 Pulmonary surfactants: -amphiphilic (dual-natured) mols -possess both hydrophobic & hydrophilic mols -mixture of mostly phospholipids (˃90% by mass); of this 40% = dipalmitoylphosphatidylcholine (DPCC) -mixture also contains small amount of proteins (Surfactant proteins A, B, C & D)  Respiratory mechanics: lung compliance & elastance https://chemistry.stackexchange.com/questions/51759/how-can-proteins-reduce-surface-tension  Respiratory mechanics: lung compliance & elastance -alveoli not individual, isolated air sacs -are complex polyhedral shapes -interconnected honeycomb of sacs, each cavity sharing its walls with many others -thus, changes in one affect surrounding alveoli, known as ‘’alveolar interdependence’’ -mechanism contributes to elastic recoil & prevents collapse of alveoli Thus, alveolar stability (prevention of its collapse) depends on a) surfactant and b) alveolar interdependence https://derangedphysiology.com/main/cicm-primary-exam/required- reading/respiratory-system/Chapter%20012/structure-and-function-alveolus  Respiratory mechanics: lung compliance & elastance Surfactant: -synthesis usually starts in 25th week of fetal development -production reaches adequate levels by 34th week of pregnancy -premature babies without adequate surfactant levels – complication known as newborn respiratory distress syndrome (NRDS) -also referred to as hyaline membrane disease -babies display stiff lungs (low compliance) & alveoli that can collapse when exhale -need significant energy to expand lungs with each breath  Respiratory mechanics: lung compliance & elastance Pulmonary elasticity Compliance Elastic recoil (elastance) Lung stability Elastic connective Alveolar surface tissue tension Prevents pulmonary -major factor Pulmonary Elastic edema (lowers alveoli compliance recoil surface tension) key functions Surfactant Counteracting forces Alveolar interdependence X Tendency for alveoli to collapse Atelectasis: complete or partial collapse of the entire lung or a lobe(s)  Respiratory mechanics: lung region ventilation & perfusion Ventilation-perfusion ratio Ventilation rate (V) = tidal volume x respiratory rate Perfusion of lungs (Q): total volume of blood reaching pulmonary capillaries per unit time V/Q standing upright: much higher in apex (3.3) versus the base (0.63) of the lung Thus, ventilation exceeds perfusion in the apex while perfusion exceeds ventilation in the base Areas of lung below the heart (e.g. base) display increased perfusion relative to ventilation due to gravity https://quizlet.com/429434680/respiratory-physiology-packet2-flash- cards/ MBChB I Respiratory Lectures 2024 Gas exchange Prof. Faadiel Essop Room 3027, BMRI Email: [email protected]  Respiratory mechanics: airway resistance Flow  P R Pressure gradient/Resistance Airway diameter (Poiseuille’s law) Length (L) of system Wider airways have less resistance Resistance (R) Viscosity (Ƞ) of flowing substance R  Lη r 4 Radius of tubes (r) in system -length & viscosity = constant -vessel radius = key determinant of resistance -90% airway resistance – trachea and bronchi -they rigid structures with smallest total cross-sectional area -such resistance generally constant Jean Poiseuille -however, mucus can increase resistance 1797-1869  Respiratory mechanics: airway resistance Flow (F)  P R Insert into above formula Thus, very small decreases in the Klabunde, 2021 radius significantly lowers the flow! -view the graph from right to left  Respiratory mechanics: airway resistance Of note, the number of airways also plays a role in resistance to air More airways reduce resistance as there are increased paths for air to flow into Thus, although terminal bronchioles possess the smallest airways (radius), their relatively higher numbers (vs. larger airways) means that bronchi display a greater total resistance  Respiratory mechanics: airway resistance Silverthorn, CH17, p587 Bronchioles are collapsible and can contribute to airway resistance Bronchoconstriction - increased resistance to airflow; bronchodilation = opposite -neural control via parasympathetic neurons, cause bronchoconstriction -no significant sympathetic innervation -smooth muscle of bronchioles contain β2-receptors for circulating epinephrine effects (bronchodilation) - paracrine signals play key role - increased CO2 in exhaled air relaxes bronchiolar smooth muscle (bronchodilation) -increased histamine release (by mast cells – allergic reactions) leads to bronchoconstriction  Respiratory mechanics: airway resistance Bronchiolar smooth muscle is sensitive to local CO2 levels More CO2 delivered by blood flow vs. CO2 exhaled, hence local levels rise Higher local CO2 levels lead to smooth muscle relaxation & lower airway resistance Airflow now increased (for same ΔP) In parallel, greater blood supply means more O2 extracted from alveoli Local decrease in O2 leads to vasoconstriction of pulmonary arterioles Sherwood, CH13, p466 Thus, blood flow decreased to match the airflow  Respiratory mechanics: airway resistance The two mechanisms for matching airflow and blood flow, function concurrently (limited neural effects) Hence very little air or blood wasted in the lung Gravitational effects: differences in ventilation & perfusion between top and bottom of the lung Sherwood, CH13, p466  Respiratory mechanics: alveolar ventilation Hyperventilation: Increased alveolar ventilation Alveolar PO2 increases & alveolar PCO2 decreases Hypoventilation: Decreased alveolar ventilation Less fresh air enters the alveoli Alveolar PO2 decreases & PCO2 increases Silverthorn CH17, p590  Respiratory mechanics: energy requirements Key factors influencing work required Decreased compliance work required to -e.g. pulmonary fibrosis expand the lungs Compliance Passive expiration Reduced elastic recoil insufficient e.g. emphysema -abdominal muscles work to expel air Airway resistance Increased airway resistance  Respiratory mechanics: airway resistance Chronic obstructive pulmonary disease (COPD): lung diseases characterized by increased airway resistance (with expiration)- includes chronic bronchitis & emphysema Chronic bronchitis: -triggered by frequent exposure to e.g. cigarette smoke, polluted air, allergens -long-term inflammatory response -airways become narrow due to thickening of airway linings & increased thick mucus production  Respiratory mechanics: airway resistance “Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation.”* Asthma: -inflammation & histamine induces edema, leading to thickening of airway walls -excessive secretion of very thick mucus -smooth muscle spasms (in response to triggers, e.g. allergens, cigarette smoke, infections) lead to severe constriction of smaller airways Such airway obstruction usually reversible vs. COPD where it is mainly irreversible & gets progressively worse *Asthma definition as stipulated in GINA 2015 report (www.ginasthma.org) Pulmonary gas exchange & transport Silverthorn, CH18, p599  Gas exchange The body needs oxygen and removes carbon dioxide Hypoxia – too little oxygen Hypercapnia – increased concentrations of carbon dioxide To avoid hypoxia and hypercapnia, the body responds to three regulated variables 1. Oxygen 2. Carbon dioxide 3. pH  Types of hypoxia and some typical causes Type Definition Typical Causes Hypoxic hypoxia Low arterial PO High altitude; alveolar hypoventilation; decreased 2 lung diffusion capacity; abnormal ventilation- perfusion ratio Anemic hypoxia Decreased total amount of O2 Blood loss; anemia (low [Hb] or altered HbO2 bound to hemoglobin binding); carbon monoxide poisoning Ischemic hypoxia Reduced blood flow Heart failure (whole-body hypoxia); shock (peripheral hypoxia); thrombosis (hypoxia in a single organ) Histotoxic hypoxia Failure of cells to use O2 Cyanide and other metabolic poisons because cells have been poisoned Normal blood values in pulmonary medicine Blank Arterial Venous PO2 95 mm Hg (85–100) 40 mm Hg PCO2 40 mm Hg (35–45) 46 mm Hg pH 7.4 (7.38–7.42) 7.37 Respiratory physiologists express plasma gas concentrations as partial pressures Oxygen diffuses down partial pressure (concentration) gradient Diffusion goes to equilibrium, i.e. PO2 of arterial blood leaving lungs = that in alveoli (100 mm Hg) When arterial blood reaches tissue capillaries then gradient is reversed  Gas exchange in lungs and tissue Breathing is bulk flow of air into and out of lungs Individual gases diffuse along partial pressure gradients until equilibrium – Total pressure of mixed gas = sum of partial pressures of individual gases – Gas exchange between alveoli and blood PO2 alveolar air  PO2 blood PCO2 blood  PCO2 alveolar air Gas exchange between blood and tissues PO2 blood  PO2 tissue PCO2 tissue  PCO2 blood Gases diffuse down concentration gradients Silverthorn, CH18, p601  Efficiency of alveolar gas exchange Influencing variables Adequate oxygen must Transfer of gases between alveoli Adequate perfusion reach the alveoli and pulmonary capillaries of alveoli Hypoxia Efficiency of alveolar gas exchange Sherwood, CH13, p470  Efficiency of alveolar gas exchange Adequate oxygen must reach the alveoli Atmosphere composition altered Atmosphere composition normal e.g. lower PO2 with a) altitude or but low alveolar ventilation b) humidity -hypoventilation Decreased lung compliance Increased airway resistance Central nervous system depression Efficiency of alveolar gas exchange Influencing variables Transfer of gases (diffusion) between alveoli and pulmonary capillaries Silverthorn, CH18, p602 Diffusion barrier between lung and blood Silverthorn, CH18, p602  Diffusion problems can cause hypoxia Diffusion rate  surface area x concentration gradient x barrier permeability Diffusion distance can also be added to this equation - diffusion rate  1/distance2 - thus, diffusion is most rapid over short distances Most of time: diffusion distance, surface area & barrier permeability = constants Hence, concentration gradient (between alveoli & blood) is the primary factor affecting gas exchange in healthy people Pathology does play a role in some cases, for e.g.: - decreased alveolar surface area - increased thickness of alveolar-capillary exchange barrier - increased diffusion distance between alveolar air space & blood Silverthorn, CH18, p602 Pathologies that can cause hypoxia Silverthorn, CH18, p602  Pathologies that can cause hypoxia Pathological changes that adversely affect gas exchange Surface area Decrease in amount of alveolar surface area Emphysema Diffusion barrier permeability Increase in thickness of alveolar membrane Fibrotic lung diseases Diffusion distance Increase in diffusion distance between alveoli and blood Pulmonary edema  Diffusion problems can cause hypoxia: gas solubility Movement of gases is directly proportional to 1) pressure gradient of the gas When temperature is constant, the amount of a gas that dissolves in a liquid depends on its a) solubility & 2) solubility of the gas in liquid b) partial pressure 3) temperature If gas pressure is higher in gaseous phase than in water, then it dissolves into the water (down the pressure gradient) At equilibrium, the movement of oxygen from air into water = movement from oxygen from water back into the air Silverthorn, CH18, p604  Diffusion problems can cause hypoxia: gas solubility Movement of gases is directly proportional to 1) pressure gradient of the gas When temperature is constant, the amount of a gas that dissolves in a liquid depends on its a) solubility & 2) solubility of the gas in liquid b) partial pressure 3) temperature If gas pressure is higher in gaseous phase than in water, then it dissolves into the water (down the pressure gradient) At equilibrium, the movement of oxygen from air into water = movement from oxygen from water back into the air Concentration of oxygen in the water is referred to as the partial pressure of the gas in solution Oxygen is not very soluble in water and hence notice the difference between O2/L for air vs. O2/L for water (refer [c] in figure) By contrast, carbon dioxide is 20x more soluble in water vs. oxygen (refer [d] in figure) Silverthorn, CH18, p604  Gas transport in blood Gas entering capillaries first dissolve in the plasma – Dissolved gas accounts only for