Chapter 22: The Respiratory System Physiology

-breathing or pulmonary ventilation consists of inspiration when air flows into the lungs and expiration when gases exit the lungs

-respiratory pressures are always described relative to atmospheric pressure -Patm is the pressure exerted by gases surrounding the body-Patm is 760 mmHg / 1atm

Intrapulmonary Pressure-intra-alveolar pressure (Ppul) -the pressure in the alveoli -pressure rises and falls with the phases of breathing but always equalizes with atmospheric pressure eventually

Intrapleural Pressure-pressure in the pleural cavity -fluctuates with breathing processes -Pip is always negative relative to Ppul

-2 forces act to pull the lungs (visceral pleura) away from the thorax wall (parietal pleura) to cause the lung to collapse

1) The Lung's Natural Tendency to Recoil-lungs always assume the smallest size possible due to their elasticity

2) The Surface Tension of the Alveolar Fluid -molecules of the fluid lining the alveoli attract each other and produces surface tension that constantly acts to draw the alveoli to their smallest possible dimension

-these lung-collapsing forces are opposed by the natural elasticity of the chest wall and tends to pull the thorax outward and enlarge the lungs -pleural fluid secures the pleurae together the way a drop of water holds 2 glass slides together -pleurae slides from side to side easily but are closely apposed -this results in a negative intrapleural pressure

-the amount of pleural fluid in the pleural cavity must remain minimal for intrapleural pressure to be maintained

-pleural fluid is actively pumped out of the pleural cavity into the lymphatics-if fluid accumulated, a positive pressure would be produced in the pleural cavity

-any condition that equalizes intrapleural pressure with intrapulmonary / atmospheric pressure causes lung collapse

-transpulmonary pressure (the difference between intrapulmonary and intrapleural pressures) keeps the air spaces in the lungs open

-the size of transpulmonary pressure determines the size of the lungs at any point in time; the greater the transpulmonary pressure, the larger

the lungs

-atelectasis or lung collapse occurs when a bronchiole becomes plugged-the associated alveoli absorb all their air and then collapse -may also occur when air enters the pleural cavity -since lungs are in separate cavities, one lung can collapse without interfering with the function of the other

Pulmonary Ventilation -consists of inspiration and expiration -a mechanical process that depends on volume changes in the thoracic cavity -volume changes lead to pressure changes and pressure changes lead to the flow of gases in order to equalize pressure

Inspiration -lung volume is changeable and can be increased by enlarging its dimensions, thus decreasing the gas pressure inside it

-a drop in pressure causes air to rush in from the atmosphere because gases flow down their concentration gradients

-during normal quiet inspiration, the inspiratory muscles (made up of the diaphragm and external intercostal muscles) are activated

1) Diaphragm Action -when the dome-shaped diaphragm contracts, it moves inferiorly and flattens out-as a result, the superior-inferior (vertical / height) dimensions of the thoracic cavity increases -the diaphragm is more important in producing volume changes that lead to normal quiet inspiration

2) Intercostal Muscle Action -contraction of the external intercostal muscles lifts the rib cage and pulls the sternum superiorly -when rib are raised and drawn together, they swing outward and expand the diameter of the thorax

-this increases the volume by 500 mL; the usual volume of air that enters the lungs during normal quiet inspiration -as thoracic dimensions increase, the lungs are stretched and intrapulmonary volume increases

-intrapulmonary pressure drops by about 1 mmHg relative to atmospheric pressure and air rushes into the lungs along the pressure gradient -inspiration ends when intrapulmonary pressure = atmospheric pressure -intrapleural pressure declines to -6 mmHg relative to atmospheric pressure during

this time

-during deep / forced inspiration that occurs during exercise the thoracic volume is further increased by activity of accessory muscles

-scalene muscles, sternocleidomastoid muscles of the neck and chest raise the ribs even more than during quiet expiration -the back extends as the thoracic curvature is straightened by the spine muscles

Expiration -quiet expiration is a passive process-quiet expiration depends on lung elasticity rather than muscle contraction -as inspiratory muscles relax and resume their resting length, the rib cage descends and the lungs recoil

-thoracic and intrapulmonary volumes decrease to about 1 mmHg above atmospheric pressure -when pulmonary pressure is greater than atmospheric pressure, gas is forced to flow out of the lungs

-forced expiration is an active process -forced expiration depends on the contraction of abdominal wall muscles -these contractions:

1) increase the intra-abdominal pressure and forces abdominal organs superiorly against the diaphragm (causing diaphragm to contract and expiration to occur)

2) depress the rib cage (decreasing thoracic volume) with the help of intercostal muscles

-control of accessory muscles is important for the precise regulation of air flow from the lungs (i.e.: important for vocalists)

Physical Factors Influencing Pulmonary Ventilation

1) Airway Resistance -friction is a major nonelastic source of resistance to gas flow

Flow = Change in Pressure / Resistance

-the factors determining gas flow in the respiratory passages and blood flow in the cardiovascular system are equivalent -the amount of gas flowing into and out of the alveoli is directly proportional to difference in pressure between the external atmosphere and the alveoli -gas flow is inversely proportional to resistance

-airway resistance is insignificant in healthy individuals because:

1) airway diameter in the first part of the conducting zone is large, relative to the low viscosity of air

2) as the airways get progressively smaller, there are progressively more branches so the total cross-sectional area is huge

-the greatest resistance to gas flow occurs in the medium-sized bronchi-at the terminal bronchioles, diffusion is the main force driving gas movement so resistance is no longer an issue

2) Neural Influences of Airways Resistance -smooth muscle of bronchiolar walls is sensitive to neural and chemical controls

-irritants activate the parasympathetic nervous system which causes constriction of bronchioles and reduce air passage

-during an acute asthma attack, histamine and other inflammatory chemicals cause bronchoconstriction and pulmonary ventilation stops

-epinephrine released during sympathetic nervous system activation dilates bronchioles and reduces airway resistance

-mucus, infectious material, and tumours in the passageway are sources of airway resistance in those with respiratory disease

3) Alveolar Surface Tension -at a gas-liquid boundary, the molecules of the liquid are more strongly attached to each other than to gas molecules causing a state of surface tension at the liquid surface

-this draws the liquid molecules closer together and reduces their contact with the gas molecules -this resists any force that tends to increase the surface area of the liquid

-water is composed of polar molecules and has a high surface tension-water is the major component that coats alveolar walls and reduces alveoli to their smallest possible size

-alveolar film contains surfactant produced by type 2 alveolar cells-surfactant decreases the cohesiveness of water molecules and reduces surface tension of alveolar fluid so less energy is needed to overcome those forces in order to expand the lungs and discourage alveolar collapse-deep breaths stimulate type 2 cells to secrete more surfactant

-infant respiratory distress syndrome occurs when there is too little surfactant present and surface tension forces collapse the alveoli

-treated by spraying surfactant into the passageway and positive pressure airway machines

4) Lung Compliance -lung compliance refers to the distensibility of the lungs-lung compliance is the measure of the change in lung volume that occurs with a given change in the transpulmonary pressure

-the more a lung expands for a given rise in transpulmonary pressure, the greater its compliance -the higher the lung compliance, the easier it is to expand the lungs at an given transpulmonary pressure

-lung compliance is determined by:

1) destensibility of lung tissue 2) alveolar surface tension

-generally, lung distensibility is high and alveolar surface tension is low due to surfactants-high compliance favours efficient ventilation

-lung compliance is diminished by inflammation, low surfactant etc.-the lower the lung compliance, the more energy is needed to breathe

-thoracic cavity distensibility affects lung compliance -the total compliance of the respiratory system is determined by the lung compliance and thoracic wall compliance

Respiratory Volumes and Pulmonary Function Tests-respiratory capacities are measured to gain information about a person's respiratory status

-they represent specific combinations of respiratory volumes which depend on the conditions of inspiration and expiration

Respiratory Volumes

1) Tidal Volume (TV)-during normal quiet breathing, about 500 mL of air moves into and out of the lungs of each breath-the amount of air inhaled or exhaled with each breath under resting conditions

2) Inspiratory Reserve (IRV)-the amount of air that can be inspired forcibly beyond tidal volume-amount of air that can be forcefully inhaled after a normal tidal volume inhalation -ranges from 2100 mL to 3200 mL

3) Expiratory Reserve Volume (ERV)-the amount of air that can be evacuated from the lungs after tidal expiration -amount of air that can be forcefully exhaled after a normal tidal volume exhalation -ranges from 1000 mL to 1200 mL

4) Residual Volume (RV)

-the amount of air that remains in the lungs after expiration which helps to keep the alveoli patent / open to prevent lung collapse-amount of air in the lungs after a forced exhalation -about 1200 mL

Respiratory Capacities-involves 2 or more lung volumes

1) Inspiratory Capacity (IC)-the total amount of air that can be inspired after a normal, tidal expiration IC = TV + IRV

2) Functional Residual Capacity (FRC)-represents the amount of air remaining in the lungs after a normal tidal expiration FRC = ERV + RV

3) Vital Capacity (VC)-the total amount of exchangeable air-the maximum amount of air that can be expired after a maximum inspiratory effort VC = TV + IRV + ERV

4) Total Lung Capacity-the sum of all lung volumes-the maximum amount of air contained in the lungs after a maximum inspiratory effort TLC = TV + IRV + ERV + RV -6000 mL in men and 4200 mL in women

Dead Space-some of the inspired air fills the conducting respiratory passageways and never contributes to gas exchange in the alveoli -dead space involves the volume of these conducting zone conduits (passageways) -around 150 mL-anatomical dead space volume in a healthy young adult is equal to 1 mL per pound of ideal body weight -if some alveoli cease to act in gas exchange, the alveolar dead space is added to the anatomical dead space to make up total dead space -if tidal volume is 500 mL, only 350 mL of it is involved in alveolar ventilation

Pulmonary Function Tests -spirometer is useful for evaluating losses in respiratory function and for following the course of certain respiratory diseases -it can distinguish between obstructive pulmonary disease involving increased airway resistance and restrictive disorders involving a reduction in total lung capacity

-more information can be obtained by assessing the rate at which gas moves into and out of the lungs

-minute ventilation is the total amount of gas that flows into or out of the respiratory tract in 1 minute

-during normal, quiet breathing the minute ventilation in healthy people is about 6L / minute (500 mL per breath and 12 breaths per minute)-200 L / minute during exercise

-forced vital capacity measures the amount of gas expelled when a subject takes a deep breath and then forcefully exhales maximally and as rapidly as possible

-forced expiratory volume determines he amount of air expelled during specific time intervals of the forced vital capacity test

-alveolar ventilation rate is a better index of effective ventilation-takes account the volume of air wasted in the dead space and measures the flow of fresh gases in and out of the alveoli during a particular time interval

AVR (mL / min) = frequency (breaths / min) x (tidal volume - dead space) in mL / breath

-AVR is about 4200 mL/minute

-anatomical dead space is constant in an individual

-increasing the volume of each inspiration enhances AVR and gas exchange more than raising the respiratory rate

-AVR drops dramatically during rapid shallow breathing because most of the inspired air never reaches the exchange sites

-as tidal volume approaches the dead space value, effective ventilation approaches zero, regardless of how fast a person is breathing

-normal rate and depth of breathing -70% effective ventilation (AVR / MVR)

-slow, deep breathing-85% effective ventilation

-rapid, shallow breathing-40% effective ventilation

Nonrespiratory Air Movements

Cough-involves taking a deep breath, closing the glottis, and forcing air superiorly from lungs against glottis-the glottis opens suddenly and a blast of air rushes upward -allows the dislodging of foreign particles or mucus from lower respiratory tract and propel such substances superiorly

Sneeze-similar to a cough; expelled air is directed through nasal cavities as well as the oral cavity-depressed uvula routes air upward through the nasal cavities-clears the upper respiratory passages

Hiccups -involves the sudden inspirations resulting from spasms of the diaphragm-believed to be initiated by irritation of diaphragm or phrenic nerves that serve the diaphragm-sound occurs when inspired air hits the vocal folds of the closing glottis

Yawn-involves very deep inspirations, taken with the jaws wide open-not triggered by levels of oxygen or carbon dioxide in blood-ventilates all alveoli

Gas Exchange Between the Blood, Lungs, and Tissues -Dalton's law of partial pressure reveals how a gas behaves when it is part of a mixture of gases-Henry's law reveals how movement of gases into and out of solution

Dalton's Law of Partial Pressure -states that the total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture-its partial pressure is directly proportional to the percentage of that gas in the gas mixture

-nitrogen makes up about 79% of atmosphere and the partial pressure of nitrogen is 78.6% (597 mmHg)

-oxygen makes of 21% of the atmosphere and the partial pressure is 159 mmHg

-the atmosphere contains 0.04% carbon dioxide and up to 0.5% water vapour and other inert gases

-at high altitudes, where the atmosphere is less influenced by gravity, partial pressure declines in direct proportion to the decrease in atmospheric pressure

-atmospheric pressure increases by 760 mmHg for each 33 feet below sea level

Henry's Law -when a gas is in contact with liquid, that gas will dissolve in the liquid in proportion to its partial pressure

-the greater the concentration of a particular gas in the gas phase, the more and the faster that gas will go into solution in the liquid-at equilibrium, the gas partial pressures in the two phases are the same-if partial pressure of the gas later becomes greater in the liquid, some of the dissolved gas molecules will re-enter the gaseous phase

-how much of a gas will dissolve in a liquid depends on the solubility of the gas in the liquid and the temperature of the liquid

-carbon dioxide is the most soluble-oxygen is 1/20 as soluble as carbon dioxide -much more CO2 than O2 dissolves in water

Composition of Alveolar Gas -the gaseous makeup of the atmosphere is different from that in the alveoli -alveoli contain more CO2 and water vapour and much less O2 -the differences in the alveoli reflect:

1) gas exchanges occurring in the lungs (O2 diffuses from the alveoli into the pulmonary blood and CO2 diffuses in the opposite direction)

2) humidification of air by conducting passages

3) the mixing of alveolar gas that occurs with each breath

-gas in the alveoli is a mixture of newly inspired gases and gases remaining in the respiratory passageways between breaths (since tidal inspiration only involves 500 mL of air)

-the alveolar partial pressures of O2 and CO2 are easily changed by increasing breathing depth and rate -a high AVR brings more O2 into the alveoli, increasing alveolar partial pressure of oxygen and rapidly eliminating CO2 from the lungs

External Respiration -during external respiration / pulmonary gas exchange, dark red blood flowing though the pulmonary circuit is transformed into the scarlet river that is returned to the heart for distribution by the systemic arteries to all body tissues-color change is due to O2 uptake and binding to hemoglobin in red blood cells but CO2 exchange (CO2 unloading) is occurring equally fast

-there are 3 factors that influence the movement of oxygen and carbon dioxide across the respiratory membrane:

1) partial pressure gradients and gas solubilities -partial pressure gradients of O2 and CO2 drive the diffusion of these gases across the respiratory membrane -there is a steep oxygen partial pressure gradient that exists across the respiratory membrane because of the partial pressure of deoxygenated blood in the pulmonary arteries is only 40 mmHg as opposed to a partial pressure of oxygenated blood of approximately 104 mmHg

-O2 diffuses rapidly from the alveoli into the pulmonary capillary blood-equilibrium (104 mmHg for oxygen on both sides of the respiratory membrane) usually occurs in 0.25 seconds (1/3 of the time of a red blood cell in a pulmonary capillary)

-blood can flow through the pulmonary capillaries 3 times as quickly and still be oxygenated

-CO2 diffuses in the opposite direction along a much gentler partial pressure gradient of 5 mmHg (45 mmHg to 40 mmHg) -CO2 is then expelled gradually from the alveoli during expiration

-even though the O2 pressure gradient for oxygen diffusion is much steeper than the CO2 gradient and equal amounts of these gases are exchanged-CO2 is 20 times more soluble in plasma and alveolar fluid than O2

2) Ventilation-Perfusion Coupling-involves the matching of alveolar ventilation and pulmonary blood perfusion -for gas exchange to be efficient, there must be a close match / coupling between the amount of gas reaching the alveoli (ventilation) and the blood flow in pulmonary capillaries (perfusion)

-local autoregulatory mechanisms continuously respond to alveolar conditions -the autoregulatory mechanism controlling pulmonary vascular muscle is the opposite of the mechanisms controlling most arterioles in the systemic circulation

-in alveoli where ventilation is inadequate, partial pressure of oxygen is low-terminal arterioles constrict and blood is redirected to the respiratory areas where the partial pressure of oxygen is high and where oxygen pickup is more efficient

-in alveoli where ventilation is maximal, pulmonary arterioles dilate to increase blood flow into the associated pulmonary capillaries

-changes in alveolar partial pressure of oxygen affect the diameter of pulmonary blood vessels (arterioles)

-changes in alveolar partial pressure of carbon dioxide changes the diameters of the bronchioles

-bronchioles servicing areas where alveolar CO2 level are high dilate to allow CO2 to be eliminated from the body more rapidly-bronchioles servicing areas where the partial pressure of CO2 is low constrict

-alveolar ventilation and pulmonary perfusion are synchronized as a result of changing the diameter of local bronchioles and arterioles

-poor alveolar ventilation results in low oxygen and high carbon dioxide levels in the alveoli; pulmonary arterioles constrict and the airways dilate, bringing blood flow and air flow into closer physiological match

-high partial pressure of oxygen and low partial pressure of carbon dioxide in the alveoli cause bronchioles serving the alveoli to constrict and promote flushing of blood into the pulmonary capillaries

-these homeostatic mechanisms never completely balance ventilation and perfusion -gravity causes regional variations in both blood and air flow in the lungs-the occasional alveolar duct plugged with mucus creates unventilated areas -blood is shunted from bronchial veins -these factors account for the slight drop in the partial pressure of oxygen from alveolar air (104 mmHg) to pulmonary venous blood (100 mmHg)

3) structural characteristics of the respiratory membrane -the thickness and surface area of the respiratory membrane affect gas movement -in healthy lungs, the respiratory membrane is 0.5 to 1 microm thick and gas exchange is very efficient -if lungs become water logged, the thickness of the membrane increases-the alveolar surface area is about 90m2 -emphysema reduces the alveolar surface area functioning in gas exchange

Transport of Respiratory Gases by Blood

Oxygen Transport-molecular oxygen is carried in blood by binding to hemoglobin within red blood cells or being dissolved in plasma -oxygen is poorly soluble in water so only 1.5% of transported oxygen is carried in the dissolved form

Association of Oxygen and Hemoglobin -Hb is composed of 4 polypeptide chains each bound to an iron-containing heme group-Hb can combine 4 molecules of oxygen; oxygen loading is rapid and reversible

-oxyhemoglobin represents the hemoglobin-oxygen combination; written as HbO2

-hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin; written as HHb

-after the first O2 molecule binds to iron, the Hb molecule changes its shape to allow it to uptake the other O2 molecules more easily-when all 4 heme groups are bound to O2, a hemoglobin molecule is full saturated -when 1, 2, or 3, oxygen molecules are bound, hemoglobin is partially saturated

-the unloading of 1 oxygen molecule enhances the unloading of the next

-the affinity of hemoglobin for oxygen changes with the extent of oxygen saturation

-both loading and unloading of oxygen are efficient

-the rate at which Hb reversibly binds or releases O2 depends on the temperature of the partial pressure of oxygen, blood pH, partial pressure of CO2, and blood concentration of BPG (2,3-biphosphoglycerate)

Influence of Partial Pressure of Oxygen on Hemoglobin Saturation -the affinity of hemoglobin for O2 changes with O2 binding as shown in the oxygen-hemoglobin dissociation curve-there is a steep slope for partial pressure values between 10 and 50 mmHg and then plateaus between 70 and 100 mmHg

-under normal resting conditions (PO2 = 100 mmHg), arteriole blood hemoglobin is 98% saturated

-100 mL of systemic arterial blood contains about 20 mL of oxygen or 20 volume %

-as arterial blood flows through the systemic capillaries, 5 mL of O2 per 100 mL of blood is released, yielding an Hb saturation of 75% and on O2 content of 15 volume %

-the complete saturation of Hb in arterial blood explains why breathing deeply increases both alveolar and arterial blood partial pressure of oxygen but causes very little increase in the oxygen saturation of hemoglobin

-the oxygen-hemoglobin dissociation curve also reveals:

1) Hb is almost completely saturated at a partial pressure of oxygen of 70 mmHg -further increases in the partial pressure of oxygen only produce small increases in O2 binding -O2 loading and delivery to the tissues can still be adequate when partial pressure of oxygen of inspired air is well below usual levels, which is common at high altitudes and in people with cardiopulmonary disease 2) because most O2 unloading occurs on the steep portion of the curve, a small drop in the partial pressure of oxygen will cause a large increase in unloading -normally only 20-25% of bound oxygen is unloaded during one system circuit and substantial amounts of O2 are still available in venous blood (venous reserve)

-if O2 drops to very low levels in the tissues (i.e.: during vigorous exercise), much more O2 will dissociate from hemoglobin to be used by the tissue cells without any increase in respiratory rate or cardiac output

Influence of Other Factors on Hemoglobin Saturation -temperature, blood pH, PCO2, and BPG all influence hemoglobin saturation at a given PO2

-BPG (2,3-biphosphoglycerate) binds reversibly with hemoglobin and is produced by RBCs as they break down glucose by the glycolysis (anaerobic)

-all these factors modify hemoglobin's 3D structure and changes its affinity for O2

-an increase in temperature, PCO2, H+, or BPG levels in blood decreases Hb's affinity for O2, enhancing oxygen unloading from the blood

-a rightward shift of the oxygen-hemoglobin dissociation curve

-a decrease in temperature, PCO2, H+, or BPG levels increases Hb's affinity for oxygen, decreasing oxygen unloading

-a leftward shift of the oxygen-hemoglobin dissociation curve

-these levels tend to be at their highest levels in the systemic capillaries where oxygen unloading is the goal

-as cells metabolize glucose and use O2, they release CO2, which increases the PCO2 and H+ levels in the capillary blood -declining blood pH (acidosis) and increasing PCO2 weaken the Hb-o2 bond known as the Bohr Effect -oxygen unloading is enhanced where it is most needed

-heat is a byproduct of metabolic activity-active tissues are usually warmer than less active ones-a rise in temperature affects hemoglobin's affinity for O2 both directly and indirectly

-it influences RBC metabolism (direct)-influences BPG synthesis (indirect)

-all these factors affect Hb so that it unloads more O2 in the vicinity of hard-working tissue cells

hypoxia- inadequate oxygen delivery to body tissues

anemic hypoxia- reflects poor O2 delivery resulting from too few RBCs or from RBC that contain abnormal Hb

ischemic (stagnant) hypoxia- results when blood circulation is impaired or blocked

histotoxic hypoxia- occurs when the body cells are unable to use O2 even though adequate amounts are delivered

hypoxemic hypoxia- indicated by reduced arterial PO2

carbon monoxide poisoning- competes with O2 for heme binding sites and Hb has a stronger affinity for CO over O2

Carbon Dioxide Transport -active body cells produce about 200 mL of CO2 / min which is equal to the amount excreted by the lungs

-blood transports CO2 from tissue cells to the lungs in 3 forms:

1) Dissolved in Plasma-7-10%-the smallest amount of CO2 is transported dissolved in plasma

2) Chemically Bound to Hemoglobin-20%-dissolved CO2 is bound and carried in the RBCs as carbaminohemoglobin

CO2 + Hb <- -> HbCO2-this reaction is rapid and does not require a catalyst -carbon dioxide transport in RBCs does not compete with oxyhemoglobin transport because CO2 binds directly to the amino acids of globin and not the heme

-CO2 loading and unloading to and from Hb are directly influenced by PCO2 and the degree of Hb oxygenation

-CO2 rapidly dissociates from Hb in the lungs where PCO2 of alveolar air is lower than that in blood -CO2 is loaded in tissues where PCO2 is higher than that in the blood-deoxygenated hemoglobin combines more readily with carbon dioxide than does oxygenated hemoglobin

3) Bicarbonate Ion in Plasma -70%-most CO2 molecules entering the plasma quickly enter the RBCs where most of the reactions that CO2 for transport as bicarbonate ions (HCO3-) in plasma occur

-when dissolved CO2 diffuses into the RBCs, it combines with water to form carbonic acid (H2CO3) which is unstable and dissociates into hydrogen ions and bicarbonate ions

-this reaction is faster in RBCs than in plasma because RBCs contain carbonic anhydrase which reversibly catalyzes the conversion of carbon dioxide and water to carbonic acid

-H+ ions released during the reaction (and CO2) bind to Hb which triggers the Bohr effect-CO2 loading enhances O2 release-because of the buffering effect of Hb, the liberated H+ causes little change in pH under resting conditions -blood only becomes slightly more acidic as it passes through tissues

-once generated, HCO3- moves from the RBCs into the plasma and is carried to the lungs -Cl- ions move from the plasma into the RBCs to counter-balance the rapid outrush

of these anions from the RBCs-this ion exchange process is called chloride shift and occurs via facilitated diffusion through a RBC membrane protein

-in the lungs, the process is reversed-as blood moves through the pulmonary capillaries, its PCO2 declines from 45 mmHg to 40 mmHg -CO2 is freed from its bicarbonate housing-HCO3- re-enters the RBCs and Cl- moves into the plasma -HCO3- binds with H+ to form carbonic acid which is then split by carbonic anhydrase to release CO2 and water-this CO2, along with the CO2 released from hemoglobin and from solution in the plasma, diffuse along its partial pressure gradient from the blood into the alveoli

The Haldane effect -the amount of CO2 transported in blood is affected by the degree of oxygenation of the blood -the lower the PO2 and the lower the extent of Hb saturation with oxygen, the more CO2 can be carried in the blood-this reflects the ability of reduced hemoglobin to form carbaminohemoglobin and to buffer H+ by combining with it -as CO2 enters the systemic bloodstream, it causes more oxygen to dissociate from Hb (i.e.: the Bohr effect) -in the pulmonary circulation, uptake of O2 facilitates release of CO2

-as Hb becomes saturated with O2, the H+ released combines with HCO3- helping to unload CO2 from the pulmonary blood

Influence of CO2 and Blood pH -the H+ released during carbonic acid dissociation is buffered by Hb or other proteins within the RBCs or in plasma -the HCO3- generated in the RBCs diffuses into the plasma, where it acts as the alkaline reserve for the blood's carbonic acid - bicarbonate buffer system

-carbonic acid-bicarbonate buffer system is important in resisting blood shifts in blood pH

-if H+ concentration in blood begins to rise, excess H+ is removed by combining with HCO3- to form carbonic acid

-if H+ concentration drops below desirable levels in blood, carbonic acid dissociates, releasing H+ ions and lowering pH again

-changes in respiratory rate or depth can change blood pH by altering the amount of carbonic acid in the blood

-slow, shallow breathing allows CO2 to accumulate in the blood-carbonic acid levels increase and blood pH drops

-rapid, deep breathing quickly flushes CO2 out of the blood and reduces carbonic acid levels and increases blood pH

-respiratory ventilation can provide a fast-acting system to adjust blood pH and PCO2

Control of Respiration

Neural Mechanisms-control of respiration primarily involves neurons in the reticular formation of the medulla and pons

Medullary Respiratory Centres -involve clustered neurons in 2 areas of the medulla oblongata

1) Dorsal Respiratory Group (DRG) -located dorsally near the root of the cranial nerve IX -integrates input from peripheral stretch and chemoreceptors and communicates the information to the VRG

2) Ventral Respiratory Group (VRG) -a network of neurons that extends in the ventral brain stem from the spinal cord that extends from the spinal cord to the pons-medulla junction -acts as a rhythm-generating and integrative centre-contains groups of neurons that fire during inspiration and others that fire during expiration

-when its inspiratory neurons fire, a burst of impulses travels along the phrenic and intercostal nerves to excite the diaphragm and external intercostal muscles respectively

-the thorax expands and air rushes into the lungs

-when its expiratory neurons fire, the output stops and expiration occurs passively as the inspiratory muscles relax and the lungs recoil

-the cyclic activity of inspiratory and expiratory neurons repeats continuously and produces a respiratory rate of 12-15 breaths per minute; inspiratory phases last 2 seconds and expiratory phase lasts 3 seconds

-this respiration rate and rhythm is referred to as eupnea

-during hypoxia, VRG generates gasping (to restores O2 to the brain)

-respiration stops completely when a certain cluster of VRG neurons is completely suppressed (i.e.: alcohol or morphine overdose)

Factors Influencing Breathing Rate and Depth -inspiratory depth is determined by how actively the respiratory centre stimulates the motor neurons serving the respiratory muscles

-greater stimulation = greater number of motor units excited = greater force of respiratory muscle contractions

-respiratory rate is determined by how long the inspiratory centre is active or how quickly it is switched off

1) Chemical Factors-the most important factors are changing levels of CO2, O2, and H+ in arterial blood -chemoreceptors respond to chemical fluctuations

-found as central chemoreceptors that are located throughout the brain stem and peripheral chemoreceptors that are found in the aortic arch and carotid arteries

Influence of PCO2-CO2 is the most potent and the most close controlled in terms of chemicals that influence respiration -arterial PCO2 is 40 mmHg and maintained within +/- 3 mmHg

-as PCO2 levels rise in the blood (hypercapnia), CO2 accumulates in the brain-as CO2 accumulates, it is hydrated to form carbonic acid-the acid dissociates-H+ is liberated-pH drops (more acidic) -the increase in H+ excites the central chemoreceptors which make abundant synapses with the respiratory regulatory centres -depth and rate of breathing are increased as a result-the enhanced alveolar ventilation quickly flushes CO2 out of the blood-blood pH increases

-elevation of 5mmHg in arterial PCO2 results in a doubling of alveolar ventilation even if O2 levels and pH are unchanged

-when O2 and pH are below normal, the response to elevated PCO2 is even greater

-increased ventilation is self-limiting; it ends when blood PCO2 levels are restored

-rising blood CO2 levels act as the initial stimulus-rising levels of H+ generated within the brain increase the activity of central chemoreceptors -CO2 diffuses across the blood-brain barrier but H+ does not

-control of breathing during rest is aimed primarily at regulating the H+ concentration in the brain

-hyperventilation involves an increase in the rate and depth of breathing that exceeds the body's need to remove CO2

-anxiety attacks may cause a person to hyperventilate involuntarily and faint-this is caused by hypocapnia (low levels of CO2 in the blood) which make cerebral blood vessels constrict and reduces brain perfusion, producing cerebral ischemia-attacks can be averted by breathing into a paper bag; the air being inspired is rich in carbon dioxide and it is then retained in the blood

-when PCO2 is low, respiration is inhibited and becomes slow and shallow -apnea (periods of breathing cessation) may occur until arterial PCO2 rises and stimulates respiration

-swimmers hyperventilate which drops PCO2 levels so they can hold their breath for longer-dangerous because they lose the urge to breath and oxygen levels may fall below 50 mmHg

Influence of PO2 -O2-sensitive cells are found in the peripheral chemoreceptors (i.e.: the aortic bodies of the aortic arch and in the carotid bodies at the bifurcation of the common carotid artery)

-main oxygen sensors are found in the carotid body

-the effect of declining PO2 on ventilation is slight and is limited to enhancing the sensitivity of peripheral receptors to increased PCO2

-arterial PO2 levels must drop substantially (i.e.: 60 mmHg) before O2 levels become a major stimulus for increased ventilation

-there is a large reservoir for Hb-Hb remains almost entirely saturated unless or until PO2 of alveolar gas and arterial blood falls below 60 mmHg

-peripheral chemoreceptor system can maintain ventilation when alveolar O2 levels are low even though brain stem centres are depressed by hypoxia

Influence of Arterial pH -changes in arterial pH can modify respiratory rate even when CO2 and O2 levels are normal -very little H+ diffuses from the blood into the brain

-the direct effect of arterial H+ concentration on central chemoreceptors is minimal-the effect of H+ generated by elevations in PCO2 is more significant

-an increased ventilation that occurs in response to falling arterial pH is mediated through peripheral chemoreceptors

-changes in PCO2 and H+ concentration are related but are distinct stimuli -a drop in blood pH may reflect CO2 retention or other metabolic causes

-as arterial pH declines, the respiratory system compensates by increasing respiratory rate to eliminate CO2 in order to raise the pH

2) Influence of Higher Brain Centres

Hypothalamic Controls -strong emotions and pain send signals to the respiratory centres and modifies respiratory rate and depth -i.e.: anger = holding breath -a rise in body temperature increases respiratory rate-a drop in body temperature decreases respiratory rate

Corticol Controls -we can exert conscious control over the rate and depth of breathing -during voluntary control, the cerebral motor cortex sends signals to motor neurons that stimulate the respiratory muscles and bypasses the medullar centres -brain stem respiratory centres automatically reinitiate breathing when blood concentration of CO2 reaches critical levels

Pulmonary Irritant Reflexes -irritants stimulate receptors in the bronchioles that promote reflex constriction of those air passages-these irritants also stimulate coughing and sneezing Inflation Reflex-Hering-Breuer Reflex -a protective response to prevent excessive stretching of the lungs

-stretch receptors in the visceral pleurae and conducting passages in the lugs are stimulated when the lungs are inflated

-stretch receptors signal the medullary respiratory centres via afferent fibres of the vagus nerve to send inhibitory impulses that end inspiration and allow expiration to occur

-when lungs recoil, stretch receptors become quiet and inspiration is initiated again

Respiratory Adjustments

Exercise -respiratory adjustments during exercise deal with the intensity and duration of exercise

-hyperpnea involves the increase in ventilation in response to metabolic needs -different from hyperventilation -changes in hyperpnea do not lead to significant changes in blood O2 and CO2 levels -hyperventilation is excessive ventilation that is characterized by low PCO2 and alkalosis

-exercise-enhanced ventilation does not appear to be prompted by rising PCO2 and declining PO2 and pH in the blood

-ventilation increases abruptly as exercise beings, followed by a gradual increase, and then a steady state of ventilation -when exercise stops there is an abrupt decline in ventilation rate, followed by a gradual decrease -arterial PCO2 and PO2 levels remain constant during exercise

-the abrupt increase in ventilation that occurs as exercise begins reflects 3 neural factors:

1) psychological stimuli (conscious anticipation of exercise)2) simultaneous cortical motor activation of skeletal muscles and respiratory centres3) excitatory impulses reaching respiratory centres from proprioceptros in moving muscles, tendons, and joints

-the gradual increase and then plateau of respiration reflects the rate of CO2 delivery to the lungs

-the small, abrupt decrease in ventilation reflects the shutting off of the 3 neural factors

-the gradual decline to baseline ventilation reflects a decline in the CO2 flow that occurs as oxygen deficit is repaid

-the rise in lactic acid levels that contributes to O2 deficit is not a result of inadequate respiratory function; it reflects cardiac output limitations or the inability of skeletal muscles to increase oxygen consumption