Cliff Csizmar

HD1 Respiratory
Summer 2013
Pulmonary Function Tests
I) Breathing Mechanics
A) Normal mechanics
1) Inspiration
(a) Contraction of the diaphragm reduces the pleural pressure
(b) Alveoli expand as air is drawn in
(c) Flow is resisted by the radius of the airway and the elastic recoil of the alveoli
(i) As the lung expands, however, airways widen and resistance decreases proportionally to 1/r4
2) Forced expiration
(a) Relaxation of the diaphragm, contraction of abdominal muscles, and alveolar elastic recoil work
to expel air from the alveoli
(b) As the lung empties, the pleural pressure increases and begins collapsing the airways
(c) As the airways collapse, resistance increases and decreases flow proportionally (1/r4)
(d) Eventually, a state of effort-independent expiration is reached, where additional effort fails to
increase expiratory flow
B) Obstructive mechanics
1) Obstructive airways have two essential problems
(a) Loss of alveolar elastic recoil
(b) Loss of tethering that normally supports open airways
2) Ultimately, the dynamic compression of airways in expiration is accentuated, and expiratory flow is
greatly reduced
II) Spirometry
A) Features
1) Measures both volume and flow rate as gas enters/exits the lungs
2) Answers two important questions
(a) How big are the lungs?
(b) How well do they empty?
3) Permits differentiation between obstructive and restrictive disease
B) Static lung volumes

Spirometry

Static Lung Volumes

1) Definitions
TV = VT = tidal volume = vol. of gas inhaled or exhaled during each
(a) Tidalrespiratory
volume (TV)
represents the volume of gas inhaled and exhaled during a normal, resting
cycle
respiratory cycle
IRV (inspiratory
reserve
vol.)represents
and ERVthe
(expiratory
(b) Inspiratory
reserve volume
(IRV)
additionalreserve
volumevol.)
of air= that could be forcibly
the
additional
volume
of
gas
that
can
be
forcibly
inhaled
or
exhaled
inhaled beyond the tidal volume
beyond the resting VT

(c) Expiratory reserve volume (ERV) represents the additional volume of air that could be forcibly
exhaled beyond the tidal volume
(d) Vital capacity (VC) represents the maximum volume of gas that can be exhaled from the total
lung capacity
(i) The vital capacity is the volume directly assessed in spirometry
(e) Residual volume (RV) represents the volume of air that remains in the lungs following maximal
expiration
(f) Total lung capacity (TLC) represents the complete and total volume of the lungs
C) Normal spirometry
1) The forced expiratory volume in 1 second (FEV1) represents the amount of air forcibly exhaled in
one second
(a) Normal is >80% of the predicted value
2) The forced vital capacity (FVC) represents the maximum amount of air forcibly exhaled following
maximum inhalation
(a) Normal is >80% of the predicted value
3) The ratio of FEV1/FVC is clinically important in distinguishing obstructive and restrictive disease
(a) Minimal value is individualized based on the patients age, height and race
(b) Traditionally, normal values are >70%
D) Obstructive spirometry
1) Decreased FEV1/FVC defines the presence of an obstruction
2) The FEV1 determines the severity of the obstruction
E) Restrictive spirometry
1) The FEV1/FVC is often normal or elevated in restrictive disease
2) The FVC is lowered
3) TLC is used to determine severity
III) Flow Volume Loops
A) Features and normal flow-volume
loop Flow-volume Loop
Normal
1) Variation of spirometry that plots flow (L/min) against volume (L)
2) Differentiates lower airway disease (e.g. asthma) from upper airway obstruction
Expiratory
limb
Flow in
liters/min

RV

TLC
Inspiratory
limb
Volume in L

B) Obstructive flow-volume loop

1) Slow emptying from the narrow airways shows up as a dip in the expiratory limb
C) Restrictive flow-volume loop
1) High flow rates can be obtained, but the lower volumes narrow the loop
D) Variable extrathoracic upper airway obstruction
1) Inhalation generates negative pressure in the large, upper airways
2) If an extrathoracic obstruction is present, the negative pressure from inhalation will accentuate the
obstruction
(a) Obstructions include tumor, stenosis, etc.
3) A flattened inspiratory limb is observed

E) Variable intrathoracic upper airway obstruction

1) Exhalation compresses the lungs and, in turn, the upper airways
2) If an intrathoracic obstruction is present, the compression from exhalation will accentuate the
obstruction
3) A flattened expiratory limb is observed
F) Fixed upper airway obstruction
1) Both inspiratory and expiratory limbs are flattened

IV) Lung Volumes

A) Gas dilution
1) Inhalation of a known volume of helium and calculating the resulting diluted concentration permits
measurement of functional residual capacity (FRC)
2) May underestimate lung volume if areas of lung communicate poorly with the bronchial tree (as in
bullous emphysema)
B) Body plethysmography
1) A patient breaths into a box and against a closed shutter
2) Boyles Law is used to correlate pressure and volume changes to the patients FRC
3) Gold standard for lung volume determination
C) Diffusing capacity of the lung for carbon monoxide (DLCO)
1) Measures the ability of inhaled CO to cross the alveolar/capillary wall and bind hemoglobin
(a) Compares inhaled [CO] to exhaled [CO]
2) Determinants of diffusing capacity
(a) Alveolar/capillary surface area
(b) Volume of blood and hemoglobin
(c) Alveolar membrane thickness is less important
3) Differentiates destructive lung diseases (e.g. COPD from asthma)
4) Interpretation of DLCO Interpretation of Diffusing Capacity
Low
Non-lung
Anemia

Pulm Vasc Dz
e.g. primary
pulmonary
hypertension

Alveoli destroyed

High

Cardiac output
e.g. left to right shunt,
exercise

Pulmonary
hemorrhage
Elevated Hgb

COPD
Fibrotic lung diseases

V) Integration
FEV1/FVC nl,
FVC & TLC

FEV1, FVC, TLC

Normal/Near
normal

Restriction

Symmetric
RV normal
in lung
or
volumes

Low DLCO

Fibrotic
lung dz

Normal
DLCO

Weakness
Poor Effort

FEV1/FVC
FEV1

Obstruction
Normal/Nearnormal
Mechanics

Low DLCO

Pulmonary
Vascular
Disease

RV/TLC
(airtrapping)

Low
DLCO

Emphysema
Minimal
reversibility

Normal
DLCO

Asthma
Mostly
reversible

Chronic Obstructive Pulmonary Disease (COPD)

I) Prevalence of COPD
A) COPD is a big deal
1) 21 million cases annualy
2) Projected to increase in prevalence
3) Affects men and women
(a) Women are more susceptible and have more co-morbidities
II) Pathophysiology of COPD
A) Risk factors
1) Smoking
(a) Important to remember that not everyone who smokes will get COPD
(b) However, the majority of COPD cases are directly linked to smoking
2) Protease/anti-protease imbalance
(a) 1-anti-trypsin deficiency
(i) Can be treated with administration of recombinant 1-anti-trypsin
3) Infection
(a) Previous case of tuberculosis, especially
4) Genetic factors
5) Air/environmental pollution
6) Lung growth and development abnormalities
7) Age
8) Gender
9) Socioeconomic status
10) Bronchial hyperreactivity
B) Can be considered an overlap of obstructive bronchiolitis and emphysema
1) Obstructive bronchiolitis is a small airway disease with two major etiologies
(a) Inflammation
(b) Remodeling
2) Emphysema is an anatomic diagnosis
(a) Dilation and destruction of air spaces distal to the terminal bronchiole
(b) Loss of supportive elastic tissue

3) Results
(a) Poorly reversible airflow limitation
(i) Smooth muscle contraction
(ii) Bronchoconstriction
(iii)Mucus hypersecretion
(iv) Loss of elastic recoil
(v) Increased cholinergic tone
(vi) Airway narrowing
(b) Progressive destruction of structural elements
(i) Alveolar destruction
(ii) Collagen deposition
(iii)Glandular hypertrophy
(iv) Airway fibrosis
(c) Abnormal inflammatory response of the lung
(i) Increased oxidative stress
(ii) Increased leukocyte activity
(iii)Protease/anti-protease imbalance
C) Clinical features
1) Dyspnea
(a) Exertional (dynamic hyperinflation)
(b) Nocturnal (circadian rhythm)
2) Cough
(a) Productive or non-productive
3) Exacerbations
(a) Serious clinical illnesses
4) Hyperinflated chest
5) Wheezing or decreased breath sounds
6) Prolonged expiratory phase
7) Use of accessory muscles of respiration
8) Peripheral edema and enlarged heart (CHF)
9) Hypoxemia cyanosis
(a) Due to V/Q mismatch, increasing shunt effect
10) Hypercarbia
(a) Due to V/Q mismatch, increasing dead space
D) Diagnosis
1) Spirometry
(a) Decreased FEV1/FVC
III) Management of COPD
A) Reduce risk factors
1) Smoking cessation
2) Influenza and Pneumococcal vaccination
B) Pulmonary rehabilitation
C) Bronchodilators
1) 2-agonists (albuterol)
2) Anticholinergics (ipratropium)
D) Inhaled corticosteroids
1) May also try other pharmacologic treatments at this stage
(a) 1-anti-trypsin therapy
(b) Antioxidants
(c) Phosphodiesterase-4 inhibitors

(i) Show promise in reducing severe exacerbations and improving FEV1

E) Palliative care
F) Oxygen
1) Commonly practiced, though the actual benefit may be overestimated
G) Surgery
1) Lung transplant
2) Lung volume reduction surgery (LVRS)
(a) By removing (either functionally or anatomically) the compromised portion of the lung, the
healthy lung is able to expand into the newly created void, effectively increasing TLC
Chest Imaging
I) Chest X-Rays (CXRs)
A) Basic imaging concepts
1) Silhouette sign
(a) Borders are generated at the interface between two materials with different densities (and thus
different opacities to X-rays)
2) Summation of shadows
(a) When multiple materials are in-line with a beam of X-rays, each individual material will still
absorb quanta of X-rays appropriate for its density
(b) Thus, the total absorbance of X-rays in that line will be the summation of the individuals
absorbencies of each material
3) Scatter and magnification with distance
(a) The farther an anatomical structure is from the film (and closer it is to the radiation source), the
more diffuse and magnified it will appear in the CXR
B) Views used for CXRs
1) Posteroanterior (PA)
(a) X-rays pass through the patient from back to front
2) Lateral view
(a) Left side is placed against the film cassette
(i) Thus, right-sided structures are magnified
3) Anteroposterior (AP)
(a) X-rays pass through the patient from front to back
(b) Often obtained from portable X-ray devices in bedridden patients
(c) Technical problems
(i) Cardiac magnification
(ii) Patient is not upright
(iii)Skin folds may be visible
4) Lateral decubitus
(a) Patient is laying on their side
(b) Demonstrates shifting fluids and pneumothorax
5) Apical lordotic view
(a) PA film with X-rays angled cranially
(b) Helps visualize apical/upper lobes
(c) Moves clavicles upwards and out of the way
6) Oblique views (LAO, RAO)
(a) Rarely used to visualize abnormalities
C) Normal anatomy of the chest
1) Lobes and fissures
2) Trachea

3) Heart

Cardiac anatomy

4) HilumHilar

anatomy

5) Mediastinum

Superior

Posterior

Mediastinal anatomy
Anterior
Middle
Posterior
Superior

6) Bone

Differential
diagnosis for a given abnormality varies depending
location

Approach to interpreting chest radiographs

7) Blind Chest
spots

Xray blind spots

D) Basic pulmonary pathology

1) Atelectasis (volume loss due to alveolar collapse)
2) Pleural effusions (fluid occupies pleural space)
(a) Can appear as pseudotumors in the interlobar fissures
3) Pneumothorax (air occupies pleural space)
4) Pneumonia (bacterial infections)
5) Pulmonary nodules
(a) Coin lesions (accidental inhalation of spare change)
(b) Neoplasms
6) COPD (hyperinflated lung fields)
II) Computed Tomography (CT)
A) Basic imaging concepts
1) Spiral CT methodology allows rapid scanning of the entire chest (~20 seconds)
2) Resolution and contrast are superior to CXR, making CT more appropriate for early detection of
neoplasms
(a) Detection of microcalcifications is another advantage/indication

Asthma
I) Introduction and Epidemiology
A) Asthma is a chronic inflammatory disorder of the airways
B) One of the most common chronic diseases
1) Estimated 300 million affected individuals
2) Health care expenditures are high
3) More common in some populations
(a) Children (<5 years old)
(b) Women
(c) Blacks
C) Types of asthma
1) Intrinsic (non-atopic)
2) Extrinsic (atopic)
(a) Major form
(b) Mediated by inflammatory mechanisms
3) Exercised induced
(a) True exercised-induced bronchoconstriction is rare
4) Aspirin-sensitive
(a) Associated with nasal polyps
5) Occupational
D) Risk factors
1) Host factors
(a) Genetic predisposition
(i) Atopy
(ii) Airway hyper-responsiveness
(b) Gender
(c) Obesity
2) Environmental factors
(a) Indoor/outdoor allergens
(b) Occupational sensitizers
(c) Tobacco smoke
(d) Air pollution
(e) Respiratory infections
(f) Diet
E) Triggers
1) Allergens
2) Respiratory infections
3) Exercise and hyperventilation
4) Weather changes
5) Sulfur dioxide
6) Food, additives, drugs
7) Acid reflux
8) Sleep apnea
9) Stress
II) Pathophysiology
A) Brief process
1) An inhaled allergen activates mast cells by cross-linking IgE on their surface
2) Mas cells release histamine, leukotrienes, and PGD2, leading to bronchoconstriction
B) Mediators that are highly implicated in this pro-inflammatory process

1) TH2 cells
2) Eosinophils
3) IL-2, 4, 5, and 10
C) Pathology
1) Smooth muscle constriction hypertrophy and hyperplasia of bronchial smooth muscle
2) Eosinophil and lymphocyte invasion airway wall edema
3) Hyperplasia of goblet cells increased mucous production
4) Airway remodeling and scarring, including thickening of the basement membrane
D) Physiology
1) Airflow obstruction
(a) Decreased FEV1, FEV1/FVC, and PEF
2) Hyperinflation
(a) Increased TLC
3) Gas trapping
(a) Increased RV, FRC, and RV/TLC
4) Normal alveolar/capillary diffusion (DLCO)
5) Spirometry may be normal in mild cases

6) Gas exchange
(a) Decreased PaO2
(b) Increased PaCO2
(c) V/Q mismatch can be corrected with application of oxygen, but shunting cannot
III) Diagnosis
A) Diagnosis is based on several key factors
1) History
2) Spirometry
(a) FEV1
(b) Peak expiratory flow rate
3) Measurement of airway responsiveness
(a) Methacholine challenge test
(b) Exercise challenge test
4) Measurement of allergic status (IgE titers and CBC)
B) Differential
1) COPD
2) Cystic fibrosis (especially important to test for in children with nasal polyps)
3) Bronchiectasis
4) CHF
5) Paroxysmal vocal cord dysfunction

10

6) Acid reflux
7) Other obstructions (tumor, foreign body, bronchiolitis, etc.)
IV) Treatment and Management
A) Goals of long-term management
1) Control symptoms
2) Maintain normal activity levels (including exercise)
3) Maintain normal pulmonary function
4) Prevent exacerbations
5) Avoid adverse medication effects
6) Prevent mortality
B) Controlling medications
1) Inhaled glucocorticoids
(a) These are the most effective, and thus the most widely used
2) Leukotriene modifiers
(a) More convenient (pill), but not as effective
3) Long-lasting inhaled 2-agonists
4) Long-lasting anti-cholinergics
5) Theophylline
6) Cromones
7) Long-acting oral 2-agonists
8) Anti-IgE therapy
9) Systemic glucocorticosteroids
C) Relieving medications
1) Rapid-acting inhaled 2-agonists
2) Systemic glucocorticosteroids
3) Anti-cholinergics
4) Theophylline
5) Short-acting oral 2-agonists
D) New treatments
1) Bronchial thermoplasty
2) Tiotropium (long-acting anti-cholinergic)
3) Intermittent corticosteroid therapy
E) Treating children (<5 years old)
1) Children may metabolize medications more rapidly
F) Treating an emergent exacerbation
1) Repetitive administration of rapid-acting inhaled 2-agonists
2) Introduction of systemic glucocorticosteroids
3) Oxygen supplementation
Acute Respiratory Failure
I) Introduction
A) Signs and symptoms of poor gas exchange (many are non-specific)
1) Hypercapnia headache or decreased level of consciousness
2) Vasodilation flushing and/or sweating
3) Hypoxemia several effects
(a) Confusion, restlessness, impaired judgement, paranoia
(b) Sympathetic response hypertension and/or tachycardia
(c) Cyanosis
4) Dyspnea (more useful when in a clinical setting where respiratory failure is likely to occur)

11

B) Detection and approach

1) Oximetry is the first approach
2) Arterial blood gas testing can be used liberally
II) Arterial Blood Gasses (ABGs)
A) PaCO2 as a measure of alveolar ventilation
1) Normally, PaCO2 is maintained at 40 mmHg by the central respiratory center
2) CO2 is poorly soluble in aqueous solutions, and is thus transported as carbonic acid in the blood
(a) This transport system is not saturable, which is the key distinguisher from O2 transport
B) Acid/Base Status
1) Respiratory acidosis
(a) Alveolar hypoventilation increases PaCO2 increased carbonic acid decreased pH
(b) In acute respiratory acidosis, the pH falls 0.08 units for each 10 mmHg increase in PaCO2
(c) In chronic respiratory acidosis, the pH falls 0.03 units per 10 mmHg increase in PaCO2
(i) The gradual increase in bicarbonate between the acute and chronic phases is due to renal
compensation
2) Respiratory alkalosis
(a) Alveolar hyperventilation decreases PaCO2 decreased carbonic acid increased pH
(b) In acute respiratory alkalosis, the pH increases 0.08 units per 10 mmHg decrease in PaCO2
(c) In chronic respiratory alkalosis, the pH increases 0.02 units per 10 mmHg decrease in PaCO2
(i) The gradual decrease in bicarbonate between the acute and chronic respiratory phases is due
to renal compensation
C) PaO2 as a measure of blood oxygenation
1) Normal arterial blood gases
(a) PaO2 = 100 mmHg
(b) PaCO2 = 40 mmHg
(c) pH = 7.40
(d) HCO3 = 25 mEq/L
2) Correlation between PaO2 values and O2 saturation
(a) Sigmoidal function, due to cooperativity of hemoglobin
(b)
Relationship between PaO2 and O2 Saturation
PaO2 (mmHg)
O2 Saturation
100
99%
90
95%
60
90%
50
85%
40
75%
28
50%

D) Efficiency of gas exchange and the A-a gradient

1) The alveolar-arterial (A-a) gradient describes the difference between alveolar and arterial oxygen
(a) In bellows failure, the A-a gradient remains normal (the hypoxemia is due only to inadequate
ventilation of the lungs)
(b) In V/Q mismatching and shunting, the A-a gradient is pathologically increased (>15 mmHg)
2) Calculation of the A-a gradient requires knowledge of several values
(a) Fraction of inspired oxygen
(b) PaCO2 (obtained from ABG testing)
(c) PaO2 (obtained from ABG testing)
3) Calculating he alveolar/arterial difference
(a) !"#!! !"#!! = !!

12

(b) Ideally, there would be no difference between arterial and alveolar PO2 because diffusion would
equilibrate the two in the pulmonary capillary beds
(i) Physiologic values, however, deviate from the ideal
o Healthy: 5 10 mmHg differential
o Pathologic: >15 mmHg differential
(c) Calculating the (Alv-Art)PO2
(i) Most often, arterial PO2 can be determined from arterial blood gas testing
(ii) Alveolar PO2 must be estimated using a combined derivation of two other equations
o If the empirical equations for arterial PO2 and PCO2 (see above) are joined by solving the
PCO2 equation for VA and substituting it into the PO2 equation, the resulting formula is:

!"#!! = !!!

!!"#!"

Where R is the respiratory quotient, and =

!!"!
! !!

= 0.8

This signifies that the volume of CO2 that we exhale is typically 80% of the
volume of O2 that we inhale
o However, we dont know the alveolar PCO2
o Fortunately, the alveolar PCO2 is virtually identical to the arterial PCO2, which is also
measured with arterial blood gas testing
o Therefore, the (Alv-Art)PO2 can be determined directly from blood gas testing via the
following equation:
!! = !"#!! !"#!! = !!!

!!"#!"
!

!"#!!

Recall that !!! = !"#$%&'#() !! ! !!! = 747 47

0.21 = 150
o If the FIO2 increases, so will the PIO2 and subsequently the A-a gradient
This can be exploited clinically by administering concentrated oxygen to a hypoxic
patient

III) Lung Models

A) The one-compartment lung model
1) Normally, arterial blood gases equilibrate with alveolar gases as blood traverses pulmonary
capillaries
2) When ventilation (VA) decreases relative to perfusion (Q), then blood will neither properly
oxygenate or unload CO2
(a) PaO2 will fall below 100 mmHg
(b) PaCO2 will increase above 40 mmHg
3) If the alveolus is completely blocked (i.e., there is shunting), then the blood will remain venous
blood and there will be no change in ABGs
4) If V > Q, then PaO2 will increase above 100 mmHg and PaCO2 will fall below 40 mmHg
(a) If this is taken to extremes (i.e., as Q approaches 0 and V/Q approaches infinity), then PaO2 will
equilibrate with PAO2 (which represents the PIO2, which equals ~150 mmHg) and the PaCO2
will fall to zero
B) The two-compartment lung model
1) This gets fairly conceptual, and a review of the relevant lecture slides is perhaps best (slides 46-55 in
Acute Respiratory Failure I)
2) Key concepts
(a) The PaO2 is determined from the average O2 saturation (per the oxygen/hemoglobin dissociation
curve) and not an average of the PaO2 from each venous component
(i) This is because oxygen transport via hemoglobin is saturable
(b) V/Q mismatch can be clinically corrected by applying increased oxygen
(c) Shunting cannot be clinically corrected by applying increased oxygen
13

(i) This is because oxygen transport via hemoglobin is saturable while CO2 transport as
dissolved carbonic acid is not (it is curvilinear)
IV) Types of Respiratory Failure
A) Bellows failure
1) No air goes in or out, and there is no gas exchange
2) Causes
(a) Insufficient effort (no drive to breathe)
(i) No message from brainstem
(b) Neuromuscular syndromes
(i) Numerous etiologies
(c) Excess work of breathing muscle fatigue
(i) COPD, asthma, fibrosis, obesity, etc.
(d) Inefficiency of bellows mechanism (effort is wasted)
(i) Flat diaphragm with hyperinflation, low tidal volume, unstable chest, etc.
3) Treatment
(a) Aggressive support is often needed
(i) Provide airway
(ii) Supply a breathing rate (if no drive is present)
(iii)Support work of breathing
B) Respiratory failure due to COPD
1) Initial ABGs
(a) PaO2 = 20-40 mmHg
(b) PaCO2 = 50-70 mmHg
(c) pH = 7.20-7.30
(i) Often times, the pH is partly compensated and resides somewhere between acute and chronic
acidosis
(d) A-a gradient is very high
2) Problem
(a) Worsening V/Q mismatch combined with increasing CO2 production
(b) Patient attempts to compensate through maximal ventilation
(c) Increased airway resistance, hyperinflation, and muscle fatigue bellows failure
(i) The maximum minute ventilation is ~35 L per liter of FEV1, and can only be sustained for
short periods of time
3) Treatment
(a) Administer oxygen to correct V/Q mismatch
(b) Non-invasive face mask ventilation
(i) Faster reduction in respiratory rate and heart rate
(ii) Faster improvement in dyspnea and gas exchange
(iii)Less chance of requiring intubation (42%)
(iv) Shorter hospital stay
(v) Lower mortality
(c) Treat bronchospasm, infection, volume overload, etc.
(d) Smoking cessation
4) ABGs post-therapy
(a) PaO2 = 50-60 mmHg
(i) Marked improvement
(b) PaCO2 = 55-70 mmHg
(c) pH = 7.20-7.30
C) Acute respiratory distress syndrome (ARDS)
1) Insult injury abnormal physiology support repair or death

14

2) Insults include surgical or non-surgical interventions

(a) Pneumonia, sepsis, aspiration, trauma, etc.
3) Injury
(a) After a lag period, injury to the capillaries causes increased permeability, and the lung is flooded
with high protein fluid
4) Abnormal physiology
(a) Edema, fibrosis, hypoxemia, shunting, etc.
5) Support
(a) High pressure ventilators and high oxygen concentrations have been shown to propagate injury
(b) Positive end-expiratory pressure (PEEP) ventilation is preferred, as it is highly beneficial
(i) Maintains a plateau pressure above atmospheric pressure
(ii) Pries the lung open to a higher lung volume
(iii)Increases FRC
(iv) Decreases shunt
(c) Prone ventilation as opposed to supine
D) Diffuse lung disease
1) V/Q mismatch
2) Oxygen will correct the hypoxemia
E) Pulmonary edema
1) Intrapulmonary shunt
2) Oxygen will not correct the hypoxemia
Bacterial Pneumonia
I) Pathogenesis
A) Four categorical mechanisms of infection
1) Aspiration
(a) Oropharyngeal secretions
(i) This is the most common cause of pneumonia
(b) Stomach contents
(c) Foreign body
2) Aerosol
(a) Transmission of small (<5 m) aerosolized particles
(i) Person-to-person transmission with high infectivity
(b) Viruses
(c) Mycoplasma
(d) Tuberculosis
(e) Legionella
(f) Fungi
3) Hematogenous
(a) Bacteremia
(b) Viremia
(i) Varicella-zoster
(ii) CMV
(c) Fungemia
(i) Histoplasmosis
(ii) Cryptococcus
(d) Miliary tuberculosis
4) Reactivation
(a) Tuberculosis

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(b) Fungal etiologies

(i) Histoplasmosis
(ii) Blastomycosis
(iii)Pneumocystis
B) Host abnormalities that predispose to infection
1) Ineffective cough and/or increased aspiration
(a) COPD, swallowing disorders, lung cancer, alcohol intoxication, etc.
2) Decreased mucociliary transport
(a) Smoking, COPD, cystic fibrosis, viral infection, etc.
(b) Ciliopathies
3) Medications
(a) Increased gastric pH (histamine blockers, proton pump inhibitors, antacids, etc.)
(b) Antipsychotics
(c) Inhaled corticosteroids
C) Abnormal flora/pathogens
1) Virulence factors
(a) Ciliary dysfunction/transport
(i) Chlamydophila pneumoniae ciliostatic
(ii) Mycoplasma pneumoniae cilofragmentation
(iii)Influenza virus decreased mucous transport
(b) Proteases
(i) IgA protease
(ii) Pneumolysin
(iii)Neruaminidase
(iv) Hyaluronidase
(v) Panton-Valentine leukocidin
(c) Antibiotic resistance
(i) Mycobacterium species
(ii) Nocardia species
(iii)Legionella species
II) Clinical Presentation
A) Pulmonary symptoms
1) Productive cough
2) Dyspnea
3) Pleuritic chest pain
B) Systemic symptoms
1) Fever, chills, sweats
2) Headache, confusion
3) Myalgias, arthralgias
4) Abdominal pain, nausea, vomiting, diarrhea
C) Physical exam findings
1) General
(a) Fever, tachypnea, tachycardia, cyanosis, altered mental status
2) Lungs
(a) Rales
(b) Dullness to percussion
(c) Bronchial breath sounds
(d) Wheezes, rhonchi, egophony
(e) Pleural friction rub
D) Pathophysiology

16

1) Decreased alveolar ventilation V/Q mismatch (approximates a shunt) hypoxemia increased

PCO2
III) Diagnosis
A) Initial evaluation
1) CXR (gold standard)
(a) Must distinguish pneumonia from bronchitis
2) Consider spectrum of vulnerability
(a) Different pathogens are more likely depending on the patients overall health
(b) Pneumonia severity index can be used to determine relative risk
B) Tests
1) First and foremost, consider the patients history
(a) Travel, animal exposure, occupational hazards, hobbies, medications, exposure to kids
2) Sputum exam is controversial in terms of utility
(a) Requires high quality specimen
(i) >25 WBCs
(ii) <10 epithelial cells
(iii)Processed within 1-2 hours
(iv) No recent antibiotic treatment
(b) Obtained via several techniques
(i) Bronchoscopy
(ii) Transtracheal aspiration
(iii)Transthoracic aspiration
(iv) Lung biopsy
3) Blood cultures
4) Pleural fluid analysis
5) Analysis of other bodily fluids
C) Do not delay antibiotic therapy while waiting for obtain microbial samples!
D) Antigen detection of pathogens is indicated in several situations
1) Legionella infection
2) Pneumococcal infection
3) Nasopharyngeal swab for influenza
E) PCR (accurate with rapid turn-around)
IV) Management
A) Syndromic approach to community acquired pneumonia (CAP)
1) Describes specific pathogens that are likely to be the culprit given the patients history
B) Empiric approach to CAP
1) This is a more commonly adopted method that focuses on selecting rational antimicrobials based on
specific criteria
(a) Most likely organism
(b) Risk factors for antimicrobial resistance
(c) Medical co-morbidities
C) Empiric treatment approaches are slightly different depending on the health/risk of the patient
1) Outpatients
(a) Previously healthy with no risk for drug-resistant Streptococcus pneumoniae (DRSP)
macrolide
(b) Co-morbidities, recent antibiotic therapy, or risk for DRSP fluroquinolone or -lactam +
macrolide
2) Inpatients
(a) Fluoroquinolone or -lactam + macrolide
3) ICU patients

17

(a) Fluoroquinolone or -lactam + macrolide

(b) Risk of Pseudomonas aeruginosa anti-pseudomonal agent + fluoroquinolone
D) If patients are not responding to treatment, consider other possibilities and expand testing protocol
1) Non-infectious cause
(a) There are many non-infectious mimics of pnemonia
2) Unusual/resistant organism
3) Superinfection
4) Metastatic infection
5) Undrained infection
6) Endobronchial obstruction
Pleural Diseases
I) Pleural Effusions
A) Presentation
1) Spirometry shows restriction
(a) Decreased FEV1 and FVC
(b) Normal FEV1/FVC
2) Increased work of breathing
3) Dyspnea
4) Pleuritic chest pain
(a) May be referred to shoulder
5) Cough (usually nonproductive)
6) Physical exam findings
(a) Respiratory distress with expanded hemithorax
(b) Dullness on percussion
(c) Diminished breath sounds on auscultation
(d) CHF, abdominal distention with ascites, arthropathy, etc.
7) Imaging
(a) Meniscus sign on CXR (cupped effusion that obscures costophrenic angle and diaphragm)
(b) Opacity on chest CT that will move with gravity
(c) Pleural effusions in the lung fissures may appear as pseudotumors
(d) Ultrasound may show separation of visceral and parietal pleura
B) Physiology and pathophysiology
1) Pleural anatomy
(a) The parietal pleura has large lymphatic stoma and pain nerves
(i) Thus, pleuritic pain is due to parietal pleural involvement
(ii) The large lymphatic stoma are responsible for removing fluid from the pleural space
o Starling forces suggest that without these stoma, capillary fluid would accumulate in the
pleural space
(b) The visceral pleura lacks pain fibers
2) Pleural pressure
(a) Balance between elastic pressure of chest wall (outward) and lung (inward)
(b) Primary determinant of lung volume
(c) Normal intrapleural pressure is -5 cmH2O
(i) There is a vertical pressure gradient, with the most negative pressure in the upper lung fields
3) Pathogenesis of effusions
(a) Non-inflammatory transudates
(i) Increased hydrostatic pressure (e.g. CHF)
(ii) Reduced capillary oncotic pressure

18

(iii)More negative pleural pressure (e.g. atelectasis)

(b) Inflammatory exudates
(i) Increased pleural surface permeability
(ii) Increased pleural oncotic pressure
(c) Transudative or exudative
(i) Impaired lymphatic drainage (blockage of stoma, e.g. cancer)
(ii) Transdiaphragmatic transport (ascites, e.g. liver failure)
C) Evaluation
1) Thoracentesis
(a) A needle is passed through the chest wall and into the pleural space
(b) Fluid is withdrawn for analysis
(c) Risks of bleeding, infection, and pneumothorax
2) Differentiating transudative and exudative effusions
(a) Lights criteria for transudate (must meet all criteria)
(i) Ratio of pleural protein to serum protein is <50%
(ii) Ratio of pleural LDH to serum LDH is <60%
(iii)Pleural LDH value is <2/3 of the upper limit of normal serum LDH
(b) Lights criteria for exudate (only need to meet one criterion)
(i) Ratio of pleural protein to serum protein is >50%
(ii) Ratio of pleural LDH to serum LDH is >60%
(iii)Pleural LDH value is >2/3 of the upper limit of normal serum LDH
3) Imaging
(a) Loculated (walled-off, localized) effusion suggests an exudate
D) Causes of transudates and exudates
1) Causes of transudative effusion
(a) CHF (typically bilateral)
(b) Nephrotic syndrome (low oncotic pressure)
(c) Liver cirrhosis (ascites tracks across right hemidiaphragm)
2) Causes of exudative effusion
(a) Parapneumonic causes
(i) These are caused by a bacterial pneumonia
(ii) There are three types
o Empyema = pus in pleural space
Treated by drainage + antibiotics
o Simple parapneumonic effusion
Treated with antibiotics alone
o Complicated parapneumonic effusion = highly inflammatory, but no pus
Treated with antibiotics, but may need drainage as well
(iii)Complications
o Bronchopleural fistula air and infection pass from lungs to pleura
o Fibrothorax restrictive lung disease
(b) Pulmonary embolism
(c) Neoplasm (e.g., mesothelioma)
(d) Rheumatologic diseases (e.g., rheumatoid arthritis, lupus, etc.)
(e) Tuberculosis
(i) Focal granuloma near pleural surface ruptures bacteria into pleural space delayed
hypersensitivity reaction granulomatous reaction
(ii) Pleural fluid will be exudative and lymphocytic, but very few acid-fast bacilli will be present
o Pleural biopsy is often needed for diagnosis
(iii)Treated the same as regular pulmonary tuberculosis (combination therapy)

19

(f) Hemothorax
(i) Trauma
(ii) Neoplasm (not often)
(iii)Pulmonary embolism (not often)
(g) Chylothorax
(i) Distinct milk appearance due to high triglyceride content
(ii) Caused by blockage of the thoracic duct
o Most often due to neoplasm in the mediastinum (e.g., lymphoma)
II) Pneumothorax
A) Presentation
1) Symptoms
(a) Pleuritic chest pain
(b) Dyspnea
2) Exam findings
(a) Hyperresonance upon percussion
(b) Decreased breath sounds
(c) Tracheal deviation towards the side of collapse
(d) Hemodynamic instability (if tension pneumothorax)
3) Imaging
(a) Air pocket with collapsed lung on CXR and chest CT
B) Classifications
1) Primary spontaneous
(a) Otherwise healthy individuals
(b) Apical subpleural blebs are common on chest CT
(c) Patients typically in their 20s, smoke, and may have a family history
2) Secondary spontaneous
(a) Underlying lung disease (COPD is most common)
(b) More often, these are life-threatening
3) Traumatic
(a) Trauma or iatrogenic
C) Management
1) Primary spontaneous
(a) <20% of chest cavity = observe
(b) >20% of chest cavity = evacuate air
2) Secondary spontaneous
(a) Evacuate air
3) Pleurodesis for severe cases
(a) Induces a chemical/inflammatory reaction that obliterates the pleural space by causing the pleura
to fibrose together
III) Atelectasis
A) Collapse of the lung
B) Diverse causes
1) External compression
(a) Fluid in pleural effusion
(b) Air in tension pneumothorax
2) Inadequate ventilation
(a) Collapse of entire lobe/lung distal to plug (mucus, foreign body, tumor)
(b) Localized to a segment or subsegment of a lobe
C) Types
1) Complete

20

2) Plate-like
3) Bibasilar dependent
Pulmonary Embolism
I) Introduction
A) Definition
1) Pulmonary emboli are thrombi from the venous circulation that embolize to the pulmonary arteries
B) Epidemiology
1) Incidence of 1/1,000 per year
2) Diagnosis is difficult
3) Untreated PE has a high mortality
4) Common cause of sudden death in hospitalized patients
C) Contributors to thrombus formation
1) Inherited risk factors
2) Relative risk factors
3) Acquired risk factors
(a) Virchows triad
(i) Venous stasis
(ii) Endothelial damage
(iii)Hypercoagulability
II) Pathophysiologic Consequences of PE
Physiology
Low VQ areas

Mechanism

Gas Exchange

Blood flow redistribution,

Bronchospasm

PvO2

Low cardiac output

Shunt

Atelectasis

High VQ areas

Partial obstruction
of vascular bed

Dead space

Complete obstruction
of vascular bed

Resp. Drive

Hypoxemia, pain,
irritant receptors

PaO2
A-a gradient

Minute ventilation
PaCO2

A) ABGs may show respiratory alkalosis, hypoxemia, and an increased A-a gradient
ABG may show respiratory alkalosis, hypoxemia, A-a gradient
1) Dead space has little effect
2) Shunt may increase PaCO2
3) V/Q mismatch
(a) High V/Q units may lower PaCO2
(b) Low V/Q units may increase PaCO2
B) Hemodynamic consequences
1) Pulmonary hypertension
2) Dilation of the RV
3) Leftward deviation of the interventricular septum
III) Clinical Presentation

21

A) Clinical presentations vary greatly and may include the following

1) Acute onset of pleuritic chest pain
2) Dyspnea
3) Hemoptysis
4) Acute cardiovascular collapse
(a) Syncope
(b) Cardiac arrest
B) CXR findings are non-specific
1) Rarely diagnostic, as it is normal in >20% of cases
2) Volume loss
3) Atelectasis
4) Patchy density (due to edema and hemorrhage)
5) Localized oligemia with proximal pulmonary artery enlargement (Westermarks sign)
6) Localized, pleural-based triangular density representing an infarct (Hamptons hump)
7) Pleural effusion
C) ECG findings
1) Tachycardia
2) P pulmonale (tall, peaked P-waves)
3) RV strain
4) RBBB
D) ABG findings
1) Hyperventilation
2) Low PaCO2
3) Normal oxygen saturation
4) PaO2 may be low, but a normal finding does not exclude PE
E) Diagnosis
1) Must have a high clinical suspicion
2) Imaging
(a) DVT
(i) Venography (contract, radionuclide, CT)
(ii) Doppler ultrasound
(b) PE
(i) Pulmonary contrast angiogiography
(ii) V/Q lung scan (rarely used anymore)
(iii)CT angiography
(iv) MRI
3) Tests
(a) D-dimer (may be elevated)
F) Assessing severity
1) Echo
(a) RV dilation
(b) RV hypokinesis
(c) Tricuspid regurgitation
(d) Deviation of the interventricular septum
(e) Clots en passage
2) Hemodynamics (BP and HR)
3) CVP
4) ABG
5) Residual clot burden
(a) Doppler ultrasound

22

(b) Heparin consumption

IV) Treatment
A) Prevent new clot formation with anticoagulants
1) Heparin (unfractionated or LMWH)
(a) Anticoagulant of choice
(b) Rapid onset of effect
2) Warfarin
(a) Less potent
(b) Oral dosing
(c) Continue for ~3 months (potentially longer)
3) Idraparinux
B) Lyse existing clots with thrombolytics
1) Urokinase
2) Streptokinase
3) Tissue plasminogen activator
C) Prevent large clots from reaching the lungs
1) Inferior vena cava filters
D) Remove existing clots
1) Thrombectomy (mechanical or suction)
E) Standard treatment approach
1) Begin with heparin
2) Overlap heparin and warfarin therapy for ~5 days
3) Continue with warfarin for 3+ months
4) Adjust warfarin dose as needed to maintain INR of 2-3
F) Prevention
1) Early ambulation
2) Graded compression stockings
3) Intermittent pneumatic compression
4) Fixed, low dose heparin
5) Adjusted dose warfarin
6) IV heparin
Pulmonary Hypertension
I) Introduction
A) Definition of pulmonary hypertension
1) Mean pulmonary artery pressure (mPAP) >25 mmHg
!
!
(a) = ! + !
B) Epidemiology
1) Not much known
C) Pulmonary vasculature
1) Dual blood supply
(a) Bronchial circulation from the aorta has systemic pressures and low compliance
(b) Pulmonary circulation from the RV has low pressure and high compliance
2) Calculating pulmonary vascular resistance
! !!
(a) = !"!" !"
(i) PPA = mean pressure in the pulmonary artery
(ii) PLA = mean pressure in the left atrium
(iii)CO = cardiac output (L/min)
(b) The transpulmonary gradient (TPG) is normally <10 mmHg

23

(i) TPG = mPAP PCWP

D) Exercise
1) During exercise, CO increases while pulmonary pressures remain relatively constant
2) This is because the pulmonary vasculature is both distendable and able to recruit otherwise
underperfused capillary beds
E) Pathological changes with pulmonary hypertension
1) Pulmonary arteries thicken and narrow
(a) Thickening may be caused by an imbalance between vasoconstrictive and vasodilative pathways
(i) The endothelin pathway promotes vasoconstriction and smooth muscle cell proliferation and
is upregulated in disease
(ii) NO and prostacyclin pathways oppose the endothelin pathway, inducing vasodilation and
antiproliferation
2) Unaffected pulmonary arteries are forced to dilate in response to increased pressure and flow
3) The RV dilates and hypertrophies in response to the increased pressure
F) Clinical findings
1) Symptoms
(a) Dyspnea (60-90%)
(b) Fatigue (19%)
(c) Chest pain (7%)
2) Physical exam
(a) Prominent P2
(b) RVH (prominent A-wave in jugular venous pulse)
(c) Right-sided heart failure
(i) S3
(ii) Tricuspid insufficiency with holosystolic murmur
(d) Hepatic congestion
(e) Peripheral edema and/or ascites
II) Classificaitons of Pulmonary Hypertension
A) Pulmonary arterial hypertension (PAH)
1) Histopathology
(a) Endothelial proliferation
(b) Intimal fibrosis
(c) Medial and smooth muscle cell hypertrophy
(d) In situ thrombosis
2) Causes
(a) Idiopathic
(b) Heritable mutations
(i) BMPR2 (bone morphogenic protein receptor 2)
o Autosomal dominant with incomplete penetrance
o Present in 70% of familial cases of pulmonary hypertension
(ii) ALK1 (activin receptor-like kinase type 1)
(iii)Serotonin transporter
(c) Drug- and toxin-induced
(d) Collagen vascular diseases
(e) HIV infection
(f) Portal hypertension
(g) Congenital heart diseases
(h) Schistosomiasis
(i) Chronic hemolytic anemia
(j) Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)

24

B) Pulmonary hypertension owing to left heart disease

1) Most common cause of pulmonary hypertension
2) Causes
(a) Increased left atrial pressure
(i) Left heart systolic/diastolic dysfunction
(ii) Left heart valvular disease
(b) Increased pulmonary vascular resistance
C) Pulmonary hypertension owing to lung diseases and/or hypoxia
1) Alveolar hypoxia
(a) Hypoxia vasoconstriction increased vascular tone decreased vascular bed
2) Exemplary diseases
(a) COPD
(b) Interstitial lung disease
(c) Sleep disordered breathing (apnea)
D) Chronic thromboembolic pulmonary hypertension (CTEPH)
1) Chronic pulmonary emboli create structural blockages that increase pressure
E) Pulmonary hypertension with unclear multifactorial mechanisms
1) Hematologic disorders
(a) Chronic myeloproliferative disorders
2) Systemic disorders
(a) Sarcoidosis
3) Metabolic disorders
(a) Type Ia glycogen storage disease
4) Miscellaneous
(a) Tumor obstruction
(b) Mediastinal fibrosis
(c) End stage renal disease
III) Diagnosis
A) Based on suspicion of pulmonary hypertension, one can progress through a diagnostic workflow
1) Echocardiogram
(a) Left heart disease
(b) Congenital heart disease
2) CXR, PFTs, and CT
(a) Obstruction
(b) Restriction
(c) Parenchymal disease
3) V/Q scan, CT angiogram, and pulmonary angiogram
(a) Chronic thromboembolic disease
4) Sleep study and overnight oximetry
(a) Sleep apnea
5) Antibody tests
(a) SLE
(b) Scleroderma
6) Liver function tests
(a) Portopulmonary hypertension
7) HIV testing
(a) HIV
8) Cardiac catheterization
(a) Shunt or heart disease
9) If all are negative, the pulmonary hypertension is classified as idiopathic

25

IV) Treatment
A) Early treatment is directed at the underlying causes
1) Pulmonary arterial hypertension
(a) Treat underlying heart disease
2) Pulmonary hypertension owing to left heart disease
(a) Treat underlying cardiomyopathy
(b) Replace valve
3) Pulmonary hypertension owing to lung diseases and/or hypoxia
(a) Treat hypoxia
(i) Long-term administration of oxygen may be beneficial
(b) Optimize lung disease
(c) Treat sleep apnea
(i) Weight loss
(ii) CPAP (continuous positive airway pressure)
(iii)Corrective airway surgery
(iv) Tracheostomy
4) Chronic thromboembolic pulmonary hypertension
(a) Thromboendarterectomy
(b) Anticoagulation
B) Advanced treatment is directed at the pulmonary hypertension itself
1) Patient functional classes (WHO)
(a) I no limitations on physical activity
(b) II ordinary physical activity causes symptoms
(c) III less than ordinary physical activity causes symptoms
(d) IV symptoms present at rest
2) Treated with pulmonary vasodilators
(a) Calcium channel blockers (nifedipine and diltiazem)
(b) Endothelin receptor antagonists
(c) NO donators
(d) Prostacyclin therapy
3) Anticoagulation
4) Lung transplantation
Interstitial Lung Disease
I) Introduction
A) Features
1) Non-infectious, non-malignant process of the lower respiratory tract (likely in an immune
compromised host)
2) May or may not have granulomatous features
3) Interstitial inflammation and fibrosis
B) Pathophysiology
1) Decreased compliance
(a) Increased respiratory rate
(b) Increased work of breathing
(c) Spirometry values are decreased in such a way that the ratio between them is preserved
2) Decreased lung volume
3) Diffusion impairment
(a) Decreased surface area for gas exchange
(b) Decreased DLCO

26

4) Impaired gas exchange

(a) Hypoxemia
(b) V/Q mismatch
5) Pulmonary hypertension and cor pulmonale
(a) Obliteration of pulmonary vasculature by a fibrotic process
(b) Hypoxemia reactive vasoconstriction
II) Clinical Features
A) History
1) Dyspnea
2) Cough (nonproductive)
B) Physical exam
1) Basilar, inspiratory crackles
2) Clubbing
3) Skin/joint changes
4) Symptoms of cor pulmonale
C) Imaging
1) Reticular changes (mesh-like, interlacing shadows)
2) Reticulonodular changes (reticular changes with fine nodules)
3) Honeycombing (coarse reticular and cystic changes)
4) Ground glass opacity (vessels are not obscured)
III) Differential diagnosis (DISCO)
A) Drug- and radiation-induced
1) Mitomycin C, methotrexate, amiodarone, etc.
2) Characteristically large, atypical type II pneumocytes
3) Radiation injury is typically confined to well circumscribed areas, creating very straight lines of
demarcated injury on CXR
B) Idiopathic
1) Pathology is called usual interstitial pneumonia
2) CXR shows reticular, interstitial infiltrates with honeycombing
3) Temporal heterogeneity
(a) Dense collagenous fibrosis is often found in close proximity to active inflammation
(b) Foci of rapidly proliferating fibroblasts may be found
4) The only definitive treatment is lung transplant
C) Sarcoid
1) Systemic disorder characterized by T-cell and macrophage activation
(a) Most frequently affects the lungs
2) Characterized by non-caseating granulomas
3) Presents with Lofgrens syndrome
(a) Erythema nodosum
(b) Arthralgias
(c) Uveitis
(d) Stage I CXR (bilateral hilar lymphadenopathy)
4) Sarcoid CXR staging system
(a) Stage 0 = normal
(b) Stage I = bilateral hilar lymphadenopathy (BHL)
(c) Stage II = BHL + infiltrates
(d) Stage III = infiltrates alone
(e) Stage IV = fibrosis
5) Treat with steroids if the disease does not spontaneously resolve
D) Connective tissue disorders

27

1) Scleroderma
2) Rheumatoid arthritis
3) SLE
4) Polymyositis/dermatomyositis
E) Occupational and environmental
1) Inorganic (metals) and organic (allergens) instigators
2) Asbestosis
(a) Pleural plaques on CXT/CT
(b) Ferruginous bodies on microscopy
3) Hypersensitivity pneumonitis
(a) Honeycombing on CT
(b) Loosely formed granulomas on microscopy
Respiratory Complications of Immunodeficiency
I) Introduction
A) The lung and the immunocompromised state
1) Environmental contact occurs via the lung, skin, and GI tract
2) The lung interface is the #1 site of infection
3) Broader differential diagnosis for infiltrates
4) PMH, occupational, and travel histories are especially important
5) Prophylactic antimicrobials are crucial in preventing infection
B) Increased risk of new infection and reactivation of old infection
1) Reactivation is primarily a consequence of T-cell dysfunction
II) Loss of Neutrophil Function (HSCT)
A) Hematopoietic stem cell transplantation (HSCT)
1) Pulmonary complications are observed in up to 60% of patients
(a) Pneumonia is the leading infectious cause of death in such patients
(b) Risk factors for infection
(i) Extended neutropenia
(ii) Medical immunosuppression (e.g. corticosteroids)
B) Aspergillus
1) Opportunistic fungal pathogen that presents as hyphae in infected tissue
2) Normal tissue is defended against infection by functioning neutrophils
3) In cases of severe neutrophil dysfunction, an invasive form of aspergillosis can develop
(a) Observed in 10-15% of HSCT patients
(b) Can spread hematogenously to other solid organs
(c) May cause tracheobronchitis
(d) Treated with a variety of anti-fungal agents and surgical resection (if necessary)
4) Chronic pulmonary aspergillosis may develop in patients with underlying lung disease and mild
immune impairment
(a) Spectrum of overlapping diseases
(b) Cough, weight loss, fatigue, hemoptysis
(c) Cavitation, fibrosis, focal pneumonia, aspergilloma
5) Allergic bronchopulmonary aspergillosis is caused by IgE and IgG reactions against aspergillus
antigens
(a) Seen primarily in patients with asthma
(b) Productive cough with brown mucus/fungus plug
C) Mucormycosis
1) Invasive lung disease similar to aspergillosis

28

2) Strong propensity to progress to invasive sinus disease

D) Candidiasis
1) Uncommon cause of pneumonia and pulmonary infection
2) T-cell deficiency mucosal infection (e.g., thrush)
3) Neutrophil deficiency deep tissue infection (e.g., dermis)
III) Loss of Cell-Mediated Immunity (HIV and AIDS)
A) Pathogenesis
1) HIV binds to lung cells that have CD4+ receptors
(a) TH cells are the most important, though macrophages are also vulnerable
2) Lysis of infected TH cells leads to lymphocytopenia
(a) CD4+ T-cell counts <200 cells/L is the definition of AIDS
(b) Specific opportunistic infections may also define AIDS
3) Lymphocytopenia produces several consequences
(a) Decreased macrophage activation
(b) Impaired cell-mediated immunity
(c) Decreased humoral immunity
B) Principles of HIV infection
1) Must consider HIV infection when presented with any diffuse or poorly responsive pneumonia
2) Risk factors
(a) Unsafe sex with infected partner
(b) IV drug use
(c) Blood transfusions (rare)
3) Highly active antiretroviral therapy (HAART)
(a) Reduces rate of CD4+ T-cell decline
(b) Lowers viral load
(c) Increases efficacy of T-cell immunity
(d) Not curative
C) Pneumocystis jiroveci
1) Considered a fungus (but not a mold like aspergillus)
2) Damages type I pneumocytes
(a) Exudates in alveoli hypoxemia
3) Presents as an atypical pneumonia (pneumocystis pneumonia)
(a) Slow progression over weeks
(b) Non-productive cough, fever, dyspnea
(c) CXR shows diffuse bilateral infiltrates
4) Bronchoalveolar lagave (BAL) samples show foamy alveolar casts
(a) Silver stain or direct fluorescent antibody (DFA) detection of central organisms
5) Treat with trimethoprim + sulfamethoxazole
(a) Add corticosteroids if the patient is hypoxemic
(b) A similar therapy can be used prophylactically in immunocompromised patients
IV) Overlapping Immunosuppressed States (Solid Organ Transplantation)
A) Solid organ transplantation
1) Requires chronic immunosuppression of both neutrophil and cell-mediated lines
B) Nocardiosis
1) Nocardia is a filamentous, gram+, branching rod
2) The majority of cases are observed in immunocompromised hosts
(a) Neutrophils and macrophages typically inhibit growth and prevent spread
(b) Cell-mediated immunity typically facilitates killing
3) Progresses to pneumonia and then disseminates to the CNS and skin
V) General Immunosuppression (Medications)

29

A) Routine community acquired pneumonia and respiratory viruses

1) Immunocompromised individuals will be infected by routine organisms as well as resistant
organisms
2) RSV, influenza, parainfluenza, adenovirus, etc.
B) Mycobacterium tuberculosis
1) Tuberculosis is the leading opportunistic infection in AIDS patients in developing nations
2) It is uncommon in HSCT, but still higher than in the general population
3) There is a greater risk of extrapulmonary disease and adenopathy in the immunosuppressed
4) Treatment is similar to the general population
C) Cytomegalovirus (CMV)
1) Commonly associated with organ transplantation
2) Infection is primarily the result of reactivation in the immunocompromised host
Bronchiectasis
I) Mucociliary Clearance
A) Normal components
1) Viscous fluid of low pH (~6.8)
2) Ciliary beating
(a) Normal cilia possess inner/outer dynein arms, nexin linkers, and a central microtubule pair
3) Barrier function of mucus
4) Tight junctions of epithelial cells
B) Reversible impairments
1) Viral infections
2) Cigarette smoke
II) Bronchiectasis
A) Features
1) Chronic dilation of bronchi or bronchioles with airway wall thickening resulting from airway
inflammation or obstruction
2) Manifests with chronic cough, excess sputum productions, malaise, and recurrent chest infections
3) Many patients have airflow obstruction, indicated by PFTs and flow-volume loops
B) Chest CT is the gold standard for diagnosis
C) Three broad types of bronchiectasis
1) Cystic fibrosis (CF) bronchiectasis
2) Non-CF bronchiectasis
(a) Almost all other causes
3) Traction bronchiectasis
(a) Airways are tethered open as opposed to having a primary disease of the airways themselves
(b) Typically seen in interstitial lung disease
D) Pathogenesis
1) Injury to airway inflammation and/or infection
(a) Impaired mucociliary function
(b) Impaired host defense
(c) Airway obstruction
2) Irreversible dilation of airways
(a) Colonization by pathogenic organisms
(i) Pseudomonas aeruginosa is especially important
(ii) Ongoing inflammation mucosal edema, ulceration, cratering, neovascularization
(iii)Recurrent infectious flares
III) Defects in Mucociliary Clearance

30

A) Primary ciliary dyskinesia

1) Autosomal recessive mutations in normal cilia componentry (e.g., Kartageners syndrome)
2) Presents with chronic sinusitis, bronchiectasis, infertility, and situs inversus (50%)
B) Cystic fibrosis (CF)
1) Autosomal recessive mutations in CFTR gene
(a) Encodes a crucial chloride channel
2) Loss of the fluid layer that normally bathes the cilia allows the overlying mucus layer to sink down
and hinder cilia movement
3) Transport anomalies altered airway secretions infection inflammation tissue damage
4) Median survival is ~37.5 years
5) Diagnosis
(a) Sweat test (gold standard)
(b) Genotyping
(c) Newborn screening
6) Requires multidisciplinary care

31