Leukocytosis and neutrophilia, elevated ESR, and C-reactive protein, and hypergammaglobulinemia
Precipitating antibodies to offending antigen are commonly present --- marker or exposure
Pulmonary alveolar proteinosis (PAP) <br />
Characterized radiologically by bilateral patchy asymmetric pulmonary opacifications
Characterized histologically by accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces.
Classification: Primary (or acquired), secondary and congenital PAP --- different pathogenesis but similar histologic changes <br />Epidemiology: Rare --- M:F = 4:1. Age of onset varies from 20-50 years old <br />Morphology<br />
Characterized by a peculiar granular precipitate within alveoli, causing focal-to-confluent consolidation of large areas of lungs
On section, turbid fluid exudes from these areas >> increase in size and weight of lung.
Alveolar precipitate is periodic acid-Schiff positive and also contains cholesterol clefts.
Immunohistochemical staining reveals abundant accumulation of surfactant protein.
Autosomal Recessive --- Caused by mutations in genes that encode for:
Serum levels below protective threshold of 11 mmol/L. Most common severe variant is the Z allele
Hyperinflation of lungs, flattening domes of hemidiaphragms, attenuation or absence of pulmonary vasculature, loss of vascular branching pattern, widened retrosternal space, large focal lucencies (bullae), bronchial wall thickening.
Attenuation of vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema.
With complicating pulmonary hypertension, the hilar vascular shadows are prominent;
With right ventricular enlargement, opacity in the lower retrosternal air space may occur.
CT scanning and HRCT are even better for assessment
Pulmonary Function Tests<br />
Necessary for diagnosis of obstructive airway disease and for assessments of its severity.
Spirometry is helpful for assessing responses to treatment and disease progression.
Decrease of forced expiratory volume in 1 second (FEV1) is the key to diagnosis.
Increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity is decreased.
Clinical Phenotypes<br />
Emphysema is the primary underlying pathology.
Results from destruction of airways distal to terminal bronchiole, includes gradual destruction of capillary bed
Less surface area for gas exchange -- but less ventilation-perfusion mismatch than blue bloaters.
Compensate by hyperventilation ("puffer" part) -- less hypoxemia (compared to blue bloaters) with "reddish"
Inflammation of pleura may result from extension of any pulmonary infection to the visceral pleura, rheumatoid arthritis, disseminated lupus erythematosus, collagen vascular disease, or pulmonary infarction
Sharp, stabbing chest pain on inspiration. Associated with pleural effusion (exudates)
Serous, serofibrinous and fibrinous pleuritis.
Fibrinous exudations generally reflect a later, more severe exudative reaction
Grossly, a grayish-white fibrinous membrane covers the inflamed pleura which lacks its normal luster.
There is frequently a small amount of fluid serous exudate that is cloudy in appearance.
Nonpleuritic chest wall pain, dyspnea, and recurrent pleural effusions.
Easy fatigability, fever, sweats, and weight loss are the other common accompanying symptoms.
Concurrent pulmonary asbestosis (fibrosis) is present in only 20% of individuals with pleural mesothelioma.
Often metastatic spread to the hilar lymph nodes and, eventually, to the liver and other distant organs.
Imaging: Chest radiographs or CT scans show obliteration of the diaphragm, nodular thickening of the pleura, decreased size of the involved chest, radiolucent sheetlike encasement of the pleura, or a combination of these.
Prognosis: The prognosis is poor, with a median survival time of 12 months after diagnosis
Commonly affects proximal leg veins (femoral vein or popliteal vein) or deep veins of pelvis.
Embolize to pulmonary arterial circulation >> develop PTE, which is usually asymptomatic.
Pathophysiologic consequences of pulmonary embolism.
Response depends on extent to which the pulmonary artery blood flow is obstructed, the size of the occluded vessel(s), the number of emboli, the overall status of the cardiovascular system, and the release of vasoactive factors such as thromboxane A2 from platelets that accumulate at the site of the thrombus.
Respiratory consequences due to the nonperfused, though ventilated, lung segment
Increased alveolar dead space, hypoxemia (ventilation-perfusion mismatch), and hyperventilation.
Pulmonary infarction is an uncommon consequence because of the rich collateral circulation
Hemodynamic consequences due to increased resistance to pulmonary blood flow by embolic obstruction.
Reduction in cross-sectional area >> pulmonary vascular resistance >> increases right ventricular afterload.
Left-to-right cardiac shunts as well as idiopathic pulmonary hypertension, thromboembolic pulmonary hypertension, and hypertension secondary to fibrotic lung disease, connective tissue diseases and hypoxia.
Due to hypoxic pulmonary vasoconstriction, loss of small vessels in regions of emphysematous lung destruction and obliteration of the pulmonary vascular bed by interstitial fibrosis and lung destruction.
Sleep apnea: hypoxemia can result in constriction of small pulmonary arteries and pulmonary hypertension
Kyphoscoliosis or extreme obesity (Pickwickian syndrome)
Lead to hypoxemia and pulmonary hypertension.
Chronic hypoxia results in muscularization of the arterioles with minimal effects on the intima.
Pulmonary hypertension due to chronic thrombotic and/or embolic disease.
Rresults from asymptomatic, episodic showers of small emboli from the periphery.
Gradually restrict pulmonary circulation, and lead to pulmonary hypertension and right ventricular failure.
Evidence of peripheral venous thrombosis, in deep leg veins, or a history predisposition to venous thrombosis.
Clinical Manifestations<br />
Present with exertional dyspnea that increases in severity over months or even years.
Exertional chest pain, syncope, and lower extremity edema >> more severe with impaired right heart function.
Increased pulmonic component of second heart sound, a right ventricular lift, and elevated jugular venous pulsations. Hepatomegaly, leg pitting edema and ascites are present in patients with decompensated right heart failure.
Medial hypertrophy of muscular and elastic arteries, atherosclerosis of pulmonary artery and branches, and RV hypertrophy.
Coexistence of diffuse pulmonary fibrosis, or severe emphysema and chronic bronchitis, points to chronic hypoxia
Atherosclerotic plaques form in pulmonary artery and its major branches, resembling systemic atherosclerosis.
Increases in muscular thickness of media (medial hypertrophy) and intimal fibrosis
Plexiform lesion: tuft of capillary formations, producing a network that spans lumens of dilated thin-walled, small arteries
Diffuse Pulmonary Hemorrhage Syndromes<br />
Hemorrhage from the lung is a dramatic complication of some interstitial lung disorders.
Superior vena cava syndrome due to obstruction >> upper extremity and facial edema, dilated neck veins<br />Left vocal cord paralysis due to recurrent laryngeal nerve impingement: hoarseness;<br />Nerve entrapment syndromes due to invasion of extreme lung apex (Pancoast tumor): <br />Involvement of brachial plexus >> shoulder pain radiating in ulnar nerve distribution down arm<br />Involvement of stellate ganglion may cause Horner syndrome<br />Characterized by enophthalmos, ptosis of upper eyelid, miosis, and anhidrosis <br />Compression of middle third of esophagus due to enlargement of subcarinal lymph nodes: dysphagia;<br />Compression of thoracic duct: chylothorax<br />