Respiratory Tract Pathology Flashcards
Rhinitis
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
Nasal polyp
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
Angiofibroma
Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue
- classically seen in adolescent males
- presents with profuse epistaxis
Nasopharyngeal carcinoma
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
Acute epiglottitis
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
Laryngotraceobronchitis (croup)
Inflammation of the upper airway
- parainfluenza virus is the most common cause
Presents with a hoarse, barking cough and inspiratory stridor
Vocal cord nodule
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
Laryngeal papilloma
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
Laryngeal carcinoma
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
Pneumonia
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:
- lobal pneumonia
- bronchopneumonia
- interstitial pneumonia
Lobar pneumonia
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:
- congestion –> due to congested vessels and edema
- red hepatization –> due to exudate, neutrophils and hemorrhage filling the alveolar air spaces, giving the normally spongy lung a solid consistency
- grey hepatization –> due to degradation of red cells within the exudate
- resolution
Bronchopneumonia
Characterized by scattered patchy consolidation centered around bronchioles
- often multifocal and bilateral
- caused by a variety of bacterial organisms
Interstitial (atypical) pneumonia
Characterized by diffuse interstitial infiltrates
- presents with relatively mild upper respiratory symptoms –> minimal sputum and low fever = atypical presentation
- caused by bacteria or viruses
Aspiration pneumonia
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
Causes of lobar pneumonia
- 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 - 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
Causes of bronchopneumonia
- Staph aureus –> 2nd most common cause of secondary pneumonia; often complicated by abscess or empyema
- Haemophilus influenzae –> common cause of secondary pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
- Moraxella catarrhalis –> CA pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD)
- 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
Causes of interstitial/atypical pneumonia
- 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 - Chlamydia pneumoniae –> second most common cause of atypical pneumonia in young adults
- Respiratory syncytial virus (RSV) –> most common cause of atypical pneumonia in infants
- CMV –> atypical pneumonia with post transplant immunosuppressive therapy
- 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 - 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
Tuberculosis
- primary TB
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
Secondary TB
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
Basic principles of COPD
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
Chronic bronchitis
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
Emphysema
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
A1AT deficiency
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
- PiM = normal allele –> two copies are usually expressed
- PiZ = most common clinically relevant mutation –> results in significantly low levels of circulating A1AT
- PiMZ = heterozygotes are usually asymptomatic with decreased circulating levels of A1AT –> significant risk for emphysema with smoking exists
- PiZZ homozygotes –> significant risk for panacinar emphysema and cirrhosis
Clinical features of emphysema
- 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
Asthma
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
- allergens induce TH2 phenotype in CD4 T cells of genetically susceptible individuals
- TH2 cells secrete…
- –> IL4 = mediates class switch to IgE
- –> IL5 = attracts eosinophils
- –> IL10 = stimulates TH2 cells and inhibits TH1 - 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
Cliniical features of asthma
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
Bronchiectasis
Permanent dilation of bronchioles and bronchi –> loss of airway tone results in air trapping
Due to necrotizing inflammation with damage to airway walls –> causes:
- CF
- 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) - 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 CF
Clinical features of bronchiectasis
- cough, dyspnea, and foul smelling sputum
- complications incude hypoxemia with cor pulmonale and secondary amyloidosis (AA) –> due to deposition of acute phase reactants
Basic principles of restrictive lung disease
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)
Idiopathic pulmonary fibrosis
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
Pneumoconioses
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
- Coal workers’
- Silicosis
- Berylliosis
- Asbestosis
Coal workers’ pneumoconiosis
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
Silicosis
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
Berylliosis
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
Asbestosis
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
Sarcoidosis
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
Clinical features and treatment of sarcoidosis
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
Hypersensitivity pneumonitis
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
Basic principles of pulmonary hypertension
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
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 –> COPD and interstitial lung disease
- increased volume in the pulmonary circuit –> e.g. congenital heart disease
- recurrent pulmonary embolism
Acute respiratory distress syndrome
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
Clinical features and treatment of ARDS
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
Neonatal respiratory distress syndrome
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
What is neonatal respiratory distress syndrome 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 ration >2 indicates adequate surfactant production - C section delivery –> due to lack of stress induced steroids; steroids increase synthesis of surfactant
- Maternal diabetes –> insulin decreases surfactant production
Clinical features and complications of neonatal respiratory distress syndrome
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
Basic principles of lung cancer
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
- 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; second most frequent cause of lung carcinoma in the US
- increased risk of lung cancer is also seen in uranium miners
Presenting symptoms of lung cancer
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
Categories of lung carcinoma
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%
Small cell carcinoma
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
Squamous cell carcinoma
Characteristic histology –> keratin pearls or intercellular bridges
- most common tumor in male smokers
- centrally located
- may produce PTHrP = hypercalcemia
Adenocarcinoma
Characteristic histology –> glands or mucin
- most common tumor in nonsmokers and female smokers
- peripherally located
Large cell carcinoma
Poorly differentiated large cells –> no keratin pears, intercellular bridges, glands, or mucin
- associated with smoking
- central or peripheral location
- poor prognosis
Bronhioloalveolar carcinoma
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
Carcinoid tumor
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
Metastasis to the lung
Most common sources are breast and colon carcinoma
- multiple cannon ball like nodules on imaging
- more common than primary tumors
TMN staging
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
Pneumothorax
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
Mesotheolioma
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
