Chapter 9: Respiratory tract pathology

Question 1

Rhinitis

Answer 1

A. Inflammation of the nasal mucosa; rhinovirus is the most common cause.

Br. Presents with sneezing, congestion, and runny nose (common cold)

C. Allergic rhinitis is a subtype of rhinitis due to a type I hypersensitivity reaction (e.g., to pollen)

1. characterized by an inflammatory infiltrate with eosinophils
2. associated with asthma and eczema.

Question 2

Nasal Polyp

Answer 2

A. Protrusion of edematous, inflamed nasal mucosa

B. Usually secondary to repeated bouts of rhinitis; also occurs in cystic fibrosis and aspirin-intolerant asthma.
1. aspirin-intolerant asthma is characterized by the triad of asthma, aspirin-induced bronchospasms, and nasal polyps; seen in 10% of asthmatic adults

Question 3

Angiofibroma

Answer 3

A. benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue; classically seen in adolescent males

B. Presents with profuse epistaxis

Question 4

Nasopharyngeal carcinoma

Answer 4

A. malignant tumor of nasopharyngeal epithelium

B. associated with EBV; classically seen in african children and Chinese adults

C. Biopsy usually reveals pleomorphic-keratin-positive epithelial cells (poorly differentiated squamous cell carcinoma) in a background of lymphocytes.

D. Often presents with involvement of cervical lymph nodes.

Question 5

Acute epiglottitis

Answer 5

A. inflammation of the epiglottis; H. influenza type b is the most common cause, especially in nonimmunized children

B. Presents with high fever, sore throat, drooling with dysphagia, muffled voice, and instpiratory stridor; risk of airway obstruction.

Question 6

Laryngotracheobronchitis

Answer 6

= Croup

A. inflammation of the upper airway; parainfluenza virus is the most common cause.

B. presents with a hoarse, “barking” cough and inspiratory stridor

Question 7

Vocal cord nodule

Answer 7

= Singer’s nodule

A. Nodule that arises on the true vocal cord

B. Due to excessive use of vocal cords; usually bilateral.
1. Composed of degenerative (myxoid) connective tissue

C. Presets with hoarseness; resolves with resting of voice

Question 8

Laryngeal papilloma

Answer 8

A. Benign papillary tumor of the vocal cord

B. Due to HPV 6 and 11; papillomas are usually single in adults and multiple in children

C. presents with hoarseness

Question 9

Laryngeal carcinoma

Answer 9

A. squamous cell carcinoma usually arising from the epithelial lining of the vocal cord

B. Risk factors are alcohol and tobacco; can rarely arise from a laryngeal papilloma

C. Presents with hoarseness; other signs include cough and striodor

Question 10

Pneumonia

Answer 10

A. Infection of the lung parenchyma

B. occurs when normal defenses are impaired (e.g. impaired cough relflex, damage to mucociliary escalator, or mucus plugging)

C. Clinical features include fever and chills, productive cough with yellow-green (pus) or rusty (bloody) sputum, tachympnea with pleuritic chest pain, decreased breath sounds, dullness to percussion, and elevated WBC count

D. Diagnosis is made by chest x-ray; sputum gram stain and culture, and blood cultures.

E. Three patterns are classically seen on chest x-ray: lobar pneumonia, bronchopneumonia (patchy) and interstitial pneumonia.

Question 11

Lobar pneumonia

Answer 11

A. Characterized by consolidation of an entire lobe of the lung

B. Usually bacterial; most common causes are Strep pneumo and kleb pneumoniae (currant jelly)

C. Classic gross phases of lobar pneumonia

1. Congestion– due to congested vessels and edema
2. Red hepatization– due to exudate, neutrophils, and hemorrahge filling the alveolar air spaces, giving the normally spongy lung a csolid consistency
3. Gray hepatization– due to degradation of red cells within the exudate
4. Resolution

Question 12

Bronchopneumonia

Answer 12

A. Characterized by scattered patchy consolidation centered around bronchioles; often multifocal and bilateral
B. Caused by a variety of bacterial organisms.

Question 13

Interstitial pneumonia

Answer 13

= atypical (usually a virus)

A. Characterized by diffuse iterstitial infiltrates

B. Presents with relatively mild upper respiratory symptoms (minimal sputum and low fever); ‘atypical” presentation

C. Caused by bacteria or viruses.

Question 14

Aspiration pneumonia

Answer 14

A. seen in patients at risk for aspiration (e.g. alcoholics and comatose patients)

B. Most often due to anaerobic bacteria in the oropharynx (e.g. Bacteroides, fusobacterium, and peptococcus)

C. Classically results in a right lower lobe abscess
1. Anatomically, the right main stem bronchus branches at a less acute angle than the left.

Question 15

Tuberculosis (TB)

Answer 15

A. Due to inhalation of aerosolized mycobacterium tuberculosis

B. Primary TB arises with initial exposure.
1. Results in focal, caseating necrosis in the lower lobe of the lung and hilar lymph nodes that undergoes fibrosis and calcifications, forming a Ghon complex.

2. Primary TB is generally asymptomatic, but leads to a positive PPD.

C. Secondary TB arises with reactivation of mycobacterium tuberculosis

1. Reactivation is commonly due to AIDS; may also be seen with aging.
2. Occurs at apex o lung (relatively poor lymphatic drainage and high oxygen tension)
3. Forms cavitary foci of caseous necrosis; may also lead to miliary pulmonary TB or tuberculous bronchopneumonia
4. Clinical features include fevers and night sweats,
5. Biopsy reveals caseating granulomas; AFB stain reveals acid-fast bacilli
6. Systemic spread often occurs and can involve any tssue; common sites include meninges (meningitis), cervical lymph nodes, kidneys (sterile pyuria) and lumbar vertebrae (Pott disease)

Question 16

COPD basic principles

Answer 16

A. Group of diseases characterized by airway obstruction; lung does not empty and air is trapped.

1. Volume of air that can be forcefully expired is decreased (FVC), especially during the first second of expiration (FEV1); results in decreased FEV1:FVC ratio.
2. Total lung capacity (TLC) is usually increased due to air trapping.

[chronic bronchitis, emphysema, asthma, bronchiectasis]

Question 17

Chronic bronchitis

Answer 17

A. Chronic productive cough lasting at least 3 months over a minimum of 2 years; highly associated with smoking.

B. Characterized by hypertrophy of bronchial mucinous glands.
1. Leads to increased thickness of mucus glands relative to bronchial wall thickness (Reid index increases to > 50%, normal is less than 40%)

C. Clinical features

1. Productive cough due to excessive mucus production
2. Cyanosis (‘blue bloaters’)– Mucus plugs trap carbon dioxide; increased PaCO2 and decreased PaO2
3. Increased risk of infection and cor pulmonale.

Question 18

Emphysema

Answer 18

A. Destruction of the alveolar air sacs
1. Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping.

B. Due to imbalance of proteases and antiproteases

1. Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages.
2. alpha-1 antitrypsin (A1AT) neutralizes proteases
3. Excessive inflammation or lack of A1AT leads to destruction of the alveolar air sacs.

Question 19

Smoking as cause of emphysema

Answer 19

most common cause.

1. Pollutants in somke lead to excessive inflammation and protease-mediated damage.
2. Results in centriacinar emphysema that ismost severe in the upper lobes.

Question 20

A1AT deficiency as cause of emphysema

Answer 20

rare cause.

1. Lack of antiprotease leaves the air sacs vulnerable to protease-mediated damage
2. Results in panacinar emphysema that is most severe in the lower lobes.
3. Liver cirrhosis may also be present.
   I. A1AT deficiency is due to misfolding of the mutated protein
   ii. Mutant A1AT accumulates in the endoplasmic reticulum of hepatocytes, resulting in liver damage.
   iii. Biopsy reveals pink, PAS-positive globules in hepatocytes
4. Disease severity is based on the degree of A1AT deficiency.
   i. PiM is the normal allele; two copies are usually expressed (PiMM)
   ii. PiZ is the most common clinically relevant mutation; results in significantly low levels of circulating A1AT
   iii. PiMZ heterozygoes are usually asymptomatic with decreased circulating levels of A1AT; however, significant risk for emphysema with smoking exists.
   iv. PiZZ homozygotes are at significant risk for panacinar emphysema and cirrhosis.

Question 21

Clinical features of emphysema include

Answer 21

1. dyspnea and cough with minimal sputum
2. proloneged expiration with pursed lips (pink-puffer)
3. Weight loss
4. Increased anterior-posterior diamter of chest (‘barrel-chest’)
5. Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications

Question 22

Asthma

Answer 22

A. Reversible airway bronchoconstriction, most often due to allergic stimuli (atopic asthma)
B. Presents in childhood; often associated with allergic rhinits, eczema, and a family history of atopy

Question 23

Pathogenesis of asthma

Answer 23

(type I hypersensitivity)
1. Allergens induce TH2 phenotype in CD4+ T cells of genetically susceptible individuals

2. TH2 cells secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils), and IL-10
3. Reexposure to allergen leads to IgE-mediated activation of mast cells.
   i. Release of preformed histamine granules and generation of leukotrienes C4, D4 and E4 lead to bronchoconstriction, inflammation, and edema (early-phase reaction)
   ii. Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late-phase reaction).

Question 24

Clinical features of asthma

Answer 24

are episodic and related to allergen exposure

1. Dyspnea and wheezing
2. Productive cough, classically with spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals)
3. Severe, unrelenting attack can result in status asthmaticus and death.

Question 25

non-allergenic causes of asthma

Answer 25

(non-atopic)

exercise, viral infection, aspirin (e.g., aspirin intolerant asthma), and occupational exposures.

Question 26

Bronchiectasis

Answer 26

Permanent dilatation of bronchioles and bronchi; loss of airway tone results in air trapping

Question 27

causes of Bronchiectasis

Answer 27

Due to necrotizing inflammation with damage to airway walls. Causes include:

1. Cystic fibrosis
2. Kartagener syndrome– inherited defect of the dynein arm, which is necessary for ciliary movement. Associated with sinusitis, infertility (poor motility of sperm), and situs inversus (position of major organs is reversed, e.g., heart is on the right side of thorax)
3. Tumor or foreign body
4. Necrotizing infection
5. Allergic bronchopulmonary aspergillosis– hypersensitivity reaction to aspergillus leads to chronic inflammatory damage; usually seen in individuals with asthma or cystic fibrosis

Question 28

Clinical features of bronchiectasis

Answer 28

1. Cough, dyspnea and foul-smelling sputum

2. complications include hypoxemia with cor pulmonale and secondary (AA) amyloidosis

Question 29

Restrictive Diseases: Basic Principles

Answer 29

A. Characterized by restricted filling of the lung; decreased TLC, FEV1 and much decreased FVC; FEV1:FVC ratio is increased

B. Most commonly due to interstitial diseases of the lung; may also arise with chest wall abnormalities (e.g. massive obesity)

Question 30

Idiopathic Pulmonary Fibrosis

Answer 30

A. Fibrosis of lung interstitium

B. Etiology is unknown. Likely related to cyclical lung injury; TGF-beta from injured pneumocytes induces fibrosis.
1. Secondary causes of interstitial fibrosis such as drugs (e.g. bleomycin and amiodarone) and radiation therapy must be excluded

C. Clinical features:

1. Progressive dyspnea and cough
2. Fibrosis on lung CT; initially seen in subpleural patches, but eventually results in diffuse fibrosis with end-stage “honeycomb” lung
3. Treatment is transplantation.