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“There’s so much pollution in the air now that if it weren’t for our lungs, ``Embryology 642
there’d be no place to put it all.”
—Robert Orben ``Anatomy 644

“Freedom is the oxygen of the soul.” ``Physiology 646

—Moshe Dayan
``Pathology 653
“Whenever I feel blue, I start breathing again.”
—L. Frank Baum ``Pharmacology 667
“Life is not the amount of breaths you take; it’s the moments that take
your breath away.”
—Will Smith, Hitch

Group key respiratory, cardiovascular, and renal concepts together

for study whenever possible. Know obstructive vs restrictive lung
disorders, V̇/Q̇ mismatch, lung volumes, mechanics of respiration, and
hemoglobin physiology. Lung cancers and other causes of lung masses
are high yield. Be comfortable reading basic chest X-rays, CT scans, and


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642 SEC TION III Respiratory   


Lung development Occurs in five stages. Initial development includes development of lung bud from distal end of
respiratory diverticulum during week 4. Every Pulmonologist Can See Alveoli.

Embryonic Lung bud Ž trachea Ž bronchial buds Errors at this stage can lead to
(weeks 4–7) Ž mainstem bronchi Ž secondary (lobar) tracheoesophageal fistula.
bronchi Ž tertiary (segmental) bronchi.
Pseudoglandular Endodermal tubules Ž terminal bronchioles. Respiration impossible, incompatible with life.
(weeks 5–17) Surrounded by modest capillary network.
Canalicular Terminal bronchioles Ž respiratory bronchioles Airways increase in diameter.
(weeks 16–25) Ž alveolar ducts. Surrounded by prominent Respiration capable at 25 weeks.
capillary network. Pneumocytes develop starting at 20 weeks.
Saccular Alveolar ducts Ž terminal sacs. Terminal sacs
(week 26–birth) separated by 1° septae.
Alveolar Terminal sacs Ž adult alveoli (due to 2° At birth: 20–70 million alveoli.
(week 36–8 years) septation). By 8 years: 300–400 million alveoli.
In utero, “breathing” occurs via aspiration
and expulsion of amniotic fluid Ž  vascular
resistance through gestation.
At birth, fluid gets replaced with air Ž  in
pulmonary vascular resistance.
Embryonic Fetal Postnatal
period period period
Canalicular BIRTH
Embryonic Surfactant

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 2 4 6 8
Weeks Years

Congenital lung malformations

Pulmonary hypoplasia Poorly developed bronchial tree with abnormal histology. Associated with congenital diaphragmatic
hernia (usually left-sided), bilateral renal agenesis (Potter sequence).
Bronchogenic cysts Caused by abnormal budding of the foregut and dilation of terminal or large bronchi. Discrete,
round, sharply defined, fluid-filled densities on CXR (air-filled if infected). Generally
asymptomatic but can drain poorly, causing airway compression and/or recurrent respiratory

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Respiratory   

Club cells Nonciliated; low columnar/cuboidal with secretory granules. Located in bronchioles. Degrade
toxins; secrete component of surfactant; act as reserve cells.

Alveolar cell types

Type I pneumocytes 97% of alveolar surfaces. Line the alveoli. 2 (surface tension)
Collapsing pressure (P) =
Squamous; thin for optimal gas diffusion. radius
Type II pneumocytes Secrete surfactant from lamellar bodies Alveoli have  tendency to collapse on expiration
(arrow in A ) Ž  alveolar surface tension, as radius  (law of Laplace).
prevents alveolar collapse,  lung recoil, and Pulmonary surfactant is a complex mix of
 compliance. Cuboidal and clustered B . Also lecithins, the most important of which is
serve as precursors to type I cells and other dipalmitoylphosphatidylcholine (DPPC).
type II cells. Proliferate during lung damage. Surfactant synthesis begins around week 20 of
gestation, but mature levels are not achieved
until around week 35.
Corticosteroids important for fetus surfactant
Type II pneumocyte production and lung development.

Type I

Alveolar macrophages Phagocytose foreign materials; release cytokines

and alveolar proteases. Hemosiderin-laden
macrophages may be seen in pulmonary

Neonatal respiratory Surfactant deficiency Ž  surface tension Screening tests for fetal lung maturity: lecithin-
distress syndrome Ž alveolar collapse (“ground-glass” appearance sphingomyelin (L/S) ratio in amniotic fluid
A of lung fields) A . (≥ 2 is healthy; < 1.5 predictive of NRDS), foam
Risk factors: prematurity, maternal diabetes (due stability index, surfactant-albumin ratio.
to  fetal insulin), C-section delivery ( release Persistently low O2 tension Ž risk of PDA.
of fetal glucocorticoids; less stressful than 3
vaginal delivery). Mature
Concentration (mg %)

Complications: PDA, necrotizing enterocolitis. 15


Treatment: maternal steroids before birth;


L/S ratio

10 Transitional
exogenous surfactant for infant.
tio Sph 1
Therapeutic supplemental O2 can result in 5 L/S ra ingo
lin Immature
Retinopathy of prematurity, Intraventricular
hemorrhage, Bronchopulmonary dysplasia 20 26 30 35 40
(RIB). Gestational age (wk)

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644 SEC TION III Respiratory   


Respiratory tree
Conducting zone Large airways consist of nose, pharynx, larynx, trachea, and bronchi. Small airways consist of
bronchioles that further divide into terminal bronchioles (large numbers in parallel Ž least airway
Warms, humidifies, and filters air but does not participate in gas exchange Ž “anatomic dead
Cartilage and goblet cells extend to the end of bronchi.
Pseudostratified ciliated columnar cells primarily make up epithelium of bronchus and extend to
beginning of terminal bronchioles, then transition to cuboidal cells. Clear mucus and debris from
lungs (mucociliary escalator).
Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond this point).
Respiratory zone Lung parenchyma; consists of respiratory bronchioles, alveolar ducts, and alveoli. Participates in gas
Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli. Cilia
terminate in respiratory bronchioles. Alveolar macrophages clear debris and participate in
immune response.

Conducting zone

Goblet cell Basal cell Ciliated cell
ciliated columnar

Smooth muscle


Club cell Ciliated cell

Simple ciliated
columnar epithelium
Smooth muscle

ciliated cells Club cell
Simple cuboidal epithelium
Smooth muscle

Respiratory zone
cells Club cell Squamous cell
bronchioles Simple cuboidal and
squamous epithelium
Smooth muscle

Type I pneumocyte
Type II pneumocyte
Alveolar sacs
Alveolar macrophage

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Respiratory   

Lung anatomy Right lung has 3 lobes; Left has Less Lobes (2) and Lingula (homolog of right middle lobe). Instead
of a middle lobe, left lung has a space occupied by the heart A .
Trachea Upper lobe
Relation of the pulmonary artery to the bronchus at each lung hilum is described by RALS—Right
Anterior; Left Superior. Carina is posterior to ascending aorta and anteromedial to descending
fissure Oblique fissure
aorta B .
Right lung is a more common site for inhaled foreign bodies because right main stem bronchus is
wider, more vertical,
Middle lobe and shorter than the left. If you aspirate a peanut:
ƒƒ While supine—usually enters right lower Lowerlobe. Lower
ƒƒ While Inferior
lying lobe
on right side—usually enters loberight upper lobe. lobe

Right Left
ƒƒ While upright—usually R enters right
L lower lobe. L R
bronchus bronchus Anterior view Posterior view

Anterior view Posterior view

Clavicle Midclavicular line C7

1 T1
Needle positioning 4
Horizontal fissure 2 for tension pneumothorax Horizontal
Oblique 5 T5
ICS2 LUL fissure fissure
3 6
4 7
ICS4 Oblique fissure 8
Oblique fissure 5
T8 Oblique fissure

7 11
Pleura Lingula 8
9 12
10 L1
ICS = intercostal space





Diaphragm structures Structures perforating diaphragm: Number of letters = T level:

Inferior vena Central tendon ƒƒ At T8: IVC, right phrenic nerve T8: vena cava
cava (T8) Esophagus ƒƒ At T10: esophagus, vagus (CN 10; 2 trunks) T10: “oesophagus”
ƒƒ At T12: aorta (red), thoracic duct (white), T12: aortic hiatus
azygos vein (blue) (“At T-1-2 it’s the red, I (IVC) ate (8) ten (10) eggs (esophagus) at
white, and blue”) (aorta) twelve (12).
Diaphragm is innervated by C3, 4, and 5
Rib C3, 4, 5 keeps the diaphragm alive.
Aorta (phrenic nerve). Pain from diaphragm
Other bifurcations:
(T12) irritation (eg, air, blood, or pus in peritoneal
Vertebra ƒƒ The common carotid bifourcates at C4.
Inferior view cavity) can be referred to shoulder (C5) and
ƒƒ The trachea bifourcates at T4.
trapezius ridge (C3, 4).
ƒƒ The abdominal aorta bifourcates at L4.

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646 SEC TION III Respiratory   


Lung volumes Note: a capacity is a sum of ≥ 2 physiologic volumes.

Inspiratory reserve Air that can still be breathed in after normal Lung volumes (LITER) Lung capacities
volume inspiration
Tidal volume Air that moves into lung with each quiet
IRV Volume
inspiration, typically 500 mL (L) IC VC TLC
Expiratory reserve Air that can still be breathed out after normal
volume expiration TV
Residual volume Air in lung after maximal expiration; RV and ERV
any lung capacity that includes RV cannot be
1.2 FRC
measured by spirometry
Inspiratory capacity IRV + TV
Air that can be breathed in after normal
Functional residual RV + ERV
capacity Volume of gas in lungs after normal expiration
Vital capacity TV + IRV + ERV
Maximum volume of gas that can be expired
after a maximal inspiration
Total lung capacity IRV + TV + ERV + RV
Volume of gas present in lungs after a maximal

Determination of Paco2 – Peco2 Taco, Paco, Peco, Paco (refers to order of

VD = VT ×
physiologic dead Paco2 variables in equation)
space VD = physiologic dead space = anatomic dead Physiologic dead space—approximately
space of conducting airways plus alveolar equivalent to anatomic dead space in normal
dead space; apex of healthy lung is largest lungs. May be greater than anatomic dead
contributor of alveolar dead space. Volume space in lung diseases with V̇/Q̇ defects.
of inspired air that does not take part in gas
V T = tidal volume.
Paco2 = arterial Pco2.
Peco2 = expired air Pco2.

Minute ventilation Total volume of gas entering lungs per minute Normal values:
V E = V T × RR Respiratory rate (RR) = 12–20 breaths/min
Alveolar ventilation Volume of gas that reaches alveoli each minute V T = 500 mL/breath
VA = (V T − VD) × RR VD = 150 mL/breath

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Respiratory   

Lung and chest wall Elastic recoil—tendency for lungs to collapse Chest wall
inward and chest wall to spring outward. 6 TLC

At FRC, inward pull of lung is balanced by

outward pull of chest wall, and system pressure wall system
is atmospheric. 4

Volume (L)
At FRC, airway and alveolar pressures equal
atmospheric pressure (called zero), and FRC
intrapleural pressure is negative (prevents 2
atelectasis). The inward pull of the lung is Lung
balanced by the outward pull of the chest wall.
System pressure is atmospheric. PVR is at a 0
−20 −10 0 10 20 30 40
minimum. Transpulmonary static pressure (cmH2O)
Compliance—change in lung volume for a
change in pressure; expressed as ΔV/ΔP and is Compliant lungs comply (cooperate) and fill
inversely proportional to wall stiffness. High easily with air.
compliance = lung easier to fill (emphysema,
normal aging), lower compliance = lung
harder to fill (pulmonary fibrosis, pneumonia,
NRDS, pulmonary edema). Surfactant
increases compliance.
Hysteresis—lung inflation curve follows a
different curve than the lung deflation curve
due to need to overcome surface tension forces
in inflation.

Respiratory system  lung compliance (loss of elastic recoil)

changes in the elderly  chest wall compliance ( chest wall stiffness)
 RV
 FVC and FEV1
Normal TLC
 ventilation/perfusion mismatch
 A-a gradient
 respiratory muscle strength

Hemoglobin Hemoglobin (Hb) is composed of 4 polypeptide Fetal Hb (2α and 2γ subunits) has a higher
subunits (2 α and 2 β) and exists in 2 forms: affinity for O2 than adult Hb, driving diffusion
β2 β1
ƒƒ Deoxygenated form has low affinity for O2, of oxygen across the placenta from mother to
thus promoting release/unloading of O2. fetus.  O2 affinity results from  affinity of
ƒƒ Oxygenated form has high affinity for O2 HbF for 2,3-BPG.
(300×). Hb exhibits positive cooperativity Hemoglobin acts as buffer for H+ ions.
and negative allostery. Myoglobin is composed of a single polypeptide
α2 α1  Cl−, H+, CO2, 2,3-BPG, and temperature chain associated with one heme moiety.
favor deoxygenated form over oxygenated Higher affinity for oxygen than Hb.
form (shifts dissociation curve right Ž  O2

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648 SEC TION III Respiratory   

Hemoglobin Lead to tissue hypoxia from  O2 saturation and  O2 content.

Methemoglobin Oxidized form of Hb (ferric, Fe3+), does not Nitrites (eg, from dietary intake or polluted/high
bind O2 as readily as Fe2+, but has  affinity for altitude water sources) and benzocaine cause
cyanide. Fe2+ binds O2. poisoning by oxidizing Fe2+ to Fe3+.
Iron in Hb is normally in a reduced state
(ferrous, Fe2+; “just the 2 of us”).
Methemoglobinemia may present with cyanosis
and chocolate-colored blood.
Methemoglobinemia can be treated with
methylene blue and vitamin C.
Carboxyhemoglobin Form of Hb bound to CO in place of O2. 20

Causes  oxygen-binding capacity with left Normal (100% Hb)

shift in oxygen-hemoglobin dissociation curve. 16

O2 bound to Hb (mL O2 /100 mL)

 O2 unloading in tissues.
CO binds competitively to Hb and with 200× 12
50% CO Hb
greater affinity than O2.
CO poisoning can present with headaches, 8
50% Hb (anemia)
dizziness, and cherry red skin. May be caused
by fires, car exhaust, or gas heaters. Treat with 4

100% O2 and hyperbaric O2.

0 20 40 60 80 100
PO2 (mm Hg)

Cyanide poisoning Usually due to inhalation injury (eg, fires). Inhibits aerobic metabolism via complex IV
inhibition Ž hypoxia unresponsive to supplemental O2 and  anaerobic metabolism. Findings:
almond breath odor, pink skin, cyanosis. Rapidly fatal if untreated. Treat with induced
methemoglobinemia: first give nitrites (oxidize hemoglobin to methemoglobin, which can trap
cyanide as cyanmethemoglobin), then thiosulfates (convert cyanide to thiocyanate, which is
renally excreted).

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Respiratory   

Oxygen-hemoglobin Sigmoidal shape due to positive cooperativity Blood returning

from tissues
Oxygenated blood
leaving the lungs
dissociation curve (ie, tetrameric Hb molecule can bind 4 O2
molecules and has higher affinity for each Hemoglobin

subsequent O2 molecule bound). Myoglobin 90 lob

is monomeric and thus does not show 80

positive cooperativity; curve lacks sigmoidal 70

Left Right
appearance. 60 (↓ P50) (↑ P50)

Hb saturation (%)
Shifting the curve to the right Ž  Hb affinity 50 P50
for O2 (facilitates unloading of O2 to tissue)
Ž  P50 (higher Po2 required to maintain 50%
Shifting the curve to the left Ž  O2 unloading 20

Ž renal hypoxia Ž  EPO synthesis 10

Venous blood Arterial blood
Ž compensatory erythrocytosis. 0
0 10 20 30 40 50 60 70 80 90 100
Fetal Hb has higher affinity for O2 than adult PO2 (mm Hg)

Hb (due to low affinity for 2,3-BPG), so its Left shift Right shift
( O₂ unloading to tissue) ( O₂ unloading to tissues)
dissociation curve is shifted left. Left = Lower Right shift – ACE Bats right handed
H+ ( pH, base) H+ ( pH, Acid)
2,3–BPG 2,3–BPG
High Altitude
Temperature Temperature

Oxygen content of O2 content = (1.34 × Hb × Sao2) + (0.003 × Pao2)

blood Hb = hemoglobin level
Sao2 = arterial O2 saturation
Pao2 = partial pressure of O2 in arterial blood
Normally 1 g Hb can bind 1.34 mL O2; normal Hb amount in blood is 15 g/dL.
O2 binding capacity ≈ 20.1 mL O2/dL of blood.
With  Hb there is  O2 content of arterial blood, but no change in O2 saturation and Pao2.
O2 delivery to tissues = cardiac output × O2 content of blood.


CO poisoning Normal  (CO competes Normal 
with O2)
Anemia  Normal Normal 
Polycythemia  Normal Normal 

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650 SEC TION III Respiratory   

Pulmonary circulation Normally a low-resistance, high-compliance A consequence of pulmonary hypertension is cor

system. Po2 and Pco2 exert opposite effects pulmonale and subsequent right ventricular
on pulmonary and systemic circulation. A failure.
 in Pao2 causes a hypoxic vasoconstriction P – P2
Diffusion: V̇ gas = A × Dk × 1 where
that shifts blood away from poorly ventilated T
regions of lung to well-ventilated regions of A = area, T = alveolar wall thickness,
lung. Dk = diffusion coefficient of gas, P1 – P2 =
Perfusion limited—O2 (normal health), CO2, difference in partial pressures.
N2O. Gas equilibrates early along the length ƒƒ A  in emphysema.
of the capillary. Diffusion can be  only if ƒƒ T  in pulmonary fibrosis.
blood flow .
DLCO is the extent to which CO, a surrogate for
Diffusion limited—O2 (emphysema, fibrosis,
O2, passes from air sacs of lungs into blood.
exercise), CO. Gas does not equilibrate by the
time blood reaches the end of the capillary.

Perfusion limited

Partial pressure
Fibrosis (diffusion limited)

Perfusion limited


Diffusion limited
Length along pulmonary capillary

Pa = partial pressure of gas in pulmonary capillary blood

PA = partial pressure of gas in alveolar air

Pulmonary vascular Ppulm artery – PL atrium Ppulm artery = pressure in pulmonary artery
resistance PVR = PL atrium ≈ pulmonary capillary wedge pressure
        cardiac output
Q = cardiac output (flow)
R = resistance
Remember: ΔP = Q × R, so R = ΔP / Q η = viscosity of blood
R = 8ηl / πr4 l = vessel length
r = vessel radius

Alveolar gas equation Pao2 = PIo2 – Pao2 = alveolar Po2 (mm Hg)
PIo2 = Po2 in inspired air (mm Hg)
Paco2 Paco2 = arterial Pco2 (mm Hg)
≈ 150 mm Hga –
0.8 R = respiratory quotient = CO2 produced/O2
a At consumed
sea level breathing room air
A-a gradient = Pao2 – Pao2. Normal range =
10–15 mm Hg
 A-a gradient may occur in hypoxemia; causes
include shunting, V̇/Q̇ mismatch, fibrosis
(impairs diffusion)

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Respiratory   

Oxygen deprivation
Hypoxia ( O2 delivery to tissue) Hypoxemia ( Pao2) Ischemia (loss of blood flow)
 cardiac output Normal A-a gradient Impeded arterial flow
Hypoxemia ƒƒ High altitude  venous drainage
Anemia ƒƒ Hypoventilation (eg, opioid use)
CO poisoning  A-a gradient
ƒƒ V̇/Q̇ mismatch
ƒƒ Diffusion limitation (eg, fibrosis)
ƒƒ Right-to-left shunt

Ventilation/perfusion Ideally, ventilation is matched to perfusion (ie,

mismatch V̇/Q̇ = 1) for adequate gas exchange.
Lung zones:
Zone 1 V . .
 V/Q
ƒƒ V̇/Q̇ at apex of lung = 3 (wasted ventilation) PA ≥ Pa > Pv Q
ƒƒ V̇/Q̇ at base of lung = 0.6 (wasted perfusion)
Both ventilation and perfusion are greater at the
base of the lung than at the apex of the lung. PA Zone 2
Pa Pv
With exercise ( cardiac output), there is Pa > PA > Pv

vasodilation of apical capillaries Ž V̇/Q̇ ratio

approaches 1.
Certain organisms that thrive in high O2 (eg, PA
TB) flourish in the apex. Pa Pv Zone 3 V . .
 V/Q
Pa > Pv > PA Q
V̇/Q̇ = 0 = “oirway” obstruction (shunt). In
shunt, 100% O2 does not improve Pao2 (eg,
foreign body aspiration).
V̇/Q̇ = ∞ = blood flow obstruction (physiologic
dead space). Assuming < 100% dead space,
100% O2 improves Pao2 (eg, pulmonary

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652 SEC TION III Respiratory   

Carbon dioxide CO2 is transported from tissues to lungs in 3 In lungs, oxygenation of Hb promotes
transport forms: dissociation of H+ from Hb. This shifts

1  HCO (70%). equilibrium toward CO2 formation; therefore,
2   Carbaminohemoglobin or HbCO2 CO2 is released from RBCs (Haldane effect).
(21–25%). CO2 bound to Hb at N-terminus In peripheral tissue,  H+ from tissue
of globin (not heme). CO2 favors metabolism shifts curve to right, unloading O2
deoxygenated form (O2 unloaded). (Bohr effect).
3  Dissolved CO2 (5–9%). Majority of blood CO2 is carried as HCO3− in
the plasma.
Cl– HCO3– 1
Tissue Plasma RBC
Capillary wa

CO2 enters RBC and

is converted to HCO3–
CO2 anhydrase
CO2 + H2O H2CO3 H+ + HCO3–

HHb H+ + Hb–

CO2 + Hb HbCO2 2

Dissolved CO2 3

Response to high  atmospheric oxygen (PO2) Ž  Pao2 Ž  ventilation Ž  Paco2 Ž respiratory alkalosis Ž altitude
altitude sickness.
Chronic  in ventilation.
 erythropoietin Ž  Hct and Hb (due to chronic hypoxia).
 2,3-BPG (binds to Hb causing left shift so that Hb releases more O2).
Cellular changes ( mitochondria).
 renal excretion of HCO3− to compensate for respiratory alkalosis (can augment with
Chronic hypoxic pulmonary vasoconstriction results in pulmonary hypertension and RVH.

Response to exercise  CO2 production.

 O2 consumption.
 ventilation rate to meet O2 demand.
V̇/Q̇ ratio from apex to base becomes more uniform.
 pulmonary blood flow due to  cardiac output.
 pH during strenuous exercise (2° to lactic acidosis).
No change in Pao2 and Paco2, but  in venous CO2 content and  in venous O2 content.

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Respiratory   


Rhinosinusitis Obstruction of sinus drainage into nasal cavity Ž inflammation and pain over affected area.
A Typically affects maxillary sinuses, which drain against gravity due to ostia located superomedially
(red arrow points to fluid-filled right maxillary sinus in A ).
Most common acute cause is viral URI; may lead to superimposed bacterial infection, most
commonly S pneumoniae, H influenzae, M catarrhalis.
Infections in sphenoid or ethmoid sinuses may extend to cavernous sinus and cause complications
(eg, cavernous sinus syndrome).

Epistaxis Nose bleed. Most commonly occurs in anterior segment of nostril (Kiesselbach plexus). Life-
threatening hemorrhages occur in posterior segment (sphenopalatine artery, a branch of maxillary
artery). Common causes include foreign body, trauma, allergic rhinitis, and nasal angiofibromas
(common in adolescent males).
Kiesselbach drives his Lexus with his LEGS: superior Labial artery, anterior and posterior
Ethmoidal arteries, Greater palatine artery, Sphenopalatine artery.

Head and neck cancer Mostly squamous cell carcinoma. Risk factors include tobacco, alcohol, HPV-16 (oropharyngeal),
EBV (nasopharyngeal). Field cancerization: carcinogen damages wide mucosal area Ž multiple
tumors that develop independently after exposure.

Deep venous Blood clot within a deep vein Ž swelling, Most pulmonary emboli arise from proximal
thrombosis redness A , warmth, pain. Predisposed by deep veins of lower extremity.
A Virchow triad (SHE): Use unfractionated heparin or low-molecular-
ƒƒ Stasis (eg, post-op, long drive/flight) weight heparins (eg, enoxaparin) for
ƒƒ Hypercoagulability (eg, defect in prophylaxis and acute management.
coagulation cascade proteins, such as Use oral anticoagulants (eg, warfarin,
factor V Leiden; oral contraceptive use) rivaroxaban) for treatment (long-term
ƒƒ Endothelial damage (exposed collagen prevention).
triggers clotting cascade) Imaging test of choice is compression ultrasound
d-dimer lab test used clinically to rule out DVT with Doppler.
(high sensitivity, low specificity).

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654 SEC TION III Respiratory   

Pulmonary emboli V̇/Q̇ mismatch, hypoxemia, respiratory alkalosis. CT pulmonary angiography is imaging test of
Sudden-onset dyspnea, pleuritic chest pain, choice for PE (look for filling defects) C .
tachypnea, tachycardia. Large emboli or May have S1Q3T3 abnormality on ECG.
saddle embolus A may cause sudden death
due to electromechanical dissociation.
Lines of Zahn are interdigitating areas of pink
(platelets, fibrin) and red (RBCs) found only in
thrombi formed before death; help distinguish
pre- and postmortem thrombi B .
Types: Fat, Air, Thrombus, Bacteria, Amniotic An embolus moves like a FAT BAT.
fluid, Tumor.
Fat emboli—associated with long bone fractures
and liposuction; classic triad of hypoxemia,
neurologic abnormalities, petechial rash.
Air emboli—nitrogen bubbles precipitate
in ascending divers (caisson disease/
decompression sickness); treat with hyperbaric
O2; or, can be iatrogenic 2° to invasive
procedures (eg, central line placement).
Amniotic fluid emboli—can lead to DIC,
especially postpartum.

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Respiratory   

Flow-volume loops
FLOW-VOLUME PARAMETER Obstructive lung disease Restrictive lung disease
RV  
FRC  
TLC  
FEV1  
FVC  
FEV1/FVC  Normal or 
FEV1 decreased more than FVC FEV1 decreased proportionately to FVC
Loop shifts to the left Loop shifts to the right
8 8 8

4 4 4
Flow (L/sec)

Volume (L)
8 6 4 2 0 8 6 4 2 0 8 6 4 2 0

4 4 4


8 8 8

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656 SEC TION III Respiratory   

Obstructive lung Obstruction of air flow Ž air trapping in lungs. Airways close prematurely at high lung
diseases volumes Ž  FRC,  RV,  TLC. PFTs:  FEV1,  FVC Ž  FEV1/FVC ratio (hallmark),
V̇/Q̇ mismatch. Chronic, hypoxic pulmonary vasoconstriction can lead to cor pulmonale. Chronic
obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema. “FRiCkin’
RV needs some increased TLC, but it’s hard with COPD!”
Chronic bronchitis Findings: wheezing, crackles, Hypertrophy and hyperplasia Diagnostic criteria: productive
(“blue bloater”) cyanosis (hypoxemia due of mucus-secreting glands cough for > 3 months in a
to shunting), dyspnea, CO2 in bronchi Ž Reid index year for > 2 consecutive years.
retention, 2° polycythemia. (thickness of mucosal gland
layer to thickness of wall
between epithelium and
cartilage) > 50%. DLCO
usually normal.
Emphysema (“pink Findings: barrel-shaped chest Centriacinar—associated with CXR:  AP diameter, flattened
puffer”) D , exhalation through pursed smoking A B . Frequently in diaphragm,  lung field
lips (increases airway pressure upper lobes (smoke rises up). lucency.
and prevents airway collapse). Panacinar—associated with
α1-antitrypsin deficiency.
Frequently in lower lobes.
Enlargement of air spaces
 recoil,  compliance,
 DLCO from destruction of
alveolar walls (arrow in C ).
Imbalance of proteases and
antiproteases Ž  elastase
activity Ž  loss of elastic
fibers Ž  lung compliance.
Asthma Findings: cough, wheezing, Hyperresponsive bronchi Ž re­ Type I hypersensitivity
tachypnea, dyspnea, vers­ible bronchoconstriction. reaction.
hypoxemia,  inspiratory/ Smooth muscle hypertrophy Aspirin-induced asthma is
expiratory ratio, pulsus and hyperplasia, Curschmann a combination of COX
paradoxus, mucus spirals F (shed epithelium inhibition (leukotriene
plugging E . forms whorled mucous overproduction Ž airway
Triggers: viral URIs, allergens, plugs), and Charcot-Leyden constriction), chronic sinusitis
stress. Diagnosis supported by crystals G (eosinophilic, with nasal polyps, and asthma
spirometry and methacholine hexagonal, double-pointed symptoms.
challenge. crystals formed from
breakdown of eosinophils in
sputum). DLCO normal or .

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Respiratory   

Obstructive lung diseases (continued)

Bronchiectasis Findings: purulent sputum, Chronic necrotizing infection Associated with bronchial
recurrent infections, of bronchi or obstruction obstruction, poor ciliary
hemoptysis, digital clubbing. Ž permanently dilated motility (eg, smoking,
airways. Kartagener syndrome),
cystic fibrosis H , allergic


Restrictive lung Restricted lung expansion causes  lung volumes ( FVC and TLC). PFTs:  FEV1/FVC ratio.
diseases Patient presents with short, shallow breaths.
A Types:
ƒƒ Poor breathing mechanics (extrapulmonary, peripheral hypoventilation, normal A-a gradient):
ƒƒ Poor muscular effort—polio, myasthenia gravis, Guillain-Barré syndrome
ƒƒ Poor structural apparatus—scoliosis, morbid obesity
ƒƒ Interstitial lung diseases (pulmonary  diffusing capacity,  A-a gradient):
ƒƒ Pneumoconioses (eg, coal workers’ pneumoconiosis, silicosis, asbestosis)
ƒƒ Sarcoidosis: bilateral hilar lymphadenopathy, noncaseating granuloma;  ACE and Ca2+
ƒƒ Idiopathic pulmonary fibrosis A (repeated cycles of lung injury and wound healing with
 collagen deposition, “honeycomb” lung appearance and digital clubbing)
ƒƒ Goodpasture syndrome
ƒƒ Granulomatosis with polyangiitis (Wegener)
ƒƒ Pulmonary Langerhans cell histiocytosis (eosinophilic granuloma)
ƒƒ Hypersensitivity pneumonitis
ƒƒ Drug toxicity (bleomycin, busulfan, amiodarone, methotrexate)
Hypersensitivity pneumonitis—mixed type III/IV hypersensitivity reaction to environmental
antigen. Causes dyspnea, cough, chest tightness, headache. Often seen in farmers and those
exposed to birds. Reversible in early stages if stimulus is avoided.

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658 SEC TION III Respiratory   

Sarcoidosis Characterized by immune-mediated, widespread noncaseating granulomas  A , elevated serum

ACE levels, and elevated CD4+/CD8+ ratio in bronchoalveolar lavage fluid. More common in
African-American females. Often asymptomatic except for enlarged lymph nodes. Findings on
CXR of bilateral adenopathy and coarse reticular opacities B ; CT of the chest better demonstrates
the extensive hilar and mediastinal adenopathy C .
Associated with Bell palsy, Uveitis, Granulomas (epithelioid, containing microscopic Schaumann
and asteroid bodies), Lupus pernio (skin lesions on face resembling lupus), Interstitial
fibrosis (restrictive lung disease), Erythema nodosum, Rheumatoid arthritis-like arthropathy,
hypercalcemia (due to  1α-hydroxylase–mediated vitamin D activation in macrophages). A facial
droop is UGLIER.
Treatment: steroids (if symptomatic).


Inhalation injury and Complication of smoke inhalation from fires A B

sequelae or other noxious substances. Caused by heat,
particulates (< 1 µm diameter), or irritants (eg,
NH3) Ž chemical tracheobronchitis, edema,
pneumonia, ARDS. Many patients present 2°
to burns, CO inhalation, cyanide poisoning, or
arsenic poisoning. Singed nasal hairs common
on exam.
Bronchoscopy shows severe edema, congestion
of bronchus, and soot deposition ( A , 18 hours
after inhalation injury; B , resolution at 11 days
after injury).

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Pneumoconioses Asbestos is from the roof (was common in insulation), but affects the base (lower lobes).
Silica and coal are from the base (earth), but affect the roof (upper lobes).
Asbestosis Associated with shipbuilding, roofing, Affects lower lobes.
plumbing. “Ivory white,” calcified, Asbestos (ferruginous) bodies are golden-brown
supradiaphragmatic A and pleural B plaques fusiform rods resembling dumbbells C ,
are pathognomonic of asbestosis. found in alveolar sputum sample, visualized
Risk of bronchogenic carcinoma > risk of using Prussian blue stain, often obtained by
mesothelioma. bronchoalveolar lavage.
 risk of pleural effusions.
Berylliosis Associated with exposure to beryllium in Affects upper lobes.
aerospace and manufacturing industries.
Granulomatous (noncaseating) D on histology
and therefore occasionally responsive to
steroids.  risk of cancer and cor pulmonale.
Coal workers’ Prolonged coal dust exposure Ž macrophages Affects upper lobes.
pneumoconiosis laden with carbon Ž inflammation and Small, rounded nodular opacities seen on
fibrosis. imaging.
Also known as black lung disease.  risk for Anthracosis—asymptomatic condition found in
Caplan syndrome (rheumatoid arthritis many urban dwellers exposed to sooty air.
and pneumoconioses with intrapulmonary
Silicosis Associated with sandblasting, foundries, Affects upper lobes.
mines. Macrophages respond to silica “Eggshell” calcification of hilar lymph nodes on
and release fibrogenic factors, leading to CXR.
fibrosis. It is thought that silica may disrupt The silly egg sandwich I found is mine!
phagolysosomes and impair macrophages,
increasing susceptibility to TB.  risk of
cancer, cor pulmonale, and Caplan syndrome.

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660 SEC TION III Respiratory   

Mesothelioma Malignancy of the pleura associated with Psammoma bodies seen on histology.
asbestosis. May result in hemorrhagic pleural Calretinin ⊕ in almost all mesotheliomas, ⊝ in
effusion (exudative), pleural thickening A . most carcinomas.
Smoking not a risk factor.

Acute respiratory distress syndrome

PATHOPHYSIOLOGY Alveolar insult Ž release of pro-inflammatory cytokines Ž neutrophil recruitment, activation,
and release of toxic mediators (eg, reactive oxygen species, proteases, etc) Ž capillary endothelial
damage and  vessel permeability Ž leakage of protein-rich fluid into alveoli Ž formation of
intra-alveolar hyaline membranes (arrows in A ) and noncardiogenic pulmonary edema (normal
Loss of surfactant also contributes to alveolar collapse.
CAUSES Sepsis (most common), aspiration, pneumonia, trauma, pancreatitis.
DIAGNOSIS Diagnosis of exclusion with the following criteria (ARDS):
ƒƒ Abnormal chest X-ray (bilateral lung opacities) B
ƒƒ Respiratory failure within 1 week of alveolar insult
ƒƒ Decreased Pao2/Fio2 (ratio < 300, hypoxemia due to  intrapulmonary shunting and diffusion
ƒƒ Symptoms of respiratory failure are not due to HF/fluid overload
CONSEQUENCES Impaired gas exchange
 lung compliance
Pulmonary hypertension
MANAGEMENT Treat the underlying cause
Mechanical ventilation:  tidal volumes,  PEEP

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Sleep apnea Repeated cessation of breathing > 10 seconds during sleep Ž disrupted sleep Ž daytime
somnolence. Diagnosis confirmed by sleep study. Normal Pao2 during the day.
Nocturnal hypoxia Ž systemic/pulmonary hypertension, arrhythmias (atrial fibrillation/flutter),
sudden death.
Hypoxia Ž  EPO release Ž  erythropoiesis.
Obstructive sleep Respiratory effort against airway obstruction. Associated with obesity, loud snoring, daytime
apnea sleepiness. Caused by excess parapharyngeal tissue in adults, adenotonsillar hypertrophy in
children. Treatment: weight loss, CPAP, surgery.
Central sleep apnea Impaired respiratory effort due to CNS injury/toxicity, HF, opioids. May be associated with
Cheyne-Stokes respirations (oscillations between apnea and hyperpnea). Treat with positive
airway pressure.

Obesity Obesity (BMI ≥ 30 kg/m2) Ž hypoventilation Ž  Paco2 during waking hours (retention);  Pao2
hypoventilation and  Paco2 during sleep. Also known as Pickwickian syndrome.

Pulmonary Normal mean pulmonary artery pressure = 10–14 mm Hg; pulmonary hypertension ≥ 25 mm Hg
hypertension at rest. Results in arteriosclerosis, medial hypertrophy, intimal fibrosis of pulmonary arteries,
plexiform lesions. Course: severe respiratory distress Ž cyanosis and RVH Ž death from
decompensated cor pulmonale.
Pulmonary arterial Often idiopathic. Heritable PAH can be due to an inactivating mutation in BMPR2 gene (normally
hypertension inhibits vascular smooth muscle proliferation); poor prognosis. Pulmonary vasculature endothelial
dysfunction results in  vasoconstrictors (eg, endothelin) and  vasodilators (eg, NO and
Other causes include drugs (eg, amphetamines, cocaine), connective tissue disease, HIV infection,
portal hypertension, congenital heart disease, schistosomiasis.
Left heart disease Causes include systolic/diastolic dysfunction and valvular disease.
Lung diseases or Destruction of lung parenchyma (eg, COPD), lung inflammation/fibrosis (eg, interstitial lung
hypoxia diseases), hypoxemic vasoconstriction (eg, obstructive sleep apnea, living in high altitude).
Chronic Recurrent microthrombi Ž  cross-sectional area of pulmonary vascular bed.
Multifactorial Causes include hematologic, systemic, and metabolic disorders, along with compression of the
pulmonary vasculature by a tumor.

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662 SEC TION III Respiratory   

Lung—physical findings
Pleural effusion  Dull  None if small
Away from side of lesion
if large
Atelectasis (bronchial  Dull  Toward side of lesion
Simple pneumothorax  Hyperresonant  None
Tension  Hyperresonant  Away from side of lesion
Consolidation Bronchial breath sounds; Dull  None
(lobar pneumonia, late inspiratory crackles,
pulmonary edema) egophony, whispered

Pleural effusions Excess accumulation of fluid A between pleural layers Ž restricted lung expansion during
inspiration. Can be treated with thoracentesis to remove/reduce fluid B .
Transudate  protein content. Due to  hydrostatic pressure (eg, HF) or  oncotic pressure (eg, nephrotic
syndrome, cirrhosis).
Exudate  protein content, cloudy. Due to malignancy, pneumonia, collagen vascular disease, trauma
(occurs in states of  vascular permeability). Must be drained due to risk of infection.
Lymphatic Also known as chylothorax. Due to thoracic duct injury from trauma or malignancy. Milky-
appearing fluid;  triglycerides.

Pretreatment Pretreatment Post-treatment Post-treatment

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Respiratory   

Pneumothorax Accumulation of air in pleural space A . Dyspnea, uneven chest expansion. Chest pain,  tactile
fremitus, hyperresonance, and diminished breath sounds, all on the affected side.
Primary spontaneous Due to rupture of apical subpleural bleb or cysts. Occurs most frequently in tall, thin, young males
pneumothorax and smokers.
Secondary Due to diseased lung (eg, bullae in emphysema, infections), mechanical ventilation with use of
spontaneous high pressures Ž barotrauma.
Traumatic Caused by blunt (eg, rib fracture), penetrating (eg, gunshot), or iatrogenic (eg, central line
pneumothorax placement, lung biopsy, barotrauma due to mechanical ventilation) trauma.
Tension Can be from any of the above. Air enters pleural space but cannot exit. Increasing trapped air
pneumothorax Ž tension pneumothorax. Trachea deviates away from affected lung B . Needs immediate needle
decompression and chest tube placement. May lead to  intrathoracic pressure Ž  venous return
Ž  cardiac function.

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664 SEC TION III Respiratory   

Lobar pneumonia S pneumoniae most frequently, also Legionella, Intra-alveolar exudate Ž consolidation A ; may
Klebsiella involve entire lobe B or the whole lung.
Bronchopneumonia S pneumoniae, S aureus, H influenzae, Acute inflammatory infiltrates C from
Klebsiella bronchioles into adjacent alveoli; patchy
distribution involving ≥ 1 lobe D .
Interstitial (atypical) Mycoplasma, Chlamydophila pneumoniae, Diffuse patchy inflammation localized to
pneumonia Chlamydophila psittaci, Legionella, viruses interstitial areas at alveolar walls; diffuse
(RSV, CMV, influenza, adenovirus) distribution involving ≥ 1 lobe E . Generally
follows a more indolent course (“walking”
Cryptogenic Etiology unknown. Secondary organizing Formerly known as bronchiolitis obliterans
organizing pneumonia caused by chronic inflammatory organizing pneumonia (BOOP). Noninfectious
pneumonia diseases (eg, rheumatoid arthritis) or pneumonia characterized by inflammation of
medication side effects (eg, amiodarone). ⊝ bronchioles and surrounding structure.
sputum and blood cultures, no response to

Natural history of lobar pneumonia

Congestion Red hepatization Gray hepatization Resolution
DAYS 1–2 3–4 5–7 8+
FINDINGS Red-purple, partial Red-brown, Uniformly gray Enzymes digest
consolidation of consolidated Exudate full of components of exudate
parenchyma Exudate with WBCs, lysed
Exudate with mostly fibrin, bacteria, RBCs, and fibrin
bacteria RBCs, and WBCs

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Respiratory   

Lung cancer Leading cause of cancer death. SPHERE of complications:

Presentation: cough, hemoptysis, bronchial Superior vena cava/thoracic outlet syndromes
obstruction, wheezing, pneumonic “coin” Pancoast tumor
lesion on CXR or noncalcified nodule on CT. Horner syndrome
Sites of metastases from lung cancer: Endocrine (paraneoplastic)
adrenals, brain, bone (pathologic fracture), Recurrent laryngeal nerve compression
liver (jaundice, hepatomegaly). (hoarseness)
In the lung, metastases (usually multiple Effusions (pleural or pericardial)
lesions) are more common than 1° Risk factors include smoking, secondhand smoke,
neoplasms. Most often from breast, colon, radon, asbestos, family history.
prostate, and bladder cancer. Squamous and Small cell carcinomas are Sentral
(central) and often caused by Smoking.
Small cell
Small cell (oat cell) Central Undifferentiated Ž very aggressive. Neoplasm of
carcinoma May produce ACTH (Cushing syndrome), SIADH, or neuroendocrine
Antibodies against presynaptic Ca2+ channels (Lambert- Kulchitsky cells Ž small
Eaton myasthenic syndrome) or neurons (paraneoplastic dark blue cells A .
myelitis, encephalitis, subacute cerebellar degeneration). Chromogranin A ⊕,
Amplification of myc oncogenes common. Managed neuron-specific
with chemotherapy +/– radiation. enolase ⊕,
synaptophysin ⊕.
Non–small cell
Adenocarcinoma Peripheral Most common 1° lung cancer. More common in women Glandular pattern on
than men, most likely to arise in nonsmokers. Activating histology, often stains
mutations include KRAS, EGFR, and ALK. Associated mucin ⊕ B .
with hypertrophic osteoarthropathy (clubbing). Bronchioloalveolar subtype:
Bronchioloalveolar subtype (adenocarcinoma in situ): grows along alveolar septa
CXR often shows hazy infiltrates similar to pneumonia; Ž apparent “thickening”
better prognosis. of alveolar walls. Tall,
Bronchial carcinoid and bronchioloalveolar cell columnar cells containing
carcinoma have lesser association with smoking. mucus.
Squamous cell Central Hilar mass C arising from bronchus; Cavitation; Keratin pearls D and
carcinoma Cigarettes; hyperCalcemia (produces PTHrP). intercellular bridges.
Large cell Peripheral Highly anaplastic undifferentiated tumor; poor prognosis. Pleomorphic giant
carcinoma Less responsive to chemotherapy; removed surgically. cells E .
Strong association with smoking.
Bronchial carcinoid Central or Excellent prognosis; metastasis rare. Nests of neuroendocrine
tumor peripheral Symptoms due to mass effect or carcinoid syndrome cells; chromogranin A ⊕.
(flushing, diarrhea, wheezing).

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666 SEC TION III Respiratory   

Lung abscess Localized collection of pus within Air-fluid levels B often seen on CXR. Fluid
parenchyma A . Caused by aspiration of levels common in cavities; presence suggests
oropharyngeal contents (especially in patients cavitation. Due to anaerobes (eg, Bacteroides,
predisposed to loss of consciousness [eg, Fusobacterium, Peptostreptococcus) or S aureus.
alcoholics, epileptics]) or bronchial obstruction Lung abscess 2° to aspiration is most often found
(eg, cancer). in right lung. Location depends on patient’s
Treatment: antibiotics. position during aspiration.

Pancoast tumor Also known as superior sulcus tumor. Carcinoma that occurs in the apex of lung A may cause
Pancoast syndrome by invading cervical sympathetic chain.
Compression of locoregional structures may cause array of findings:
ƒƒ Recurrent laryngeal nerve Ž hoarseness
ƒƒ Stellate ganglion Ž Horner syndrome (ipsilateral ptosis, miosis, anhidrosis)
1st rib
ƒƒ Superior vena cava Ž SVC syndrome
Mass ƒƒ Brachiocephalic vein Ž brachiocephalic syndrome (unilateral symptoms)
ƒƒ Brachial plexus Ž sensorimotor deficits

Superior vena cava An obstruction of the SVC that impairs blood B

syndrome drainage from the head (“facial plethora”;
note blanching after fingertip pressure in A ),
neck (jugular venous distention), and upper
extremities (edema). Commonly caused by
malignancy (eg, mediastinal mass, Pancoast clot
tumor) and thrombosis from indwelling
catheters B . Medical emergency. Can raise RA
intracranial pressure (if obstruction is severe)
Ž headaches, dizziness,  risk of aneurysm/
rupture of intracranial arteries.

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Respiratory   
respiratory—pharmacology SEC TION III 667


Histamine-1 blockers Reversible inhibitors of H1 histamine receptors.

First generation Diphenhydramine, dimenhydrinate, Names contain “-en/-ine” or “-en/-ate.”
CLINICAL USE Allergy, motion sickness, sleep aid.
ADVERSE EFFECTS Sedation, antimuscarinic, anti-α-adrenergic.
Second generation Loratadine, fexofenadine, desloratadine, Names usually end in “-adine.”
ADVERSE EFFECTS Far less sedating than 1st generation because of
 entry into CNS.

Guaifenesin Expectorant—thins respiratory secretions; does not suppress cough reflex.

N-acetylcysteine Mucolytic—liquifies mucus in chronic bronchopulmonary diseases (eg, COPD, CF) by disrupting
disulfide bonds. Also used as an antidote for acetaminophen overdose.

Dextromethorphan Antitussive (antagonizes NMDA glutamate receptors). Synthetic codeine analog. Has mild opioid
effect when used in excess. Naloxone can be given for overdose. Mild abuse potential. May cause
serotonin syndrome if combined with other serotonergic agents.

Pseudoephedrine, phenylephrine
MECHANISM α-adrenergic agonists, used as nasal decongestants.
CLINICAL USE Reduce hyperemia, edema, nasal congestion; open obstructed eustachian tubes.
ADVERSE EFFECTS Hypertension. Rebound congestion if used more than 4–6 days. Can also cause CNS stimulation/
anxiety (pseudoephedrine).

Pulmonary hypertension drugs

Endothelin receptor Competitively antagonizes endothelin-1 Hepatotoxic (monitor LFTs).
antagonists receptors Ž  pulmonary vascular resistance. Example: bosentan.
PDE-5 inhibitors Inhibits PDE-5 Ž  cGMP Ž prolonged Also used to treat erectile dysfunction.
vasodilatory effect of NO. Contraindicated when taking nitroglycerin or
other nitrates.
Example: sildenafil.
Prostacyclin analogs PGI2 (prostacyclin) with direct vasodilatory Side effects: flushing, jaw pain.
effects on pulmonary and systemic arterial Examples: epoprostenol, iloprost.
vascular beds. Inhibits platelet aggregation.

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668 SEC TION III Respiratory   

Asthma drugs Bronchoconstriction is mediated by (1) inflammatory processes and (2) parasympathetic tone;
therapy is directed at these 2 pathways.
β2-agonists Albuterol—relaxes bronchial smooth muscle (short acting β2-agonist). Used during acute
Salmeterol, formoterol—long-acting agents for prophylaxis. Adverse effects are tremor and
Inhaled Fluticasone, budesonide—inhibit the synthesis of virtually all cytokines. Inactivate NF-κB, the
corticosteroids transcription factor that induces production of TNF-α and other inflammatory agents. 1st-line
therapy for chronic asthma. Use a spacer or rinse mouth after use to prevent oral thrush.
Muscarinic Tiotropium, ipratropium—competitively block muscarinic receptors, preventing
antagonists bronchoconstriction. Also used for COPD. Tiotropium is long acting.
Antileukotrienes Montelukast, zafirlukast—block leukotriene Exposure to antigen
receptors (CysLT1). Especially good for (dust, pollen, etc)
aspirin-induced and exercise-induced asthma.
Zileuton—5-lipoxygenase pathway inhibitor. Avoidance
Blocks conversion of arachidonic acid to
leukotrienes. Hepatotoxic.
Antigen and IgE Omalizumab
Anti-IgE monoclonal Omalizumab—binds mostly unbound serum on mast cells
therapy IgE and blocks binding to FcεRI. Used in
allergic asthma with  IgE levels resistant to
inhaled steroids and long-acting β2-agonists.

Methylxanthines Theophylline—likely causes bronchodilation Mediators

by inhibiting phosphodiesterase Ž  cAMP (leukotrienes, histamine, etc)
levels due to  cAMP hydrolysis. Usage is
limited because of narrow therapeutic index β-agonists
(cardiotoxicity, neurotoxicity); metabolized Theophylline Steroids
by cytochrome P-450. Blocks actions of Muscarinic Antileukotrienes
Mast cell stabilizers Cromolyn, nedocromil—prevent release of
inflammatory mediators from mast cells. Used
for prevention of bronchospasm, not for acute Early response: Late response:
bronchoconstriction inflammation

Bronchodilation AC β-agonists

Bronchial tone
PDE Theophylline
ACh Adenosine

Muscarinic Theophylline

Methacholine Nonselective muscarinic receptor (M3) agonist. Used in bronchial challenge test to help diagnose

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