Chapter 7 - Respiratory Physiology

Question 1

Path of Oxygen and CO2

Answer 1

Oxygen: Air ==> Lungs ==> Circulation ==> Cells
CO2: reverse

Question 2

Structure of Respiratory System

Answer 2

Pharynx is back of mouth and nasal cavity, larynx is beginning of upper airway, trachea is in the lower airway, bronchus is the main stem, bronchioles are smaller branches and alveoli are smallest

Question 3

Alveoli

Answer 3

Microscopic air sacs made up of monolayer of airway epithelial cells, surrounded by capillary network where O2 and CO2 are rapidly exchanged between alveolar air and pulmonary capillary blood via diffusion

Question 4

Spirometer

Answer 4

Measures lung volumes by measuring the volume of air moving into and out of lungs during inspiration and expiration (persons mouth is connected by a tube and their nose is clipped to prevent movement of air through nostrils), in spirometric reading, upward movement indicates inspiration (breathing in) and downward movement indicates expiration (breathing out)

Question 5

Tidal Volume (TV)

Answer 5

Volume of air that enters into and exits from the lungs during expiration and inspiration

Question 6

Inspiratory Reserve Volume (IRV)

Answer 6

A maximal inspiration reveals the IRV (the lung volume that can be inspired to maximize the tidal volume)

Question 7

Expiratory Reserve Volume (ERV)

Answer 7

A maximal inspiration also reveals ERV, the lung volume that can be expired to maximize the volume of expiration

Question 8

Residual Volume (RV)

Answer 8

Volume of air that remains in the lungs at the end of maximal respiration (cannot be measured by spirometry) because it cannot be expired from the lungs, can be measured by dilution with tracer gas

Question 9

Lung Capacities

Answer 9

Each lung capacity is the sum of two or more lung volumes, normal ranges can be estimated from height, body weight, and sex (lung diseases can lead to abnormalities)

Question 10

Vital Capacity (VC)

Answer 10

Vital capacity is the maximum tidal volume of ventilation, the sum of inspiratory reserve volume, normal tidal volume, and expiratory reserve volume

VC = IRV + TV + ERV

Question 11

Total Lung Capacity (TLC)

Answer 11

Total amount of air in maximally inflated lung, vital capacity plus reserve volume

TLC = VC + RV

Question 12

Inspiratory Capacity (IC)

Answer 12

Maximum Volume of inspiration, the sum of tidal volume and inspiratory reserve volume

IC = TV + IRV

Question 13

Functional Reserve Capacity (FRC)

Answer 13

The lung volume at the end of quiet breathing, the sum of expiratory reserve capacity and residual volume, end of expiration, no air flow

FRC = ERV + RV

Question 14

Pneumothorax

Answer 14

Collapse of a lung, results in substantial decrease in vital capacity, pleural space becomes leaky and filled with air, intrapleural pressure = atmospheric pressure

Question 15

Lung Hyperinflation

Answer 15

Common in asthmatic patients, caused by airway obstruction, can lead to significant decrease in inspiratory reserve volume and significant increase in expiratory reserve volume

Question 16

Drivers of Movement of air into and out of lungs (airflow equation)

Answer 16

Movement is driven by the difference in atmospheric pressure and alveolar pressure (alveolar pressure is the variable that drives airflow into and out of lungs)

Airflow = (atmospheric pressure - alveolar pressure) / airway resistance

Question 17

Determinants of Alveolar Pressure (EQ)

Answer 17

Alveolar Pressure is dependent on balance between lung recoil driving lung collapse and transpulmonary pressure driving lung expansion

Lung recoil consists of elastic force of connective tissues and surface tension at the air-liquid interface on the alveolar surface, lung recoil increases with lung volume (lung volume causes increase in lung recoil)

Transpulmonary pressure is pressure difference across the wall of a lung:

Transpulmonary Pressure = Alveolar Pressure - Intrapleural Pressure

Intrapleural pressure is the pressure in the pleural space between the lung surface and the chest wall, in healthy person the pleural space is filled with small amount of fluid and no air

Question 18

Alveolar Pressure at 0

Answer 18

At stable lung volumes the alveolar pressure is at 0 (this is reached at the end of expiration and inspiration), lung recoil is balanced by transpulmonary pressure, alveolar pressure is 0 and airflow is 0

Question 19

Alveolar Pressure During Inspiration

Answer 19

During inspiration alveolar pressure is negative, the beginning of inspiration (increase in lung volume) is driven by decrease in alveolar pressure as a result of a decrease in intrapleural pressure caused by contractions of diaphragm and intercostal muscles (resulting in contraction of thoracic cavity)

Transpulmonary pressure > lung recoil

Contraction of diaphragm and intercostal muscles ==> contraction of thoracic cavity ==> Decrease in intrapleural pressure ==> Decrease in alveolar pressure and increase in transpulmonary pressure above lung recoil ==> negative alveolar pressure relative to atmospheric pressure ==> inspiration ==> increase in lung volume ==> increase in lung recoil until it reaches level that balances transpulmonary pressure and alveolar pressure becomes 0 ==> lung volume stabilizes at the end-inspiratory volume (3 Liters)

Question 20

Alveolar Pressure During Expiration

Answer 20

During expiration alveolar pressure is positive, decrease in lung volume is drives by increase in alveolar pressure coming from increase in intrapleural pressure

Transpulmonary pressure Increase in intrapleural pressure ==> decrease in transpulmonary pressure to below lung recoil ==> increase in alveolar pressure relative to atmospheric pressure ==> Expiration (decrease in lung volume) - until lung recoil reaches level that balances transpulmonary pressure and alveolar pressure becomes zero, lung volume stabilizes at the end-expiratory volume (2.5 L)

Question 21

Lung Compliance

Answer 21

Measure of lung flexibility (when lung is inflated away from its resting position it tends to recoil back), the slope at any one point of the lung volume - transpulmonary pressure relation (how much pressure change is required to produce a given change in volume)

Lung Compliance = delta lung V / delta transpulmonary P

Lung compliance is highest at intermediate lung volume (why least effort is needed for breathing at intermediate lung volumes), it is very low at small and large volumes, it is inversely related to mechanical forces that tend to collapse the lungs

Question 22

Laplace’s Law

Answer 22

Laplace’s Law determines the transmural pressure P necessary for stabilizing the structure at radius R against a wall tension (T) that tends to collapse the structure

delta P = 2T/R

Question 23

Wall Tension (tissue elasticity and surface tension)

Answer 23

Wall tension that tends to collapse lungs consists of tissue elasticity and surface tension

tissue elasticity consists of protein filaments inside cells and connective tissues in the ECM, excessive production of ECM in lung fibrosis (scarring) can cause abnormally low lung compliance whereas degradation of elastic fibers in smoking-induced lung emphysema can cause abnormally high lung compliance due to destruction of connective tissue in lungs

surface tension is the force in an air-liquid interface produced by the adhesion between liquid molecules, it can be sufficiently large to support the weight of an object on the liquid surface (indentation derives the force necessary to oppose weight of object), water has a relatively high surface tension because of high adhesive force between water molecules, reduced if cover water with amphiphilic molecules (like phospholipids) and this is what pulmonary surfactant is made out of and covers the aqueous layer on the alveolar surface, reducing surface tension (it is secreted by Type 2 alveolar cells), pulmonary surfactant enhances lung compliance by reducing surface tension on alveolar surface (deficiency in newborns can lead to difficulty breathing) and it also enhances host defense against air-borne pathogens

pulmonary surfactant reduces surface tension on alveolar cells, reducing transpulmonary pressure required to inflate lungs

Surface tension of surfactant increases with alveolar radius (surface tension is higher in larger alveoli and lower in smaller alveoli), thereby stabilizing interconnected alveoli of different sizes

Question 24

Obstructive and Restrictive Lung Disease and Tests for Difference

Answer 24

(ex. asthma as obstructive due to airway narrowing from tightened muscles and inflammation) characterized by abnormally high airway resistances and low airflow, obstructive is difficulty exhaling all air from lungs, restrictive is difficulty fully filling lungs with air

Test in order to see difference - record lung volume as a function of time during forced expiration from total lung capacity to calculate FEV1/FVC ratio (ratio lower than 70% suggests airway obstruction)

FEV1 - expired volume during first 1 second
FVC - forced vital capacity, difference in lung volume between end of maximal inspiration and end of forced expiration

Can also differentiate by measuring measuring airflow and lung volume during cycles of maximal inspiration of expiration and looking at airflow-lung volume loop, obstructive lung disease is characterized by significant decrease in peak expiratory flow and restrictive lung disease is characterized by significant decrease in lung volume with relatively small change in peak expiratory flow

Question 25

Gas Exchange Units and Dead Space

Answer 25

Respiratory bronchioles and alveoli, airway system not capable of gas exchange is anatomical dead space and gas exchange units not perfused by circulation are considered physiological dead space

Dead space does not contribute to gas exchange because it retains alveolar air at the end of expiration which is then mixed with inspired air for transport to alveoli

Tidal Volume (TV) of each breath consists of the dead space volume (Vd) and alveolar space volume (Va)

TV = Vd + Va

Question 26

Minute Ventilation

Answer 26

Overall lung ventilation (minute ventilation) is the product of tidal volume and breathing frequency (f), these vary with age, body size, gender and metabolic activity

Minute Volume = TV x f

Typical TV = 500 mL, Typical f = 12/min, Typical minute volume = 6L/min

Question 27

Alveolar Ventilation

Answer 27

To calculate ventilation of gas exchange units (alveolar ventilation), need to subtract dead space ventilation from overall lung ventilation (minute ventilation), this is the physiological significant ventilation for gas exchange over minute ventilation, can change alveolar ventilation with different TV and f without changing minute ventilation

Alveolar Ventilation = (TV x f) - (Vd x f) = (TV-Vd)*f

For an adult, typical value for dead space is 150 mL

Question 28

Deep Breathing/Shallow Breathing and Alveolar Ventilation

Answer 28

By increasing TV and decreasing frequency (deep breathing) you can increase alveolar ventilation at the same minute ventilation, generally, deep breathing improves alveolar ventilation

Question 29

Determinants of Alveolar Gas Composition

Answer 29

Alveolar ventilation maintains physiological levels of blood PO2 and PCO2, at sea level, PO2 and PCO2 in each alveolus and its surrounding capillary blood are identical due to rapid diffusion between the two

Determinants of Gas composition: PO2 and PCO2 in inspired air, metabolic rates (O2 consumption and CO2 production) and alveolar ventilation

Question 30

Determinants of Alveolar PCO2

Answer 30

Inspired PCO2 is typically near zero so alveolar PCO2 is determined just by rate of metabolic CO2 production and CO2 removal by alveolar ventilation, normal PCO2 is 40 mmHg

Metabolic CO2 production –> alveolar PCO2 –> CO2 removal by alveolar ventilation

Rate of CO2 removal = Alveolar ventilation x fraction of CO2 in alveolar air (Fa CO2) which is proportional to PCO2

K = proportional constant for PCO2/FCO2 ratio in alveolar air

Alveolar PCO2 = K x VCO2/alveolar ventilation

Alveolar PCO2 is predicted by VCO2/alveolar ventilation ratio so maintenance of normal PCO2 level depends on matching of the metabolic rate by alveolar ventilation, increase in CO2 production must be matched by proportional increase in alveolar ventilation

PCO2 is a major determinant of blood pH

Systemic arterial blood PCO2 is essentially identical because of rapid diffusion between blood and surrounding capillary, venous blood PCO2 is organ specific because ratio of organ metabolic rate / organ metabolic blood flow differs by organ

Question 31

Determinants of Alveolar PO2

Answer 31

O2 supply by alveolar ventilation –> Alveolar PO2 –> Metabolic O2 consumption

Inspired PO2 represents oxygen content of inspired air and is the upper limit of alveolar PO2 (normally 21% O2)

Inspired PO2 = 0.21 x (barometric pressure - 47)

Normal PO2 = 100 mmHg

Difference in oxygen content between inspired air and alveolar air equals the metabolic rate of O2 consumption

(volume of O2 per volume of inspired O2 - volume of O2 per volume of alveolar O2) x alveolar ventilation = metabolic O2 consumption

Alveolar PO2 = inspired PO2 - (K x metabolic O2 consumption/alveolar ventilation)

Alveolar PO2 is determined by inspired PO2, metabolic rate of O2 consumption and alveolar ventilation

During exercise, O2 metabolism rate increases as a result of increase in metabolism which then requires a matching increase in alveolar ventilation), when O2 in the air decreases, need a decrease in the ratio of O2 metabolism/alveolar ventilation

Alveolar PO2 has an upper limit of Inspired PO2

Question 32

Alveolar Gas Equation

Answer 32

Alveolar Ventilation is an important determinant for both PCO2 and PO2 so a alveolar ventilation induced change in PCO2 must be accompanied by opposite change in PO2

Hypoventilation-induced increase in PCO2 must be accompanied by decrease in PO2 and hyperventilation decrease in PCO2 must be accompanied by increase in PO2

Alveolar Gas Equation: PO2 = Inspiratory PO2 - 1.2* alveolar PCO2

Can use this to estimate PO2 from inspiratory PO2 and PCO2 (inspiratory can be found from barometric pressure and PCO2 can be approximated from PCO2 in air exhaled by lungs at the end of expiration

Question 33

Ventilation/Perfusion Ratio and Mechanisms

Answer 33

Ratio of ventilation of alveolus with air versus perfusion of capillaries surrounding the alveolus (ideal would be 1) and heterogeneity in the V/P ratios among alveoli is inefficient for gas exchange (but still exists to a small degree)

Mechanism 1: low PCO2 induced bronchoconstriction for decreasing ventilation in alveoli having abnormally high V/P ratio (distributes airflow to alveoli that receive blood perfusion)

Mechanism 2: hypoxic pulmonary vasoconstriction for decreasing perfusion of alveoli having abnormally high V/P ratio (distributes blood flow to alveoli that receive ventilation)

Extremes - no airflow, V/P=0 and it is a shunt
OR no blood flow, V/P = infinity and it is called extra dead space

Question 34

Blood Transport of O2 and CO2

Answer 34

Most of O2 in blood is carried by hemoglobin and CO2 in blood is carried by bicarbonate (there is also a small amount of dissolved directly in plasma)

At 100% saturation (it is around this at sea level), O2-binding capacity of heme is 1.36 mL O2/g, using this

Blood [O2} = Hemoglobin Saturation x 1.36 x [Hb]

Arterial venous difference in oxygen content is a function of oxygen consumption rate and cardiac output, also known as Fick principle

Oxygen Consumption Rate = Cardiac Output x ([arterial O2] - [venous O2})

Venous O2 concentration tends to be about 75%

Moderate increase in oxygen consumption can be compensated for using increase in cardiac output alone but intense exercise usually requires increases in both cardiac output and arterial-venous oxygen extraction

Question 35

Anemia

Answer 35

Anemia = low Hb concentration, arterial and venous saturations remain same so the arteriovenous difference will decrease by 20% and if cardiac output remains the same O2 consumption rate will also decrease by 20% (can put limitations on physical activity)

Can be compensated for with an increase in cardiac output (at rest) but doesn’t work during intense exercise

Question 36

Hematocrit/Steroids

Answer 36

Hematocrit measures RBC volume, blood hemoglobin concentration is important determinant of exercise performance, the stimulation of RBC synthesis by administration of erthyropoietin (regulates RBC synthesis) is a type of illegal blood doping used by some athletes

Question 37

P50 of Hemoglobin/2,3-DPG/H+

Answer 37

P50 of hemoglobin is fairly high in blood caused by the negative regulation of hemoglobins binding affinity by pH and 2,3-DPG

2,3 - DPG (intermediate of glycolysis), a decrease in it will cause an abnormally low P50 (high binding affinity) that can hinder unloading of oxygen

During intense exercise, more DPG, H+, lactic acid and temperature increase in muscle cells reduces binding affinity of hemoglobin for oxygen and enhances unloading of O2 to muscle cells

Question 38

CO2 Transport in Blood

Answer 38

10% - dissolved CO2 directly
30% - Carbamino-hemoglobin, reaction between CO2 and amino termini of Hb (charged molecule)
60% - Transported as bicarbonate HCO3 generated from CO2 and H2O (takes place inside RBCs where enzyme is and then transported back out to plasma via an exchanger)

Question 39

Regulation of Ventilation by Chemoreceptors

Answer 39

Respiratory center regulates ventilation in response to sensory input from central chemoreceptors (brain) and peripheral chemoreceptors (aortic arch and carotid bodies)

Central detect changes in cerebrospinal fluid [H+] which reflects blood PCO2 and peripheral receptors detect changes in arterial blood PCO2 and [H+]

Minute ventilation increases in response to severe hypoxia but is relatively insensitive to changes in PO2 at levels higher than 50 mmHg (but is important at high altitudes when arterial PO2 is near that level)

H+ sensing peripheral chemoreceptors are important for stimulating ventilation during extremely intense exercise when lactic acid levels increase in plasma

PCO2-sensing by central chemoreceptors play critical role in ventilation regulation (and hypoxia increases their sensitivity), this contributes to hyperventilation effect at high altitude

Question 40

Adaptation to High Altitude

Answer 40

Difficulty surviving at high altitude is decrease in inspired PO2 (cannot get it back to 100 mmHg), body adapts to have smaller arterial-venous PO2 difference for oxygen delivery and there is also an increase in RBC synthesis and Hb concentration stimulated by kidneys in response to hypoxia