Respiratory

Question 1

Rhinitis

Answer 1

Inflammation of the nasal mucosa; adenovirus is the most common cause, Presents with sneezing, congestion, and runny nose (common cold)

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

• Protrusion of edematous, inflamed nasal mucosa
• Usually secondary to repealed bouts of rhinitis; also occurs in cystic fibrosis and aspirin-intolerant asthma

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

• Benign tumor of nasal mucosa composed oflarge blood vessels and fibrous tissue; classically seen in adolescent males
• Presents with profuse epistaxis

Question 4

Nasopharyngeal carcinoma

Answer 4

• Malignant tumor of nasopharyngeal epithelium
• Associated with EBV; classically seen in African children and Chinese adults
• Biopsy usually reveals pleomorphic keratin-positive epithelial cells (poorly differentiated squamous cell carcinoma) in a background of lymphocytes
• Often presents with involvement of cervical lymph nodes

Question 5

Acute Epiglottitis

Answer 5

• Inflammation of the epiglottis; H influenzae type b is the most common cause, especially in rionimmunized children,
• Presents with high fever, sore throat, drooling with dysphagia, muffled voice, and inspiratory stridor; risk of airway obstruction

Question 6

Laryngotracheobronchitis

Answer 6

• Croup
• Inflammation of the upper airway; parainfluenza virus Is the most common cause
• Presents with a hoarse, “barking” cough and inspiratory stridor
• Presents with hoarseness; resolves with resting of voice

Question 7

Laryngeal Papilloma

Answer 7

• Benign papillary tumor of the vocal cord
• Due to HPV 6 and 11; papillomas are usually single in adults and multiple in children.
• Presents with hoarseness

Question 8

Laryngeal Carcinoma

Answer 8

• Squamous cell carcinoma usually arising from the epithelial lining of the vocal cord
• Risk factors are alcohol and tobacco; can rarely arise from a laryngeal papilloma
• Presents with hoarseness; other signs include cough and stridor.

Question 9

Pneumonia

Answer 9

• Infection of the lung parenchyma
• Occurs when normal defenses are impaired (e.g.. impaired cough reflex, damage to mucociliary escalator, or mucus plugging)
• Clinical features include fever and chills, productive cough with yellow-green (pus) or rusty (bloody) sputum, tachypnea with pleuritic chest pain, decreased breath sounds, dullness to percussion, and elevated WBC count.
• Diagnosis is made by chest x-ray, sputum gram stain and culture, and blood cultures.

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

Question 10

Lobar Pneumonia

Answer 10

• Characterized by consolidation ol an entire lobe ol tile lung
• Usually bacterial; most common causes are Streptococcus pneumoniae (95%) and Klebsiella pneumoniae
• Classic gross phases of lobar pneumonia
  
  • Congestion—due to congested vessels and edema
  • Red hepatization—due to exudate, neutrophils, and hemorrhage tilling the alveolar air spaces, giving the normally spongy lung a solid consistency
  • Gray hepatization—due to degradation of red cells within the exudate
  • Resolution

Question 11

Bronchopneumonia

Answer 11

• Characterized by scattered patchy consolidation centered around bronchioles; often multifocal and bilateral
• Caused by a variety of bacterial organisms (Table 9.2)

Question 12

Interstitial (Atypical) Pneumonia

Answer 12

• Characterized by diffuse interstitial infiltrates
• Presents with relatively mild upper respiratory symptoms (minimal sputum and low fever); ‘atypical’ presentation
• Caused by bacteria or viruses

Question 13

Aspiration Pneumonia

Answer 13

• Seen in patients at risk tor aspiration (e.g., alcoholics and comatose patients)
• Most often due to anaerobic bacteria in the oropharynx (e.g., Bacteroides, Fusobacterium, Peptococcus)
• Classically results in a right lower lobe abscess
  • Anatomically- the right main stem bronchus branches at a less acute angle than the left.

Question 14

Causes of Lobar Pneumonia

Answer 14

• Streptococcus pneumoniae: Most common cause of community-acquired pneumonia; usually seen in middle- aged adults and elderly
• Klebsiella pneumoniae : Affects malnourished and debilitated individuals, especially elderly in nursing homes, alcoholics, and diabetics (enteric flora that is aspirated). Ihick mucoid capsule results in gelatinous sputum (currant jelly); often complicated by abscess

Question 15

Causes of Bronchopneumonia

Answer 15

• Staphylococcus aureus: Most common cause of secondary pneumonia (bacterial pneumonia superimposed on a viral upper respiratory tract infection); often complicated by abscess or empyema
• Haemophilus: Common cause of secondary pneumonia and pneumonia superimposed on COPD (leads toxic exacerbation of COPD)
• Pseudomonas: Pneumonia in cystic fibrosis patients
• Moraxella: Community-acquired pneumonia and pneumonia super imposed on COPD (leads to exacerbation of COPD)
• Legionella: Community-acquired pneumonia, pneumonia superimposed on COPD, or pneumonia in immunocompromised states; transmitted from water source Intracellular organism that is best visualized by silver stain

Question 17

Causes of interstitial pneumonia

Answer 17

• Mycoplasma: Most common cause of atypical pneumonia, usually alfecls young adults (classically, military recruits or college students living in a dormitory). Complications include autoimmune hemolytic anemia (IgM against I antigen on RBCs causes cold hemolytic anemia) and erythema multiforme. Not visibie on gram stain due to lack of cell wall
• Chlamydia pneumoniae: Second most common cause of atypical pneumonia in young adults
• Respiratory Syncytial Virus (RSV): Most common cause of atypical pneumonia in infants
• Ctyomegalovirus (CMV): Atypical pneumonia with posttransplant immunosuppressive therapy
• Influenza virus: Atypical pneumonia in the elderly, immunocompromised, and those with preexisting lung disease. Also increases the risk for superimposed S aureus or H influenzae bacterial pneumonia
• Coxiella: Atypical pneumonia with high fever (Q fever); seen in farmers and veterinarians (Coxiella spores arc deposited on cattle by ticks or are present in cattle placentas). Coxiella is a rickettsial organism, but it is distinct from most rickettsiae because it (I) causes pneumonia, (2) does not require arthropod vector for transmission [survives as highly heat-resistant endospores), and (3) dnes not produce a skin rash.

Question 18

Tuberculosis

Answer 18

• Due to inhalation of aerosolized Mycobacterium tuberculosis B. Primary TB arises with initial exposure.
• Results in focal, caseating necrosis in the lower lobe of the lung and hilar lymph nodes that undergoes fibrosis and calcification, forming a Ghon complex
• Primary TB is generally asymptomatic, but leads to a positive PPD.
• Secondary TB arises with reactivation with Mycobacterium tuberculosis
• Reactivation is commonly due to AIDS; may also be seen with agin
• Occurs at apex of lung (high oxygen tension)
• Forms cavitary foci of caseous necrosis; may also lead to miliary pulmonary TB or tuberculous bronchopneumonia
• Clinical features include fevers and night sweats, cough with hemoptysis, and weight loss.
• Biopsy reveals caseating granulomas; AFB stain reveals acid-fast bacilli
• Systemic spread often occurs and can involve any tissue; common sites include meninges (meningitis), cervical lymph nodes, kidneys (sterile pyuria), and lumbar vertebrae (Pott disease).

Question 20

Chronic Bronchitis

Answer 20

• Chronic productive cough lasting at least 3 months over a minimum of2 years; highly associated with smoking
• Characterized by hypertrophy of bronchial mucinous glandsLeads to increased thickness of mucus glands relative to overall bronchial wall thickness (Reid index increases to > 50%; normal is < 40%).
• Clinical features
  • Productive cough due to excessive mucus production
  • Cyanosis (‘blue bloaters’) —Mucus plugs trap carbon dioxide; increase PaCO2 and decreased PaO2
  • Increased risk of infection and cor pulmonale

Question 21

Emphysema

Answer 21

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

• Due to imbalance of proteases and antiproteases
  
  • Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages.
  • alpha antitrypsin (A1AT) neutralizes proteases.
  • Excessive inflammation or lack of AIA T leads to destruction of the alveolar air sacs.

Smoking is the most common cause of emphysema.

• Pollutants in smoke lead to excessive inflammation and protease-mediated damage.
• Results in centriacinar emphysema that is most severe in the upper lobes

AIA T deficiency is a rare cause of emphysema.

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

Clinical features of emphysema include

• Dyspnea and cough with minimal sputum
• Prolonged expiration with pursed lips (‘pink puffer’)
• Weight loss
• Increased anterior-posterior diameter of chest {‘barrel-chest)
• Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications.

Question 22

Asthma

Answer 22

Reversible airway bronchoconstriction, most often due to allergic stimuli (type I hypersensitivity)

Presents in childhood; often associated with allergic rhinitis, eczema, and a family history of atopy

Pathogenesis

• Allergens induce TH2 phenotvpe in CD4’ T cells of genetically susceptible individuals
• TH2 cells secrete IL-4 (mediates class switch to IgE), 1L-5 (attracts eosinophils), and IL-10 (stimulates TH2 cells and inhibits TH1).
• Reexposure to allergen leads to lgE-mediated activation of mast cells.
• Release of preformed histamine granules and generation of leukotrienes C4, D4, and E4 lead to broncho constrict ion, inflammation, and edema (early- phase reaction)
• Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchocon strict ion (late-phase reaction).

Clinical features are episodic and related to allergen exposure.

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

Asthma may also arise from nonallergic causes such as exercise, viral infection, aspirin (e.g., aspirin intolerant asthma), and occupational exposures.

Question 23

Bronchietasis

Answer 23

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

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

• Cystic fibrosis
• 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 right side of thorax)
• Tumor or foreign body
• Necrotizing infection
• Allergic bronchopulmonary aspergillosis—Hypersensitivity reaction to
• Aspergillus leads to chronic inflammatory damage; usually seen in individuals with asthma or cystic fibrosis
• Clinical features
  
  • Cough, dyspnea, and tbul-smelling sputum
  • Complications include hypoxemia with cor pulmonale and secondary (AA) amyloidosis.

Question 24

Idiopathic Pulmonary Fibrosis

Answer 24

Fibrosis of lung interstitial

Etiology is unknown. Likely related to cyclical lung injury; TGF-p from injured pneumocytes induces fibrosis.

• Secondary causes of interstitial fibrosis such as drugs (e.g., bleomycin and amiodarone) and radiation therapy must be excluded.

Clinical features

• Progressive dyspnea and cough
• Fibrosis on lung CT; initially seen in subpleural patches, but eventually results in diffuse fibrosis with end-stage ‘honeycomb’ lung
• Treatment is lung transplantation.

Question 25

Sarcoidosis

Answer 25

Systemic disease characterized by noncaseating granulomas in multiple organs; classically seen in African American females

Etiology is unknown; likely due to CD4+ helper T-cell response to an unknown antigen

Granulomas most commonly involve the hilar lymph nodes and lung leading to restrictive lung disease.

• Characteristic stellate inclusions (‘asteroid bodies’) are often seen within giant cells of the granulomas

Other commonly involved tissues include the uvea (uveitis), skin (cutaneous nodules or erythema nodosum), and salivary and lacrimal glands (mimics Sjogren syndrome); almost any tissue can be involved)

Clinical features

1. Dyspnea or cough (most common presenting symptom)
2. Elevated serum ACE
3. Hypercalcemia (1-alpha hydroxylase activity of epithelioid histiocytes converts vitamin D to its active form)
4. Treatment is steroids; often resolves spontaneously without treatment.

Question 26

Coal Worker’s Pneumoconiosis

Answer 26

• Exposure to carbon dust; seen in coal miners
• Massive exposure leads to diffuse fibrosis (‘black lung’); associated with rheumatoid arthritis (Caplan syndrome)
• Mild exposure to carbon (e.g., pollution) results in anthracosis (collections of carbon-laden macrophages); not clinically significant)

Question 27

Silicosis

Answer 27

• Exposure: silica, seen in sand blaster and silica miners
• Pathologic Finding: Fibrotic nodules in upper lobes of the lung
• Increased risk for TB; silica impairs phagolysosome formation by macrophages.

Question 28

Berylliosis

Answer 28

• Exposure: Beryllium, seen in beryllium miners and workers in the aerospace industry
• Pathologic finding: Noncaseating granulomas in the lung, hilar lymph nodes, and systemic organs
• Increased risk for lung cancer

Question 29

Asbestosis

Answer 29

• Exposure: Asbestos fibers; seen in construction workers, plumbers, and shipyard workers
• Pathologic Finding: Fibrosis of lung and pleura [plaques) with increased risk for lung carcinoma and mesothelioma; lung carcinoma is more common lhan mesothelioma in exposed individuals.
• Lesions may contain long, golden- brown fibers with associated iron (asbestos bodies), which confirm exposure to asbestos

Question 30

Hypersensitivity Pneumonitis

Answer 30

• Granulomatous reaction to inhaled organic antigens (e.g., pigeon breeder’s lung)
• Presents with fever, cough, and dyspnea hours after exposure; resolves with removal of the exposure
• Chronic exposure leads to interstitial fibrosis.

Question 31

Pulmonary Hypertension

Answer 31

High pressure in the pulmonary circuit (mean arterial pressure > 25 mm Hg; normal is 10 mm Hg)

Characterized by atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries, and intimal fibrosis; plexiform lesions are seen with severe, long-standing disease

Leads to right ventricular hypertrophy with eventual cor pulmonale D. Presents with exertional dyspnea or right-sided heart failure
Subclassified as primary or secondary based on etiology

PRIMARY PULMONARY HYPERTENSION

• Classically seen in young adult females
• Etiology is unknown; some familial forms are related to inactivating mutations of BMPR2, leading to proliferation of vascular smooth muscle.

SECONDARY PULMONARY HYPERTENSION

• Due to hypoxemia (e.g., COPD and interstitial lung disease) or increased volume in the pulmonary circuit (e.g., congenital heart disease); may also arise with recurrent pulmonary embolism

Question 32

Acute Respiratory Distress Sydrome

Answer 32

Diffuse damage to the alveolar-capillary interface (diffuse alveolar damage)

Leakage of protein-rich fluid leads to edema and formation of hyaline membranes in alveoli

Clinical features

• Hypoxemia and cyanosis with respiratory distress—due to thickened diffusion barrier and collapse of air sacs (increased surface tension)
• ‘White-out’ on chest x-ray

Secondary to a variety of disease processes including sepsis, infection, shock, trauma, aspiration, pancreatitis, DIG, hypersensitivity reactions, and drugs.

• Activation of neutrophils induces protease-mediated and free radical damage of type 1 and II pneumocytes

Treatment

• Address underlying cause
• Ventilation with positive end-expiratory pressure (PEEP)

Recovery may be complicated by interstitial fibrosis; damage and loss of type 11 pneumocytes leads to scarring and fibrosis.

Question 33

Neonatal respiratory Distress Syndrome

Answer 33

Respiratory distress due to inadequate surfactant levels

• Surfactant is made by type II pneumocytes; phosphatidylcholine (lecithin) is the major component.
• Surfactant decreases surface tension in the lung, preventing collapse of alveolar air sacs after expiration.
• Lack of surfactant leads to collapse of air sacs and formation of hyaline membranes.

Associated with

• Prematurity—Surfactant production begins at 28 weeks; adequate levels are not reached until 34 weeks.
• Amniotic fluid lecithin to sphingomyelin ratio is used to screen for lung maturity.
• Phosphatidylcholine (lecithin) levels increase as surfactant is produced; sphingomyelin remains constant. A ratio > 2 indicates adequate surfactant production.
  
  • Caesarian section delivery—due to lack of stress-induced steroids; steroids increase synthesis of surfactant,
  • Maternal diabetes—Insulin decreases surfactant production, and grunting

Clinical features

• Increasing respiratory effort after birth, tachypnea with use of accessory muscles
• Hypoxemia with cyanosis
• Diffuse granularity of the lung (‘ground-glass’ appearance) on x-ray

Complications

• Hypoxemia increases the risk for persistence of patent ductus arteriosus and necrotizing enterocolitis.
• Supplemental oxygen increases the risk for free radical injury. Retinal injury leads to blindness; lung damage leads to bronchopulmonary dysplasia

Question 34

Lung Cancer

Answer 34

Most common cause of cancer mortality in the US; average age at presentation is 60 years.

Key risk factors are cigarette smoke, radon, and asbestos.

• Cigarette smoke contains over 60 carcinogens; 85% of lung cancer occurs in smokers,
• Polycyclic aromatic hydrocarbons and arsenic are particularly mutagenic.
• Cancer risk is directly related to the duration and amount of smoking (‘pack-years’).

Radon is formed by radioactive decay of uranium, which is present in soil.

• Accumulates in closed spaces such as basements
• Responsible for most of the public exposure to ionizing radiation; 2nd most frequent cause of lung carcinoma in US
• Increased risk of lung cancer is also seen in uranium miners.

Presenting symptoms are nonspecific (e.g., cough, weight loss, hemoptysis, and postobstructive pneumonia).

Imaging often reveals a solitary nodule (‘coin-lesion’); biopsy is necessary for a diagnosis of cancer

• Benign lesions, which often occur in younger patients, can also produce a ‘coin- lesion
• Examples include
  
  • Granuloma—often due to TB or fungus (especially Hittoplasma in the Midwest)
  • Bronchial hamartoma—benign tumor composed of lung tissue and cartilage; olien calcified on imaging

TNM staging

1. T—Tumor size and local extension

• Pleural involvement is classically seen with adenocarcinoma,
• Obstruction ofSVC leads to distended head and neck veins with edema and blue discoloration of arms and face (superior vena cava syndrome).
• Involvement of recurrent laryngeal (hoarseness) or phrenic (diaphragmatic paralysis) nerve
• Compression of sympathetic chain leads to Horner syndrome characterized by ptosis (drooping eyelid), miosis (pinpoint pupil), and anhidrosis (no sweating); usually due to an apical (Pancoast) tumor

2. N—spread to regional lymph nodes (hilar and mediastinal)
3. M—unique site of distant metastasis is the adrenal gland.

Overall, 15% 5-year survival; often presents late due to the absence of an effective screening method

Question 35

Pneumothorax

Answer 35

Accumulation of air in the pleural space

Spontaneous pneumothorax is due to rupture of an emphysematous bleb; seen in young adults

• Results in collapse of a portion of the lung (Fig. 9.24); trachea shifts to the side of collapse.

Tension pneumothorax arises with penetrating chest wall injury.

• Air enters the pleural space, but cannot exit; trachea is pushed opposite to the side of injury.
• Medical emergency; treated with insertion of a chest tube

Question 36

Mesothelioma

Answer 36

Malignant neoplasm of mesotheiial cells; highly associated with occupational exposure to asbestos

Presents with recurrent pleural effusions, dyspnea, and chest pain; tumor encases the lung