This document summarizes pulmonary physiology including mechanics of breathing, lung volumes and capacities, pressure changes during breathing, forced expiration in COPD, transmural pressures, pulmonary compliance, hysteresis, diffusion of gases, V/Q ratios, and O2 and CO2 transport. Key points include that in COPD, forced expiration can cause airway collapse due to decreased alveolar pressure, and that V/Q defects and right-to-left shunts can cause hypoxemia. O2 is transported primarily bound to hemoglobin while CO2 is transported primarily dissolved in plasma.

1. PULMONARY REVIEW

2. PHYSIOLOGY

3. Mechanics of Breathing
• Pressure difference is the driving force for air flow, Q = ΔP / R
• Between breaths, alveolar pressure = atmospheric pressure
• Inspiration: Diaphragm contracts → lung volume increases → alveolar pressure decreases
→ air flows into the lungs until alveolar pressure = atmospheric pressure again
• Tidal volume (VT) = volume inspired in one normal breath (500mL)
• Volume in lungs after inspiration = FRC + VT
• Functional residual capacity: the volume in the lungs at the end-expiratory position
• Expiration: diaphragm relaxes → lung volume decreases → alveolar pressure increases →
air flows out of the lungs
• Forced expiration: contraction of expiratory muscles further increases alveolar pressure to
force air out. Intrapleural pressure increases too, but as long as the transmural pressure is
still positive, the lungs will not collapse. Expiration will be rapid and forceful.
• COPD: Lung elasticity is decreased, so during forced expiration, intrapleural pressures
increase to normal values but alveolar pressures are lower because of their increased
compliance. The gradient becomes negative & airways collapse.

4. Lung Volumes and Capacities

5. Pressure Changes during Breathing

7. Forced Expiration and COPD
In a person with COPD forced expiration may cause the airways to collapse.
In COPD, lung compliance increases because of loss of elastic fibers. During forced expiration,
intrapleural pressure is raised to the same value as in the normal person. However, because the
structures have diminished elastic recoil, alveolar pressure and airway pressure are lower than in a
normal person. The large airways collapse because the transmural pressure gradient across them
reverses, becoming a negative (collapsing) transmural pressure. Obviously, if the large airways
collapse, resistance to airflow increases and expiration is more difficult.

8. Transmural Pressures
• Transmural pressure:
• Pressure difference across a structure
• Transpulmonary pressure:
• Difference between intra-alveolar pressure & intrapleural pressure
• Calculated as alveolar pressure minus intrapleural pressure
• Transthoracic pressure:
• Difference between intrapleural pressure & pressure outside the chest wall (outside
the body)

9. Pulmonary Compliance

10. Hysteresis
• Hysteresis: the phenomenon that the compliance curves for inspiration
and expiration are different.
• For a given pressure, lung volume is higher during expiration than during inspiration,
therefore compliance is greater during expiration.
• Inspiration –
• Low volume; liquid molecules are closely packed; intermolecular forces are high
• Surfactant is released to break the forces (Surfactant = a phospholipid produced by type II
alveolar cells that acts as a detergent to reduce surface tension & increase lung
compliance)
• Lung volume increases faster than surfactant can be added → curve starts off flat &
gradually steepens as more surfactant is added.
• Expiration –
• Starts at high volume; intermolecular forces are low
• Surface area decreases faster than surfactant can be removed → increasing density of
surfactant per surface area decreases surface tension & increases compliance → curve
starts off flat
• As expiration proceeds – surfactant is removed at a similar rate as volume decreases, so
the compliance curve has a fairly constant slope

11. Compliance and Elastance
• Compliance: Describes distensibility of system. ΔV/ΔP
• “How easily an object stretches”
• Elastance: inversely correlated with compliance. ΔP/ΔV "Snap back"
or elastic recoil force.
• “Ability of an object to return to its original position or shape”
• Emphysema  increased compliance, decreased elastance
• Fibrosis  decreased compliance, increased elastance

12. Compliance of Lung and Chest Wall

13. Pneumothorax
• Normally, the intrapleural space has a negative pressure
• This negative intrapleural pressure is created by two opposing elastic
forces pulling on the intrapleural space
• When a sharp object punctures the intrapleural space, air is
introduced (pneumothorax), and intrapleural pressure suddenly
becomes equal to atm pressure; thus, instead of its normal negative
value, intrapleural pressure becomes ZERO
• Two main consequences of pneumothorax
• Without negative intrapleural pressure to hold lung open, lung collapses
• Without negative intrapleural pressures to keep the chest wall from expanding, the
chest wall springs out

14. Compliance and Elastance Pathology

15. Emphysema and Compliance
• Emphysema is associated with loss of elastic fibers in the lungs 
increased compliance  increased (steeper) slope of the volume-versus-
pressure curve  at a given volume, the collapsing (elastic
recoil) force is decreased.
• At the original value for FRC, chest wall expansion outweighs lung’s
collapsing force. In order for the opposing forces to be balanced,
volume must be added to the lungs to increase their collapsing force.
• Thus, the combined lung and chest-wall system seeks a new higher
FRC, where the two opposing forces can be balanced; the new
intersection point, where airway pressure is zero, is increased.
• A patient with emphysema is said to breathe at higher lung volumes
(in recognition of the higher FRC) and will have a barrel-shaped
chest.

16. Fibrosis and Compliance
• Fibrosis (decreased lung compliance). Fibrosis, a so-called
restrictive disease, is associated with stiffening of lung tissues
and decreased compliance.
• A decrease in lung compliance is associated with a decreased
slope of the volume-versus-pressure curve for the lung.
• At the original FRC, the tendency of the lungs to collapse is
greater than the tendency of the chest wall to expand, and the
opposing forces will no longer be balanced. To reestablish
balance, the lung and chest-wall system will seek a new lower
FRC; the new intersection point, where airway pressure is zero,
is decreased.

17. FRC
• Functional Residual Capacity (FRC) is the volume of air present in the
lungs at the end of passive expiration.
• At FRC, the elastic recoil forces of the lungs and chest wall are equal
but opposite. There is no exertion at this point by any of the
respiratory muscles.
• FRC is the sum of Expiratory Reserve Volume (ERV) and Residual
Volume (RV) and since it includes the residual volume, it cannot be
measured by spirometry.
• RV can be measured by helium dilution or body pleythysmography.

18. Air Flow and Resistance
The medium-sized bronchi are the sites of highest airway resistance.
It would seem that the smallest airways would provide the highest resistance to
airflow, based on the inverse fourth power relationship between resistance and
radius.
However, because of their parallel arrangement, the smallest airways do not
have the highest resistance.

19. Pulmonary vascular resistance is about
1/10 of systemic vascular resistance
It has a minimum value at intermediate
lung volumes

20. Blood Gas Pressures

21. Respiratory Volumes
TLC Total Lung
capacity
6.0L
FRC Functional
Residual Capacity
2.4L
VC Vital Capacity 4.7L
VT Tidal Volume 0.5L
FVC Forced Vital
Capacity
4.7L
VA Alveolar
Ventilation
N/A
FEV1 Volume of FVC in
1 second
N/A

22. Constants

23. • Anatomic dead space (~ 150 mL) = the volume of the conducting airways
(nose/mouth, trachea, bronchi, bronchioles)
• Alveolar ventilation = total rate of air movement into and out of the alveoli,
expressed in mL/min. (500 mL/breath - 150 mL/breath) x 15 breaths/min =
5250 mL/min

24. Alveolar Ventilation
• VT = tidal volume
• RR = respiratory rate
• VD = dead space
• Total ventilation (aka minute ventilation) = VT x RR
• Normal: 500 mL/breath x 15 breaths/min = 7500 mL/min
• Alveolar ventilation (VA) = (VT - VD) x RR

25. Alveolar Ventilation Equation
• Fundamental Equation of Physiology: Interdependence of CO2 and Ventilation
• Increasing VA decreases PACO2 and PaCO2 and increases pH : ALKALOSIS
• Decreasing VA increases PACO2 and PaCO2 and decreases pH : ACIDOSIS

26. Alveolar Gas Equation
• Predicts PAO2 based on alveolar PACO2
• PIO2 = (760-47) mmHg * 0.21 = 150mmHg
• PAO2 = 150 – (40mmHg/0.8) = 100mmHg

28. A-a Gradient
• PAO2 – PaO2
• In a normal person, the A-a difference is close to zero (but not zero),
because while O2 will equilibrate in the alveoli, there is a small
amount of blood (~2%) that bypasses the alveoli (aka the
"physiological shunt"), and PaO2 (obtained via a blood sample) is a
mixture of all blood, including shunted blood.
• To calculate the estimated normal A-a gradient : [Person’s Age/4] + 4
• Three scenarios that result in an increased gradient:
• Diffusion defects (e.g. fibrosis, pulmonary edema)
• V/Q defects
• Right-to-left shunts (cardiac, intrapulmonary)
• NOT Hypoventilation and High altitude

29. Dead Space
• Anatomic dead space: Volume of conducting airways
• (nose/mouth, trachea, bronchi, bronchioles)
• Physiologic dead space: Total volume of the lungs that does not
participate in gas exchange = “anatomic dead space” plus any
functional dead space in the structures that contain alveoli
• Dead space ventilation is usually approximately 2ml/kg (ideal body
weight)

30. If you increase your RR and your VT by
20% respectively, you will see a
GREATER increase in alveolar ventilation
with an increase in VT
BIGGER DEEPER BREATHS WORK

31. Diffusion of Gases

32. Diffusion Changes
• In emphysema, DL decreases because destruction of alveoli results in
a decreased SA for gas exchange.
• In fibrosis or pulmonary edema, DL decreases because the diffusion
distance (membrane thickness or interstitial volume) increases.
• In anemia, DL decreases because the amount of hemoglobin in red
blood cells is reduced (recall that DL includes the protein-binding
component of O2 exchange).
• During exercise, DL increases because additional capillaries are
perfused with blood, which increases the SA for gas exchange.

33. Diffusion Limited vs. Perfusion Limited
• Gas exchange across the alveolar/pulmonary capillary barrier is either
diffusion-limited or perfusion-limited
• CO is a diffusion-limited gas meaning that as long as the partial
pressure gradient is maintained, diffusion will continue across the
length of the capillary, so it can be used to measure the diffusing
capacity.
• Partial pressure gradient maintained because CO is bound to
hemoglobin in capillary blood so CO does not equilibrate by the end
of the capillary
• Nitrous oxide (N2O) is a perfusion limited gas so it can be used to
measure perfusion capacity

34. The slower equilibration of O2 at
high altitude is exaggerated in a person
with fibrosis. Pulmonary capillary blood
does not equilibrate by the end of the
capillary, resulting in values for PaO2 as
low as 30 mm Hg, which will seriously
impair O2 delivery to the tissues.

35. Hypoxemia and Hypercapnia
• Hypoxemia: a decrease in arterial Po2
• Causes of hypoxemia: high altitude, hypoventilation, diffusion
defect, V/Q defect, right-to-left shunt
• Hypercapnia: abnormally elevated levels of CO2 in the
blood
• Causes of hypercapnia: hypoventilation, lung disease, respiratory
acidosis

36. CO2 moves from alveolar gas to
pulmonary capillary blood 20 times faster
than O2 due to a 20 times higher CO2
diffusion coefficient

38. Blood Flow is Highest in Zone 3 of the
lung due to pressure. It is 20X higher.

39. Ventilation Rates are highest in Zone 3 of
the lung due to gravity

40. V/Q
• V/Q ratio is the ratio of alveolar ventilation to pulmonary blood flow
(ventilation/perfusion ratio, measured in L/min over L/min).
• The normal value is 0.8.
• If V/Q ratio is normal, then PaO2 will be at its normal value (100 mm
Hg), as is PaCO2 (40 mm Hg).

41. V/Q and Gas Exchange

42. V/Q Defects

43. Physiological vs. Pathological Shunt
• Physiologic shunt -A small fraction of the pulmonary blood flow (about
2%) bypasses the alveoli
• Result is that PaO2 will always be slightly less than PAO2
• Made up of 2 components
• Bronchial blood flow, which serves metabolic functions of bronchi
• Coronary blood flow that drains directly into the left ventricle via the thebesian veins
• Pathologic Shunts-
• Right-to-left-Blood can pass from the right to left heart if there is a defect
in the wall between the ventricles
• Hypoxemia ALWAYS occurs because significant fraction of output is never delivered
to the lungs for oxygenation
• Hypoxemia CANNOT be corrected by having the person breathe a high O2 gas
• Usually only minimal increase in PaCO2 (systemic arterial blood PCO2)
• Left-to-right-More common and does not cause hypoxemia
• Can be from patent ductus arteriosus or traumatic injury
• Elevated PO2 in the right side of the heart

44. 2% of blood bypasses pulmonary
circulation in physiological shunt of
healthy people

45. O2 CO2 TRANSPORT

46. Dissolved O2 is free in solution and
accounts for approximately 2% of the total
O2 content of blood.
The remaining 98% of the total O2
content of blood is reversibly bound to
hemoglobin inside the red blood cells.

47. O2 Content

48. O2 Delivery
• Cardiac Output x O2 Content

49. Henry’s Law
Henry’s law deals with gases dissolved in solution (e.g., in blood). To calculate
a gas concentration in the liquid phase, the partial pressure in the gas phase
first is converted to the partial pressure in the liquid phase; then, the partial
pressure in liquid is converted to the concentration in liquid.
ONLY APPLIES TO DISSOLVED (NOT BOUND) GAS

50. O2 Hemoglobin Dissociation Curve

51. The percent saturation of heme sites does
not increase linearly as PO2 increases.
Rather, percent saturation increases
steeply (change in affinity) as PO2
increases from zero to approximately 40
mm Hg, and it then levels off between 50
mm Hg and 100 mm Hg.

52. Unloading
• This sigmoidal shape explains the mechanism of oxygen
unloading in the capillaries. In regions of low PO2 such as
40 mmHg in mixed venous blood, the affinity between
hemoglobin and oxygen is decreased and oxygen
dissociates and enters tissues. The opposite is true in
regions of high PO2 such as in the alveoli (100 mmHg).
• Also related to concentrations of CO2 (Bohr and Haldane
Effect)

53. P50
• A change in the value of P50 is used as an indicator for a
change in affinity of hemoglobin for O2.
• An increase in P50 reflects a decrease in affinity – RIGHT SHIFT
• A decrease in P50 reflects an increase in affinity – LEFT SHIFT

54. Shifts in O2 Hemoglobin curve
• Right Shifts
• P50 is higher: DECREASED AFFINITY
• Increased PCO2 (Bohr Effect)
• Decreased pH
• Increased Temperature
• Increased 2,3,-DPG
• Left Shifts
• P50 is lower: INCREASED AFFINITY
• Decreased PCO2
• Increased pH
• Decreased Temperature
• Decreased 2,3-DPG

55. 2,3-DPG
• 2,3-DPG is a byproduct of glycolysis in red blood cells.
• 2,3-DPG binds to the b chains of deoxyhemoglobin and
reduces their affinity for O2.
• This decrease in affinity causes the O2-hemoglobin
dissociation curve to shift to the right and facilitates unloading
of O2 in the tissues.
• 2,3-DPG production increases under hypoxic conditions. For
example, living at high altitude causes hypoxemia, which
stimulates the production of 2,3-DPG in red blood cells.
• In turn, increased levels of 2,3-DPG facilitate the delivery of O2
to the tissues as an adaptive mechanism.

56. The Effect of CO
• Decreases O2 bound to hemoglobin and also causes a
left shift of the O2-hemoglobin dissociation curve
• Decreases O2 content of hemoglobin AND decreases unloading in
the tissues
• BAD.

57. The Effect of Anemia

58. CO2 Transport
• Dissolved CO2 (5%), straight up in the blood
• Carbaminohemoglobin (3%), bound to hemoglobin, albumin or other
proteins
• HCO3- (>90%), chemically modified by carbonic anhydrase
• Exact percentages vary, but the vast majority is in HCO-
3

59. Chloride Shift and CO2 Transport
• Carbonic Anhydrase in RBCs catalyzes the combination of COand
2 HO to form HCO223
• HCOdissociates into H+ and HCO-
23 3
• H+ remains in the RBC and HCO3
- is filtered into plasma in exchange
for Cl-
• H+ is buffered in RBCs by deoxyhemoglobin

60. Haldane vs. Bohr Effect

61. PFTS

62. Spirogram

63. Important Values
• VT = 500mL
• IRV = 3000 mL
• ERV = 1200mL
• RV = 1200mL
• VC = 4700 mL
• FRC = 1200mL
• TLC = 5900mL
• Dead Space = 150mL

64. 4 Volumes, 4 Capacities
• 4 Volumes
• Tidal volume
• Inspiratory reserve volume
• Expiratory reserve volume
• Residual volume
• Four Capacities:
• Inspiratory Capacity  IRV + TV
• Functional residual capacity  ERV + RV
• Vital Capacity  TV + IRV + ERV
• Total Lung Capacity  IRV +TV + ERV + RV

65. Residual Volume cannot be measured by
Spirometry

66. Flow Volume Curve

68. Diffusion, DLCO
• DLCO : lung diffusing capacity
• DL can be measured using carbon monoxide.
• The test involves breathing in air with low concentrations of
CO, and the rate of disappearance of CO from the gas mixture
is proportional to the DL.
• In certain pathological processes the DL changes predictably.
• Emphysema, the DL goes down because destruction of alveoli
decrease surface area for gas exchange.
• Pulmonary fibrosis or edema, DL decreases because the diffusion
distance increases.
• Exercise, the DL increases because more capillaries are perfused with
blood, thus increasing the surface area for exchange.
• Anemia, the DL decreases because the amount of hemoglobin in
RBCs decreases.

69. 3 Categories of Lung Disease
• Obstructive
• Restrictive
• Interstitial
• Primary neurologic
• Primary muscular
• Primary skeletal
• Vascular

70. Localizing Disease
• Airway
• Asthma
• COPD (chronic bronchitis & emphysema)
• Interstitium and Alveoli
• ILD
• Emphysema
• Alveolar Filling (WBC, RBC, Water, Protein)
• Blood Vessels
• PE
• PAH
• Pulm Ven HTN
• Neuromuscular and Chest Wall
• Pleural disease
• Neurologic deficiency
• Muscular weakness

71. Algorithm
FEV1/FVC
Low
Obstructed
Reversible
Yes: Asthma No: COPD
DLCO
Low:
Emphysema
Normal:
Bronchitis
Normal
FVC/ TLC
Low: Restrictive
DLCO
Low: ILD
Normal:
Neuromuscular
Normal
DLCO
Low: Vascular Normal: Normal

72. Normal Values
• FEV1/FVC: 80 to 120% of predicted for most PFTs
• Exceptions - FEV1/FVC: > 70%
• Use actual value not % predicted
• Change with bronchodilator
• > 12% in FEV1 or FVC and 200 cc’s
• TLC: 80 to 120% of predicted for most PFTs
• TLC : Low (Restricted), High (Hyper-inflated)
• DLCO : < 80% is considered abnormal

73. ACUTE RESPIRATORY
FAILURE

75. Types of ARF
• Typical (normal) ABG values: >60 mmHg for PaO2 and <50 mmHg for
PaCO2
• There are two types of acute respiratory failures: in both types there
will be decreased PaO2 (<60 mmHg). Thus in order to distinguish
between the two types, we evaluate the PaCO2.
• 1. Acute Hypoxemic Respiratory Failure: PaCO2 ≤ 40 mmHg
• Hypoxemia without hypercapnia
• Inability to properly take up oxygen
• There is insufficient oxygen in the blood but near normal CO2
• 2. Acute Hypercapnic Respiratory Failure: PaCO2 > 40 mmHg
• Hypoxemia with hypercapnia
• Inability to eliminate carbon dioxide
• There is too much carbon dioxide in the blood

76. A-a Gradient
• In a patient w/ hypoxemia and PaCO2 ≤ 40 mmHg:
• Increased A-a gradient → intrapulmonary issue
• Normal A-a gradient → extrapulmonary issue
• An increase in the A-a gradient suggests an inability to extract enough
oxygen (e.g., defects in diffusion, V/Q mismatch, or right-to-left
shunting).
• If the patient is hypoxic and has a normal A-a gradient, it suggests
the problem is not in extracting O2 from the blood pointing to other
etiologies like being at a higher elevation.

77. Hypoxemic Respiratory Failure with
Increased A-a Gradient
• 1. Pulmonary embolism
• 2. Atelectasis
• 3. Pneumonia
• 4. Interstitial lung disease
• 5. Infection
• 6. ARDS

78. Hypoxemic Respiratory Failure with
Normal A-a Gradient
• High Altitude
• Decreased FIO2 (asphyxia, drowning)
• Airway Obstruction
• Foreign body
• Laryngeal spasm
• Obesity and external compression of larynx
• Obstructive sleep apnea
• Obstruction of airway apparatus – kinking / obstruction of endotracheal tube
• Asthma
• Tumor

79. Hypercapnic Respiratory Failure
• Depression of the neurologic system
• Narcotics
• Overdose
• Coma
• Disease of the chest wall or neuromuscular apparatus
• Myesthenia Gravis
• Guillian Barre Syndrome
• COPD or other lung diseases

80. Clinical Signs and Sx
• Breathing rate
• Tidal volumes
• Labored respiration/Paradoxical breathing
• Asynchronous ventilatory patterns
• Prolonged inspiratory phase: Stridor and upper airway obstruction
• Prolonged expiratory phase: Asthma/COPD
• Patient posture (cannot lay flat)
• Ability to converse
• Tachycardia with increased work of breathing
• Patient tell you they are exhausted
• Pulse ox <90%
• PaO2 < 60 mmHg
• PaCO2 > 50 mmHg

81. Clinical Utility of Venous Blood Gas
• Venous blood gas is sometimes used when arterial blood cannot be
obtained due to diminished pulses or patient movement.
• Venous blood gas gives a picture of how critical the patient is. If the
venous O2 is really low, then the body is extracting the majority of O2
from blood and the patient is very critical. Normal mixed venous O2
saturation is 65-70%.
• Central venous blood is preferred over peripheral venous blood
because of their better correlation to arterial blood gases.
• Central venous pH is usually 0.03-0.05 pH units lower than arterial
pH. PCO2 is usually 4 to 5 mmHg higher than arterial PCO2.
• Peripheral venous pH is usually 0.02-0.04pH units lower than arterial
pH. The venous PCO2 is about 3-5mmHg higher than arterial PCO2.

82. Identify the patient who may require
intubation and mechanical ventilation.
• Patients with severe dyspnea
• Respiratory rate 35bpm
• Unable to gasp more than 3 words
• Very abnormal breathing pattern
• Tachycardia/arrhythmias
• Hyper/hypotension
• Sweating
• Abnormal arterial blood gases-60/50 club
• Arterial PCO2 has risen to cause
• Lowered pH (below 7.25-7.30)
• Impaired mental status
• PO2 over 60 mmHg cannot be achieved with inspired O2 concentration less
than 40% - 60%

83. NEURAL CONTROL OF
BREATHING

84. Lung Volume and Airway Patency
• 2 types of striated muscles regulate the flow of air in and out of lungs:
• Pump and Airway muscles
• Pump muscles: Define volume of chest cavity: motor neurons in the
spinal cord
• Inspiratory: diaphragm and external intercostals
• Expiratory: internal intercostals and abdominal (passive process at rest)
• Airway muscles: regulate the flow of air through the airway: motor
neurons located in the lower brainstem
• Two aspects of ventilatory control:
• (1) degree of inspiratory drive or central inspiratory activity
• (2) the timing mechanism (which controls the termination of inspiration).
• Determining factors act in concert to set the respiratory rate and tidal volume
and thus the minute ventilation and specific pattern of breathing.”

85. 3 Phases of Breathing
• Inspiration: The diaphragm is recruited in an incremental fashion
during inspiration: Innervated by phrenic nerve
• Passive Expiration (E1): Air is forced out of the lungs due to the recoil
of the elastic fibers in the lungs.
• During this phase the phrenic nerve is still active but at lower level than it was
in inspiration.
• The expiratory branch of the recurrent laryngeal nerve activates the laryngeal
constrictors, which oppose lung recoil.
• The activity of these two nerves produces a smoother expiratory flow and
results in better gas exchange in the lungs.
• Active expiration (E2): only occurs if chemoreceptors are stimulated
by hypoxia or hypercapnia or during exercise.
• Expiratory muscles activity is essential to speed up breathing frequency.
Inspiratory duration is virtually invariant in a healthy individual. The breathing
rate increases almost entirely via shortening of expiratory phase. L
• Lumbar nerve innervates muscles of phase 2

86. Rhythm vs. Pattern Generation
• Pattern: the orderly recruitment of pump and airway muscles during
the respiratory cycle:
• pontomedullary network of neurons
• pattern generator is regulated by
• cortex (volitional control)
• limbic system (emotions)
• state of vigilance (sleep vs awake)
• blood gases (chemoreception)
• feedbacks from lung and chest sensory afferents
• Rhythm: generates the respiratory rate
• PreBotzinger complex: controls timing of inspiration

87. Neural Breathing Centers
• Ventral respiratory column refers to a bilateral stretch of reticular
formation that contains rhythm generating and pattern-generating
respiratory neurons
• The preBötzinger Complex is a small segment of the VRC where the eupneic
breathing rhythm is generated.
• Located in the ventrolateral medulla
• Pneumotaxic center in dorsal pons
• The nucleus solitary tract (NTS) receives sensory afferents including
afferents from the lungs and carotid bodies.
• The region is also sometimes called dorsal respiratory group and, in some
species, contains phrenic premotor neurons.
• Inspiratory motoneurons including phrenic motor neurons receive
most of their input from the brainstem

88. Mechanoreceptors vs. Chemoreceptors
• Central Chemoreceptors: detect PCO2 and acid
• Hypoxia in the CNS suppresses breathing
• Peripheral Chemoreceptors (the carotid and aortic) detect artery hypoxia
and arterial PCO2
• Respond more quickly to a change in arterial PCO2 than central chemoreceptors
• Irritant receptors: (rapidly adapting) chemosensitive C fibers
• Respond to cold, airflow, pollutants, irritants and inflammation
• Mechanoreceptors (slowly adapting)
• Lung inflation stretches the terminal endings of mechanosensitive sensory afferents
located in the trachea and bronchi.
• Activation of these afferents is sustained when the stretch is maintained
• Initiate Hering Breuer reflex (see LO6)
• Mechanoreceptors (rapidly adapting)
• Encode rate of change of tension

89. Chemoreceptors
• Peripheral chemoreceptors are located in the carotid bodies and in
the aortic body, located between the pulmonary artery and aortic arch.
• Detect CO2 and O2
• REACT FASTER THAN CENTRAL CHEMORECEPTORS
• Central respiratory chemoreceptors reside at the ventral surface of
the medulla oblongata.
• Detect only CO2
• Retrotrapezoid nucleus
• Fissura pontomedullaris
• Inferior olive
• Precerebellar structure.
• CNS Hypoxia depresses breathing

90. MOA Peripheral Chemoreception
• Hypoxia depolarizes type I cells (glomus cells) by turning off
potassium conductances.
• The depolarization causes Ca to enter and produces the exocytosis of
transmitters (most important: ACh, ATP).
• ACh and ATP depolarize the peripheral end of sensory afferents.
• Carotid body afferents project to the nucleus solitary tract via the
glossopharyngeal nerve where the information is relayed to the
central pattern generator to cause an increase in breathing rate and
amplitude.

91. MOA Central Chemoreception
• RTN neurons (bright green) are glutamatergic. They innervate only
the regions involved in respiratory rhythm and pattern generation
• RTN neurons are activated by acidification
• A mutation of transcription factor Phox2b in man prevents the
development of RTN neurons. The result is Congenital Central
Hypoventilation Syndrome (Ondine’s curse), a disease in which
breathing is no longer stimulated by CO2 and breathing stops during
sleep (breathing while awake is Ok although PCO2 is less tigthly
regulated).
• These patients are ventilator-dependant throughout their life.

92. Hering Breur Reflex
• Reflex triggered to prevent overinflation of the lung mediated by slowly adapting
mechanoreceptors.
• Initiated by lung inflation, which stretches the terminal endings of slowly adapting
mechanosensitive sensory afferents located in the trachea and bronchi  influx of
sodium  depolarization and action potential generation
• The axons travel in thoracic branches of the vagus nerve, and the cell bodies are
found in the nodose ganglion.
• Via the NTS, the information is relayed to the pons and the ventral respiratory
column, resulting in decreased activity of inspiratory motoneurons, which helps
terminate inspiration.
• They are termed “slowly adapting” because their activation is sustained when the
stretch is maintained.
• This reflex is weaker in the adult and stronger in the neonate and is of minor
medical importance.

93. Rapid Mechanoreceptors
• Respond only briefly to a stretch. They encode the rate of change of
the tension as opposed to its absolute level. Rapidly adapting
mechanoreceptors also exist in the lung but they are not involved in
the H-B reflex.

94. Chemosensitive C Fiber Afferents
• Present throughout the trachea and bronchi and can produce a
variety of skeletomotor and autonomic reflexes.
• Exposure to pollutants and irritants triggers activation of both rapidly
adapting receptors and C-fiber afferents, which then mediate mucus
production, glottal closure and apnea, bronchoconstriction, and
cough.
• Glottis closure prevents further inhalation of particulate matter,
irritants or toxins, and cough is a powerful expiratory effort against a
closed glottis.

95. Sighs
• Sighs are periodic unusually large inspirations.
• Their frequency is increased by (1) being awake as opposed to sleep,
and (2) by hypoxia, probably by stimulation of the carotid bodies.
• Most likely serve to prevent atelectasis

96. Automaticity and Voluntary Control
• In general, the process of breathing is a normal rhythmic activity that
occurs without conscious effort. It is controlled by the central
respiratory generator located in the medulla, which sends signals to
the respiratory muscles. Input from the pons to the generator is
necessary for a normal, coordinated breathing pattern.
• The cerebral cortex exerts a conscious or voluntary control over
ventilation. This cortical override of automatic control can be seen
with either voluntary breath holding or hyperventilation.

97. CO2 is the variable most tightly regulated
by breathing

98. Waking vs. Sleeping Drives
• Breathing automaticity is maintained by several classes of
mechanisms. The chemical drive is the excitatory influence of
chemoreceptors (both central and peripheral) on the central
respiratory pattern generator (CPG).
• When one is awake, the CPG also receives excitatory inputs from
“waking drives” including neural feedback that gauges the metabolic
activity of skeletal muscles and the reticular activating system.
• When one is asleep (non-REM sleep), however, the waking drive is
greatly reduced or absent, and the chemical drive becomes the
dominant influence.
• Clinical significance: During sleep, breathing is more shallow, less
stable (more prone to stop → apnea), and depends highly on the
chemoreceptor drive.

99. CNS hypercapnia will produce sleep
disturbance and promote awakening, like
in sleep apnea. The increases in CO2
leads to a sudden urge and stimulation to
breathe.
CNS hypoxia has a depressant effect

100. Morphine and Breathing
• Morphine depresses the brainstem respiratory pattern generator
(including the central chemoreflex). The resulting slow and shallow
breathing causes hypoxia and hypercarbia.
• Carotid body stimulation by hypoxia/CO2 maintains a modicum of
breathing but only up to a point.
• If morphine exceeds a certain brain concentration, its direct CNS
depressant effect combined with the depressant effects of brain
hypoxia cannot be overcome by carotid body stimulation and
breathing stops, leading to cardiovascular collapse and death.

101. SIDS
• Rare but responsible for a significant % of early infant deaths
• Potential causes and contributing factors
• Defect in arousal elicited by hypercapnia or hypoxia.
• Overactive / abnormal airway protective reflexes (cough, laryngeal reflexes).
• Developmental problems (abnormality of lower brainstem serotonergic
neurons, possibly)
• Environmental factors (air pollution, tobacco smoke, nicotine).
• Treatment:
• Preventative (eliminate presumed contributing factors).
• Supine sleeping position (most effective; reduction of mortality estimated at >
50% in the US).
• Alarm to detect loss of breathing

102. SIDS Mechanism
• During prone sleeping re-breathing exhaled air can increase CO2 and
decrease O2 levels
• Initiates the arousal response that begins with sigh.
• Successful arousal results in head lifting and repositioning
• If arousal fails, a more severe hypoxic state is reached and eupneic
breathing will transition to gasping
• This transition is mediated by respiratory network reconfiguration of
the preBötC.
• Should an infant fail to both arouse and autoresuscitate, the
irreversible hypoxic insult leads to asphyxiation and the occurrence of
SIDS

103. Hypercapnia
• When is hypercapnia really bad for you?
• Acutely, when PaCO2 is greater than 8.0 to 9.3 kPa (60 to 70 mmHg)
• Patients with chronic hypercapnia may not develop symptoms until
the PaCO2 rises acutely to greater than 90 mmHg because they have
a compensatory increase in the plasma bicarbonate concentration;
• As a result, a larger elevation in PaCO2 is required to produce the same reduction
in pH.

104. O2 and COPD Patients
• Oxygen given to COPD patients may cause secondary hypercapnia
• 1. Ventilation perfusion mismatching (MOST IMPORTANT):
• Your lungs have a finite supply of blood flow. In COPD, you have alveoli that are
well ventilated, and alveoli that are poorly ventilated. Under normal conditions,
there is proper matching between perfusion and ventilation. Less oxygen in
certain alveoli → less blood flow to those alveoli. This frees blood flow to the well
ventilated ones so you can effectively remove CO2. If pure O2 is given, the trickle
of pure O2 is sufficient to cause perfusion of poorly ventilated alveoli, reducing
blood flow to well ventilated ones. Less blood flow to well ventilated alveoli → less
CO2 removal and hypercapnia
• 2. The affinity of CO2 for hemoglobin decreases (Haldane effect).
• -The Haldane effect refers to the rightward displacement of the CO2-hemoglobin
dissociation curve in the presence of increased oxygen saturation
• 3. Minute ventilation decreases because the hypoxic activation of the carotid
chemoreceptors is removed (very small impact on hypercapnia)

105. Altitude Effects
• Short term:
• If PO2 < 60mmHg, hypoxemia is severe enough to stimulate
peripheral chemoreceptors (carotid and aortic bodies) → increased
ventilation
• Increased ventilation means that extra CO2 will be expired and arterial
PCO2 will decrease causing a respiratory alkalosis (pH increase)
• pH increase will inhibit central and peripheral chemoreceptors and
offset the increase in ventilation rate
• Long term:
• 1) Body increases production of 2,3 DPG to shift heme dissociation
curve to the right and unload more O2 into tissues
• 2) Within several days, HCO3- excretion increases (renal
compensation for respiratory alkalosis). This takes away the
chemoreceptor inhibition, allowing for a higher ventilation rate

106. Diving Reflex
• Exposure of the face, nostrils and upper airway to water triggers
diving reflex.
• Triggered by activation of facial and ethmoid nerve sensory afferents.
• First component: Airway protection.
• Breathing is instantaneously stopped.
• Second component: O2 saving strategy.
• Reduced O2 consumption is caused by sympathetically mediated
vasoconstriction in muscles and GI.
• Parasympathetically-mediated bradycardia. Cardiac O2 consumption and
cardiac output are reduced
• Brain perfusion is maintained at a normal level

107. Shallow Water Black Out
• Forced and prolonged hyperventilation before a dive is practiced to
stay under water longer. This is done under the mistaken assumption
that hyperventilation increases stores of blood PO2.
• This is not the case since Hb is saturated with O2 even with normal
ventilation. What hyperventilation does is to lower PaCO2
(respiratory alkalosis) which allows the diver to stay submerged a little
longer because it delays the urge to breathe which is largely driven by
CO2 accumulation.
• The practice of excessive hyperventilation before a dive is dangerous
because a prolonged dive may cause sufficient CNS hypoxia to
produce loss of consciousness and drowning.

108. Exercise and Breathing
• During exercise, ventilation first arises in a stepwise fashion and then
exponentially before leveling out. When exercise is stopped, there is
an initial stepwise fall followed by a steady decline back to baseline
ventilation.
• Central command (top down control of breathing during exercise) and
reflexes from muscles and joint mechanoreceptors cause the initial
rise in ventilation at the onset and the rapid fall at the end of dynamic
exercise
• Humoral factors and reflexes from metabotropic receptors probably
accounts for the delayed increase in ventilation at the onset of
exercise and the slow recovery at the end of dynamic exercise

109. Exercise and Blood Gas Values
• During light to moderate exercise, the lungs are able to compensate
for muscles using more oxygen and producing more carbon dioxide.
Thus, the arterial gases should not change unless the exercise
becomes severe.

110. SLEEP APNEA

111. Prevalence of Sleep Apnea
• 20% in patients over 60 years old!
• 9% in Women
• 24% in Men
• Prevalence increases with age until midlife but is constant after age
60ish.

112. Types of Apnea
• Apnea:
• >10 second cessation of breathing, especially during sleep
• Hypopnea:
• Abnormally slow or shallow breathing
• Reduction of airflow by 30% or more with 4% drop in SaO2 OR
• Reduction of airflow by 50% or more with 3% drop in SaO2 + arousal
• according to class, also lasts at least 10 seconds
• Respiratory-event related arousal:
• Arousals from sleep that do not meet the definition of apnea or hypopnea, but DO disturb sleep.
• Obstructive sleep apnea:
• Disruption of airflow while asleep due to narrowed, blocked, or floppy airway.
• Central sleep apnea:
• Absent respiratory effort. Breathing stops and starts due to lack of proper neuromuscular function.
• Mixed sleep apnea:
• Apnea due to a combination of Central Sleep Apnea and Obstructive Sleep Apnea
• Typically begins as central (without ventilatory effort) and presents with airway obstruction when
ventilatory effort resumes (OSA)

113. Apnea-hypopnea index (AHI):
• Number of apneic and hypopneic episodes per hour
• Normal <5
• Mild 5-15
• Moderate 15-30
• Severe >30

114. Pathogenesis of Sleep Apnea
• Upper airway size naturally decreases during sleep due to decreased
neural stimulation of the upper airway dilator muscles. This itself does
not cause apnea. OSA occurs in individuals with naturally smaller
airways and increased airway collapsibility.
• Upper airway size: smaller in OSA
• Craniofacial disorders
• Enlarged tonsils and adenoids: major risk factor in children between ages 3-5
• Increased tongue size (Down’s Syndrome patients)
• Increased Airway Collapsibility
• In obesity, soft tissues of neck can push down and constrict airway.
• OSA is more common in patients with nasal obstruction (mouth breathing leads
to negative pressure that collapses the pharynx)

115. Risk Factors
• Obesity
• Single most important risk factor for OSA in middle-age adults”
• Enlarged tonsils, Enlarged Adenoids
• Surgery in children, not adults
• Enlarged Tongue (as seen in Down’s Syndrome)
• Craniofacial/ Airway abnormalities
• Mallampati Classification 3 or 4
• Neck size >17 inches
• For women: Post-menopause
• Age
• Prevalence of OSA increases with age until age 60
• Endocrine changes:
• Hypothyroidism => thick and beefy tongue
• Acromegaly

116. Clinical Presentation OS
• Snoring (majority of pts - 50% of pts partners report sleeping in a
separate bedroom)
• Apneic episodes
• Unrefreshing or restless sleep
• Excessive daytime somnolence or fatigue
• Drowsiness while driving
• Decreased libido
• Declines in cognition
• Weight gain

117. Clinical Presentation OS in Children
• Overweight
• Craniofacial Abnormalities
• Large tonsils
• Nightmares
• Daytime somnolence
• Daytime mouth breathing
• Use Polysomnography to confirm
• First line treatment: tonsillectomy, adenoidectomy

118. Differential Diagnosis
• Restless Leg Syndrome
• Narcolepsy
• Delayed sleep-phase syndrome
• Insufficient Sleep Syndrome
• Sleepiness due to meds

119. Diagnosis
• The “gold standard” for the diagnosis of OSA is full overnight
polysomnography, performed in an attended laboratory setting. This
includes monitoring of sleep with electroencephalography (EEG), chin
and anterior tibialis electromyography (EMG), monitoring of breathing
with oronasal airflow and snoring, thoracic and abdominal effort and
pulse oximetry, electrocardiography (ECG), and body position.
• Scoring of sleep stages and arousals from sleep is performed from
the EEG and EMG data.
• Apneas and hypopneas are scored according to the combination of
oronasal airflow data, thoracoabdominal effort, and oxyhemoglobin
saturation
• Unattended sleep studies can be used in patients with very severe
disease. NOT RECOMMENDED IN CENTRAL APNEA.

120. Obstructive vs. Central Apneas
Obstructive
Central

121. Sequelae of OS
• Pathophysiologic mechanisms
• 1. Apneic events lead to sleep fragmentation - disturbs sleep and patient
stuck in lighter stages of sleep
• OSA can lead to sexual dysfunction
• Increased risk of depression
• Significantly increased risk for motor vehicle accidents (2x more)
• 2. Deoxygenation/reoxygenation causes oxidative stress similar to
ischemia/reperfusion events  increase in proinflammatory molecules
• Refractory Hypertension
• Arrhythmias
• Cardiovascular Events
• Stroke
• Atherosclerosis
• Insulin resistance
• INCREASED MORTALITY

122. Treatment of OS
• CPAP
• Delivers constant pressurized air during both inspiration and expiration
• Bilevel positive airway pressure (BPAP)
• Delivers high fixed level of pressure during inspiration and lower fixed pressure during expiration
• Easier to tolerate for severe patients
• Weight loss
• Positional therapy
• Oral appliance therapy
• Patients with mild - moderate OSA
• Those who are unable or unwilling to use PAP
• Surgical Treatment
• Optimal for children
• Unpredictable and less effective in adults

123. Causes of Central Apnea
• Hypocapnic:
• Alteration of CO2 apnea threshold during sleep
• Periodic breathing at high altitude
• Cheynes Stokes
• Instability of Respiratory Control System
• Hypercapnic
• Neuromuscular Diseases
• Sleep-Related Hypoventilation
• Brain stem lesions (syringomyelia specifically mentioned)
• Spinal cord disorders
• Stroke
• Muscle disorders (muscular dystrophy)

124. Cheyne Stokes Breathing
Cycles of 60-120 seconds
Waxing and waning pattern w/ lack of rib cage or abdomen movement

125. Causes of Cheyne-Stokes Apneas
• Systolic heart failure
• Stroke
• Encephalopathies

126. Some things to know from quiz…
• A.
• The airway in obesity is decreased in size primarily in the lateral dimension.
• B.
• The upper airway has properties of a Starling resistor and demonstrates a critical
pressure at which the airway collapses. In normal individuals, this is a negative
pressure, but in those with many obstructive apneas, this pressure is positive
• C.
• Following sleep onset, the neural input to the upper airway dilator muscles
decreases significantly, much more so than to the phrenic nerves.
• D.
• Individuals with obstructive sleep apnea develop what has been called the
pharyngeal myopathy of OSA. It is hypothesized that vibrations from snoring
initiate an inflammatory response within the muscles.

127. Obesity Hypoventilation Syndrome
• BMI > 30
• Awake alveolar hypoventilation
• Sleep-disordered breathing
• Daytime hypoxemia
• Dyspnea on exertion
• Serum Bicarbonate Level > 27 mEq/L (elevated bicarb)
• indicates increased paCO2
• Diagnosis with ABGs

128. Treatment of Obesity Hypoventilation
• CPAP
• 50% of patients need CPAP + Supplemental Oxygen
• Non-invasive ventilation BPAP + Backup Rate
• For use if CPAP + Oxygen is ineffective
• Weight Loss
• Bariatric surgery in some patients, but patients with obesity
hypoventilation syndrome are not recommended for bariatric surgery.

129. ASTHMA

130. Cytokines and TH2 Response
• IL-4, IL-5, IL-9, IL-13
• Lymphocytes of TH2 phenotype (CD4+) are thought to be a prominent
component of the inflammatory response in asthma.
• IL-5 has a chemoattractant effect for eosinophils, stimulates growth, stimulates
activation, and stimulates eosinophilic degranulation.
• IL-4 is inflammatory by activating B lymphocytes, enhancing synthesis of IgE,
and promoting TH2 differentiation.
• IL-13 also induces IgE synthesis, as well as mediating many various effects of
cells involved with the inflammation of asthma.
• IL-9 promotes growth of TH2 cells, B cells and Mast cells, IgE production and
production of cytokines by smooth muscle cells

131. IL-4 and IgE
• IL-4 promotes release of IgE antibodies from B cells

132. 3 Functions of IL-4
• 1. B cell activation
• 2. IgE synthesis
• 3. Differentiation of Th2 cells

133. IL-4 vs. IL-13
• Similarity: Both play a role in making Th2 cells. IL-4 induces the
differentiation while IL-13 induces the production of Th2 cells. Both
make lung endothelium produce VCAM, making it “sticky” for
eosinophils. Both induce IgE production
• Differences: IL-13 has broader effects on epithelium and smooth
muscle cells

134. IL-5
• IL-5 is the only known eosinophil hematopoietin aka it causes
production of eosinophils from bone marrow stem cells
• IL-5 is an important survival factor for eosinophils
• IL-5 is chemotactic for mature eosinophils and a priming factor for
enhanced functional activities

135. Clinical Asthma and Allergen Removal
• Removal from environment improves but does not eliminate asthma
• Studies show improvement in lung function, quality of life, allergic
mediator release, and rescue medication use
• However, bronchial hyperreactivity (“twitchy” airways) and airway
inflammation persist FOREVER

136. Innate vs. Adaptive Immunity in Asthma
• If asthma were a disease of the adaptive immune system, then
therapies targeting adaptive immune responses would be curative:
• Anti-IgE
• Anti-Thelper/Thelper cytokines
• Immunotherapy
• Allergen/antigen avoidance
• With an authentic allergic, T cell-mediated disease (i.e. seasonal
allergic rhinitis), exposure actually correlates with symptoms, and the
disease resolves in the absence of exposure
• New Theory:
• Epigenetic programming of epithelial cells promotes release of cytokines IL-25, IL-
33 and TSLP even in absence of T cells driving eosinophilia and day-to-day
symptoms
• Adaptive immune responses via T/B cell responses primarily drive exacerbations
and are well treated by targeted immune therapies

137. Remodeling-prone Asthma
• Airway remodeling likely results from chronic inflammation and the
associated production and release of mediators like growth factors
• Remodeling  epithelial damage, airway fibrosis (collagen), and
smooth muscle hyperplasia
• Increase in SMCs  hyperresponsiveness of the airway to stimuli 
Persistent airflow obstruction
• Overdistention of the lungs and airway occlusion by thick mucous
plugs
• Histology:
• Edema and cellular infiltrates within the bronchial wall
• “Fragile” appearance of the epithelium and detachment of epithelial cells
• Hypertrophy and hyperplasia of the smooth muscle layer
• Increased deposition of collagen (basement membrane thickening) = fibrosis.
• Hypertrophy of mucous glands

138. Steroid Resistance
• Inhaled corticosteroids are the recommended standard medication for
persistent asthma
• Start at low dose in mild disease and move to higher doses
• Most of the clinical efficacy of ICS’s is obtained at lower doses
• Steroid-resistant asthma is defined by the failure to improve FEV1 by
15% after treatment with high oral corticosteroid doses for 2 weeks
• Characterized by persistent eosinophilia despite a high dose of inhaled
corticosteroid
• Largely a T lymphocyte problem (continued production of cytokines IL4, IL5, and
IL13) despite corticosteroid presence.
• Steroid resistance does NOT affect the side effect profile (i.e.
osteoporosis, metabolic syndrome, HBP, DM, obesity, myopathy,
glaucoma/cataracts, etc.)
• Corticosteroids are ineffective in resistant asthma,
• DON’T prescribe them

139. Eosinophilic vs. Non-eosinophilicAsthma
• Eosinophilic asthma = steroid sensitive (except in steroid-resistant)
• Non-eosinophilic asthma = steroid resistant
• May exacerbate symptoms by inhibiting apoptosis of PMNs

140. Omalizumab
• Allergen-exacerbated asthma is diagnosed by:
• 1) evidence of a specific IgE (via skin prick or IgE immunoassay)
• 2) evidence of allergen-exacerbation of symptoms (allergic rhinitis, asthma)
• Omalizumab binds free IgE in the serum at the same site that the
high-affinity IgE receptor (on mast cells) binds. Thus, IgE cannot bind
to its receptor on mast cells. Eventually, the number of IgE receptors
on mast cells decreases over time.
• Omalizumab seems to significantly improve the number of asthma
exacerbations, but it does NOT eliminate asthma
• It has a minimal influence on lung function, symptoms, or severity
• This is likely because allergens exacerbate asthma but have little to
do with day-to-day asthma symptoms or severity

141. Aspirin Sensitive Asthma
• Some people have asthma exacerbation after taking ASA or NSAIDs
b/c the inhibition of COX results in a shifting of arachidonic acid
pathways toward the production of bronchoconstrictor leukotrienes.
• AERD is characterized by pathognomonic elevation of LTC4 synthase
expression with profoundly increased, constitutive, and aspirin-induced
leukotriene production. It also has a pathognomonic
elevation of leukotriene receptor expression.
• Leukotriene Modifiers significantly improve sx in these patients
• Leukotriene receptor antagonists (Montelukast, Zafirlukast) improve lung
function, decrease bronchodilator use, reduce symptoms, and improve quality
of life
• Zileuton - may be effective in reducing upper airway symptoms (loss of smell,
rhinorrhea, congestion)

142. ASTHMA
MANAGEMENT

143. Asthma Predictive Index

148. Exacerbating Factors
• Viral Infections
• Most common cause of asthma symptoms in the 0-4 age group.
• Allergies
• GERD
• Chronic sinusitis
• Obstructive sleep apnea
• Allergic bronchopulmonary aspergillosis

149. PHARMACOLOGY

150. Beta Agonists
• MOA:
• Stimulation of B2 receptors in SMCs activates Gs adenylyl cyclase 
increased cAMP  increased conductance of Ca++-sensitive K+ channels 
Hyperpolarization
• Airway smooth muscle relaxation and bronchodilation
• cAMP also inhibits histamine release from mast cells and TNF release from
monocytes
• Clinical Use: Primary therapy for Asthma and COPD
• Short acting: albuterol, levalbuterol
• Long acting: Salemterol, Fomoterol
• Side Effects
• Tachyarrhythmia
• Tremulousness (trembling)
• Muscle cramps
• Nervousness
• Hypokalemia

151. Anticholinergics
• MOA:
• Competitive inhibition of ACh at muscarinic receptors relaxes bronchial constriction
normally caused by parasympathetic (ACh) stimulation of M3 receptors
• Parasympathetic stimulation of M1 and M3 receptors causes mucus secretion as
well, so anticholinergics decrease mucus secretion
• Clinical Use: First line for COPD also used in asthma
• Short acting: Ipratropium
• Long acting: Tiotropium
• Side Effects
• Constipation
• Xerostomia (dry mouth)
• Pharyngitis
• Urinary retention
• Sinusitis
• Upper respiratory infection

152. Methylxanthines
• Theophylline (1,3 dimethylxanthine)
• rarely used today
• MOA:
• Nonselective PDE inhibitor (increases cAMP) and an adenosine receptor antagonist
→ relaxes smooth muscle through blocking adenosine receptors on mast cells
• Also inhibits synthesis and secretion of inflammatory mediators from numerous cell
types, including mast cells and basophils
• Clinical Use: Rare, Acute and chronic asthma
• Side Effects:
• NARROW THERAPEUTIC WINDOW
• Nausea & vomiting
• tremors
• irritability
• restlessness
• tachyarrhythmias (Afib)

153. Corticosteroids
• MOA: Suppression of inflammatory responses by interference with multiple signal
transduction and gene expression pathways.
• Decrease cytokine formation
• Decrease PAF production
• Inhibit cysteinyl leukotrienes
• Clinical Use:
• FIRST LINE THERAPY (inhaled not systemic)
• Risk of adverse effects increases with dose
• Side Effects:
• HPA Suppresion
• Hypertension
• Immunosuppression
• Osteoporosis
• Myopathy
• Cataracts
• Growth arrest
• Fat redistribution

154. Leukotriene Modifiers
• MOA:
• LTD4 receptor antagonists (zafirlukast, montelukast)
• Reversible inhibitor of cysteinyl leukotriene-1 receptor
• 5-lipoxygenase inhibitors (zileuton)
• Prevents conversion of arachidonic acid to leukotriene A4
• LB4 is also decreased
• Clinical Use:
• Preventative treatment of asthma, especially AERD
• Anti-leukotriene agents can be effective as monotherapy in the treatment of
mild to moderate persistent asthma.
• Not as effective as ICGCs.
• Side Effects
• Abnormal LFTs
• Headache
• Eosinophilic Vasculitis.

155. Omalizumab
• MOA:
• DNA-derived humanized monoclonal Ab
• At recommended doses, omalizumab reduces free IgE by more than
95%, thereby limiting the amount of IgE bound to Fc R1-bearing cells
• Also decreases amount of FcRI receptor expressed on these cells
• Clinical Use
• Allergic Asthma
• Chronic Idiopathic Urticaria
• Side Effects:
• Thrombocytopenia,
• Anaphylaxis,
• Dermatologic
• Costly

156. PDE Inhibitors
• PDE4 Inhibitor: increases intracellular cAMP and reduces neutrophil
and eosinophil infiltration
• PDE4 is a major enzyme that hydrolyzes and inactivates cAMP
• Romflumilast
• Clinical Use: Prevention of COPD Exacerbations
• Side Effects:
• Diarrhea, nausea
• Headache
• Decreased appetite
• Weight loss
• Suicidal thoughts

157. Mucolytics
• 1) Hypertonic Agents
• Ex: Inhaled hypertonic saline or mannitol
• MOA: Hypertonic agents draw water into the airway to lower mucus viscosity.
• Side Effects: Can cause bronchospasm  therefore used following a bronchodilator
• General: cheap with good results (disadvantage: time consuming)
• 2) N-acetyl cysteine (NAC): CF and Bronchiectasis
• MOA: Lowers mucus viscosity by cleaving disulfide bonds via its free sulfhydryl group.
• Side Effects: bronchospasms (use 15 min. after bronchodilator), smells, expensive
• 3) Inhaled DNAse: CF
• MOA: Breaks down purulent sputum by cleaving DNA strands.
• Side Effects: laryngitis, pharyngitis, chest pain, conjunctivitis, dyspnea, expensive, change in
voice
• 4) Ivacaftor: CF
• MOA: CFTR protein potentiator for G551D mutation of CF. Decreases [Cl-] in sweat.
• Side Effects: Increased LFTs, rash, abdominal pain, HA, nausea, dizziness, nasal congestion,
nasopharyngitis, upper resp infxn.

158. Therapy for Pulmonary Hypertension

159. Prostanoids
• MOA:
• Prostacyclin stimulates adenylate cyclase to convert ATP to cAMP 
decrease in intracellular Ca SMC relaxation
• Prostacyclin also inhibit platelet aggregation
• Clinical Use:
• Pulmonary Hypertension
• Side Effects:
• Hypotension
• Flushing
• Jaw pain
• Headache
• Nausea/vomiting,
• Hypersplenism,
• Line infection

160. Guaifenesin
• MOA: Irritant of vagal receptors in the gastrum activating
parasympathetic reflexes which result in secretion of a less viscous
mucous.
• Clinical Use: Expectorant used to help with clearing of phlegm in
setting of acute respiratory infections
• Does not suppress cough reflex
• Use Dextromethorphan
• Side Effects:
• Minimal Side Effects

161. COMMON COLD

162. Seasonal Patterns of Viruses
• Rhinovirus
• Sharp increase in September
• Parainfluenza
• October/November peak
• Coronavirus/RSV
• Winter months
• Influenza
• Mid to late winter
• Adenovirus
• Year round

163. Frequency of Infection
• 1 to 5 year olds (preschool children): 8+ colds per year
• 6 to 12 year olds (school children): 5 to 6+ colds per year
• Adolescents: 4 to 5 colds per year
• Adults: 2 to 3 colds per year

164. Modes of Transmission
• 3 Modes
• “Hand contact: Self-inoculation of one’s own conjunctivae or nasal mucosa after
touching a person or object contaminated with cold virus -most efficient transmission
• MOST COMMON
• Inhalation of small particle droplets that become airborne from coughing (droplet
transmission) -more so with influenza
• Deposition of large particle droplets that are expelled during sneezing and land on
nasal or conjunctival mucosa

165. Pathogenesis
• Deposition on nasal mucosa
• Mucociliary transport to nasopharynx
• Virus enters epithelial cell after receptor binding
• Replication begins within 8 to 10 hrs of inoculation
• Influx of PMN’s in nasal submucosa and epithelium
• Increase albumin and inflammatory mediators in nasal secretions
• Nasal mucosa remains intact
• Symptoms begin in 1 to 2 days

166. Natural History
• Day 1 to 2: Sore or scratchy throat, congestion
• Day 2 to 3: Nasal obstruction, sneeze and rhinorrhea
• Day 4 to 5: Cough
• Day 7: Resolved
• May last up to 2 weeks in 25% of adults

167. Differential Diagnosis
• Common cold
• Allergic or seasonal rhinitis
• Bacterial pharyngitis
• Sinusitis
• Influenza
• Pertussis
• Nasal foreign body

168. Allergic Rhinitis Itchy, watery eyes, nasal congestion,
sneezing, scratchy throat, fever uncommon
“Allergic Shiners”
Bacterial Pharyngitis Prominent sore throat, Absent nasal
congestion/cough, fever common, purulent
exudate, swollen tonsils, erythema of pharynx
Sinusitis Presents after a cold begins to improve, facial
or tooth pain, purulent nasal/post-nasal
drainage, don’t respond to decongestants,
fever, malaise
Influenza Abrupt onset, fever, myalgias, headache,
malaise, nasal congestion, cough, sore throat
Pertussis Catarrhal phase: 1 week, low-grade fever,
rhinorrhea, malaise, sneeze, mild cough
Paroxysmal phase: 1-6 weeks, bursts of
rapid coughs, gasp, whoop, apnea, emesis
Nasal Foreign Body Nasal congestion, purulent nasal
discharge(usually uniteral), sneeze, halitosis,
young child

169. Children < 6
◦ Fever
◦ Nasal congestion
◦ Rhinorrhea
Clear to green
◦ Sneeze
◦ Cough
◦ Irritability
◦ Swollen glands
◦ 7 to 14 days
Older children and adults
◦ Nasal congestion
◦ Rhinorrhea
Clear to green
◦ Sore, scratchy throat
◦ Malaise
◦ Sinus fullness
◦ Hoarseness
◦ Sneeze, cough
◦ 5 to 7 days
Symptoms and Signs

170. Prophylaxis
• Frequent handwashing with non-antibacterial soap and water
• Hand sanitizers may be less effective
• Virucidal tissues may decrease secondary transmission of respiratory
infection within the household or other close-contact settings
• Physical barriers: gloves, masks, gowns, etc.
Likely beneficial Maybe beneficial Unclear benefit No benefit
Zinc Probiotics Gargling Vitamin C
Ginseng Vitamin D
Exercise Echinacea
Garlic

171. Symptomatic Treatment for Adults
• Nasal symptoms
• Single dose of nasal decongestant in adults
• Antihistamine/decongestant combinations
• Newer non-sedating antihistamines not effective
• Guaifenesin
• Cough
• Dextromethorphan
• Inhaled ipratropium bromide
• Fever, achiness
• Acetaminophen
• NSAID’s
• ANTIBIOTICS ARE NOT EFFECTIVE

172. Symptomatic Treatment for Children
• Very few effective treatments!!!

173. Complications
• Secondary effects of localized inflammation - Bacterial superinfection
• Inflammatory response in susceptible host- Asthma
• More extensive viral infection in susceptible host
• Viral-induced wheezing:
• Bronchiolitis
• Pneumonia : rhinovirus and RSV may cause severe lower respiratory
tract infection in infants and children
• Bacterial acute otitis media : may complicate 30% to 50% of URIs in
young children
• Paranasal sinus abnormalities
• Bacterial sinusitis : may complicate 8% to 10% of URIs in children
• Pre-orbital cellulitis
• Orbital cellulitis
• Orbital abscess

174. ALLERGIC RHINITIS
AND SINUSITIS

175. List three functions of the sinuses.
• Insulate brain
• Crumple zone to protect brain from injury
• Decrease weight of skull

176. Sinusitis
• Inflammation of mucous membranes lining paranasal sinuses
• In adults sinusitis most often occurs in maxillary sinus, whereas in
children it is most common in ethmoid sinus

177. You are born with 4 sinuses

178. Anatomic landmarks of the nasal cavity
and paranasal sinuses.

179. Key clinical features of Migraine
• Unilateral throbbing pain
• Phonophobia / photophobia
• Nausea / Vomiting
• Lasting hours to days (but probably less than a week)
• Triggers can include: allergies (histamine release), sinusitis, sinonasal
contact points
• Can trigger vasomotor symptoms including: rhinorrhea/nasal
congestion, ocular tearing
• Migraine triggers the maxillary branch of the trigeminal nerve, and the nerve winds
up also triggering ocular tearing, rhinorrhea, symptoms of nasal congestion. =

180. Allergic vs. Nonallergic Rhinitis
• Rhinitis: irritation and inflammation of mucous membrane in nose
• Rhinorrhea: nasal cavity is filled with a significant amount of mucus
• Allergic Rhinitis
• Paroxysmal sneezing with seasonal variation
• Pruritus
• Anterior/Clear rhinorrhea
• Allergic conjunctivitis
• Positive Family history
• + skin allergy test
• Non-allergic Rhinitis
• Less sneezing
• No pruritis
• Posterior drainage

181. Pathognomonic Signs of Allergic Rhinitis
• Allergic shiners; periocular edema
• Dennie’s Morgan’s lines – wrinkles from long term edena
• Supratip nasal creases
• Large bluish turbinate – venous blood due to congestion

182. Treatment for Allergic Rhinitis
• First Line: Nasal Corticosteroids
• Environmental Control
• Saline Irrigation
• Antihistamines
• Reduce production of clear secretions
• Reduces pruritus and sneezing
• Clinically much less effective than nasal steroids
• Decongestants
• Ephedrine, Phenylephrine, Dextromorphan
• Vasoconstriction by alpha-agonists (epinephrine, NE) will decrease the blood flow and
therefore decrease inflammation and mucus formation at the site of application.
• Leukotriene modifiers
• Montelukast/Zafirlukast
• Zileuton
• Nasal cromolyn
• Allergen immunotherapy

183. Immunotherapy in Allergic Rhinitis
• Clinical Indications:
• Poor response to pharmacotherapy/allergen avoidance
• Unacceptable adverse effects of medications
• Desire to avoid long-term pharmacotherapy and reduce costs
• Possible prevention of asthma in children
• 85-90% of patients who receive high-dose maintenance IT report
significant efficacy:
• reduced symptoms
• reduction in medication requirements
• IT must be administered in a setting where prompt recognition and
treatment of anaphylaxis is assured

184. Acute Infectious Rhinosinusitis
• Symptoms:
• Purulent nasal discharge
• Nasal obstruction
• Facial pain/pressure/fullness
• Almost always viral
• Acute Bacterial Rhinosinusitis (ABRS) vs. Viral Acute Rhinosinusitis
(Viral ARS)
• 0.5-2.0% of VRS progresses to ABRS
• Diagnosis based on duration and/or pattern
• More likely to be ABRS if symptomatic for >10 days or if the symptoms improve,
then worsen

185. Antibiotic Therapy
• Antibiotics ONLY indicated in ABRS, ineffective for VRS
• First line therapy: Amoxicillin/Clavulanic Acid
• PCN allergy:
• Adults: Doxycyclin
• Children: Respiratory quinolone or Clindamycin + 3rd gen Cephalosporin
• NO ROLE for macrolides

186. Treatment for Viral Sinusitis
• Supportive
• Saline Irrigations (no evidence)
• Topical vs. Systemic decongestants
• Oxymetazoline (Afrin)
• Phenylephrine (Neosynephrine, Sudafed PE)
• Pseudoephedrine (Sudafed)
• Pain control
• Systemic steroids – no evidence
• Topical steroids – weak evidence

187. Rhinitis/Sinusitis and Asthma
• Sinonasal pathology is the most common co-morbidity among
patients with asthma
• In patients with asthma, inflammation in the nose and sinuses share
features of disease in the lung
• Allergic rhinitis is a risk factor for asthma
• Childhood allergic rhinitis significantly associated with the presence of
asthma
• Asthmatics with sinusitis are more likely to have nasal polyps
complicating their sinus disease than non-asthmatics, and asthmatics
are more likely to have persistent disease over years that requires
multiple surgeries

188. Chronic Rhinosinusitis w/ or w/out Polyps
• Diagnosis:
• 1. Twelve weeks or longer of two or more of the following:
• Mucopurulent drainage
• Nasal obstruction → congestion
• Facial pressure-fullness
• Decreased sense of smell
• 2. AND documentation of inflammation by one or more of the
following findings:
• Purulent mucus OR edema in the middle meatus or ethmoid region
• Polyps in nasal cavity OR middle meatus
• Radiographic imaging showing inflammation of the paranasal sinuses

189. Nasal polyps are often associated with
Cystic Fibrosis

190. Rhinosinusitis with Nasal Polyposis
• The characteristic presentation of CRS with NP is gradually
worsening nasal congestion/obstruction, sinus fullness and pressure,
fatigue, posterior nasal drainage, and hyposmia or anosmia.
• In contrast, fever and severe facial pain are uncommon.
• On physical examination, large polyps are often visible with anterior
rhinoscopy, while smaller polyps require nasal endoscopy or imaging.
Nasal polyps lack sensation.

191. Eosinophilic Sinusitis
• More likely to have polyps and/or asthma
• 32% of asthmatics have polyps
• 20% of patients with polyps have asthma
• Less likely to have pain
• Th2-mediated process
• Mucous is laden with eosinophils, leukotrienes, IL-4 and IL-5
• Treatment: Corticosteroids
• Saline Irrigations
• Leukotriene or IgE Inhibitors

192. Sinus Surgery
• Rhinosinusitis Sinus Surgery = Functional Endoscopic Sinus Surgery
• Reserved for medical failures
• Improves quality of life in 72-76% of patients
• Average improvement of 16-22%
• Sinus Surgery Improves Asthma
• Reduces symptoms, lowers steroid dose & frequency of steroid use
• Improves lung function
• Decreases bronchial hyperreactivity
• NOT SUPERIOR TO MEDICAL THERAPY

193. Nasal Polyps can develop from Rhinitis,
Cystic Fibrosis and Aspirin Intolerant
Asthma

194. OTOLARYNGOLOGY
PATHOLOGY

195. Differential Diagnosis of Hoarseness
 Infectious
 Acute laryngitis: common cold, URI (virus) or voice strain
 Neoplastic
 Squamous cell carcinoma
 Idiopathic
 Papilloma
 Iatrogenic
 Injury to recurrent laryngeal nerve (e.g. thyroid surgery)
 Functional
 Laryngeal polyp/nodule (Singer’s nodule)
 Smoking
 GERD
 LPRD (laryngopharyngeal reflux)
 Parkinson’s or stroke
 Allergies
 Thyroid problems

196. Define stridor and evaluate the child who
presents with stridor.
• High pitched inspiratory and expiratory sound that serves as a sign of
fixed upper airway obstruction
• Epiglottitis: H. Influenzae
• Croup: Parainfluenza

197. Pleomorphic Adenoma
• Most common salivary gland neoplasm
• Clinical features
• Wide age distribution
• Most common in 4th decade
• Female > male
• Most common location: parotid gland
• Gross features
• Overall well-circumscribed
• Often with small protrusions into adjacent normal tissue; may lead to local recurrences
• Microscopic features
• Biphasic: Admixture of epithelial and stromal elements
• Epithelium: Glands or cords of small cuboidal cells
• Stroma: Fibromyxoid +/- cartilaginous differentiation
• Prognosis
• Vast majority are benign, Recurrence rate is highly dependent on adequacy of original resection
• Malignant transformation: Occurs in ~5% of cases

198. Warthrin Tumor
• Clinical features
• Wide age distribution
• Most common in 6th and 7th decades
• Male >> female
• Most common location: parotid gland
• Bilateral in 10% of cases
• Gross features
• Well-delineated, lobulated mass
• May be cystic or multicystic
• Microscopic features
• Epithelium:
• Oncocytic - large, eosinophilic, granular cells
• Lymphoid tissue:
• May form lymphoid follicles
• Prognois: Benign

199. Mucoepidermoid Carcinoma
• Clinical features
• Most common in 5th decade
• Most common malignant salivary gland tumor in children
• Female > male
• Low-grade and high-grade types
• Gross features
• Low-grade: Well-circumscribed mass with cystic areas
• High-grade: Solid, infiltrative pattern of growth
• Microscopic features
• Three distinct cell types:
• Squamous
• Mucin-producing
• Intermediate
• Low-grade: well-differentiated
• High-grade: poorly-differentiated
• Prognosis
• Highly dependent on grade
• Low-grade: 5 yr survival of 98%
• High-grade: 5 yr survival of 56%

200. Adenoid Cystic Carcinoma
• Clinical features
• Most common malignant tumor of minor salivary glands
• Wide age distribution: 20 - 80 yo
• Median age = 50 yo
• Gross features
• Solid infiltrative pattern of growth
• Can invade nerves and move to brain
• Microscopic features
• Small, cuboidal, cytologically bland cells
• Arranged in cribriform patterns
• Some of the lumen-like spaces contain distinctive eosinophilic materia
• Prognosis: Poor, highly malignant, perineural invasion

201. Laryngeal Polyp
• Distinctive non-inflammatory reactive change
• Etiology: Injury - “misuse” of voice
• S/sx: Hoarseness
• Gross: Polypoid mass on vocal cords
• Microscopic: Varies with stage of evolution of lesion
• Prognosis: benign

202. Juvenile Laryngeal Papillomatosis
• Age: presents in children / adolescents
• Etiology: human papilloma virus (HPV)
• Gross:
• Multiple papillary growths on vocal cords
• May spread throughout larynx
• Microscopic features
• Papillary growths of well-differentiated squamous epithelium
• Prognosis
• Repeated recurrences
• Usually benign
• Vary rarely development of squamous cell carcinoma

203. Squamous Cell Carcinoma
• Clinical Features
• > 90% of laryngeal carcinomas are SCC
• Age - 5th decade or older
• Male > > > female
• Risk factors:
• Cigarette smoking
• Heavy alcohol consumption
• Gross features
• Mass protruding into airway, may be ulcerated
• Typically 1 - 4 cm
• Microscopic features
• Cytologically malignant squamous epithelium
• Prognosis
• Glottic tumors
• Arise from true vocal cords
• Tend to remain localized
• Transglottic tumors
• Tumor crosses laryngeal ventricle
• High rate of lymph node metastases

204. COPD AND
BRONCHIETETASIS

205. Emphysema
• Pathophysiology:
• Abnormal enlargement of air spaces distal to terminal bronchioles
• Destruction of alveolar walls resulting from elastase-antielastase imbalance
• Centriacinar (respiratory bronchioles) in upper lobes vs panacinar (alveolar
ducts; associated with alpha-1 antitrypsin deficiency) in lower lobes
• Collapse of airways due to loss of alveolar compliance
• Gross Morphology:
• Hyperinflated lungs, Air trapping, Dilated alveoili
• Bullae on surface of lungs (panacinar)
• Smoking  upper lobe (Centriacinar)
• Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space
on CXR
Microscopic:
• Inflammation, fibrosis and carbonaceous pigment common in adjacent alveolar
and bronchial walls

207. Barrel Chest
Prolonged expiration with pursed lips,
forces walls open to allow expiration

208. Chronic Bronchitis
• Pathophysiology:
• Enlargement of the bronchial mucous glands and expansion of goblet cell
population. Hypersecretion of mucus  mucous plugs.
• Gross Morphology:
• Visible bronchi
• Principal sites of increased air resistance in COPD are the small distal airways
• Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space
on CXR
• Microscopic:
• Brown-pigmented macrophages with sparse neutrophil and lymphocytes in
walls of terminal bronchioles
• Fibrosis, goblet cell and squamous cell metaplasia of epithelium, smooth
muscle enlargement, scattered regions of mucous plugging
• Seromucinous gland hyperplasia

210. Chronic Bronchitis is diagnosed clinically:
Chronic productive cough lasting 3
months over at least 2 years

211. Asthma
• Pathophysiology
• Bronchial asthma is a chronic relapsing inflammatory disease with hyper-reactive
airways, leading to episodic, reversible bronchoconstriction owing to
increased responsiveness of the tracheobroncheal tree to various stimuli.
• Gross Morphology
• Lungs are greatly distended with air and show patchy atelectasis with
occlusion of airways by thick mucus plugs.
• Microscopic
• Sub-basement membrane fibrosis
• Edema and inflammatory infiltrate in bronchial walls with eosinophils.
• Hypertrophy of bronchial wall musculature and submucosal glands.
• Whorls of shed epithelium forming mucous plugs (Curschmann’s spirals)
• Collection of crystaloid made up of debris of eosinophil membranes (Charcot-
Leyden crystals)

212. Asthma is most often associated with
allergic stimuli: Type 1 HSR
IL4 (IgE), 5 (Eos) , and 10 (TH2)
Also IL-13 and IL-9

213. Bronchiectasis
• Abnormal permanent dilatation of the bronchi and bronchioles.
• Caused by repeated cycles of airway infection/inflammation
• Distal airways become thickened
• Mucosal surfaces develop edema and suppuration
• Neovascularization of the adjacent bronchial arterioles occurs.
• Hemoptysis, Sputum
• Bronchiectasis shares many clinical features with chronic obstructive
pulmonary disease (COPD)
• Inflamed and easily collapsible airways
• Obstruction to airflow
• Frequent office visits and hospitalizations.
• Dx: Chronic daily cough with viscid sputum production and presence
of bronchial wall thickening and luminal dilatation on HRCT.

214. Bronchiectasis
• Presentation
• Cough
• Purulent sputum production
• Hemoptysis
• Recurrent infection
• Bronchial hyper-reactivity
• Obstructive lung disease

216. Localizing Bronchiectasis
• Upper Lobe
• Cystic Fibrosis
• Lower Lobe
• Aspiration Syndromes
• Right Middle Lobe and Lingula
• Nontuberculous Mycobacterial Infection
• Central
• Allergic Bronchopulmonary Aspergillosis

217. Treatment of Bronchiectasis
• 1. Antibiotics
• 2. Bronchopulmonary drainage
• 3. Bronchodilators
• Chest Physical Therapy
• Inhaled DNA-ase for CF patients

218. Presence of P. Aeroginosa portends a
worse prognosis in bronchiectasis

219. Pink Puffers and Blue Bloaters
• Pink Puffers - associated with severe emphysema
• Cachexia, unrelenting dyspnea, severe lung hyperinflation, normal
(or near normal) ABG at rest because the body compensates by
hyperventilating (hence the puffer). Low cardiac output  muscle
wasting and weight loss. The pink can be from a number of things,
one of which is using neck and chest muscles to breathe.
• Blue Bloaters - associated with chronic bronchitis
• Stout body habitus, chronic cough and sputum, dyspnea, severe
hypoxia and hypercapnia (leading to polycythemia and signs of
right-sided heart failure)

221. COPD vs. Asthma
• Factors that favor COPD over Asthma
• Older age
• current/past smoker
• Hx acute bronchitis
• chronic cough, sputum production or wheezing
• Factors that favor Asthma over COPD
• Young age
• No smoking history
• Atopy
• Variability of Sx over time
• Reversible obstruction

222. Natural Progression of COPD
• Chronic obstructive pulmonary disease (COPD) is characterized by
poorly reversible airflow obstruction and an abnormal inflammatory
response in the lungs
• Innate and adaptive immune responses to long term exposure to noxious
particles and gases, particularly cigarette smoke.
• This amplified response may result in mucous hypersecretion (chronic
bronchitis), tissue destruction (emphysema), and disruption of normal
repair and defence mechanisms causing small airway inflammation and
fibrosis (bronchiolitis).
• 1. Inflammation
• 2. Imbalance of Proteases and Antiproteases
• 3. Oxidative Stress

223. COPD Diagnosis
Airflow limitation measured by FEV1 % Predicted
All patients with FEV1/FVC reduced to < 0.70
GOLD 1 Mild >80%
GOLD 2 Moderate 50 – 80%
GOLD 3 Severe 30 – 50%
GOLD 4 Very Severe <30%

224. COPD Classification
Patient
Category
Characteristics
GOLD
FEV1
Frequency
Exacerbation
CAT MMRC
A Low Risk
Less Symptoms
GOLD 1-2
FEV1 > 50% ≤ 1 < 10 0-1
B Low Risk
More Symptoms
GOLD 1-2
FEV1 > 50% ≤ 1 ≥ 10 ≥ 2
C High Risk
Less Symptoms
GOLD 3-4
FEV1 < 50% ≥ 2 <10 0-1
D High Risk
More Symptoms
GOLD 3-4
FEV1 < 50% ≥ 2 ≥ 10 ≥ 2

225. Patient
Category
Characteristics
GOLD
FEV1
Frequency
Exacerbation
CAT MMRC
A
Low Risk
Less Symptoms
GOLD 1-2
FEV1 > 50%
≤ 1 < 10 0-1
Patient
Category
1st Choice Tx 2nd Choice Tx 3rd Choice Tx
A
SAMA PRN
or
SABA PRN
LAMA or
LABA or
SAMA+SABA
PDE inh
(Theophylline)
Category A Therapy

226. Patient
Category
Characteristics
GOLD
FEV1
Frequency
Exacerbation
CAT MMRC
B
Low Risk
More Symptoms
GOLD 1-2
FEV1 > 50%
≤ 1 ≥ 10 ≥ 2
Patient
Category
1st Choice Tx 2nd Choice Tx 3rd Choice Tx
B
LAMA or
LABA
LAMA+LABA
SABA and/or SAMA
Theophylline
Category B Therapy

227. Patient
Category
Characteristics
GOLD
FEV1
Frequency
Exacerbation
CAT MMRC
C
High Risk
Less Symptoms
GOLD 3-4
FEV1 < 50%
≥ 2 <10 0-1
Patient
Category
1st Choice Tx 2nd Choice Tx 3rd Choice Tx
C
ICS and
LAMA or LABA
LAMA+LABA or
LAMA+PDE4I or
LABA+PDE4I
SABA and/or SAMA
Theophylline
Category C Therapy

228. Patient
Category
Characteristics
GOLD
FEV1
Frequency
Exacerbation
CAT MMRC
D
High Risk
More Symptoms
GOLD 3-4
FEV1 < 50%
≥ 2 ≥ 10 ≥ 2
Patient
Category
1st Choice Tx 2nd Choice Tx 3rd Choice Tx
D
ICS and
LAMA and/or
LABA
ICS+LAMA+LABA or
ICS+LAMA+PDE4I or
ICS+LABA+PDE4I
Mucolytics
SABA and/or SAMA
Theophylline
Category D Therapy

229. First Line: Tiotropium + SABA prn
Steroids for exacerbations (Advair)

230. Pharmacotherapy

231. Alpha 1 Antitrypsin Deficiency
• α1-antitrypsin is a protease inhibitor and protects lung tissue against
neutrophil elastase and other proteases.
• Encoded by the gene PI
• M: Normal wild type
• Z: Most common mutant leading to deficiency
• ZZ homozygous: Severe Disease
• Symptoms
• Lung
• COPD: Panacinar emphysema
• Possible bronchiectasis or asthma
• Suspected from uncontrolled destruction by neutrophil elastase in the lung
• Liver
• Childhood liver disease
• Adulthood cirrhosis of liver & hepatocellular carcinoma
• Suspected from abnormal deposition of dysfunctional AAT protein
• Skin
• Necrotizing panniculitis, vasculitis, urticaia, angioedema

232. Alpha 1 Antitrypsin Diagnosis
• Emphysema in a young age (< 45 yo)
• Emphysema in non-smokers
• Basilar distribution of emphysema
• Concurrent liver or skin disease
• Serum levels of AAT: below 50 mg/dL
• Genotyping to look for S or Z alleles

233. PFTS
Disease PFT Pattern
Asthma Obstructive and Reversible
Chronic Bronchitis Obstructive, Irreversible, Normal DLCO
Emphysema Obstructive, Irreversible, Low DLCO
Bronchiectasis Obstructive
Cystic Fibrosis Obstructive, FEV1 correlates with outcomes

234. Cystic Fibrosis
• Autosomal Recessive defect in CFTR chloride channel
• CFTR dysfunction reduces chloride secretion from the epithelialial
cells into the airway lumen  sodium absorption into the cell is
markedly increased  thinning of the airway surface’s liquid lining
layer  impaired mucociliary clearance.
• Chronic infection  PMN-dominated inflammatory response.
• Neutrophil products (proteolytic enzymes and oxidants) mediate the
subsequent pathologic changes: bronchiectasis, bronchiolectasis, bronchial
stenosis, and fibrosis.
• Mucous plugging of airways
• 1. Production of thick, tenacious secretions from exocrine glands
• 2. Elevated concentrations of sodium, chloride, and potassium in
sweat

235. Cystic Fibrosis
• Clinical Presentation
• Pancreatic insufficiency
• Recurrent episodes of tracheobronchial infection
• Bronchiectasis
• Intestinal obstruction
• Sterility in males
• Diagnosis:
• (1) Identification of mutations known to cause cystic fibrosis in both
CFTR genes
• (2) Characteristic abnormalities in measurements of nasal mucosal
electrical potential difference
• (3) Abnormal sweat electrolytes

236. CF Work Up
• Cystic fibrosis causes obstructive lung disease, initially with
decreased flows at low lung volumes.
• Forced expiratory volume in 1 second (FEV1) is the best correlate of outcome and
starts to differ markedly from normal during adolescence.
• The rate of decline in FEV1 often predicts the clinical course.
• Early in the disease, the chest radiograph demonstrates hyperinflation
and peribronchial thickening. Computed tomography can demonstrate
bronchiectasis early in the course of the disease.
• Airway infection, which is the key clinical manifestation, can be
detected by sputum culture or bronchoalveolar lavage.

237. INTERSTITIAL LUNG
DISEASE

238. Overview
• Patients have dyspnea, tachypnea, end-inspiratory crackles, and
eventual cyanosis, without wheezing or other evidence of airway
obstruction.
• The classic functional abnormalities are reductions in diffusion capacity,
lung volume, and lung compliance.
• Chest radiographs show bilateral lesions that take the form of small
nodules, irregular lines, or ground-glass shadows, all corresponding to
areas of interstitial fibrosis.
• Eventually, secondary pulmonary hypertension and right-sided heart
failure associated with cor pulmonale may result.
• Although the entities can often be distinguished in the early stages, the
advanced forms are hard to differentiate because all result in scarring
and gross destruction of the lung, often referred to as end-stage lung or
honeycomb lung.

239. Causes
• Idiopathic
• Idiopathic interstitial pneumonias
• Granulomatous
• Sarcoidosis
• Occupational and environmental : Pneumoconioses
• Coal worker pneumoconiosis (CWP)
• Silicosis
• Asbestosis
• Berylliosis
• Drug induced
• Amiodarone
• Bleomycin and busulfan
• Cyclophosphamide
• Methotrexate and methysergide
• Nitrosourea and nitrofurantoin
• Connective tissue disease
• Systemic sclerosis
• SLE
• RA
• Collagen vascular disease

240. Idiopathic Interstitial Pneumonias
• Idiopathic pulmonary fibrosis
• Non-specific interstitial pneumonia
• Respiratory bronchiolitis-associated interstitial lung disease
• Desquamative interstitial pneumonia
• Cryptogenic organizing pneumonia
• Acute interstitial pneumonia
• Lymphoid interstitial pneumonia

241. Clinical Features
• History:
• Subacute or chronic
• Chronic
• pulmonary hypertension
• right sided heart failure (cor pulmonale).
• Symptoms:
• Progressive dyspnea
• Cough
• Late inspiratory crackles
• Respiratory alkalosis
• No wheezing
• Signs:
• Restrictive PFTs (reduced FEV1 and FVC with normal ratio, decreased TLC)
• Reduced DLCO.
• Variable inflammation and fibrosis of the interstitial, alveolar, and vascular
compartments of the lungs.
• Decreased PaO2

242. IPF Clinical Course
• IPF begins insidiously with gradually increasing dyspnea on exertion
and dry cough.
• Most patients are 55 to 75 years old at presentation.
• Hypoxemia, cyanosis, and clubbing occur late in the course.
• Usually there is a gradual deterioration in pulmonary status despite
medical treatment with immunosuppressive drugs such as steroids,
cyclophosphamide, or azathioprine.
• The median survival is about 3 years after diagnosis.
• Lung transplantation is the only definitive therapy.

243. IPF: Gross and Microscopic Morphology
• Gross Morphology
• Cobblestoned Pleura as a result of the retraction of scars along the
interlobular septa.
• Fibrosis occurs preferentially in the lower lobes, the subpleural
regions, and along the interlobular septa.
• Spacial/Temporal Heterogeneity
• Microscopic
• 1) Patchy interstitial fibrosis
• 2) Fibroblastic foci
• 3) Honeycomb fibrosis
• The dense fibrosis causes the destruction of alveolar architecture and
formation of cystic spaces lined by hyperplastic type II pneumocytes or
bronchiolar epithelium
• Early: exuberant fibroblastic proliferation
• Late: areas become more collagenous and less cellular.

246. UIP NSIP
Spacial/temporal heterogeneity Spacial/temporal homogeneity

247. In order to diagnose ILD, you need to use
a combination of history, clinical findings,
histologic findings, and/or radiographic
findings.
You cannot rely on one modality alone

248. PFTs
• Reduced FEV1
• Reduced FVC
• Normal FEV1/FVC ratio
• Decreased TLC
• Reduced DLCO
• PFTs At Rest: Diagnosis
• PFTs With Exercise
• Monitor the effectiveness of treatments
• Monitor the course of the disease
• The reductions in lung volumes become more pronounced with disease progression.
• 3 reasons to do physiologic testing
• 1) Clues to diagnostic category
• 2) Assess the severity of impairment
• 3) Assess change objectively

249. 2 criteria for diagnosis of IPF:
1) Exclude other known causes of ILD
(ex: sarcoidosis, pneumoconiosis, etc)
2) Diagnose UIP either by HRCT or
surgical lung biopsy

250. HRCT
• Interlobular septal thickening and reticulation
• Symmetrical, lower lobe, subpleural
• Macroscopic honeycombing
• Symmetrical, lower lobe, subpleural
• Traction bronchiectasis
• Bilateral infiltrative lesions in the form of small nodules, irregular lines,
or ground-glass shadows

251. HRCT
Interlobular septal thickening Reticulation
Honeycombing
Traction bronchiectasis

252. Mosaic Attenuation: Air Trapping
Expiratory Normal

253. Bronchoscopy and Surgical Lung Biopsy
• Bronchoscopy is diagnostic for sarcoidosis in >90% of cases
• Perform bronchoscopy if:
• Hemoptysis and radiographic ILD findings are present
• Acute onset of ILD
• Subacute or chronic presentation of ILD if sarcoidosis, hypersensitivity pneumonitis, pulmonary
Langerhans histiocytosis, or infection are suspected
• Bronchoscopy is less helpful in patients with radiographic findings that suggest IPF
• No established role in assessment of progression or response to therapy
• Obtain a lung biopsy in patients with atypical or progressive symptoms and signs:
• Age less than 50 years
• Fever
• Weight loss
• Hemoptysis
• Signs of vasculitis
• Atypical radiographic features
• Unexplained extrapulmonary manifestations
• Rapid clinical deterioration, or sudden change in radiographic appearance

254. Treatment
• General Lung Disease
• Stop smoking
• Supplemental oxygen if needed
• Immunization against S. pneumoniae and flu
• Pulmonary rehabilitation
• Consider lung transplantation
• Enrollment in clinical trials
• End-of-life planning
• Specific to ILD
• No specific therapy works for IPF
• Quality of data for effectiveness of therapy is poor
• Immunosuppressive therapy may be effective in some but not others
• Immunosuppressive therapy side-effects are common and dangerous
• Duration and intensity of appropriate treatment differs markedly

255. Anatomy: Pulmonary Interstitium
• Definition: Collection of support tissues within the lung that includes
the alveolar epithelium + pulmonary capillary endothelium +
basement membrane + perivascular and perilymphatic tissue
• Divided into 3 zones-
• Axial (surrounding bronchovascular tree)
• Parenchymal (surrounding pulmonary parenchyma)
• Peripheral (adjacent to the pleura)

257. Anatomy: Secondary Pulmonary Lobule
• Smallest unit of lung structure marginated by connective tissue septa:
fundamental unit of lung structure
• Irregularly polyhedral, variable size (1-2.5 cm)
• Contains:
• Small bronchiole
• Pulmonary artery branch
• 12 or fewer acini usually
• Marginated by interlobular septa
• Contain pulmonary veins and lymphatics
• Septa allow for visualization

259. Autoimmune Diseases such as SLE,
Rheumatoid Arthritis, Scleroderma, and
Dermatomyositis-Polymyositis can cause
ILD, but have a much better prognosis
and can be treated with
immunosuppresive therapy.

260. Hypersensitivity Pneumonitis
• Spectrum of immunologically mediated, predominantly interstitial, lung
disorders caused by intense, often prolonged exposure to inhaled
organic antigens
• In contrast to Asthma, involves pathologic changes of ALVEOLAR WALLS
• A common and potentially treatable cause of ILD
• Farmer’s lung (thermophilic actinomyces), Bird-fancier’s lung, Indoor mold
• Histology:
• Centered on bronchioles
• (1) Interstitial pneumonitis, consisting primarily of lymphocytes, plasma cells, and
macrophages (NOT EOSINOPHILS)
• (2) Noncaseating granulomas in 2/3 of patients
• (3) Interstitial fibrosis with fibroblastic foci, honeycombing, and obliterative bronchiolitis
(late stages).
• Centrilobular nodules on HRCT

261. HP Clinical Course
• Acute attacks, which follow inhalation of antigenic dust in sensitized
patients, consist of recurring episodes of fever, dyspnea, cough, and
leukocytosis.
• Micronodular interstitial infiltrates may appear in the chest radiograph
• Pulmonary function tests show an acute restrictive disorder.
• Symptoms usually appear 4 to 6 hours after exposure and may last
for 12 hours to several days. They recur with reexposure.
• If exposure is continuous and protracted, a chronic form of the
disease supervenes, leading to progressive respiratory failure,
dyspnea, and cyanosis and a decrease in total lung capacity and
compliance.

262. Chronic Inflammatory Infiltrate centered
on small airways: bronchiolitis
Lymphocytic Bronchiolitis Noncaseating Granuloma

264. IPF vs. Hypersensitivity Pneumonitis
• Timing
• IPF: Gradual onset, chronic non productive cough
• HP: Subacute, Symptoms within hours of exposure
• Prognosis
• IPF: Survival is less than 3 years
• HP: Good prognosis if diagnosed in subacute phase
• Treatment
• IPF: Only lung transplant
• HP: Immunosuppression and antigen avoidance

265. Sarcoidosis
• Systemic disease characterized by non-caseating granulomas in
multiple organs/systems
• African American Females, non-smokers, 20-39
• Diagnosis of exclusion: NEVER A SURE THING
• Gross Morphology:
• Symmetric hilar and mediastinal lymphadenopathy +/- lung infiltrates
• Histology
• Well-formed nonnecrotizing granulomas composed of aggregates of tightly
clustered epithelioid macrophages, often with giant cells.
• Granulomas  fibrosis and hyalinization
• Stellate inclusions (‘asteroid bodies’) often seen within giant cells of
granulomas
• Diagnosis w/ bronchoscopy in 90% of cases

267. Granulomas

268. Clinical Course
• Clinical manifestations:
• Lymph node enlargement
• Eye involvement (sicca syndrome,
iritis, or iridocyclitis)
• Skin lesions (erythema nodosum,
painless subcutaneous nodules)
• Visceral (liver, skin, marrow)
involvement.
• Lung involvement occurs in 90% of
cases, with formation of granulomas
and interstitial fibrosis.
Organ Involvement % of patients (n = 725)
Lungs & thoracic nodes 95.0
Skin 15.9
Extrathoracic nodes 15.2
Eye 11.8
Liver 11.5
E. nodosum 8.3
Neurologic 4.6
Parotid or salivary
3.9
glands
Hypercalcemia 3.0
Cardiac 2.3

271. Staging and Therapy of Sarcoidosis
• Stages -- based on CXR:
• 0 normal
• I Bilateral hilar adenopathy (BHL)
• II Parenchymal disease and BHL
• III Parenchymal disease
• IV Fibrosis (perivascular)
• 75-90% go into spontaneous remission. The remainder need steroids
for treatment. We treat stages 3 and 4.
• 10-15% develop severe fibrosis leading to cor pulmonale and death.

272. Take Home Point
• IPF is a terrible disease; don’t make this diagnosis unless you are
positive you are right.
• IPF accounts for about half of ILDs
• It is a disease of older adults
• Prognosis comparable to advanced cancers
• No specific treatment works
• Diagnosed based on UIP histology without identifiable cause

273. PLEURAL EFFUSION

274. Development of Pleural Cavities
• After cranio-caudal and ventral folding, the coelom is a closed tube that extends
from neck to pelvis. The cranial end of the coelom expands and flexes ventrally,
while the caudal end expands linearly. These two ends are in communication with
one another by narrow, paired pericardialperitoneal canals. These canals will
become pleural cavities.
• When the lung buds emerge, they expand into the right and left pleural cavities.
The portion of the pleural cavity in contact with the lung is the visceral pleura; the
portion of the pleura opposite the expanding viscera and in contact with the body
wall is the parietal pleura.
• INNERVATIONS:
• Pleural visceral layer: in contact with expanding organ
• Derived from splanchnic mesoderm innervated by autonomic neurons
• Visceral pain = dull and poorly localized
• Pleural parietal layer: in contact with body wall
• Derived from somatic mesoderm and innervated by somatic neurons (C3-C5)
• Somatic pain = sharp and well localized

275. Rib and Organ Relationships

277. Vasculature and Innervation of Chest Wall
• Blood supply:
• Subclavian artery → internal thoracic (mammary) artery → Anterior intercostal
arteries in each intercostal space, enter the costal groove on the internal
surface of a rib.
• Descending (thoracic) aorta → posterior intercostal arteries in each intercostal
space, anastomose with anterior intercostal arteries
• Innervation: intercostal nerves (ventral rami of T1-T11 spinal nerves),
sympathetic trunk also runs down the vertebral column near the
costovertebral joints.

280. Describe the course of the azygos vein in
the thorax and abdomen. Discuss the
significance of the azygos system.
• Azygos vein collects blood from right intercostal veins as well as from
hemiazygos vein (& sometimes accessory hemiazygos vein), which
collects blood from multiple posterior intercostal veins on left 
azygos vein drains into superior vena cava immediately superior to
root of the right lung
• Azygos vein also connects with inferior vena cava in abdomen
providing alternate route of venous drainage from thorax, abdomen,
and back in case of obstruction of either superior or inferior vena
cava.

282. Changes in Pleural Spance
• Pneumothorax: air introduced into pleural cavity and develops further as
lungs begin to collapse due to their own elastic recoil
• Tension Pneumothorax : Air enters pleural cavity but cannot exit causing
mediastinum to shift to opposite side of the chest
• CONTRALATERAL MEDIASTINAL SHIFT
• Open: occurs when parietal pleura is pierced and air enters and exits  loss of
negative intrapleural pressure  collapsed lung
• IPSILATERAL MEDIASTINAL SHIFT
• Spontaneous: occurs when air enters pleural cavity usually due to ruptured bleb
(bulla) of diseased lung
• Chylothorax: lymph accumulates in pleural cavity due to surgery or
trauma that injures thoracic duct
• Hemothorax: blood enters the pleural cavity as a result of trauma or
rupture of blood vessel

283. 1° vs 2° Spontaneous Pneumothorax
• Primary spontaneous pneumothorax: Occurs without a precipitating
event in a person who does not have known lung disease
• Risk factors: Smoking, Family history, Marfan Syndrome, Homocystinuria, &
Thoracic endometriosis
• Secondary spontaneous pneumothorax: Occurs as a complication of
underlying lung disease
• Risk factors: nearly every lung disease can be complicated by 2° spontaneous
pneumothorax
• COPD, Cystic Fibrosis, Primary or Metastatic Malignancy, and Necrotizing
Pneumonia (bacterial or fungal)

284. Management of Pneumothorax
• Observe and give 100% O2 if:
• Asymptomatic
• Pneumothorax is < 20% of the hemithorax
• 100% O2 decreases partial pressure of nitrogen in capillary
blood, which increases the rate of absorption of the
pneumothorax.
• Treat with chest tube if:
• Symptomatic, or
• Pneumothorax is >20% of the hemithorax
• Chest tubes and needles inserted to decompress a
pneumothorax are inserted in the 2nd ICS at the midclavicular
line or 4th/5th ICS in midaxillary line.

285. Management of Tension Pneumothorax
• If there is hemodynamic compromise then the pressure must be
relieved immediately by inserting a needle into the pleural space to
decompress and then placing a chest tube (tube thoracostomy) to
prevent reaccumulation of air.

286. Tube Thoracostomy
• Purpose: To decompress a tension pneumothorax or spontaneous
pneumothorax
• Placement: 2nd ICS in the midclavicular line or 4th or 5th ICS in
midaxillary line, with patient lying supine. Hook over top of ribs to
avoid vasculature and nerves.

287. MCC Pleural Effusion
• CHF
• Pneumonia
• Cancer
• PE

288. Pleural thickening is associated with
restrictive PFTs

289. Pneumothorax vs. Pleural Effusion
• Exam findings pleural effusion
• Dullness to percussion
• Absence of fremitus
• Diminished or absent breath sounds
• Exam findings for pneumothorax:
• Hyperresonant sounds on percussion
• Diminished fremitus
• Diminished/absent breaths sounds

290. Fluid attenuates sound waves; air
enhances them.

291. Signs of Pleural Effusion
• Precordial Exam
• S3 gallop  CHF
• RV Heave  PE, PAH, Left CHF
• Assess Abdomen
• Hepatomegaly  CHF, Cancer, Cirrhosis
• Splenomegaly
• Ascites
• Neck
• JVD  CHF
• Lymphadenopathy  Cancer
• Extremities
• Clubbing
• Cyanosis
• Thrombophlebitis  Pneumonia

292. Diagnostic Imaging

293. Thoracentesis
• >10 mm of effusion
• Seen on US or Lateral Decubitus
>10 mm Effusion
Yes
CHF?
Yes
Asymmetric
effusions, chest
pain, fever?
Yes: TAP No: OBSERVE
No: TAP
No: OBSERVE

294. Guidelines for Thoracentesis
• A Chest X-Ray is NOT needed post diagnostic tap unless:
• Air is obtained during the procedure
• Patient develops coughing, chest pain, or dyspnea post-procedure
• Fremitus is lost over the superior part of the aspirated hemothorax

296. Bloody vs. Turbid Taps
• Bloody pleural fluid
• PF-HCT <1%: Insignificant
• PF-HCT 1-20%: Cancer, PE, Trauma
• PF/S-HCT >50% : Hemothorax
• Turbid fluid: cloudy/opaque
• Infection/Empyema- WBCs in the 100,000s
• Chylous- Lymphatic blockage  Check triglyceride level
• Occurs when lymph accumulates in the pleural cavity due to surgery or trauma
that injures the thoracic duct. Can also be caused by malignancy

297. Light’s Criteria
SENSITIVITY: 98%
SPECIFICITY: 83%

299. Transudate vs. Exudate
• Transudate: Clear, Protein Poor
• Exudate: Cloudy, Protein Rich
• Transudate effusion
• CHF, Nephrotic syndrome, or Hepatic cirrhosis
• Systemic conditions and hydrostatic pressures that allow leakage from
vasculature through an intact endothelium.
• Proteins stay inside the blood vessel
• Exudate effusion
• Malignancy, pneumonia, collagen vascular disease, trauma
• Increased Vascular permeability causes increased protein content

300. WBC Count
• >50% Neutrophils  Acute Process
• Parapneumonic Effusion, PE, Pancreatitis
• <50% Neutrophils  Chronic Process
• Cancer, TB
• >85% Lymphocytes
• Post CABG
• TB
• Cancer
• RA
• Trapped Lung
• Lung Rejection
• Sarcoidosis

301. Eosinophils >10%
• Blood in pleural space: Hemothorax
• Air in Pleural space: Pneumothorax
• Drugs
• Asbestos exposure
• Pargonimiasis
• Churg Strauss Syndrome
• RULES OUT TB

302. Glucose Levels
• LOW pleural fluid glucose level is:
• <60 mg/dl
• PF-S glucose ratio < 0.5
• DDx for low glucose effusions:
• Most common
• Complicated parapneumonic effusion (<10 with empyema)
• Malignant effusion
• Somewhat common
• Hemothorax
• Rheumatoid arthritis (really low, <10)
• TB
• Least common
• Churg-Strauss syndrome
• Paragonimiasis (lung fluke)
• SLE

303. Amylase
• >200 IU/L
• Pancreatic Disease
• Neoplasm
• Malignant
• Paramalignant
• TB
• Esophageal Rupture

304. Diagnosis of TB
• If lymphocytosis is detected in the pleural fluid (PF), test for TB
• Most specific, most sensitive test: Pleural Adenosine Deaminase
• If PF ADA is >40 U/I, the patient has TB
• A PF interferon-gamma level of 140 has similar results to PF ADA
• Other tests are not as sensitive or specific.
• Less than 40% of PF cultures show TB in TB positive patients.
• Other results present in TB pleuritis
• <50% neutrophils
• >85% lymphocytes
• <10% eosinophils (Greater than 10% indicates it is NOT TB)
• Positive PF culture
• Low PF glucose <60 mg/dl

305. Diagnosis of Cancer
• WBC differential
• > 50% neutrophils = Acute: Pneumonia, PE, Pancreatitis
• < 50% neutrophils = Chronic: Cancer or TB
• > 85% lymphocytes → Suspect Leukemia (Hodgkin’s or CLL), TB
• Cytology
• Variable yield: Perform 3 successive thoracentesis studies
• If negative yet suspicion is high → VATS
• Amylase
• > 200 = suggestive of neoplasm
• > 600 = poor prognosis
• pH
• < 7.20 = Poor prognosis (~30 days to live), DRAINAGE INDICATED

306. Most common malignancies: lung, breast
ovarian…

307. Cytology Variability

308. Mesothelioma
• NONSPECIFIC PULMONARY SYMPTOMS
• Cough (usually non-productive)
• Dyspnea
• Focal ache on chest wall (unique symptom)
• Pleural effusion signs
• Dull to percussion
• Decreased respiratory sounds
• 60% right-sided, 5% bilateral Effusions
• Palpable mass / soft tissue fullness
• Ipsilateral splinting or scoliosis
• Paraneoplastic syndromes such as hypercalcemia, hypoglycemia,
autoimmune hemolytic anemia, hypercoagulable states, and
disseminated intravascular coagulation

309. Risk Factors for Mesothelioma
• Personal asbetos exposures
• Proximity to persons exposed to asbestos
• Smoking
• Radiation therapy
• Carbon nanotubes
• Exposure to Simian Virus 40 (SV40)

310. Lower Respiratory Infections
• Lower respiratory tract infection is usually synonymous with pneumonia, but also
includes other things such as bronchitis and lung abscess.
• General symptoms include shortness of breath, weakness, high fever, coughing,
and fatigue.
• Pneumonia - inflammatory condition of the lung, particularly the alveoli, most
commonly caused by bacteria or viruses, less commonly by other
microorganisms, drugs, or autoimmune conditions
• Productive cough
• Fever with shaking chills
• Shortness of breath
• Sharp/stabbing chest pain with deep breaths
• Increased respiratory rate
• Confusion in elderly
• Acute Bronchitis - self-limited infection of lower respiratory tract causing
inflammation of bronchi
• Acute, lasting less than 3 weeks
• Coughing is main symptom
• Wheezing, sputum production, chest pain

311. Parapneumonic Effusions Criteria
• Parapneumonic exudate - Exudative effusion on the same side as the pneumonia
• 3 Criteria for Assessment: These criteria help us decide if a chest tube is indicated for
drainage.
• A - Size of effusion
• 0 - Minimal, <10 mm on lateral decubitus
• 1 - Moderate, free flowing, >10mm on lateral decubitus and <½ hemithorax
• 2 - Large free flowing effusion >½ hemithorax or loculated effusion or thickened parietal
fluid on CT scan
• B - Bacteriology
• X - Unknown
• 0 - Negative culture and gm stain
• 1 - Positive culture and gram stain
• 2 - Pus
• C - pH
• X - Unknown
• 0 - >7.20
• 1 - <7.20

312. Criteria for Drainage:
If A is 2
B is 1 or 2
C is 1
Drainage is indicated

313. If exudative effusion but there are no
definitive result from all tests, consider PE

314. LUNG TUMORS AND
MEDIASTINALMASSES

315. EVALUATING NODULES

316. Borders
Benign Malignant Malignant

317. Benign Calcifications

318. Malignant Calcifications

319. Quality of Nodule
Ground Glass is more likely malignant.

320. Overview
• Size:
• > 3 cm considered a mass and is malignant about 90% of the time
• < 1 cm is most likely benign (~15% are malignant)
• Location:
• Upper lobe lesions more likely to be malignant
• Border:
• Smooth borders more likely benign whereas a spiculated or lobulated border more likely
malignant
• Calcifications:
• Densely calcified lesions or lesions with central calcifications are often seen in old
granulomatous disease
• Lamellar or popcorn calcifications more likely to be benign and can be seen in hamartomas
• Eccentric or punctate calcifications more likely to be malignant
• Quality:
• Both solid and ground glass nodules may be malignant
• Pure ground glass or mixed nodules more likely malignant than pure solid lesions
• Growth Rate:
• Most malignancies double in size (doubling time) in less than 400 days.
• If a nodule is stable in size for more than 2 years, it’s most likely benign

321. Clincial Features Increasing Malignancy
• Older age
• Tobacco use
• History of prior malignancy
• Presence of underlying lung disease

322. “Most commonly, solitary or multiple
pulmonary nodules are the sequelae of a
prior granulomatous infection. Other
etiologies include benign/malignant
tumors, active infection, inflammatory
disease, bronchogenic cysts, and
vascular malformations.”

323. Hamartoma
• Most common benign pulmonary tumor
• Often exhibit specific characteristics (smooth border, lamellar
calcifications, fat density) that allow for the appropriate diagnosis without
intervention.
• The lung is the site of > 90% of all hamartomas that are diagnosed.
• Histopathologic:
• Islands of cartilage and entrapped respiratory epithelium
• Connective tissue intersected by epithelial clefts of columnar cells
• Radiologic:
• Smooth, well-circumscribed round nodules that are less than 3-4 cm in diameter
• CT
• May demonstrate lamellar or popcorn calcifications and also often have variable soft
tissue density (including fatty density)

324. Hamartoma

325. Genetic Characteristics of Lung Cancer

326. Adenocarcinoma
• Adenocarcinoma is the most common cell type of lung cancer and is
notably the most common lung cancer diagnosed in nonsmokers
• Histopathology
• Presence of glandular differentiation and/or mucin production (80%) within the tumor
• Distinct growth patterns defined including acinar, papillary, bronchioalveolar, and
solid
• Vesicular nuclei
• Intact sheets on fine needle aspiration
• Clinical Presentation
• Hypertrophic Osteoarthropathy
• Pancoast Syndrome
• PERIPHERAL LESIONS
• Grow more slowly than Squamous Cell Carcinoma but metastasize
widely and early

327. Adenocarcinoma

328. Squamous Cell Carcinoma
• Smoking is a key risk factor
• Histopathology:
• Presence of keratinization and/or intercellular bridges
• Often presents with central lesion found near lung hila
• Clinical Presentation
• Production of PTHrp results actions identical to that of PTH with what may be
profound hypercalcemia with associated hypophosphatemia. Endogenous
PTH is suppressed.

329. Squamous Cell Carcinoma

330. Small Cell Lung Cancer
• SCLC is derived from neuroendocrine cells within the lung.
• Histopathology
• The cells are relatively small with scant cytoplasm and small hyperchromatic
nuclei.
• The chromatin exhibits a salt and pepper granular pattern.
• The mitotic counts are typically very high.
• Clinical Presentation
• Clinically, these tumors often present at late stages when the disease is widely
metastatic given the rapid proliferation rate.
• Central lesion with endobronchial growth.
• SVC Syndrome
• SIADH (Hyponatremia)
• Eaton Lambert Syndrome
• Cushings and Antineuronal Antibody
• Very Aggressive, Poor Prognosis

331. SCLC

332. Pancoast Syndrome
• Destruction of nerve roots of brachial plexus causes neuropathic pain
in ulnar distribution
• Horner’s syndrome (ptosis, miosis, anhidrosis) due to extension into
sympathetics
• Common in adenocarcinoma (PERIPHERAL)

333. SVC Syndrome
• Obstruction of SVC by tumor
• Enlarged mediastinal lymph nodes
• Dyspnea - worse with leaning forward or laying down
• Chest pain
• Facial/upper extremity edema
• Headache
• Common in SCLC

334. Malignant Pleural Effusion
• Large
• Frequently bloody (hemorrhagic pleuritis)
• Cytologic examination may reveal malignant and inflammatory cells
• Dyspnea, cough, uncomfortable feeling/pain in chest
• Pleural fluid will likely have low glucose (<60 mg/dl), >85%
lymphocytes. Amylase (>600 IU/L) and pH <7.20 indicate a poor
prognosis

335. Paraneoplastic Syndromes
• Eaton-Lambert syndrome: SCLC
• Pesynaptic Ca2+ channel autoAb reduction in ACh in synaptic cleft
 muscle weakness
• improves with repetitive stimulation
• SIADH: SCLC
• increased antidiuretic hormone  resorption of excess H2O and
hyponatremia  confusion/seizures
• cerebral edema
• neurologic dysfunction
• Cushing’s Syndrome: SCLC
• Increased ACTH  Increased Glucocorticoid Action
• HTN, weight gain, truncal obesity, “moon facies”, “buffalo hump”,
hyperglycemia, glycosuria, polydipsia, osteoporosis, increased
infection risk, hirsutism, menstrual abnormalities, mental disturbances

336. IHC Staining
• EGFR → use erlotinib and gefitinib - kinase inhibitors
• ALK → Crizotinib - tyrosine kinase inhibitor
• Found in Adenocarcinoma and Squamous Cell Carcinoma

337. Mediastinal Tumors
• Anterior mediastinal masses: 4 T’s
• Thymoma/thymic tumors (rare in children) = associated w/ myasthenia
gravis.
• Thyroid (including goiter)
• Teratoma/germ cell tumor
• Terrible lymphoma
• Middle
• Thyroid tumor or goiter
• Tracheal tumors
• Bronchogenic cysts
• Lymphoma
• Lymphadenopathy - from metastatic spread or infection
• Posterior
• Neurogenic tumors
• Esophageal tumors
• Hiatal hernias

339. Teratoma
• Tumor consisting of cells derived from all three germ layers
• Originate from totipotent cells of the ovaries or testes.
• Often these tumors are cystic in nature and when they’re resected
things like teeth, hair and sebaceous material are found inside

340. Thymoma
• Most common primary tumor of
the anterior mediastinum in adults
(20-30%)
• Rarely seen in children.
• Paraneoplastic syndromes
• Myasthenia gravis is present in 50-70%
of thymomas.
• Pure red cell aplasia and
hypogammaglobulinemia.
• Most thymomas are well
encapsulated and have a benign
prognosis.
• Histopathology: Thymic epithelial
cells with mixed lymphocytic cells

341. Myasthenia Gravis
• Muscle weakness is caused by circulating auto antibodies that block
acetylcholine receptors at the postsynaptic neuromuscular junction,
inhibiting the excitatory effects of the neurotransmitter acetylcholine
on nicotinic receptors at neuromuscular junctions.
• Improves with acetylcholinesterase inhibitor
• 30-65% of people with thymomas (highly associated!)
• Does improve when thymoma removed

342. Lymphoma
• Proliferation of lymphocytes that appears typically as a
distinct mass
• Medial mediastinum

343. ACID BASE

344. ARDS

345. Diagnostic Criteria
• ARDS Definition
• Acute pulmonary symptoms within one week
• Bilateral opacities consistent with pulmonary edema on CXR
• Respiratory failure not explained by cardiac failure or fluid overload
• Moderate to severe impairment of oxygenation must be present
defined by a ratio of arterial oxygen tension to fraction of inspired
oxygen (PaO2/FiO2) <300.
• The severity of the hypoxemia defines the severity of the ARDS

347. Pulmonary Edema

348. Direct Causes of ARDS
• Community acquired pneumonia
• Influenza pneumonia - common flu.
• Toxic Gas Inhalation
• Nitrogen dioxide
• High concentrations of oxygen
• Aspiration
• Gastric contents - chemical burn from acidic contents
• Damage to alveolar epithelium
• Salt water - hypertonic to plasma
• Draws fluid from the circulation
• Fresh water - hypotonic to plasma and cellular contents
• Cellular edema; also inactivates surfactant
• Aspirated hydrocarbons
• Toxic to distal parenchyma; also inactivates surfactant

349. Indirect Causes of ARDS
• Sepsis - MOST common.
• Pancreatitis
• Trauma
• Transfusion
• Neurogenic causes
• Intracranial bleeding
• Increased ICP
• Generalized Seizures
• Disseminated Intravascular Coagulation (DIC)
• Intoxication (ASA, cocaine, opioids)

350. Pathologic Changes
• Early exudative phase: Reaction
• Alveolar lumen and septa
• Scattered bleeding and regions of alveolar collapse related to inactivation of surfactant by
protein rich exudates and reduced surfactant production resulting from damage to type II
alveolar cells
• Nonspecific inflammatory response resulting in infiltration of neutrophils and
macrophages
• Hyaline membranes (thin layer of protein tissue) forming from the protein rich edema
(fibrin, cellular debris, plasma proteins) that deposits on the alveolar membrane
• Later proliferative phase: Repair
• Occurs approx. 1 to 2 weeks
• Alveolar type II epithelial cell hyperplasia to replace damaged type I cells
• Accumulation of fibroblasts in the pulmonary parenchyma
• Fibrotic Phase:
• Development of scar tissue
• Extensive remodeling of small pulmonary vessels including intimal and medial
proliferation
• Formation of in situ thrombi

351. Shunting and V/Q Mismatch
• V/Q Mismatch in ARDS: Results from nonuniform distribution of the
pathologic process within the lungs
• Areas of more edematous interstitium and where more fluid is present in the
alveoli have more impaired ventilation
• Changes in blood flow do not follow the same distribution as the nonuniform
changes in ventilation
• Pulmonary vascular remodeling – constriction and pressure lead to decreased
size of lumen
• True Shunting: regions where V/Q ratio = 0
• Results from alveolar flooding
• Act as regions where blood is shunted from the pulmonary arterial to venous
circulation without being oxygenated
• Secondary alterations to surfactant:
• Surfactant production can be reduced due to type II cell damage in alveoli
• Extensive fluid within the alveoli results in inactivation of surfactant

352. The decreased compliance and low FRC
in ARDS are not associated with
homogeneously affected alveoli but rather
with heterogeneous disease involvement.

353. Low Tidal Volume Ventilation
• It is thought that ventilating ARDS patients at a low tidal volume
prevents distension of alveoli leading to release of deleterious
inflammatory markers.

354. SMOKING CESSATION

355. 5 A’s for Treating Tobacco Use
• Ask if a patient uses tobacco
• Providers should identify and document tobacco use status for
every patient at every visit
• Advise to quit
• Assess willingness to make a quit attempt
• Assist in quit attempt
• If a patient is willing to make the attempt, offer medications and
provide/refer for counseling or additional treatment to help the
patient quit
• Arrange follow up
• Quit date should be within the next two weeks
• Followup contacts should be within the first week after the quit date

356. Stages of Change
• The Stages of Change model suggests that people move through a
series of steps before making a change in their lives
• Pre-contemplation - not thinking about making a change
• Contemplation- unsure about the change
• Preparation- ready for change
• Action- engaged in change
• Maintenance- sticking with the change/keeping it going
• Eventually there is a 6th phase known as extinction, where the ‘agony
of temptation’ disappears. There is also a relapse stage, which is
defined as regression to an earlier stage. Most successful changes
have likely cycled through all or some of these stages several times
before reaching maintenance or extinction.

357. Clinicians can understand a person’s stated
readiness to change in greater depth by exploring
their expectations of the costs and benefits of
change and their confidence in remaining
abstinent.
The assumption is that for a person to move into
the preparation stage (‘I’m ready to try’) they must
believe that change is worthwhile (‘motivation’) and
they can succeed (‘confidence’).

358. Motivational Interviewing
• Motivational interviewing: A directive, client-centred counseling style
for helping client explore and resolve ambivalence about behaviour
change
• Building patient rapport
• Assessing patient’s place on the Stage of Change scale
• The examination of pros and cons
• Information giving
• Addressing low confidence and help with decision making
• Express empathy
• Develop discrepancy
• Roll with resistance
• Support self-efficacy

359. LOWER RESPIRATORY
INFECTIONS

360. Mechanisms of Immune Protection
• Innate
• 1. Removal of microbial organisms by entrapment in mucous blanket and
movement on mucociliary elevator
• 2. Phagocytosis by alveolar macrophages (which are then transported out by
mucociliary elevator)
• 3. Phagocytosis and killing by neutrophils recruited by macrophage factors
• 4. Activation of alternative complement pathway and opsonin C3b enhances
phagocytosis
• 5. Organisms, including those ingested by phagocytes, may reach draining
lymph nodes to initiate immune responses
• Adaptive
• 1. Secreted IgA blocks attachment of microorganism to epithelium in the upper
respiratory tract
• 2. Serum antibodies (IgM, IgG) in the lower respiratory tract activate
complement via the classic pathway
• 3. Accumulation of T cells controls infections by viruses and other intracellular
microorganisms

361. 2 Modes of Entry
Inhalation
Aspiration
Rarely Hemtogenous

362. Factors Predisposing to Infection
• Factors that affect resistance to infection in general
• Chronic disease
• Immunologic deficiency
• Immunosupressants
• Leukopenia
• Compromise of local defense mechanisms
• Loss or suppression of cough reflex
• Injury to the mucociliary apparatus
• smoking, inhalation of hot/corrosive gases, viral disease, or genetic defects
(e.g. immotile cilia syndrome)
• Accumulation of secretions
• CF, bronchial obstruction
• Interference with phagocytosis
• Alcohol, tobacco smoke, anoxia, oxygen intoxication
• Pulmonary congestion and edema

363. Pneumonia Clinical Presentation
• Symptoms
• Fever (with or without chills)
• Cough (with or without sputum production)
• Nonproductive cough suggests viral or mycoplasmal pneumonia
• Blood tinged or rusty suggests bacteria pneumonia
• Dyspnea
• Pleuritic chest pain due to inflammation adjacent to the pleura
• Signs/Physical exam findings
• Fever
• Tachycardia, tachypnea
• Crackles over affected area on auscultation
• Bronchial breath sounds, increased tactile fremitus, egophony
• Dullness to percussion with frank consolidation or effusion
• Elevated WBC count

364. Typical vs. Atypical Pneumonia
• Typical pneumonias: lobar and bronchopneumonia
• More lobar consolidation, alveolar exudate, sputum production than
atypical pneumonias
• Pathogens
• S. pneumonia : lobar
• Staph aureus : bronchopneumonia
• Haemophilus : bronchopneumonia
• Klebsiella : lobar
• Legionella : : bronchopenumonia
• Atypical pneumonias: interstitial pneumonias
• Pathogens
• Mycoplasma ; interstitial
• Chlamydophila : interstitial
• Coxiella : interstitial
• Viruses : interstitial

365. ▪ The term atypical organisms is used for
Mycoplasma pneumoniae, Chlamydophila
pneumoniae, Coxiella burnetii, and
viruses since they are not detectable on
Gram stain nor do they grow on the
standard bacteriologic culture media.
Intracellular organisms (also include
Legionella)

366. Sputum Sampling
• Taken early morning after patient wakes up
• Prior to antibiotic treatment
• Mouth rinsed before expectoration
• No food 1-2 hours before
• Quick transport to lab for culturing
• Fewer than 10 squamous epithelial cells
• >10 indicates it is spit as oppose to a sample from lower tract
• Sputum use is controversial b/c of varying quality of sputum samples
• Poor quality specimen may provide inadequate or inaccurate
information
• Can be difficult to assess b/c of contamination with upper respiratory
species

367. LRIs
• Pneumonia: any infection of the lung parenchyma/alveoli; fever,
cough, dyspnea, leukocytosis, pleuritic chest pain
• Causative viruses: Influenza, adenovirus, RSV, SARS-coronavirus,
measles, hantavirus
• Causative bacteria: S. pneumoniae , S. aureus, M pneumoniae, M.
catarrhalis, Legionella, Klebsiella, Pseudomonas, Coxiella Burnetti
• Bronchitis: infection of the trachea and large bronchi; hallmark
is cough, sputum production
• Causative viruses: any respiratory virus
• Bronchiolitis: infection of the small airways; cough, dyspnea;
often seen in infants
• Causative viruses: RSV, metapneumovirus

368. Bronchitis vs. Pneumonia
• It is important to distinguish acute bronchitis from pneumonia, which usually
indicates need for antibiotic therapy.
• Fever is an unusual sign in patients with acute bronchitis and suggests the
presence of either influenza or pneumonia.
• Patients with the combination of cough, fever, sputum production, and
constitutional symptoms are more likely to have influenza or pneumonia.
• Patients with acute bronchitis have few systemic symptoms.
• They may have chest wall tenderness related to muscle strain from coughing.
Wheezing may also occur. Cough in patients with acute bronchitis usually
lasts from 10 to 20 day

369. S. Pneumonia
• Normal inhabitant of the oropharynx
• Gram-positive coccus seen in pairs or diplococci.
• MOST COMMON cause of community acquired pneumonia
• Frequently occurs following a viral upper respiratory tract infection.
• The organism has a polysaccharide capsule that interferes with
phagocytosis and therefore is an important factor in its virulence
• Typically causes lobar pneumonia
• Test sputum
• Vaccine available

370. S. Pneumonia Vignette
• An elderly woman presents with a cough producing rusty-colored
sputum. She complains of sharp right-sided chest pains, chills, and
fevers. Physical exam reveals increased fremitus, dullness to
percussion, and bronchial breath sounds on the lower right side. CXR
shows right lower lobe consolidation, and Gram stain of sputum
shows Gram diplococci. Physicians begin treatment with
cephalosporins.

371. H. Influenza
• Gram negative coccobacillia, encapsulated and nonencapsulated
• 6 capsule serotypes, B is most virulent; B is in vaccine.
• H. influenzae pneumonia is a pediatric emergency and has a high
mortality rate.
• Descending laryngotracheobronchitis results in airway obstruction as
the smaller bronchi are plugged by dense, fibrin-rich exudates
containing neutrophils, similar to that seen in pneumococcal
pneumonias.
• Pulmonary consolidation is usually lobular and patchy but may be
confluent and involve the entire lung lobe
• H. influenzae is the most common bacterial cause of acute
exacerbation of COPD.

372. S. Aureus
• Staphylococcus aureus is an important cause of secondary bacterial
pneumonia in children and healthy adults following viral respiratory
illnesses
• Causes bronchopneumonia
• Staphylococcal pneumonia is associated with a high incidence of
complications, such as lung abscess and empyema.
• Intravenous drug users are at high risk for development of
staphylococcal pneumonia in association with endocarditis.
• It is also an important cause of hospital-acquired pneumonia.

373. Legionella
• Gram negative coccobacilli
• Flourishes in artificial aquatic environments
• Mode of transmission is either inhalation of aerosolized organisms or
aspiration of contaminated drinking water.
• Legionella pneumonia is common in individuals with predisposing
conditions such as cardiac, renal, immunologic, or hematologic disease.
• Organ transplant recipients are particularly susceptible.
• Rapid diagnosis is facilitated by demonstration of Legionella antigens in
the urine or by a positive fluorescent antibody test on sputum samples;
culture remains the diagnostic gold standard.
• Often seen in elderly smokers

374. Legionella Vignette
• A 67-year-old man with a history of heavy smoking comes to the
doctor complaining of “the flu.” He has a fever, loss of appetite,
headache, chest pain, and a mild cough producing little sputum. The
doctor believes that the watery diarrhea that the man also suffers from
is related. Sputum sample reveals many neutrophils but no bacteria.
CXR reveals nodular infiltrates. Serum tests are negative for cold
agglutinins

375. Aspiration Pneumonia
• Aspiration pneumonia occurs in markedly debilitated patients or those
who aspirate gastric contents either while unconscious (e.g., after a
stroke) or during repeated vomiting.
• Abnormal gag and swallowing reflexes that predispose to aspiration.
• The resultant pneumonia is partly chemical due to the irritating effects of
gastric acid, and partly bacterial (from the oral flora)
• Typically, more than one organism is recovered on culture, aerobes being
more common than anaerobes.
• This type of pneumonia is often necrotizing, pursues a fulminant clinical
course, and is a frequent cause of death.
• In those who survive, lung abscess is a common complication.
• ANAEROBIC, right lower lobe!!!

376. Nosocomial Pneumonia
• Bacteria
• Staphylococcus aureus, methicillin-sensitive and resistant
• Pseudomonas aeruginosa
• Streptococcus pneumoniae
• Gram-negative rods
• Enterobacteriaceae ( Klebsiella spp., Serratia marcescens, Escherichia coli)
• Pseudomonas spp.
• Risk Factors
• Hospitalization of at least 2 days within the recent past
• Presentation from a nursing home or long-term care facility
• Attending a hospital or hemodialysis clinic
• Recent intravenous antibiotic therapy
• Chemotherapy or wound care.

377. Mycoplasma
• Mycoplasma pneumoniae most commonly affects young people,
especially those in close quarters (prisons, military bases).
• CXR often looks worse than symptoms suggest.
• Mycoplasmas are the smallest free-living organisms and are the only
bacteria to (1) have no cell wall and (2) have cholesterol in their
membranes
• Diagnosis: cold hemagglutination, no cell wall, fried-egg appearance
on culture, serology
• Complications: autoimmune hemolytic anemia or erythema nodosum
• Beta lactam resistant

378. Mycoplasma Vignette
• A young woman at an army base thinks she has a cold and goes to
her doctor. She complains of malaise, chills, sore throat, and dry
cough. CXR shows interstitial infiltrate more severe than suggested
by her symptoms. Laboratory tests indicate that the woman’s serum
was capable of agglutinating erythrocytes when incubated at 4°C. The
doctor prescribes erythromycin.

379. Chlamydia
• A 22-year-old student presents with a nonproductive cough, fever,
and sore throat. CXR demonstrates diffuse interstitial infiltrate.
Sputum Gram stain shows many PMNs but no organisms, and a
Giemsa stain reveals intracytoplasmic inclusions in epithelial cells.
Doxycycline treatment is begun.
• Atypical Pneumonia
• Affects young people
• Phagocytosed by macrophages  Intracellular replication
• Giemsa stain to visualize intracytoplasmic inclusions

380. Bacterial pneumonias are characterized
by predominantly intra-alveolar
neutrophilic inflammation
Viral pneumonia shows interstitial
lymphocytic inflammation. Characteristic
viral inclusions may be seen.

381. Viral Pneumonia
• RSV
• Most common cause of Atypical Pneumonia in infants
• Influenza
• Atypical pneumonia in elderly, immunocompromised and patients
with preexisting lung disease
• Increases risk of secondary bacterial pneumonia
• CMV
• Atypical pneumonia post-transplant

382. Coccidiodes
• An old man and his great grandson visit Death Valley National Park in
the deserts of Southern California. Upon returning from their visit, the
man develops breathing difficulties along with arthralgias, periarticular
swellings, and erythema nodosum. X-rays reveal a pneumonic
infiltrate as well as granulomas. A diagnosis is confirmed by observing
spherules containing individual endospores in tissue specimens. As
expected, the child remains unaffected but several weeks later tests
positive for a fungal antigen DTH reaction.
• Affects Immunocompromised
• Dx:
• Serology
• Culture at different temperatures:
• Branched hyphae at 25°C
• Single cells at 37°C

383. Histoplasmosis
• An elderly cave explorer in Ohio complains to his physician of
weakness in the last few months. A physical exam reveals sores in his
mouth, and X-ray shows small calcifications throughout the body. A
lung biopsy reveals small budding cells within macrophages. Based
on his age, location, and biopsy results, the physician begins the
patient on oral amphotericin B.
• Normal individuals can develop a mild pneumonia after prolonged
exposure to bird droppings (e.g., chicken farmers).
• Disseminated histoplasmosis is often a sign of AIDS
• Dx:
• Culture at different temperatures:
• Branched hyphae at 25°C
• Singgle cells at 37°C
• Tissue biopsy: yeast cells within macrophages
• Serology

384. Pneumocystis Jirocevi
• A homeless man arrives at the EW complaining of difficulty in
breathing. His medical history is not obtainable, but the man does
report increasing fatigue and weight loss over the past few months.
Physical exam reveals lymphadenopathy, tachypnea, and bilateral
rales in the lung bases. Chest X-ray shows diffuse infiltrates
bilaterally. The doctor decides to perform a bronchial lavage and, with
silver stain, reveals numerous cysts containing several dark oval
bodies. The doctor begins the patient on TMP-SMX and orders an
HIV and blood test.
• Opportunistic infection in immunocompromise!!

385. DIAGNOSIS
• Microbiological
• Direct microscopy
• Culture
• Histopathological
• Microscopy
• Immunohistochemistry (research only)
• Immunologic and biochemical
• Serum antibody
• Antigen

386. DIRECT MICROSCOPY
Fungus Microscopic Appearance
Cryptococcus
neoformans
Spherical, budding yeasts, 2–15
μm dia; ± capsule; no hyphae or
pseudohyphae
Blastomyces
dermatitidis
8–15 μm dia, thick-walled,
budding yeast cells; broad-based
junction; may appear
multinucleate
Histoplasma
capsulatum
2–4 μm dia, intracellular,
budding yeasts
Coccidioides
immitis
Spherical, thick-walled
spherules, 20–30 μm dia;
mature spherules contain small,
2–5 μm diameter endospores

387. DIRECT MICROSCOPY
Fungus Microscopic Appearance
Pneumocystis
jiroveci
Cysts are round, collapsed, or
crescent shaped; trophozoites seen
on staining with giemsa or
immunofluorescent stains
Aspergillus spp. Hyaline, septate, dichotomously
branching hyphae of uniform width
(3–6 μm dia)
Candida spp. 4-6 μm dia, thin-walled, ovoid
yeasts; budding and pseudohyphae
may be seen, but are not invariably
present
Zygomycetes (aka
Mucormycotina)
Broad, thin-walled, pausi-/aseptate
hyphae, 6–25 μm dia with
nonparallel sides and random

388. CULTURE
• Limitations
• Colonization of respiratory tract without invasion is
common with Candida, Aspergillus, other molds
• Lack of growth of molds in culture not uncommon even
when seen on histopathology
• Full identification may require several weeks
• Blood Cx need to be ordered as separate fungal
Cx

389. HISTOPATHOLOGICAL
• Evidence of tissue invasion is gold standard for Candida,
Aspergillus, Zygomycetes, other molds
• Biopsy findings:
• Caseating or necrotizing granulomas with intracellular organisms
inside macrophages (eg, H. capsulatum, C. immitis)
• Fungal hyphae in infection with Aspergillus and Mucor species
• Intracellular yeast organisms in Candida species infections

390. Complications of Pneumonia
• Lung abscess
• area of suppurative necrosis w/in lung parenchyma
• abscess has a wall and a cavity filled with pus and organisms
• complication of necrotizing bacterial pneumonias
• Anaerobes, S. aureus, S. pyogenes, K. pneumoniae,
Pseudomonas
• Common in lower lobe from aspiration
• Empyema
• Pus in the pleural cavity
• Purulent material, high white cell count
• Normally-existing cavity
• May be caused by abscess rupture
• May be caused by bacteria invading the pleural space

391. Treatment of Pneumonia
• Ceftriaxone and Azithromycin

392. Pertussis
• Pertussis, also known as "whooping cough," is a highly contagious, acute
respiratory illness caused by Bordetella pertussis.
• Clinical Presentation: 3 phases
• Catarrhal
• Paroxysmal
• Convalescent
• Diagnosis
• Culture and PCR
• Treatment
• Antibiotic therapy late in disease will not affect symptoms but may prevent spread of
the illness
• Antibiotics are recommended for patients with sx <2 weeks
• Azithromycin or Clarithromycin
• TDAP vaccine and boosters
• Postexposure prophylaxis

393. Pertussis Clinical Presentation
• Catarrhal - 1-2 weeks
• Begins after incubation period of 3-12 days
• Nondistinctive symptoms of congestion, rhinorrhea, low-grade fever, sneezing,
lacrimation and conjunctival suffusion
• Paroxysmal - 2-6 weeks
• Marked by the onset of cough - dry intermittent, irritative hack, paroxysmal
cough
• Convalescent - 2 or more weeks
• Number, severity, and duration of coughing episodes diminish
• Infants < 3 months of age do not display the classic stages

394. Paroxysmal Cough
• Cough begins as dry, intermittent, irritative hack
• Evolves into paroxysms:
• Machine gun burst of uninterrupted cough on a single
exhalation
• Chin and chest forward
• Tongue protruding maximally
• Eyes bulging and watering
• Face purple
• This goes on until coughing ceases and a loud whoop follows
as inspired air traverses the still partially closed airway
• Post-tussive emesis common

395. Croup
• Croup is a respiratory illness characterized by inspiratory stridor,
cough, and hoarseness. These symptoms result from inflammation in
the larynx and subglottic airway. A barking cough is the hallmark of
croup among infants and young children, whereas hoarseness
predominates in older children and adults.
• Parainfluenza virus is the most common cause
• Dx: The diagnosis of croup is clinical, based on the presence of a
barking cough and stridor.
• Neither radiographs nor laboratory tests are necessary to make the diagnosis.

396. Tuberculosis
• Clinical Presentation
• Caseous necrosis
• Malaise
• Anorexia
• Weight loss
• Low grade fever
• Night sweats
• Sputum
• Hemoptysis
• Pleuritic pain
• Many extrapulmonary complications
• Rx:
• Active: Daily rifampin, isoniazid, pyrazinamide, and ethambutol for 2
months, then isoniazid and rifampin for 4 months
• Latent TB: 9 months daily isoniazid

397. TB Diagnosis
• HPI, travel history, HIV history, exposure history, etc.
• Radiology
• Calcified primary complexes
• Large air space/cavitary lesion(s)
• Sputum smears for AFB
• Bacterial culture
• 17-21 days but can take up to 6 weeks

398. TB Transmission
• Human transmission through respiratory droplets
• Droplet nuclei are very small
• 1-5 μm
• Remain airborne and infectious for 30 min
• Inhaled to alveoli
• Phagocytosed by alveolar macrophages
• Replication inside macrophage triggers local immune response

399. PULMONARY
EMBOLISM

400. Risk Factors: Venous Thromboembolism
• Immobilization (e.g., bed rest, prolonged sitting during travel,
immobilization of an extremity after fracture)
• Postoperative state
• Congestive heart failure
• Obesity
• Underlying carcinoma
• Pregnancy and the postpartum state
• Oral contraceptives
• Chronic deep venous insufficiency.
• Patients at particularly high risk are those who had trauma or surgery
related to the pelvis or lower extremities, especially hip fracture or hip or
knee replacement.
• A number of genetic predispositions to hypercoagulability are recognized
• Deficiency or abnormal function of, antithrombin III, protein C, protein S
• Abnormal variants of some of factor V and prothrombin

401. Virchow’s Triad
• Hypercoagulability - an increased chance of producing a thrombus.
Many genetic defects can cause hypercoagulability. The most
commonly found is factor V Leiden, which causes the factor V protein
to become resistant to protein C.
• Hemodynamic changes - this mainly refers to stasis, which allows
thrombi to form predominantly in the lower extremity venous system.
• Endothelial injury/dysfunction - mainly caused by shear stress or
hypertension. Can release factors and expose proteins that incite
thrombus formation.

402. Hypoxemia in PE
• Occlusion by an embolus  perfusion of pulmonary capillaries normally supplied
by that vessel ceases
• DEAD SPACE and V/Q MISMATCH
• Hyperventilation and hypocapnia
• Increase in pulmonary vascular resistance.
• Right ventricle cannot cope with the acute increase in afterload
• BP falls  syncope or cardiogenic shock.
• Thrombi result in release of chemical mediators
• Platelets tare an important source of histamine, serotonin, and prostaglandins.
• Increased release of endothelin-1 (potent vasoconstrictor)
• Decreased production of NO (vasodilator)
• Bronchoconstriction
• Synthesis of surfactant in the affected alveoli is compromised
• Alveoli may be more likely to collapse, and liquid may more likely leak into alveolar spaces.
• Shunt physiology may also contribute to hypoxemia because of either perfusion of
atelectatic lung or elevated right heart pressures producing intracardiac shunting
across a patent foramen ovale.

403. Diagnosis
• Diagnosis of acute pulmonary embolism can be challenging, and the
approach depends on the clinician's level of suspicion, or pretest
probability, of pulmonary embolism.
• For patients in whom the diagnosis is considered less likely, the clinician
may start with a d-dimer assay. Most patients who present with acute
dyspnea or chest pain will have a chest radiograph and oxygen
saturation checked by finger oximetry.
• Traditionally, the major screening test for pulmonary embolism has been
the perfusion lung scan but contrast computed tomographic angiography
(CTA) is increasingly used either instead of or in addition to perfusion
lung scanning.
• Evaluation of the large veins in the lower extremities, typically using
ultrasound techniques, is another commonly used diagnostic strategy.
Identification of a clot in a vein above the popliteal fossa warrants the
same treatment as a documented pulmonary embolus and often obviates
the need for further evaluation.

404. Clinical Presentation
• Commonly the embolus produces no significant symptoms, and
the entire episode goes unnoticed by the patient and physician.
• Dyspnea is the most frequent complaint.
• Less common is pleuritic chest pain or hemoptysis.
• Syncope is an occasional presentation
• On physical examination:
• Tachycardia and tachypnea.
• May show decreased air entry, localized crackles, or wheezing.
• With pulmonary infarction extending to the pleura, pleural friction rub
• Second heart sound (P2), right S4, and a RV heave may be present.
• If RV fails, right S3 may be heard, and JVD seen
• Tenderness, swelling, or a cord on lower extremities

405. CXR
• Frequently the chest radiograph is normal.
• When it is not, the abnormalities often are nonspecific, including
areas of atelectasis or elevation of a hemidiaphragm, indicating
volume loss
• Westermark sign: localized area of decreased lung vascular markings
corresponding to the region where the vessel has been occluded
• Hampton hump: Both congestive atelectasis and infarction may
appear as an opacified region on the radiograph. Classically the
density is shaped like a truncated cone, fanning out toward and
reaching the pleural surface.

406. Atelectasis

407. Westermark Sign

408. Hamptom Hump

409. ECG
• S1Q3T3 sign is seen in 15-25% of patients diagnosed with PE. It is a
sign of acute cor pulmonale (acute pressure and volume overload of
the right ventricle because of pulmonary hypertension) and reflects
right ventricular strain. This sign consists of a prominent S wave in
lead I and inverted Q and T waves in lead III.
• Other ECG findings are sinus tachycardia, T wave inversion in leads
V1-V3, right bundle branch block, and low amplitude deflections.
• “The ECG is often abnormal in PE, but findings are neither sensitive
nor specific for the diagnosis of PE.”

410. D-Dimer
• D-dimer is a degradation product of cross-linked fibrin, and therefore
levels are increased in the setting of thrombosis of any type.
• Plasma levels of d-dimer increase in the setting of venous thrombosis
but are also increased in many other conditions, including trauma,
surgery, cancer, and inflammation.
• D-dimer testing for venous thrombosis or pulmonary embolism is very
sensitive, but nonspecific.
• Thus, a normal d-dimer level is helpful, especially in the patient with a
low pretest probability of having a pulmonary embolus, but an
elevated level is considered nonspecific and therefore nondiagnostic.

411. V/Q Scan
• Perfusion (Q) lung scan
• Inject radiolabeled albumin particles into a peripheral vein
• If results of the scan are normal, pulmonary embolism is, for all practical
purposes, excluded.
• OBSTRUCTED = Absence of perfusion to the region of lung supplied by the
occluded vessel
• Abnormalities do not automatically indicate embolic disease
• Ventilation (V) scan
• Inhalation of a xenon radioisotope
• Added because if regions of decreased blood flow are secondary to airway
disease, corresponding abnormalities should be seen on the ventilation scan.
• Perfusion defect due to PE = ventilation still will be present in the area, and the
perfusion defect will be mismatched
• Perfusion defect due to parenchymal disease (e.g., pneumonia) =
corresponding abnormality should be seen on the chest radiograph.
• NOT DEFINITIVE

412. CTA
• Pros:
• Significant advantage of high-quality visualization of the lung
parenchyma
• CTA is more likely to be diagnostic than perfusion scanning, and it
is less invasive than traditional pulmonary angiography
• Can be performed quickly and is more readily available than
ventilation-perfusion scanning.
• Cons:
• Radiation dose associated with CTA, especially to the breast and
chest, is significantly higher than with ventilation-perfusion
scanning
• Must weigh the risk and benefits for the individual patient as well as
the practical issues of test availability and interpretation for each
patient in whom the diagnosis of PE is being considered.

414. Treatment
• Anticoagulation: Gold standard, immediate onset of action
• Initially, IV unfractionated heparin or subcutaneous LMWH, and then an oral
warfarin (for at least 3-6 months)
• Thrombolysis: for severe, sustained hemodynamic compromise
• tPA, streptokinase, urokinase, tenecteplase (TNK)
• Inferior vena caval filter: Anticoagulation not an option
• Trap thrombi from the LE en route to the pulmonary circulation
• Used if there are contraindications to anticoagulant therapy, thromboemboli
have recurred, or if the patient has such limited pulmonary vascular reserve
that additional clot to the lungs would be fatal.

416. Prognostic Significance of RH Strain
• RV enlargement in this setting is associated with an increased
likelihood of death within 30 days

417. Thrombolysis is used for severe,
sustained hemodynamic compromise
Patients in shock and hypotensive have
more adverse outcomes.

418. IV Heparin is the first line therapy used for
low risk category patients

419. Prevention of DVT
• 1. External compression of the lower extremities with an intermittently
inflating pneumatic device (IPC)
• 2. Heparin administered subcutaneously in low dosage.