Respiratory Tract Pathology

Question 1

Rhinitis

Answer 1

Inflammation of the nasal mucosa –> rhinovirus is the most common cause
- presents with sneezing, congestion and runny nose (common cold)

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

• characterized by an inflammatory infiltrate with eosinophils
• associated with asthma and eczema

Question 2

Nasal polyp

Answer 2

Protrusion of edematous, inflamed nasal mucosa

• usually secondary to repeated bouts of rhinitis; also occurs in CF and aspirin-intolerant asthma
• aspirin intolerant asthma –> characterized by the triad of asthma, aspirin induced bronchospasms, and nasal polyps

Question 3

Angiofibroma

Answer 3

Benign tumor of nasal mucosa composed of large 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. influenza type b is the most common cause, especially in non-immunized children

Presents with high fever, sore throat, drooling with dysphagia, muffled voice, and inspiratory stridor –> risk of airway obstruction

Question 6

Laryngotraceobronchitis (croup)

Answer 6

Inflammation of the upper airway
- parainfluenza virus is the most common cause

Presents with a hoarse, barking cough and inspiratory stridor

Question 7

Vocal cord nodule

Answer 7

Nodule that arises on the true vocal cord

• due to excessive use of vocal cords
• usually bilateral
• composed of degenerative (myxoid) connective tissue

Presents with hoarseness; resolves with resting of voice

Question 8

Laryngeal papilloma

Answer 8

Benign papillary tumor of the vocal cord

• due to HPV 6 +11
• papillomas are usually single in adults and multiple in children

Presents with hoarseness

Question 9

Laryngeal carcinoma

Answer 9

Squamous cell carcinoma usually arising from the epithelial lining of the vocal cord

Risk factors:

• alcohol
• tobacco
• can rarely arise from a laryngeal papilloma

Presents with hoarseness
- other signs include cough + stridor

Question 10

Pneumonia

Answer 10

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

• fever and chills
• productive cough with yellow-green (pus) or rusty (bloody) sputum
• tachypean with pleuritic chest pain
• decreased breath sounds
• dullness to percussion
• elevated WBC count

Diagnosis –> made by chest x ray, sputum gram stain + culture, and blood cultures

3 patterns classically seen on chest x ray:

1. lobal pneumonia
2. bronchopneumonia
3. interstitial pneumonia

Question 11

Lobar pneumonia

Answer 11

Characterized by consolidation of an entire lobe of the lung
- usually bacterial –> most common causes are streptococcus pneumoniae (95%) + Klebsiella pneumoniae (5%)

Classic gross phases of lobar pneumoina:

1. congestion –> due to congested vessels and edema
2. red hepatization –> due to exudate, neutrophils and hemorrhage filling the alveolar air spaces, giving the normally spongy lung a solid consistency
3. grey hepatization –> due to degradation of red cells within the exudate
4. resolution

Question 12

Bronchopneumonia

Answer 12

Characterized by scattered patchy consolidation centered around bronchioles

• often multifocal and bilateral
• caused by a variety of bacterial organisms

Question 13

Interstitial (atypical) pneumonia

Answer 13

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 14

Aspiration pneumonia

Answer 14

Seen in patients at risk for aspiration –> alcoholics + comatose patients

• most often due to anaerobic bacteria in the oropharynx –> 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 15

Causes of lobar pneumonia

Answer 15

1. Strep pneumo –> most common cause of CA pneumonia and secondary pneumonia (bacterial pneumonia superimposed on a viral upper respiratory tract infection)
   - usually seen in middle aged adults and the elderly
2. Klebsiella pneumoniae –> part of enteric flora that is aspirated, affects malnourished and debilitated individuals, especially elderly in nursing homes, alcoholics and diabetics
   - thick mucoid capsule results in gelatinous sputum = currant jelly
   - often complicated by abscess

Question 16

Causes of bronchopneumonia

Answer 16

1. Staph aureus –> 2nd most common cause of secondary pneumonia; often complicated by abscess or empyema
2. Haemophilus influenzae –> common cause of secondary pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
3. Moraxella catarrhalis –> CA pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
4. Llegionella pneumophilia –> CA 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/atypical pneumonia

Answer 17

1. Mycoplasma pneumoniae –> most common cause of atypical pneumonia, usually affects young adults
   - complications include autoimmune hemolytic anemia (IgM against I antigen on RBCs causes cold hemoltyic anemia) + erythema multiforme
   - not visible on gram stain due to lack of cell wall
2. Chlamydia pneumoniae –> second most common cause of atypical pneumonia in young adults
3. Respiratory syncytial virus (RSV) –> most common cause of atypical pneumonia in infants
4. CMV –> atypical pneumonia with post transplant immunosuppressive therapy
5. Influenza virus –> atypical pneumonia in the elderly, immunocompromised, and those with pre-existing lung disease
   - also increases the risk for superimposed S. aureus or H. flu bacterial pneumonia
6. Coxeilla burnetti –> atypical pneumonia with high fever (Q fever), seen in farmers and vets
   - coxiella spores are deposited on cattle by ticks or are present in cattle placentas
   - coxiella is a rickettsial organism, but distinct from most rickettsiea because it…
   - –> causes pneumonia
   - –> does not require arthropod vector for transmission (survives as highly heat resistant endospores)
   - —> does not produce a skin rash

Question 18

Tuberculosis

- primary TB

Answer 18

Due to inhalation of aerozolized mycobacterium tuberculosis

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

Question 19

Secondary TB

Answer 19

Arises with reactivation of mycobacterium tuberculosis

• reactivation is commonly due to AIDS, may also be seen with aging
• occurs at apex of lung –> relatively poor lymphatic drainage + high oxygen tension
• forms cavitary foxi of vaseous necrosis, may also lead to miliary pulmonary TB or tuberculous bronchopneumonia

Clinical features

• fevers
• night sweats
• cough with hemoptysis
• weight loss

Biopsy revelas caseating granulomas; AFB stain reveals acid fast bacilli

Systemic spread often occurs and can involve any tissue –> common sites:

• meninges –> meningitis
• cervical lymph nodes
• kidneys –> sterile pyuriva
• lumbar vertebrae –> Pott disease

Question 20

Basic principles of COPD

Answer 20

Group of diseases characterized by airway obstruction –> lung does not empty, and air is trapped

• volume of air that can be forcefully expired is decreased (decreased FVC), especially during the first second of expiration (very decreased FEV1) –> results in decreased FEV1: FVC ratio
• total lung capacity is usually increased due to air trapping

Question 21

Chronic bronchitis

Answer 21

Chronic productive cough lasting at least 3 months over a minimum of 2 years –> highly associated with smoking

Characterized by hypertrophy of bronchial mucinous glands –> leads to increased thickness of mucus glands relative to bronchial wall thickness

• Reid index increases to >50%, normal is mucus plugs trap CO2 = increased PaCO2 + decreased PaO2
• increased risk of infection and cor pulmonale

Question 22

Emphysema

Answer 22

Destruction of alveolar air sacs –> loss of elastic recoil and collapse of airway during exhalation results in obstruction and air trapping

Due to imbalance of protease and antiproteases

• inflammation in the lung normally leads to release of proteases by neutrophils and macrophages
• alpha1 antitrypsin (A1AT) neutralizes proteases
• excessive inflammation of lack of A1AT –> 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

Question 23

A1AT deficiency

Answer 23

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
• –> mutated A1AT accumulates in the ER of hpatocytes, resulting in liver damage
• –> biopsy reveals pink, PAS-positive globules in hepatocytes

Disease severity is based on the degree of A1AT deficiency

1. PiM = normal allele –> two copies are usually expressed
2. PiZ = most common clinically relevant mutation –> results in significantly low levels of circulating A1AT
3. PiMZ = heterozygotes are usually asymptomatic with decreased circulating levels of A1AT –> significant risk for emphysema with smoking exists
4. PiZZ homozygotes –> significant risk for panacinar emphysema and cirrhosis

Question 24

Clinical features of emphysema

Answer 24

• dyspnea and cough with minimal sputum
• prolonged expiration with pursed lips
• 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 25

Asthma

Answer 25

Reversible airway bronchoconstriction, most often due to allergic stimuli (atopic asthma) - presents in childhood --> often associated with allergic rhinitis, eczema, and a family history of atopy Pathogenesis = type I hypersensitivity 1. allergens induce TH2 phenotype in CD4 T cells of genetically susceptible individuals 2. TH2 cells secrete... - --> IL4 = mediates class switch to IgE - --> IL5 = attracts eosinophils - --> IL10 = stimulates TH2 cells and inhibits TH1 3. reexposure to allergen leads to IgE-mediated activation of mast cells --> release of preformed histamine granules and generation of leukotrienes C4, D4 + E4 lead to bronchoconstriction, inflammation and edema (early phase reaction) - inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late phase reaction) Asthma may also arise from nonallergic causes (non-atopic asthma) such as exercise, viral infection, aspirin, and occupational exposures

Question 26

Cliniical features of asthma

Answer 26

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

Question 27

Bronchiectasis

Answer 27

Permanent dilation of bronchioles and bronchi --> loss of airway tone results in air trapping Due to necrotizing inflammation with damage to airway walls --> causes: 1. CF 2. Kartagener syndrome --> inherited defect of the dynein arm, whichis necessary for ciliary movement - --> associated with sinusitis, infertility (poor motility of sperm), and situs inversus (position of major organs is reversed) 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 CF

Question 28

Clinical features of bronchiectasis

Answer 28

- cough, dyspnea, and foul smelling sputum - complications incude hypoxemia with cor pulmonale and secondary amyloidosis (AA) --> due to deposition of acute phase reactants

Question 29

Basic principles of restrictive lung disease

Answer 29

Characterized by restricted filling of the lung - decreased TLC, decreased FEV1, and extremely decreased FVC - FEV1: FVC ratio is increased Most commonly due to interstitial disease of the lung - may also arise with chest wall abnormalities (e.g. massive obesity)

Question 30

Idiopathic pulmonary fibrosis

Answer 30

Fibrosis of lung interstitium - etiology is unknown --> likely related to cyclical lung injury; TFG-beta from injured pneumocytes induces fibrosis - secondary causes of interstitial fibrosis such as drugs (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 --> lung transplant

Question 31

Pneumoconioses

Answer 31

Interstitial fibrosis due to occupational exposure; requires chronic exposure to small particles that are fibrogenic - alveolar macrophages engulf foreign particles and induce fibrosis Types of pneumoconioses 1. Coal workers' 2. Silicosis 3. Berylliosis 4. Asbestosis

Question 32

Coal workers' pneumoconiosis

Answer 32

Exposure: Carbon dust --> seen in coal miners Pathologic findings: Massive exposure leads to diffuse fibrosis ('black lung'); associated with rheumatoid arthritis (Caplan syndrome) Comments: - mild exposure to carbon (e.g. pollution) results in anthracosis = collections of carbon laden macrophages --> not clinically significant

Question 33

Silicosis

Answer 33

Exposure: Silica -->seen in sandblasters and silica miners Pathologic findings: Fibrotic nodules in upper lobes of the lung Comments: - Increased risk for TB --> silica impairs phagolysosome formation by macrophages

Question 34

Berylliosis

Answer 34

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

Question 35

Asbestosis

Answer 35

Exposure: Asbestos fibers --> seen in construction workers, plumbers, and shipyard workers Pathologic findings: Fibrosis of lung and pleura (plaques) with increased risk for lung carcinoma and mesothelioma - lung carcinoma is more common than mesothelioma in exposed individuals Comments: - lesions may contain long, golden brown fibers with associated iron (asbestos bodies) --> confirm exposure to asbestos

Question 36

Sarcoidosis

Answer 36

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 gian cells of the granulomas Other commonly involved tissues include - uvea = uveitis - skin = cutaneous nodules or erythema nodosum - salivary and lacrimal glands = mimics sjogren syndrome - almost any tissue can be involved

Question 37

Clinical features and treatment of sarcoidosis

Answer 37

Clinical features - dyspnea or cough --> most common presenting symptom - elevated serum ACE - hypercalcemia --> 1 alpha hydroxylase activity of epitheliod histiocytes converts vit D to its active form Treatment is steroids --> often resolves spontaneously without treatment

Question 38

Hypersensitivity pneumonitis

Answer 38

Granulomatous reaction to inhaled organic antigens (e.g. pigeon breeders lung) - presents with fever, cough, and dyspnea hours after exposure; resolves with removal of the exposure - chronic exposure leads to interstitial fibrosis

Question 39

Basic principles of pulmonary hypertension

Answer 39

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 - presents with exertional dyspnea or right sided heart failure Subclassified as primary or secondary based on etiology

Question 40

Primary pulmonary hypertension

Answer 40

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

Question 41

Secondary pulmonary hypertension

Answer 41

- due to hypoxemia --> COPD and interstitial lung disease - increased volume in the pulmonary circuit --> e.g. congenital heart disease - recurrent pulmonary embolism

Question 42

Acute respiratory distress syndrome

Answer 42

Diffuse damage to the alveolar capillary interface (diffuse alveolar damage) - leakage of protein rich fluid leads to edema that combines with necrotic epithelial cells to form hyaline membranes in alveoli Occurs secondary to a variety of disease processes - sepsis - infection - shock - trauma - aspiration - pancreatitis - DIC - hypersensitivity reactions - drugs - --> activation of neutrophils induces protease and free radical mediated damage of type I and type II pneumocytes

Question 43

Clinical features and treatment of ARDS

Answer 43

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 Treatment - address underlying cause - ventilation with positive end expiratory pressure (PEEP) - recovery may be complicated by interstitial fibrosis --> damage and loss of type II pneumocytes leads to scarring and fibrosis

Question 44

Neonatal respiratory distress syndrome

Answer 44

Respiratory distress due to inadequate surfactant levels - surfactant is made by type II pneumocytes --> phosphatidylcholine (lecithin) is the major component - surfactant decreased 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

Question 45

What is neonatal respiratory distress syndrome associated with?

Answer 45

1. 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 ration >2 indicates adequate surfactant production 2. C section delivery --> due to lack of stress induced steroids; steroids increase synthesis of surfactant 3. Maternal diabetes --> insulin decreases surfactant production

Question 46

Clinical features and complications of neonatal respiratory distress syndrome

Answer 46

Clinical features - increasing respiratory effort after birth - tachypnea with use of accessory muscles - grunting Complications - Hypoxemia increases the risk for persistence of PDA and necrotizing enterocolitis - supplemental Ox increases the risk for free radical injury - --> retinal injury leads to blindness - --> lung damage leads to bronchopulmonary dysplasia

Question 47

Basic principles of lung cancer

Answer 47

Most common cause of cancer mortality in the US - average age of presentation is 60 years Key risk factors are cigarette smoke, radon, and asbestos 1. 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") 2. 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; second most frequent cause of lung carcinoma in the US - increased risk of lung cancer is also seen in uranium miners

Question 48

Presenting symptoms of lung cancer

Answer 48

Non specific --> cough, weight loss, hemoptysis, and postobstructive pneumonia Imaging often reveals a solitary nodule ("coin lesion") --> biopsy is necessary for diagnosis of cancer Benign lesions, which often occur in younger patients, can also produce a coin lesion - granuloma --> often due to TB of fungus - bronchial hamartoma --> benign tumor composed of lung tissue and cartilage; often calcified on imaging

Question 49

Categories of lung carcinoma

Answer 49

Small cell carcinoma = 15% - usually not amenable to surgical resection --> treated with chemo Non-small cell carcinoma = 85% --> treated upfront with surgical resection, does not respond well to chemo - adenocarcinoma = 40% - squamous cell carcinoma = 30% - large cell carcinoma = 10% - carcinoid tumor = 5%

Question 50

Small cell carcinoma

Answer 50

Poorly differentiated small cells --> arises from neuroendocrine (Kulchitsky) cells - male smokers - centrally located - rapid growth and early metastasis - may produce ADH of ACTH or cause eaton lambert syndrome

Question 51

Squamous cell carcinoma

Answer 51

Characteristic histology --> keratin pearls or intercellular bridges - most common tumor in male smokers - centrally located - may produce PTHrP = hypercalcemia

Question 52

Adenocarcinoma

Answer 52

Characteristic histology --> glands or mucin - most common tumor in nonsmokers and female smokers - peripherally located

Question 53

Large cell carcinoma

Answer 53

Poorly differentiated large cells --> no keratin pears, intercellular bridges, glands, or mucin - associated with smoking - central or peripheral location - poor prognosis

Question 54

Bronhioloalveolar carcinoma

Answer 54

Columnar cells that grow along preexisting bronchioles and alveoli --> arises from clara cells - not related to smoking - peripherally located - may present with pneumonia-like consolidation on imaging - excellent prognosis

Question 55

Carcinoid tumor

Answer 55

Well differentiated neuroendocrine cells --> chromogranin positive - not related to smoking - central or peripheral location --> when central, classically forms a polyp like mass in the bronchus - low grade malignancy - rarely, can cause carcinoid syndrome

Question 56

Metastasis to the lung

Answer 56

Most common sources are breast and colon carcinoma - multiple cannon ball like nodules on imaging - more common than primary tumors

Question 57

TMN staging

Answer 57

T - tumor size and local extension - pleural involvement is classically seen with adenocarcinoma - obstruction of the SVC leads to distended head and neck veins with edema and blue discoloration of arms and face (SVC syndrome) - involvement of recurrent laryngeal nerve can leads to hoarseness or phrenic nerve can cause diaphragmatic paralysis - compression of sympathetic chain leads to horner syndrome --> ptosis (drooping eyelid),d miosis (pinpoint pupil) and anhidrosis (no sweating) --> usually due to an apical tumor (pancoast) N - spread to regional lymph nodes (hilar and mediastinal) M - unique site of distant metastasis is the adrenal gland - also brain Overall, 15% 5 years survival - often presents late due to absence of an effective screening method

Question 58

Pneumothorax

Answer 58

Accumulation of air in the pleural space Spontaneous pnuemothorax --> due to rupture of an emphysematous bleb, seen in young adults - results in collapse of a portion of the lung --> 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 59

Mesotheolioma

Answer 59

Malignant neoplasm of mesothelial cells --> highly associated with occupational exposure to asbestos - presents with recurrent pleural effusions, dyspnea, and chest pain - tumor encases the lung