Condition	Pathology	Clinical features	Morphology	
Congenital Anomalies	
Congenital Cysts	•	Formed by abnormal detachment of a fragment of primitive foregut.	Complications:
•	Infection with suppuration.
•	Abscess formation.
•	Rupture into bronchi or pleural cavity, causing hemorrhage or hemoptysis & pneumothorax.	•	Bronchogenic cysts are most common & consist of cystic spaces lined by bronchial-type epithelium.	
Bronchopulmonary Sequestration	•	Presence of lung tissue without a normal connection to airway system & with vascular supply derived from aorta.
•	Extralobular: found in infants as abnormal mediastinal masses & in association with other congenital abnormalities.
•	Intralobular: found within lung parenchyma; most common in adults & associated with recurrent infections.		•		
Atelectasis	•	Incomplete expansion or collapse of parts of or a whole lung.
•	Resorption: complete obstruction of an airway.
•	Compressive: pleural space is expanded by fluid. 
•	Patchy: loss of pulmonary surfactant.		•		
Pulmonary Vascular Disease	
Pulmonary Edema	Hemodynamic:
•	Left-sided heart failure
•	Mitral stenosis
•	Volume overload
•	Pulmonary vein obstruction
•	Neprotic syndrome
•	Liver disease
•	Lymphatic obstruction

Microvascular injury:
•	Infectious agents: viruses
•	Inhaled gases: oxygen, sulfur dioxide, smoke
•	Liquid aspiration: gastric contents	•	Impairment of respiratory function.
•	Chronic edema predisposes to infection.	Gross:
•	Lungs are heavy, wet & subcrepitant.
•	Fluid accumulates, especially in the dependent, basal regions of lower lobes.

Histology:
•	Engorged capillaries.
•	Filling of intra-alveolar airspaces by a granular pink precipitate.
•	Chronic congestion & edema: interstitial fibrosis with hemosiderin-laden macrophages.	
Adult Respiratory Distress Syndrome	•	Basic lesion is diffuse damage to alveolar wall.
•	Damage leads to increased capillary permeability & edema, fibrin exudation, formation of hyaline membranes & septal inflammation.

Mechanisms of damage:
•	Oxygen-derived free radicals
•	Aggregation of activated neutrophils.
•	Activation of lung macrophages which release oxidants.
•	Loss or damage to surfactant.	•	Diffuse alveolar capillary damage.
•	Severe pulmonary edema.
•	Respiratory failure
•	Arterial hypoxemia	•	Acute stage: lungs are diffusely firm, red, boggy, & heavy with acute diffuse alveolar damage.
•	Proliferative: patchy areas of interstitial fibrosis & type II epithelial proliferation. 	
Pulmonary Embolism	•	Occlusions of pulmonary arteries are almost always embolic.
•	Greater than 95% of pulmonary emboli arise in deep veins of the legs. 	Large emboli (5%):
•	Impact in major pulmonary arteries & astride the bifurcation.
•	Instantaneous death
•	Cardiovascular collapse

Middle-sized embolic (20-35%) induces infarction.

Small emboli (60-80%):
•	Clinically silent
•	Transient chest pain
•	Pulmonary hemorrhage
•	Hemoptysis	•		
Pulmonary Hypertension	•	Caused by increased pulmonary vascular resistance.

Secondary to:
•	Chronic obstructive or interstitial lung disease.
•	Left-sided heart disease
•	Recurrent pulmonary emboli	•	Primary pulmonary hypertension is uncommon, seen in children or women aged 20-40.

Generally progresses to:
•	Severe respiratory insufficiency.
•	Cor pulmonale
•	Death over several years	•	Atheroma in large elastic arteries.
•	Intimal fibrosis or medial hypertrophy in medium-sized muscular arteries.
•	Presence of numerous organized thrombi.	
Chronic Obstructive Pulmonary Disease
•	Obstructive disease: increased resistance to airflow.
•	Restrictive disease: reduced expansion of lung parenchyma, with decreased total lung capacity.	
Emphysema	•	Abnormal enlargement of airspaces distal to the terminal bronchioles, with destruction of their walls.

Centriacinar:
•	Destruction & enlargement of acinus, sparing distal alveoli
•	Involves upper lobes & apices.

Panacinar:
•	Uniform destruction & enlargement of acinus.
•	Involves lower basal zones.
•	Association with 1-antitrypsin deficiency.

Paraseptal:
•	Involves mostly distal acinus.
•	Found near pleura & adjacent to fibrosis or scars.
•	Underlying lesion of spontaneous pneumothorax.

Irregular:
•	Irregular involvement of acinus
•	Associated with scarring.
•	Asymptomatic.	•	Destruction of alveolar walls in emphysema stems from an imbalance between proteases & their inhibitors in the lung.

Tobacco smoking contributes to emphysema by:
•	Recruiting neutrophils into the lung
•	Stimulating release of elastase from neutrophils.
•	Enhancing macrophage elastase activity.
•	Inactivation of 1-antitrypsin by oxidants in tobacco smoke. 	•	Diffuse forms: lungs become voluminous & pillowy.
•	Enlarged airspaces.
•	Thinned walls.
•	Septal capillaries compressed & bloodless.
•	Rupture of walls may produce honeycombing. 	
Chronic Bronchitis	•	Defined clinically as persistent cough with sputum production for at least 3 months in at least 2 consecutive years.
•	Caused by chronic irritation of airways by inhaled substances.

Irritants cause bronchitis by:
•	Hypersecretion of mucus.
•	Subsequent hypertrophy of mucous glands.
•	Goblet cell metaplasia in bronchiolar epithelium.
•	Bronchiolitis. 
•	Infections (secondary factor)	•		•	Hyperemia & edema of mucous membranes of the lung.
•	Mucinous secretions or casts filling airways.
•	Increase in size of the mucous glands.
•	Bronchial or bronchiolar mucous plugging, inflammation, & fibrosis.
•	Squamous metaplasia or dysplasia of bronchial epithelium. 	
Bronchial asthma	•	Chronic relapsing inflammatory disorder: increased responsiveness of tracheobronchial tree to various stimuli, resulting in paroxysmal contraction of bronchial airways.

Two types: 
•	Extrinsic atopic: allergen-mediated
•	Intrinsic nonreaginic: precipitated by various factors.

Atopic asthma:
•	Type I IgE-mediated hypersensitivity.
•	Acute phase with binding of antigen by IgE-coated mast cells leading to release of mediators.
•	Late phase reaction mediated by recruited leukocytes.

Acute phase mediators result in:
•	Bronchospasm
•	Edema
•	Mucus secretion
•	Recruitment of lymphocytes

Late phase:
•	Persistent bronchospasm & edema.
•	Leukocytic inflitration.
•	Loss of damaged epithelial cells.

Nonatopic asthma is triggered by:
•	Respiratory tract infections.
•	Chemical irritants.
•	Drugs.	•		Gross:
•	Overinflated lungs
•	Patchy atelectasis
•	Occlusion of airways by mucous plugs

Histology:
•	Lungs exhibit edema.
•	Inflammatory infiltrate in bronchial walls with numerous eosinophils.
•	Hypertrophy of bronchial wall musculature & of submucosal mucous glands.
•	Whorled mucous plugs
•	Crystalloid debris of eosinophil membranes within airways. 	
Bronchiectasis	•	A chronic necrotizing infection of bronchi & bronchioles leading to abnormal permanent dilation of these airways.

Seen in association with:
•	Bronchial obstruction, such as by tumor or foreign bodies.
•	Congenital conditions: cystic fibrosis.
•	Immotile cilia syndromes: Kartagener syndrome.
•	Necrotizing pneumonia. 	Clinical features:
•	Fever
•	Cough
•	Abundant purulent sputum
•	Obstructive respiratory insufficiency in severe cases

Complications:
•	Cor pulmonale
•	Metastatic abscesses
•	Systemic amyloidosis

Persistent obstruction leads to atelectasis. 	•	Most severe changes seen in distal airways of lower lobes.
•	Mild to necrotizing acute & chronic inflammation of the airways.
•	Fibrosis develops in chronic cases.
•	Extension of bronchial infection may lead to abscess formation.	
Pulmonary Infections
Pathogenesis:
•	Loss of or decreased cough reflex leading to aspiration.
•	Injury to mucociliary apparatus.
•	Decreased phagocytic or bactericidal function of alveolar macrophage.
•	Edema or congestion
•	Accumulation of secretions	
Bronchopneumonia	Marked by patchy exudative consolidation of lung parenchyma, caused most commonly by:
•	Staphylococci
•	Streptococci
•	Pneumococci
•	Haemophilus influenzae
•	Pseudomonas aeruginosa
•	Coliform bacteria		Gross: lungs show dispersed, elevated, focal areas of palpable consolidation & suppuration.

Histology:
•	Acute suppurative exudate filling airspaces & airways.
•	Resolution of exudate usually restores normal lung structure.
•	Organization may occur & result in fibrous scarring. 	
Lobar pneumonia	•	Involves a large portion of an entire lobe of lung.
•	Most lobar pneumonias are caused by pneumococci, which enter the lungs via the airways.
•	Other causative agents: Klebsiella, staphylococci, streptococci, H.influenzae.

Stages of uncomplicated pneumonia:
•	Congestion: predominates in first 24 hours.
•	Red hepatization: lung tissue with confluent acute exudation containing neutrophils & red cells, giving a red, firm, liver-like gross appearance.
•	Gray hepatization: follows as red cells disintegrate & remaining fibrinosuppurative exudate persists, giving a gray-brown gross appearance. 
•	Resolution: consolidated exudate undergoes enzymatic & cellular degradation & clearance.	Complications:
•	Abscess formation
•	Empyema: spread of infection to pleural cavity.
•	Organization of exudate into fibrotic scar tissue.
•	Bacteremia & sepsis, with infection of other organs.		
Atypical Pneumonia	Infection by viruses:
•	Influenza A or B
•	Respiratory syncytial virus
•	Adenovirus
•	Rhinovirus
•	Herpes simplex
•	Cytomegalovirus
•	Mycoplasma pneumoniae
•	Certain viruses cause necrosis of bronchial or alveolar epithelium in severe infections. 	•		•	Patchy or lobar areas of congestion seen without consolidation of bacterial pneumonias.
•	Predominance of interstitial pneumonitis with widened, edematous alveolar walls containing a mononuclear inflammatory cell infiltrate.
•	Formation of hyaline membranes, reflecting diffuse alveolar damage.
•	Frequent superimposed bacterial infection.	
Lung Abscess	•	Marked by localized, suppurative necrosis of lung tissue of infectious origin.

Commonly involved are:
•	Staphylococci
•	Streptococci
•	Gram-negative species
•	Anaerobes

Initiation of infections by:
•	Aspiration of infective material.
•	Antecedent primary bacterial infection.
•	Septic emboli from infected thrombi.
•	Obstructive tumors
•	Direct traumatic punctures	Complications:
•	Extension into the pleural cavity.
•	Hemorrhage
•	Septic embolization
•	Secondary amyloidosis	•	Abscesses vary in number & size.
•	Aspiration abscesses contain pus & air.
•	Chronic abscesses are surrounded by a reactive fibrous wall.	
Tuberculosis	•	Chronic, communicable disease caused by Mycobacterium tuberculosis.
•	Marked by a necrotizing caseating granulomatous tissue response to seeded organisms.
•	Transmission is by inhalation of infected droplets.
•	Predisposing factors are debilitating or immunosuppressive condition.
•	Delayed hypersensitivity develops in 2-4 weeks after initial infection.

Primary pulmonary tuberculosis:
•	Occurs in individuals lacking previous contact with tubercle bacilli.
•	Begins as a granulomatous lesion, a Ghon focus, in the inferior upper lobe or superior lower lobe.
•	Infection does not progress & results in local scarring & calcification.

Secondary pulmonary tuberculosis:
•	Active infection in a previously sensitized individual.
•	Reactivation of dormant bacilli from primary lesions.
•	Found in apices of the lungs.	•	Primary tuberculosis is usually asymptomatic.

Secondary form causes:
•	Insidious fever
•	Night sweats
•	Weight loss
•	Productive cough with blood-streaked sputum
•	Hemoptysis

Hematogenous spread of tubercle bacilli may produce miliary tuberculosis with myriad minute foci of infection in many organs.	•	Diagnosis relies on culture of organism or demonstration of acid-fast bacilli in sputum or biopsy tissue. 	
Interstitial Lung Disease	•	Initial event: injury to epithelium or endothelium via inhaled or blood-borne toxins or agents.
•	Early acute changes: alveolitis & recruitment by chemotactic factors.
•	Late effect: interstitial fibrosis.	Clinical:
•	Dypnea
•	Decreased lung volume & compliance

Radiologic:
•	Diffuse infiltrates
•	Ground-glass shadows	•	Diffuse, chronic inflammation or fibrosis of alveolar interstitum.	
Carbon dust-Coal Workers’ Pneumoconiosis	•	Pneumoconioses: disorders caused by inhalation of mineral dusts, organic dusts, fumes, & vapors.
•	Anthracosis: small harmless accumulations in lungs of urban dwellers & smokers.
•	Simple coal workers’ pneumoconiosis: numerous aggregates of coal dust-laden macrophages.
•	Progressive massive fibrosis: severe fibrosis & scarring in areas of dust accumulation.	•	Cough
•	Blackish sputum	Simple coal workers’ pneumoconiosis:
•	Black coal macules composed of dust-filled macrophages 1-5mm in diameter.
•	Present diffusely in upper zones of upper & lower lobes.

Progressive massive fibrosis: large, blackened scars in upper zones.	
Silicosis	•	Prolonged inhalation of silica particles produces a chronic, nodular, dense pulmonary fibrosis.
•	Persistent inflammation & fibrosis.
•	Ingested silica leads to macrophage activation & release of mediators that cause fibroblast proliferation & collagen deposition.	•		•	Distinct collagenous nodules start as small lesions in the upper lung.
•	Coalescence of lesions forms large areas of dense scar.
•	Calcification & blackening by coal dust.
•	Hyalinized whorls of collagen with scant inflammation.	
Asbestosis	•	Inhaled fibers in alveoli are ingested by macrophages, stimulating release of C5a & other chemoattractants.
•	Interstitial fibrosis & injury due to release of enzymes, free radicals, cytokines & growth factors by macrophages.	Associated with increased risk of:
•	Bronchogenic carcinoma
•	Malignant mesothelioma	Induces pleural reactions manifested by:
•	Benign effusions
•	Fibrous pleural adhesions
•	Dense fibrocalcific plaques	
Sarcoidosis	•	Common disease of unknown etiology, affecting women more frequently than men.
•	Characterized by noncaseating granulomas in virtually any tissue.
Affects:
•	Lymph nodes
•	Liver: diffuse, scattered granulomas
•	Spleen & liver: enlargement
•	Skin: discrete subcutaneous nodules, erythematous scaling plaques, & lesions in the mucous membranes. 
•	Eye: iritis or choroid retinitis.	•	Asymptomatic
•	Cutaneous or ocular lesions
•	Peripheral lymphadenopathy
•	Hepatosplenomegaly
•	Insidious onset of respiratory difficulties.
•	Fever, night sweats, weight loss.
•	Acute onset: fever, erythema nodosum, polyarthritis.	•	Microscopic granulomas composed of tightly clustered epithelioid histiocytes.
•	Rarely central necrosis.
•	Schaumann bodies: laminated, calcified proteinaceous concretions.
•	Asteroid bodies: stellate inclusions within giant cells.
	
Idiopathic pulmonary fibrosis	•	Progressive pulmonary fibrosis that results in hypoxemia.
•	Most common between 30-50 years of age.	•	Pulmonary insufficiency
•	Cor pulmonale
•	Cardiac failure	Early stages:
•	Interstitial & intra-alveolar edema
•	Interstitial infiltration by leukocytes
•	Type II pneumonocyte proliferation

Intermediate stages: interstitial & intra-alveolar fibrosis

End stages: lungs consists of spaces lined by pneumocytes & separated by inflammatory fibrous tissue.	
Hypersensitivity Pneumonitis	•	Immunologically mediated disorder caused by inhaled dusts or antigens.
•	Farmer’s lung: spores of actinomycetes in hay.	•	Cough
•	Dyspnea
•	Fever
•	Diffuse & nodular radiographic densities
	•	Interstitial pneumonitis & fibrosis
•	Noncaseatin.g, loosely formed granulomas.	
Diffuse pulmonary hemorrhage	•	Goodpasture syndrome: a necrotizing, hemorrhagic interstitial pneumonitis & progressive glomerulonephritis.
•	Idiopathic pulmonary hemosiderosis: chronic, episodic hemorrhage of lung, resulting in hemosiderin deposition & fibrosis.
•	Vasculitis-associated hemorrhage: seen with Wegener granulomatosis, SLE & hypersensitivity angitis.	•		•		
Tumors	
Bronchogenic Carcinoma	•	90-95% of lung tumors.
•	Most common cause of cancer death in both men & women.
•	Tobacco smoking is most important etiologic factor.
•	Hyperplastic & atypical changes in bronchial epithelium.
•	Other etiologic factors: radiation, exposure to asbestos. 	Clinical features:
•	Cough
•	Weight loss
•	Chest pain
•	Dyspnea
•	Hoarseness of voice
•	Pneumonia, abscess, lobar collapse
•	Diaphragm paralysis
•	Superior vena caval syndrome
•	Pericarditis, tamponade

Etopic production of hormones: ADH, ACTH, calcitonin, gonadotropins, serotonin.

Paraneoplastic syndromes:
•	Cushing syndrome
•	SIADH
•	Myopathy
•	Peripheral neuropathy
•	Acanthosis nigricans
•	Clubbing of fingers

5-year survival rate: 9%	Adenocarcinoma:
•	Most common lung cancer in women & men.
•	Presents as a peripheral mass.
•	Gland formation
•	Mucin production

Squamous cell carcinoma:
•	Closest correlation with smoking.
•	Arise in or near hilus of lung.
•	Vary from well-differentiated keratinizing neoplasms to anaplastic tumors.

Small cell carcinoma:
•	Most malignant
•	Presents as a central or hilar tumor.
•	Strongly associated with cigarette smoking.
•	Small oatlike cells with little cytoplasm.
•	May contain neurosecretory granules.

Large cell carcinoma: poorly differentiated squamous cell carcinomas or adenocarcinomas.	
Bronchioalveolar Carcinoma	•	Uncommon form of adenocarcinoma arising in terminal bronchioalveolar regions.
•	Occur in men & women equally.
•	Not usually associated with smoking. 	Prognosis is favorable after resection of a solitary nodule but dismal for those with diffuse involvement.	•	Single or multiple nodules.
•	Diffuse consolidation with tumor.
•	Tall, columnar mucin-producing tumor cells line up along alveolar septa, forming papillary projections within spaces. 	
Bronchial Carcinoid	•	1-5% of all lung tumors
•	Neuroendocrine differentiation	Surgical resection is curative in 90-95%.	•	Gross: intrabronchial, highly vascular, polypoid masses less than 3-4cm in diameter.
•	Histology: uniform, small, round cells in nests or cords.	
Diseases of the Pleura: secondary to underlying lung disease.	
Pleural effusions	Accumulation of transudate with:
•	Heart failure
•	Pneumonia
•	Nephrotic syndrome
•	Atelectasis
•	Carcinomatosis		•		
Pleuritis	•	Serofibrinous or suppurative.
•	Organization exudates with dense fibrous adhesions affect lung expansion.
•	Hemorrhagic: occurs with bleeding disorders, neoplastic involvement & certain rickettsial diseases.		•		
Pneumothorax	•	Air or gas in pleural cavity
•	Traumatic: air escape from the lung after rib fracture.	Serious, potentially fatal complication.	•		
Malignant mesothelioma	•	Uncommon tumor of mesothelial cells.
•	Occurs most often on pleura.	•	Chest pain
•	Dyspnea
•	Recurrent pleural effusions
•	Highly malignant
•	Invade lung & metastasize widely.
•	Few patients survive longer than two years. 	•	Tumor spreads diffusely over surface of lung & tissues. 
•	Sarcomatoid conformation: malignant, spindle-shaped cell.
•	Epithelioid growth form tubules & papillary projections.