Professional Documents
Culture Documents
Learning Objectives
1. To list and briefly discuss some of the most important diseases of the
respiratory (pulmonary) system
2. To describe the five major disease categories of the respiratory system
3. To understand the most common presenting symptoms & signs suggestive of
respiratory disease
4. To introduce the etiologic & pathologic factors, clinical features and
treatment approach for select respiratory diseases, including:
Infections
Obstructive Pulmonary Disease
Restrictive Lung Disease
Cystic Fibrosis
Lung Cancer
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Marc Imhotep Cray, M.D.
Baron SJ and Lee CI. Lange Pathology Flash Cards. New York: McGraw-Hill, 2009
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Most important diseases of respiratory
(pulmonary) system:
Collapse of alveoli (atelectasis) and pneumothorax
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Obstructive Pulmonary Diseases (OPDs)
Chronic obstructive pulmonary disease (COPD) is characterized by a
reduction of pulmonary air flow as determined by spirometric function
tests with normal or increased total lung capacity (TLC), decrease forced
vital capacity (FVC) in combination with decreased forced expiratory
volume (FEV)
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Marc Imhotep Cray, M.D.
OPDs (2)
COPD can be caused by a number of different respiratory diseases,
including:
Chronic bronchitis
bronchiolitis
Asthma
cystic fibrosis (CF)
bronchiectasis or
α1-antitrypsin deficiency
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Restrictive lung diseases (RLDs)
In RLDs lungs have a limited potential to expand thus, compliance is
reduced
Although extrapulmonary disorders such as chest abnormalities, intraabdominal
masses, and neuromuscular diseases also can limit lung expansion term RLD is
generally reserved for intrapulmonary parenchymatous diseases
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Vascular Lung Diseases
Most common vascular lung diseases fall into 2 major categories:
1. clotting disorders with secondary vascular occlusion and
2. primary structural diseases of blood vessels
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Pulmonary Infectious Diseases
Infections of lung present with different pathologic patterns and are
classified as:
bacterial pneumonias
atypical and viral pneumonias
parasitic (e.g., Pneumocystis carinii pneumonia)
fungal pneumonitis
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Tumors of Lung and Pleura (2)
Both tumor classification and documentation of its spread (grading and
staging) are important responsibilities of diagnostic pathology and form
basis for determining therapeutic intervention
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Marc Imhotep Cray, M.D.
The Pleura
Pneumothorax
Pleural Effusion
Pleuritis
Tumors of the Pleura
Solitary Fibrous Tumor of Pleura
Malignant Mesothelioma
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Presenting Symptoms
Cough
Acute: viral or bacterial bronchitis, URI, or pneumonia
Chronic: asthma, postnasal drip, bronchitis, GERD
Hemoptysis
Ask patient to estimate amount of blood
Distinguish between epistaxis, hematemesis, and hemoptysis
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Marc Imhotep Cray, M.D.
Presenting Symptoms (2)
Dyspnea
Timing, acuity of onset, exacerbating and alleviating factors,
degree of functional impairment
Acute (pulmonary embolus) vs chronic (COPD)
Exertional or resting, episodic or continuous
Paroxysmal nocturnal dyspnea (PND)
Orthopnea
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Presenting Symptoms (3)
What is dyspnea?
Shortness of breath
What is orthopnea?
Dyspnea occurring when pt. is in supine position as a result of a decrease
in vital capacity caused by abdominal contents exerting force against
diaphragm
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Marc Imhotep Cray, M.D.
Presenting Symptoms (4)
Chest pain
Many causes (cardiac, pulmonary, GI, musculoskeletal, etc.)
Pulmonary causes: pleural disease, pulmonary vascular
disease, musculoskeletal
o lung parenchyma has no pain fibers
Pleuritic chest pain: sharp or stabbing pain on inspiration
that can be positional
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Marc Imhotep Cray, M.D.
Presenting Symptoms (5)
Evaluation of Pain
Use the PQRST mnemonic to improve diagnostic precision
P: provocative and palliative factors
Q: quality
R: region and referral
S: severity
T: timing
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Other important history
Cigarette smoking
Quantified as # of packs smoked/d X # of cumulative years
(60pk year = 1 ppd X 60yrs or 2ppd X 30 yrs.)
Risk of lung disease is directly related to # of pack-years
exposure and inversely to age at onset of smoking
Other environmental exposures, travel
Pneumoconiosis (Silicosis, Coal Worker, Anthracosis)
Asbestosis
Family history (CF, alpha-1 antitrypsin deficiency)
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Physical Exam*
Watch the patient breath
RR, use of accessory muscles, paradoxical abdominal
breathing, ability to speak in full sentences
Shape of patient’s chest cavity
AP diameter suggestive of COPD
Auscultation
Rhonchi, rales, wheezing, rub
Clubbing
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Marc Imhotep Cray, M.D.
Signs of acute respiratory failure
Signs of acute respiratory failure include:
tachypnea (respiratory rate >40/min)
inability to speak because of dyspnea
accessory muscle use with fatigue despite maximal therapy
confusion
restlessness
agitation
lethargy
a rising PCO2 level
extreme hypoxemia
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Respiratory Infections
Upper respiratory infection
Most are viral: common cold, pharyngitis, etc.
Lower respiratory infection
Frequently viral
Bronchitis: cough, wheezing, dyspnea
Pneumonia: cough, fever, rapid respiration, dyspnea
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Case 1
A 68-year-old man presents to the emergency department complaining of a
fever, dyspnea, and a cough productive of green sputum. Physical
examination reveals an ill-appearing man, breathing heavily.
On lung examination, you note bronchial breath sounds and dullness to
percussion over the right lower lung lobe. A chest x-ray demonstrates
circumscribed opacity over the region of his right lower lung lobe. You obtain
sputum and blood cultures and then admit this patient to the hospital for
antibiotic treatment.
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Pneumonia: Overview
Pneumonia is a respiratory disease characterized by inflammation of lung
parenchyma (excluding bronchi) caused by viruses, bacteria, fungi, or
irritants
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Common causes of pneumonia
Neonates Children Adults Adults Elderly
(< 4 Wks.) (4 Wks.–18 Yrs.) (18–40 Yrs.) (40–65 Yrs.)
Group B Viruses (RSV) Mycoplasma S. pneumoniae S. pneumoniae
streptococci Mycoplasma C. pneumoniae H. influenzae Influenza virus
E. coli C. trachomatis S. pneumoniae Anaerobes Anaerobes
(infants–3 yr.) Viruses H. influenzae
C. pneumoniae Mycoplasma Gram-negative
(school-aged rods
children)
S. pneumoniae
Redrawn and modified from: Le T and Bhushan V. First Aid for the USMLE Step 1 2015
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Marc Imhotep Cray, M.D.
Lobar Pneumonia
S. pneumoniae most frequently, also Legionella, Klebsiella
Intra-alveolar exudate consolidation (A) may involve entire lobe (B) or lung
A B
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Bronchopneumonia
S. pneumoniae, S. aureus, H. influenzae, Klebsiella
Acute inflammatory infiltrates (C) from bronchioles into adjacent alveoli
patchy distribution involving ≥ 1 lobe (D)
C D
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Interstitial (atypical) pneumonia
Viruses (influenza, CMV, RSV, adenoviruses), Mycoplasma, Legionella,
Chlamydia
Diffuse patchy inflammation localized to interstitial areas at alveolar walls;
diffuse distribution involving ≥ 1 lobe (E)
Generally follows a more indolent course (“walking” pneumonia)
A B
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Case 2
A 21-year-old woman presents to the university health clinic
complaining of general weakness and a low-grade fever of 3 days’
duration. Upon directed history, you learn that she has had an
occasional cough and dyspnea and that her two roommates have been
suffering from similar symptoms. When a chest x-ray reveals patchy
infiltrates, you prescribe her a course of azithromycin and schedule her
for a follow-up visit to make sure that her symptoms have resolved.
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Lung Abscess
Localized collection of pus within parenchyma (A next slide)
Caused by aspiration of oropharyngeal contents (especially in patients
predisposed to loss of consciousness [e.g., alcoholics, epileptics]) or
bronchial obstruction (e.g., cancer)
Treatment: clindamycin
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Lung Abscess
A B
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Case 3
A 42-year-old HIV-positive man presents to the emergency department
with hemoptysis. He states that he has lost 15 pounds over the last 2
months and has had an intermittent fever, cough, and chills. He has not
been taking any of his HIV medications and his CD4 count is 130. A chest
x-ray reveals a lesion in his apical right lung. He is able to cough up green
mucous coated with blood. You send the sample off for staining and
culture. The sample reveals acid-fast bacilli and you decide to admit this
patient to an isolation room and begin him on a multidrug treatment
regimen while drug susceptibility tests are run.
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Marc Imhotep Cray, M.D.
Pulmonary Tuberculosis
Caused by Mycobacterium tuberculosis
Major global problem; Seen in pts with HIV,
other immunocompromised states,
developing countries, etc.
Contracted by inhalation
Scanning electron micrograph of
Mycobacterium tuberculosis
Diagnosis suggested by:
chronic cough
hemoptysis
weight loss
fevers
night sweats
M. tuberculosis bacterial colonies 38
Marc Imhotep Cray, M.D.
Pulmonary Tuberculosis (2)
Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Stamford, CT: Appleton& Lange, 1998: 523
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Pulmonary Tuberculosis (3)
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Pulmonary TB (4)
Diagnosis: confirmed by CXR, PPD, sputum smears and culture
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Pathophysiology (2)
Loss of elastic recoil
COPD: loss of airway tone and decreased tethering by
surrounding lung
Asthma: bronchoconstriction and mucus plugging allowing
airways to collapse at higher lung volumes and trap excessive
air
Increased ventilation: increased airflow resistance may not
allow lungs to completely empty during expiration
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Marc Imhotep Cray, M.D.
Chronic Obstructive Lung Disease (COPD)
Slowly progressive, irreversible airway obstruction
Again, it is closely linked to smoking
Exacerbations of disease by bacterial/viral infections, heart
failure, medication non-compliance, etc.
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COPD: types
Chronic bronchitis (defined clinically)
persistent cough with sputum production for at least 3
months in 2 or more consecutive years
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Case 4
A 44-year-old man presents to your office complaining of a persistent
cough, which is productive of copious sputum. He admits that he is a
heavy smoker and has suffered from similar coughs for several years.
Physical examination reveals diffuse wheezing and crackles. You
suspect that this patient will have a decreased FEV1/FVC ratio and
strongly suggest that he stop smoking.
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Bronchitis
Chronic bronchitis (“blue bloater”)
Pathology
Hyperplasia of mucus-secreting glands in bronchi Reid index
(thickness of gland layer/total thickness of bronchial wall) >
50%.
Features
Productive cough for > 3 months per year (not necessarily
consecutive) for 2 or more years
Findings: wheezing, crackles, cyanosis (early onset
hypoxemia due to shunting), late-onset dyspnea, CO2
retention (hypercapnia), 2° polycythemia
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Marc Imhotep Cray, M.D.
Case 5
A63-year-old man presents to your office complaining of worsening
shortness of breath over the past year. You know that this patient has
smoked two packs of cigarettes a day for the past 45 years. As you are
talking to the patient, you notice that he is using his accessory
muscles of respiration to breathe, that his chest is barrel shaped and
that he is breathing carefully through pursed lips. Using a spirometer,
you determine that he has a decreased FEV1/FVC ratio and an
increased TLC. You tell the patient that it is imperative that he stop
smoking and prescribe him a tiotropium inhaler.
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Marc Imhotep Cray, M.D.
Emphysema
Emphysema (“pink puffer”)
Pathology
Enlargement of air spaces, dec. recoil, inc. compliance, dec. diffusing
capacity for CO resulting from destruction of alveolar walls (arrow in A )
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015) 50
Marc Imhotep Cray, M.D.
Emphysema (2)
Two types:
Centriacinar—associated with smoking (B, C)
B C
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Emphysema (3)
Panacinar—associated with α 1-protease (α 1-antitrypsin) inhibitor
deficiency
Features
Inc. elastase activity loss of elastic fibers inc. lung compliance
Exhalation through pursed lips to inc. airway pressure and prevent airway
collapse during respiration D
Barrel-shaped chest (D)
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COPD: Hyperinflation
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COPD: flattened diaphragms, lucency
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COPD
Treatment
STOP smoking (if this is cause)
Treat exacerbations of bronchitis with antibiotics
Most meds have not been found to be helpful
Ipratropium bromide MDI (atrovent MDI) is helpful (anti-
cholinergic)
Steroids not usually helpful unless inflammatory component
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Marc Imhotep Cray, M.D.
Case 6
A 25-year-old man presents to the emergency department with
hemoptysis associated with a chronic productive cough. He reports
suffering from chronic sinusitis and has had several bouts of severe
pneumonia that have required hospitalization in the past. Pulmonary
function tests reveal a decreased FEV1/FVC ratio. When CT scan reveals
dilated bronchioles with signet-ring appearance, you decide to check for
situs inversus because his present condition may be associated with a
rare genetic disorder.
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Marc Imhotep Cray, M.D.
Bronchiectasis
Etiology Caused by bronchial obstruction (tumor, foreign body, mucus), chronic
necrotizing infections of bronchi, or cystic fibrosis
Pathology Lung: Dilated airways usually in lower lobes; inflammation within bronchial
walls; fibrosis of bronchial walls in chronic disease
Clinical Manifestations Chronic cough with copious purulent sputum; hemoptysis;
cyanosis; anemia
Complications include lung and brain abscesses or cor pulmonale
Imaging: Dilated bronchioles with signet-ring appearance on CT scan
Lab findings: Decreased FEV1/FVC ratio, decreased Hct
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Asthma
Hypersensitivity of bronchial airways Obstruction of lumen of bronchiole by mucoid
results in symptomatic bronchospasm exudate, goblet cell metaplasia, epithelial basement
Can be triggered by viral URIs, membrane thickening and severe inflammation of
bronchiole in a patient with asthma
allergens, stress
Test with methacholine challenge
Findings: cough, wheezing, tachypnea,
dyspnea, hypoxemia,
inspiratory/expiratory ratio, pulsus
paradoxus, mucus plugging
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015 60
Marc Imhotep Cray, M.D.
Asthma (2)
Pathology:
Bronchial hyperresponsiveness causes reversible bronchoconstriction
Smooth muscle hypertrophy, Curschmann spirals (shed epithelium forms
whorled mucus plugs[A]), and Charcot-Leyden crystals (eosinophilic,
hexagonal, double-pointed, needle-like crystals formed from breakdown of
eosinophils in sputum [B])
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015
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Asthma (3)
Chronic, inflammatory disorder of the airways
3-5% of the population is affected
Imbalance between proinflammatory and inhibitory cytokines
Episodic airway narrowing, increased airway reactivity, and
reversibility
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Asthma (4)
Trigger: extrinsic allergens, intrinsic factors, or no identifiable
cause
Types: extrinsic, intrinsic, exercise induced, ASA(acetyl salicylic
acid) sensitive, occupational, allergic bronchopulmonary
aspergillosis (ABPA)
Precipitants of asthma: postnasal drip, GERD, cold exposure,
gases/fumes, emotional stress, hormones, resp. infections
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Marc Imhotep Cray, M.D.
Asthma (5)
Diagnosis (one or combination):
wheeze, chronic episodic dyspnea, and chronic cough
Sputum production, chest pain or tightness
Testing:
History, CXR (to rule out other causes), pulmonary function
testing (with or without challenge)
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Asthma (6)
Treatment
Education (removal of offending agents)
Peak flow meters
Inhaled corticosteroids (ex. fluticasone)
Long and short acting bronchodilators
oEx. salmeterol, albuterol
Leukotriene inhibitors (ex. montelukast)
Theophylline (limited use today due to potential toxicity)
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Case 8
A 2-year-old girl is brought to the emergency department because of
shortness of breath and a productive cough. Upon questioning her
parents, you discover that this patient has a history of pulmonary
infections and bulky stools that float. Physical examination reveals a
thin girl with a barrel-shaped chest, crackles over both lungs, and
digital clubbing. Later, a sweat test demonstrates high levels of chloride
ions. You realize that this girl will have a severely shortened life span
owing to her condition.
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Cystic Fibrosis
An Obstructive Lung Disease
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Marc Imhotep Cray, M.D.
Cystic Fibrosis (2)
Abnormal chloride channel leads to thick and viscous
secretions in resp, hepatobiliary, GI, and reproductive
tracts
Resp tract: persistent inflammation and infection
causes bronchial wall destruction; mucus plugging of
small airways causing parenchymal destruction
• colonization by S. aureus, H. influenza, P. aeruginosa
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Marc Imhotep Cray, M.D.
Cystic Fibrosis (3)
Testing:
Chloride sweat test
Genetic testing
Median survival
14 years in 1969 to 30 yrs. since 1995
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Marc Imhotep Cray, M.D.
Cystic Fibrosis (4)
Pathology:
Pulmonary: cough, sputum production, clubbing
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Cystic Fibrosis Summary
Mutation: Cystic fibrosis transmembrane conductance
regulator (CFTR) gene on chromosome 7
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http://en.wikipedia.org/wiki/Cystic_fibrosis 73
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CF Treatment
Aggressive airway hygiene
Nutritional support including pancreatic enzyme
replacement
Antibiotics
Bronchodilators
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Case 9
A 49-year-old man presents to your clinic complaining of mild shortness of
breath over the past year. He does not smoke, although he has worked in
a glass-manufacturing factory for over 20 years. A chest x-ray reveals
eggshell calcification of the hilar lymph nodes. You make a diagnosis and
suggest that he have a PPD placed because his condition is associated
with increased susceptibility to tuberculosis.
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Restrictive lung disease (Interstitial
lung disease [ILD])
Many pulmonary disorders are characterized by interstitial
inflammatory infiltrates and have similar clinical and radiologic
presentations
grouped as interstitial, infiltrative or restrictive diseases
may (1) be acute or chronic, (2) be of known or unknown etiology and
(3) vary from minimally symptomatic to severely incapacitating and
lethal interstitial fibrosis
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Restrictive lung disease (2)
Restricted lung expansion causes ↓ lung volumes (↓ FVC and
TLC) PFTs FEV1/FVC ratio > 80%.
Types:
1. Poor breathing mechanics (extrapulmonary, peripheral
hypoventilation):
a. Poor muscular effort polio, myasthenia gravis
b. Poor structural apparatus scoliosis, morbid obesity
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Restrictive lung disease (3)
2. Interstitial lung diseases
(pulmonary, lowered diffusing capacity):
a. Adult respiratory distress syndrome (ARDS)
b. Neonatal respiratory distress syndrome (hyaline membrane disease)
c. Pneumoconioses (coal miner’s silicosis, asbestosis)
d. Sarcoidosis
e. Idiopathic pulmonary fibrosis (repeated cycles of lung injury and
wound healing with ↑ collagen)
f. Goodpasture’s syndrome
g. Wegener’s granulomatosis
h. Eosinophilic granuloma (histiocytosis X)
i. Drug toxicity (bleomycin, busulfan, amiodarone)
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Case 10
A 63-year-old man presents to your office after noticing that his left eyelid is
droopy. Upon further questioning, he admits to some shortness of breath
over the past 2 months, but attributes that to his 40-year-long heavy smoking
habit. Physical examination reveals ptosis and miosis of the left eye and
extremely dry skin of the left face. A chest x-ray demonstrates an irregular
mass in the apex of his left lung. You admit the patient to the hospital for a
biopsy of the mass, but you fear that the prognosis is not good.
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Lung Cancer
Lung cancer is a leading
cause of cancer death
Presentation: cough,
hemoptysis, bronchial
obstruction, wheezing,
pneumonic “coin” lesion on
x-ray film
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Lung Cancer (2)
Risk Factors
Leading cause of death
Cigarette smoking is responsible for >90% of lung cancers
Risk increases with dose and length of exposure to cigarette
smoking
Heavy occupational exposure to asbestos is second most
important cause
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Lung Cancer: Types
Bronchial carcinoid tumors
Small cell cancer (oat cell carcinoma, assoc. with smoking)
Non-small cell cancer
oSquamous cell cancer (assoc. with smoking)
oAdenocarcinoma
oLarge cell
oAnaplastic carcinoma Note:
Oat cell is a neoplasm of neuroendocrine
Metastasis: breast, liver, renal, colon Kulchitsky cells
Non small cell carcinomas (NSCC) are any
Pleural Ca epithelial derived lung cancers that are not
oMesothelioma small cell carcinoma (SCC)
o They are relatively insensitive to
• associated with asbestosis chemotherapy
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Lung Cancer: Types (2)
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Lung Cancer: Clinical Presentation
Symptoms can be quite non-specific
Symptoms may relate to location and size of tumor
Cough, hemoptysis, post-obstructive pneumonia, chest pain,
wheezing, hoarseness
bone metastases: swelling, pain
hepatic metastases: jaundice, hepatomegaly
weight loss, anorexia
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Lung Cancer: Evaluation
History and physical examination
CXR/CT scan
No lab is helpful
Bronchoscopy
VATS (video-assisted thoracic surgery)
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Lung Cancer: Treatment
Options depend on tumor type, size, stage of disease, and
performance status of the pt.
Surgical removal with Stage I, II, IIIA non-small cell cancer (if
operable)
Chemotherapy with radiation for limited stage disease in small
cell cancer
ofrequent metastases to the brain
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Lung Cancer: Survival
15-25% survival 5 years after the diagnosis
Considerable debate about screening for lung cancer
orecent discussion on chest C.T. as screening tool
oCXR is not a sensitive way to screen for cancer
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Further study:
eLearning:
IVMS General and Systems Pathology Cloud Folder
IVMS Respiratory Module Cloud Folder
Textbooks:
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. Philadelphia:
Saunders, 2014
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine,
6th Ed. Baltimore: Lippincott Williams & Wilkins, 2012
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e-Medicine (Medscape) Articles
Obstructive Airway Diseases
Alpha1-Antitrypsin Deficiency
Asthma
Bronchiectasis
Bronchiolitis
Bronchitis
Chronic Bronchitis
Chronic Obstructive Pulmonary Disease
Emphysema
Status Asthmaticus
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