The Lung
1.Pneumonia
2.COPD
3.Pneumoconiosis
4.Lung vessels diseases
5.Chronic cor pulmonale
6. Lung cancer
7.Tuberculosis
Pathology Department, Zhejiang University School of Medicine,
Zhu keqing 竺可青，zhukeqing@yahoo.com, 2007-11-27
What is the diagnosis?
1. Pneumonia
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Lobar pneumonia
Lobular pneumonia
Legionella pneumonia
Viral pneumonia
Mycoplasmal pneumonia
Lobar pneumonia
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4 stages
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Lobar pneumonia is an acute bacterial infection resulting in
fibrinosuppurative consolidation of a large portion of a lobe or of an
entire lobe.
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Moreover, the same organisms may produce bronchopneumonia in
one patient, whereas in the more vulnerable individual, a full-blown
lobar involvement develops.
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Most important from the clinical standpoint are identification of
the causative agent and determination of the extent of disease.
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In lobar pneumonia, four stages of the inflammatory response have classically been
described: congestion, red hepatization, gray hepatization, and resolution.
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Present-day effective antibiotic therapy frequently slows or halts the progression.
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In the first stage of congestion, the lung is heavy, boggy, and red. It is characterized
by vascular engorgement, intra-alveolar fluid with few neutrophils, and often the
presence of numerous bacteria. 充血水肿期
The stage of red hepatization that follows is characterized by massive confluent
exudation with red cells (congestion), neutrophils, and fibrin filling the alveolar spaces.
On gross examination, the lobe now appears distinctly red, firm, and airless, with a
liver-like consistency, hence the term hepatization. 红色肝样变期
The stage of gray hepatization follows with progressive disintegration of red cells
and the persistence of a fibrinosuppurative exudate, giving the gross appearance of a
grayish brown, dry surface. 灰色肝样变期
In the final stage of resolution, the consolidated exudate within the alveolar spaces
undergoes progressive enzymatic digestion to produce a granular, semifluid, debris
that is resorbed, ingested by macrophages, coughed up, or organized by fibroblasts
growing into it.溶解消散期
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Pneumococcal pneumonia
A, Acute pneumonia. The congested septal capillaries and extensive neutrophil exudation into alveoli
corresponds to early red hepatization. Fibrin nets have not yet formed.
B, Early organization of intra-alveolar exudate, seen in areas to be streaming through the pores of
Kohn (arrow).
C, Advanced organizing pneumonia (corresponding to gray hepatization), featuring transformation of
exudates to fibromyxoid masses richly infiltrated by macrophages and fibroblasts.
Lobar pneumonia-gray hepatization
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Complications of pneumonia include
(1) tissue destruction and necrosis, causing abscess formation
(particularly common with type 3 pneumococci or Klebsiella
infections);
(2) spread of infection to the pleural cavity, causing the intrapleural
fibrinosuppurative reaction known as empyema;
(3) organization of the exudate, which may convert a portion of the
lung into solid tissue; pulmonary carnification
(4) bacteremic dissemination to the heart valves, pericardium,
brain, kidneys, spleen, or joints, causing metastatic abscesses,
endocarditis, meningitis, or suppurative arthritis.
Bronchopneumonia
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Foci of bronchopneumonia are consolidated areas of acute
suppurative inflammation.
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The consolidation may be patchy through one lobe but is more often
multilobar and frequently bilateral and basal because of the
tendency of secretions to gravitate into the lower lobes.
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Well-developed lesions are usually 3 to 4 cm in diameter, slightly
elevated, dry, granular, gray-red to yellow, and poorly delimited at
their margins.
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Histologically, the reaction usually elicits a suppurative, neutrophilrich exudate that fills the bronchi, bronchioles, and adjacent alveolar
spaces.
Comparison of bronchopneumonia and lobar pneumonia
Clinical Course
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The major symptoms of community-acquired acute pneumonia are
abrupt onset of high fever, shaking chills, and cough productive of
mucopurulent sputum; occasional patients may have hemoptysis.
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When fibrinosuppurative pleuritis is present, it is accompanied by
pleuritic pain and pleural friction rub.
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The characteristic radiologic appearance of lobar pneumonia is that
of a radio-opaque, usually well-circumscribed lobe, whereas
bronchopneumonia shows focal opacities.
Legionella pneumonia
• Legionella pneumophilia
ATYPICAL (VIRAL AND MYCOPLASMAL) PNEUMONIAS
• Viral pneumonia
• Mycoplasmal pneumonia
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The term "primary atypical pneumonia" was initially applied to an acute
febrile respiratory disease characterized by patchy inflammatory changes in
the lungs, largely confined to the alveolar septa and pulmonary
interstitium.
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The term "atypical" denotes the moderate amount of sputum, no physical
findings of consolidation, only moderate elevation of white cell count, and
lack of alveolar exudate.
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The pneumonitis is caused by a variety of organisms, the most common
being Mycoplasma pneumoniae.
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Other etiologic agents are viruses, including influenza virus types A and B,
the respiratory syncytial viruses, adenovirus, rhinoviruses, rubeola, and
varicella viruses; Chlamydia pneumoniae; and Coxiella burnetti (Q fever).
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The histologic pattern depends on the severity of the disease.
Predominant is the interstitial nature of the inflammatory
reaction, virtually localized within the walls of the alveoli.
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The alveolar septa are widened and edematous and usually have a
mononuclear inflammatory infiltrate of lymphocytes, histiocytes, and
occasionally plasma cells. In acute cases, neutrophils may also be
present.
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The alveoli may be free from exudate, but in many patients, there is
intra-alveolar proteinaceous material, a cellular exudate, and
characteristically pink hyaline membranes lining the alveolar walls.
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病毒包涵体
Usual interstitial pneumonia.
The fibrosis, which varies in intensity, is more pronounced in the
subpleural region.
Usual interstitial pneumonia.
Fibroblastic focus with fibers running parallel to surface and bluish
myxoid extracellular matrix.
Pyemic lung abscess in the center of section with complete destruction
of underlying parenchyma within the focus of involvement
2. COPD
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Chronic bronchitis
Pulmonary emphysema
Bronchial asthma
Bronchiectasis
Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Chronic bronchitis
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Bronchus
Mucous gland hyperplasia, hypersecretion
Tobacco smoke, air pollutants
Cough, sputum production
Bronchiectasis
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Bronchus
Airway dilation and scarring
Persistent or severe infections
Cough, purulent sputum, fever
Asthma
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Bronchus
Smooth muscle hyperplasia, excess mucus, inflammation
Immunologic or undefined causes
Episodic wheezing, cough, dyspnea
Emphysema
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Acinus
Airspace enlargement; wall destruction
Tobacco smoke
Dyspnea
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Clinical Term
Anatomic Site
Major Pathologic Changes
Etiology
Signs/Symptoms
2.1 Chronic bronchitis
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Chronic bronchitis, so common among habitual smokers and
inhabitants of smog-laden cities, is not nearly as trivial as was once
thought.
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When persistent for years, it may (1) progress to chronic obstructive
airway disease, (2) lead to cor pulmonale and heart failure, or (3)
cause atypical metaplasia and dysplasia of the respiratory
epithelium, providing a rich soil for cancerous transformation.
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Chronic bronchitis per se is defined clinically. It is present in any
patient who has persistent cough with sputum production for at least
3 months in at least 2 consecutive years, in the absence of any
other identifiable cause.
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In simple chronic bronchitis, patients have a productive cough but
no physiologic evidence of airflow obstruction.
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Some individuals may demonstrate hyperreactive airways with
intermittent bronchospasm and wheezing. This condition is called
chronic asthmatic bronchitis.
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Finally, some patients, especially heavy smokers, develop chronic
airflow obstruction, usually with evidence of associated emphysema,
and are classified as showing obstructive chronic bronchitis.
Morphology
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Grossly, there may be hyperemia, swelling, and edema of the mucous
membranes, frequently accompanied by excessive mucinous to
mucopurulent secretions layering the epithelial surfaces.
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The characteristic histologic features of chronic bronchitis are chronic
inflammation of the airways (predominantly lymphocytes) and enlargement
of the mucus-secreting glands of the trachea and bronchi.
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This increase can be assessed by the ratio of the thickness of the mucous
gland layer to the thickness of the wall between the epithelium and the
cartilage (Reid index). The Reid index (normally 0.4) is increased in chronic
bronchitis, usually in proportion to the severity and duration of the disease.
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The bronchial epithelium may exhibit squamous metaplasia and dysplasia.
There is marked narrowing of bronchioles caused by goblet cell metaplasia,
mucus plugging, inflammation, and fibrosis.
Clinical Features
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The cardinal symptom of chronic bronchitis is a persistent cough productive
of sputum. For many years, no other respiratory functional impairment is
present, but eventually, dyspnea on exertion develops.
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With the passage of time, and usually with continued smoking, other
elements of COPD may appear, including hypercapnia高碳酸血症,
hypoxemia, and mild cyanosis.
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Differentiation of pure chronic bronchitis from that associated with
emphysema can be made in the classic case, but, as has been mentioned,
many patients with COPD have both conditions.
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Long-standing severe chronic bronchitis commonly leads to cor pulmonale
with cardiac failure.
2.2 Pulmonary emphysema
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Emphysema is a condition of the lung characterized by abnormal
permanent enlargement of the airspaces distal to the terminal
bronchiole, accompanied by destruction of their walls and without
obvious fibrosis.
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In contrast, the enlargement of airspaces unaccompanied by
destruction is termed "overinflation," for example, the distention of
airspaces that occurs in the remaining lung after unilateral
pneumonectomy.
Types of Emphysema
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Although the term "emphysema" is sometimes loosely applied to
diverse conditions, there are four major types: (1) centriacinar, (2)
panacinar, (3) paraseptal, and (4) irregular.
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Only the first two cause clinically significant airflow obstruction.
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Centriacinar emphysema is far more common than the panacinar
form, constituting more than 95% of cases.
Pathogenesis of emphysema.
The protease-antiprotease imbalance and oxidant-antioxidant imbalance are additive in their
effects and contribute to tissue damage. α1-antitrypsin (α1-AT) deficiency can be either
congenital or "functional" as a result of oxidative inactivation.
Thus, emphysema is seen to result from the destructive effect of high protease activity in
subjects with low antiprotease activity.
A, Diagram of normal structures within the acinus, the fundamental unit of the lung. A terminal
bronchiole (not shown) is immediately proximal to the respiratory bronchiole.
B, Centriacinar emphysema with dilation that initially affects the respiratory bronchioles. C, Panacinar
emphysema with initial distention of the peripheral structures (i.e., the alveolus and alveolar duct); the
disease later extends to affect the respiratory bronchioles.
Centriacinar emphysema.
Central areas show marked emphysematous damage (E), surrounded
by relatively spared alveolar spaces.
Panacinar emphysema involving the entire pulmonary architecture
Bullous Emphysema
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Bullous emphysema refers merely to any form of emphysema that produces
large subpleural blebs or bullae (spaces more than 2 cm in diameter in the
distended state).
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They represent localized accentuations of one of the four forms of
emphysema, are most often subpleural, and occur near the apex,
sometimes in relation to old tuberculous scarring.
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On occasion, rupture of the bullae may give rise to pneumothorax.
Bullous emphysema with large subpleural bullae
Interstitial Emphysema
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The entrance of air into the connective tissue stroma of the lung, mediastinum, or
subcutaneous tissue is designated interstitial emphysema.
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In most instances, alveolar tears in pulmonary emphysema provide the avenue of
entrance of air into the stroma of the lung, but rarely, a wound of the chest that allows
air to be sucked in or a fractured rib that punctures the lung substance may underlie
this disorder.
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Children with whooping cough and bronchitis, patients with obstruction to the airways
(by blood clots, tissue, or foreign bodies) or who are being artificially ventilated, and
individuals who suddenly inhale irritant gases provide classic examples.
Predominant Bronchitis
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Predominant Emphysema
Age (yr)
40-45
50-75
Dyspnea
Mild; late
Severe; early
Cough
Early; copious sputum
Late; scanty sputum
Infections
Common
Occasional
Respiratory insufficiency Repeated
Terminal
Cor pulmonale
Common
Rare; terminal
Airway resistance
Increased
Normal or slightly increased
Elastic recoil
Normal
Low
Chest radiograph
Prominent vessels; large heart
Hyperinflation; small heart
Appearance
Blue bloater
Pink puffer
2.3 Bronchial asthma
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Asthma is a chronic inflammatory disorder of the airways that causes
recurrent episodes of wheezing, breathlessness, chest tightness, and cough,
particularly at night and/or in the early morning.
It is thought that inflammation causes an increase in airway responsiveness
(bronchospasm) to a variety of stimuli. Some of these stimuli would have
little or no effect on nonasthmatics with normal airways.
Many cells play a role in the inflammatory response, in particular
eosinophils, mast cells, macrophages, T lymphocytes, neutrophils, and
epithelial cells.
2.3 Asthma
Airway remodeling
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Thickening of the basement membrane of the bronchial epithelium
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Edema and an inflammatory infiltrate in the bronchial walls, with a
prominence of eosinophils and mast cells
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An increase in size of the submucosal glands
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Hypertrophy of the bronchial wall muscle
2.4 Various forms of atelectasis in adults
2.5 Bronchiectasis
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Bronchiectasis is a disease characterized by permanent dilation of
bronchi and bronchioles caused by destruction of the muscle and
elastic tissue, resulting from or associated with chronic necrotizing
infections.
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To be considered bronchiectasis, the dilation should be permanent;
reversible bronchial dilation often accompanies viral and bacterial
pneumonia.
Morphology
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Bronchiectasis usually affects the lower lobes bilaterally, particularly
air passages that are vertical, and is most severe in the more distal
bronchi and bronchioles.
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The airways are dilated, sometimes up to four times normal
size.
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These dilations may produce long, tubelike enlargements
(cylindrical bronchiectasis) or, in other cases, may cause
fusiform or even sharply saccular distention (saccular
bronchiectasis).
Bronchiectasis in a patient with cystic fibrosis, who underwent lung transplantation
Bronchiectasis in a patient with cystic fibrosis, who underwent lung transplantation
3. Pneumoconiosis
• Silicosis
• Sarcoidosis
Major Categories of Chronic Interstitial Lung Disease
Fibrosing
• Usual interstitial pneumonia (idiopathic pulmonary fibrosis)
• Nonspecific interstitial pneumonia
• Cryptogenic organizing pneumonia
• Associated with collagen vascular diseases
• Pneumoconiosis尘肺
• Drug reactions
• Radiation pneumonitis
Granulomatous
• Sarcoidosis
• Hypersensitivity pneumonitis
EosinophilicSmoking-Related
• Desquamative interstitial pneumonia
• Respiratory bronchiolitis-associated interstitial lung disease
Other
• Pulmonary alveolar proteinosis
Progressive massive fibrosis superimposed on coal workers' pneumoconiosis
Silicosis
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Silicosis is a lung disease caused by inhalation of crystalline silicon
dioxide (silica).（5um）
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Currently the most prevalent chronic occupational disease in the
world, silicosis usually presents, after decades of exposure, as a
slowly progressing, nodular, fibrosing pneumoconiosis.
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Workers in a large number of occupations are at risk, especially
sandblasters and many mine workers.
Morphology
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Silicosis is characterized grossly in its early stages by tiny, barely palpable, discrete
pale to blackened (if coal dust is also present) nodules in the upper zones of the
lungs.
As the disease progresses, these nodules may coalesce into hard, collagenous
scars.
Histologically, the nodular lesions consist of concentric layers of hyalinized collagen
surrounded by a dense capsule of more condensed collagen.
Examination of the nodules by polarized microscopy reveals the birefringent silica
particles.
Advanced silicosis seen on transection of lung.
Scarring has contracted the upper lobe into a small dark mass (arrow).
Note the dense pleural thickening.
Several coalescent collagenous silicotic nodules
Large saddle embolus from the femoral vein lying
astride the main left and right pulmonary arteries
Hemorrhagic pulmonary infarct
4. Lung vessels diseases
• ARDS
• Chronic pulmonary hypertension
Diffuse alveolar damage (acute respiratory distress syndrome)
Vascular changes in pulmonary hypertension
5. Chronic cor pulmonale
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Cor pulmonale, as pulmonary HHD is frequently called, consists of
right ventricular hypertrophy, dilation, and potentially failure
secondary to pulmonary hypertension caused by disorders of the
lungs or pulmonary vasculature.
Chronic cor pulmonale
Disorders Predisposing to Cor Pulmonale
Diseases of the Pulmonary Parenchyma
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Chronic obstructive pulmonary disease
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Diffuse pulmonary interstitial fibrosis
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Pneumoconioses
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Cystic fibrosis
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Bronchiectasis
Diseases of the Pulmonary Vessels
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Recurrent pulmonary thromboembolism
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Primary pulmonary hypertension
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Extensive pulmonary arteritis (e.g., Wegener granulomatosis)
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Drug-, toxin-, or radiation-induced vascular obstruction
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Extensive pulmonary tumor microembolism
Disorders Affecting Chest Movement
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Kyphoscoliosis
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Marked obesity (pickwickian syndrome)
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Neuromuscular diseases
Disorders Inducing Pulmonary Arterial Constriction
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Metabolic acidosis
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Hypoxemia
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Chronic altitude sickness
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Obstruction to major airways
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Idiopathic alveolar hypoventilation
6. Lung cancer
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Squamous cell carcinoma (25% to 40%)
Adenocarcinoma (25% to 40%)
Small cell carcinoma (20% to 25%)
Large cell carcinoma (10% to 15%)
Cytologic diagnosis of lung cancer is often possible
Lung carcinoma
Histologic appearance of lung carcinoma
Numerous metastases from a renal cell carcinoma
Malignant mesothelioma
Malignant mesothelioma
Hilar mass that was considered radiographically to be carcinoma but proved
pathologically to be organized pneumonia.
7. Tucberulosis
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Mycobacterium tuberculosis
Tuberculin reaction
Tuberculous granuloma/tubercle
Caseous necrosis
基本病变
• 渗出：浆液纤维蛋白性炎
• 增生：结核结节
• 变质：干酪样坏死
The morphologic spectrum of tuberculosis
结局
转向愈合
• 吸收消散（吸收好转期）
• 纤维化钙化（硬结钙化期）
转向恶化
• 侵润进展（侵润进展期）
• 溶解播散（溶解播散期）
The natural history and spectrum of tuberculosis
Primary Tuberculosis
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In countries where bovine tuberculosis and infected milk have been
eliminated, primary tuberculosis almost always begins in the lungs.
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Typically, the inhaled bacilli implant in the distal airspaces of the lower part
of the upper lobe or the upper part of the lower lobe, usually close to
the pleura. As sensitization develops, a 1- to 1.5-cm area of gray-white
inflammatory consolidation emerges, known as the Ghon focus.
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In most cases, the center of this focus undergoes caseous necrosis.
Tubercle bacilli, either free or within phagocytes, drain to the regional nodes,
which also often caseate. This combination of parenchymal lung lesion and
nodal involvement is referred to as the Ghon complex.
Primary tuberculosis
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Primary tuberculosis is the form of disease that develops in a
previously unexposed, and therefore unsensitized, person.
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About 5% of newly infected people develop clinically significant
disease. The elderly and profoundly immunosuppressed persons
may lose their immunity to the tubercle bacillus and so may develop
primary tuberculosis more than once.
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With primary tuberculosis, the source of the organism is exogenous.
Primary pulmonary tuberculosis, Ghon complex.
The gray-white parenchymal focus is under the pleura in the lower part of the upper lobe.
Hilar lymph nodes with caseation are seen on the left.
结
局
1 痊愈
2 恶化
支气管播散
淋巴道播散
血道播散/ Systemic miliary tuberculosis
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Acute systemic miliary tuberculosis
Chronic systemic miliary tuberculosis
Acute pulmonary miliary tuberculosis
Chronic pulmonary miliary tuberculosis
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Miliary pulmonary disease occurs when organisms drain through
lymphatics into the lymphatic ducts, which empty into the venous
return to the right side of the heart and thence into the pulmonary
arteries.
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Individual lesions are either microscopic or small, visible (2-mm) foci
of yellow-white consolidation scattered through the lung
parenchyma (the word "miliary" is derived from the resemblance of
these foci to millet seeds).
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With progressive pulmonary tuberculosis, the pleural cavity is
invariably involved, and serous pleural effusions, tuberculous
empyema, or obliterative fibrous pleuritis may develop.
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Systemic miliary tuberculosis ensues when infective foci in the
lungs seed the pulmonary venous return to the heart; the organisms
subsequently disseminate through the systemic arterial system.
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Almost every organ in the body can be seeded. Lesions resemble
those in the lung.
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Miliary tuberculosis is most prominent in the liver, bone marrow,
spleen, adrenals, meninges, kidneys, fallopian tubes, and
epididymis.
Miliary tuberculosis of the spleen. The cut surface shows
numerous gray-white granulomas.
Secondary tuberculosis
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Secondary tuberculosis is the pattern of disease that arises in a
previously sensitized host.
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It may follow shortly after primary tuberculosis, but more commonly,
it arises from reactivation of dormant primary lesions many
decades after initial infection, particularly when host resistance is
weakened.
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It may also result from exogenous reinfection because of waning
of the protection afforded by the primary disease or because of a
large inoculum of virulent bacilli.
Secondary pulmonary tuberculosis
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Focal pulmonary tuberculosis
Infiltrative pulmonary tuberculosis
Chronic fibro-cavitative pulmonary tuberculosis
Caseous pneumonia
Tuberculoma
Tuberculous pleuritis
Posteroanterior radiograph of
a 54-year-old man with cough, fever, and a right upper lobe cavitary process
due to Mycobacterium tuberculosis infection
Secondary pulmonary tuberculosis
Extrapulmonary tuberculosis
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Intestinal tuberculosis 回盲部
Tuberculosis peritonitis
Tuberculosis meningitis
Tuberculosis of the kidney
Tuberculosis of the genital system
Tuberculosis of the bone/joint 冷脓肿
Tuberculosis of the lymph node
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Isolated-organ tuberculosis may appear in any of the organs or
tissues seeded hematogenously and may be the presenting
manifestation of tuberculosis.
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Organs that are typically involved include the meninges (tuberculous
meningitis), kidneys (renal tuberculosis), adrenals (formerly an
important cause of Addison disease), bones (osteomyelitis), and
fallopian tubes (salpingitis).
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When the vertebrae are affected, the disease is referred to as Pott's
disease. Paraspinal "cold" abscesses in these patients may track
along the tissue planes to present as an abdominal or pelvic mass.
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In years past, intestinal tuberculosis contracted by the drinking of
contaminated milk was fairly common as a primary focus of
tuberculosis.
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In developed countries today, intestinal tuberculosis is more often a
complication of protracted advanced secondary tuberculosis,
secondary to the swallowing of coughed-up infective material.
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Typically, the organisms are trapped in mucosal lymphoid
aggregations of the small and large bowel, which then undergo
inflammatory enlargement with ulceration of the overlying mucosa,
particularly in the ileum.
Mycobacterium avium infection in a patient with AIDS, showing
massive infection with acid-fast organisms
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