Respiratory Pathology

• Inflammation of the nasal mucosa
• Adenovirus is the most common cause
• Presentation: sneezing, congestion, runny nose
• Allergic rhinitis: type I hypersensitivity reaction
• - eosinophils
• - associated with asthma and eczema

• Protrusion of edematous, inflamed nasal mucosa
• Secondary to repeated bouts of rhinitus, CF, aspirin-intolerant asthma

• Benign tumor of nasal mucosa
• -large blood vessels and fibrous tissue
• Presentation: profuse epistaxis
• Males >> females

• Malignant tumor of nasopharyngeal epithelium
• Associated with EBV, African children, Chinese adults
• Bx: pleomorphic keratin-positive epithelial cells

• INflammation of epiglottis
• H. influenzae type b is most common (non-immunized children)
• Presentation: fever, sore throat, drooling with dysphagia, muffled voice, inspiratory stridor
• Risk of airway obstruction

• Inflammation of the upper airway
• Parainfluenza virus is most common cause
• Presentation: hoarse, "barking" cough, inspiratory stridor

• Nodule that arises on the true vocal cord
• Cause: excessive use
• Usually bilateral
• Degenerative (Myxoid) connective tissue
• resolves with rest

• benign papillary tumor of the vocal cord
• HPV 6 and 11
• Usually single in adults, multiple in children
• Presentation: hoarseness

• Squamous cell carcinoma
• Origin: epithelial lining of the vocal cord
• Risk factors: alcohol, tobacco
• Presentation: hoarseness, cough, stridor

• Epidemiology:
• -young adult females

• Presentation:
• -exertional dyspnea
• -R-sided heart failure

• Pathophysiology:
• -PAH ≥ 25 mmHg or > 35 mmHg during exercise
• -results in arteriosclerosis, medial hypertrophy and intimal fibrosis of pulmonary arteries
• -inactivating mutation in BMPR2 gene (normally inhibits vascular SM proliferation)

• Complications:
• -RVH
• -eventual cor pulmonale

• Prognosis:
• -poor prognosis

• Pathophysiology:
• -COPD (lung parenchyma destruction)
• -Mitral stenosis (increase resistance leads to increased pressure)
• -Recurrent thromboemboli (decrease cross-sectional area of vascular bed)
• -Autoimmune disease (systemic sclerosis: inflammation → intimal fibrosis → medial hypertrophy)
• -Left to Right Shunt (increase shear stress → endothelial injury)
• -Sleep apnea/living at high altitude (hypoxic vasoconstriction)

• Pathophysiology:
• -most common source is femoral, iliac, or popliteal vein
• -predisposed by Virchow's Triad
•      -Stasis
•      -Hypercoagulability
•      -Endothelial damage

• Presentation:
• -Homans' Sign: calf pain with dorsiflexion of foot

• Complications:
• -can lead to PE

• Treatment:
• -heparin for prevention and acute management
• -warfarin for long-term prevention of recurrence

• Presentation: most often clinically silent
• -sudden-onset dyspnea
• -chest pain
• -tachypnea
• -may present as sudden death

• Pathophysiology:
• -95% arise from DVTs

• Diagnosis:
• -CT pulmonary angiography

• Pathology:
• -Fat (long bone fractures and liposuction)
• -Air
• -Thrombus
• -Bacteria
• -Amniotic fluid
• -Tumor
• "An embolus moves like a FAT BAT"
• 
• -lines of Zahn (platelets/fibrin and RBCs): only happen premortem
• 

• Fat Emboli:
• -(long bone fractures and liposuction)
• -Triad: hypoxemia, neurologic abnormalities, petechial rash

• Amniotic Fluid Emboli:
• -can lead to DIC, especially post partum

• Pathophysiology:
• -obstruction of air flow resulting in air trapping in the lungs
• -airways close prematurely at high lung volumes
• -V/Q mismatch

• PFTs:
• -↑ RV
• -↑ TLC
• -↓ FVC
• -↓↓ FEV1
• -↓ FEV1/FVC ratio

• Types:
• -Chronic Bronchitis
• -Emphysema
• -Asthma
• -Bronchiectasis

"Blue Bloater"

• Pathophysiology:
• -highly associated with smoking

• Pathology:
• -form of COPD
• -hypertrophy of mucus-secreting glands in bronchi
• -Reid index > 50% (thickness of gland layer/total wall thickness)

• Presentation:
• -productive cough for > 3 months per year for > 2 years
• -wheezing
• -crackles
• -cyanosis (early onset hypoxemia due to shunting)
• -late-onset dyspnea

"Pink Puffer"

• Pathophysiology:
• -↑ elastase activity
• -↑ lung compliance due to loss of elastic fibers
• -destruction of alveolar air sacs
• 

• Centriacinar:
• -associated with smoking
• -inflammation leads to protease mediated damage
• -mostly in upper lobes

• Panacinar:
• -α1-antitrypsin deficiency
• -lack of antiprotease
• -mostly in lower lobes
• -also get liver cirrhosis

• Presentation:
• -dyspnea and cough (minimal sputum)
• -pursed lip expiration
• -weight loss
• -barrel-chest
• -late-onset hypoxemia

• Pathophysiology:
• -bronchial hyperresponsiveness
• -reversible bronchoconstriction
• -can be triggered by viral URIs, allergens and stress
• -most often due to type I hypersensitivity

• Diagnosis:
• -methacholine challenge

• Presentation:
• -cough
• -wheezing
• -tachypnea
• -dypsnea
• -hypoxemia
• -↓ I/E ratio
• -pulsus paradoxus
• -mucus plugging

• Pathology:
• -smooth muscle hypertrophy
• -Curschmann's spirals (shed epithelium forms mucus plugs)
• -Charcot-Leyden crystals (formed from breakdown of eosinophils in sputum)

• Pathophysiology:
• -chronic necrotizing infection of bronchi
• -causes permanently dilated airways

• Causes:
• -Cystic Fibrosis
• -Smoking (poor ciliary motility)
• -Kartagener's Syndrome
• -Allergic bronchopulmonary aspergillosis
• -Bronchial obstruction

• Presentation:
• -purulent sputum (foul smelling)
• -recurrent infections
• -hempotysis

• Complications:
• -hypoxemia with cor pulmonale
• -secondary AA amyloidosis

• Pathophysiology:
• -restricted lung expansion causes decreased lung volumes

• PFTs:
• -↓ FVC
• -↓ TLC
• -FEV1/FVC > 80%

• 1. Poor Breathing Mechanics
• -Pathophysiology: extrapulmonary, periperal hypoventilation, normal A-a gradient
• -poor muscular effort: polio, myasthenia gravis
• -poor structural apparatus: scoliosis, morbid obesity

• 2. Interstitial Lung Diseases
• -Pathophysiology: pulmonary, lowered diffusing capacity, ↑ A-a gradient)
• -ARDS
• -Neonatal respiratory distress syndrome
• -Pneumoconioses (anthracosis, silicosis, asbestosis)
• -Sarcoidosis (bilateral hilar adenopathy, noncaseating granulomas, elevated ACE and Ca2+)
• -Idiopathic pulmonary fibrosis
• -Goodpasture's Syndrome
• -Wegener's
• -Langerhans cell histiocytosis (eosinophilic granuloma)
• -Hypersensitivity pneumonitis
• -Drug toxicity (bleomycin, busulfan, amiodarone, methotrexate)

↑ risk of cor pulmonale and Caplan's syndrome

• Anthracosis: coal miner's lungs, "black lung" (upper lobes)
• -mild exposure results in anthracosis; not clinically significant

• Silicosis: sand blasting, foundries, mines (upper lobes)
• -"Eggshell" calcification of hilar lymph nodes
• -Macrophages respond to silica and release fibrogenic factors
• -↑ susceptibility to TB
• -↑ risk of bronchogenic carcinoma

• Berylloisis: beryllium miners, workers in aerospace
• -Noncaseating granulomas in the lung, hilar lymph nodes, systemic organs
• -↑ risk for lung cancer

• Asbestosis: ship building, roofing, plumbing (lower lobes)
• -"Ivory white" calcified pleural plaques are pathognomonic of exposure, not precancerous
• -↑ incidence of bronchogenic carcinoma and mesothelioma
• 
• -long, golden-brown fibers with associated iron  (asbestos bodies)

• Cause/features:
• -Surfactant deficiency → ↑ surface tension, resulting in alveolar collapse
• -Lecithin:sphingomyelin ratio <1.5 in amniotic fluid is predicitive
• -Persistently low O2 tension → risk of PDA
• -Diffuse granularity of lungs ("ground glass" appearance on CXR)

• Risk factors:
• -Prematurity
• -Maternal diabetes (elevated fetal insulin)
• -Cesarean delivery (↓ release of fetal glucocorticoids)

• Tx:
• -maternal steroids before birth
• -artificial surfactant for infants
• -*Supplemental O₂ can result in retinopathy of prematurity and bronchopulmonary dysplasia

Diffuse alveolar damage → ↑ alveolar capillary permeability → protein-rich fluid leakage into alveoli

• Features:
• -hyoxemia
• -cyanosis
• -respiratory distress
• -"White-out" on chest X-ray

• Cause: initial damage due to release of neutrophilic substances toxic to alveolar wall, activation of coag cascade, oxygen derived free radicals...
• -Trauma
• -Sepsis
• -Shock
• -Gastric aspiration
• -Uremia
• -Acute pancreatitis
• -Amniotic fluid embolism

• Histology:
• -Formation of intra-alveolar hyalin membrane
• 

• Tx:
• -Treat underlying cause
• -Ventilation with PEEP
• -**Most have normal lungs 1yr following

Normal lung

• Obstructive lung volumes > normal
• ↑ TLC, ↑ FRC, ↑ RV
• FEV₁ is more dramatically reduced compared to FVC

• Restrictive lung disease
• Volumes < normal

• -Repeated cessation of breathing > 10 seconds during sleep → disrupted sleep → daytime somnolence
• -Hypoxia → ↑ EPO release → ↑ erythropoiesis
• Central sleep apnea: no respiratory effort
• Obstructive sleep apnea: respiratory effort against airway obstruction
• -Associated with obesity, loud snoring, systemic/pulmonary hypertension, arrhythmias, and possibly sudden death

Tx: weight loss, CPAP, surgery

• ↓ breath sounds
• Dull to percussion
• ↓ fremitus
• no tracheal deviation

• ↓ breath sounds
• Dull to percussion
• ↓ fremitus
• Tracheal deviation toward side of lesion

• ↓ breath sounds
• Hyperresonant to percussion
• ↓ fremitus
• Tracheal deviation toward side of lesion

• ↓ breath sounds
• Hyperresonant to percussion
• ↓ fremitus
• Tracheal deviation away from side of lesion

• Bronchial breath sounds; late inspiratory crackles
• Dull to percussion
• ↑ fremitus
• No tracheal deviation

• -Leading cause of cancer death
• -Metastatic cancer is most common cause
• (breast, colon, prostate, bladder cancer)
• -Sites of metastases: adrenals, brain, bone (pathologic fracture), liver (jaundice, hepatomegaly)
• Presentation:
• -Cough
• -hemoptysis
• -bronchial obstruction
• -wheezing
• -weight loss
• -pneumonic "coin" lesion on CXR
• -noncalcified nodule on CT

• Complications: SPHERE
• -Superior vena cava syndrome
• -Pancoast tumor
• -Horner's syndrome
• -Endocrine (paraneoplastic)
• -Recurrent laryngeal symptoms (hoarseness)
• -Effusions (pleural or pericardial)

• Smoking:
• -All are associated with smoking except brronchioalveolar and bronchial carcinoid

• Small cell carcinoma: 15%
• -no surgical resection
• -treat with chemotherapy

• Non-small cell carcinoma: 85%
• -Adenocarcinioma (40%)
• -Squamous cell carcinoma (30%)
• -Large cell carcinoma (10%)
• -Carcinoid tumor (5%)

• Location: peripheral
• -Most common lung cancer in nonsmokers and females
• -Activating mutations in k-ras common
• -Associated with hypertrophic osteoarthropathy (clubbing)

• Bronchioloalvolar subtype: CXR often shows hazy infiltrates similar to pneumonia; excellent prognosis
•  -Histology: grows along alveolar septa → apparent "thickening" of alveolar walls

• Location: Central
• Hilar mass arising from bronchus
• Cavitation
• Cigarrettes (linked to smoking)
• hyperCalcemia (produces PTHrP)
• Most common tumor in male smokers
• Histology: keratin pearls and intercellular bridges
• 

• Central
• Undifferentiated → very aggressive
• May produce ACTH, ADH, or Antibodies against presynaptic calcium channels (Lambert-Eaton syndrome)
• Amplification of myc oncogenes common
• Male smokers
• Tx: Inoperable; treated with chemotherapy
• Histology: neoplasm of neuroendocrine Kulchitsky cells → small dark blue cells
• 

• Location: peripheral (or central)
• Highly anaplastic undifferentiated tumor (no keratin pearls, intracellular bridges, glands or mucin)
• poor prognosis
• less responsive to chemotherapy
• surgical resection
• Smoking
• Histology: Pleomorphic giant cells

• Location: -
• Excellent prognosis; metastasis is rare
• Not smoking related
• Sx usually due to mass effect
• Occasionally carcinoid syndrome (serotonin secretion → flushing, diarrhea, wheezing)
• Histology: Nets of neuroendocrine cells; chromogranin positive

• Location: Pleural
• Malignancy of the pleura associated with asbestosis
• Results in hemorrhagic pleural effusions and pleural thickening
• Histology: Psammoma bodies

• Carcinoma that occurs in apex of lung may affect cervical sympathetic plexus
• Horner's syndrome: ipsilateral ptosis, miosis, anhidrosis

• Obstruction of the SVC that impairs blood drainage from:
• -head ("facial plethora")
• -neck (jugular venous distention)
• -upper extremities (edema)

• -Commonly caused by malignancy and thrombosis from indwelling catheters
• -Medical emergency!
• -Can raise intracranial pressure (if obstruction severe) → headaches, dizziness, and ↑ risk of aneurysm/rupture of cranial arteries

• Lobar: S. pneumoniae most frequently, Klebsiella
• -Intra-alveolar exudates → consolidation
• -May involve entire lung
• -Phases: congestion → red hepatization → gray hepatization → resolution
• 

• S. pneumoniae, S. aureus, H. influenzae, Klebsiella
• Acute inflammatory infiltrates from bronchioles into adjacent alveoli
• Patchy distribution involving ≥ 1 lobe
• 
• 

• Viruses (influenza, RSV, adenovirus), Mycoplasma, Legionella, Chlamydia
• Diffuse patchy inflammation localized to interstitial areas at alveolar walls
• Distribution involving ≥ 1 lobe
• Generally follows a more indolent course
• -Atypical presentation: mild upper respiratory symtoms
• 

• Seen in pts at risk for aspiration (alcoholics and comatose patients)
• Bacteria of the oropharynx (e.g., Bacteroides, Fusobacterium, Peptococcus)

• Localized collection of pus within parenchyma
• Causes:
• -bronchial obstruction (e.g., cancer)
• -aspiration of oropharyngeal contents (pts predisoposed to loss of consciousness - alcoholics, epileptics)
• -Air-fluid levels seen on CXR
• -S. aureus or anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus)

Mycobacterium tuberculosis

• Primary: focal, caseating necrosis in the lower lobes and hilar LNs
• -Generally asymptomatic

• Secondary: reactivation in the apex of lung (high O₂ tension)
• -Cavitary foci of caseous necrosis
• -may progress to miliary TB or TB bronchopneumonia
• Features: nigh sweats, fevers, cough with hemoptysis, weight loss
• -Bx: caseating granulomas
• -AFB stain +

• Mixed type III/IV hypersensitivity reaction to environmental antigen
• Granulomatous reaction to inhaled organic antigens
• Presentation: dyspnea, cough, chest tightness, headache
• Who: farmers, those exposed to birds
• Chronic exposure leads to interstitial fibrosis

Transudate: ↓ protein content

-Due to CHF, nephrotic syndrome, hepatic cirrhosis

Exudate: ↑ protein content, cloudy

• -Due to malignancy, pneumonia, collagen vascular disease, trauma (occurs in states of ↑ vascular permeability)
• -Must be drained in light of risk of infection

• aka chylothorax
• Due to thoracic duct injury from trauma, malignancy
• Milky-appearing fluid
• ↑ triglycerides

• Unilateral chest pain and dyspnea
• unilateral chest expansion
• ↓ tactile fremitus
• hyperresonance
• diminished breath sounds

• Accumulation of air in the pleural space
• Most frequently in tall, thin, young males (caused by rupture of apical blebs)
• Trachea deviates toward affected lung
• 

• Usually occurs in setting of trauma or lung infection
• Air is capable of entering pleural space, but not exiting
• Trachea deviates away from affected lung
•