Respiratory Pathology and Pathophysiology- Global Overview

Marc Imhotep Cray, M.D.
Learning Objectives
2
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

Marc Imhotep Cray, M.D. 3
Baron SJ and Lee CI. Lange Pathology Flash Cards. New York: McGraw-Hill, 2009

Most important diseases of respiratory
(pulmonary) system:
4
 Collapse of alveoli (atelectasis) and pneumothorax
 Circulatory disturbances, such as pulmonary edema and chronic passive
congestion, and adult respiratory distress syndrome (ARDS)
 Infections such as rhinitis, laryngitis, bronchitis, and pneumonia
 Immunologically mediated diseases, such as asthma
 Environmentally induced diseases, such as pneumoconioses, asbestosis,
and silicosis
 Tumors

Five Major Pulmonary Disease Categories:
5
1. Obstructive Pulmonary Diseases (OPDs)
2. Restrictive Lung Diseases (RLDs)
3. Vascular Lung Diseases
4. Pulmonary Infectious Diseases
5. Tumors of the Lung and Pleura

Obstructive Pulmonary Diseases (OPDs)
6
 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)
 COPD follows either increased resistance to airflow (e.g., by luminal
narrowing of air ducts) or loss of elastic recoil (by passive widening of air
spaces=increase lung complience)

OPDs (2)
7
 COPD can be caused by a number of different respiratory diseases,
including:
 Emphysema
 Chronic bronchitis
 Bronchiolitis
 Asthma
 Cystic fibrosis (CF)
 Bronchiectasis or
 α1-antitrypsin deficiency
 COPD may lead to progressive and destructive emphysema  cor
pulmonale
 characterized by reduced intrapulmonary blood flow pulmonary
hypertension right-sided heart failure

Restrictive lung diseases (RLDs)
8
 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
 Spirometric tests show a reduced FVC with nml or proportionately reduced
FEV
 RLD occurs in acute and chronic forms
 Classic examples of acute RLD are the adult respiratory distress syndrome (ARDS) and
acute hypersensitivity pneumonitis
 Chronic forms include such pathogenetically different entities as idiopathic pulmonary
fibroses (fibrosing alveolitis), chronic interstitial pneumonitis in collagen-vascular
diseases, pneumoconioses, and sarcoidosis

RLDs (2)
9
 Only patients in early stages of acute RLD may recover completely
 Later stages and especially chronic forms remit to scarring or progress
to extensive interstitial pulmonary fibrosis with honeycombing
pulmonary hypertension and development of cor pulmonale
 Recurrent superimposed infections further complicate course of RLD
 Idiopathic pulmonary fibrosis (A) (repeated cycles of lung injury and wound healing
with collagen deposition)
Le T and Bhushan V. First Aid for the
USMLE Step 1 2015 (McGraw-Hill 2015)
A

Marc Imhotep Cray, M.D. 10
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
Obstructive vs. restrictive lung disease

Vascular Lung Diseases
11
 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
 Clotting disorders may cause occlusion of pulmonary vessels by
embolization (DVT to PE) or by in situ thrombosis (e.g., after
contraceptive medication with high estrogen content or after clotting
disorders in pancreatic carcinoma)
 In situ pulmonary thrombosis also may be a consequence of
primary structural diseases of lung vasculature

Pulmonary Infectious Diseases
12
 Infections of lung present with different pathologic patterns and are
classified as:
 bacterial pneumonias
 atypical and viral pneumonias
 Parasitic (e.g., Pneumocystis carinii pneumonia)
o yeast-like fungus originally classified as protozoan, now classified as a fungus
 fungal pneumonitis
 Most bacterial and viral pneumonias initially are acute inflammatory
diseases and, with adequate treatment, may resolve completely
 however, pneumonias caused by intracellular bacteria (e.g., Mycobacterium
tuberculosis), parasites, or fungi run a protracted and chronic course entailing an
immune response and incomplete resolution
o heal with focal or diffuse scarring and risk of chronic restrictive pulmonary
disease

Tumors of the Lung and Pleura
13
 As in other organs, tumors of lung are identified as carcinomas (e.g., of
bronchial epithelium, bronchial glands, or alveolar lining cells) or as
sarcomas (a cancer of connective tissue)
 They are classified according to their cell of origin (squamous cell
carcinoma [SCC], adenocarcinoma [AC], small-cell carcinoma [oat cell
carcinoma]) and to their degree of differentiation
 Their local extension and metastatic spread determine their prognosis

Tumors of Lung and Pleura (2)
14
 Both tumor classification and documentation of its spread (grading and
staging) are important responsibilities of diagnostic pathology and form
basis for determining therapeutic intervention
 In addition, lungs are frequent sites of metastases from other locations
(e.g., breast, pancreas, testes, bone, malignant melanoma of the skin,
and others), which must be distinguished from primary lung tumors

The Pleura
15
Pneumothorax
Pleural Effusion
Pleuritis
Tumors of the Pleura
 Solitary Fibrous Tumor of Pleura
 Malignant Mesothelioma

Presenting Symptoms
16
Cough
 Acute: viral or bacterial bronchitis, URI, TB, drugs or
pneumonia
 Chronic: asthma, postnasal drip, chronic bronchitis, GERD
Hemoptysis
 Ask patient to estimate amount of blood
 Distinguish between epistaxis, hematemesis, and hemoptysis

Presenting Symptoms (2)
17
Dyspnea (difficulty breathing)
 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

18
 What is dyspnea?
 difficulty breathing
 Shortness of breath
 What is orthopnea?
 Dyspnea occurring when pt. is in supine position as a result, for
example, of a decrease in vital capacity caused by abdominal contents
exerting force against diaphragm
 What is paroxysmal nocturnal dyspnea (PND)?
 Dyspnea occurring several hours after lying down and is often
associated with congestive heart failure
o It is caused by an increase in venous return to heart resulting in
mild pulmonary edema

19
Chest pain
 Many causes (cardiac, pulmonary, GI, musculoskeletal, etc.)
 Pulmonary causes: pleural disease, pulmonary vascular
disease, musculoskeletal
olung parenchyma has no pain fibers
 Pleuritic chest pain: sharp or stabbing pain on inspiration
that can be positional
High-Yield Point: If pain is a symptom also determine the following:
– site
– radiation
– character, e.g. ache, pressure, shooting, stabbing, dull
– severity, e.g. ‘Did it interfere with what you were doing?
Does it keep you awake?’ – have you ever had this pain before?
– is the pain associated with nausea, sweating, e.g. angina?

Evaluation of Pain
20
Use the PQRST mnemonic to improve diagnostic precision
 P: provocative and palliative factors
 Q: quality
 R: region and referral
 S: severity
 T: timing

Other important history
21
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 (work history), travel
 Pneumoconiosis (Silicosis, Coal Worker, Anthracosis)
 Asbestosis
Family history (CF, alpha-1 antitrypsin deficiency)

Physical Exam*
22
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
*See Pulmonary Physical Examination folder on thumb drive data.

Signs of acute respiratory failure
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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

Respiratory Infections
24
Upper respiratory infection
 Most are viral: common cold, pharyngitis, rhinitis, sinusitis
etc.
Lower respiratory infection
 Frequently viral
 Bronchitis (or) asthma: cough, wheezing, dyspnea
 Pneumonia: cough, fever, (chills), rapid respiration, dyspnea

Case 1
25
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.

Pneumonia: Overview
26
 Pneumonia is a respiratory disease characterized by inflammation of lung
parenchyma (excluding bronchi) caused by viruses, bacteria, fungi, or
irritants
 General clinical signs and symptoms of pneumonia include:
 Fever, chills, muscle stiffness, pleuritic chest pain, cough, blood-tinged or rusty sputum,
shortness of breath, rapid heart rate, and difficulty breathing
 Diagnosis is made by several laboratory methods and (or) diagnostic
procedures, including:
 Chest x-ray; Gram stain and culture (bacterial); bronchoalveolar lavage (Pneumocystis
carinii pneumonia [PCP]); serodiagnosis (Mycoplasma)
 Classic laboratory findings associated with bacterial pneumonia are a
neutrophilic leukocytosis with an increase in band neutrophils (left shift)

Pneumonia: Overview (2)
27
The four most common bacteria causing sinus and respiratory
infections are:
1. Streptococcus pneumoniae
2. Hemophilus influenzae
3. Staphylococcus aureus
4. Mycoplasma pneumoniae
Three common morphologic patterns of pneumonia are:
1. Lobar pneumonia
2. Bronchopneumonia and
3. Interstitial pneumonia

Pneumonias: Classification
28

Common causes of pneumonia
29
Neonates
(< 4 Wks.)
Children
(4 Wks.–18 Yrs.)
Adults
(18–40 Yrs.)
Adults
(40–65 Yrs.)
Elderly
Group B
streptococci
E. coli
Viruses (RSV)
Mycoplasma
C. trachomatis
(infants–3 yr.)
C. pneumoniae
(school-aged
children)
S. pneumoniae
Mycoplasma
C. pneumoniae
S. pneumoniae
S. pneumoniae
H. influenzae
Anaerobes
Viruses
Mycoplasma
S. pneumoniae
Influenza virus
Anaerobes
H. influenzae
Gram-negative
rods
Redrawn and modified from: Le T and Bhushan V. First Aid for the USMLE Step 1 2015
Note: Most common pneumonias in childhood are Viral pneumonias
Most commonly implicated viruses are Influenza, parainfluenza,
respiratory syncytial virus, rhinovirus, and adenovirus

Common causes of pneumonia (2)
30
Special groups
Alcoholic/IV drug user S. pneumoniae, Klebsiella, S. aureus
Aspiration Anaerobes (e.g., Peptostreptococcus, Fusobacterium,
Prevotella, Bacteroides)
Atypical Mycoplasma, Legionella, Chlamydia
Cystic fibrosis Pseudomonas, S. aureus, S. pneumoniae
Immunocompromised S. aureus, enteric gram-negative rods, fungi, viruses, P.
jirovecii (with HIV)
Nosocomial (hospital
acquired)
S. aureus, Pseudomonas, other enteric gram-negative rods
Postviral S. aureus, H. influenzae, S. pneumoniae
Redrawn from: Le T and Bhushan V. First Aid for the USMLE Step 1 2015

Lobar Pneumonia
31
 S. pneumoniae most frequently, also Legionella, Klebsiella
Intra-alveolar exudate consolidation (A) may involve entire lobe (B) or lung
A B

Bronchopneumonia
32
 S. pneumoniae, S. aureus, H. influenzae, Klebsiella
 Acute inflammatory infiltrates (C) from bronchioles into adjacent alveoli
 patchy distribution involving ≥ 1 lobe (D)
C D

Interstitial (atypical) pneumonia
33
 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)
Le T and Bhushan V. First Aid for the USMLE
Step 1 2015 (McGraw-Hill 2015)

Interstitial & Lobar Pneumonias Compared
34
Compare diffuse, patchy bilateral infiltrates of “atypical” interstitial
pneumonia (A) with the localized, dense lesion of lobar pneumonia (B)
A B

Case 2
35
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.

Lung Abscess
36
 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
 Air-fluid levels (B next slide) often seen on CXR
Fluid levels common in cavities presence suggests cavitation
 Due to anaerobes (e.g., Bacteroides, Fusobacterium, Peptostreptococcus)
or S. aureus

Lung Abscess
37
A B

Case 3
38
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.

Pulmonary Tuberculosis
39
 Caused by Mycobacterium tuberculosis
 Major global problem; Seen in pts with HIV, other
immunocompromised states, developing countries,
etc.
 Contracted by inhalation
Diagnosis suggested by:
 chronic cough
 hemoptysis
 weight loss
 fevers
 night sweats
M. tuberculosis bacterial colonies
Scanning electron micrograph of
Mycobacterium tuberculosis

Pulmonary Tuberculosis (2)
40
Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Stamford, CT: Appleton& Lange, 1998: 523

Pulmonary Tuberculosis (3)
41

Pulmonary TB (4)
42
Diagnosis: confirmed by CXR, PPD, sputum smears and culture
Chest X-ray of a person with advanced tuberculosis
http://upload.wikimedia.org/wikipedia/commons/
9/9c/Tuberculosis-x-ray-1.jpg
Mycobacterium tuberculosis Ziehl-Neelsen stain
 Treatment: 4 drug therapy
• Rifampin
• Isoniazid
• Pyrazinamide
• Ethambutol

Obstructive Lung Disease: General
43
Obstruction of air flow through airways
Major causes:
 asthma
 bronchiectasis,
 emphysema and bronchitis (COPD)
 Obstructive lung disease (COPD) Obstruction of air flow resulting in air
trapping in lungs Airways close prematurely at high lung volumes,
resulting in ↑ RV and ↓ FVC
 PFTs: ↓↓ FEV1, ↓ FVC→ ↓↓ FEV1/FVC ratio (hallmark)
 V/Q mismatch

Pathophysiology of Obstructive Lung Disease
44
Air flow is decreased by: airway narrowing and/or loss of elastic
recoil of the lung
Airway Narrowing
 Airway inflammation
otobacco smoke, recurrent infection, immunologic
dysfunction
 Bronchoconstriction

Pathophysiology (2)
45
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

Chronic Obstructive Lung Disease (COPD)
46
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.
Characterized by dyspnea, sputum production (with chronic
bronchitis)

COPD: types
47
Chronic bronchitis (defined clinically)
 persistent cough with sputum production for at least 3
months over 2 or more consecutive years
Emphysema (defined based on pathologic findings)
 abnormal enlargement of air spaces
 permanently dilated airways distal to terminal bronchioles
with alveolar destruction and bullae formation
 degree of obstruction in patients with COPD correlates
more closely with severity of emphysema

Marc Imhotep Cray, M.D. 48Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. 2014
Schematic representation of
overlap between chronic
obstructive lung diseases:

Case 4
50
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.

Bronchitis
51
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

Case 5
52
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.

Emphysema
53
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 )

Emphysema (2)
54
Two types:
Centriacinar—associated with smoking (B, C)
B C

Emphysema (3)
55
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
 Barrel-shaped chest (D)
D
Le T and Bhushan V. First Aid for the
USMLE Step 1 2015 (McGraw-Hill 2015)
High-Yield Tip: Alpha 1 -
protease inhibitor is capable of
inhibiting several types of
proteases, including neutrophil
elastase, which is implicated in
the genesis of emphysema

COPD
56
Physical Exam
  AP diameter,  RR
Laboratory data;
 Pulmonary function test is sensitive way to make diagnosis
in early stages
 ABG: hypoxia, hypercarbia (advanced)
 CXR: hyperinflation, flattened diaphragms, increased AP
diameter, widened retrosternal air space (with emphysema)

COPD: Hyperinflation
57

COPD: flattened diaphragms, lucency
58

COPD
59
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

Case 6
60
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.

Bronchiectasis
61
 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
 Treatment Antibiotics; bronchodilators; surgical resection for localized disease
High-Yield Note: Kartagener syndrome is caused by a defect in dynein,
leading to immotile cilia. Clinical manifestations include bronchiectasis,
sterility, recurrent sinusitis, and situs inversus (dextrocardia)

Case 7
62
An 8-year-old girl is brought into an urgent-care clinic complaining
of shortness of breath. Her past medical history is significant for
multiple allergies. Upon physical examination, you hear expiratory
wheezes and you observe that the patient is using her accessory
muscles of respiration. You decide to administer an inhaled β2-
adrenergic agonist for relief of her symptoms.

Asthma
63
Obstruction of lumen of bronchiole by mucoid
exudate, goblet cell metaplasia, epithelial basement
membrane thickening and severe inflammation of
bronchiole in a patient with asthma
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Hypersensitivity of bronchial airways
results in symptomatic bronchospasm
 Can be triggered by viral URIs,
allergens, stress
 Test with methacholine challenge
 Findings: cough, wheezing, tachypnea,
dyspnea, hypoxemia,
inspiratory/expiratory ratio, pulsus
paradoxus, mucus plugging

Asthma (2)
64
Pathology:
 Bronchial hyperresponsiveness causes reversible bronchoconstriction
 Smooth muscle hypertrophy, Curschmann spirals (shed epithelium forms
whorled [A] ) , and Charcot-Leyden crystals (eosinophilic, hexagonal,
double-pointed, needle-like crystals formed from breakdown of
eosinophils in sputum) mucus plugging [B]
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015
[A] [B]

Asthma (3)
65
 Chronic, inflammatory disorder of airways
 3-5% of the population is affected
 Imbalance between proinflammatory and inhibitory cytokines
 Episodic airway narrowing, increased airway reactivity, and
reversibility

Asthma (4)
66
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

Asthma (5)
67
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 methacholine challenge)

Asthma (6)
68
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)

Case 8
69
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.

Cystic Fibrosis
70
 An Obstructive Lung Disease
Autosomal recessive genetic
disorder
Affects Pulm, GI and GU systems
Most common lethal genetic
disorder
 1/25 carrier frequency
 1/3200 live births affected
A breathing treatment for cystic fibrosis, using a mask
nebulizer and a ThAIRapy Vest
http://en.wikipedia.org/wiki/File:CFtreatmentvest2.JPG

Cystic Fibrosis (2)
71
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

Cystic Fibrosis (3)
72
Testing:
 Chloride sweat test
 Genetic testing
Median survival
 14 years in 1969 to  30 yrs. since 1995

Cystic Fibrosis (4)
73
Pathology:
 Pulmonary: cough, sputum production, clubbing
 Upper Resp tract: nasal polyps, sinusitis
 GI: exocrine pancreatic dysfunction, diabetes, cirrhosis,
salivary gland inflammation
 GU: azoospermia, decreased fertility rate in women,
nephrolithiasis

Cystic Fibrosis Summary
74
Mutation: Cystic fibrosis transmembrane conductance
regulator (CFTR) gene on chromosome 7
Epidemiology: 1 in 3500 live births; whites predominantly;
uncommon in Asians and African Americans
Mechanism: Impaired resorption of chloride from lumen of
sweat ducts resultant impaired absorption of sodium
impaired secretion of chloride into airways, pancreatic ducts,
and gastrointestinal tract resulting in less secretion of
sodium and water and, therefore, viscid secretions

Cystic Fibrosis Summary (2)
75
Manifestations of cystic fibrosis
 Fibrosis of pancreas
 Recurrent pulmonary infections with Pseudomonas aeruginosa,
Staphylococcus aureus, and Burkholderia cepacia
 Chronic bronchitis, bronchiectasis
 Meconium ileus
 Biliary cirrhosis leading to impaired absorption of the fat soluble
vitamins A, D, E, and K
 Infertility in males secondary to absence of vas deferens
Laboratory studies: Increased concentration of chloride in
sweat (i.e., positive sweat chloride test)

Marc Imhotep Cray, M.D. 76http://en.wikipedia.org/wiki/Cystic_fibrosis

CF Treatment
77
 Aggressive airway hygiene
 Nutritional support including pancreatic enzyme replacement
 Antibiotics
 Bronchodilators

Case 9
78
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.

Restrictive lung disease (Interstitial
lung disease [ILD])
79
 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
 Restrictive lung diseases are characterized by decreased lung volume
and decreased oxygen diffusing capacity on pulmonary function studies

Restrictive lung disease (2)
80
 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

Restrictive lung disease (3)
81
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)

Case 10
82
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.

Lung Cancer
83
Squamous cell carcinoma in the right lower lobe First Aid
for the USMLE Step 1 2008
 Lung cancer is a leading
cause of cancer death
 Presentation: cough,
hemoptysis, bronchial
obstruction, wheezing,
pneumonic “coin” lesion on
x-ray film

Lung Cancer (2)
84
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

Lung Cancer: Types
85
 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
 Metastasis: breast, liver, renal, colon
 Pleural Ca
oMesothelioma
• associated with asbestosis
Note:
 Oat cell is a neoplasm of neuroendocrine
Kulchitsky cells
 Non small cell carcinomas (NSCC) are any
epithelial derived lung cancers that are not
small cell carcinoma (SCC)
o They are relatively insensitive to
chemotherapy

Lung Cancer: Types (2)
86
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015

Lung Cancer: Clinical Presentation
87
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

Lung Cancer: Evaluation
88
 History and physical examination
 CXR/CT scan
 No lab is helpful
 Bronchoscopy
 VATS (video-assisted thoracic surgery)

Lung Cancer: Treatment
89
 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

Lung Cancer: Survival
90
 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

Further study:
92
eLearning:
IVMS General and Systems Pathology Cloud Folder
IVMS Respiratory Module Cloud Folder
Internet Pathology Laboratory for Medical Education
Pulmonary Pathology
Each section consists of a series of images demonstrating gross and microscopic pathologic
findings for a variety of disease processes. A short description accompanies each image.
http://library.med.utah.edu/WebPath/webpath.html#MENU
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

e-Medicine (Medscape) Articles
93
Obstructive Airway Diseases
 Alpha1-Antitrypsin Deficiency
 Asthma
 Bronchiectasis
 Bronchiolitis
 Bronchitis
 Chronic Bronchitis
 Chronic Obstructive Pulmonary Disease
 Emphysema
 Status Asthmaticus

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