Chapter 13: Respiratory

Question 1

13.2-13.4

Answer 1

1. Steps of Respiration
2. Ventilation and Lung Mechanics
3. Boyle’s Law
4. Pressure Measurements
   A. Intrapulmonary
   B. Intrapleural
   C. Transpulmonary
5. Pressure Changes During the Respiratory Cycle
6. Lung Compliance
7. Lung Volumes and Capacities
8. Minute Ventilation
9. Anatomical Dead Space
10. Alveolar Ventilation
11. Airway Resistance & Ventilation

Question 2

13.5-13.10

Answer 2

1. Exchange of Gases in Alveoli and Tissues
   A. Partial Pressures of Gases
   B. Alveolar Gas Pressures
   C. Gas Exchange Between Alveoli and Blood
   D. Matching of Ventilation and Perfusion in Alveoli
2. Transport of Oxygen in Blood
   A. Oxygen-Hemoglobin Dissociation Curve
   B. Effect of Hemoglobin Binding to Oxygen
   C. Oxygen Movement in Lungs and Tissues
3. Transport of Carbon Dioxide in Blood
4. Transport of Hydrogen Ions Between Tissues and Lungs
5. Effects of Various Factors on Hemoglobin Saturation
   A. DPG and Temperature
   B. Acidity and Fetal Hemoglobin
6. Brainstem Respiratory Control Centers
7. Peripheral Chemoreceptors
8. Effect of Po2, Pco2, and H+ Concentration on Ventilation
9. Control of Ventilation by PO2, PCO2, and H+ Concentration
10. Hypoxia
11. Carbon Monoxide Poisoning

HAVE TO BE ABLE TO INTERPRET AND DRAW HEMOGLOBIN LOADING GRAPHS

Question 3

13.1 Organization of the Respiratory System

Answer 3

• RESPIRATION
  • two meanings
  • CELLULAR (INTERNAL) RESPIRATION: oxygen utilization by cells
  • PULMONARY RESPIRATION: exchange of O2 and CO2 between the lungs and the environment

*RESPIRATORY SYSTEM:

- consists of lungs, airways (leading to lungs), and chest structures (that induce movement of air into and out of the lungs and airways)
- CONDUCTING ZONE of the airways (no gas exchange with blood)- composed of upper airways (NOSE, PHARYNX, LARYNX [(location of VOCAL CORDS)] → lower airways (TRACHEA, BRONCHI, and TERMINAL BRONCHIOLES) 
- RESPIRATORY ZONE of the airways (gas exchange with blood)- composed of RESPIRATORY BRONCHIOLES →  ALVEOLAR SACS containing ALVEOLI 
- ALVEOLI (sites of gas exchange): lined by epithelial cells, including type I and some type cells (that produce surfactant in a thin layer of a fluid coating)
- THORAX (CHEST) (also contains the heart): the thorax includes the SKELETAL MUSCLES OF RESPIRATION (drive the respiratory cycle), which are the DIAPHRAGM (separates thorax from the abdomen) and INTERCOSTAL MUSCLES (run between ribs). The thorax also is composed of CONNECTIVE TISSUE (elastic properties). 
- PLEURA: two membranous layers covering the lungs (VISCERAL PLEURA) and interior of the thorax (PARIETAL PLEURA) 
- INTERPLEURAL FLUID: an extremely thin layer of lubricating fluid between two pleural layers 

• LUNGS: elastic structures surrounded by pleura; LUNG VOLUME depends on:

  - pressure difference across the lungs   
  - how compliant (stretchable) the lungs are 
  - a thin layer of fluid and MUCUS  that coats and protects the airways 
  - airways fluid abnormal in CYSTIC FIBROSIS (CF)- caused by a mutation in the (CF) TRANSMEMBRANE CONDUCTANCE REGULATORY (CFTR) protein 

• RESPIRATORY CYCLE
  • INSPIRATION (INHALATION): the movement of air from the external environment through the airways into the alveoli during breathing
  • EXPIRATION (EXHALATION): air moves from the respiratory system to the environment

*Steps involved in respiration are
- VENTILATION: exchange of air by bulk flow
- exchange of oxygen and carbon dioxide between alveolar gas and pulmonary capillary blood by diffusion
- cellular consumption of oxygen and carbon dioxide between the tissue capillary blood and cells by diffusion
- cellular consumption of oxygen and production of carbon dioxide

*STEADY STATE: occurs when net volume of oxygen and carbon dioxide exchange per unit time in the lungs are equal to the net volumes exchanged per unit time in tissues

GENERAL SUMMARY:
- the lungs consist mainly of tiny air-containing sacs called ALVEOLI; the alveoli are the sites of gas exchange in with the blood; the AIRWAYS are the tubes through which air flows from the external environment to the alveoli and back
- INSPIRATION (INHALATION): the movement of air from the external environment through the airways into the alveoli during breathing
- EXPIRATION (EXHALATION): air moves from the respiratory system to the environment
- inspiration and expiration make up the RESPIRATORY CYCLE in which right ventricle of the heart pumps blood through the pulmonary arteries and arterioles and into the capillaries surrounding each alveolus; in a healthy adult at rest, 4L of fresh air enters and leaves the alveoli per minute while 5L of blood (cardiac output) flows through the pulmonary capillaries

AIRWAYS AND BLOOD VESSELS SUMMARY:
- during INSPIRATION, air passes through NOSE OR MOUTH → into PHARYNX → LARYNX (two tubes there- ESOPHAGUS and LARYNX) which is a part of the airways and houses the VOCAL CORDS that produce sounds > COLLECTIVELY CALLED THE UPPER AIRWAYS
- the airways beyond the larynx can be divided into two zones: the CONDUCTING ZONE (top of trachea to end of terminal bronchioles) and the RESPIRATORY ZONE (respiratory bronchioles down in which alveoli perform gas exchange with blood)
- the oral and nasal cavities trap airborne particles with hairs and mucus, and epithelial surfaces with cilia secrete mucus and macrophages to kill pathogens; this mucus is slowly moved to the pharynx and then swallowed to dispose of the pathogens to keep the airways clear and the body healthy (think of microbiology)
a. cystic fibrosis results from a recessive mutation in which the CF transmembrane conductance regulatory (CFTR) protein affected and causes issues because mucus layer of the airway epithelium becomes dehydrated and so obstructs the airway; it improves with therapy or antibiotics
b. cigarette smoking also disrupts ciliary activity so that mucus that would normally be cleared by cilia is not cleared and so coughed up
c. constriction of bronchioles in response to irritation helps to prevent particulate matter and irritants from entering the sites of gas exchange; also macrophages are also present in the airways and alveoli to destroy any foreign things
- moving from the CONDUCTING ZONE (trachea → bronchi → bronchioles → terminal bronchioles) to the RESPIRATORY ZONE (respiratory bronchioles → alveolar ducts → alveolar sacs) , it goes from 1 tube in each branch to 8 × 10^6 tubes in each branch

SITE OF GAS EXCHANGE: THE ALVEOLI SUMMARY:
- the alveoli are tiny, hollow sacs with open ends that are continuous with the lumens of the airways; a single alveolar wall is lined by a continuous one-layer-thick layer of flat epithelial cells termed TYPE I ALVEOLAR CELLS and with thicker, specialized TYPE II ALVEOLAR CELLS that provide surfactant dispersed along the wall in between the type I alveolar cell layer
- alveolar walls contain capillaries and a small interstitial space with lots of interstitial fluid and a loose meshwork of connective tissue; this ensures that the blood within the alveolar-wall capillary is separated from the air within the alveolus by a thin barrier so that the total surface area of alveoli in contact with capillaries that allows for efficient transfer of oxygen/carbon dioxide and energy between compartments and easy diffusion of substances (coevolved with necessity for exchange)

RELATION OF THE LUNGS OF THE THORACIC (CHEST) WALL SUMMARY:
- LUNGS are situated in the THORAX (the compartment of the body between the neck and abdomen)
- the thorax is a closed compartment bounded by muscles and connective tissue and completely separated from the abdomen by a large, dome-shaped sheet of skeletal muscle called the DIAPHRAGM
- the wall of the thorax is formed by the spinal column, the ribs, the breastbone, and several groups of muscles between the ribs called INTERCOSTAL MUSCLES
- each lung is surrounded by a closed sac called the PLEURAL SAC consisting of a thin sheet of cells called PLEURA; the pleural sac of one lung is completely separate from the other lung
- the VISCERAL PLEURA is the pleural surface coating the lung diaphragm and is firmly attached to it by connective tissue
- PARIETAL PLEURA is the outer layer which is firmly attached to and lines the interior thoracic wall and diaphragm
- INTERPLEURAL FLUID is the thin layer of fluid that separates the pleura and is a total volume of only a few milliliters; it totally surrounds and lubricates the pleural surfaces so they can slide over each other during breathing
- INTRAPLEURAL PRESSURE (Pip) is the hydrostatic pressure of the intrapleural fluid and causes the lungs and thoracic wall to move in and out together during normal breathing

Question 4

13.2 Principles of Ventilation

Answer 4

• BULK FLOW (F) OF AIR: between the atmosphere and alveoli
  • F = (Palv - Patm) / R where Palv = alveolar pressure, Patm= atmospheric pressure, and R = airway resistance
• BOYLE’S LAW: P1V2 = P2V2
  • if the volume of a container in state “1” increases, the pressure must decrease leading to state “2” where volume is greater, but the pressure is lower
  • explains how expanding the lungs lowers the pressure inside the lungs, causing air to move in from the atmosphere
• TRANSPULMONARY PRESSURE (Ptp) = Palv - Pip
  • TRANSMURAL PRESSURE of the lung represents the pressure inside the alveolus (Palv) minus pressure surrounding the lung (intrapleural pressure [Pip]). (transmural means “across a wall”)
  • pressure that determines volume inside lung (if Ptp is positive [>0], there is air in the lung)
  • PNEUMOTHORAX: air enters the pleural cavity (e.g., through a hole in chest wall) such that Pip = Patm; therefore, Ptp = 0 and lungs collapse because there is no positive
  • between breaths: at the end of an unforced expiration just before start of inspiration (called the functional residual capacity [FRC], described in the next section)
  • Patm = Palv, so no air is flowing (no pressure gradient between atmosphere and alveoli)
  • dimensions of the lungs and thoracic cage are stable (because of opposing elastic forces).
  • ELASTIC RECOIL: lung is stretched and attempting to recoil (collapse)
  • chest wall: compressed and attempting to move outward (expand)
  • SUBATMOSPHERIC INTRAPLEURAL PRESSURE: “negative” (compared to Patm) due to opposing forces- lungs tend to collapse, and chest well tends to expand (keeps lungs from collapsing)
• INSPIRATION: air moving from atmosphere into lungs
  • contractions of the diaphragm (driven by PHRENIC NERVES) and the inspiratory EXTERNAL INTERCOSTAL MUSCLES lead to an increase in the volume of thoracic cage
  • INTERPLEURAL PRESSURE becomes more subatmospheric → transpulmonary pressure increases → lung expands
  • lung expansion → decreases alveolar pressure (Palv < Patm) via Boyle’s law → air flow into lung
• EXPIRATION: air moving from lungs into atmosphere
  • inspiratory muscles cease contracting
  • elastic recoils of the lungs returns lung volume to the FRC
  • it compresses the alveolar air and increases Palv (so Palv > Patm) via Boyle’s law, which forces air out of lungs
  • forced expirations: the contraction of expiratory intercostal muscles and abdominal muscles causes the chest dimensions to decrease more rapidly, which increases Palv even more and makes the expiration more rapid

• PRINCIPLES OF VENTILATION SUMMARY:
  
  • overview of physical processes and steps involved in respiration
    1. ventilation: exchange of air between atmosphere and alveoli by bulk flow
    2. exchange of O2 and CO2 between alveolar air and blood in lung capillaries by diffusion
    
    3. transport of O2 and CO2 through pulmonary and systemic circulation by bulk flow
    4. exchange of O2 and CO2 between blood in tissue capillaries and cells in tissues by diffusion
    5. cellular utilization of O2 and production of CO2
• VENTILATION SUMMARY:
  
  • VENTILATION: the exchange of air between the atmosphere and alveoli; air moves by bulk flow from region of high pressure to low pressure
  • F = (Palv - Patm) / R:
    a. flow is proportional to the pressure difference between two points and inversely proportional to the resistance
    b. for airflow into or out of the lungs, the relevant pressures are the gas pressure in alveoli, the ALVEOLAR PRESSURE (Palv), and the gas pressure at the nose and mouth/the pressure of the air surrounding the body, the ATMOSPHERIC PRESSURE (Patm)
    c. all pressures given are relative to the atmospheric pressure
  • during ventilation, air moves into and out of the lungs because the alveolar pressure is alternately less than and greater than the atmospheric pressure
    a. when Palv is less than Patm, Palv - Patm is negative and airflow is inward (inspiration)
    b. when Palv is greater than Patm, Palv - Patm is positive and airflow is outward (expiration)
    c. alveolar pressure changes are caused by changes in the dimensions of the chest wall and lungs
• BOYLE’S LAW SUMMARY:
  
  • P1V1 = P2V2
  • this helps us understand changes in lung dimension causing changes in alveolar pressure
  • at constant pressure, the relationship between the pressure exerted by a fixed number of gas molecules and the volume of the containers is:
    a. increase in volume of container → decrease in pressure exerted by gas molecules → decrease in volume of container
    b. AKA pressure of a gas and volume of container are inversely proportional
• TRANSMURAL PRESSURE SUMMARY:
  
  • no muscles attached to the lung surface to pull the lungs open or push shut them- they are passive structures
  • TWO FACTORS THAT DETERMINE THE PRESSURE INSIDE AND OUTSIDE OF THE LUNG:
    a. TRANSPULMONARY PRESSURE (Ptp) is the difference in pressure between the inside and outside of the lung
    b. stretchability because it determines how much the lungs expand for a given change in Ptp
  • transpulmonary pressure = Palv - Piv
  • Ptp = Palv - Pip
  • transpulmonary pressure is TRANSMURAL PRESSURE that governs the static properties of the lungs (meaning across a wall) and is represented by the pressure inside the structure (Pin) and the pressure outside the structure (Pout); inflation of the structure requires an increase in the transmural pressure so that Pin increases relative to the Pout
• HOW IS A STABLE BALANCE OF TRANSMURAL PRESSURES ACHIEVED BETWEEN BREATHS? SUMMARY:
  
  • if there is no airflow and the airways are open to the atmosphere, Palv must equal Patm
  • because the lungs always have air in them, the transmural pressure of the lungs must always be positive, therefore, Palv > Pip
  • at rest, there is no airflow and Palv = 0 and Pip must be negative, providing the force that keeps the lungs open and the chest wall in
  • ELASTIC RECOIL of the lungs, defined as the tendency of an elastic structure to oppose stretching or distortion
  • Pip is forced to be negative because even at rest, the lungs contain air and their natural tendency is to collapse because of the elastic recoil; the lungs are held open by the positive Ptp which at rest exactly opposes the elastic recoil; also, the chest wall also has elastic recoil and a natural tendency to expand; at rest, these transmural pressures balance each other out
    a. pneumothorax occurs when atmospheric air enters the intrapleural space through a wound, and the intrapleural pressure increases from -4 mmHg to 0 mmHg so that the Pip is equal to Patm so the transpulmonary pressure holding the lung open is eliminated and the lung collapses

*INSPIRATION SUMMARY:
- summary of the events of inspiration at rest
1. diaphragm and inspiratory intercostals contract
2. thorax expands
3. Pip becomes more subatmospheric
4. transpulmonary pressure increases
5. lungs expand
6. Palv becomes subatmospheric
7. air flows into alveoli
- summary of alveolar (Palv), intrapleural (Pip), and transpulmonary (Ptp) pressure changes and airflow during a typical respiratory cycle
1. at the end of expiration, Palv = Patm and there is no airflow
2. at mid inspiration, the chest wall is expanding, lowing Pip and making Ptp more positive. this expands the lung, making Palv negative, and results in an inward airflow
3. at the end of inspiration, the chest wall is no longer expanding but has yet to start passive recoil. because the lung size is not changing and the airway is open to the atmosphere, Palv = Patm and there is no airflow. as the respiratory muscles relax, the lungs and chest wall start to passively collapse due to elastic recoil.
4. at mid-expiration, the lung is collapsing, thus compressing alveolar gas. as a result, Palv > Patm and airflow is outward. the cycle starts over again at the end of expiration. notice that throughout a typical respiratory cycle with a normal tidal volume, Pip < Patm.
- contraction of the inspiratory muscles, by actively increasing the thorax, upsets the stability set up by purely elastic forces between breaths

*EXPIRATION SUMMARY:
- summary of the sequence of events that occur during expiration:
1. motor neurons to the diaphragm and external intercostal muscles decrease their firing so the diaphragm and inspiratory intercostals stop contracting
2. the chest wall and diaphragm are no longer actively pulled outward by the muscle contractions, so they start to recoil inward to their original smaller dimensions that existed between breaths. the chest wall recoils inward
3. Pip moves back toward pre-inspiration value
4. transpulmonary pressure moves back toward pre-inspiration value
5. lungs recoil toward pre-inspiration size
6. air in alveoli becomes compressed
7. air in alveoli becomes compressed
8. Palv becomes greater than Patm
9. air flows out of lungs

Question 5

13.3 Lung Mechanics

Answer 5

• LUNG COMPLIANCE (CL) = ∆V/∆P (change in lung volume divided by change in Ptp)
  • determined by the elastic connective tissues of lungs and surface tension of the fluid lining the alveoli
• LAW OF LAPLACE: P = 2T/R (P is alveolar pressure, T is surface tension, and r is radius of alveolus
  • as the radius of an alveolus decreases, the pressure increases
  • an increase in surface tension increases the alveolar pressure
  • surface tension is decreased by SURFACTANT (produced by type II alveolar cells), which is a detergent
  • surfactant also stabilizes alveoli (decreases surface tension in smaller alveoli to decrease their pressure, preventing airflow into large alveoli with lower pressure)
• RESPIRATORY DISTRESS OF THE NEWBORN is a condition characterized by high surface tension in alveoli of premature infants
  • it is caused by surfactant deficiency
  • high surface tension greatly decreases compliance, making inspiration difficult
• AIRWAY RESISTANCE determines how much air flow into the lungs
  • F = (Palv - Patm) / R
  • determined primarily by the radii of the airways (governed by transmural pressure across airways)
  • lateral traction: connective tissues help to decrease resistance by holding airways open
  • ASTHMA: intermittent airway smooth muscle contraction reduces airway radius and increases resistance to airflow; is treated with ANTI-INFLAMMATORY DRUGS and BRONCHODILATORS
  • CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): EMPHYSEMA (increased compliance) and chronic bronchitis (excess mucus and inflammation of small airways)
• LUNG VOLUMES AND CAPACITIES: “capacities” are the sum of two or more volumes
  • TIDAL VOLUME (Vt): enters lung in single aspiration
  • INSPIRATORY RESERVE VOLUME (IRV): maximum inspired volume above Vt
  • EXPIRATORY RESERVE VOLUME (RV): remaining in lungs after maximal expiration
  • FUNCTIONAL RESIDUAL CAPACITY (FRC): at rest (RV + ERV)
  • VITAL CAPACITY: maximal volume inspired from RV = sum of resting TIDAL VOLUME, INSPIRATORY RESERVE VOLUME, AND EXPIRATORY RESERVE VOLUME
  • FORCED EXPIRATORY VOLUME IN ONE SECOND (FEV1): expired during the first second of a FORCED VITAL CAPACITY MEASUREMENT
• PULMONARY FUNCTION TESTS: evaluate airway compliance and resistance

*LUNG MECHANICS SUMMARY:
- LUNG MECHANICS characterize the physical interactions of the lungs, diaphragm, and chest wall during breathing and breath-holding
- 3 major physiological functions:
1. the ability to add air and remove air from the inside of the lungs (compliance)
2. lung mechanics describe the mechanisms for overcoming the surface tension that exists between the air and the extracellular fluid coating the alveoli
3. explain the different lung volumes that are used to clinically assess static and dynamic pulmonary function

*LUNG COMPLIANCE:
- the degree of lung expansion is proportional to the transpulmonary pressure Palv - Pip
- LUNG COMPLIANCE (CL): the magnitude of the change in lung volume (∆VL) produced by a given change in the transpulmonary pressure
CL = ∆VL/ ∆Ptp
- the greater the lung compliance, the easier to expand the lungs at any given change in transpulmonary pressure
- the less lung compliance, the more energy required to produce a given amount of expansion
- determinants of lung compliance:
A. stretchability of lung tissues: especially true for elastic connective tissues, thickening of lung tissues decreases compliance
B. surface tension (at the air-water interfaces within the alveoli): SURFACE TENSION is the attractive forces between water molecules, the alveoli are air-filled sacs lined with a thin layer of liquid, the water lining of the alveoli make it the structure one that constantly tends to shrink back and resists
C. type II alveolar cells secrete detergent-like surfactant which reduces the cohesive forces between water molecules on the alveolar surface; this is good because pure water surface tension is so strong it would require great energy for the lungs to contract where instead the surfactant lowers the surface tension which increases lung compliance and makes it easier to expand the lungs
D. surfactant isa mixture of both lipids and proteins; it is a phospholipid with a hyrophilic end inserted into the water layer of the alveoli; the hydrophobic ends form a monomolecular layer between the air and water at the alveolar surface; when breaths are small and constant, surfactant decreases
E. LAW OF LAPLACE: describes the relationship between pressure (P), surface tension (T), and radius (r) of an alveolus; decrease in surface tension ensures that pressure is maintained in smaller alveoli so that they are equal to larger ones; this gives stability to the alveoli
F. RESPIRATORY DISTRESS SYNDROME OF NEWBORN: surfactant is deficient because surfactant-providing cells are not developed sufficiently

*AIRWAY RESISTANCE SUMMARY:
- the volume of air that flows into or out of the alveoli per unit time is directly proportional to the pressure difference between the atmosphere and alveoli and is inversely proportional to the resistance to flow of airways
- determined by:
A. tube length
B. tube radius
C. interactions between moving molecules
- airway resistance is inversely proportional to the fourth power of the airway radii
- transpulmonary pressure exerts a distending force on the airways and so affects resistance; because transpulmonary pressure increases during inspiration, the airway radius becomes larger, and airway resistance lowers as the lungs expand during inspiration (opposite during expiration)
- the second physical factor holding the airways open is LATERAL TRACTION- the elastic connective-tissue fibers that link the outside of the airways to the surrounding alveolar tissue; the tissues are pulled up as the lungs expand in inspiration and help pull the airways open even more than between breaths; both transpulmonary pressure and lateral traction act in the same direction, decreasing airway resistance during inspiration
- neuroendocrine and paracrine factors also influence airway smooth muscle and thereby airway resistance
A. epinephrine relaxes airway smooth muscle on beta-adrenergic receptors
B. leukotrienes contract the muscle during inflammation
- ASTHMA: a disease characterized by intermittent episodes in which airway smooth muscle contracts strongly, increasing airway resistance; this is usually in response to chronic inflammation of the airways and sensitivity to environmental factors
A. ANTIINFLAMMATORY DRUGS leukotriene inhibitors and inhaled glucocorticoids
B. BRONCHODILATOR DRUGS relax the airways
C. CHRONIC OBSTRUCTIVE PULMONARY DISEASE: COPD refers to emphysema, chronic bronchitis, or a combination of the two; cause severe difficulties in ventilation and oxygenation in the blood; not due to smooth muscle contraction like in asthma
D. CHRONIC BRONCHITIS: excessive production of mucus in the bronchi and chronic inflammation changes in the small airways; often coexists with emphysema and bronchitis often

*LUNG VOLUMES AND CAPACITIES SUMMARY:
- TIDAL VOLUME (VT): the volume of air entering the lungs during a single inspiration is approximately equal to the volume leaving on the subsequent expiration; normal quiet breathing → typically 500 mL
- INSPIRATORY RESERVE VOLUME (IRV): the maximal amount of air that can be increased above VT during the deepest inspiration; TYPICALLY → 3000 mL
- FUNCTIONAL RESIDUAL CAPACITY (FRC): the resting position of the lungs and chest wall when there is no contraction of the respiratory muscles; typically → 2400 mL
- EXPIRATORY RESERVE VOLUME (ERV): through maximal active contraction of the expiratory muscles, it is possible to expire more of the air remaining after the resting tidal volume has been expired; typically → 1200 mL
- RESIDUAL VOLUME (RV): after maximal active expiration, 1200 mL of air remains in the lungs; lungs are never completely emptied of air
- VITAL CAPACITY (VC): the maximal volume of air a person can expire after a maximal inspiration; the person is expiring both resting tidal volume and inspiratory reserve volume plus the expiratory reserve volume; vital capacity is the sum of these three volumes and is important to assess pulmonary function
- FORCED EXPIRATORY VOLUME IN 1 SEC (FEV1): a variant of the vital capacity measurement; the person takes maximal inspiration and then exhales maximally as fast as possible; the fraction of the total “forced” vital capacity expired in 1 sec.; most healthy individuals can expire at least 80% of the vital capacity in 1 second
- PULMONARY FUNCTION TESTS: measurement of vital capacity and FEV1
- OBSTRUCTIVE LUNG DISEASES: increased airway resistance, typically FEV1 less than 80% of VC
- RESTRICTIVE LUNG DISEASES: characterized by normal airway resistance but impaired respiratory movements because of abnormalities in the lung tissue, the pleura, the chest wall, or the neuromuscular machinery; reduced vital capacity but normal ratio of FEV1 typically

Question 6

13.4 Alveolar Ventilation

Answer 6

• MINUTE VENTILATION: product of tidal volume and respiratory rate
• DEAD SPACE: volume of inspired air that does not take part in the gas exchange; composed of:
  • ANATOMICAL DEAD SPACE: air that remains in the conducting airways during a respiratory cycle
  • ALEVOLAR DEAD SPACE: air that reaches the alveoli that are not perfused or are poorly perfused
• ALVEOLAR VENTILATION = (tidal volume minus anatomical dead space) × respiratory rate

• ALVEOLAR VENTILATION SUMMARY:
  
  • MINUTE VENTILATION (VE): the total ventilation per minute is equal to the tidal volume multiplied by the respiratory rate
    VE (mL/min) = VT (mL/breath) × f (breaths/min)
    -healthy adult

Question 7

13.5 Exchange of Gases in Alveoli and Tissues

Answer 7

• RESPIRATORY QUOTIENT (RQ) is carbon dioxide production divided by oxygen consumption
  • at a typical RQ (0.8), oxygen consumption is ~250 mL per minute and carbon dioxide production is ~200 mL per minute
• PARTIAL PRESSURES OF GASES: DALTON’S LAW states that pressures of individual gases are independent of each other in a mixture of different gases
  • partial pressure of a gas = total pressure × precentage of that gas in the mixture
  • determine the rate of diffusion of gases in lungs and tissues: gases diffuse from a region of higher partial pressure to one of lower partial pressure
• normal ALVEOLAR GAS PRESSURE (at sea level)
  • oxygen ~ 105 mmHg; carbon dioxide ~ 40 mmHg
• ratio of tissue oxygen consumption (metabolic rate) to alveolar ventilation determines alveolar PO2- the higher the ratio, the lower the alveolar PO2
• ratio of tissue oxygen consumption (metabolic rate) to alveolar ventilation determines alveolar PCO2
• HYPOVENTILATION AND HYPERVENTILATION
  • HYPOVENTILATION: decreased ratio of alveolar ventilation to carbon dioxide production (metabolism). if alveolar ventilation decreases in proportion to a decrease in metabolic rate, this is not hypoventilation because arterial PCO2 does not increase
  • HYPERVENTILATION: increased ratio of alveolar ventilation to carbon dioxide production (metabolsm). if alveolar ventilation increases in proportion to an increase in metabolic rate, this is not hyperventilation because arterial PCO2 does not decrease
• HENRY’S LAW: the amount of gas dissolved in a liquid is directly proportional to partial pressure in a gas with which the liquid is in equilibrium
  • the amount of gas dissolved in a liquid is a function of the partial pressure and solubility of the gas in the liquid
• SYSTEMIC BLOOD GAS PARTIAL PRESSURES (at sea level)
  • arterial ~100 mmHg; venous PO2 ~40 mmHg arterial PCO2 ~40 mmHg; venous PCO2 ~46 mmHg

*PULMONARY CAPILLARIES: site of gas exchange between blood alveolar gas

- net diffusion of oxygen from alveoli to blood 
- net diffusion of carbon from blood to alveoli 
- at the end of each pulmonary capillary (in healthy respiratory zone), the blood gas partial pressures are equal to alveoli 
- inadequate gas exchange between alveoli and pulmonary capillaries occurs when the function ] alveolar-capillary surface area is decreased (e.g, with PULMONARY EDEMA), when the alveolar walls thicken (e.g., FIBROSIS), or when there are ventilation-perfusion inequalities 

• VENTILATION-PERFUSION INEQUALITIES: unbalanced distribution of blood flow and ventilation
  • cause the systemic arterial PO2 to be reduced
  • low local PO2 causes local bronchoconstriction, diverting air away from poorly perfused areas
  • low local PCO2 causes local bronchoconstriction, diverting air away from poorly perfused areas
• TISSUE GAS EXCHANGE: net diffusion of oxygen occurs from blood to cells, net diffusion of carbon dioxide from cells to blood

Question 8

13.6 Transport of Oxygen in Blood

Answer 8

• SYSTEMIC ARTERIAL BLOOD: normal contains ~200 mL oxygen per liter
  • more than 98% of oxygen is bound to HEMOGLOBIN
  • the remainder is dissolved (and free to diffuse into the tissues)
• HEMOGLOBIN (in ERTHYROCYTES)
  • four subunits: each containing heme and globin
  • HEME: contains iron that binds oxygen
  • GLOBIN: polypeptide
  • DEOXYHEMOGLOBIN (Hb) has less oxygen than OXYHEMOGLOBIN (HbO2): they are in equilibrium
• hemoglobin OXYGEN SATURATION: determined by blood PO2 and the shape of the OXYGEN-HEMOGLOBIN DISSOCIATION CURVE (sigmoid curve demonstrating cooperative binding)
  • almost 100% saturated at the NORMAL SYSTEMIC ARTERIAL PO2 of 100 mmHg
  • ~90% saturated at a PO2 of 60 mmHg (modest reduction from normal); permits a relatively normal pulmonary uptake of oxygen into the blood; safety factor for mild lung disease
  • ~75% saturated at NORMAL SYSTEMIC MIXED VENOUS PO2 of 40 mmHg (only 25% of the oxygen has dissociated from hemoglobin and diffused into the tissues)
• hemoglobin OXYGEN AFFINITY:
  • decrease binding 2, 3 DIPHOSPHOGLYCERATE ([DPG] is synthesized by the erythrocytes); DPG increases with inadequate oxygen supply (helps maintain oxygen release into the tissues)
  • decreased by an increase in pco2, H+ concentration (decreased pH), and temperature; facilitates dissociation (unloading of oxygen from hemoglobin in tissues
  • increased in FETAL HEMOGLOBIN; allows adequate uptake of O2 in the placenta and delivery to the fetal circulation
  • CARBON MONOXIDE POISONING and ANEMIA: decrease blood OXYGEN-CARRYING CAPACITY
  • carbon monoxide: occupies O2-binding sites on hemoglobin
  • anemia: decrease in the blood hemoglobin concentration (red cell concentration [hematocrit]) in the blood

Question 9

13.7 Transport of Carbon Dioxide in Blood

Answer 9

• CARBON DIOXIDE: net diffusion from the tissues into the blood, ~10% remains dissolved in plasma and erythrocytes
  • 25 to 30% combines in the erythrocytes with deoxyhemoglobin to form CARBAMINO COMPOUNDS
  • 60% TO 65% combines in the erythrocytes with water to form CARBONIC ACID (catalyzed by the enzyme CARBONIC ANHYDRASE)
  • carbonic acid dissociates to yield HCO3- AND H+
  • HCO3- moves out of the erythrocytes into the plasma in exchange for chloride ions
• Venous blood: returns to the right side of the heart and is pumped into the pulmonary circulation
  • blood PCO2 decreases because of diffusion of carbon dioxide into the alveoli; unloads carbon dioxide and reduces carbamino compounds and HCO3-
  • unloading of carbon dioxide in the lung is facilitated by loading of oxygen onto Hb to form HbO2, which has a lower affinity for carbon dioxide than Hb

Question 10

13.8 Transport of Hydrogen Ion Between Tissues and Lungs

Answer 10

• H+ in capillaries of metabolizing tissues
  • generated from carbon dioxide in the erythrocytes from carbonic acid during blood passage through tissue capillaries
  • binds to deoxyhemoglobin; formed as oxygen unloads from oxyhemoglobin
• H+ bound to deoxyhemoglobin is released in the lung capillaries
  • combines with HCO3- to yield carbon dioxide and water; carbon dioxide exhaled
• RESPIRATORY ACIDOSIS: due to hypoventilation; results in arterial carbon dioxide retention leading to increased H+
• RESPIRATORY ALKALOSIS: due to hyperventilation; results in a decrease in arterial carbon dioxide leading to decreased H+

Question 11

13.9 Control of Respiration

Answer 11

• breathing depends upon cyclical inspiratory muscle excitation by the nerves to the diaphragm and intercostal muscles
  • neural activity triggered by the medullary inspiratory neurons
• MEDULLARY RESPIRATORY CENTER composed of:
  • DORSAL RESPIRATORY GROUP: contains inspiratory neurons
  • VENTRAL RESPIRATORY GROUP: location of RESPIRATORY RHYTHM GENERATOR (in PRE-BOTZINGER COMPLEX)
  • INPUT for the involuntary control of ventilation: from peripheral chemoreceptors (CAROTID AND AORTIC BODIES) and the CENTRAL CHEMORECEPTORS (located in the medulla)
• PONTINE RESPIRATORY CENTERS
  • APNEUSTIC CENTER: fine-tunes activity of the medullary inspiratory neurons and helps terminate inspiration
  • PNEUMOTAXIC CENTER (also called the PONTINE RESPIRATORY GROUP): modulated activity of apneustic center; helps o smooth transitions between inspiration and expiration
• PULMONARY STRETCH RECEPTORS: located in airway smooth muscle
  • input from the stretch receptors decreases medullary inspiratory neurons
  • HERING-BREUER REFLEX: increasing lung volume terminates inspiration
• VENTILATORY REFLEXES: physiological responses to perturbations
  • HYPOXIA (decreased arterial PO2): breathing is stimulated via the peripheral chemoreceptors (only when the decrease in PO2 is large)
  • HYPERCAPNIA (increased arterial PCO2): breathing is stimulated by peripheral and central chemoreceptors (even when an increase in arterial PCO2 is small). the stimulus for this reflex is not the increased PCO2 itself but the concomitant increased H+ concentration in arterial blood and brain extracellular fluid
  • rate and depth of breathing are increased by an increase in arterial H+ concentration resulting from causes other than an increase in PCO2. breathing increases to restore H+ concentration toward normal by lowering PCO2
  • rate and depth of breathing are inhibited by an increase in arterial PO2 (HYPEROXIA) and by a decrease in arterial PCO2 (HYPOCAPNIA)
• MODERATE EXERCISE: ventilation increases in proportion to metabolism; arterial PO2, PCO2, and H+ concentrations remain unchanged
  • signals driving increase in ventilation (HYPERPNEA) are not certain
• STRENUOUS EXERCISE: ventilation increases more than metabolism (true hyperventilation)
  
  • arterial H+ concentration increases because of increased lactic acid production. this stimulus accounts for some of the hyperventilation
• ventilation is also controlled by reflexes originating in airway receptors and by conscious intent (e.g.; speaking, singing, voluntary breath holding)
  • J RECEPTORS: stimulated by increases in pulmonary interstitial fluid pressure (e.g., with pulmonary edema); can give sensation of difficulty breathing (DYSPNEA)

Question 12

13.10 Hypoxia

Answer 12

• definition of HYPOXIA: deficiency of tissue oxygen
• HYPOXIC HYPOXIA: decreased arterial PO2; caused by:
  • HIGH ALTITUDE: decreased barometric pressure (“thinner air”); fewer oxygen molecules in atmosphere (although O2 remains 21%)
  • HYPOVENTILATION: caused by defects in respiratory neural control, chest wall abnormalities, obstruction of upper airway, drugs that suppress breathing (e.g., opiates)
  • DIFFUSION IMPAIRMENT: thickening of alveolar membranes (e.g., fibrosis) or accumulation of fluid in alveoli or lung interstitium
  • SHUNT: mixed venous blood bypasses ventilated areas of the lung (e.g., through a hole between the right and left heart, such as a PATENT FORAMEN OVALE [PFO]) or perfusion of unventilated alveoli
  • VENTILATION-PERFUSION INEQUALITY: most common cause of hypoxic hypoxia; uneven distribution of ventilation and perfusion throughout the lung
• EMPHYSEMA: loss of elastic tissue in lung and destruction of bronchiolar and alveolar walls
  • increased compliance leading to airway collapse
  • alveolar wall loss decreases total surface area (limiting diffusion)
  • in addition to bronchitis, one of the causes of CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
  • CIGARETTE SMOKING is the most common cause of COPD
• ACCLIMATIZATION TO HIGH ALTITUDE: oxygen supply to the tissues is maintained by (at least) five adaptations:
  • increased peripheral chemoreceptor activity leading to hyperventilation
  • increased ERYTHROPOIETIN secretion into the blood from the kidneys, which stimulates erythrocyte production by bone marrow (increased hematocrit increases O2-carrying capacity of the blood)
  • increase in skeletal muscle capillary density, mitochondria (more efficient use of oxygen), and myoglobin (binding of oxygen in the tissues)
  • decreased plasma volume (increased red cell concentration)
• OTHER FORMS OF HYPOXIA
  • ANEMIA OR CARBON MONOXIDE HYPOXIA: reduces oxygen-carrying capacity of the blood
  • ISCHEMIC HYPOXIA (hypoperfusion): inadequate blood flow to tissues decreases oxygen delivery
  • HISTOTOXIC HYPOXIA : poisoning of cellular respiration (e.g., cyanide poisoning)

Question 13

13.11 Nonrespiratory Functions of the Lungs

Answer 13

• the lungs influence blood concentrations of biologically active substances by removing some substances from pulmonary artery blood and adding others to pulmonary venous blood
• the lungs also act as sieves that trap and dissolve small blood clots formed in the systemic tissues