Basic Science: Pulmonology

What receptor mediates bronchodilation, and which ANS branch?

β2 receptors; sympathetic

What receptor mediates bronchoconstriction, and which ANS branch?

M3 muscarinic receptors; parasympathetic

What three variables in Fick's law affect diffusion rate?

Surface area (↑=faster), pressure gradient (↑=faster), membrane thickness (↑=slower)

What defines dead space?

Alveoli that are ventilated but NOT perfused

What defines shunt?

Alveoli that are perfused but NOT ventilated

What is the "empty truck" analogy for dead space?

Air (truck) reaches the alveolus but no blood is there to exchange with — the "delivery" comes back empty (unchanged)

What is the "flooded road" analogy for shunt?

Blood (workers) shows up ready to work, but the "road" (airway) into the alveolus is blocked/flooded (mucus plug, atelectasis, pneumonia/edema) — nothing to pick up

What effect does dead space have on the PaCO2-PECO2 gradient, and why?

Widens it — "clean" CO2-free dead-space air dilutes the measured exhaled (PECO2) CO2 down compared to true arterial PaCO2

Does shunt hypoxemia correct with 100% supplemental O2?

No — the problem is blood never reaching a ventilated alveolus, so more O2 in the air doesn't help

What is anatomical dead space?

Conducting airways (trachea, bronchi) with no alveoli — no gas exchange possible there, ever

What is alveolar dead space?

Ventilated alveoli with little/no blood flow (perfusion) reaching them

What classically increases alveolar dead space pathologically?

Pulmonary embolism (blocks perfusion to normally-ventilated alveoli)

Is a baseline amount of dead space normal in healthy people?

Yes — both anatomical and some alveolar dead space (e.g., zone 1/lung apex) exist normally

What volume is left in the lungs after MAXIMAL forced exhalation, and can it be measured by spirometry?

Residual Volume (RV); CANNOT be measured (air never leaves the body)

What volume is left in the lungs after a NORMAL relaxed exhalation?

Functional Residual Capacity (FRC)

What is the formula for FRC?

FRC = ERV + RV

What is the formula for TLC?

TLC = VC + RV

Why can't FRC or TLC be measured directly by spirometry?

Both formulas contain RV, which spirometry can never capture

Which lung volumes/capacities CAN be measured by spirometry?

TV, IRV, ERV, VC

What is the difference between FRC and RV?

FRC = volume after a normal relaxed exhale (contains ERV you could still push out + RV); RV = volume after MAXIMAL forced exhale (truly unexhalable air only)

What does FVC stand for and measure?

Forced Vital Capacity — total air forcefully exhaled after maximal inhalation

What does FEV1 stand for and measure?

Forced Expiratory Volume in 1 second — how much of that air came out in the first second

In obstructive disease (asthma/COPD), what happens to FVC, FEV1, and the ratio?

FVC normal or mildly ↓; FEV1 ↓↓; ratio ↓ (<70%)

In restrictive disease (fibrosis), what happens to FVC, FEV1, and the ratio?

FVC ↓↓; FEV1 ↓; ratio normal or ↑

What is the straw/bottle analogy for obstructive vs. restrictive disease?

Obstructive = normal bottle, narrow straw (all the air eventually gets out, just slowly — FEV1 tanks, FVC stays near normal). Restrictive = smaller bottle, normal straw (less total air, but comes out at a normal rate — ratio stays normal)

Why does FVC stay closer to normal in obstructive disease despite airway narrowing?

FVC has no time limit — given enough time, most trapped air eventually escapes through the narrow airway

Why is FEV1 low in BOTH obstructive and restrictive disease, for different reasons?

Obstructive: narrowed airways slow the RATE of airflow in that first second. Restrictive: total available VOLUME is smaller, so naturally less comes out in 1 second too

What is the formula for minute ventilation (VE)?

VE = Tidal Volume × Respiratory Rate

What is the formula for alveolar ventilation (VA)?

VA = (Tidal Volume − Dead Space) × Respiratory Rate

What's the key functional difference between minute and alveolar ventilation?

Minute ventilation = ALL air moved (crude, includes wasted dead space air); Alveolar ventilation = only air reaching functional alveoli (what actually determines gas exchange/PaCO2)

What is minute ventilation clinically useful for?

Tracking overall breathing effort/pattern, setting ventilator targets, spotting hyper/hypoventilation patterns

What equation relates PaCO2 to metabolism and ventilation?

PaCO2 ∝ VCO2 / VA

If VCO2 is constant and VA increases, what happens to PaCO2?

PaCO2 decreases

If VA is constant and VCO2 increases (e.g., fever, exercise), what happens to PaCO2?

PaCO2 increases

What is the only physiologic lever to bring an elevated PaCO2 back to normal?

Increase alveolar ventilation (VCO2/metabolic rate isn't directly controllable in the moment)

Does ↑PaCO2 cause acidosis or alkalosis, and via what reaction?

Acidosis (respiratory); CO2+H2O→H2CO3→H+ +HCO3−

Does ↓PaCO2 (e.g., from hyperventilation) cause acidosis or alkalosis?

Alkalosis (respiratory) — e.g., seen at high altitude

What does the alveolar gas equation calculate — PAO2 or PaO2?

PAO2 (alveolar O2, calculated) — NOT PaO2 (arterial O2, measured via ABG)

What is the alveolar gas equation?

PAO2 = PIO2 − PaCO2/R

What does the A-a gradient compare, and how is it calculated?

Compares calculated "should be" alveolar O2 to actual measured arterial O2; A-a gradient = PAO2 − PaO2

What does a NORMAL A-a gradient with low PaO2 suggest?

Problem upstream of the alveolus — hypoventilation or high altitude (nothing wrong with the lung/membrane itself)

What does a WIDENED A-a gradient with low PaO2 suggest?

Problem AT or beyond the alveolar membrane — diffusion defect, V/Q mismatch, OR shunt

Does shunt always widen the A-a gradient? Does a widened gradient always mean shunt?

Shunt always widens it; but a widened gradient could ALSO be diffusion defect or V/Q mismatch (not always shunt)

What is the primary inspiratory muscle, and its nerve supply?

Diaphragm; phrenic nerve (C3-C5) — "C3,4,5 keep the diaphragm alive"

Is the vagus nerve responsible for accessory muscle innervation?

No — vagus mainly handles autonomic functions (e.g., bronchoconstriction, HR); accessory muscles have their own separate spinal/CN XI supply

What cell produces surfactant?

Type II pneumocytes

What does surfactant do, and why does it matter more for small alveoli?

Reduces alveolar surface tension, preventing collapse — smaller alveoli have higher surface tension and would collapse into larger ones without it

What is the soap bubble analogy for surfactant?

Surfactant acts like dish soap — lowers surface tension so bubbles of all sizes (alveoli) stay open, rather than small ones collapsing/being swallowed by larger ones

What condition results from insufficient surfactant in premature infants, and why?

NRDS (Neonatal Respiratory Distress Syndrome) — immature type II pneumocytes haven't developed enough to produce adequate surfactant yet

Who receives antenatal dexamethasone to prevent NRDS — the mother or the baby?

The MOTHER (crosses placenta, accelerates fetal type II pneumocyte maturation before birth)

What creates the normal negative intrapleural pressure?

Two opposing elastic forces: lung's tendency to collapse inward vs. chest wall's tendency to spring outward

At FRC, how do lung and chest wall recoil forces relate?

They are exactly balanced (equilibrium/resting point)

Above FRC (e.g., during inhalation), which direction do BOTH the lung and chest wall pull?

Both pull inward (chest wall has been stretched past its own resting point)

Below FRC (e.g., forced exhale), do the lung and chest wall pull in the same or opposite directions?

Opposite directions again — chest wall wants to spring back out, lung still wants to collapse further in

What happens to lung volume when a pneumothorax breaks the negative pressure seal, and why?

Lung collapses inward — loses the chest wall's outward pull that was holding it open; unopposed elastic recoil takes over

What happens to compliance and FRC in emphysema, and why (2 separate mechanisms)?

↑Compliance (floppy) and ↑FRC (air trapping) — destroyed elastic tissue causes BOTH loss of recoil (↑compliance) AND loss of alveolar surface area (separate diffusion effect)

What happens to compliance and FRC in pulmonary fibrosis?

↓Compliance (stiff) and ↓FRC — scarred tissue resists stretching, reducing usable lung volume

Are membrane thickening (diffusion problem) and reduced compliance/volume (mechanical problem) in fibrosis the same mechanism or separate ones?

Separate — thickening affects diffusion (Fick's law); stiffness affects volume/compliance. Not cause-and-effect of each other

What law governs airway resistance, and what's the key relationship?

Poiseuille's law — resistance ∝ 1/radius⁴ (small radius change = huge resistance change, "16-fold")

What is transmural pressure, and what must it stay to keep an airway open?

Pressure inside the airway minus pressure outside (intrapleural); must stay POSITIVE

How does diaphragm contraction help keep airways open?

Chest expands → ↓intrapleural pressure → ↑transmural pressure → airway pulled open (radial traction)

Why do airways collapse during forced expiration in COPD?

Intrapleural pressure spikes very positive + loss of elastic tissue/radial traction → transmural pressure goes negative → airway collapses

What are the approximate PO2/PCO2 values in dry inhaled (room) air?

PO2 ~160, PCO2 ~0

What are the approximate PO2/PCO2 values in alveolar air?

PO2 ~100, PCO2 ~40

What are the approximate PO2/PCO2 values in mixed venous blood?

PO2 ~40, PCO2 ~46

What are the approximate PO2/PCO2 values in pulmonary capillary (post-exchange/arterial) blood?

PO2 ~100, PCO2 ~40

Why does mixed venous blood have lower PO2 and higher PCO2 than arterial blood?

Tissues consume O2 and produce CO2 during metabolism as blood passes through

Is "mixed venous blood" a normal term or a pathologic one?

Normal — just venous blood from all body tissues blended together before returning to lungs (NOT the same as pathologic "venous admixture" from a shunt)

What effect does emphysema have on diffusing capacity (DL), and why?

↓DL — loss of alveolar surface area (Fick's law)

What effect does pulmonary fibrosis have on DL, and why?

↓DL — increased membrane thickness increases diffusion distance

What effect does pulmonary edema have on DL, and why?

↓DL — fluid increases the diffusion distance gas must travel (same "thickness" variable as fibrosis, different cause)

What defines a perfusion-limited gas, and give examples

Gas fully equilibrates EARLY in capillary transit; O2 (normally), CO2, N2O

How do you increase gas transfer for a perfusion-limited gas?

Increase blood flow (more unequilibrated blood delivered per minute)

What defines a diffusion-limited gas, and give examples

Gas never fully equilibrates across the capillary, limited by the membrane; CO (always), O2 (in fibrosis/emphysema/heavy exercise)

Why is CO diffusion-limited even in a healthy lung?

Extremely high Hgb affinity (~200×) keeps free CO plasma concentration low, maintaining a gradient that never flattens across the capillary — used clinically to measure DLCO

What is the "water balloon spigot" analogy for perfusion vs. diffusion limited gases?

Perfusion-limited = fast spigot, thin balloons fill instantly (need MORE balloons/blood flow to move more gas). Diffusion-limited = slow trickling spigot (thick membrane) — balloon never fully fills no matter how long it waits

At high altitude, what is the direct effect of ↓barometric pressure?

↓PIO2 → ↓PAO2 and ↓PaO2 together, with a NORMAL A-a gradient

What ventilatory response occurs at high altitude, and what secondary effect does it have?

Hyperventilation (via peripheral chemoreceptors) → also blows off CO2 → respiratory alkalosis

What are the long-term compensations for chronic high altitude exposure?

↓Renal HCO3 excretion (buffers alkalosis), ↑2,3-DPG, ↑EPO/RBC production (secondary polycythemia)

What is the O2 content equation?

O2 content = (1.34 × Hgb × SaO2) + (0.003 × PaO2)

How does CO reduce O2-carrying capacity (2 separate mechanisms)?

1) Occupies Hgb binding sites (~200× O2 affinity) 2) Shifts curve LEFT — remaining O2 bound to same Hgb molecule won't unload at tissue either

Why is PaO2 normal in CO poisoning despite severe hypoxia?

PaO2 measures dissolved O2 in plasma only (unaffected by CO); the problem is O2 BOUND to hemoglobin (SaO2/content), which PaO2 doesn't capture — classic diagnostic trap

What is the "parking garage" analogy for CO poisoning?

CO cars take open spots (and some contested ones) AND cause remaining O2 cars to grip their spots tighter (left shift) — garage looks fine from outside (normal PaO2) but almost nothing is being delivered (low SaO2/content)

What percentage of CO2 is transported dissolved, bound to Hgb, and as bicarbonate?

~7% dissolved, ~23% carbaminohemoglobin, ~70% bicarbonate (predominant)

What enzyme catalyzes bicarbonate formation from CO2?

Carbonic anhydrase

What is the Bohr effect?

↑CO2/↓pH at tissue shifts the O2 dissociation curve RIGHT, promoting O2 unloading where it's needed

What is the Haldane effect?

Deoxygenated Hgb has higher affinity for CO2/H+ — as Hgb releases O2 at tissue, it picks up more CO2 for the return trip to lungs

Is the Haldane effect a baseline/constant process, or only a compensation mechanism?

Baseline — happens continuously with every pass through tissue, in everyone, not just during compensation

What is the "delivery van" analogy for Bohr/Haldane effects?

Hgb drops off O2 cargo (Haldane) → empty space available → picks up CO2 as return cargo. Bohr effect = the trigger: busy/acidic tissue "waves the van down" to unload there

How does the pulmonary vasculature respond to local alveolar hypoxia, and why (compare to systemic circulation)?

VASOCONSTRICTS (opposite of systemic circulation, which vasodilates) — redirects blood away from poorly-ventilated areas toward well-ventilated ones, avoiding wasted perfusion

What is the "restaurant staffing" analogy for hypoxic pulmonary vasoconstriction?

Send waiters (blood) to busy, well-stocked tables (well-ventilated alveoli), not empty ones

Does hypoxic pulmonary vasoconstriction resolve once the underlying cause resolves?

Yes — it's a dynamic, ongoing response tracking local conditions in real time

What pressure relationship defines Zone 1 (apex), and what V/Q results?

PA > Pa > Pv; HIGH V/Q (dead-space-like) — alveolar pressure compresses vessels, reducing perfusion relative to ventilation

What pressure relationship defines Zone 2 (mid-lung), and what V/Q results?

Pa > PA > Pv; balanced/intermediate V/Q — flow governed by the arterial-alveolar pressure gap ("vascular waterfall")

What pressure relationship defines Zone 3 (base), and what V/Q results?

Pa > Pv > PA; LOW V/Q (shunt-like) — gravity favors blood flow, vessels stay open easily

Why is a LOW V/Q mismatch more clinically dangerous than a HIGH V/Q mismatch for hypoxemia?

Low V/Q sends underoxygenated blood back into circulation, diluting overall blood O2 content. High V/Q wastes ventilation, but blood from other regions is still fully oxygenated

What effect does a right-to-left shunt have on PaO2, and does it correct with 100% O2?

↓PaO2 (deoxygenated blood bypasses the lungs entirely); does NOT correct with 100% O2

What effect does a left-to-right shunt have on PaO2, and what's the long-term risk?

Doesn't directly cause hypoxemia; chronic volume overload on pulmonary circulation → risk of pulmonary hypertension over time

Where are central chemoreceptors located, and what do they primarily sense?

Medulla; ↑H+ in CSF (from CO2 crossing the BBB) — the MAIN driver of normal ventilation

Where are peripheral chemoreceptors located, and what do they primarily sense?

Carotid and aortic bodies; ↓PaO2 (only responds once quite low, <60 mmHg)