Physiology Lecture 52 3/12/07 Lecturer: Dr.

Forester Writer: Ben Keller Overview of Lung Mechanics For a very complete co-op with extra information not included this year, see the 2008 co-op. Before lecture material was introduced, Dr. Forester noted the following: • Lecture notes are intended to be complete. • If you want to use a book, both Guyton and the Physiology of Respiration text (on reserve in the library) are good resources. • This is a “big picture” lecture and will be broken down in subsequent lectures. Function of the Respiratory System a. oxygenation of blood c. thermoregulation (only in some non-human animals) b. elimination of CO2 d. maintain blood gas homeostasis The definitions and vocabulary words on pg 572-73 should be committed to memory. Some important points noted were: • Pressure (P) of a gas will change with elevation. Concentration (F) of gas will never change regardless of elevation. • Recognize subscripts; PACO2 and PaCO2 are different things!! • The suffix –nea refers to breathing. • Hyperventilation/hypoventilation differs from hyperpnea/hypopnea. • Periodic breathing is a hallmark pointing to problems involving the neurological center for breathing • Dyspnea is the #1 reason people visit a pulmonary clinician. Behavior of Gases as Gases • • • • • Avogadro's hypothesis: for all gases, an equal number of molecules in the same space at the same temperature will exert the same pressure. o Pressure is dependent on the number of gas molecules and the temperature. Dalton's law: (the law of partial pressures) In a gas mixture, the pressure exerted by each individual gas is independent of the pressures of the other gases in the mixture. (No interaction between gas molecules. Ptot = P1 + P2 + ... Pn) Boyle's law: as a gas is compressed, the volume decreases in exactly the same proportion as its pressure increases. (P1V1 = P2V2) Charles law: if the volume of a gas is kept constant, the pressure of the gas is proportional to the temperature. Increasing the temperature increases the particles' kinetic energy, thus increasing the pressure. (P is proportional to T) Ideal Gas law: PV = nRT (n is # of molecules, R is the gas constant, T is temperature)

Henry's law: the concentration of a dissolved gas is equal to the partial pressure of the gas times its solubility coefficient.

A mole of gas contains 6 x 1023 molecules and occupies a volume of 22.4 liters, at a temperature of 0° C and pressure of 760 mmHg O2 and CO2 flux: Global picture of the respiratory system Breathing: is the gas exchange between the atmosphere and the alveoli in our lungs. This is an active process, requiring energy to move the inspiratory muscles. There are two important physiological components: 1. Mechanics of breathing: the forces necessary to move the air (compliance and volume) 2. Control of breathing: central and peripheral regulatory mechanisms and the body's response • Pulmonary ventilation: VE is the total amount of air going in and out of the lungs in a given time period, usually per minute. It can be further broken down into alveolar and dead space ventilation. • Alveolar ventilation: VA refers to the fresh air reaching the lung alveoli in a given period of time. It is the amount of air that can actually participate in gas exchange. • Dead space ventilation: VD refers to the amount of air does not participate in gas exchange because it fills the trachea and bronchi where alveoli are not present. A certain percentage of each inspired breath fills the dead space only. During inhalation, the first gas that contacts the alveoli is not fresh air, it is the gas left over in the dead space from the last exhalation. Alveolar-Capillary Exchange: this is a passive process (no energy required) in the lungs by which gas moves between the alveoli and the blood. 1. Diffusing capacity: measures the ease with which the blood moves from the lungs into the bloodstream. When air fills the alveolus, it must move through the alveolar membrane, through the fluid space between the alveolus and the capillary, and finally through the capillary wall itself. 2. Ventilation-perfusion matching: for gas exchange to occur, air and blood must come in close contact which occurs at the alveoli-capillary interface. Blood Gas Transport: this is an active process, requiring energy from the heart. 1. Dissolved: can move into tissues down its concentration gradient 2. Bound: oxygen that is bound to hemoglobin cannot move into tissues. It can only move within circulation and its movement is dependent on the pumping of the heart. Capillary-Tissue Exchange: a passive process. 1. Diffusion: movement from systemic capillaries into the tissue 2. Pressure Gradient: a gradient must exist and O2 movement only occurs down its gradient. P02 Graph (576) • As one might predict, oxygen concentrations are highest in the atmosphere and carbon dioxide is highest in venous blood. • Alveolar oxygen pressure is less than that of the atmosphere due to the face that:

o some of the CO2 rich air that was just exhaled being re-inhaled o our lungs do not fully empty with each breath (40% of air in lungs is residual) o there is continual gas exchange which lowers PO2 • Arterial blood is lower than alveolar blood because the venous drainage from the bronchi goes back to the left side of the heart. • The mixed venous lower than alveolar due to the fact that O2 has been utilized. PCO2 Graph (576) • The mixed venous blood supply has a slightly larger PCO2 than the arterial blood supply. This is due to the difference in dissociation curves for oxygen and carbon dioxide. This will be discussed at a later time. P02 Graph for Anemic Patient (577) • Hemoglobin does not determine an individuals arterial PO2. The lungs do! In fact, arterial one can look at arterial PO2 to ascertain whether the lung is functioning properly or not. • Alveolar and arterial oxygen pressures are basically unaffected by the low hemoglobin because anemia is not a lung disease it is due to low hemoglobin. PCO2 Graph for Anemic Patient (577) • PCO2 does not change significantly. P02 Graph for Resident of Pike’s Peak (578) • PO2 is reduced at each step in the pathway (there is simply less O2 around at high altitude), though the amount of change at each level is not uniform. • Hypoxemia stimulates chemoreceptors which cause a compensatory increase in breathing rate (hyperventilation). This causes PO2 in the alveolar and arterial to increase. • At the mixed venous level there is only a small difference between the altitude and sea level graphs. This is due to the effect hyperventilation has on the PO2. PC02 Graph for Resident of Pike’s Peak (578) • PCO2 is also below normal at each step because hyperventilation eliminates excess CO2 P02 & PC02 Graph for Patient with Alveolar Hypoventilation (579) • This person is not breathing enough to meet the body's metabolic requirements. • Alveolar and arterial PO2 levels are decreased by about the same amount that alveolar and arterial PCO2 levels are increased. • The increase in venous PCO2 is larger than the decrease in venous PO2. This indicates a general increase in carbon dioxide levels in the body. P02 & PC02 Graph for Patient with Alveolar- Capillary Exchange Problem (580) • The key indicator of exchange problems is a large difference in PO2 levels in the alveolar vs. the levels in arterial blood. The alveolar PO2 is increased, demonstrating that sufficient oxygen is reaching the alveolar membrane. On the other hand arterial PO2 is decreased which hints at a problem with the structures through which the gas diffuses occurs. • The problem could be due to the inability of the air and blood to get together. (ventilationperfusion mismatch)

The body's response to the hypoxemia due to the exchange problems is hyperventilation. As in the altitude graph, the hyperventilation lowers PCO2 at the alveolar, arterial, and mixed venous levels.

P02 & PC02 Graph for Patient with Alveolar-Capillary Exchange and Hypoventilation (581) • Hypoventilation is evident because PCO2 levels are elevated as opposed to being decreased as seen with hyperventilation. • Breathing rate cannot be increased to minimize the drop in PO2 • PO2 in this graph is much more depressed than in the last graph in which hyperventilation helped to compensate for the low PO2 levels. • Such symptoms might be seen in emphysema or chronic obstructive pulmonary disease. Anatomy of the Respiratory System The respiratory system can be broken down into three separate components: • The airway portion consists of the conducting system: oral passages, pharynx, larynx, trachea, bronchi, and bronchioles. • The exchange portion is the flow-through system, including the pulmonary artery, pulmonary capillaries and pulmonary veins. The "business end" of this system is the site of gas exchange between the alveolus and the pulmonary capillary. The total number of alveoli is very important, because these comprise the surface area for gas exchange. o In emphysema, there is a significant reduction in the number of functional alveoli, which reduces this area. • The muscular system is comprised of pump muscles and airway muscles that function to keep the airway open. The pump muscles include the diaphragm and external intercostals which help with inspiration, while the internal intercostals and abdominal muscles assist in expiration. The state of contraction of these muscles, and especially the involuntary smooth muscle, is critical to controlling flow through the system. Smooth muscles are found in the bronchioles and skeletal muscle in the upper airways. o Problems may occur in the pharyngeal airway because it has two functions (breathing and swallowing). These functions must be coordinated to prevent problems. • Elasticity is also an important anatomical concept to keep in mind. o The chest wall is elastic and has an equilibrium position that is 60% of total lung inflation. The lungs on the other hand want to be collapsed in their equilibrium position of 0% lung inflation. The differences in equilibrium positions between the chest wall and lungs help to prevent the lungs from collapsing. One last thing mentioned was the two different types of respiratory deficiencies o Central – those who won’t breathe o Obstructive – those who can’t breath (ex. Sleep apnea)