Respiratory Pathology and Pathophysiology-Global Overview

Marc Imhotep Cray, M.D.
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
2
Baron SJ and Lee CI. Lange Pathology Flash Cards. New York: McGraw-Hill, 2009
3
Most important diseases of respiratory
(pulmonary) system:
 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
4
Five Major Pulmonary Disease Categories:
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
5
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)
 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)
6
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
 COPD may lead to progressive and destructive emphysema  cor

pulmonale
 characterized by reduced intrapulmonary blood flow pulmonary
hypertension right-sided heart failure
7
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
 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
8
RLDs (2)
 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
9
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
 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
10
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
 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 the risk of chronic restrictive pulmonary
disease
11
Tumors of the Lung and Pleura
 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
12
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
 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
13
The Pleura
Pneumothorax
Pleural Effusion
Pleuritis
Tumors of the Pleura
 Solitary Fibrous Tumor of Pleura
 Malignant Mesothelioma
14
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
15
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
16
 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
 What is paroxysmal nocturnal dyspnea (PND)?

 Dyspnea occurring several hours after lying down and is often associated
with congestive heart failure It is caused by an increase in venous return
to the heart resulting in mild pulmonary edema
17
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
18
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
19
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)
20
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
*See Pulmonary Physical Examination folder on thumb drive data.
21
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
22
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
23
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.
24
Pneumonia: Overview
 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)
25
Pneumonia: Overview (2)
The four most common bacteria causing sinus and respiratory
infections are:
1. Streptococcus pneumoniae
2. Haemophilus influenzae
3. Staphylococcus aureus
4. Mycoplasma pneumoniae
Three common morphologic patterns of pneumonia are:

1. Lobar pneumonia
2. Bronchopneumonia and
3. Interstitial pneumonia
26
Pneumonias: Classification
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
27
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
Note: Most common pneumonias in childhood are Viral pneumonias

Most commonly implicated viruses are Influenza, parainfluenza,
respiratory syncytial virus, rhinovirus, and adenovirus
28
Common causes of pneumonia (2)
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 S. aureus, Pseudomonas, other enteric gram-negative rods
acquired)
Postviral S. aureus, H. influenzae, S. pneumoniae

Redrawn from: Le T and Bhushan V. First Aid for the USMLE Step 1 2015
29
Lobar Pneumonia
 S. pneumoniae most frequently, also Legionella, Klebsiella
Intra-alveolar exudate consolidation (A) may involve entire lobe (B) or lung
A B
30
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
31
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)
Le T and Bhushan V. First Aid for the USMLE

Step 1 2015 (McGraw-Hill 2015) 32
Interstitial & Lobar Pneumonias Compared
A B
Compare diffuse, patchy bilateral infiltrates of “atypical” interstitial

pneumonia (A) with the localized, dense lesion of lobar pneumonia (B)
33
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.
34
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
 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
35
Lung Abscess
A B
36
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.
37
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
Pulmonary Tuberculosis (2)
Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Stamford, CT: Appleton& Lange, 1998: 523
39
Pulmonary Tuberculosis (3)
40
Pulmonary TB (4)
Diagnosis: confirmed by CXR, PPD, sputum smears and culture
Mycobacterium tuberculosis Ziehl-Neelsen stain
 Treatment: 4 drug therapy

• Rifampin
• Isoniazid Chest X-ray of a person with advanced tuberculosis
• Pyrazinamide http://upload.wikimedia.org/wikipedia/commons/9/9
c/Tuberculosis-x-ray-1.jpg
• Ethambutol
41
Obstructive Lung Disease: General
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
42
Pathophysiology of Obstructive Lung Disease
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
43
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
44
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.
Characterized by dyspnea, sputum production (with chronic

bronchitis)
45
COPD: types
Chronic bronchitis (defined clinically)
 persistent cough with sputum production for at least 3
months in 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
46
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.
47
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
48
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.
49
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
Emphysema (2)
Two types:
Centriacinar—associated with smoking (B, C)
B C
51
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)
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
Le T and Bhushan V. First Aid for the 52
Marc Imhotep Cray, M.D. USMLE Step 1 2015 (McGraw-Hill 2015)
COPD
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)
53
COPD: Hyperinflation
54
COPD: flattened diaphragms, lucency
55
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
56
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.
57
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
 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)
58
Case 7
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.
59
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
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
61
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
62
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
63
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)
64
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)
65
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.
66
Cystic Fibrosis
 An Obstructive Lung Disease
Autosomal recessive genetic

disorder
Affects Pulm, GI and GU systems
Most common lethal genetic

disorder A breathing treatment for cystic fibrosis, using a mask
 1/25 carrier frequency nebulizer and a ThAIRapy Vest
 1/3200 live births affected http://en.wikipedia.org/wiki/File:CFtreatmentvest2.JPG
67
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
68
Cystic Fibrosis (3)
Testing:
 Chloride sweat test
 Genetic testing
Median survival
 14 years in 1969 to  30 yrs. since 1995
69
Cystic Fibrosis (4)
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
70
Cystic Fibrosis Summary
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
71
Cystic Fibrosis Summary (2)
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)
72
http://en.wikipedia.org/wiki/Cystic_fibrosis 73
CF Treatment
 Aggressive airway hygiene
 Nutritional support including pancreatic enzyme
replacement
 Antibiotics
 Bronchodilators
74
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.
75
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
 Restrictive lung diseases are characterized by decreased lung volume

and decreased oxygen diffusing capacity on pulmonary function studies
76
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
77
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)
78
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.
79
Lung Cancer
 Lung cancer is a leading
cause of cancer death
 Presentation: cough,
hemoptysis, bronchial
obstruction, wheezing,
pneumonic “coin” lesion on
x-ray film
Squamous cell carcinoma in the right lower lobe First Aid

for the USMLE Step 1 2008
80
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
81
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
82
Lung Cancer: Types (2)
83
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
84
Lung Cancer: Evaluation
 History and physical examination
 CXR/CT scan
 No lab is helpful
 Bronchoscopy
 VATS (video-assisted thoracic surgery)
85
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
86
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
87
88
Further study:
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
89
e-Medicine (Medscape) Articles
Obstructive Airway Diseases
 Alpha1-Antitrypsin Deficiency
 Asthma
 Bronchiectasis
 Bronchiolitis
 Bronchitis
 Chronic Bronchitis
 Chronic Obstructive Pulmonary Disease
 Emphysema
 Status Asthmaticus
90

Respiratory Pathology and Pathophysiology-Global Overview

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Respiratory Pathology and Pathophysiology-Global Overview

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Marc Imhotep Cray, M.D.

 Circulatory disturbances, such as pulmonary edema and chronic passive

 Infections such as rhinitis, laryngitis, bronchitis, and pneumonia

 Immunologically mediated diseases, such as asthma

 Environmentally induced diseases, such as pneumoconioses, asbestosis,

2. Restrictive Lung Diseases (RLDs)

3. Vascular Lung Diseases

4. Pulmonary Infectious Diseases

5. Tumors of the Lung and Pleura

 COPD follows either increased resistance to airflow (e.g., by luminal

 COPD may lead to progressive and destructive emphysema  cor

 Spirometric tests show a reduced FVC with nml or proportionately

 RLD occurs in acute and chronic forms

 Chronic forms include such pathogenetically different entities as idiopathic

 Later stages and especially chronic forms remit to scarring or progress

 Recurrent superimposed infections further complicate course of RLD

 Clotting disorders may cause occlusion of pulmonary vessels by

 Most bacterial and viral pneumonias initially are acute inflammatory

 They are classified according to their cell of origin (squamous cell

 Their local extension and metastatic spread determine their prognosis

 In addition, lungs are frequent sites of metastases from other locations

 What is paroxysmal nocturnal dyspnea (PND)?

*See Pulmonary Physical Examination folder on thumb drive data.

 General clinical signs and symptoms of pneumonia include:

 Diagnosis is made by several laboratory methods and (or) diagnostic

 Classic laboratory findings associated with bacterial pneumonia are a

Three common morphologic patterns of pneumonia are:

Note: Most common pneumonias in childhood are Viral pneumonias

Immunocompromised S. aureus, enteric gram-negative rods, fungi, viruses, P.

Postviral S. aureus, H. influenzae, S. pneumoniae

Le T and Bhushan V. First Aid for the USMLE

Compare diffuse, patchy bilateral infiltrates of “atypical” interstitial

 Air-fluid levels (B next slide) often seen on CXR

 Due to anaerobes (e.g., Bacteroides, Fusobacterium, Peptostreptococcus)

Mycobacterium tuberculosis Ziehl-Neelsen stain

 Treatment: 4 drug therapy

 Obstructive lung disease (COPD) Obstruction of air flow resulting in air

Characterized by dyspnea, sputum production (with chronic

Emphysema (defined based on pathologic findings)

High-Yield Tip: Alpha 1 -

 Treatment Antibiotics; bronchodilators; surgical resection for localized disease

Autosomal recessive genetic

Affects Pulm, GI and GU systems

Most common lethal genetic

 Upper Resp tract: nasal polyps, sinusitis

 GI: exocrine pancreatic dysfunction, diabetes, cirrhosis,

 GU: azoospermia, decreased fertility rate in women,

Epidemiology: 1 in 3500 live births; whites predominantly;

Mechanism: Impaired resorption of chloride from lumen of

Laboratory studies: Increased concentration of chloride in

 Restrictive lung diseases are characterized by decreased lung volume

Squamous cell carcinoma in the right lower lobe First Aid

Internet Pathology Laboratory for Medical Education

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