Lecture 17 - Respiratory Physiology

in what two forms is oxygen carried in the blood? what are the normal quantities (in milliliters per liter) for each form in arterial blood?

(1) Dissolved in plasma and erythrocyte cytosol; and (2) reversibly bound to hemoglobin (Hb) molecules within the erythrocytes. Normal quantities are: dissolved = 3 ml/L; bound to Hb = 197 ml/L.

List the physical factors that alter airway resistance

(1) Transpulmonary pressure exerts a distending force on the airways. This is a major factor keeping the smaller airways from collapsing. (2) The elastic connective tissue fibers that link the outside of the airways to the surrounding alveolar tissue exert a lateral traction on the airways during inhalation/inspiration, helping them to expand even more.

Functions of the RESPIRATORY SYSTEM

(1) Ventilation: Exchange of air between atmosphere & alveoli by bulk flow (2) Exchange of O2 & CO2 between alveolar air & blood in lung capillaries by diffusion (3) Transport of 02 & CO2 through pulmonary & systemic circulation by bulk flow (4) exchange of O2 & CO2 between blood in tissue capillaries & cells in tissues by diffusion (5) Cellular utilization of O2 & production of CO2

state the alveolar partial pressures for oxygen and carbon dioxide in a healthy person at rest

Alveolar PO2 is normally 105 mmHg at rest. Alveolar PCO2 is normally 40 mmHg.

State the formula or calculating alveolar ventilation. What is an average value for alveolar ventilation?

Alveolar ventilation (ml/min) = (Tidal volume - Dead space volume) × Respiratory rate Anatomic dead space is normally about 150 ml. Therefore, alveolar ventilation = (500 - 150) ml/breath × 12 breaths/min = 4200 ml/min.

Alveolar Ventilation

Alveolar vetiation = (tidal volume - dead space) x respiratory rate

Describe the effects of increased Pco2, H+ concentration, and temperature on the oxygen-hemoglobin dissociation curve. How are these effects adaptive for oxygen unloading in the tissues?

An increase in any of the above at any given PO2 would cause the curve to shift toward the right, meaning that hemoglobin would have less affinity for oxygen under these conditions. The more active a tissue is, the greater its PCO2, H+ concentration and temperature, and the greater also is its requirement for oxygen. The rightward shift affords a mechanism whereby active tissues have increased oxygen delivery to them because the right shift of the curve in the tissues would unload more oxygen.

What happens to arterial Po2, Pco2, & H+ concentration during moderate & strenuous exercise? List other factors that may stimulate ventilation during exercise.

Arterial PO2, PCO2, and H+ all remain constant during moderate exercise, and arterial PO2 remains constant even at maximal activity. Arterial PCO2 actually decreases during the progression from moderate to heavy exercise. Arterial H+ concentration does increase if exercise intensity goes beyond moderate, and so it undoubtedly plays a role in increased ventilation during severe exercise. Other factors that may stimulate ventilation during exercise include: (1) reflex input from mechanoreceptors in joints and muscles; (2) an increase in body temperature; (3) inputs to the respiratory neurons via branches from axons descending from the brain to motor neurons supplying the exercising muscles; (4) an increase in the plasma epinephrine concentration; (5) an increase in the plasma K+ concentration (because of movement out of the exercising muscles; and (6) a conditioned (learned) response mediated by neural input to the respiratory centers.

Contrast the causes of increased airway resistance in asthma, emphysema, & chronic bronchitis

Asthma is a disease characterized by intermittent attacks in which airway smooth muscle contracts strongly, markedly increasing airway resistance. The basic defect is chronic inflammation of the airways. Emphysema is a chronic obstructive pulmonary disease that causes increased airway resistance as a result of destruction and collapse of the smaller airways. Chronic bronchitis is another chronic obstructive pulmonary disease that is characterized by excessive mucus production in the bronchi and chronic inflammatory changes in the small airways. The cause of obstruction is an accumulation of mucus in the airways and thickening of the inflamed airways.

State typical values for oxygen consumption, carbon dioxide production, & cardiac output at rest. How much oxygen (in milliliters per liter) is present in systemic venous & systemic arterial blood?

At rest, typically 250 ml of oxygen is consumed, 200 ml of carbon dioxide is produced, and the cardiac output is 5 L, all per minute. The oxygen content in systemic venous blood is 150 ml/L, and that for systemic arterial blood is 200 ml/L.

Between breaths at the end of unforced expiration, in what directions do the lungs & chest wall tend to move? What prevents them from doing so?

At the end of an unforced exhalation/expiration, the lungs tend to recoil inward, and the chest wall tends to move out or expand. The resultant subatmospheric intrapleural pressure keeps the lungs partially expanded and the chest wall partially compressed between breaths.

Draw an oxygen-hemoglobin dissociation curve. Put in the points that represent systemic venous and systemic blood (ignore the rightward shift of the curve in systemic venous blood). What is the adaptive importance of the plateau? Of the steep portion?

Certain situations, such as high altitude and pulmonary disease, are characterized by a moderate reduction in alveolar and therefore arterial PO2. Because of the plateau in the dissociation curve, even if the systemic arterial PO2 decreased from the normal value of 100 to 60 mmHg, the total quantity of oxygen carried by hemoglobin would decrease only 10% since hemoglobin saturation is still close to 90% at a PO2 of 60 mmHg. The plateau thus provides an excellent safety factor in the supply of oxygen to the blood. Similarly, when arterial PO2 decreases due to altitude or lung disease, the steep portion of the curve ensures that as much oxygen as possible is delivered to the tissues for cellular respiration (oxygen consumption).

Compliance Chart

Comliance = change in lung volume/change in (Palv-Piv)

Branches of the Respiratory Tract

Conduction zone-Trachea(1 tube), Bronchi (2 tube 4, & 8), Bronchioles (16 tubes), & terminal bronchioles (32 - 6x10^4) Respiratory Zone - Respiratory bronchioles (5x10^5), Alveolar ducts & sacs (8x10^6)

What happens to most of the H+ formed in the erythrocytes from carbonic acid? What happens to blood H+ concentration as blood flows through tissue capillaries?

Deoxyhemoglobin has a high affinity for H+, and so it binds (buffers) most of them. Because of this buffering effect, the H+ concentration in venous blood is only slightly greater than that in arterial blood.

Describe the sequence of events that cause air to move into the lungs during inspiration & out of the lungs during expiration. Diagram the changes in intrapleural pressure & alveolar pressure.

During inhalation/inspiration, the diaphragm and inspiratory intercostal muscles contract, causing the thorax to expand. As the thorax enlarges, the thoracic wall moves slightly farther away from the lung surface, causing the intrapleural fluid pressure to become more subatmospheric (more negative relative to atmosphere). This decrease in intrapleural pressure increases the transpulmonary pressure and causes the lungs to expand. By Boyle's law, an increase in lung volume with no change in the number of gas molecules causes a decrease in pressure. Therefore, the Palv becomes subatmospheric and air flows into the alveoli. During exhalation/expiration, the diaphragm and inspiratory intercostals stop contracting. The chest wall recoils inward, and Pip moves back toward preinhalation/preinspiration value. This causes the transpulmonary pressure to be reduced back toward preinhalation/inspiration value, and the lungs to recoil back toward preinhalation/inspiration size. Air in the alveoli becomes compressed, and Palv becomes greater than Patm. Consequently, air flows out of the lungs.

Slide: What happens when you exhale?

During normal breathing elastic recoil does the work, during exercise expiratory muscle contract To exhale the diaphragm relaxes forcing it into a dome shape which pushes up on the pleural cavity decreasing the volume of the pleural cavity. The pressure in the pleural cavity increases which squeezes the lungs into a smaller volume. The decrease in volume of the lungs increases the pressure inside the lung eventually above zero forcing air to exit the lungs in an exhale.

What keeps the lungs open at rest?

Elastic recoil of lungs would cause lungs to collapse if not countered Trans pulmonary positive pressure caused by negative pressure from pleura activity

Write the equation relating airflow into or out of the lungs to alveolar pressure, atmospheric pressure, & airway resistance

F = (Palv - Patm )/R, where F = airflow, Palv = alveolar pressure , Patm is atmospheric pressure, and R = airway resistance.

Decreased alveolar Po2 causes reflex vasodilation of the pulmonary arterioles

FALSE

Of the CO2 returning from the tissues in venous blood, more is dissolved in plasma as CO2 than is bound to hemoglobin

FALSE

Most of the O2 carried in the blood is dissolved in plase

FALSE, dissolved in the tissue

what is the mechanism of as exchange between alveoli and pulmonary capillaries? in a healthy person at rest, what are the gas pressures at the end of the pulmonary capillaries relative to those in the alveoli?

Gas exchange occurs by diffusion of oxygen from the alveoli to the capillary blood, and diffusion of carbon dioxide from the capillary blood to the alveoli. In a normal person at rest, the gas pressures at the end of the pulmonary capillaries are nearly identical to those in the alveoli (i.e., PO2 = 100 mmHg; PCO2 = 40 mmHg).

describe the structure of hemoglobin

Hemoglobin is a protein made up of four subunits. Each subunit consists of a molecular group known as heme, which contains an iron atom, and a polypeptide attached to the heme. The four polypeptides are collectively called globin. One molecule of oxygen binds to each iron in the heme groups. Since each hemoglobin molecule has four iron atoms, and each iron atom can bind one molecule of oxygen, each hemoglobin can bind four molecules of oxygen.

Alveolar Ventilation & Alveolar P02 & Pco2

Hypoventilation Lower respiratory rate Hyperventilation Increased respiratory rate

At rest, how many liters of air flow in & out of the lungs & how many liters of blood flow through the lungs per minute?

In a healthy adult at rest, approx 4L of fresh air enters & leaves the alveoli per min, while 5L of blood, the cardiac output

Would breathing pure oxygen cause a large increase in oxygen transport by the blood in a healthy person? In a person with low alveolar P02?

In a normal person at sea level, breathing pure oxygen would add very little additional oxygen to the blood because hemoglobin is already almost completely saturated. (A little more oxygen would dissolve, but this amount is negligible.) In a person with low alveolar PO2, however, breathing pure oxygen would increase the alveolar, and thus the arterial PO2, and result in significantly more oxygen transport.

List four general causes of hypoxic hypoxia

In hypoxic hypoxia (hypoxemia), arterial PO2 is reduced. Exposure to high altitude is one cause. There are also four disease conditions that result in hypoxic hypoxia: (1) hypoventilation, which may be caused by a defect anywhere along the respiratory control pathway, by severe thoracic cage abnormalities, and by major obstruction of the upper airway; (2) diffusion impairment, which results from thickening of the alveolar membranes or a decrease in their surface area; (3) a shunt, which is either an anatomic abnormality of the cardiovascular system that causes mixed venous blood to bypass ventilated alveoli in passing from the right heart to the left heart, or an intrapulmonary defect in which mixed venous blood perfuses unventilated alveoli; and (4) ventilation-perfusion inequality, which is by far the most common cause of hypoxemia and occurs in chronic obstructive lung diseases and other lung diseases.

Which are normal values for intrapleural pressure, alveolar pressure, & transpulmonary pressure at the end of an unforced expiration?

In relation to atmospheric pressure, at the end of an unforced exhalation/expiration, intrapleural pressure (Pip) is -4 mmHg; alveolar pressure (Palv) is 0 mmHg; and transpulmonary pressure (Palv-Pip) is 4 mmHg.

Describe the effects of increased DPG on the oxygen-hemoglobin dissociation curve. What is the adaptive importance of the effect of DPG on the curve?

Increased DPG also makes the dissociation curve shift to the right. Erythrocytes produce DPG during glycolysis. An increase in DPG concentration is triggered by a variety of conditions associated with inadequate oxygen supply to the tissues, such as anemia and exposure to high altitude, and the response in the shift of the oxygen-hemoglobin dissociation curve helps to maintain oxygen delivery.

describe the pathways by which increased arterial Pco2 stimulates ventilation. what pathway is more important?

Increased arterial PCO2 stimulates ventilation in two ways. In one pathway, arterial H+ concentration is increased secondary to the increased PCO2. This increase in arterial H+ concentration stimulates the peripheral chemoreceptors to increase their rate of firing, triggering reflexes via medullary respiratory neurons that increase the rate of contraction of the respiratory muscles and thus ventilation. Increased ventilation allows for more carbon dioxide to be eliminated by the lungs, thereby returning arterial PCO2, and thus H+ concentration, toward normal. The second pathway involves central chemoreceptors. Because carbon dioxide readily diffuses into the extracellular fluid of the brain, an increase in arterial PCO2 will lead to an increase in brain extracellular-fluid PCO2. Carbonic anhydrase in brain extracellular fluid catalyzes the conversion there of carbon dioxide and water to carbonic acid, which dissociates to HCO3- and H+. This increased H+ concentration stimulates the central chemoreceptors. These receptors trigger the same reflexes described above, resulting in the return of arterial, and thus brain extracellular-fluid, PCO2 and H+ concentration back toward normal. Of the two sets of receptors, the central chemoreceptors are more important, accounting for about 70% of the increased ventilation.

What distinguishes lung capacities, as a group, from lung volumes?

Lung capacities are the sum of two or more lung volumes. The lung residual volume, expiratory reserve volume, resting tidal volume, and inspiratory reserve volume add up to the total lung capacity.

The Lung at Rest

Lung tissue is kind of like a rubber band in that it wants to contract to a smaller shape we call it "elastic". At rest the only way to keep the lungs from collapsing is to make sure that there is just a little more pressure inside the lung than in the pleural cavity. So the pressure in the pleural cavity normally is just a little below zero. When the pleural cavity is punctured this raises the pressure in the pleural cavities above normal, high enough that now there is no pressure to oppose the elastic recoil of the lungs, and as a result the lungs collapse on themselves.

What generates the diffusion gradients for oxygen and carbon diocide in the tissues?

Metabolic reactions occurring within cells are constantly consuming oxygen and producing carbon dioxide. Therefore, intracellular PO2 is lower and PCO2 higher than in blood. The lowest PO2 of all is in the mitochondria, the site of oxygen utilization. As a result, there is a net diffusion of oxygen from the blood into cells (and, within the cells, into the mitochondria), and a net diffusion of carbon dioxide from cells into blood.

State the formula relating minute ventilation, tidal volume, & respiratory rate. Give representative values for each in a normal person at rest.

Minute ventilation (ml/min) = Tidal volume (ml/breath) × Respiratory rate (breaths/min) At rest, tidal volume is ~500 ml/breath, respiratory rate is 12 breaths/min, and so minute ventilation is 6000 ml/min.

List two types of sleep apnea. Why does nasal CPAP prevent obstructive sleep apnea?

Obstructive and central sleep apnea. Continuous positive airway pressure (CPAP) increases airway pressure greater than the atmospheric pressure thus preventing the collapse of the upper airway.

What two factors determine lung compliance? Which is most important?

One factor determining lung compliance is the stretchability of the lung tissues, particularly their elastic connective tissues. The other is the surface tension at the air-water interfaces within the alveoli. The surface tension is typically more important.

Boyle's law

P1V1=P2V2

Alveolar Macrophages (Dust Cells)

Patrol the alveoli & "eat" any foreign cells or particles

Slide: What Happens when you inhale?

Ptp = Palv - Pip = -1 - (-6) = 5 atm (Lungs expand, air flows in) At rest the pressure in the lung and in the atmosphere are equal To start inhaling the diaphragm contracts pulling down on and stretching the pleural cavity Stretching the pleural cavity increases the volume of the pleural cavity and according to Boyle's law when the volume increased the pressure in that cavity decreases, this will lead the pressure in the lung to drop below the pressure of atmosphere so now air can flow into the lung from high pressure to low pressure.

Describe the function of the pulmonary stretch receptors

Pulmonary stretch receptors lie in the airway smooth muscle layer and are activated by large lung inflation. Action potentials in the afferent nerve fibers from the stretch receptors travel to the brain and inhibit the medullary inspiratory neurons, thus providing a cutoff signal for inhalation/inspiration.

is respiratory control more sensitive to small changes in arterial P02 or in arterial Pco2?

Respiratory control is much more sensitive to changes in arterial PCO2.

respiratory rates & ventilation measures

Respiratory rate AVG about 12 breaths / minute Minute Ventilation (VE) Respiratory rate x tidal volume Volume of air moved per minute Alveolar Ventilation (VA) Respiratory rate x (tidal volume - dead air space) Volume of fresh air into the alveoli per minute Determines rate of gas exchange

Draw figures showing the reactions carbon dioxide undergoes entering the blood in the tissue capillaries & leaving the blood in the alveoli. What fractions are contributed by dissolved carbon dioxide, HCO-3, & carbaminohemoglobin?

Ten percent of carbon dioxide is dissolved in plasma. Thirty percent is carried as carbamino hemoglobin. Sixty percent is carried as HCO3-.

The Pleura Cavities

The amount of fluid in the intrapleural fluid & the parietal pleura is small The fluid itself is conductive in transferring fluids

Describe 4 functions of the conducting portion of the airways

The conducting zone of the airways: (1) provides a low-resistance pathway for airflow; resistance is physiologically regulated by changes in contraction of airway smooth muscle (leading to changes in the airway diameter) and by physical forces acting on the airways; (2) defends against microbes, toxic chemicals, and other foreign matter; cilia, mucus, and phagocytes perform this function; (3) warms and moistens the air; and (4) phonates (contains the vocal cords).

Explain how ventilation-perfusion mismatch due to regional lung disease can cause hypoxic hypoxia but not hypercapnia.

The difference lies in the way oxygen and carbon dioxide are transported. The majority of oxygen is bound to hemoglobin which is subject to saturation, whereas carbon dioxide is carried primarily in solution which does not display saturation. Blood leaving poorly ventilated alveoli lowers PO2. Blood from well ventilated alveoli can't compensate because the hemoglobin is already highly saturated and further substantial increases in oxygen content aren't possible. While poorly ventilated alveoli do have elevated PCO2, this causes increased ventilation which lowers PCO2 in well ventilated alveoli.

How is airway resistance influenced by airway radii?

The factors that determine airway resistance are analogous to those determining vascular resistance in the circulatory system: tube length, tube radius, and interactions between moving molecules. As in the circulatory system, the most important factor by far is tube radius: Airway resistance is inversely proportional to the fourth power of the airway radii.

what factors determine alveolar partial pressures?

The factors that determine the value of alveolar PO2 are: (1) the PO2 of atmospheric air; (2) the rate of alveolar ventilation; and (3) the rate of total-body oxygen consumption. The factors for PCO2 are similar except that there is normally essentially no carbon dioxide in inspired air, and the third factor is the rate of total-body carbon dioxide production.

what are the effects of P02 on carbaminohemoglobin formation and H+ binding by hemoglobin?

The higher the PO2, the lower the affinity of hemoglobin for CO2 and H+. In other words, deoxyhemoglobin has a much stronger affinity for these compounds than does oxyhemoglobin.

Describe two general ways in which the lungs can alter the concentrations of substances other than oxygen, carbon dioxide, & H+ in the arterial blood

The lungs influence arterial blood concentrations of biologically active substances by removing some from systemic venous blood and adding others to systemic arterial blood.

what is the major result of ventilation -perfusion inequalities throughout the lungs? describe homeostatic responses that minimize mismatching.

The major result of ventilation-perfusion inequality is to lower the PO2 of systemic arterial blood. One local homeostatic response that minimizes mismatching is the vasoconstriction of small pulmonary blood vessels in response to locally low PO2. If an alveolus is receiving too little air for its blood supply, the PO2 in the alveolus and its surrounding area will be low. The net adaptive effect is to supply less blood to poorly ventilated areas and more blood to well-ventilated areas.

The partial pressure of a gas is dependent upon what two factors?

The partial pressure that a gas in a mixture exerts is proportional to (1) the temperature and (2) the concentration of the gas.

What changes stimulate the peripheral chemoreceptors? The central chemoreceoptors?

The peripheral chemoreceptors (the carotid and aortic bodies) are stimulated mainly by decreased PO2 and increased H+ concentration in the arterial blood. The central chemoreceptors are stimulated by increased PCO2 (via associated changes in H+ concentration) in the brain extracellular fluid.

Describe the pathway by which a change in arterial H+ concentration independent of altered carbon dioxide influences ventilation. what is the adaptive value of this reflex?

The peripheral chemoreceptors respond to increased (or decreased) arterial H+ concentration, whatever its cause. If the cause is not increased arterial PCO2 (respiratory acidosis) or decreased arterial PCO2 (respiratory alkalosis), then it is termed metabolic acidosis or alkalosis. For example, during very strenuous exercise, blood concentration of lactic acid can increase (metabolic acidosis), and this increase stimulates the peripheral chemoreceptors to trigger the reflex increase in ventilation described above. This increased ventilation has the effect of bringing blood H+ concentration back toward normal. Thus, the lungs can help to correct a problem that they did not bring about.

why is the moderate anemia or carbon monoxide exposure does not stimulate the peripheral chemoreceptors?

The peripheral chemoreceptors respond to the actual PO2 of arterial blood, not to the oxygen-carrying capacity of the blood. When alveolar PO2 is normal or nearly normal, the peripheral chemoreceptors will not respond to a decrease in the binding of hemoglobin to oxygen (as with carbon-monoxide exposure) or to a decrease in circulating erythrocytes (as in anemia).

Describe the area of the brain in which automatic control of rhythmic respiration resides

The respiratory center is located in the medulla oblongata. Neurons in the dorsal respiratory group and ventral respiratory group are responsible for controlling the automatic, rhythmical contractions of respiratory

How does surfactant increase lung compliance? How does surfactant stabilize alveoli by preventing small alveoli from emptying into large alveoli?

The surface tension of pure water is so great that, were the alveoli lined with it, lung expansion would require exhausting muscular effort and the lungs would collapse. Surfactant is a detergent-like substance produced by type II alveolar cells that markedly reduces the cohesive forces between water molecules on the alveolar surface. Therefore, surfactant lowers the surface tension in the fluid lining the alveoli and thus increases lung compliance. Because the molecules of surfactant are closer in smaller spaces, the surface tension is lower in smaller alveoli and, thus, surfactant stabilizes them preventing them from emptying into larger alveoli.

why does thickening of alveolar membranes impair oxgyen movement but has little efect on carbon dioxide exchange?

Thickening of alveolar membranes increases the distance across which the gases must diffuse. Carbon dioxide diffuses much more readily than oxygen, and so it is not affected as much by such thickening.

The Alveoli

Thin sacs surrounded by a rich capillary bed

Minue Ventilation

Total ventilation per minute (lpm) minute ventilation =Tidal volume x respiratory rate

Slide: The Respiratory Tract

Upper Respiratory Tract Lower respiratory Tract

The diaphragm & ventilation

Volume increase contraction- Poutside = Pinside pressure inside falls, so air flows in Volume Decrease Poutside = Pinside Pressure inside rises, so air flows out

Which of the following is NOT a function of the respiratory system? a) net uptake of carbon dioxide from the air & removal of oxygen from the blood b) regulation of blood H+ concentration c) trapping of blood clots

a) net uptake of carbon dioxide from the air & removal of oxygen from the blood

Which of the following is NOT TRUE about pulmonary surfactant?

answer: it is secreted by Type 1 alveolar cells INcorrect Answers" it reduces the surface tension of water, helps to prevent lung collapse, & is composed of phospholipids & proteins

Carbonic anhydrase cataylze a reaction that combines which of the following a)H2O & O2 b) H2O & CO2 c) H2O & CO

b) H2O & CO2

Regarding the partial pressures of O2 & CO2, which of the following statements is NOT true in a normal person at rest? a) atmospheric Po2 is greater than alveolar Po2 b) the Pco2 in air is less than alveolar Pco2 c) the Po2 in systemic arteries is typically greater than the alveolar Po2

c) the Po2 in systemic arteries is typically greater than the alveolar Po2

Slide: Lung Compliance

change in lung volume caused by a given change in transpulmonary pressure the greater the lung compliance, the more readily the lungs are expanded Determined by: Lung tissue thickness Surface tension of fluid on the inner lung surface COPD

Surfactant

detergent-like phospholipid-protein mixture produced by pulmonary type II alveolar cells reduces surface tension of fluid film lining alveoli

Ventilation

flow of air = Palv-Patm(760 mmHg)/ resistance

Type 2 cells

secretes surfactant lowers blood (mostly water) surface tension helps to prevent lung collapse

Type 1 cells

simple squamous cells specialized for allowing gas changes