2 - Pulmonology

Question 1

Define TLC, FRC, and RV.

Answer 1

Total Lung Capacity - volume from max inhalation to max exhalation (Inspiratory Reserve Volume + Tidal Volume + Expiratory Reserve Volume)Functional Reserve Capacity - volume in lungs after normal exhalation (ERV + RV)Reserve Volume - volume in lungs after max exhalation

Question 2

Define compliance of lung tissue.

Answer 2

Compliance is a measure of the relationship between the change in pressure required to change the volume of the lungs. C=dV/dP

Question 3

Why don’t alveoli collapse on themselves?

Answer 3

Interconnected alveoli are exposed to the same airflow, but according to Law of LaPlace (P=2T/r) the alveoli with smaller radii see more pressure (to collapse). To compensate, the Type II pneumocytes secrete surfactant. The high lipid concentration decreases surface tension. So as the radius decreases, the surfactant becomes more concentrated and decreases the surface tension. This creates a balance in tension between the larger and smaller alveoli, thus maximizing surface area available for gas exchange.

Question 4

Discuss changes in the rate of inhalation and exhalation with progressive increases in effort.

Answer 4

Inhalation - increasing effort results in proportional increase in volume and rate of air flow until max effort is reached Exhalation - increading effort results in a proportional increase in volume, changes in rate are limited. The increased contractions during forced exhalation place pressure on the smaller (without cartilage) bronchioles. This causes them to narrow and increases the resistance to flow. Therefore, the rate of exhalation is mostly set regardless of effort.

Question 5

Describe the layers of the Respiratory Membrane. How is O2/CO2 transported across this membrane during inhalation and exhalation?

Answer 5

The Respiratory Membrane is everything that O2/CO2 must pass through when traveling between the alveoli lumen to the RBC.
Air -> water/surfactant layer -> Type I pneumocyte -> interstitial space -> capillary endothelium -> blood plasma -> RBC
All transport is by SIMPLE DIFFUSION.

Question 6

What is the partial pressure of a gas? Are the partial pressures of the alveolar air the same as atmospheric air? Why?

Answer 6

Partial pressure = total pressure x fractional gas concentration
NO - since the concentrations of the different components of air are different in the alveolar space, the partial pressures are different. This is driven by 4 factors:
1) alveolar air is moistened during inhalation (water vapor UP)
2) alveolar air is not replaced completely replaced with each breath
3) CO2 is constantly entering from blood
4) O2 is constantly exiting to blood

Question 7

What factors drive the rate of diffusion of fluids through the Respiratory Membrane?

Answer 7

Factors that affect rate of diffusion PROPORTIONALLY:
1) solubility of gas
2) difference in partial pressures across membrane(MAJOR)
3) cross-sectional area for diffusion (MAJOR)
4) temperature
Factors that affect the rate of diffusion INVERSELY:
1) molecular weight (technically the square root of MW)
2) distance of diffusion (MAJOR)

Question 8

What are the typical partial pressures for O2 and CO2 in the RBCs and in the lungs?

Answer 8

O2 - Lung->104mmHG; RBC -> 40mmHG

CO2 - Lung -> 40mmHG; RBC -> 45mmHG

Question 9

Describe the effect of allosteric binding in hemoglobin. Why is this important for O2 transport?

Answer 9

When one O2 molecule binds to a heme in hemoglobin (Hb), there is a conformational change in Hb that makes it easier to bind O2 to the three other hemes.
This makes it possible for Hb to preferentially release O2 in tissue (where O2 concentration is low) and bind it in the lung (where O2 concentration is high). Without this effect there would be a linear pattern of binding and release of O2, leaving the distant tissue badly deoxygenated.

Question 10

What are the factors that affect the shape of the oxygen-hemoglobin dissociation curve?

Answer 10

1) hydrogen ions (pH)
2) CO2
3) Temperature
4) 2,3-biphosphoglycerate (2,3-BPG is a glycolysis biproduct)

Increases in each of these items (drop in pH) shifts the curve to the right. This means hemoglobin has a DECREASED affinity for O2.

Question 11

What is the affect of exercise on O2-hemoglobin binding?

Answer 11

Exercise uses O2 in tissue. This causes the tissue PO2 to drop and “pull” more O2 from hemoglobin. At rest Hb saturation only drops to 72% (a 25% drop from the lungs). However, during exercise Hb saturation drops as low as 7%. This results in a 93% O2 delivery to the tissue!
The low saturation during exercise is helped by a shift in the O2-Hb dissociation curve to the RIGHT by increases in:
1) hydrogen ion concentration (pH drop)
2) CO2 concentration
3) temperature (minor)
4) 2,3-BPG

Question 12

What is the affect of anemia on O2 tansport?

Answer 12

Anemia decreases the blood’s capacity to transport O2 to the tissue. This means that even though there is no change in PO2 or percent Hb saturation, MUCH less O2 is reaching the tissue. This can be partially compensated for by increased cardiac output, but will likely be evident during strenuous exercise.

Question 13

How is CO2 transported in the blood?

Answer 13

1) Dissolved CO2 (7%) -> due to increased solubility of CO2 (20x»>O2) the small pressure difference allows CO2 to just diffuse into the blood plasma
2) As bicarbonate ions (HCO3 -) (70%) -> CO2 + H2O -> H2CO3 -> H+ + HCO3- –> HCO3- is transported across RBC membrane and is dissolved in plasma
3) as carbamino compounds (Hb-CO2) (23%) -> CO2 reacts slowly with proteins (especially Hb) in RBC which makes it more soluble in RBCs and plasma

Question 14

What is a the chloride shift with regard to CO2 transport in blood?

Answer 14

This is referring to an increase in chloride inside RBCs when there is a high concentration of CO2 in the blood (venous blood).
This is due to how the bicarbonate ion is transported out of the RBC. Once CO2 and H2O have formed bicarbonate, it is transported out of the RBC by facilitated diffusion via the BICARBONATE-CHLORIDE EXCHANGER. This allows HCO3- to travel down its concentration gradient and pulls Cl- into the RBC => Chloride Shift. This is reversed when CO2 concentration falls.

Question 15

Why does CO2 form H2CO3 more rapidly in RBC vice plasma?

Answer 15

1) RBCs have a high concentration of CARBONIC ANHYDRASE (the enzyme catalyst for this reaction)
2) Cl/HCO3- Exchanger removes HCO3- from the cell, preventing a build up of HCO3- from slowing the reaction
3) the intracellular buffers (mostly Hb) prevent a build up of H+ from slowing the reaction

Question 16

What is the Haldane Effect with regard to CO2 transport in blood?

Answer 16

O2 binding to Hb promotes the release of CO2 from blood, thus doubling the amount of CO2 exchanged at physiological pressure differences.

1) O2 binding to Hb makes it a stronger acid, therefore releasing H+ it had been “buffering” –> this pushes the HCO3- equilibrium back to H2CO3 and CO2/H2O
2) O2 binding to Hb also displaces CO2 that had been bound as carbamino compounds
3) The resulting increase in CO2 concentration in the RBCs increases the pressure difference across the Respiratory Membrane and helps with diffusion

Question 17

What is the affect of CO2 concentration on blood pH?

Answer 17

CO2 + H2O -> H2CO3 -> HCO3- + H+
This means that as CO2 increases, pH drops. Normally arterial pH is ~7.41 where venous pH is ~7.38.
This change is related to CO2 concentration by the Henderson-Hasselbach Eqn, which is how CO2 is measured in a standard Arterial Blood Gas sample.

Question 18

Define Respiratory Acidosis. What are some (general) physiologic causes?

Answer 18

Acidosis: Arterial Pco2 > 44mmHG (norm=40) OR Blood pH drop pH

1) poor ventilation (mechanical breathing failure)
2) poor diffusion (pulmonary edema/alveoli injury)
3) low pressure difference (high atm CO2 ie. rebreathing)

Question 19

Define Respiratory Alkalosis. What are some (general) physiologic causes?

Answer 19

Alkalosis: Arterial Pco2 7.45 (norm=7.41)
Causes: decreased CO2 concentration -> pH rise
1) hyperventilation (blow off too much CO2)
2) fever (temperature affects CO2 diffusion)

Question 20

What sensory receptors are involved in respiratory control?

Answer 20

1) Central chemoreceptors -> H+ (this is driven by CO2 concentration, but H+ interacts directly with receptor)
2) Peripheral chemoreceptors -> O2, CO2, H+
3) Pulmonary receptors -> stretch
4) Joint/Muscle receptors -> stretch and tension

Question 21

What neurologic areas are responsible for automatic respiratory control? What is their GENERAL function?

Answer 21

1) Upper pons -> Pneumotaxic Center -> “off switch” to transition from inspiration to expiration
2) Lower pons -> Apneustic Center -> unknown; may be involved with taking deep breaths
3) Medulla -> Dorsal Regulatory Group -> innervate “breathing muscles” to help with forced breathing
4) Medulla -> Ventral Regulatory Group -> pacemaker function to control rate of breathing

Question 22

How do central chemoreceptors respond to changes in blood chemistry?

Answer 22

CO2 diffuses freely across the blood brain barrier. This shifts the equilibrium with HCO3-, freeing more H+. These ions directly stimulate the chemoreceptors and cause increased ventilation.

Question 23

Describe the peripheral mechanical pulmonary receptors.

Answer 23

Slow adapting stretch - located in smooth muscle of airways; respond to changes in air volume
Rapidly adapting stretch - located in epithelium of airways; respond to the rate of change of air volume
J (Juxtaposed) Receptors - located near pulmonary capillaries to respond to changes in capillary interstitial pressure (as in edema) -> these are responsible for sense of dyspnea during edema

Question 24

Describe the Hering-Breuer Reflex.

Answer 24

Summary: mechanically inflating the lungs promotes exhalation, and a decrease in lung volume promotes inhalation

Inspiration -> lung inflation -> stretch receptors (slow/fast activate @~1.5L) -> vagal fibers increase stimulation -> Apneustic center inhibition -> “stop” inhalation -> exhalation

Question 25

What is the function of peripheral chemoreceptors with regard to pulmonary regulation?

Answer 25

Located in the CAROTID BODIES (major) at the bifurcation of internal/external carotids and in the aortic arch (minor).
Sense changes in O2, CO2 and H+. O2 is the most powerful factor, but changes in CO2 illicit a faster response. However, the CO2 response is much less than the centrally mediated response to changes in CO2.

Question 26

What changes in respiratory regulation are noted in COPD?

Answer 26

Chronically elevated CO2, therefore the central receptors become desensitized and no longer increase respiration.
Peripheral O2 receptors continue to drive increased respiration.
A common complication is when giving high levels of O2, there can be induced respiratory depression and a build up of CO2.

Question 27

What changes in respiratory regulation are noted in Obstructive Sleep Apnea? Central Sleep Apnea?

Answer 27

OSA occurs when there is a physical obstruction to airflow (relaxed throat muscles). This increases CO2 and decreases O2. Dyspnea-like sensations causes arousal, which sends a signal to upper airway to re-open and breathing resumes temporarily.
Most common in the obese.
Central Sleep Apnea is a failure of the brain to send the “inhalation” signal from the Dorsal Regulatory Group. This results in the same physical changes, but can be more dangerous since they don’t snore to alert others of the condition.

Question 28

What are the five causes of hypoxemia?

Answer 28

1) V/Q mismatch
2) Shunt
3) Diffusion abnormality (as in edema)
4) Low inspired O2 content (high altitude)
5) Hypoventilation (rare)

Question 29

What is the alveolar gas equation? What are normal values?

Answer 29

PAO2 = FiO2(Pb-PH20)-PaCO2/RQ
PAO2 - partial pressure Alveolar O2 (102mmHg)
FiO2 - percent O2 in “atmosphere”(0.21)
Pb - barometric pressure(760mmHg)
PH2O - partial pressure water in atmosphere (humidity)(47mmHg)
PaCO2 - partial pressure arterial CO2 (40mmHg)
RQ - respiratory quotient (0.8)

Question 30

Define V/Q matching.

Answer 30

The lungs attempt to perfectly match alveolar ventilation (V) with capillary perfusion (Q). This provides the most efficient gas exchange. Normal V/Q is 0.8, but can change with age, activity level, digestion, or pathology.

Question 31

Define Dead Space.

Answer 31

Dead Space is where there is more ventilation than blood flow (V/Q=infinity).
Alveolar Dead Space -> physiologic dead space based on capillary pressure vs alveolar pressure; this space is recruitable when needed (as in exercise or disease)
Anatomic Dead Space -> anatomic dead space (trachea) that is not recruitable

Question 32

Define Shunt.

Answer 32

A Shunt is when ventilation is less than blood flow (V/Q=0).
Bronchial and thebesian veins “bypass” lungs and therefore produce a 1-2% shunt.
Test via Shunt Study. When breathing 100% O2, PaO2 should increase to 700. Any reduction is proportional to how much blood is being “shunted” by the lungs. Every 100mmHg below 700 = 5% of cardiac output not being oxygenated.

Question 33

Define hypoxemia.

Answer 33

Hypoxemia - decrease partial pressure of O2 in blood

PO2<90%

Question 34

What is the significance of the A-a gradient?

Answer 34

A-a gradient is the difference between Alveolar O2 and arterial O2 partial pressures. This serves as a good general test of lung-respiratory function. If there is a respiration derangement, but the A-a gradient is normal, look elsewhere for cause (anemia, obstruction, cellular O2 use, etc)
Normal<20

Question 35

How can hypoxemia be recognized/measured?

Answer 35

Symptoms of O2 deficiency/CO2 build up include dyspnea, tachypnea, confusion, fatigue, cyanosis, tachycardia, etc. A-a gradient can be calculated using pulse oximeter or ABG. X-Ray can also help in diagnosis.

Question 36

What are some methods of oxygen supplementation?

Answer 36

Nasal prongs - good for conscious patients in mild distress
Face Mask - better delivery of O2, but cannot control FiO2
Venturi mask - relatively precise control of FiO2
High Flow System - can deliver high flow of controlled O2
Positive Pressure breathing (mask/ETtube) - closed system, 100% O2, doesn’t help with CO2 elimination