Pulm Week 1 Flashcards
The conducting airways consist of ___ dichotomous branching tubes starting with _____ and ending at _________. The first ____ branches are just for conduction
23
Trachea –> terminal bronchioles
16 (branch point 17 has alveolar tissue)
Gas exchange units begin distal to _________ and includes _______, _________, and _______
terminal bronchiole
respiratory bronchioles, alveolar ducts, alveoli
Type I Pneumocytes
simple squamous
95% of alveolar surface area, fuse with capillary endothelium for gas transfer
Type II pneumocytes
Secretory
- Produce surfactant → lower alveolar surface tension
- Can further differentiate into Type I to repair or replace them
Ventilation
air movement in and out of the lung
Respiration
gas exchange - exchange O2 and CO2 across the alveolar capillary membrane
-Heart and pulmonary circulation needed to provide blood flow to alveoli
Lung bud develops from _________ and branches multiple times into the ____________
embryonic gut tube endoderm
splanchnic mesenchyme
Lung bud develops from an out pouching between the ______ and ______ in a region called the _________
4th and 6th brachial arteries
Laryngotracheal groove
Pulmonary circulation develops from ________
mesenchyme
Stages of lung development (5)
1) Embryonic stage 4-7 weeks
2) Pseudoglandular stage 8-16 weeks
3) Canalicular stage 17-26 weeks
4) Saccular (Terminal Sac) Stave 26-36 weeks (term)
5) Alveolar Stage (Postnatal Stage) 36 weeks - 3 years
Embryonic stage
- foregut endoderm extends into surrounding mesenchyme
- 3 rounds of branching establish lung lobes
- to level os subsegmental bronchi
- begin to fill bilateral pleural cavities
- branching determined by mesoderm
Pseudoglandular stage
-14 rounds of branching form terminal bronchioles
Canalicular stage
- terminal bronchiole divides into 2+ respiratory bronchioles
- delineation of pulmonary acinus
- fetal “breathing” detected
- epithelial cell differentiation begins
- initial development of pulmonary capillary bed
- possible fetus can survive but respiratory distress trouble
Saccular stage
-Respiratory bronchioles subdivide to produce terminal sacs (these continue to develop well into childhood)
-Epithelial differentiation is hallmark
(Type II secretory cells –> surfactant production, fetal survival improves)
Alveolar Stage
- Lung grows and alveoli mature
- Septae thin
- Single capillary network in alveolar wall
- Gas exchange unit established (presence of true alveoli - 90% of 300 million appear after birth)
Pulmonary arteries (and arterioles) run with ______
bronchi (and bronchioles)
Pulmonary veins do not run with airways but are more peripheral
Lymphatics run near ______ and _____ to help cope with ________
pulmonary arteries and veins
extravascular lung water
Pulmonary arteries embryonic origin is the ________, whereas pulmonary veins originate from _________
6th aortic arce
outgrowths of left atrium
______ cells line the lungs
mesothelial
Branching pattern of conduction system
_______ → _______→ ___________→ _______ (how many on right vs. left)
trachea → primary bronchus → secondary bronchus → segmental bronchi (10 on the right, 8 on left)
Trachea differs from the bronchus in that is has no ___________ layer and no __________
no muscularis mucosa layer
no submucosal glands
Wall layers of bronchus from surface to deep (7)
1) Epithelium (ciliated cells, goblet cells, basal cells, neuroendocrine cells)
2) Basal lamina
3) Alveolar connective tissue
4) Musclaris Mucosa
5) Dense CT of submucosa
6) Hyaline cartilage
7) Adventitia
Epithelium in walls of broncus made up of what 4 types of cells with what functions?
1) ciliated cells (constantly move mucous up airway)
2) goblet cells (secrete mucus onto bronchial surface)
3) basal cell (stem cell for other cells in epithelium)
4) Neuroendocrine cells also present - do reflexive control of airway size
Alveolar connective tissue
- made up capillaries and nerve cells
- Contains leukocytes that wander around in loose CT
- Mucosal associated lymphoid tissue
Lamina Propria
Lamina propria = area right under epithelium in alveolar connective tissue (lots of leuks here)
Muscularis mucosa
smooth muscle layer
Everything below this layer = submucosa
above = mucosa
Contracts to help movement of secretions out of submucosal glands onto surface
(NOT in trachea, but in bronchi)
In the hyaline cartilage chondrocytes reside in _______
lacunae
Adventitia of lung conduction system
Contains large blood vessels, nerves, etc. coursing along outside
Layers of Bronchioles (5)
1) Epithelium (Club cells + ciliated cells)
2) Basal lamina
3) Lamina propria
4) Smooth muscle
5) blends into tissue that begins to become alveolar septa
Epithelium of bronchioles consist of what 2 cell types?
1) Club cells - contain surface active substance that are secreted onto surface and maintain patentcy of bronchioles
(No longer have cartilage to keep them open)
2) Ciliated cells
Respiratory bronchioles –> _______ –> _______ –> ________
alveolar ducts
alveolar septa
alveolar saccules (where gas exchange occurs)
Muscles involved in inspiration (4)
1) Diaphragm
2) External intercostals
3 and 4) Sternomastoids and scalenes
Diaphragm
contracts during inspiration, pulled DOWN and flattens out
- Innervated by phrenic nerve
- Max force/tension of diaphragm at 130% of resting length, and decrease steeply for reductions in length –> disease pathology
Effect of COPD on the diaphragm
COPD (asthma, chronic bronchitis, emphysema) - breath at higher than normal lung volumes
-Diaphragm more contracted (flatter) and reduced in length
External intercostals
pull ribs forward and OUTWARD
Sternomastoids and scalenes
- accessory inspiratory muscles
- Generally silent during normal breathing, only used with ventilation or respiratory load increased (e.g. exercise)
- Elevates the rib cage
Expiration is _______, but during active/forced expiration the _______ and _______ muscles are used
PASSIVE
Abdominal Wall Muscles (Push diaphragm upwards)
Internal Intercostals (pull ribs inward and downward → decrease thoracic volume)
Intrapleural Pressure (PIP)
- pressure outside lung developed in intrapleural space due to intrinsic elastic properties of lung and chest wall
- Lung is trying to shrink to its intrinsic equilibrium, chest cavity trying to expand equilibrium → Opposing forces generate negative pressure
- Acts as to “glue” lung to chest cavity
Intrapleural space
thin film of fluid between lung and chest cavity
Transpulmonary pressure (PTP)
difference between pressure in lungs (PL) and intrapleural pressure (PIP)
Inspiration –>
Inspiration → expanding chest cavity pulls lung opens, expands lung volume
-Lung pressure (PL) becomes negative with respect to mouth pressure (PM) –> sucks O2 into the lungs
Expiration –>
Expiration → PL becomes positive with respect to PM
Chest wall begins to contract → “releases” lung from more inflated state acquired during inspiration
At very end of expiration, no air-flow because PL = 0
Elastic Recoil Pressure
inherent tendency of lung to recoil back toward intrinsic equilibrium → transient positive pressure inside of lung → effectively pushes air out lung
Lung Compliance
- change in volume/change in pressure
- Provides measure of elastic properties of lung
- High compliance at rest, but at high volumes, compliance decreases → makes expansion more difficult
- Compliance is inversely proportional to Elasticity
- increased compliance means a greater transpulmonary pressure required to effect a given volume change during inspiration
Lung Compliance:
Fibrosis → ?
Emphysema → ?
Fibrosis → low lung compliance → makes inspiration difficult
Emphysema → loss of elastic tissue → high lung compliance → easy inspiration but difficult expiration
-Elastic recoil less with high compliance → push less air out
Chest wall compliance:
reduced chest wall compliance –> ?
reduced change in volume that lung undergoes during normal breathing = reduced tidal volume (reduced airflow in lung)
EX) obesity, old age, abnormalities of bony thorax
Problems created by surface tension in alveoli: (3)
1) Reduced lung compliance
2) Fluid accumulation in alveoli
3) Collapse of small alveoli
Small alveoli = higher internal pressures → small alveoli empty their air down pressure gradient into larger ones
Surface tension
Important for determining compliance
Tension between liquid and air
Surfactant
Physical properties?
mixture of lipids and proteins
Secreted by alveolar epithelial type II cells
Surfactant
Function?
- reduces surface tension of water by intercalating between water molecules, reducing attractive forces
- Increases lung compliance, prevents collapse of small alveoli, and prevents accumulation of fluid inside alveoli
Efficacy of surfactant increases at smaller alveolar radii, why?
decreased surface area = increased concentration of surfactant molecules on alveolar surface → decrease surface tension
Respiratory Distress Syndrome in Infants
surfactant deficiency
Stiff, noncompliant lungs prone to collapse
Surfactant produced at fetal week 24
Airway Resistance
- gross mechanical property of lung that can impact breathing
- Respiratory airways oppose the flow of air through them
At low flow rates you have ______ flow while at high flow rates you have _____ flow. In the lungs we have ______ flow
laminar
turbulent
transitional
Airway resistance equation
R = 8nl/(pi)(r^4)
Tube RADIUS very important
Does NOT depend on density of gas
_____ and _____ make turbulent flow more likely
large diameters and high flow rates
major site of airway resistance is __________
intermediate-sized bronchi
Factors that alter airway resistance (3)
1) Lung Volume
2) Bronchial smooth muscle tone
3) Dynamic airway collapse
Lung volume affect on airway resistance
Large lung volumes = airways expand and resistance decreases
Small lung volumes = airways narrower, resistance increases
Control of bronchial smooth muscle tone and impact on airway resistance
bronchostriction from...(4) bronchodilation from (2)
Contraction of bronchial smooth muscle → narrow airway, increase resistance
Bronchoconstriction via ACh (vagus nerve), histamine, arachidonic acid metabolism products, and low CO2 in airways
Bronchodilation via activation of B2 receptors (Epinephrine, NE) and high CO2 in airway
Dynamic airway collapse occurs when…
Positive intrapleural pressures develop outside airway
If transpulmonary pressure is positive –> airway stays open
If transpulmonary pressure is negative –> airway collapses
- When intrapleural pressure (PIP) is positive, transpulmonary pressure can be negative (i.e. during forced expiration, chest wall exerts force on intrapleural space)
- Normal conditions, PIP is negative, and thus PTP is positive and airway stays open
why does airway collapse occur in emphysema?
What compensatory mechanism attempts to prevent airway collapse?
Primary problem: higher tendency for lung to deflate, resulting in reduced elastic recoil pressure (higher compliance)
Compensatory attempt: use muscles for forced expiration –> chest wall exerts positive force/compression of intrapleural space (PIP positive)
Results in airway collapse
-Prevent airway collapse with pursed lip expiration –> increases airway pressure during exhalation
Minute Ventilation
volume of air that flows into or out of the lung in one minute
Includes air flowing in the conducting paths AND alveoli
Always larger than alveolar ventilation
normal = 6 L
Tidal Volume (VT) x frequency of breathing (ml/min)
Alveolar ventilation
volume of air that flows into or out of alveolar space in one minute
normal = 4.2 L
Factors influencing lung ventilation (5)
1) Bronchodilators and constrictors
2) Exercise
3) Altitude
4) Obstructive diseases and restrictive diseases
5) Gravity
Effect of bronchodilators and bronchoconstrictors on ventilation
Bronchodilators → increase alveolar ventilation
Bronchoconstrictors → decrease alveolar ventilation
Effect of exercise on ventilation
Moderate exercise → increase ventilation x10 in order to meet demands of increased CO2 production
Effect of altitude on ventilation
Ventilation increases to meet increased demands of O2
Effect of obstructive disease and restrictive disease on ventilation
what happens in emphysema?
Increase airway resistance or alter lung compliance
EX) Emphysema → reduce ventilation by increasing airway resistance (due to dynamic airway collapse) and increasing lung compliance
Regional variations in ventilation due to gravity
Intrapleural pressure (PIP) smaller at base of lung than apex → bronchioles and alveoli have larger volumes at apex → larger volume = less well ventilated (because less compliant)
Bottom of lung ventilates approx 2.5x more than the top
Work of breathing done against ___________ and _______________
elastic recoil of lungs (increase work with increased elastic recoil/decreased compliance)
airway resistance (increased work with increased airway resistance)
Small tidal volume → work required to overcome elastic recoil is _______, but work required to overcome airway resistance is ________
Large tidal volume → work required to overcome elastic recoil is _______, but work required to overcome airway resistance is _______
Small tidal volume → work required to overcome elastic recoil is small, but work required to overcome airway resistance is large
Large tidal volume → work required to overcome elastic recoil is large, but work required to overcome airway resistance is small
Total work
Elastic + resistance work
low point on curve at which least amount of work is required → where a person typically breathes
Physiologic Dead Space = ___________ + ___________
Physiologic Dead Space = Anatomic Dead Space + Alveolar Dead Space
Physiologic dead space
Volume of lung that does not engage in gas exchange → Not all air breathed in reaches sites of gas exchange
-Increased dead space reduces the efficiency of breathing, increases the work involved in breathing
Anatomic dead space
what 2 conditions can increase anatomic dead space?
500 ml of air in each breath - 150ml remains in conducting path → Anatomic Dead Space
EX) rapid breathing at small tidal volumes
EX) snorkel increases anatomic dead space
Anatomic dead space in a healthy person is approx equal to physiologic dead space
Alveolar Dead Space
1 condition causing alveolar dead space?
alveoli that are well ventilated but do not participate in gas exchange, typically in unperfused regions of lung (no blood flow)
EX) PE stopping blood flow to alveoli makes it dead space
Residual Volume (RV)
volume of air remaining in lungs after max expiration (=1.5L)
Functional Residual Capacity (FRC)
volume of gas present in lung and upper airway at end of normal expiration (=2.5L)
Total Lung Capacity (TLC)
volume of air inside lungs at end of max inspiration (=7.5L)
Tidal Volume (VT)
difference in lung volume between a normal inspiration and normal expiration
-Volume of air that enters and exits lungs in one normal breathing cycle
VT = 500 ml
Vital Capacity (VC)
volume of air exhaled after a max inspiration and max expiration
VC = TLC - RV
Pulmonary Fibrosis
Impact on TLC, VC, RV, FRC, and FEV/FVC (rate of airflow)
decreased lung compliance, difficult inspiration
→ reduced TLC, VC, small decrease in RV and FRC
NO impact on airway resistance or rate of airflow (FEV/FVC)
Bronchitis
Impact on TLC, VC, RV, FRC, and FEV/FVC (rate of airflow)
increased airway resistance
→ reduced rate of airflow (FEV/FVC), small decrease in VC
small increase RV and FRC
NO change in TLC
What is PIO2
normal value?
partial pressure of oxygen just inspired
represents the upper limit of PAO2 (partial pressure of oxygen in Alveoli)
normal = 150 Torr, in Denver though, closer to 120 Torr
Dalton’s Law equation
PIO2 = (PB-47 torr) x FO2
FO2 = 0.21 (% of O2 in air), unless breathing in 100% O2
Respiratory Exchange ratio (R)
relationship between O2 consumed and CO2 produced
R = VCO2/VO2
R = 0.8 for a typical diet
Why is the respiratory exchange ratio (CO2 produced/Oxygen consumed) less than 1?
What makes R = 1?
Why does R vary for different metabolites?
-R less than 1, but O2 levels do NOT go up because N2 compensates for deficit in total pressure
R = 1 if patient breathing 100% O2
R varies for different metabolites because each molecule of O2 consumed in metabolizing different products produces a different amount of CO2
Alveolar Gas Equation
PAO2 = PIO2 - (PACO2/R)
partial pressure of oxygen in alveoli = partial pressure of inspired O2 - (partial pressure of CO2 in alveoli/respiratory exchange ratio)
Normal values:
R=0.8
PACO2 = 40 torr
Is diffusion or ventilation the rate-limiting step for CO2 removal?
Diffusion step is extremely fast → CO2 in alveoli and pulmonary capillaries equilibrates near-perfectly → PACO2 = PaCO2
Ventilation step (how CO2 is transported between alveoli and outside air) is rate-limiting for CO2 removal -If alveolar ventilation (Va) decreases → build up of PACO2 → increased PaCO2 in blood (THATS BAD)
Alveolar Ventilation Equation
PACO2 = (VCO2/VA) x k
VA = alveolar ventilation in one minute VCO2 = CO2 production in one minure
PACO2 = PaCO2
Implications of alveolar ventilation equation for blood CO2 and blood O2
Blood CO2 DIRECTLY regulated by alveolar ventilation
Blood O2 is INDIRECTLY regulated by alveolar ventilation via its effects on alveolar CO2
Hypoventilation
increase in PaCO2 (decrease in VA)
- Refers to abnormally low alveolar ventilation (NOT frequency of breathing)
- Occurs in severe obstructive disease
Hyperventilation
-decrease in PaCO2 (increase in VA)
-Refers to abnormally high alveolar ventilation (NOT frequency of breathing)
(Tachypnea = higher than normal frequency)
-Occurs in high altitude
Hyperpnia
increase in alveolar ventilation (VA) not accompanied by a decrease in PaCO2
-Occurs during exercise
Arterial oxygen content (CaO2) = ______ + _______
In what state is most of the O2 in our blood?
what is a normal CaO2 value?
CaO2 = Hgb-O2 + free O2
98% of O2 bound to Hgb
Freely dissolved O2 = PaO2
Normally:
CaO2 = 20.7 mlO2/100ml blood in a healthy person
Solubility coefficient
aO2?
aCO2?
tendency of any molecule to dissolve in a liquid
O2 does not dissolve very well in blood and binds quickly to Hgb → very little freely-dissolved O2
O2 solubility coefficient = aO2 = 0.0013 mM/Torr
**Only 0.13 mM O2 freely dissolved in blood
CO2 solubility coefficient = aCO2 = 0.03 mM/Torr
Oxy-Hemoglobin Dissociation Curve relates ______ to ________.
Implications of shape of curve?
relates SO2 (oxygen saturation) and PO2 in blood
Implications:
For PO2 = 100 Torr (normal arterial oxygen), SO2 = 97.5%
→ in arterial blood Hgb is very close to full saturation and increasing PO2 has very little impact on amount of O2 carried by Hgb
Diffusion
rate of gas transfer across a tissue plane.
Diffusion is a function of… (4)
1) Difference in partial pressure of gas on the two side of the membrane
2) Tissue plane area (A)
3) Tissue thickness (d)
4) Constant k reflecting tissue solubility and molecular weight of the gas
Factors that promote rapid oxygen diffusion between alveoli and pulmonary capillaries? (3)
1) Large surface area (A) of the alveolar membrane
2) Thin membrane width (d)
3) Mechanism that helps maintain a large O2 pressure gradient between alveoli and capillaries
→ Diffusion is FAST between capillaries and alveoli - PaO2 reaches PAO2 in ⅓ the time it takes for blood to pass through capillary bed
-Safety net (disease, exercise)
What mechanisms maintain a large O2 pressure gradient between alveoli and capillaries? (2)
Low solubility of O2 in blood + O2 quick to bind to Hgb → free O2 in capillaries remains low
Disease and Diffusion:
1) Interstitial Disease
2) Emphysema
3) Polycythemia
4) Anemia
Interstitial disease → thickening of alveolar walls → slows diffusion
Emphysema → break down in lung tissue decreases surface area for diffusion
Polycythemia (increased Hgb) → diffusion increases
(Much larger effect on oxygen delivery to tissues rather than diffusion)
Anemia (decreased Hgb) → perfusion decreases
(Much larger effect on oxygen delivery to tissues rather than diffusion)
O2 vs. CO2 Diffusion
O2 diffusion much more affected by disease
-Because only dissolved O2 can cross the alveolar membrane, and O2 has poor solubility in blood
CO2 diffusion much less affected by disease
- Will always get down to ideal levels of 40 Torr
- Based on higher solubility of CO2
Minute Perfusion (Q)
blood flow into ventilated regions of lung in 1 min= CO = 5 L/min
Factors that influence perfusion (4)
1) alveolar O2 tension
2) Other chemical agents
3) Capillary recruitment
4) Gravity
Effect of Alveolar O2 Tension on minute perfusion (Q)
Low alveolar PO2 → constrict nearby arterioles = hypoxic pulmonary vasoconstriction
DECREASES local blood flow and shifts it to other regions of lung that have higher O2
Opposite to what happens in the rest of the body in response to hypoxia
Effect of thromboxane and prostacyclin on minute perfusion (Q)
Thromboxane A2 → vasoconstriction (local)
Prostacyclin (PGI2) → vasodilation
Effect of capillary recruitment on minute perfusion (Q)
Moderate exercise → increase CO → increased pulmonary circulation via recruitment of new capillaries
Pulmonary capillary volume is 75 ml at rest and can increase to 200 ml during exercise
Regional variations in minute perfusion (Q) due to gravity
- Causes lower BP at apex of lung than base of lung
- Base of lung has higher BP and thus more open capillaries and higher blood flow
- Perfusion increases from apex to bottom of lung
*Significant effect! 6x more perfusion at bottom of lung
Alveolar Dead space
e. g. blockage in pulmonary capillary
- Alveoli well ventilated but do not engage in gas exchange
Extreme of HIGH V/Q mismatch→ V/Q=infinity
Shunts
blood perfusion where there is no ventilation
- extreme of LOW V/Q → V/Q=0, essentially becomes dead space
- Normal shunting is 1-2% of CO
- Can significantly decrease arterial oxygenation
- E.g. pneumonia
If you have 3 areas with different V/Q in the lung, what will happen? (2)
1) High V/Q region → can’t add much O2 as compared to normal V/Q branch and thus can’t make up for low V/Q branch
(Because Hgb already near saturation)
2) CO2 levels will NOT be affected
Regulating V/Q mismatch:
In areas with high V/Q…
In areas with low V/Q…
In lung areas with high V/Q, alveolar PCO2 drops → increases local airway resistance and decreases ventilation
-High PCO2 in bronchioles → bronchodilation
In lung areas with low V/Q, alveolar PO2 drops → hypoxic vasoconstriction and decreasing local perfusion
-Vasoconstriction due to low PO2
Causes of V/Q mismatch (2)
1) Resistance/Compliance problems
2) Gravity
Effect of Gravity on V/Q
Gravity →
Ventilation 2.5 x greater at bottom
Perfusion 6 x greater at bottom
Oxygen “off-loading” from Hgb
Fast unbinding allows for tissues to take up and use freely-dissolved O2
Without this, total O2 levels might be high, but most O2 molecules would stay bound to Hgb and be unavailable for use
While O2 unbinding is fast, O2 binding is even faster
_______, ________, and _______ shift the curve to the right this is called the __________.
When the curve is shifted right this means…
When the curve is shifted left, this means…
low pH, increased CO2, increased temp
Bohr Effect
Shift curve right –> (O2 less tightly bound to Hgb)
Shift curve left –> O2 bound too tightly to Hgb and less unloading in peripheral tissues
What affect does 2,3-DPG have on the oxy-hemoglobin dissociation curve?
Increased 2,3-DPG → shift curve right
Occurs during chronic hypoxia at altitude
What is DO2?
quantity of O2 delivery in one minute
DO2 equation
CaO2 equation
DO2 = Q x CaO2
CaO2 = SaO2 x [Hb] x 1.39 mlO2/gm Hgb
Units are ml O2/100 ml blood
Calculating oxygen consumption (VO2)
VO2 = Q x (SaO2 -SvO2) x [Hb] x 1.39
Hypoxia
low O2 at level of tissue
PO2 less than 1-2 Torr in mitochondria
Causes of Hypoxia (3)
1) Low Q (cardiac output)
2) Low SaO2 associated with low PaO2 (Hypoxemia)
3) Delivery problems
- Low Hgb (anemia)
- Carbon monoxide poisoning
Hypoxemia
reduced arterial free oxygen (PaO2 less than 80 Torr or 65 Torr in Denver) and reduced SaO2→ decreased O2 delivery
If in a state of hypoxemia, then you are hypoxic but the reverse is NOT true
Reduces CaO2 by reducing %Sat of Hgb (SaO2) and free O2
Causes of Hypoxemia (5)
1) Low ambient PO2 in inspired air (PIO2) - altitude
2) Hypoventilation
3) Diffusion limitations
4) V/Q mismatch
5) Shunt
4 ways to measure arterial oxygenation
1) Arterial oxygen tension (PaO2)
2) Oxy-hemoglobin saturation (SaO2)
3) Alveolar-Arterial (A-a) pressure gradient for oxygen
4) Blood oxygen content (CaO2)
Low SaO2 and normal PaO2 indicates what?
something competing with O2 for Hgb → Carbon Monoxide
Carbon Monoxide Poisoning
Carbon Monoxide (binds Hgb with 210x greater affinity than O2)
Shifts oxy-Hgb curve left, decreases O2 off loading
Poisons electron transport chain → anaerobic metabolism
Odorless, colorless, does not cause cyanosis
Alveolar-Arterial (A-a) pressure gradient for oxygen
Difference in PAO2 and PaO2
Measured directly by measuring arterial CO2
Normal A-a gradient is less than 5-10 Torr
What makes the A-a wider?
What disease processes maintain a normal A-a?
Wide A-a gradient
-Shunt, V/Q mismatch and diffusion problems
Normal A-a:
-Hypoventilation, Low ambient PO2 inspired air
3 ways CO2 is carried in blood?
1) Carbon dioxide (dissolved gas) - 1.2mM
2) Bicarbonate ion (HCO3-) - 24mM
3) Carbamino Compounds (Hgb) - 1.2mM
Haldane effect
Deoxygenated Hgb carries CO2 better than oxygenated Hgb
Low PIO2 (high altitude)
What is your PaO2, SaO2, PaCO2, A-a gradient?
What special tests?
PaO2 - decreased
SaO2 - decreased
PaCO2 - decreased (breathing more = increased CO2)
A-a gradient - normal
Special tests - measure PaCO2
Low PAO2 (hypoventilation or COPD)
What is your PaO2, SaO2, PaCO2, A-a gradient?
What special tests?
PaO2 - decreased
SaO2 - decreased
PaCO2 - increased
A-a gradient - normal
Special tests - measure PaCO2
Diffusion problem (interstitial disease)
What is your PaO2, SaO2, PaCO2, A-a gradient?
What special tests?
PaO2 - decreased
SaO2 - decreased
PaCO2 - normal (diffusion = no effect on CO2 due to high solubility)
A-a gradient - increased (normal A, low a)
Special tests - CO single breath
V/Q mismatch (moderate COPD)
What is your PaO2, SaO2, PaCO2, A-a gradient?
What special tests?
PaO2 - decreased
SaO2 - decreased
PaCO2 - normal
A-a gradient - increased (normal A, low a)
Special tests - give 100% O2 to differentiate with shunt (will respond)
Shunt (pneumonia)
What is your PaO2, SaO2, PaCO2, A-a gradient?
What special tests?
PaO2 - decreased
SaO2 - decreased
PaCO2 - normal
A-a gradient - increased
Special tests - give 100% O2 to differentiate from V/Q mismatch - will not respond
Henderson-Hasselbalch for bicarbonate and CO2
pH = 6.1 + log ([HCO3-]/(0.03xPaCO2))
H2O + CO2 H2CO3 H+ + HCO3-
Via carbonic anhydrase to make carbonic acid
Why is bicarb a good buffer? (3)
1) Present in high concentration
2) pKa is relatively close to arterial pH
3) Conjugate acid, CO2 is readily controlled by ventilation by lungs
Acidemia vs. Alkalemia
How good is compensation?
Acidemia = more acid in blood than normal → lower pH, pH less than 7.40
Alkalemia = more base in blood than normal → higher pH, pH>7.40
*Compensation will NEVER completely correct to normal pH nor will it overcompensate
Arterial and venous pH ranges
Arterial pH = 7.4 (7.38-7.43)
(Range compatible with life is 6.8-7.8)
Venous pH = 7.34-7.37 (maintain pH in venous blood due to buffering effects of deoxyhemoglobin)
Normal PaCO2 and [HCO3-]
PaCO2 = 40 Torr [HCO3] = 24 meq/L
Respiratory Acidosis
increase in PaCO2 → lower pH
- Typically always due to ineffective ventilation = Hypoventilation
- can be acute or chronic
Acute = before kidneys can compensate Chronic = kidneys attempt to compensate
Causes of Chronic Respiratory Failure (respiratory acidosis) (3)
1) Chronic lung diseases (Emphysema, Chronic bronchitis (COPD), bronchiectasis) → chronic hypercapneic respiratory failure
2) Central hypoventilation due to obesity or neuromuscular diseases (ALS)
3) Hypothyroidism
Causes of Acute Respiratory Failure (2)
1) Drugs that suppress breathing centers in brainstem (opiates, benzos, alcohol)
2) Respiratory muscle fatigue (e.g. pneumonia causing tachypnea that tires muscles with increased work of breathing)
Compensation for respiratory acidosis
Acutely, every ___ Torr increases in ____ → pH decreases by _____
Chronically, every ___ Torr increase in ____ → HCO3- increases by ____ meq/L
- conservation of HCO3- by kidneys / secrete NH4Cl
- Slow, takes 2-3 days to complete
Acutely, every 10 Torr increases in CO2 → pH decreases by 0.08
Chronically, every 1 Torr increase in CO2 → HCO3- increases by 0.4 meq/L
Respiratory Alkalosis
decrease in PaCO2 → higher pH
- Typically due to hyperventilation
- can be chronic or acute
Causes of chronic alveolar hyperventilation (respiratory alkalosis) (4)
1) high altitude
2) neurological disorders that decrease inhibitory input to respiratory brain centers (brain injury)
3) chronic salicylate (ASA) toxicity
4) pregnancy
Causes of acute alveolar hyperventilation (4)
1) pain
2) anxiety
3) fever
4) mechanical ventilation
Compensation for respiratory alkalosis
- increase excretion of HCO3- and lower pH toward normal value
- Slow, takes hours or days
Metabolic Acidosis
addition of an acid (other than CO2) leading to a reduction in bicarbonate and lower pH
either anion or non-anion gap metabolic acidosis
Compensation for metabolic acidosis
increased ventilation → remove CO2, RAPID
-Occurs quickly
How do you determine if a patients compensatory response to metabolic acidosis is sufficient?
Winter’s Formula: pCO2 = 1.5[HCO3-] + 8 +/- 2
- Indicates expected pCO2
- *KNOW THIS EQUATION
Higher pCO2 than normal, then compensation incomplete
Normal pCO2, then compensation complete
Metabolic Alkalosis
primary increase in a base (HCO3-), or decrease in acid (other than CO2)
Causes of Metabolic Alkalosis (4)
1) Over-ingestion of antacid tablets or sodium bicarbonate
2) Acid loss with vomiting (gastric acid)
3) Hypovolemia (causes reabsorption of HCO3- in kidney) → contraction alkalosis
4) Diuretics (increase loss of H+)
Compensation for metabolic alkalosis
Increase in ______ of ___ mEq/L increases PaCO2 by ____ Torr
increase in pH causing a decrease in ventilation and an increase in PCO2, RAPID
BUT brain does not allow you to hypoventilate to point of hypoxemia, so COMPENSATION OFTEN INCOMPLETE
Increase in [HCO3-] of 1 mEq/L increases PaCO2 by 0.7 Torr
Metabolic acidosis:
pH? pCO2? HCO3-?
Metabolic alkalosis:
pH? pCO2? HCO3-?
Metabolic acidosis:
decrease pH, pCO2, and HCO3-
Metabolic alkalosis:
increase pH, pCO2, and HCO3-
Respiratory acidosis: Acute: pH? pCO2? HCO3-? Chronic: pH? pCO2? HCO3-?
Respiratory alkalosis: Acute: pH? pCO2? HCO3-? Chronic: pH? pCO2? HCO3-?
Respiratory acidosis:
- Acute: decrease pH, increase pCO2, no change in HCO3-
- Chronic: decrease pH, increase pCO2, increase HCO3-
Respiratory alkalosis:
- Acute: increase pH, decrease pCO2, no change in HCO3-
- Chronic: increase pH, decrease pCO2, decrease HCO3-
Anion Gap
difference between Na+ concentration and concentration of the 2 anions
Blood is normally electrochemically neutral ([cations] = [anions])
- Cations = Na+
- Anions = Cl- and HCO3-
AG = Na+ - (Cl- + HCO3-) = 12-14 under normal circumstances
Ion gap metabolic acidosis
Increased anion gap, low pH → additional acids in blood = increased bicarbonate buffering (increased HCO3-)→ anion gap metabolic acidosis
Common causes of ion gap metabolic acidosis
MUDPILES
Methanol Uremia Diabetic ketoacidosis (also starvation and alcoholism) Propylene glycol Isoniazid Lactate Ethylene glycol Salicylates
Non-ion gap metabolic acidosis
Normal anion gap, but low pH → non-gap metabolic acidosis, caused by loss of bicarbonate
Causes of non-ion gap metabolic acidosis
Typically due to GI losses (diarrhea, with high [HCO3-]) or renal losses (fail to absorb HCO3-, or retain H+)
Can also be caused by too much IV saline
Main Respiratory Center in Brain = Medulla
Function?
- generates respiratory rhythm spontaneously without any input
- Drives respiratory motor neurons and interneurons in spinal cord → drive respiratory muscles (inspiratory and expiratory)
- Expiratory muscles only actively stimulated by medulla due to inputs under conditions of exercise or forced breathing
Carotid Peripheral Chemoreceptors location?
in carotid bodies found bilaterally at bifurcation of common carotid arteries into internal and external carotids
Function of carotid peripheral chemoreceptors
sense:
1) low arterial O2 (relatively insensitive until PaO2 less than 55 Torr)
2) high arterial PCO2 (FAST, seconds)
3) high arterial [H+] (FAST, only mediator of response to metabolic acid/base insults)
Dominant action on respiration
Aortic peripheral chemoreceptors location
aortic bodies in arch of aorta between arch and pulmonary artery
Location of central chemoreceptors
ventral surface of medulla
Central chemoreceptors function
- bind H+, but sense arterial CO2
- SLOW
- Mediate 80% of ventilatory response to high PaCO2 under long term conditions
- most important day-to-day regulator of ventilation
Why do central chemoreceptors bind H+, but sense arterial CO2?
CO2 crosses B-B barrier → dissociate into H+ and HCO3- → H+ binds chemoreceptors → stimulate breathing (increases VA)
-H+ is charged and thus cannot cross B-B barrier
Blood-Brain barrier and central chemoreceptors
- Separates brain and surrounding CSF from blood stream
- Significantly restricts diffusion of ions such as H+ between blood and CSF, while it allows free diffusion of fat-soluble substances like CO2
- Minimal buffering capacity of CSF → big change in CSF pH for given change in PCO2 → strong response to changes in blood PCO2
Which receptors type mediates an increase in ventilation?
1) Climbing mount everest
2) Ketoacidosis (metabolic acidosis)
3) Climbing stairs
4) Bronchitis
1) Climbing mount everest –> peripheral O2 receptors
2) Ketoacidosis (metabolic acidosis) –> peripheral H+ receptors
3) Climbing stairs –> peripheral CO2 receptors
4) Bronchitis –> central H+ receptors/CO2 sensors
What steps lead to the initial (but incomplete) recovery of PaO2 at altitude, the subsequent inhibition of ventilation, and the final near normal PaO2? (7 steps)
How long does this process take?
1) decrease PIO2 –> decrease PaO2
2) activation of peripheral O2 receptors –> increase ventilation –> increase PaO2
3) decrease PaCO2 –> decrease PCO2 in CSF –> decrease [H+] in CSF
4) activation of central H+ receptors to inhibit initial increase in ventilation
=RESPIRATORY ALKALOSIS (increased pH due to low CO2)
5) compensatory response in kidney to respiratory alkalosis = is to increase loss of HCO3-
6) –> decreased [HCO3-] in blood = decreased [HCO3-] in CSF –> frees up H+ in CSF
7) drive to increase ventilation and return to near normal PaO3
Takes 2-3 days
Exercise and control of respiration
- Exercise = increased metabolism and demands for O2 delivery/CO2 elimination
- Central and peripheral chemoreceptors ensure CO2 removal keeps up with production
- Increase PaCO2 → decrease pH → activate peripheral and central chemoreceptors → signal respiratory center in brain to increase ventilation (frequency AND tidal volume)
- Moderate exercise → linear relationship between O2 consumption/CO2 production and ventilation
- Intense exercise → ventilation increases more steeply due to increases in lactic acid initiating proton-mediated ventilatory stimulus
Kussmaul breathing
rapid deep breaths, trying to breathe out CO2 during metabolic acidosis
Cheyne-Stokes, what is is and what is it associated with….
an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing
CHF
Tactile fremitus
palpable vibrations when patient speaks, “99”
Tactile fremitus is decreased when?
excess air in lungs, fluid in pleural space, atelectasis due to obstructed bronchus (anything that interferes with connection of lungs to chest wall)
Tactile fremitus is increased when?
consolidation in lung (pneumonia or pulmonary edema)
Trachea pushed away?
large pleural effusion, tension pneumothorax
Trachea pulled away?
atelectasis, fibrosis, resection
Dull percussion indicative of
fluid or solid tissue replaces air-containing lung or pleural space (large pleural effusions, lobar pneumonia, areas of atelectasis)
Resonant percussion indicative of
anything that increases air in lung (pneumothorax, emphysema, large air filled bullae in lung)
Vesicular sounds
(soft, low pitched) - heard through inspiration and stop ⅓ through expiration
i.Heard throughout normal chest
Bronchovesicular sounds
(moderate pitch and intensity) - heard during inspiration → silent gap → again during expiration
i. Heard over major bronchi
ii. Can be abnormal if heard in periphery
Bronchial sounds
(high pitched) heard over trachea
i.Can be abnormal if heard in periphery
Crackles (rales)
- heard during inspiration due to disruptive airflow through small airways
i. Pulmonary edema, pneumonia, interstitial lung disease, fibrosis
Rhonchi
rumbling, continuous
i.Passage of air through partially obstructed airway by mucus or secretions
Wheezes
continuous high pitched during inspiration or expiration
i. Due to airflow through narrowed airway
ii. Diffuse → widespread narrowing (asthma)
iii. Localized → focal obstruction (bronchiolitis)
Egophony
change in timbre but not pitch or volume (“Eee → Aaa” change)
i.Occurs due to compressed fluid filled areas of lung (pneumonia)
Stridor
musical sounds audible without stethoscope on inspiration or expiration
i. Due to upper airway pathology
ii. Inspiratory → laryngeal pathology (laryngospasm, laryngeal edema, subglottic stenosis, vocal cord dysfunction)
iii. Expiratory → central airway obstruction within thorax (tumor obstructing trachea)
Friction Rub
heard during inspiration due to inflammation of pleural surfaces, harsh sounding
i.Infection, malignancy, lupus pleuritis, pulmonary infarct
PFTs address 6 aspects of respiratory system… what are they?
a. *Lung Volumes
b. *Airflow = volume/time
c. *Gas Exchange
d. Airway responsiveness
e. Respiratory muscle strength
f. Compliance of lung
Give the four volumes and what they represent
i. Tidal Volume (TV) = volume of normal, even respirations at rest
- Inspiration requires effort, expiration is passive
ii. Inspiratory Reserve Volume (IRV): max inspiration above normal tidal volume with max effort of respiratory muscles (end of TV → highest inspiration possible)
iii. Expiratory Reserve Volume (ERV): volume of gas that can be expelled at the end of a tidal breath with active work of respiratory muscles (end of TV → lowest expiration possible, RV)
iv. Residual Volume (RV): volume of gas retained in lung even after max expiration
1. Cannot be measured directly
Functional residual capacity
FRC = RV + ERV
i. Amount of gas in lung at end of a normal exhalation
ii. **Point at which respiratory system is in equilibrium
Inspiratory capacity
(IC) = TV + IRV
- Amount of gas that can be inhaled from FRC (equilibrium)
- Requires max effort of respiratory muscles
Vital capacity
VC = ERV + TV + IRV
1.Amount of gas that can be inhaled from end of max expiration (starting at RV) to max inflation
Total lung capacity
TLC = VC + Rv
Spirometry
pt inhales and exhales with great effort, measure airflow (change in volume over time)
Forced Vital capacity (FVC)
total volume gas exhaled (from TLC to RV)
a. Same as VC (which is measured slowly), but done at max effort
b. If FVC and VC differ significantly → possible dynamic collapse
FEV1
forced expiratory volume in first second
FEV1/FVC
Compares volume expelled in first second to total gas exhaled
a.Normalizes lung mechanics of pts with different lung volumes
b. Normal = 0.7-0.8 (70-80% air exhaled in first second)
- Higher the younger you are, lower when older
What is considered when classifying a spirometry test as acceptable and reproducable? (2)
Acceptable test:
a. 6 second expiratory time
b. Curve plateaus for at least 1 sec
- Reproducible test:
a. 3FEV1 maneuvers within 200 ml
Expiration phase of flow-volume loop
positive deflection
a. Rapidly reach peak expiratory rate
b. Latter ⅔ of expiration is “effort independent”
i. NOT increased by increased effort
ii. Linear decline in flow, limited by resistance in airway and elastic recoil in lungs
iii. Determined by elastic recoil of lung and airway resistance
Inspiration phase of flow-volume loop
negative deflection
-Inspiratory limb typically symmetric
2 ways to test lung volumes
- Helium dilution method
2. Plethysmography
Helium dilution method
Inhale inert gas (not readily absorbed into bloodstream) hold it for 10 seconds, and then breath out - measure what original concentration is now diluted to
a. Requires uniform diffusion of gas throughout lungs for accuracy
i. Less accurate in obstructive diseases because of air trapping → underestimates lung volume
Plethysmography
Most accurate - does not require diffusion of gas (important for patients with air trapping - emphysema, asthma)
- Uses pressure-volume relationship
Obstructive patterns of PFTs
asthma, COPD, bronchiolitis/bronchiectasis
1.Flow Volume Loops: lung volumes increase, curve shifted left
a. Airflow decreased due to increased resistance to flow
b. “Coving” of expiratory loop
c. .Functional Categories of Upper Airway Obstruction
- *FEV1/FVC: hallmark is a reduced ratio
- Lung volume INCREASED, decreased ability to exhale
a. TLC (>120%), RV (>140%), and FRC (>120%) all increased → hyperinflated
b. If just RV elevated → air trapping
Restrictive patterns in PFTs
pulmonary edema, interstitial lung disease, neuromuscular weakness, pleural disease, obesity
1.Flow Volume Loops: curve shifted right, total lung volume decreased
a. Max airflow decreased due to reduced total volume gas in lung
b. “Supranormal airflows”
- FEV1/FVC: normal or increased ratio (NOT diagnostic of restrictive lung disease)
- Lung volume (TLC or FRC) DECREASED (less than 120%)= DIAGNOSTIC
a. Can only be diagnosed by lung volume, not airflow
Diffusing capacity
DLCO (diffusion limitation of carbon monoxide)
i.Marker of adequacy of gas-exchange (occurs at alveolar-capillary interface)
How do you measure DLCO
Small, known concentration of CO → breathe in and hold it for 10 seconds → blow out and measure CO at expiration
- [CO] at expiration inversely related to amount absorbed by system
- CO diffusion only limited by SA, membrane thickness, and blood flow/Hb
DLC is corrected for:
TLC (resection of lung, chest wall or pleural diseases, e.g. obesity) and Hb in blood
Things that cause decreased DLCO (less than 80%) (5)
- Emphysema: due to destruction of alveolar surfaces
- Pulmonary fibrosis: due to increased membrane thickness
- Alveolar filling (pulmonary edema or pneumonia): reduced DLCO due to decreased SA and increased diffusion distance
- Pulmonary vascular disease: decreased pulmonary blood flow, less Hb
- Anemia
Thing that cause increased DLCO (>120%) (4)
- Polycythemia
- Interstitial edema (e.g. L sided heart failure)
- Asthma (unknown reason why)
- Alveolar hemorrhage: Increased Hb → increased DLCO
Major factors affecting DLCO (4)
1) Hemoglobin
2) Surface area (alveolar-capillary interface area)
3) Thickness of membrane
4) Diffusion gradient of gas - NOT a factor in DLCO test
Variable extrathoracic obstruction
problem in trachea, neck, or above
i. Increased pressure in trachea → push air out during expiration (no problems with expiration)
1. Problem is in inspiration when lumen is drawn in, obstruction narrows
2. Pointed up top = extrathoracic (lesion higher)
Variable intrathoracic obstruction
problem in central airway within thorax
i. Causes problem with expiration because lungs are pushing in narrowing obstruction
1. No problem with inspiration because lungs are expanding, thus expanding area of obstruction
ii. Pointed down low (lesion lower)
iii. E.g. tumor in airway
Fixed obstruction
no change with inspiration or expiration
Measuring compliance
change in volume/change in pressure
i. Catheter in esophagus measures intrathoracic pressure + measured TLC → plot graph of pressure and volume
ii. EX) Obesity shifts curve slightly down, but slope is the same
iii. EX) Asthma shifts curve slightly up, but slope is the same
Respiratory Muscle Strength:
breathe in or expire against a closed valve and measure pressure during max effort
i.Can be tests for neuropathies and myopathies
Airway responsiveness: Bronchoprovocation
Determine whether obstruction is reversible (i.e. asthma)
- Asthma = episodic reversible airflow obstruction
ii. Give bronchodilator challenge with albuterol - Obstructive pattern improves with administration of bronchodilator (B-agonist, albuterol)
- > 12% improvement of FEV1 or FVC and > 200cc increase in volume of FEV1 or FVC
iii. Methacholine Challenge (give increasing dose of bronchoconstrictor - asthma patients have low threshold for reactivity)
Physiologic dead space
work without benefit
- Increased respiratory effort to compensate for waste - work without benefit
a. Increase in work does pose a clinical problem - Does NOT alter gas-exchange, and does NOT lead to arterial gas abnormalities unless severe
Alveolar dead space
ventilation of unperfused or high V/Q alveoli
a.Severe disease conditions → decreased arterial oxygenation and CO2 removal
Minute ventilation (VE) =
Alveolar ventilation (VA) + (anatomic dead space + alveolar dead space)
How normal people maintain PaCO2
CO2 production increases (exercise)
i. Minute ventilation increases to compensate
ii. Exercise causes decreased dead space
b. Dead space increases
i. Minute ventilation increases to compensate
Shunt
blood perfusion where there is no ventilation → significant decrease in arterial oxygenation with mixing of well-ventilated and shunted blood
- Arterial hypoxemia = Low PaO2 and arterial hypercapnea = high PaCO2
- Does NOT cause increase in arterial PCO2 because tendency for rise in CO2 countered by central chemoreceptors that increase ventilation if PCO2 increases
a. PCO2 can actually be lower due to hypoxemic stimulus to ventilation
V/Q mismatch
Low PaO2, high PaCO2
Can be differentiated from shunt (another cause of low PaO2) because it will respond to administration of 100% O2 (increases PaO2)
Regional abnormalities in V/Q mismatch
Upper lobes - ventilated but relatively underperfused (V/Q=2.5)
Lower lobes - perfused but relatively underventilated (V/Q=0.6)
Normal - slightly less than ideal (V/Q=0.8)
Major causes of increased dead space
1) Increased anatomic dead space → rapid, shallow breathing (most tidal volume in conducting airways)
2) Increased alveolar dead space →
1. Acute PE
2. Changes in cardiac output (decreased CO, acute pulmonary HTN)
3) Ventilation in excess of perfusion
- Positive pressure ventilation (ventilator)
- Alveolar septal destruction (emphysema)
Minimize dead space with what kind of respirations
deep steady
Major causes of low V/Q and shunt
1) Anatomic:
1. Congenital heart problems (atrial or ventricular septal defects)
2. Pulmonary disorders (arterial-venous fistulas, pneumonia)
3. Vascular lung tumor
2) Capillary shunting
1. Acute atelectasis
2. Alveolar fluid
3. Consolidation (pneumonia)
3) Ventilation in excess of perfusion
1. Hypoventilation
2. Uneven distribution of ventilation
3. Diffusion defect
Pulse oximetry
i. Measures ratio of deoxy-Hb and oxy-Hb
1. Deoxy-Hb absorbs maximally in visible red band
2. Oxy-Hb absorbs maximally in IR band
ii. Ratio = % oxy-Hb = SpO2
1. Different from SaO2
Pulse oximetry and CO
Can be tricked by carbon monoxide (SaO2 will not)
Pulse oximetry and Met-Hb
Met-Hb can result in a low SaO2, with a stable SpO2 (brown blood)
Hypoxemia at sea level
PaO2 less than 80
Hypoxemia in Denver
PaO2 less than 65
Hypoxemia at 2124 High St. Denver, CO. 80205
Bitch, we got plenty of oxygen
Five causes of hypoxemia
- Low ambient PO2
- Hypoventilation
- V/Q mismatch
- Shunt
- Diffusion limitations
2 causes of hypoxemia that have normal A-a gradients
- Low ambient PO2
2. Hypoventilation
A-a gradients in diffusion limitations
(ARDS, RDS, ILD, etc.)
- Wide A-a
- Occurs when blood travels through the alveoli so quickly that it does not have time to equilibrate with the alveoli
- E.g. at exercise in altitude - PaO2 is so low that the red cell does not equilibrate with the alveoli, so the blood leaves with an oxygen tension lower than the alveoli
A-a gradients for V/Q mismatch and shunts
i. Wide A-a (> 10)
ii. Blood flows past poorly ventilated (low V/Q) or unventilated (shunt) alveoli
iii. Blood comes into complete equilibrium with the alveoli, but the PO2 is lower since the alveoli are poorly ventilated
iv. The more blood the encounters poorly ventilated alveoli the farther the arterial blood is from the “idea” and the wider the A-a gradient is
