41 Pathology 5: Air Space Filling and Pulmonary Vascular Disease Flashcards

1
Q

Acute respiratory distress syndrome (ARDS):
Diffuse alveolar damage (DAD)

  • General
  • “Diffuse”
  • May involve…
  • Interstitial pneumonia or Hamman-Rich disease
A
  • General
    • The pathologic manifestations in patients with acute respiratory distress syndrome (ARDS)
  • “Diffuse”
    • “Diffuse” is usually interpreted as synonymous to “widespread,” and “diffuse alveolar” is inferred to mean all the alveoli in the lung
    • Here “diffuse” refers to changes in a single alveolus and indicates that all parts of the alveolus including epithelium, endothelium, and interstitial space are affected by the process
  • May involve the lung either diffusely or focally
  • Interstitial pneumonia or Hamman-Rich disease
    • DAD that rarely occurs in a previously healthy individual with no identifiable etiology
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2
Q

Acute respiratory distress syndrome (ARDS):
Gross and histologic findings

  • Gross findings
    • In the acute stage,…
    • The lung weight
    • The cut surface
  • Histologic findings: DAD may be divided into two stages
    • Early
    • Later
A
  • Gross findings
    • In the acute stage, the lungs are heavy, firm, red, and boggy
    • The lung weight is usually three to five times more than normal
    • The cut surface is beefy red and firm
  • Histologic findings: DAD may be divided into two stages
    • An early, acute or exudative stage is most prominent in the first week of injury and is characterized by edema and hyaline membranes
    • A later, proliferative or organizing stage in which fibrosis predominates, occurs after one to two weeks
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3
Q

Acute respiratory distress syndrome (ARDS):
Histologic findings

  • The earliest microscopic changes in the acute stage of DAD
  • Hyaline membranes
  • A proteinaceous exudate
  • A minimal interstitial inflammatory infiltrate
  • Fibrin thrombi
  • Hyperplasia of type 2 pneumocytes
A
  • The earliest microscopic changes in the acute stage of DAD
    • Visible twelve to twenty-four hours following injury
    • Consist of interstitial and airspace edema associated with hemorrhage and fibrin deposition
  • Hyaline membranes
    • The histologic hallmark of the acute stage
    • Develop one or more days following injury
    • Are more numerous after three to seven days
    • Appear as homogenous, densely eosinophilic structures that are plastered along the alveolar septa
    • Composed of cytoplasmic and nuclear debris from sloughed cells admixed with fibrin
  • A proteinaceous exudate
    • Contains cellular debris that fills the air spaces
    • Often accompanies the hyaline membranes
  • A minimal interstitial inflammatory infiltrate
    • Consists of lymphocytes, plasma cells, and macrophages
    • Becomes more prominent after one week
  • Fibrin thrombi
    • In various stages of organization
    • Often present in capillaries and small pulmonary arteries
  • Hyperplasia of type 2 pneumocytes
    • Develops 3 to 7 days following injury
    • Most prominent toward the end of the acute stage of DAD
    • Persists throughout the organizing stage
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4
Q

Acute respiratory distress syndrome (ARDS):
Histologic findings:
The organizing stage of DAD

  • Characterized by…
  • Begins…
  • Minimal interstitial inflammation and pneumocyte hyperplasia
  • Edema and hyaline membranes
  • Some of the residual airspace exudate
  • Extensive interstitial fibrosis
  • Arterial changes
  • In fatal cases, fibrosis may…
  • Bronchial epithelium frequently shows…
  • Although the etiology of most cases of DAD cannot be determined histologically, the cause of the damage can usually be obtained from…
  • Infection
A
  • Characterized by fibroblast proliferation, mainly within the interstitium but also focally within airspaces
  • Begins after one or more weeks but is more prominent two or more weeks following injury
  • Minimal interstitial inflammation and pneumocyte hyperplasia
    • Still present
  • Edema and hyaline membranes
    • Not prominent
  • Some of the residual airspace exudate
    • Incorporated into the alveolar septa and remnants of hyaline membranes
    • Can sometimes be identified in the alveolar septum
  • Extensive interstitial fibrosis
    • May develop
  • Arterial changes
    • Seen late in the course
    • Consist of medial hypertrophy and intimal fibrosis
  • In fatal cases, fibrosis may…
    • Progress for several weeks with extensive restructuring of lung parenchyma and formation of honeycomb lung
  • Bronchial epithelium frequently shows…
    • Squamous metaplasia and cytological atypia
  • Although the etiology of most cases of DAD cannot be determined histologically, the cause of the damage can usually be obtained from…
    • The clinical history and laboratory examination
  • Infection
    • The only cause of DAD that can be documented in some cases by biopsy results
    • The presence of acute inflammation, granulomas, or necrosis in a background of DAD are strongly suggestive of an underlying infectious etiology
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5
Q

Acute bacterial pneumonia:
Two gross patterns of anatomic distribution

  • Lobar pneumonia
    • General
    • The most common bacterial cause of lobar pneumonia
  • Bronchopneumonia (lobular)
    • Characterized by…
    • Effective antibiotic therapy for any form of pneumonia…
    • The same organisms may produce…
A
  • Lobar pneumonia
    • An acute bacterial infection involving a large portion of the lobe or an entire lobe
    • The most common bacterial cause of lobar pneumonia is Streptococcus pneumoniae
  • Bronchopneumonia (lobular)
    • Characterized by patchy consolidation of the lung parenchyma
      • Difficult to apply in individual cases because the patterns overlap
      • The patchy involvement may become confluent, producing virtually total lobar consolidation
    • Effective antibiotic therapy for any form of pneumonia may limit involvement to a subtotal consolidation
    • The same organisms may produce bronchopneumonia in one patient, and lobar pneumonia in a more compromised patient
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6
Q

Bacterial pneumonia:
Pathology:
Lobar pneumonia:
Four stages of the inflammatory response

  • (1)
    • Generally lasts…
    • It is uncommon for patients to…
    • The cut surface shows…
    • Microscopically,…
    • Gram stain
  • (2)
    • On gross examination,…
    • The cut surface is…
    • Microscopically,…
    • The pneumococci are …
A
  • (1) Congestion
    • Generally lasts less than 24 hours
    • It is uncommon for patients to die so early in the disease, but when such cases are seen at the autopsy, the affected lobe is more or less uniformly involved and appears disproportionate and large in comparison to other lobes
    • The cut surface shows a blood stained, frothy fluid
    • Microscopically, there is dilatation of alveolar capillaries and the air spaces are filled with a pale eosinophilic fluid admixed with a few red blood cells and neutrophils
    • Gram stain highlights numerous bacteria within air spaces
  • (2) Red hepatization
    • On gross examination, the lobe is distinctly red, firm, and airless with a liver-like consistency, and there is usually an associated serofibrinous pleuritis
    • The cut surface is dry
    • Microscopically, airspaces are filled with edema fluid, fibrin, and numerous neutrophils
    • The pneumococci are numerous and many of them have been ingested by neutrophils
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7
Q

Bacterial pneumonia:
Pathology:
Lobar pneumonia:
Four stages of the inflammatory response

  • (3)
    • The affected lobe…
    • This change usually starts…
    • This stage is a result of…
    • The cut surface is…
    • Microscopically,…
    • The organisms are…
  • (4)
    • ​Proceeds in a…
    • Grossly,…
    • Microscopically,…
    • Pleural fibrinous reaction
A
  • (3) Gray hepatization
    • After two to three days, the affected lobe gradually loses its red color and assumes a gray appearance
    • This change usually starts at the hilum and spreads toward the periphery
    • This stage is a result of decreased capillary congestion and migration of a large number of leukocytes into the alveoli
    • The cut surface is grayish brown and dry
    • Microscopically, there is disintegration of red cells and the persistence of a fibrinopurulent exudate
    • The organisms are less numerous and usually present in degenerated forms.
  • (4) Resolution
    • Proceeds in a patchy but progressive manner by enzymatic digestion of fibrinopurulent exudates within the airspaces
    • Grossly, the affected lobe is more crepitant
    • Microscopically, granular, semifluid debris may be ingested by macrophages or organized by fibroblasts growing into it
    • Pleural fibrinous reaction, often present in the early stages, may similarly resolve, however more often it undergoes organization leaving fibrous thickening and permanent adhesions
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8
Q

Bacterial pneumonia:
Pathology:
Bronchopneumonia

  • On gross examination, bronchopneumonia usually shows…
  • Microscopically,…
  • The most frequent causes of bronchopneumonia
  • Complications of pneumonia
A
  • On gross examination, bronchopneumonia usually shows…
    • Patchy yellow white tan infiltrates
  • Microscopically,…
    • Numerous neutrophils are present in the bronchi, bronchioles, and the adjacent airspaces
  • The most frequent causes of bronchopneumonia
    • Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, Klebsiella pneumonia, and Legionella pneumophila
  • Complications of pneumonia
    • Tissue destruction and necrosis resulting in abscess formation
      • This is particularly common with type 3 pneumococci or Klebsiella infection
    • Empyema
    • Organization of the exudate resulting in parenchymal scarring
    • Bacteremic dissemination to the heart valves, pericardium, brain, kidneys, spleen, or joints causing metastatic abscesses, endocarditis, meningitis, or suppurative arthritis
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9
Q

Pneumonia in immunocompromised patients

  • Opportunistic infectious agents
  • The most common etiologic agents
  • The abnormalities in the immune system of the immunocompromised patient
  • Often the only histologic reaction
A
  • A wide variety of so-called opportunistic infectious agents
    • Many rarely cause infection in normal hosts
    • Can cause pneumonias in immunocompromised patients
    • Mortality from these opportunistic infections is high
  • The most common etiologic agents
    • Bacteria (gram-negative and gram-positive, including Pseudomonas aeruginosa, Mycobacterium sp, Legionella pneumophilia, and Listeria monocytogenes)
    • Viruses (CMV, HSV)
    • Fungi (Pneumocystis jiroveci, Candida sp, Aspergillus sp, the Phycomycetes, and Cryptococcus neoformans)
  • The abnormalities in the immune system of the immunocompromised patient
    • Usually affect the inflammatory response
    • There may be little or no inflammatory reaction to fungi or bacteria, which under usual conditions would cause significant acute inflammation
  • Often the only histologic reaction
    • Acute lung injury or diffuse alveolar damage
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10
Q

Pneumonia in immunocompromised patients:
Atypical mycobacteria

  • Mycobacterium avium-intracellulare complex (MAC)
  • MAC infections
  • Depending on the patient’s immune status, the pathological changes produced by opportunistic Mycobacteria could be…
  • A high proportion of cases usually lack…
  • The other histological features which are characteristic but not specific for atypical mycobacteria
  • In a severely immunocompromised patient, the lesion may consist of…
A
  • Mycobacterium avium-intracellulare complex (MAC)
    • Mycobacterium avium and Mycobacterium intracellulare
    • Cause very similar infections
  • MAC infections
    • Can be seen in any immunocompromised patients
    • Are especially common in AIDS patients and in patients with therapeutic immunosuppression and autoimmune diseases
  • Depending on the patient’s immune status, the pathological changes produced by opportunistic Mycobacteria could be…
    • Very similar, if not identical, to those of Mycobacterium tuberculosis
    • However they may show more airway involvement leading to bronchiectasis
  • A high proportion of cases usually lack…
    • The classic granulomatous response
  • The other histological features which are characteristic but not specific for atypical mycobacteria
    • The presence of microabscesses
    • Ill-defined granulomas with absence of necrosis and with a small number of giant cells
  • In a severely immunocompromised patient, the lesion may consist of…
    • Numerous swollen macrophages, all of which contain large numbers of acid-fast bacilli
    • Necrosis is usually not seen, and the granulomas are poorly formed or completely absent
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11
Q

Pneumonia in immunocompromised patients:
CMV pneumonia

  • Microscopically, the diagnostic histologic feature of CMV infection is…
  • The cytoplasmic inclusions
  • Macrophages
  • Other cells involved
  • Most cases of CMV infection show…
  • Commonly associated findings
  • A variety of other infectious agents that may be associated with CMV
A
  • Microscopically, the diagnostic histologic feature of CMV infection is…
    • Cellular enlargement combined with intranuclear and intracytoplasmic inclusions
    • The intranuclear inclusions are central, dark purple, and separated from the surrounding chromatin by a nuclear halo
  • The cytoplasmic inclusions
    • Found in many, but not all infected cells
    • Appear as coarse basophilic granules
    • Contain a mucopolysaccharide envelope that stains with PAS
  • Macrophages
    • The most frequently infected cell
  • Other cells involved
    • Pneumocytes, endothelial cells, and bronchial epithelial cells
  • Most cases of CMV infection show…
    • A focal or diffuse interstitial pneumonia
  • Commonly associated findings
    • Hyaline membranes
    • Proteinaceous alveolar exudate
    • Intraalveolar hemorrhage
    • Necrosis is usually not present
  • A variety of other infectious agents that may be associated with CMV
    • Different types of bacteria and fungi, particularly Pneumocystis
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12
Q

Pneumonia in immunocompromised patients:
Pneumocystis pneumonia

  • The most common and the classical manifestation
  • The most common morphologic manifestation of pneumocystis infection…
    • In AIDS patients
    • In non-AIDS patients
  • The organisms are found within…
  • The other less common manifestations
  • GMS stain highlights…
  • Pneumocystis organisms are distinguished from fungal yeasts by…
  • Monoclonal antibodies to pneumocystis
A
  • The most common and the classical manifestation
    • A prominent frothy, foamy, or honeycomb exudate within the airspaces associated with an interstitial pneumonia
    • Reflects the presence of large numbers of cysts
  • The most common morphologic manifestation of pneumocystis infection…
    • In AIDS patients
      • The classical manifestation
    • In non-AIDS patients
      • DAD
  • The organisms are found within…
    • The hyaline membranes
  • The other less common manifestations
    • Granulomatous inflammation, fibrosis, intraalveolar macrophage accumulation, interstitial pneumonia, calcification, necrosis, vasculitis, and pulmonary alveolar proteinosis-like areas
  • GMS stain highlights…
    • The cysts, which are round and often indented or helmet-shaped and measure 4 to 6 μm in diameter
    • One or two dot-like foci of enhanced staining are often seen within the cyst and can be useful in their identification
  • Pneumocystis organisms are distinguished from fungal yeasts by…
    • Their lack of budding forms and location within the alveolar spaces
  • Monoclonal antibodies to pneumocystis
    • Commercially available
    • Readily applicable to tissue sections using immunoperoxidase or immunofluorescence techniques
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13
Q

Pneumonia in immunocompromised patients:
Aspergillosis

  • Aspergillus lung infection is divided into three forms
  • Aspergillus pneumonia
  • Histologically, the classic tissue reaction is…
  • The amount of inflammation depends on…
  • Aspergillus organisms
    • H & E
    • Other stains
  • Morphologically, they are…
  • The mycelia are typically…
  • What may be helpful in identifying the organisms
A
  • Aspergillus lung infection is divided into three forms
    • Invasive, saprophytic, and allergic
  • Aspergillus pneumonia
    • The most common form of invasive aspergillosis
    • The two terms are often used synonymously
  • Histologically, the classic tissue reaction is…
    • Hemorrhagic infarction with minimal inflammation
    • Fungal hyphae are found invading blood vessel walls and alveolar septae
    • Arterial lumens can be completely occluded by plugs of fungi
  • The amount of inflammation depends on…
    • The patient’s immune status
  • Aspergillus organisms
    • Can be seen on routine H & E sections in which they appear as pale, blue elements
    • Can also be highlighted by GMS and PAS stains
  • Morphologically, they are…
    • Long, thin septate mycelia usually 4 μm in diameter with 45-degree branching points
  • The mycelia are typically…
    • Arranged in parallel and radiate outward from a central point
  • What may be helpful in identifying the organisms
    • Immunohistochemistry using monoclonal antibodies
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14
Q

Pneumonia in immunocompromised patients:
Cryptococcosis

  • A broad spectrum of histologic features occurs in cryptococcosis varying from…
  • In immunologically intact individuals,…
  • Cryptococci
  • The yeasts
  • The organism’s capsule
  • Immunocompromised patients usually do not manifest…
  • The gross appearance
A
  • A broad spectrum of histologic features occurs in cryptococcosis varying from…
    • No reaction to necrotizing granulomatous inflammation
  • In immunologically intact individuals,…
    • A granulomatous reaction resembling an ordinary well-circumscribed necrotizing granuloma is usually found
    • Non-necrotizing granulomas associated with large numbers of multinucleated histiocytes or organizing pneumonia can also be seen
  • Cryptococci
    • Appear as a pale blue or gray round yeast on H & E stained slides
    • Vary considerably in size, from 2 to 15 μm
    • Fragmentation is a prominent feature
  • The yeasts
    • Usually separated from surrounding necrotic debris by an unstained clear space, which is an artifact caused by retraction of their thick mucinous capsule
  • The organism’s capsule
    • Stains bright red with mucicarmine, which is considered to be diagnostic of cryptococcosis
  • Immunocompromised patients usually do not manifest…
    • A granulomatous reaction to the organism
    • In such cases, sheets of organisms are present within the alveolar spaces and there is no or little inflammatory reaction
  • The gross appearance
    • Often mucoid because of the presence of confluent masses of the encapsulated yeasts
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15
Q

Pulmonary embolism

  • Occlusion of the large pulmonary arteries is almost always caused by…
  • Large-vessel in situ thromboses
  • Pulmonary emboli result in two main pathophysiologic consequences
A
  • Occlusion of the large pulmonary arteries is almost always caused by…
    • Embolic blood clots from the deep venous circulation of the lower extremities, pelvic veins, or large veins cannulated by catheters
  • Large-vessel in situ thromboses
    • Rare and develop only in the presence of pulmonary hypertension, pulmonary atherosclerosis, and heart failure
  • Pulmonary emboli result in two main pathophysiologic consequences
    • Respiratory compromise due to the nonperfused but ventilated alveoli
    • Hemodynamic compromise due to increased resistance to pulmonary blood flow resulting in pulmonary hypertension and acute rightsided heart failure
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16
Q

Pulmonary embolism

  • The morphologic consequences of embolic occlusion of the pulmonary arteries depend on…
  • Large emboli may…
  • Sudden death…
  • Death may also be caused by…
  • Smaller emboli can…
  • Of all infarcts
A
  • The morphologic consequences of embolic occlusion of the pulmonary arteries depend on…
    • The size of the emboli
    • The general state of the circulation
  • Large emboli may…
    • Impact in the main pulmonary artery or its major branches
    • Lodge at the bifurcation as a saddle embolus
  • Sudden death…
    • Often ensues because of the blockage of blood flow through the lungs
  • Death may also be caused by…
    • Right sided acute core pulmonale
  • Smaller emboli can…
    • Travel into the more peripheral vessels, where they may cause infarction
  • Of all infarcts
    • About ¾ affect the lower lobes
    • In more than half, multiple lesions occur
    • They vary in size from barely visible to massive involvement of large parts of an entire lobe
    • Typically, they are wedge shaped with the apex pointing toward the hilum of the lung
17
Q

Pulmonary embolism

  • In many cases, an occluded vessel can be identified near…
  • Infarcts in early stages
  • Fibrous replacement eventually results in…
  • Histologically, ischemic necrosis of the lung parenchyma affects…
  • In patients with adequate cardiovascular function, the bronchial arterial supply…
  • Under these circumstances,…
  • Hemorrhage is distinguished from infarct by…
  • The hallmark
  • Resolution of this process results in…
A
  • In many cases, an occluded vessel can be identified near…
    • The apex of the infarct
  • Infarcts in early stages
    • Hemorrhagic and appear as raised, red-blue areas
    • Become pale and eventually red-brown as hemosiderin is produced
  • Fibrous replacement eventually results in…
    • A contracted scar
  • Histologically, ischemic necrosis of the lung parenchyma affects…
    • The alveolar septae, airways, and blood vessels
  • In patients with adequate cardiovascular function, the bronchial arterial supply…
    • Can often sustain the lung parenchyma despite obstruction of the pulmonary arterial system
  • Under these circumstances,…
    • Hemorrhages may occur, but there is no infarction of the underlying lung parenchyma
  • Hemorrhage is distinguished from infarct by…
    • The preservation of the pulmonary parenchyma
  • The hallmark
    • Airspace filling with red blood cells and hemosiderin-laden macrophages
  • Resolution of this process results in…
    • Reconstitution of the preexisting lung architecture
18
Q

Pulmonary hypertension

  • A variety of vascular lesions occur in pulmonary hypertension
  • Several histologic appearances that have diagnostic and prognostic implications
  • The vessel changes can involve…
  • In the most severe cases,…
  • The arterioles and small arteries (40 to 300 μm in diameter)
  • These changes are present…
  • One extreme in the spectrum of pathologic changes, present most prominently in primary pulmonary hypertension or congenital heart disease with left-to-right shunts
  • Biopsy of the lung may be done in some cases to…
A
  • A variety of vascular lesions occur in pulmonary hypertension
    • Not always specific
    • Frequently overlap between primary (idiopathic; IPAH) and secondary forms
  • Several histologic appearances that have diagnostic and prognostic implications
    • The presence of many organizing or recanalized thrombi favors recurrent pulmonary emboli as the cause
    • The coexistence of diffuse pulmonary fibrosis, or severe emphysema and chronic bronchitis, points to chronic hypoxia as the initiating event
  • The vessel changes can involve…
    • The entire arterial tree, from the main pulmonary arteries down to the arterioles
  • In the most severe cases,…
    • Atheromatous deposits form in the pulmonary artery and its major branches
    • Resembles (but being lesser in degree than) systemic atherosclerosis
  • The arterioles and small arteries (40 to 300 μm in diameter)
    • Most prominently affected, with striking increases in the muscular thickness of the media (medial hypertrophy) and intimal fibrosis, sometimes narrowing the lumina to pinpoint channels
  • These changes are present…
    • In all forms of pulmonary hypertension but are best developed in the primary (idiopathic; IPAH) form
  • One extreme in the spectrum of pathologic changes, present most prominently in primary pulmonary hypertension or congenital heart disease with left-to-right shunts
    • Plexogenic pulmonary arteriopathy, so called because a tuft of capillary formations is present, producing a network, or web, that spans the lumens of dilated thin-walled, small arteries
  • Biopsy of the lung may be done in some cases to…
    • Grade the degree of pulmonary hypertensive vascular abnormalities and thereby aid therapeutic decision making
    • Especially in congenital heart disease, in which severe secondary pulmonary vascular changes may preclude surgical repair of the underlying cardiac anomaly
19
Q

Nomenclature and classification:
Pulmonary arterial hypertension (PAH)

  • Two types
  • Associated with…
  • Associated with significant venous or capillary involvement
A
  • Two types
    • Sporadic (idiopathic) (IPAH)
    • Familial (FPAH)
  • Associated with…
    • Collagen vascular disease
    • Congenital systemic-to-pulmonary shunts
    • Portal hypertension
    • HIV infection
    • Drugs and toxins
    • Other
  • Associated with significant venous or capillary involvement
    • Pulmonary venoocclusive disease
    • Pulmonary capillary hemangiomatosis
    • Persistent pulmonary hypertension of the newborn
20
Q

Nomenclature and classification

  • Pulmonary venous hypertension
  • Pulmonary hypertension associated with hypoxia
  • Pulmonary hypertension due to chronic thrombotic and/or embolic disease
  • Miscellaneous
A
  • Pulmonary venous hypertension
    • Left-sided atrial or ventricular heart disease
    • Left-sided valvular heart disease
  • Pulmonary hypertension associated with hypoxia
    • Chronic obstructive pulmonary disease
    • Interstitial lung disease
    • Sleep-disordered breathing
    • Alveolar hypoventilation disorders
    • Chronic exposure to high altitude
  • Pulmonary hypertension due to chronic thrombotic and/or embolic disease
    • Thromboembolic obstruction of proximal pulmonary arteries
    • Thromboembolic obstruction of distal pulmonary arteries
  • Miscellaneous
    • Sarcoidosis
    • Histiocytosis X
    • Lymphangiomatosis
    • Compression of pulmonary vessels