Diseases of respiratory

system
Chronic Obstructive Pulmonary Diseases
Chronic Bronchitis
Emphysema
Acute Bacterial Pneumonias
Primary Bronchogenic Carcinoma
 Structure of respiratory system
• Review
– Nose
– Pharynx
– Larynx
– Trachea
– Bronchi
– Bronchioles
– Alveolar ducts
– Alveoli
 COPD
Chronic Obstructive Pulmonary
Diseases
A group of diseases with objective evidence
of persisting and irreversible air flow
obstruction.
Chronic bronchitis; bronchiectasis; asthma;
emphysema
Chronic
Bronchiti
s
• Definition
– A persistent productive cough for at least
3 consecutive months in at least 2
consecutive years.
– Main symptoms:
• Cough
• Sputum
• Wheezing
• Etiology
– Chronic irritation by inhaled substances
• Cigarette smoking, air pollution.
– It is common among cigarette smokers and urban
dwellers in smog-ridden cities, especially men of
more than 40 years old.
– These predispose to infection of respiratory
epithelia
– Microbiologic infections
• Bacteria: Haemophilus influenzae,
streptococcus pneumoniae
• Viruses: respiratory syncytial virus,
adenovirus.
 Recall of the histology of bronchus
• Epithelium: ciliated
columnar epithelial
cells with a small
number of goblet cells.
• Two types of bronchial
glands.
– One secrets mucus
– the other secrets serum
• Pathogenesis
Cigarette smoking or other air pollutants
→hypersecretion of bronchial mucus glands
→mucin-secreting goblet cells ↑
maintaining inflammation
fibrosis
→narrowing of bronchioles and coexistent
emphysema.
 Morphology
• Grossly
– the mucosa is usually hyperemia and swollen
– mucus or mucopurulent secretions
• Histologically
– Injury and repair of mucosa epithelium
• Columnar epithelia: degeneration,
necrosis, desquamation, cilia lost.
• Squamous metaplasia
–changes of glands (feature)
–Mucous glands: hyperplasia and
hypertrophy (the larger glands lead to the
thickening of bronchial walls and narrowing
of bronchial lumina )
–Goblet cells: proliferation.
–Serous glands: begin secreting mucus
– Lesion of bronchial wall
• Inflammatory infiltrate: mononuclear
cells in the absence of infection,
admixed neutrophils when microbe
infects.
• Proliferation of smooth muscle,
degeneration, calcification and
ossification of cartilage.
Pulmona
ry
emphyse
ma
• Definition
– Abnormal permanent enlargement of the
airspaces distal to the terminal
bronchioles accompanied by destruction
of their walls, without obvious fibrosis.
• respiratory bronchiole
• alveolar duct
• alveolus
• Etiology
– heavy cigarette smoking
– Small airway infection: chronic bronchitis
– Air pollution
– Pneumoconiosis
• Incidence
– common, approximately 50% of middle to late
adults
• Pathogenesis
– Chronic airflow obstruction:
• Obstruction of the small airways (often occurs in
chronic bronchitis ) induces increased expiratory
effort to overcome the airways resistance,
compressing the small airways, which lack
cartilaginous support.
• Thus residual air in acini increases to induce the
enlargement of acini.
recall of lung’s histology

acinus----the part of the

lung distal to the
terminal bronchiole
(including respiratory
bronchiole, alveolar duct and
alveolus ).
lobule----a cluster of 3
to 5 acini
• Type of Emphysema
– Alveolar emphysema
• Centriacinar emphysema
• Periacinar/paraseptal emphysema
• Panacinar emphysema

– Interstitial emphysema
• Accumulation of air in the
interstitial tissues
–Other types
•Paracicatrical emphysema: near
lung scarring area
•Bullous emphysema: with bulla
(emphysema space more than 1cm in
diameter)
•Senile emphysema: increased
volume of lung often found in
aged
•Compensatory emphysema: alveolar
dilatation that follows collapse
or loss of lung substance
　　　　　　　　　左肺下叶大泡性肺气肿
　　　　　　　在全腺泡型肺气肿基础上，有直径超过 1cm 的大囊泡
bullous emphysema
 Centriacinar emphysema
• the involvement of the lobule lies in the
central or proximal parts of the acini:
– respiratory bronchioles are affected, while
distal airspaces are spared.
– both emphysematous and normal airspaces
exist within the same acinus and lobule.
Periacinar/Paraseptal emphysema

• Distal alveolar sacs and alveolar ducts are

predominately involvement.
• The proximal portion of the acinus is normal
 Panacinar emphysema
• The acini are uniformly enlarged from the
respiratory bronchiole to the terminal
alveoli.
中央型和全腺泡型
度呼
狭吸 　
窄细 　
支　　
气　
管腺
呈
囊泡
状中
扩央
张型
，肺
伴
行气
肺肿
动
脉
管
壁
增
厚
，
管
腔
极
度呼 　
狭吸 　
窄细 　
支　
气　
管腺
呈泡
囊
状中
扩央
张型
，肺
伴气
行
肺肿
动
脉
管
壁
增
厚
，
管
腔
极
panacinar (panlobular) emphysema
　　　　　　　　　　全腺泡型肺气肿
　末梢呼吸道弥漫性扩张，呈小囊状遍布于肺小叶内
 Morphology
• Grossly
– Pale
– voluminous (so called barrel-shaped)
– emphysematous bullae may be grossly visible
in extreme cases
　　　　　　　　　 emphysematous bullae
• Microscopic features
– Abnormal enlargement of airspaces.
– Thinning and destruction of septal wall,
sometimes bullae form.
– The number of septal capillaries is diminished
because of the compression. Fibrous
thickness of intima of pulmonary small arteries
– Accompanying bronchiolitis
emphysema: increased residual capacity
• Clinical course:
– Dyspnea– the first symptom, much more
severe during expiration.
– Cough-- mucoid or purulent sputum and
wheezing sounds
– Weight loss
– Pulmonary function reduces
– Barrel-chested
 Barrel chest
Because of increased posteroanterior
diameter of chest
 Cause of death
• Respiratory acidosis and coma
• Right-sided heart failure
• Massive collapse of lungs secondary to
pneumothorax.
pneumonia
 Definition
• Pneumonia is usually due to infection
affecting distal airways,especially
alveoli,with the formation of inflammatory
exudates.
 Classification
• Etiological agent
– Bacterial
– Viral
– Fungal
– Others: mycoplasma
• Other criteria
– Clinical circumstances
– Host reaction
– Anatomical pattern
 Bacterial Pneumonias
Definition
Bacterial pneumonia is a generic term that
refers to inflammation and consolidation
(solidification) of the lung parenchyma evoked by
bacteria invasion.
•Consolidation — A process of becoming solid
and firm because air spaces are filled with
exudate.
• classification:
– Lobar pneumonia
– Lobular pneumonia (Bronchopneumonia)
 Lobar pneumonia
• Lobar pneumonia is an acute bacterial
infection of a large portion of a lobe or an
entire lobe.
• Etiology
– 90%~95% of lobar pneumonias are caused by
pneumococi(Streptococcus pneumoniae).
– Klebsiella pneumoniae, staphylococci,
streptococci, H. Influenza are occasional
cause.
• Incidence: It occurs in typically otherwise
healthy adults between 20 and 50 year of
age.
 Morphology

• Four stages:
– Congestion
– Red hepatization
– gray hepatization
– Resolution
 The stage of congestion
• Macroscopically
– the affected lobe(s) is(are) heavy, boggy, red.
Red, edematous
 The stage of congestion
• Histologically
– Alveolus walls vascular congestion and
dilation
– alveoli contain proteinaceous fluid, scattered
neutrophils and numerous bacteria
 The stage of red hepatization
• Macroscopically
– the lung lobe is distinctly red, firm and airless
with liver-like consistency.
 Confluent
consolidation of
all or the majority
of a lobe of the
lung

• Red
• Solid
• Consistency resembling fresh liver
 The stage of red hepatization
• Histologically
– Alveolar wall vascular congestion becomes
more evident
– the alveolar spaces are packed with red cells,
fibrin and neutrophils.
– the pleura usually demonstrates a fibrinous or
fibrinopurulent exudate (plueritis).
 The stage of gray hepatization
• Macroscopically
– the lung is dry 、 gray 、 firm and liver-like in
consistency.
gray hepatization in
the lower lobe of the
lung
• Dry Pale Firm
 The stage of gray hepatization
• Histologically
– Alveolus wall vascular congestion diminishes
– the fibrinous exudate, neutrophils persist and
increase within alveoli
– the number of RBC relatively reduces
(disintegration)
– The pleuritis is most intense.
　　　　　　图注：大叶性肺炎
灰色肝变期，肺泡腔完整，肺泡隔内毛细血管明显扩张充
血。腔内渗出的纤维素网络了大量的中性粒细胞。 　　
　
灰色肝样变期 ( 低倍 )
灰色肝样变期 ( 高倍 )
 The stage of resolution
• Macroscopically
– the lung is edematous (boggy and wet).
• Histologically
– Alveolus wall vascular congestion reoccurs
– Exudates within the alveoli are enzymatically digested
and either reabsorbed or expectorated, leaving the
basic architecture intact.
– The pleural reaction may similarly resolve or undergo
organization, leaving fibrous thickening or permanent
adhesions.
 Clinical Course
• The onset is abrupt, with high fever and an
episode of a severe shaking chill
• Chest pain
• A cough productive of rusty-colored purulent
sputum (when?)
• Dyspnea, most severe during the second
stage of red hepatization.
 Complications
• Suppurative pleuritis and empyema
• Pulmonary carnification: organization of
the exudate
• Bacteremic dissemination: may cause
septicemia, pyemia or infective shock
• Lung abscess
Pulmonary
carnification
 Lobular pneumonia
• Lobular pneumonia has a characteristic
patchy distribution, centered on inflamed
bronchioles and bronchi with subsequent
spread to surrounding alveoli. Because
lobule is made of bronchiole and
surrounding alveoli, we also call lobular
pneumonia bronchopneumonia.
 Etiology
• The common agents are staphylococci,
streptococci, pneumococci, Haemophillus
influenza, Pseudomonas aeruginosa, etc.
 Incidence
• These people are vulnerable because of
lower defensive mechanism.
– Infants
• With whooping cough, measles.
– The old age
• With influenza, chronic bronchitis, etc.
– People suffering from chronic debilitating
illness or immunosuppression
 Morphology
• Macroscopically
– foci of inflammatory consolidation are distributed in
patches throughout one or several lobes, most frequently
bilateral and basal.
– The lesions are gray-red to yellow, varying in size up to
0.5 to 1 cm in diameter, poorly delimited in margin.
– in severe cases, they may confluent.
– The surrounding areas of consolidation is usually
hyperemia and edematous, but the large intervening
areas are generally normal.
Bronchopneumonia
 Morphology
• Histologically
– focal suppurative exudate fills the
bronchi 、 bronchioles and adjacent alveolar
spaces.
– The centers of suppurative lesions lie in
bronchi and bronchioles.
 Clinical course
• The onset is insidious, often overshadowed
by the predisposing condition.
• Low-grade fever
• Cough with purulent sputum
• Course is irregular, lying on the treatment
and patient’s condition.
• Most can be cured.
 Complications
• Respiratory failure
• Heart failure
• Pyemia
• Abscess
小叶性肺炎并发肺脓肿
Primary Lung Tumor
• Primary lung tumor— the tumor arises from
the lung tissue
– 95% from the bronchial epithelium –
bronchogenic carcinomas
– 5% are miscellaneous
Bronchogenic Carcinoma
• Incidence:
– The number one cause of cancer-related deaths
– about 1/3 of cancer deaths in men
– the leading cause of cancer deaths in women
– The peak incidence of lung cancer occurs
between ages 40 and 70 years.
• Etiology and Pathogenesis:
– Cigarette smoking
– air pollution
– Genetic changes
 Classification
• Macroscopic Classification
– Central pattern
• the cancers tend to arise centrally in major bronchi.
– Peripheral pattern
• the cancers are usually peripherally located.
– Diffuse pattern
• the cancers are multiple diffuse nodules that may
coalesce to produce pneumonia-like consolidation.
Central pattern
Peripheral pattern
Diffuse pattern
• Histologic Classification
– Non-Small Cell Carcinoma (NSCLC)
• Squamous cell carcinoma
• Adenocarcinoma
• Large cell undiffereniated carcinoma
– Small Cell Lung Carcinoma (SCLC)
– Combined Patterns
• Several common features:
– The majority arise in the lining epithelium of
major bronchi, usually close to the hilus of the
lung.
– All patterns are associated with cigarette
smoking; the strongest association is with
squamous cell and small cell carcinoma.
– All patterns are aggressive
 Squamous cell carcinoma
• Incidence:
– the most common histologic pattern
• 30-50% of all lung cancers
• 80-85% of the central pattern
– more common in men than in women
 Squamous cell carcinoma
• lMorphology:
– Macroscopically :
• well-defined tumor mass central in major bronchi
– Histologically
hyperplasia→
squamous mateplasia→
atypical hyperplasia of squamous cells→
carcinoma in situ→ squamous cell carcinoma
 Squamous cell carcinoma
– Histologically
• squamous cell carcinoma
– Well-differentiated squamous cell
carcinomas show keratin pearls and
intercellular bridges.
– Poorly-differentiated squamous cell
carcinomas have only minimal residual
squamous cell features.
• Metastasis:
– squamous cell carcinoma are prone to
metastasize by lymph
– local hilar lymph nodes are usually affected
 Small cell lung carcinomas(SCLC)
• Incidence:
– relatively common (20-25%), and also more
common in men than in women.
• Morphology:
– Macroscopically
• pale, gray, centrally located masses with extension into
the lung parenchyma and early involvement of the hilar
and mediastinal lymph nodes.
 Small cell lung carcinomas(SCLC)

• Histologically:
– “oat cell”
• small 、 dark 、 round-to-oval 、 spindle-shaped or
lymphocyte-like cancer cells
• with scant cytoplasm
• with hyperchromatic nuclei
• mitoses are numerous
SCLC
• Metastasis:
– They tend to early metastasize by blood
stream
– SCLCs have invariably spread by the time
they are first detected, even if the primary
tumor appears small and localized.
– They are very sensitive to chemotherapy but
invariably recur.
 Traits of SCLC

• SCLCs are rapidly growing lesions that

tend to infiltrate widely and metastasize
early in their course and so are rarely
resectable.
• They are derived from neuroendocrine
cells of the lung, which are characterized
by secreting a host of polypeptide
hormones including ACTH, calcitonin,
gastrin-releasing peptide, and so on.
Hence, these tumors are associated with a
variety of paraneoplastic syndromes.
 Clinical course
• often silent and insidious lesions that have
spread so as to be unresectable before
they produce obvious symptoms.
• Chronic cough and expectoration may be
the common symptoms in the early stage.
 Clinical course
• Vena Caval Syndrome:
– Clinical signs:
• Puffiness of the head and neck;
• Varicosity of cervical and thoracic veins.
– Reasons:
• The tumors (usually in the upper lobes) compress or
infiltrate the superior vena cava to cause venous
congestion.
• Horner’s Syndrome:
– Clinical signs:
• Ipsilateral enophthalmos
• Ipsilateral Ptosis
• Miosis
• Anhidrosis of thoracic skin
– Reasons:
• The apical neoplasms (sometimes so called Pancoast’s
tumors) compress or invade the cervical sympathetic
plexus.
• other symptoms:
– The severe pain or atrophy of the muscles in
the distribution of the ulnar nerve.
• Reason:
– The apical neoplasms compress or invade the
brachial plexus.
Paraneoplastic Syndrome(usually in SCLCs)
• Signs: • Reasons:
Hypercalcemia --------------------------------- Secretion of a parathyroid hormone-related
(often with squamous cell carcinomas) peptide
Hematologic manifestations
(often with adenocarcinomas)
including migratory thrombophlebitis,
nonbacterial endocarditis and DIC
Cushing’s syndrome--------------------------- increased production of ACTH
SIADH (hypertension, puffiness)----------- inappropriate secretion of antidiuretin (ADH)
Neuromuscular syndrome including
myasthenic syndrome, neuropathy,
polymyositis
Clubbing of the fingers
Hypertrophic pulmonary osteoarthropathy
• Symptoms emanating from metastases
– Mental or neurologic changes
– Hepatomegaly
– Bones pain
Attention: when hoarseness 、 chest
pain 、 superior vena caval
syndrome 、 pericardial or pleural effusion 、 or
persistent segmental atelectasis makes its
appearance, the prognosis is grim.