Quiz Yourself Respiratory
• The FEV1 is reduced when:
– airway obstruction is present as with these diseases:
• Asthma
• Emphysema
• FEV1/FVC ratio is reduced when
– airway obstruction is present. The normal ratio is:
• 70-75
• The FVC is reduced with
– restrictive lung disease
• Pulmonary fibrosis
Lung Volumes in Disease States
What does each of these represent?
What is the alveolar gas equation?
• PAO2 = FIO2 x (PB – PH2O) – PaCO2/RQ
What is the standard version (room air/temp)?
• PAO2 = 150 – PaCO2/RQ
RQ = 0.8 – 1.0
What are the 2 ways to alter V/Q ratio?
Dead space
• Regions of the lung that are ventilated but not perfused
– Anatomic?
• Normal. Like the trachea. About 30% of tidal volume.
– Physiologic?
• Includes anatomic, but in theory, when there are unperfused regions,
as with a pulmonary embolism
Shunt
• Regions of the lung that are perfused but not ventilated!
– V/Q mismatch = incomplete shunt. Responsive to O2 therapy
– Shunt is refractory to O2 therapy
Key pt: regions with a high V/Q ratio cannot compensate for
regions with a low V/Q ratio b/c the high V/Q is normal!
What are the causes of hypoxemia and how
do we distinguish them?
•
•
We distinguish between them using blood gas and A-a gradient
Hypoventilation
–
–
•
•
V/Q mismatch
Shunt
–
–
•
indicated by hypoxemia with a high pCO2, normal A-a.
Increasing frequency of breathing while lowering tidal volume increased
the proportion of dead space ventilation to alveolar ventilation
indicated by hypoxemia with a HUGE A-a difference
Common causes include intracardiac lesions, structural abnormalities of
the pulmonary vasculature, filling of alveolar spaces w/ fluid or
complete alveolar collapse
Low inspired O2 (Low altitude)
What is the diffusing capacity?
–
–
–
–
Measured by DLCO
Impacted by diffusion barrier and aggregate surface area of
alveoli
Measured with CO (but possible errors if the hemoglobin
levels are low)
What does emphysema do?
• reduces the area  reduced DLCO
–
What does fibrosis do?
• increases the thickness  reduced DLCO
What are the volume patterns for the
following diseases?
• Obstructive diseases?
– larger TLCs
• Chronic bronchitis?
–
increased RV, increased FRC
• Emphysema?
–
increased RV, VERY increased TLC
• Restrictive diseases?
–
smaller TLCs
• Fibrosis?
–
all lung volumes decreased
• Obesity?
–
FRC reduced
• Inspiratory muscle weakness?
–
TLC reduced
• Expiratory muscle weakness?
–
RV is elevated
Mechanisms of Hypoxemia
–
–
–
–
Hypoventilation
V/Q Mismatch
Shunt
Low Inspired pO2
• How do we measure lung volumes?
• Helium dilution
–
–
Used to measure absolute FRC
Doesn’t work if there’s lots of obstructed airways where a
• Plethysmography
–
–
The small sealed box
Makes measurements using Boyle’s law
What patterns of impairment
are associated with:
• Obstructive lung disease?
– Diminished rates of expiratory flow (increased FEV1,
decreased FEV1/FVC)
• Restrictive lung disease?
– Diminished lung volumes
– Preserved expiratory flow
• What gives a characteristic scooped appearance in the
expiratory phase of flow-volume loops?
– Airway obstruction like emphysema
• When is obstruction increased during inspiration?
– When it’s an extra-thoracic variable obstruction
• When is obstruction increased during expiration?
– When it’s an intra-thoracic variable obstruction
Normal
What’sAlveoli!
this?
Dilated bronchi
Muco-Purulent Debris in Dilated Bronc
Bronchiectasis
Bronchiectasis
• What is it?
– A chronic dilation of bronchi or bronchioles secondary to
inflammation or obstruction
• Pre-disposing syndromes?
– Cystic fibrosis (CF)
– Primary ciliary dyskinesia syndrome (Kartagener’s s.)
• Radiology?
– Airway dilation which extends to the periphery
• Pathology?
– Permanent dilation of bronchi
– peri-bronchial inflammation and organization (fibrosis)
– Can sometimes see mucopurulent debris in bronchioles
Eosinophil
Charcot-Leyden crystals – eosinophil granule contents
What disease is this?
This is ASTHMA!!!!
Asthma
Curschmann Spirals – mucus
casts
Asthma
• Clinical:
–
–
–
–
Airway hyperresponsiveness
Triggers: antigens, exercise, drugs, infections, stress
Acute, usually reversible diffuse bronchial narrowing
Sxs: Wheezing, dyspnea
• Radiology:
– Alternating atelectasis and overexpansion
• Pathology:
–
–
–
–
–
–
–
–
Edema
smooth muscle thickening
BM thickening
mucous cell hyperplasia
increased submucosal eosinophils
thickened intralumenal mucus
Curschmann spirals – mucus casts
Charcot-Leyden crystals – eosinophil granule contents
Chronic Bronchitis
Increased numbers of mucinous glands in submucosa
• A Clinical Diagnosis!
– Definitional: Productive cough > 3months/year x >
2 years
• Radiology is non-specific
• Pathology:
– Mucous cellular and glandular hyperplasia
– May have submucosal chronic inflammation
– May have respiratory bronchiolitis
• Might look like this:
Centrilobular
Emphysema in COPD
Emphysema
• Clinical:
– Associated with cigarette smoking (component of COPD)
– 1-antitrypsin deficiency, esp PIZZ mutation
• Radiology:
– Increased lucency (dark region)
• Upper>lower lobe suggests centrilobular type
• Lower>upper lobe suggests panlobular type
– Possible increased AP diameter
– Possible flattened diaphragm
• Pathology:
– Dilation of distal airspaces with septal destruction
– Locations:
• Centrilobular: Cigarette smoke
• Panlobular: A1AT deficiency or cigarette smoke
– Increased elastase activity
Bronchiolitis Obliterans/Organizing
Pneumonia (BOOP)
• Clinical:
– Acute onset cough, dyspnea, fever, and malaise
– Multiple associations, e.g. collagen-vascular dz
– Most patients respond to corticosteroids
• Radiology:
– Multiple patchy airspace infiltrates
• Pathology:
– Patchy fibromyxoid plugs in distal bronchioles – the BO
– Fibromyxoid plugs in alveoli, +/- endogenous lipid
pneumonia – the OP
– Think bronchiolar and alveolar airspace fibroblasts
Classification of Asthma
Intrinsic Asthma– No allergic or (personal family)
history
– Usually adult onset
– Often follows severe
respiratory illness
– Symptoms usually perennial
– More refractory to treatment,
become other diseases,
progress to vasculitis
– Eosinophils still impt
Extrinsic Asthma– Strong family history of allergies
– Usually onset at a young age
– Other allergic manifestations in
patients
– History of specific allergic
association triggers (e.g. pollen,
animal dander)
– Correlation with skin and
inhalation responses to specific
antigens
– Type I hypersensitivity rxn
– IgE mast cell and eosinophils
ALLERGIC SHINER: Edema/
What does this demonstrate? What is it?
Discoloration Around the Eye
• What are the important cells in asthma?
– Eosinophils (in sputum)
– B lymphocytes in mediating the asthma – more impt
• What’s the point of the methacholine challenge?
– It demonstrates that there’s something different in the architecture of the
asthmatic’s airways that makes them non-specifically hyperreactive
• What is a key feature of the pathophysiology of asthma that
contributes to death?
– Mucous plugs occluding airways
• What are Creola bodies?
– Agglomerated bronchial epithelial cells, seen in asthma
• What happens when you administer a beta-agonist?
– You initially decrease the O2 saturation via V/Q mismatch.
• What is AM dipping?
– When peak flow is decreased in the morning; associated w/ more severe
asthma
• What is the late phase reaction?
– Delayed reduction in FEV1 due to IgE and influx of inflammatory cells
• What is the cornerstone of asthma therapy?
– Corticosteroids (effective in reducing late phase reaction)
Findings/Diagnosing Asthma?
1.
2.
3.
Spirometry
Increase lung volumes (TLC, FRC, RV)
Decreased peak flow, FVC, FEV1, FEV1/FVC
Auto peak end expiratory pressure (auto-PEEP)-with rate
respiratory rate.
DLCO
Increased - useful in establishing dx
4.
Methacholine challenge
Hyper-responsive
5.
b-agonist
Reversible airflow obstruction when treated; albuterol
6.
Eosinophils
Increased in blood and found in sputum
7.
ABG
Low PO2, low PCO2
Treatment of Asthma
• Avoid asthmatic triggers
• Use bronchodilators
– Sympathomimetics – usually B2-AR specific to increase cAMP.
• albuterol
• Salmeterol is a long acting B2
– Methylxanthines – inhibits PDE  increased cAMP
– Anticholinergics – reserved for COPD
• Use anti-inflammatory drugs
–
–
–
–
Corticosteroids – the cornerstone of therapy
Cromolyn and nedocromil – inhaled prophylactics
Zileuton, Zafirlukast – decreases leukotrienes
Omalizumab – anti IgE antibody
General Strategy for Management of Asthma
• Infrequent attacks?
– Inhaled sympathomimetics (B2)
• More frequent?
– Add an anti-inflammatory as maintenance, usually a
corticosteroid
• Still not good enough?
– Regular use of inhaled B2 agonists
– Add methylxanthines (theophylline)
• Significant attack?
– Systemic steroids
• Status asthmaticus?
– IV corticosteroids
– Aggressive bronchodilators
Classification of asthma?
•
•
•
•
Mild intermittent
Mild persistent – more than 2X/week, but <1QD
Moderate persistent – daily symptoms
Severe persistent – continual symptoms
• Common precipitating stimuli of asthma?
– Allergen exposure – involves histamines, leukotrienes
»
Leukotrienes = why NSAIDS can precipitate asthma!
– Inhaled irritants
– Respiratory tract infections
– Exercise (cool air)
• When is airflow most compromised in asthmatics?
– Expiration
• Why is FRC chronically increased in asthma?
– Dynamic hyperinflation – can’t fully exhale all air
– Persistent activity of inspiratory muscles
• What are the common symptoms of asthma?
–
–
–
–
Cough
Dyspnea
Wheezing – airflow through narrowed airways
Chest tightness
• What is the mechanism of low PO2, low PCO2 in asthmatics?
– V/Q mismatch
• What are the 2 disorders under COPD? Basic defs?
– Chronic bronchitis – diagnosis based on chronic cough and
sputum production
– Emphysema – diagnosis based on destruction of lung
parenchyma and enlargement of air spaces distal to the
terminal bronchiole
• What’s the pathogenesis of alveolar destruction?
– Protease and protease inhibitors are in balance in lung
– Smoking inhibits protease inhibitors
– Neutrophils and macrophages in inflammation release
damaging proteases
• What are the risk factors for COPD?
• Cigarette Smoking (also 2nd hand)
• Hyperresponsive Airways
• Occupational Factors (firemen)
• Alpha1-antitrypsin Deficiency – PIZZ is BAD!
» Normally keeps elastase in check to maintain lung elastin
Mechanisms of Airflow limitation in COPD?
•
•
•
•
•
loss of alveolar attachments
obstruction of the airway due to inflammation
airway-wall fibrosis
airway smooth muscle constriction
luminal obstruction with mucus.
• Loss of elastic recoil in emphysema results in:
– Decreased expiratory flow rates
• Lower driving pressure for expiratory airflow
• Loss of radial traction from supporting alveolar walls
• Functional abnormalities in COPD?
–
–
–
–
–
–
Decreased FVC, FEV1, FEV1/FVC
Increased RV, FRC, TLC
Decreased DLCO in emphysema
Increased Reid index in chronic bronchitis
Hypoxia
Hypercapnia in chronic bronchitis
• Major secondary problem with COPD? Causes?
– Pulmonary HTN  cor pulmonale (more common in chronic
bronchitis patients)
•
•
•
•
Major Cause: Hypoxia  vasoconstriction
Hypercapnia
Polycythemia
Destruction of the pulmonary vascular bed
• What is the protease-antiprotease hypothesis?
–
–
–
–
Alveolar integrity is maintained via a balancing act
Smoke increases the # of PMNs in the lung
PMNs produce elastase  degrades elastin
Smoke oxidants, oxidants from inflammatory cells impair
A1AT anti-elastase activity
– Neutrophil elastase stimulate mucus release
– PMNs and macrophages make matrix metalloproteinases 
shift balance towards degradation
Clinical Distinctions Between Blue Bloater
and Pink Puffer COPD Pathophysiology
Feature
Pink Puffer
Blue Bloater
Pathophys.
Type A
Type B
Disease Association
Emphysema
Chronic Bronchitis
Major Sxs
Dyspnea
Cough & sputum
Appearance
Thin, wasted
Cyantoic, obese
PO2
Decreased
Decreased
PCO2
Normal or decreased Normal or increased
Elastic recoil
Decreased
Normal
DLCO
Decreased
Normal
Hematocrit
Normal
Increased
Cor pulmonale
Infrequent
Common
Treatment of COPD
•
•
•
•
•
•
•
Bronchodilators
Antibiotics
Corticosteroids
Supplemental O2
Exercise rehab
Chest PT, postural drainage
Surgery (last resort)
– Lung transplant
– Lung volume reduction
• Vaccines: pneumovax, flu
• Plasma A1AT if the patient is A1AT deficient
• Mechanical ventialtion
Major Points from Smoking
Cessation Lecture
• Tobacco dependence is chronic and requires repeated
intervention
– If at first you don’t succeed, try, try again!
• ALL pts who smoke should be offered at least ONE
tobacco dependence treatment.
– Pharmacotherapy CAN be helpful
– Nicotine withdrawal can be fairly severe
• Clinicians, hospitals, etc must institute consistent ID,
documentation, and tx of tobacco users
• Brief tobacco dependence tx is VERY effective – all pts
should be offered at least brief tx
• Strong dose-response relation between tobacco
dependence tx and it’s effectiveness
Major Points from Smoking
Cessation Lecture
• The 3 types of counseling/behavioral therapy found to be very
effective and should be used:
– Social Support within treatment
– Social Support outside treatment
– Skills training/problem solving
• Unless contraindicated, use of effective pharmacotherapies for
smoking cessation in all pts trying to quit should be used
• Tobacco dependence treatments are both clinically effective and
cost-effective relative to other medical and disease prevention
interventions
• Setting a quit date is IMPT!
• Set up follow-up dates after quit date to see your pt.
• People tend to gain weight upon quitting…
5 first line pharmacotherapies for smoking
abstinence that WORK
–
–
–
–
–
Bupropion SR
Nicotine gum
Nicotine inhaler
Nicotine nasal spray
Nicotine patch
2 second line pharamcotherapies for smoking:
- clonidine
- nortiptyline
• What is the most successful self-help format to quit
smoking?
– Hotline “quitlines”
• Person-to-Person contact – how much helps?
– Even <3min is (moderately) better than none!
– 10min or more is best
• Asking your pt to quit smoking helps/doesn’t help?
– It DOES!
• What are 3 things associated with unsuccessful attempts
at quitting?
– Not practicing total abstinence
– Drinking alcohol
– Other smokers in da’ house
Peribronchovascular space
Is dilated
Giant cell
Sarcoidosis
What disease?
Sarcoidosis
• Clinical:
o
o
o
Multi-system granulomatous disease
Adults, B>W, F>M
Dyspnea
• Radiology:
o
o
Interstitial infiltrates in bronchovascular distribution (= lympagenic
distribution)
Usually have hilar adenopathy (picked up on routine CXR)
• Pathology:
o
o
Tight, well-formed non-caseating granulomata
Def of granulomata: Focal accumulations of epithelioid histiocytes
Hypersensitivity Pneumonia
Loose
Granulomas
Interstitial expansion
Peri-Bronchiolar
Expansion
Hypersensitivity Pneumonitis
(Extrinsic Allergic Alveolitis)
• Clinical:
o
Organic dusts


o
o
Doesn’t mean carbon based
Means related to organic products
Occupational or environmental exposure
Acute and chronic: dyspnea, cough, fatigue
• Radiology:
o
Bilateral interstitial linear or nodular pattern
• Pathology:
o
Patchy peri-bronchiolar and interstitial chronic inflammation with
loosely formed granulomata
Coal dust macules
Coal-worker’s Pneumoconiosis
Patchy Sub-Pleural Fibrosis
Ferruginous Body
Asbestosis
Fibrotic Nodules
Late Silicosis
UIP: Sub-pleural fibrosis adjacent to normal lung
UIP
Usual Interstitial Pneumonia
(UIP)
• Clinical:
o
o
Syn. with “Idiopathic pulmonary fibrosis (IPF)”
Adults, mean 51 yo; poor response to steroids, 66% mortality
• Radiology:
o
Patchy subpleural infiltrates, DDx asbestos, rheum
• Pathology:
o
o
o
Patchy interstitial inflammation; fibrosis alternating with
normal parenchyma
Temporally heterogeneous = ongoing injury to lung
Morph overlap with rheum dzs, e.g. scleroderma
Fibroblasts in the interstitium
Alveolus
Proliferative phase DAD
Proliferative (Organizing)
Phase Diffuse Alveolar
Damage (DAD)
• Clinical:
o
o
o
> 1-2 wks after identifiable acute lung injury (ex: MVA, septic
shock, kidney stone, inhalation of noxious chemical)
Decreased pulm compliance -> mechanical ventilation
50% mortality
• Radiology:
o
Diffuse, interstitial>alveolar pattern
• Pathology:
o
o
Interstitial + intra-alveolar fibroblastic proliferation
Temporally uniform

o
If it’s temporally heterogeneous = UIP
You HAVE to see interstitial fibroblastic proliferation

If it’s purely intra-alveolar = BOOP
What characterizes Pulmonary
function in Restrictive Lung Disease?
o
Characterized by reduced FVC, normal or high FEV1/FVC ratio
Identify which is interstitial
lung disease, obesity,
Muscle
and inspiratory
& expiratory
muscle weakness.
Obesity
Normal
ILD
Weakness
TLC
TLC
FRC
FRC
RV
TLC
FRC
RV
TLC
FRC
RV
RV
• What’s the differential diagnosis for bilateral diffuse infiltrates that
mimic diffuse parenchymal disease?
o
o
o
Congestive heart failure
Pulmonary infection
Lymphangitic carcinomatosis
• What are known causes of diffuse parenchymal lung disease?
o
o
o
Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis
Inhaled organic antigens  hypersensitivity pneumonitis
Iatrogenic (drugs – amniodirone, radiation)
• What are unknown etiological diffuse parenchymal lung diseases?
o
o
o
o
o
o
IPF/UIP
Sarcoidosis
BOOP
Goodpasture’s
Wegener’s
And many more… (Connective tissue disease associated, Chronic eosinophilic
pneumonia, Lymphangioleiomyomatosis, Pulmonary Langerhan’s cell
histiocytosis, Alveolar proteinosis, Pulmonary vasculitides)
Pathophysiology of
Parenchymal Lung Diseases
• Decreased lung compliance (increased stiffness)
o
o
Reduced FVC, reduced FEV1, normal ratio
Reduced lung volumes TLC, FRC, RV
• Diffusion impairment
o
Destruction of alveolar-capillary interface by inflammation and
fibrosis, reducing the surface area for gas exchange (there is a
reduced DLCO on testing)
• Pulmonary Hypertension
o
o
Hypoxemia
Obliteration of small pulmonary vessels by fibrosis
Clinical Features of
Parenchymal Lung Diseases
• Symptoms
o
o
Dyspnea
Cough (non-productive)
• Signs
o
o
o
Dry crackles or rales (sound like velcro)
Clubbing
Cor pulmonale



JVD
Loud P2, TR murmer
edema
• What’s the major benefits of high resolution CT in diffuse
parenchymal lung diseases?
o
o
Detects sub-radiographic disease
Distinguishes inflammation from fibrosis

Ground glass appearance suggests inflammation
• What is thought to be the pathogenesis of sarcoidosis?
o
A chronic systemic granulomatous idiopathic disease where there’s
an immune response to an exogenous agent in a genetically
predisposed individual
• What key cells are thought to be involved in sarcoidosis?
o
Macrophages

o
Results in increased release of TNF
T cells (specifically CD4)




BAL will reveal CD4>CD8
There may be lymphopenia on peripheral blood smears
MHC II is more impt than MHC I
Results in increased IL-2, INF-gamma, and other cytokines
• What are the presentations/associated diseases of
sarcoidosis?
o
Lofgrens






o
Acute onset
Bilateral hilar lymphadenopathy
Eythema nodosum
Fever
Arthralgias
Associated with a good prognosis
Eye manifestations

Acute or chronic uvetitis




o
Sjorgens – destruction of exocrine glands, specifically partoid and lacrimal
Heerfordts – uvetis + uveoparotid fever, facial palsies, parotid swelling
Keratoconjunctivitis sicca – decreased tear production  conjuctival and
corneal inflammation
Papilledema
Lupus pernio


Associated with chronic sarcoidosis
Usually on face, sometime butt and extremities
• What are common abnormalities/diagnostic test results in
sarcoidosis?
o
o
o
o
o
o
o
o
Hypergammaglobulinemia – T cells non-specifically activate Bcells  lots of Igs
Hypercalcemia, hypercalciuria – increased Ca2+ absorption from
GI tract due to increased vitamin D formation
Lymphopenia – lymphocytes involved in granuloma formation
CD4 > CD8 in BAL – CD4 plays a greater role in granuloma
formation
ACE elevated – due to vascular epithelial cells of granulomas
CXR or HRCT – parenchymal infiltrates, hilar adenopathy,
sublpleural micronodules, upper lobe predominant, honeycombing,
ground glass appearance
Gallium-67 scan – panda sign
Diagnosis is one of exclusion and heavily reliant on biopsy
• How do we treat sarcoidosis?
o
o
o
Systemic corticosteroids
anti-TNF may be best tx (infliximab)
hydroxychloroquine
• What is the staging of sarcoidosis?
o
o
o
o
Stage I – adenopathy
Stage II – parenchymal infiltrates & adenopathy
Stage III – just parenchymal infiltrates
Stave IV – fibrosis, hilar retractionm, cysts, bullae, honeycombing
changes
UIP/IPF
• Pathogenesis?
o
o
Inflammatory process of the walls  fibrosis due to dyregulated response to
damage of alveolar epithelial cells
Factors that are dysregulated  fibrosis?





Cytokines
Chemokines
Matrix metallic proteases and balance with inhibitors
Decreased fibrinolysis
Eicosanoid imbalance: increased luekotrienes, decreased prostaglandins
• Commonly presents in?
o
Older adults, M>F
• Signs and Symptoms?
o
o
o
Exertional dyspnea that increases over time
Non-productive cough
Possible clubbing
• What are common abnormalities/diagnostic test results in
UIP?
o
o
o
o
Velcro-like dry crackles
Peripheral edema or cor pulmonale in advanced stages
Hypoxemia, cyanosis, clubbing
CXR



o
Honeycombing
Diffuse reticulations
NO hilar enlargement
HRCT

Patchy, peripheral subpleural densities associated with small cystic spaces
• Pathology of UIP?
o
o
o
Honeycombing
Fibrosis
Temporal heterogeneity
What Occupational Exposure Materials
can cause inflammatory reactions in
the Airways?
o
Secretory Inflammation




o
Formaldehyde – upper airways
Ammonia – upper airways
Particulates (coal, dust, cotton) – bronchitis
Nitrogen dioxide – bronchiolitis
Hyperreactive Airways


Ozone, cotton dust – non-specific reactivity
TDI – occupational asthma
What Occupational Exposure Materials
can cause Parenchymal responses
Acutely? Chronically?
o Acutely


o
Pulmonary Edema due to toxic reactions
 Chlorine, phosgene
 Acute silicosis
Hypersensitivty Pneumonia
 Organic materials – farmer’s lung (mold spores in hay)
 Inorganic materials
Chronically



Nodular fibrosis
 Coal – macules
 Silica – collagenous lamellated nodules
 Beryllium – Granulomata
Diffuse Fibrosis
 Asbestosis
Cancer
 Asbestos
 Chloromethyl Ether, Coke oven emissions
• What are the causes/common types of pneumonoconiosis?
o
Nodular or diffuse fibrosis…




Silicosis
Asbestosis
Berylliosis
Coal Worker’s
• Important things to do to make a diagnosis in occupational
exposure related respiratory diseases?
o
o
o
o
o
o
o
Take a detailed history
CXR to document pneumonoconoiosis
Blood studies to document specific exposures
Lung tissue analysis
Measure peak flow throughout week
Specific inhalational challenges
Investigation of workplace by industrial hygienist
Respiratory Diseases due to Asbestos
I.
Non-Malignant
A. Pleural Disease
1. Pleural Effusion
2. Diffuse Pleural Thickening
3. Localized Pleural Thickening (Plaques)
II.
B. Diffuse Pulmonary Fibrosis (asbestosis)
Malignant
A. Malignant Mesothelioma
- bad stuff
- cigarette smoking is NOT related
- latency is 30-40 years
B. Bronchogenic Carcinoma
C. Possibly Laryngeal Carcinoma
Asbestosis – a restrictive Lung Dz
• Latency period?
o
20-30days
• Pathologic features?
o
o
o
o
Ferruginous bodies!
Peri-bronchiolar inflammation and fibrosis
May eventually honeycomb
Tendency towards the lower lobes of the lungs
• Clinical Symptoms and CXR?
o
o
o
o
o
Dyspnea on exertion
Dry cough
Late inspiratory crackles in bases
Opacification in bases
Pleural thickening
Occupational Asthma
• Definition?
o
Clinically significant variable airflow obstruction due to specific workplace
agent in lower [ ]s than should cause non-specific irritant response in normals or
asthmatics who are not sensitized
• Risk factors?




Potency of sensitizing material
Level of exposure
Accidental high exposures
Individual patient – atopy and smoking
• Types of presentations:
o
o
o
o
Typical immediate onset – w/in 30 minutes; clears hrs after leaving work. AM
cough & sputum. Responds to bronchodilators
Typical late onset – may not have wheezing; 4-8hrs afterwards with longer
duration. Refractory to bronchodilators
Dual Response
Recurrent Attacks Post Exposure – at night after exposure
• Standard Treatment:
o
Inhaled steroids and bronchodilators
Reactive Airways Dysfunction Syndrome
(RADS)
• Characteristics:
o
o
o
o
o
o
No preceding respiratory symptoms.
Onset of symptoms after single high level exposure to an irritant.
Onset of symptoms is abrupt (without 24 hours) and symptoms
persist for at least 3 months.
Symptoms of variable airway obstruction and/or
hyperresponsiveness.
Non-specific airway hyperresponsiveness present (methacholine
challenge).
Persistent airway inflammation but lack of eosinophils
Pleural Diseases
• What is pleuritic pain?
o
Caused by inflammatory processes that intensify upon breathing
• What’s going on with a tension pneumothorax?
o
o
Air escapes into pleural space  positive pressure
Air can’t escape on exhalation
• How can a tension pneumothorax cause shock?
o
By compromise of venous return
• How can ANY pneumothorax be caused?
o
o
o
o
Trauma  sucking wound
Iatrogenic - Overzealous use of positive pressure ventilation,
central lines, lung biopsies
Abnormal lungs  air trapping (think asthma)
Spontaneous in very tall people
• What kind of pneumothorax?
o
o
o
o
21 y o center for BB team
Has sudden onset of R sided chest pain & mild dyspnea
Patient is uncomfortable but vital signs are WNL
Not Sean May hopefully!


o
o
o
Pneumothorax disease
b/c it’s a popped lung, the pneumothorax is limited and should spontaneously resolve
20 y o severe asthmatic
Intubated & on mechanical ventilation
Suddenly becomes hypotensive & cyanotic

This is a tension pneumothorax – must decompress the patient emergently!
• What will the CXR look like on a pneumothorax?
o
On side of pneumothorax



o
Absent vascular markings
Appearance of a little nub near hilum (atelectic lung)
Diaphragm depressed downwards
On side opposite of pneumothorax

Mediastinum, trachea, other structures shifted over
o
It’s a dark and stormy night… And a patient is brought into your
ER with:





o
o
After you’re told he’s NOT possessed and isn’t just freaked out
after watching that scary movie, you get a CXR.
That CXR shows:



o
Pleuritic chest pain
Dyspnea
Dullness of lungs to percussion
Egophony at upper level
Pleural friction rub
Blunting of the right costaphrenic angle
Elevation or flattening of right hemi diaphragm
And the mediastinum shifted to the left side
Then the scary, menacing attending asks you what does he
have. You, being the superstar that you are, reply:
“Why A Pleural Effusion, DUH!”
• How is normal pleural fluid made?
o
Generated by Starling forces across a capillary bed
• Radiographic signs of pleural effusion include:
o
o
o
o
Blunting of costophrenic angle on upright film
Elevation or flattening of hemi diaphragm on upright film
Diffuse haziness of hemi thorax on supine film
If large, will cause shift of mediastinum to contra-lateral side
• How do you relieve a massive pleural effusion?
o
Thoracentesis



Helpful diagnostically
Helps relieve symptoms
Remove 1500cc or less!


Otherwise, you might suddenly inflate the lung.
Too little surfactant  pulmonary edema
How do you relieve a massive pleural effusion?
• Thoracentesis
o
o
o
Helpful diagnostically
Helps relieve symptoms
Remove 1500cc or less!


Otherwise, you might suddenly inflate the lung.
Too little surfactant  pulmonary edema
• How do you safely do a thoracentesis?
o
Make sure the fluid is freely flowing and not loculated

o
o
Use a lateral decubitus film
Use ultrasound to locate effusion
Be sure to draw close to the upper part of the rib directly below the
needle you’re using, or you might hit an intercostal artery, vein,
nerve
What are Lyte’s Criteria? Why do we use
them in the first place?
• Helps us distinguish between an exudate and a transudate
pleural effusion
o
o
o
o
Ratio of pleural-fluid protein to serum protein > 0.5
Ratio of pleural-fluid LDH > 0.6
Pleural fluid LDH level > 2/3 upper limits of normal for serum
Any one of these characteristics means the fluid is an exudate
• What other studies might you do on fluid from a pleural
effusion
o
cell count & differential, glucose, cytology, Gram stain, AFB stain
& culture, amylase, cholesterol, triglyceride level, pH, adenosine
deaminase
• What if the effusion is borderline according to Lyte?

Look at albumin gradient - If difference btw albumin in serum minus pleural
fluid is > 1.2 than more likely a true transudate
What are the potential causes of a
Transudate?
o
o
o
o
o
CHF – due to increased pulmonary venous pressures, usually
bilateral, usually resolves in 48 hours after diuresis
Nephrosis – low oncotic pressures
Cirrhosis
Atelectasis – increased negative pleural pressure
Ascites – can preferentially form in pleural space, hepatichydrothorax
• What are the potential causes of a massive exudate?





Malignancy
Trauma - hemothorax
Empyema – bacterial infections
Chylothorax – disruption of thoracic duct
Rarely, TB
o
Causes of bloody exudates?






o
Cancer
Pulmonary infarction
Penetrating & nonpenetrating trauma
Central line malplacement
Chondrosarcoma
S/P CABG
Causes of turbid exudates?


Chylothorax
Empyema
• How do you define a hemothorax?
o
o
o
Defined as pleural fluid hematocrit of 50% of blood hematocrit
Will coagulate & may lead to loculation with complications of
fibrothorax & possible empyema
If small, may defibrinate & remain free flowing
So the good doctor said there’s a good
exam question in here…
o
What kind of cell count in an exudate would make
you suspect cancer or Tb?

o
>50% lymphocytes!
Now what additional information on this exudate
could help you decide that it’s probably NOT Tb?

>5% mesothelial cells

Remember, mesothelial cells are normally found in pleural fluid to some degree
since they are the cells that comprise the pleura!
Empyemas
• Why should you distinguish between an empyema and a
parapneumonic effusion?
o
b/c empyemas need to be drained STAT!
• What the hell IS a parapneumonic effusion?


Effusion secondary to a pneumonia
Resolves with antibiotics. Course is usually very benign
• Great, so what about an empyema and why do I care?


Implies active bacterial infection in the pleural space.
Failure to recognize & drain can lead to unresolved sepsis & fibro thorax
• So how do I tell the difference between the two?
o
Well if it’s an empyema, there should be:




o
Gross pus
pH < 7.1
glucose < 40
positive Gram stain or cultures
And if it’s all borderline you need to retap that…um…lung…
Ack! It’s an Empyema! What Do I do?
o
o
o
Well a tube thoracostomy for one
Antibiotics to get those microbes
Thrombolytics if loculated or stops draining despite fluid present
on X-ray
Helps combat if the thing is trying to wall itself off
 Don’t let it hide – go and get it!

o
Decortication if unable to achieve drainage & lung is trapped in
fibrinous peel

o
Yeah – RIP off that clot and scar tissue that I wish you saw…
So what if I don’t and say I did?


Untreated you might get empyema necessitans (where it attempts to drain
through the chest wall b/c you were too lazy to drain it)
Or you might get a bronchopleural fistula causing overwhelming sepsis
Cartilage in excess and disarray
Solitary
Pulmonary
Nodule
STOP!
Hamartoma!
Hamartoma
o
o
It’s BENIGN!!!!
Clin:


o
Rad:


o
Adolescence  adulthood
None in newborns - not congenital
Solitary nodule +/- popcorn calcification
Peripheral > central
Path:


Gross: solitary, lobulated, cartilagenous
Micro: normal tissues in excess/disarray
 If it’s calcified, it’s comforting b/c it tends to be nonmalignant!
What are the Malignant epithelial
neoplasms (Carcinomas)?
o
o
o
o
Squamous cell carcinoma
Adenocarcinoma
Large cell undifferentiated carcinoma
Small cell undifferentiated carcinoma
One of these things is not like the others.
One of these things just doesn’t belong…
Small cell is treated differently and has a much
more severe progression!
Desmosomes
Keratin
Squamous Cell Carcinoma
Normal
Squamous cell carcinoma
• Clin:
o
Smokers association?

o
Prevalence?

o
YES
20-30% of common carcinomas
May secrete PTH-like compound
• Radiology:
o
central > > peripheral
• Path:
o
o
Bronchi > Larynx > Trachea
KEY CHARACTERISTICS?
+/- Desmosomes (intercellular bridges)
+/- Keratin production, e.g. keratin pearls
Primary
Gland formation
Adenocarcinoma
Pleural effusion
Mucin production (red on PASd stain)
Adenocarcinoma
• Clin:
o
o
30-40% of common carcinomas
Smoking association?

Most common carcinoma in non-smokers, but 80% of adenoCAs
occur in smokers
• Rad:
o
peripheral > central
• Path:
o +/- glands
o +/- mucin
o
Bronchiolo-alveolar carcinoma subset
Bronchiolo-alveolar carcinoma
- Note the mucin in the alveoli. Gas exchange is gonna suck in this patient!
Bronchioloalveolar
carcinoma (BAC)
• Subset of?
o
Adenocarcinoma
• Incidence?
o
o
Rising incidence (presently 20-25%)
Associated w/ smoking?

Not associated with cigarette smoking
• Rad:
o
Peripheral, can be multifocal and bilateral
• Path:
o
o
o
Lepidic (butterfly-like) growth pattern
Mucinous or non-mucinous
Unifocal or multifocal
Large cell undifferentiated carcinoma
Large cell undifferentiated
carcinoma
o
o
o
Clin:
 10% of common carcinomas
Rad:
 non-specific
Path:
 H&E: Undifferentiated
 cDNA microarrays: distinct disease
 Basically,
it’s a carcinoma with no distinguishing features
Necrotic
carcinoma
Viable carcinoma
Normal lymphocytes
At diagnosis
Response to therapy
Small Cell Carcinoma
Small cell carcinoma
• Clin:
o
Smokers?

o
o
20 % of common carcinomas
Paraneoplastic Syndromes:

o
o
YES
Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s.
Commonly high stage at presentation
Responsive to chemo/RT, but low 5 yr survival
• Rad:
o
o
Central in >90%
Frequent metastases to LNs and distant sites
• Path:
o
Malignant cytology; high N:C ratio
No nucleoli; punctate salt and pepper nucleoli
High mitotic activity and tumor cell necrosis
o
Think small round blue cells!
o
o
Thin delicate microvilli
Associated w/ ferruginous bodies
Visible
C-P
Angle
Mesothelioma
Loss of C-P Normal
Angle thickness pleura
Thickened pleura
= Pleural effusion or mass
Most Common Metastatic carcinomas in
the Lung?
Breast adenoCA
 GI adenoCA
 Renal adenoCA
 Head/neck squamous cell CA

Lung Cancer - Basics
• What are the 2 most impt risk factors for lung cancer?
o
o
Genetics
Smoking (15% smokers will get lung cancer; 85% CA in smokers)
• What types of molecules are the predominant carcinogens in
cigarettes?
o
Polycyclic hydrocarbons
• What sex is more susceptible to lung CA? Theories why?
o
o
o
WOMEN
Differences in metabolism, CYP450
Hormonal effects in lungs
• What are some mutations that have been implicated?
o
o
o
o
o
o
3p – NSCLC
Ras – adenocarcinoma
Myc – small cell
NSCLC – p53
Rb – small cell
Random breaks in 1, 3, 5, 7, 15, 17
More Lung Cancer Basics
• Most common sites of metastases:
o
o
o
o
Liver
Bone
Brain
Adrenals
• What are the paraneoplastic syndromes associated w/
NSCLC?
o
Clubbing, Hypertrophic orthropathy (adeno), Hypercalcemia
(squamous)
• What are the paraneoplastic syndromes associated w/
SCLC?
o
SIADH (hyponatremia), Cushings, Lambert-Eatons, peripheral
neuropathy, cerebellar degeneration
Diagnostic Tools for Lung CA
• The Basics
o
o
o
o
Detailed hx and physical (esp lungs and supraclavicular nodes)
CXR
Chest CT
Lab tests: CBC, liver fxn, alkaline phosphatase, serum Ca2+
• The Good, Special Stuff
o
For central, endobronchial lesions


Sputum cytology (3+ specimens for 90% yield)
Bronchoscopy

o
Can also do transtracheal needle aspirate of nodes near trachea and
bronchi
For peripheral lesions


Transthoracic needle biopsy (CT guided)
Thoracentesis (effusions)

Malignant (w/ CA cells in exudate) or paramalignant
Staging Lung CA
• SCLC
o

o
What’s Useful?
Limited stage disease vs. extensive stage disease
 Limited stage - confined to hemithorax; within a radiation port
 Extensive - Tumor beyond a radiation port, includes malignant pleural
effusion; what most pts present with
What’s not so useful?

TNM system (which is used in NSCLC)



T – location, size
N – nodes
M – metastases
-
IIIA, IIIB = locally
advanced
IIIB, IV =
advanced, effusion
Stage I – no nodes involved
EARLY
Stage II – nodes on the same side/hilum of CA
Stage III – nodes/mediastinum
Stage IV – another organ involved or a second lesion in the lung
• Tricks to help us stage NSCLC?
o
Intrathoracic



o
Chest CT
FDG PET Scan
Mediastinoscopy
Extrathoracic




Bone scan
CT/MRI of brain
Abdominal CT (liver, adrenals)
Biopsies of extrathoracic lesions
• Treating NSCLC
o
o
o
Early – surgical resection + chemo
Locally Advanced – chemo + surgery or radiation
Advanced – chemo

Can help improve sxs, cost effective, increases 1yr survival
• Treating SCLC
o
o
Limited – chemo + radio
Extensive – chemo, w/ palliative radio as needed
 Adenocarcinoma






Most common NSCLC in US
Smokers and non-smokers
Peripheral (in the lung parenchyma)
May arise in area of previous scarring
More likely to spread to lymph nodes and outside of the chest
Hypotrophic orthopathy or clubbing alone may be present
 Bronchioloalveolar carcinoma





Subtype of adenocarcinoma
More common in women
More common in non-smokers than smokers for poorly defined
reasons
Cough and bronchorrhea (frothy sputum production)
Variable radiographic presentation: solitary nodule, multiple
nodules, infiltrate/consolidation with air-bronchograms
 Squamous cell carcinoma





Exclusively in smokers
Generally arise in proximal airways
May cause obstruction of the airway with distal atelectasis, post obstructive
pneumonia
May cavitate
Hypercalcemia due to PTH like substance (weakness, dehydration, mental
status changes), clubbing
 Small Cell Lung Cancer







15-20% of all lung CAs (decreasing)
The least common lung CA
Exclusively in smokers
Generally originate within bronchial wall
Bulky central tumor with extensive mediastinal lymph node involvement
Rapid grown and early distant metastases
Paraneoplastic syndromes especially SIADH (low sodium or hyponatremia
associated with mental status changes)
Got Your Sound On?
Time to Take a
Study Break!!!
Is it close to midnight?
And that exam is lurking in the morn
Types of inflammatory responses/cells in
infections and likely disease process
 Neutrophils
 Acute pneumonia (usually bacterial)
 Usually in alveoli
 Lymphocytes
 Usually viral or atypical pneumonia
 Usually in interstitium
 Granulomatous inflammation (epitheloid
histiocytes, lymphocytes, giant cells)
 Usually mycobacterial or fungal
pneumonia
Neutrophils filling alveolar space in acute pneumonia
Interstitial lymphocytes in viral pneumonia
Giant Celll
Histiocytes and multinucleated giant cells (granulomatous inflammation)
in mycobacterial pneumonia
Common bacterial pneumonia microbes
• Community acquired
 normal flora, common agents
 Pneumococcal (streptococcus pneumoniae)
 Klebsiella
 Hemophilus, Staph aureus, other strep
• Nosocomial (hospital acquired)
 Pseudomonas aeruginosa

especially in cystic fibrosis patients
 Methicillin resistant staphylococcus aureus (MRSA)
• Types of pneumonia patterns on CXR
 Lobar (entire lobe
 Bronchopneumonia (patchy in more than one lobe
surrounding a bronchus
What is the agent of Pneumococcal pneumonia?
How do you get it? Sxs? Pathology?
• Streptococcus pneumoniae is the prototype of bacterial
pneumonia
 Encapsulated gram + cocci (diplococcus)
 Normal resident of the nasopharynx
 Often preceded by a viral infection  sets you up for
bacterial pneumonia
 Clinical: fever, chills, chest pain, purulent or bloody
sputum, opacified chest X ray
 Pathology


Early: pulmonary edema and proliferation of bacteria, intraalveolar accumulation of neutrophils and erythrocytes (“red
hepatization”)
Later: serum and fibrinous exudates, intra-alveolar organization,
macrophages (“gray hepatization”)
What are the sxs of Legionella pneumonia?
• “Legionnaires’ disease”
 Acute onset of malaise, fever, pneumonia, myalgias,
abdominal pain, diarrhea
• Type of bact? Gram stain? How do you see it?
 Small gram negative bacillus
 Need special stains to visualize
• What does CXR look like?
 Pathology: bronchopneumonia with multiple lobes
involved, alveoli filled with fibrin and inflammation
 X ray is frequently more worrisome than clinical
symptoms would suggest
What patients are susceptible to pneumonias
caused by anaerobic bacteria?
 Anesthetized patients
 Alcoholics
 Seizure disorder
• What are characteristics of anaerobic
pneumonias?
 Normal inhabitants of oral cavity
 Streptococci, fusobacteria, bacteroides
 Often cause necrosis
 Foul smelling sputum
 May develop abscess formation
What are common complications of
bacterial pneumonias?
• Lung abscesses
 Walled off area of infection with destruction of pulmonary
parenchyma  destruction of all normal architecture
 Clinical: fever, cough, foul smelling sputum, mortality 5-10%
• Pyothorax/empyema
 Infection of pleural fluid with purulent material within the pleural
space.
 May become loculated (fibrous walls around the inflammation),
which requires drainage as well as antibiotics to treat.

A clinical problem b/c it doesn’t have normal blood flow for tx
with antibiotics AND it doesn’t drain normally w/ a chest tube
• Bacteremia
 Bacteria within the bloodstream
 May seed distant sites
 Endocarditis, meningitis, pericarditis
What does this
demonstrate?
Center of pulmonary abscess showing acute
inflammation with destruction of
Normal pulmonary architecture (no alveolar walls)
Alcoholics on the right
lung b/c that’s where
aspiration goes!
An abscess.
Who’s likely to get it and
where?
necrotizing granulomatous inflammation
Peripheral focus of granulo
Inflammation (Ghon focus)
Granulomatous inflammation
In hilar lymph node
Beaded look to the bact
Positive AFB
Initial tuberculous infection: Ghon complex
(Ghon focus + involved hilar nodes)
Tuberculosis
• Primary tuberculosis
 Inhalation of aerosolized droplets  settle in periphery of lower lobes
 Ghon complex: Peripheral focus of infection (granuloma, Ghon focus,
often in a lower lobe) and the infected hilar/ mediastinal lymph node
 Pathology: caseous (cheese like) necrotizing granulomatous
inflammation
 90% of primary infections are asymptomatic; 10% progressive primary
Tb (enlarged lesion >6cm, spread to other parts of the lung, children or
immunosuppressed patients)
• Secondary tuberculosis
 Reactivation of primary Tb OR a new infection in previously sensitized pt
 Clinical: fever, fatigue, weight loss, sweats, cough, hemoptysis
 Numerous caseating granulomas most common in the apical and
posterior segments of upper lobes (highest aeration)
 These may heal and calcify, but some may erode into a bronchus,
leading to tuberculosis cavity
 Usually 3-10 cm, often in apex of lung
 Communication with bronchus allows dissemination of organisms
throughout lung
Complications of tuberculosis
• Miliary Tb
 Multiple small (millet seed size) granulomas in many organs
 Results from hematogenous dissemination
 Kidneys, adrenals, bone marrow, spleen, liver lymph nodes are
common sites
• Hemoptysis
 Erosion of inflammatory response/Tb granuloma into a
pulmonary artery
• Bronchopleural fistula
 Erosion of inflammatory response/granuloma into the pleural
space, resulting in Tb empyema
• Unusual complications – you cough up Tb and swallow it, and it’s
happy to colonize somewhere else


Tuberculous laryngitis
Intestinal tuberculosis
Other mycobacterial diseases
• Mycobacterium avium-intracellulare
 Found in soil, water, food
 Causes disease in immunocompromised patients,
particularly HIV+ (HIV Tb)
• Mycobacterium kansasii
 Associated with Hairy cell leukemia
• Mycobacterium bovis
 Infection from ingested milk (the bow Tb)
Histoplasmosis
• Found in:
 in infected dust, bird droppings
• Appearance:
 dimorphic fungus with tiny yeast forms
• Common location:
 Endemic in midwest and southeast US, particularly Mississippi and
Ohio valleys
• Clinical and pathologic findings
 Similar to Tb
 Yeast phagocytosed by macrophages and PMNs
 result in focal infections with parenchyma and hilar lymph nodes
 granulomas and caseating necrosis
 Old granulomas frequently calcify
 Immunosuppressed patients may have disseminated disease involving
lungs, liver, adrenals, intestines
Coccidioidomysis
• Appearance:
 dimorphic fungi with large thick walled sporangia 30-60
microns filled with endospores 1-5 microns
• Geography/location:
 Endemic in southwestern US, particularly San Joaquin
valley.
• Clinical and pathologic findings
 Similar to Tb and histoplasmosis,
 Immunocompromised patients may have release of
endospores into lung causing with fulminant disease with
purulent response
 Meningeal and MSK involvement possible
Cryptococcosis
• Appearance?
 yeast 4-9 microns with mucinous capsule
• Found in?
 pigeon droppings
• Clinical and pathological presentation?
 Clinical disease almost exclusively in immunocompromised
patients
 Lung is the portal of entry
 CNS is the most common symptomatic site (especially
cryptococcal meningitis)
 Organism may be demonstrated in CSF, lung
washings/BAL and biopsy with special stains (India Ink,
mucin stains). Cryptococcus is one of the few fungi with
mucicarmine positive capsule.
Cryptococcus: mucicarmine positive capsule
Cryptococcus on GMS stain showing narrow based budding
Blastomycosis
• Appearance:
 a large dimorphic fungus with broad based budding.
• Geography/location:
 In US in Mississipi and Ohio River valleys and Great
Lakes regions
• Pathology:
 Disease usually confined to lungs, causes mixed
granulomatous and suppurative inflammation
Blastomycosis: Large yeast with broad based budding
Aspergillosis
• Appearance:
 septate hyphae with acute angle branching, found in soil and
decaying plant material
• Diseases/Presentation
 Aspergilloma (Mycetoma, “fungus ball”)


Grows with preexisting cavity, often Tb cavity
Tangled mat of hyphae within cavity, X-ray may
show mass and air within cavity
 Allergic-Bronchopulmonary aspergillosis (ABPA)



Asthmatics develop immunological reaction to
Aspergillus, w/ infiltrates on CXR, eosinophilia of
blood/sputum, wheezing, cough and sputum
production
Treatment with steroids to control immune
response
It’s not the fungus that hurts you, it’s your body’s
response
Aspergilloma
showing
non-invasive
fungus
within granulation
tissue line
Aspergilloma
(fungus
ball) within
pre-existing
cavity
cavity
Aspergillus: septate hyphae with 45 degree branching
Aspergillus within
blood vessel wall
Invasive aspergillus
Mucormycosis (Zygomycosis)
• Caused by inhalation of spores of several fungi
(Mucor, Rhizopus, Absidia) ubiquitous in soil,
food, decaying vegetable material
• Appearance?
 grow as non-septate hyphae
• Common patients?
 patients with underlying illness, particularly diabetics
• Common presentation?
 rhinocerebral (nasal sinuses and brain) and
pulmonary. Causes vascular invasion, septic
infaction, hemorrhage
Mucomycosis
Pneumocystis carinii
• What is it?
 A common pulmonary pathogen causing pneumonia in
immunosuppressed patients, especially HIV
• What do you see?
 Trophozoites and cysts, latter identifiable with GMS
stain, fills alveolar spaces with organisms and
proteinaceous fluid, preventing gas exchange
• Bronchoalveolar lavage useful for diagnosis
• Causes dyspnea and CXR with infiltrates
• Dx by cytology
Pneumocystis on GMS stain: cup shaped organisms within alveolar spaces
Viral pneumonias
• Cytomegalovirus – most common viral infxn
 Interstitial pneumonia in infants and immunocompromised
patients, especially organ transplant patients, now we screen
(donor & recipient)
 Large cell, big nucleus w/ large, single basophilic intranuclear
inclusion
• Measles
 Multinucleated giant cells with nuclear inclusions
• Varicella (chicken pox and herpes zoster) are usually
asymptomatic
 Interstitial mononuclear cell pneumonia, may produce
focal necrosis
 Nuclear eosinophilic viral inclusions, may be
mutlinucleated
• Herpes simplex
 necrotizing tracheobronchitis and diffuse alveolar damage
• Other viruses (especially in children)
 Adenovirus
 Respiratory syncytial virus
Measles pneumonia: multinucleated giant cells with viral inclusions
Cytomegalovirus pneumonia
Viral inclusion
Herpes virus on cytology specimen
Mycoplasm pneumonia: sparse lymphocytic interstitial inflammation
Mycoplasma
• Small free-living prokaryote, common cause of acute selflimited pneumonia and tracheobronchitis,
• milder than usual bacterial pneumonia (“walking
pneumonia”)
• Highly transmissible through airborne droplets
• Cause of 15-20% of pneumonias in developed countries
• Pathology: patchy consolidation, mononuclear
infiltrate, usually of a lower lobe
• Very common but not very bad
• You’ll see something on CXR but not lots of sxs
 Really common at college/in dorms
What are common host defenses to
respiratory infection?
 ANATOMIC



Upper Airway (nose)
Epiglottis/Larynx
Epithelial Tight Junctions
 MECHANICAL (“INNATE”)

Mucociliary and Cough Clearance
 IMMUNE


“Innate” (lysozyme; lactoferrin; “defensins”)
Immune Response



Secretory IgA (nasal/bronchial)
Humoral Antibody
Cellular
 GENERAL


Alveolar Macrophages (AM)
Inflammatory Response (PMNs, etc.)
• What defenses are protecting the proximal airways and
nose?
 Primary Components: cilia, liquid/mucus, submucosal gland
secretions
 Mucociliary clearance – respond to neurohormonal and
mechanical stimuli
 Secretions of the submucosal glands – what’s in this?
Lysozymes
 IgA – neutralizing; secreted as a dimer
 IgG – opsonizing
• What are the defenses in the alveoli/distal airways?

 No cilia or mucus
 Macrophages – they can seek and phagocytose pathogens, as well
as coordinated the cellular response via chemotactic factors and
cytokines
 IgG
• Secondary defense mechanisms thoughout the lung?
 Neutrophils and other inflammatory cells
Lung Defense Failures
• Common:
 viral infection - after influenza, other infxns can occur
 cigarette smoking
 COPD
 patients w/ underlying lung disease
• Severe failures of lung defense include:
 AIDS
 Medications (corticosteroids like prednisone, other
immunosuppressives, chemotherapy
 Malignancies (leukemia, lymphoma) – can lower cell
and antibody mediated immunity
 Endotracheal tubes – HAP
Routes of Infection of Lung
• Aspiration
 Microaspiration of pathogens colonizing the
oropharynx (your upper away)
 Gross aspiration of mouth/GI tract contents into
lungs
• Inhalation
 Ambient droplets/particles entrained (e.g. TB,
fungi)
• Hematogenous
 e.g. Staph. aureus with IVDA, endocarditis, or a
catherter
Typical vs Atypical Pneumonia
Typical Pneumonia
• Rapid onset
• Ill appearing
• High fever, rigors (shaking
chills), chest pain, purulent
sputum
Atypical Pneumonia
• Indolent onset (7-10days)
• Less ill appearing
• Low-grade fever, malaise,
headache, dry cough
• Consolidation, rales on exam
• Leukocytosis (15-20K)
• Rales without consolidation
• Mild/no leukocytosis;
negative cultures
• Airspace filling/lobar
infiltrate on CXR with air
bronchograms
• Meant to describe: S.
pneumo, S. aureus, GN bacilli
like Klebsiella
• Patchy/interstitial infiltrates
on CXR
• Meant to describe:
Mycoplasma, or Chlamydia
NOT HIGHLY PREDICTIVE OF SPECIFIC PATHOGENS!!!
This is the most important test that
needs to be done in diagnosing pneumonia?
• Chest Radiography
 May distinguish pneumonia from other problems (bronchitis,
CHF, TB, PE, cancer)
 Assesses severity/distribution (multilobar) of disease and
identifies complications (pleural effusion, abscess, empyema)
 Many patterns observed



Airspace filling processes (lobar; patchy
“bronchopneumonia”)
Interstitial patterns
Location, cavitation, adenopathy…
CXR will ESTABLIGH THAT YOU HAVE
PNEUMONIA…
But CXR won’t tell you what the
responsible pathogen is
Since CXR and clinical presentation only tells you the
patient has pneumonia, do you even care what the
causative microbe is?
• YES
 The pathogen determines how you treat it (and in my case, how
much I freak out)
• Great, so how do I figure out WHAT the pathogen is
then?
 Sputum Gram’s stain and culture: used but utility debated
due to high false+ and false- rates
 Blood cultures: for hospitalized patients (specific, but not
sensitive); much better.

Strep pneumoniae causes the most + blood cultures
 Ancillary testing for specific organisms




Legionella: Urinary antigen immunoassay
(serotype 1) DFA, selective media
Chlamydia, Mycoplasma: serologies, but these are
relatively unhelpful in the acute setting
TB: AFB smear/culture
Fungus: KOH/culture
So when is this sputum Gram stain & Culture
going to be worth me missing sleep?
• When you’ve got…
 Large numbers of bacteria with a single morphology
observed in setting of many PMN’s and few/no
squamous epithelial cells (i.e. lower airway specimen)
 Obtained before antibiotics
 Detection of a non-colonizer (mycobacteria, endemic
fungi, Legionella, PCP)
 That’s when I go:
Yeeeeeeeearrrrrrhhhhh!!!
(yes I know I’m a dork, but you’re laughing – admit it.
And I have to entertain myself SOMEHOW!)
This is a sputum sample and it tells us?
That it was probably an incompetent
med student who this specimen, b/c
it SUCKS. Look at all the squamous
epithelial cells and where are the
inflammatory cells?!?!?
So after you fix that previous
person’s mistake, you see
this. What are you thinking?
Besides thinking “damn, I’m good
you should be thinking STREP!!!
When Do I give up on the whole idea of a bacterial
pneumonia and consider TB/fungal agents?
• CXR:
 Upper lobe cavitary infiltrate: TB!!
• Clinical course:
 Indolent course x weeks/months
 Non-resolving on treatment
• Exposure history:
 Outdoorsman (Blastomycosis)
 Desert southwest (Coccidioidomycosis)
 TB contacts or from endemic area
The patient asks you to predict how bad the infxn is.
You’ll assess the severity looking at what? And
what’ll make you panic?
Demographics:
 Age >60 years,
 comorbidities (cancer, “organ failures”, immunosuppressed
conditions, CHF)
• Clinical findings:
 altered mental status
 severe vital sign abnormalities
(RR>30; SBP < 90; T>40 or <35; HR >125)
• Lab data:

 WBC >30k or <4k;
 hypoxemia;
 acidosis
• CXR:
 multilobar involvement,
 fulminant progression

or you could just use a magic eight ball…
Pathogens ~ Modifying Risk Factors
• Aerobic GN bacilli
Alcoholism, nursing home, cariopulmonary disease
like Klebsiella
• Anaerobes
Loss of consciousness (alcohol, seizure), swallowing
dysfunction, poor dental hygiene, airway obstruction
• H. influenzae
COPD, smoker
• S. aureus
Nursing home, post-influenza, IVDA, bronchiectasis
• P. aeruginosa
Structural lung disease (bronchiectasis, CF), recent
broad spectrum antibiotics therapy, malnutrition,
chronic steroids
• DRSP
Age > 65; b-lactam therapy within 3 months; exposure
to child in daycare; underlying medical co-morbidities
drug resistant S. pneumoniae
What are your basic Treatment
Groups for Pneumonia?
Outpatient
1.
No underlying. disease or
modifying factors
2.
Underlying comorbidities
or modifying factors
(COPD, CHF,
alcoholism,…)
Inpatient
3.
Inpatients not needing ICU
care
a. No comorbidities
b. Underlying comorbidities
4. Severe pneumonia requiring
ICU care
a. Low risk for
pseudomonas
b. Risk for pseudomonas
How do you treat each group?
Outpatient: No cardiopulmonary
disease or modifying factors
Advanced generation macrolide
(azithromycin, clarithromycin)
OR
Antipneumococcal fluoroquinolone
(levofloxacin, moxifloxacin)
Outpatient: With
Cardiopulmonary
Disease/Modifying Risk Factors
Antipneumococcal fluoroquinolone
OR
2nd/3rd generation cephalosporin +
macrolide
Inpatient: Not needing ICU
IV 3rd generation cephalosporin + macrolide
OR
IV antipneumococcal fluoroquinolone
Inpatients: ICU requiring
IV 3rd generation cephalosporin + macrolide
OR
IV antipneumococcal fluoroquinolone
Consider Vancomycin (MRSA and PRSP)
If there is a Pseudomonas risk, add these:
Anti-pseudomonal B-lactam + cipro
HAP Pathogens and Treatment
• Treatment based upon the local hospital flora

Commonly available along w/ the drug resistances!
• Common pathogens:









P. aeruginosa,
Enterobacter,
E. coli,
Klebsiella,
Proteus,
Serratia,
S. aureus,
Acinetobacter,
anaerobes
• HAP more likely to be polymicrobial
• Resistant GN’s and S. aureus (MRSA) more common,
and may spread rapidly to at risk patients
So in the Immunocompromised Host, what is
reflective of the specific immune deficit?
• Risk for pathogens reflect specific immune
deficit
 Neutropenia:
 bacteria,
 aspergillus,
 candida
 Splenectomy:
 encapsulated organisms
 T-cell number (HIV) or function
(immunosuppressives):
 fungi,
 mycobacteria,
 viruses (CMV, EBV),
 bacteria
HIV lung infections reflect what?
• Risk for infection proportional to CD4 count:
 >500: lower risk (M. tuberculosis, bacterial pneumonia)
 <200: Pneumocystis carinii
 <50: disseminated M. avium complex
• Higher frequency of bacterial pneumonia, esp. S.
pneumoniae and H. influenzae, and tuberculosis
at all CD4 counts
• How do you avoid PCP in HIV+ patients?
 Prophylactic therapy in compliant patients quite
effective
 trimethoprim/sulfa – also used to treat
 Dapsone
 inhaled pentamidine – also used to treat
AIDS and Pneumocystis carinii
• Clinical Presentation
 Dyspnea, dry cough, fever – insidious onset
 Diffuse infiltrates typical (normal in 5%; atypical with
inhaled pentamidine)
 Hypoxemia prominent feature
• Diagnosis
 Visualization (DFA, silver stain) of organisms in lower
resp. secretions (induced sputum; bronchoalveolar
lavage 85-95% sensitive in HIV)
• Treatment:
 Trimethoprim-Sulfamethoxazole (Bactrim)
 IV pentamidine
 Corticosteroids: for pO2 < 70 mmHg or A-a grad >35
mmHg (reduces risk of resp. failure and death)
AIDS and Non-TB mycobacteria
• Primary species are within M. avium complex
• Risk when CD4 count < 50 (prophylaxis with
clarithromycin)
• Primarily cause disseminated disease, rather
than pulmonary disease
 Fever, weight loss, anemia/leukopenia, diarrhea,
hepatitis, adenopathy
 MAC cultured from blood, bone marrow, stool
• Treated with Clarithromycin + ethambutol
AIDS and Fungal Pneumonia
• Cryptococcus neoformans:
 Common cause of meningitis, usually without
pneumonia
 May cause local or diffuse pulmonary disease;
disseminate
• Histoplasmosis, Coccidiodomycosis:
 Usually disseminated disease in HIV
• Invasive Aspergillosis:
 End-stage (CD4 < 50) disease, concomitant
neutropenia (e.g. meds…) are risk factors
AIDS and Non-infectious Lung Diseases
• Kaposi’s sarcoma: infiltrates, nodules, pleural
effusions, adenopathy, and airway lesions all
possible (Gallium scan negative)
 human herpesvirus-8
• Lymphocytic interstitial pneumonitis (LIP)
 especially children with HIV
• Non-specific interstitial pneumonitis (NSIP)
• Pulmonary Hypertension
 Pathology identical to primary pulmonary
hypertension
What is bronchiectasis? 2 modes of
pathogenesis? Its vicious cycle?
“Irreversible dilation of airways caused by inflammatory
destruction of airway walls”
Pathogenesis
 Infection/Inflammation

bacterial pneumonia, tuberculosis, measles,
pertussis
 Airway obstruction
Cystic Fibrosis (CF)
 Primary Ciliary Dyskinesia (PCD; Kartagener’s
Syndrome)
 Hypogammaglobulinemia (total; IgG2/IgG4; IgA)
• Airway
obstruction/Infection
 Airway wall damage/dilation
 Impairment of mucus clearance
 Promotion of Airway Infection

Other Etiologies of Bronchiectasis
 “Traction bronchiectasis” - ILD
 Airway obstruction (e.g. foreign body)
 ABPA (Allergic bronchopulmonary aspergillosis)
 1-antitrypsin deficiency
 COPD
 Rheumatologic diseases (Sjogren’s syndrome, RA)
 Young’s syndrome (bronchiectasis, obstructive
azoospermia, sinusitis; normal sweat Cl- and CFTR
genotype)
• What happens to the bronchial arteries in
bronchiectasis and why?
 Marked hypertrophy of bronchial arteries due to
chronic inflammatory stimuli
Clinical features of bronchiectasis
• Chronic cough
• copious purulent sputum production
 ~10% with “dry bronchiectasis”
• Periodic hemoptysis
 May be massive, as source is hypertrophied bronchial
arteries, which are at system blood pressure
• Abnormal lung sounds and clubbing variably
present
What is suggestive history of bronchiectasis?
How do we diagnose bronchiectasis?
HRCT – procedure of choice to demonstrate presence,
location, and extent of disease
So you have a pt and the HRCT shows
bronchiectasis. Now what?
• Figure out what the cause is!
 CF:

Sweat chloride or CFTR genotyping
 Immunoglobulin deficiency:

IgG/subclasses, IgA
 PCD:

nasal scrape for cilia structure; exhaled NO level
 1-antitrypsin
 ABPA:
immediate aspergillus skin test; IgE
• Treatment?

 Antibiotics aimed at airway flora
 Airway clearance

Chest percussion (manual, devices), exercise
 b-agonists

Reduces reversible airway obstruction and promotes
mucociliary clearance
 Surgery
Cystic Fibrosis
• What are the major defects?
 Production of thick, tenacious secretions from exocrine glands
 Elevated concentrations of Na2+, K+, and Cl- in sweat
• What are the major clinical problems from CF?
 Pancreatic insufficiency
 Recurrent episodes of tracheobronchial infections
 Bronchiectasis
• What is the genetic basis of CF?
 Most common lethal genetic disease in Caucasian population

Affects 1 : 3,300 Caucasian births
 Monogenetic, autosomal recessive
 Affected gene is called “Cystic Fibrosis Transmembrane
Conductance Regulator”, or CFTR.
 >1000 individual CFTR mutations identified, but DF508 mutation
accounts for 2/3 of CF alleles worldwide
What is the Cascade to Lung Disease in CF?
CFTR Gene Mutation
Altered Ion Transport
Abnormal airway surface liquid (volume depletion)
Impaired airway defenses (reduced mucociliary clearance)
Chronic airway infection/inflammation
Progressive bronchiectasis
Sodium is reabsorbed WAY too much from the airways. Water follow
inwards. This leads to the collapse of mucociliary clearance.
How do you diagnose CF?
• 1+ typical phenotypic features and evidence of CFTR malfunction
 CFTR malfxn:
 Sweat Chloride Test – gold standard; > 60 mmol/L
 CFTR Mutation Analysis – genotyping; 2 mutations required
 Nasal Potential Difference (PD) testing – demonstrates ion transport
abnormalities
 Phenotypic features:
 Chronic Sinopulmonary Disease:







GI:






Persistent infection with P. aeruginosa, S. aureus
Chronic cough/sputum
PFTs (obstruction)
Radiographs: bronchiectasis (upper lobe)
Nasal Polyps, sinusitis
Digital Clubbing
Meconium ileus, rectal prolapse, Distal Intestinal Obstruction Syndrome (DIOS)
Pancreatic insufficiency
Malnutrition
Fat soluble vitamin deficiency
Focal biliary cirrhosis
Others:


Salt loss syndromes: acute salt depletion, chronic metabolic alkalosis
Obstructive azoospermia (CBAVD)
How do you get pseudomonas in CF?
 Impaired mucociliary clearance
 Static, hypoxic mucus layer
 Pseudomonas growth in biofilms by altering
metabolism from aerobic  anaerobic
 Intense inflammation with resolution of infection
• What are serious complications of CF?
 Pneumothorax
 Massive hemoptysis due to dilation of bronchial
arteries
 Respiratory insufficiency
 Cor pulmonale
What is the standard maintenance therapy for CF?
• Airway obstruction from thick secretions




Airway clearance
DNase, mucolytics
Hypertonic saline – speeds up clearance of mucus
Bronchodilators
• Infection
 Inhaled and oral antibiotics
• Inflammation
 Ibuprofen
 Corticosteroids
 Azithromycin – also an antibiotic! Shown to slow disease
• Nutritional Support
 High fat/calorie diet
 Pancreatic enzyme supplementation
 Fat soluble vitamin supplementation (A,D,E,K)
• Screening for other complications
 CF-related diabetes
 Liver disease
 Bone disease
Occluded artery
Parenchymal infarct
with hemorrhage
Pulmonary Thromboembolism
Pulmonary Thromboemboli (pulmonary
embolism, PE)
• Clinical:
 Dyspnea, hemoptysis
 Commonly due to lower extremity thrombi
• Radiology:
 Decreased flow, V/Q mismatch  abnormal V/Q
scan
• Pathology:
 Pulmonary arterial thromboemboli
 Survivors may have peripheral wedge-shaped
infarction
Medial and intimal hypertrophy
Plexiform lesion
Pulmonary Artery Hypertension
• Clinical:
 Sporadic Primary PH: Idiopathic; young adults; 5%
 Familial Primary PH: Autosomal dominant; 5%
 Secondary PH: Identifiable cause of increased pulmonary blood
flow and/or increased resistance; 90%
• Radiology:
 Non-specific
• Pathology:




Medial hypertrophy
intimal proliferation
intimal fibrosis
plexiform vascular lesions
Necrotizing
Granulomatous
Vasculitis
Elastica disruption = vascular injury
Hemosiderin-laden macrophages = prior hemorrhage
Wegener’s Granulomatosis
What are the 2 Mechanisms That are Used when
there’s increased blood flow through the lungs?
What’s going on with the
pulmonary vasculature resistance as you inhale?
• Total pulmonary vasculature resistance
increases as you inhale/increase lung volumes
 Alveolar components increase with inspiration
 Extra-alveolar components decrease w/ inspiration
• How do you define pulmonary hypertension?
 Defined as mean pulmonary artery pressure >25 mm
Hg at rest or 30 mm Hg during exercise
• What is the general progression of disease w/
increased pulmonary vasculature resistance?
 Pulmonary vascular obstruction  increased
pulmonary vascular resistance  pulmonary HTN 
increased RV work  cor pulmonale
What is the vicious cycle of
pulmonary HTN?
Pulmonary HTN
Decreased CrossSectional Area
Vascular Changes
Intimal proliferation
Medial hypertrophy
Angiomatoid transformation
Fibrinoid necrosis
What are the Mechanisms of
Pulmonary Hypertension
• Passive:
 increased left atrial pressure, e.g. mitral
stenosis, mitral regurgitation, LV failure
• Hyperkinetic:
 high flow states: VSD, ASD
• Occlusive:
 Chronic PE
• Obliterative:
 emphysema, interstitial lung disease, vasculitis,
sarcoidosis
• Vasoconstrictive:
 hypoxia, scleroderma
What is the basis of
Primary Pulmonary Hypertension
• Potential etiologies






•
•
•
•
•
 PGIS,
endothelin,
Kv-channels,
eNOS,
mutant BMPR2,
ANP
Mean age at diagnosis is 36
More common in females than males
No racial predilection
Familial Disease accounts for ~10% of cases
Disease progresses to cor pulmonale and premature
death if not treated with median survival of 2.5-3
years
Symptoms of PPH
 Progressive exertional dyspnea—virtually 100%








Patient may faint upon exercise
Fatigue
Chest pain—due to right ventricular
Ischemia
Exercise syncope or near syncope
Hemoptysis
Hoarseness
Peripheral edema
• Physical Exam Findings
Jugular venous distention
Accentuated second heart sound (P2)
Right ventricular heave @ left sternal border
Right sided gallops (S3, S4) @ sternal border
Tricuspid regurgitation murmur (systolic) or pulmonic (diastolic)
murmur
 Peripheral edema due to RHF





Therapy of Pulmonary Hypertension
 Anticoagulation– improves survival
 Oxygen – in hypoxemic patients
 Ca2+ channel blockers – may improve exercise
tolerance and hemodynamics in patients (~25%) with
mild-moderate disease
 Prostacyclin—intravenous/subcutaneous
administration improves hemodynamics, exercise
tolerance, and prolongs survival in severe PPH
 Bosentan—endothelin receptor antagonist that
improves exercise tolerance.
 Transplantation – the last resort
What are the Pathophysiological
Consequences of Pulmonary Embolism
• Pulmonary consequences






Increased alveolar deadspace
Pneumoconstriction—described in animals
Hypoxemia—shunt, V/Q mismatch
Hyperventilation
Depletion of alveolar surfactant—takes ~24 hr
Pulmonary infarction
• Hemodynamic consequences
 Decrease in x-section area of pulmonary vascular bed:

50-60% reduction  significant pulmonary
HTN, RHF, hypotension
 Humoral reflex mechanisms—hypoxic vasoconstriction,
mediator release (like 5HT)
Diagnostic Tests for DVT
•
•
•
•
•
Venography
Impedance Plethysmography
Duplex Scanning
Dopper flow velocity
MRI scans
•
Symptoms






•
Tachycardia
Increased P2
Thrombophlebitis – in lower extremeties
S3,S4 gallop
Diaphoresis
Edema
Murmur
Cyanosis
Laboratory Studies




•
•
•
Dyspnea
Pleuritic pain
Apprehension
Cough
Hemoptysis
Syncope
Signs








•
Diagnosis of Acute Pulmonary Embolism
ECG- non-specific, sign of Right heart strain S1Q3 pattern in precordial leads
CXR
Blood Gases
D-Dimers – more useful to r/o
Ventilation Perfusion Scanning – w/ good sxs, it’s fairly reliable
Spiral or helical CT scanning
Pulmonary Angiography
Contraindications to Heparin Therapy
• Absolute:
 Recent (w/in two weeks) hemorrhagic CVA.
 Recent neurosurgery, ocular or spinal surgery
• Relative:
 Recent major surgery
 Major trauma
 Intracranial neoplasm
 Recent gastrointestinal bleeding
 Concurrent guaiac positive stool
 Mild to moderate hemostatic defects
 Severe uncontrolled hypertension >200mm Hg
Systolic or >110mm Hg diastolic
 Hematuria
• In these situations, you would use an IVC!
So you’ve got edema in the distal airways
and alveolar epithelium. What cell helps you deal?
• TYPE II pneumocytes (main cell)
 By increasing Na-K ATPase on basolateral surface, you
can increase influx of Na+ from the airspaces via ENaC
 Water follow Na+
 Na-K ATPase is inhibited by oubain
 ENaC is inhibited by amiloride
 This process is accelerated by beta-agonists
 Can upregulate in at risk infants w/ corticosteroids
to mom and infant  more type II cells  more
surfactant and more efflux
 Dexamethasone also helps increase expression of
ENaC
• How can you measure the efficacy of alveolar
fluid clearance in the lung?
 Inject a mix of regular and radioactive albumin
Fibrin-rich “hyaline membranes”
Alveolar filling pattern
with air bronchograms
Exudative (Acute) Phase Diffuse
Alveolar Damage (DAD)
• Clinical:
 Adult respiratory distress syndrome (ARDS)
 Identifiable lung injury 0-2 wks before
 Acute dyspnea, hypoxemia, decreased
compliance
• Radiology:
 Diffuse alveolar filling pattern
• Pathology:
 Endo- or epithelial injury, Type II cell
hyperplasia
 First 2 wks after injury: edema  fibrin
Respiratory distress syndrome of
newborns
• Clinical:
 Prematurity
 Tachypnea, intercostal muscle retraction,
hypoxemia
• Radiology:
 Diffuse alveolar filling pattern with air
bronchograms
• Pathology:
 Insufficient surfactant production by type II cells
 Atelectasis  hypoxia/acidosis  epith necrosis
 Diffuse intra-alveolar hyaline membrane formation
(exudative DAD)
RBCs filling
alveolar spaces
Alveolar Hemorrhage Syndrome
Causes of
Alveolar Hemorrhage Syndrome
• Goodpasture’s syndrome
• Acute lupus pneumonitis
• Wegener’s granulomatosis
Goodpasture’s syndrome
• Clinical:
 Young adults, M>F
• Radiology:
 Diffuse alveolar pattern
• Pathology:
 Anti-basement membrane IgG antibodies
damage pulmonary and renal basement
membranes
 Linear IgG and C’ deposition by
ImmunoFluorescence and Electron microscopy
 Anti-GBM IgG is detectable in serum
Acute lupus pneumonitis
• Clinical:
 Component of systemic lupus erythematosus (SLE)
 Children & adults, F>M
• Radiology:
 Diffuse alveolar pattern
• Pathology:
 Necrotizing capillaritis due to immune complexes
 Granular IgG/C’ deposition by IF and EM
 ANA or anti-dsDNA Ab detectable in serum
Lipid
Aspiration of cooked fat
Aspiration
• Clinical:
 Children - foreign bodies
 Adults - gastric acid, food
 Lipids, e.g. mineral oil laxatives or nasal
drops (“exogenous lipid pneumonia”)
• Radiology:
 Focal alveolar pattern
 typically RLL
• Pathology:
 Gastric acid  DAD
 Foreign material  foreign body giant cell
reaction with exogenous material
Endogenous lipoid pneumonia
(“post-obstructive”, “golden” pneumonia)
• Clinical:
 Central major airway obstruction
• Radiology:
 Peripheral infiltrates +/- central mass
• Pathology:
 Increased numbers of foamy alveolar macrophages
distal to an airway obstruction, +/- cholesterol clefts,
without foreign material
Foamy
Macrophages
Endogenous (Post-Obstructive) Lipid Pneumonia
Transudate in interstitium and alveolar airspaces
Capillary congestion
Severe Pulmonary Edema
Pulmonary Edema
• Clinical:
 Cardiogenic: LV pump failure, mitral valve
stenosis
• Radiology:
 Incr. vascular markings, reticular +/- nodular
 Think Kerley B lines
• Pathology:
 Venous and capillary congestion
 Incr. free water in the interstitium +/- alveoli
Define ARDS
• Acute Respiratory Distress Syndrome
– A clinical definition
– Acute onset
– Bilateral infiltrates on CXR
– Pulmonary Artery wedge pressure <18 or no evidence of left atrial
hypertension
• PaO2/FIO2 < 300: Acute Lung Injury
• PaO2/FIO2 < 200: ARDS
• Common Causes? Most Common Cause?
Direct Lung Injury
Pneumonia
Aspiration
Pulmonary Contusion
Fat Emboli
Inhalational Injury
Near Drowning
Indirect Lung Injury
Sepsis
Multiple Trauma
Other Shock
Acute Pancreatitis
Multiple Transfusions
Drug Toxicity
Septic Shock
Inflammatory Cytokines
Nitric Oxide from Vasc. Endothelium
Low Systemic Vascular Resistance
High Cardiac Output Hypotension
Wide pulse pressure ex: (90/30)
Decreased urine output
Brisk capillary refill
Decreased mental status
Hyperdynamic
Lactic Acidosis –
b/c all these tissues are underperfused
•
Infection
Continuum and Definitions of
Septic Shock
– Inflammatory response to microorganisms, or
– Invasion of normally sterile tissues
•
Systemic Inflammatory Response Syndrome (SIRS)
– Systemic response to a variety of processes
•
•
•
•
Fever,
tachypnea,
tachycardia,
Leukocytosis
– Be careful; there are some infections that resemble sepsis but AREN’T despite the
overlap with SIRS
– It all comes down to is it multiorgan?!?!
•
Sepsis
– Infection plus
– 2 SIRS criteria
•
Severe Sepsis
– Sepsis
– Organ dysfunction (ex: hypotension, hypoxemia)
•
Septic shock
– Sepsis
– Hypotension despite fluid resuscitation
•
Multiple Organ Dysfunction Syndrome (MODS)
– Altered organ function in an acutely ill patient
– Homeostasis cannot be maintained without intervention
Acute or Exudative Phase of ARDS
Exposure to a Risk Factor
Alveolar Capillary Injury
Epithelial Cell Injury
Leak of Protein Rich Fluid into Interstitium
and Alveolus
Arterial hypoxemia refractory to oxygen = SHUNT!
Bilateral patchy infiltrates
VERY Decreased lung compliance (need PEEP)
Rapid onset respiratory failure
Proliferative or Fibrotic Phase of ARDS
• Fibrosing Alveolitis
– Procollagen III peptide present day 1 or 2
– Histologic changes day 5-7
• Clinical Evidence Day 5-10
–
–
–
–
Persistent hypoxemia
Increased alveolar dead space
Further decrease in compliance
Pulmonary hypertension - Obliteration of pulmonary capillary bed
• Steroids are helpful in this stage (but not in the
acute/exudative phase)
• When ventilating a patient, make sure you don’t overdo it
– You don’t want to injure the healthy parts of the lung
– Use a low tidal volume at a higher frequency (despite the inability
to get rid of CO2)
2 General Classes of
Respiratory Failure
Hypoxemic - inadequate O2 delivery
Hypercapnic - respiratory acidosis (high PCO2)
secondary to failure to adequately ventilate
Hypoxemic Failure
Physiological Causes
A. Decreased PIO2
B. Decreased VA
C. Ventilation/Perfusion [V/Q] Mismatch
D. RL Shunt
E. Diffusion Limitation only problematic during exercise
Physiologic Causes of Hypoxemic Failure
• Decreased PIO2
– As with high altitude
• Decreased VA
– Hypoxia (PAO2) secondary from hypercapnia (PACO2)
• V/Q Mismatch
– Can be corrected by supplemental O2
• RL Shunt
– Refractory to O2 treatment
• Diffusion Limitation
– Only a problem under exercise stress due to
increased CO (common in pulmonary fibrosis)
Physiologic Causes of Hypercapnic Failure
•
Increased VE 2o  VCO2
–
•
Increased VE 2o  VD/VT
–
•
pulmonary embolism, emphysema
Decreased VA
–
•
fever, trauma
Many, many causes
Causes of Decreased Minute Ventilation
1. Respiratory drive
(e.g., narcotic overdose)
2. Nerve conduction
(e.g., cervical cord trauma, Guillain-Barre syndrome)
3. Neuromuscular (e.g., myasthenia gravis, muscle atrophy)
4. Chest wall (e.g., flail chest,
kyphoscoliosis)
5. Lung disease (e.g., asthma, COPD)
6. Upper airway obstruction
Arterial blood gases and diagnosis
pH
pCO2 HCO3-
7.40
40
24
Normal
7.30
55
26
Acute Failure
7.37
55
31
Compensated Failure
7.25
85
36
Acute and Chronic Failure
Clinical signs of
respiratory muscle weakness
1. Tachypnea
2. Decreasing Vital Capacity
3. Decreasing Maximum Inspiratory Force
4. Ineffective cough
Note: Hypercapnea is a late sign of respiratory failure
due to neuromuscular limitations.
Support ventilation prior to Resp. Failure
How do you TREAT Hypercapnic Failure?
A. Diagnose and treat underlying cause
B. Consider respiratory stimulants
1. Naloxone (opioid antagonist)
2. Controlled hypoxemia (in proper clinical settings)
3. Chemicals (rarely effective; xanthines, progesterone)
C. Assist devices
1. Negative pressure - Iron lung, Cuirass ventilator
2. Nasal/Face Mask CPAP - Continuous Positive Airway Pressure
3. Cycled CPAP (BiPAP) - Bilevel Positive Airway Pressure
D. Threshold for tracheal intubation and positive pressure ventilation usually low pH.
E. Mechanical ventilation techniques
1. Breath initiation/Respiratory Rate
2. Tidal volume
3. Patient regulation of VE
-Spontaneous breaths
- Tidal volume
4. PEEP = Positive End Expiratory Pressure
Damage to these parts of the brain are associated
with what types of breathing patterns?
• Forebrain
– Post hyperventilation apnea
– Cheyne Stokes Respiraton:
• crescendo-decrescendo
• Due to problems w/ CNS or HF
• Hypothalamus
– Central reflex hypernea
• Pons
– Apneustic breathing – pause btw inspiration and expiration
– Cluster breathing
– Ataxic breathing
• Medullary
– Ondine’s Curse – no involuntary control of breathing
– Ataxic breathing
What is Sleep Apnea?
•
•
•
Repetitive episodes of diminished air flow associated with oxygen desaturation
or arousal
Patients may have hundreds of events per night
Two types:
– Obstructive
• You try to breath, but the airway is closed
• Relaxation of upper airway muscles
– Central
• There is no stimulus to breath
• Relaxation of lower airway muscles
•
Associated w/:
–
–
–
–
–
–
–
Snoring
Obesity (can still occur in normal body habitus)
Mixed w/ Cheyne-Stokes or hypoventilation
HTN
Tachycardia
Narrow airway, edema, large neck
Risk factors: smoking, alcohol, GERD, brain disease, heart disease, ADHD (any kid
who snores, evaluate!)
– IS a risk factor for: HTN, MI, Stroke, RHF, pulmonary HTN, Diabetes, Motor vehicle
accidents, HA, Depression, Shorter life span by 7-10yrs
Who needs evaluated for OSA ?
• Snoring associated with HTN, obesity, DM, or any
vascular disease.
• Snoring in individuals with unrefreshing sleep,
excessive sleepiness or insomnia.
• All children who snore (American Academy
Pediatric).
OSA Treatment
• Continuous Positive Airway Pressure (CPAP,
BiPAP)
• Surgery – 50-50 chance of success
• Dental Device
• Weight Loss
• Medication
• Avoidance of alcohol
• Sleep on side
Respiratory Failure
Lung Failure
Gas Exchange Failure
Hypoxemia
Ventilation Failure
Hypercapnia
Low Inspired O2
Diffusion Limit
CNS Depression
Shunt
Muscular Fatigue
Poor VA
VQ Mismatch
Mechanical Failure
Causes of Hypercapnic Failure
• Normal Ventilation
– Increased Production of CO2 (fever,
tramua)
• Normal Ventilation with Increased
Deadspace (VQ Mismatch)
– Pulmonary Embolus
– Emphysema
• Decreased Ventilation (lots of causes)
– Breath Holding
– Obesity
– Drugs
What’s the Poor Mans Rule of Thumb for
Acute versus Chronic Respiratory Acidosis?
• Acute Respiratory Acidosis
-HCO3 rise by 1 mEq/L for each 10 mmHg PCO2
• Chronic Respiratory Acidosis
-HCO3 rise by 4 mEq/L for each 10 mmHg PCO2
– The body has had time to renally/metabolically compensate for the
respiratory acidosis by increasing HCO3- amts to counteract the
drop in pH.
What are the causes of dyspnea?
• Abnormal gas exchange or acidosis
– Hypercapnia – sensed in medulla, carotid bodies
– Hypoxemia – sensed in carotid bodies
– Low pH - sensed in medulla, carotid bodies
• Increased neuromuscular stimuli
– Chest wall muscle receptors
– Parenchymal and airway receptors
• Abnormal perception/psychogenic
If given these Sxs in the history, what diseases
should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
If given these diagnostic results,
what diseases should you be thinking about?
What are these diagnostic tests useful for
in making diagnoses?
Congrats!
You’re Done!
Good luck on the exam
&