Transcript Pulmonary Infections

Pneumonia
Lecture on pathomorphology by Filonenko T.G.
Pathology of
respiratory system
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Pneumonia
Patterns of Lung disorders:
• Airway
– Bronchitis, Bronchiectasis, Bronchiolitis.
– Tumors / Cancer
• Parenchyma
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Infections
Pneumonia.
Lung abscess, TB
Hyaline membrane dis (HMD & ARDS)
Pneumoconiosis
Tumors / Cancer
• Pleura:
– Pleural effusion (TB)
– Tumors / Cancer
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Pneumonia
PNEUMONIAS
• Pneumonia is defined as acute
inflammation of the lung parenchyma
distal to the terminal bronchioles
which consist of the respiratory
bronchiole, alveolar ducts, alveolar
sacs and alveoli.
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Pneumonia
Pathogenesis of Pulmonary Infections
Step 1: Entry
• Aspiration (ie Pneumococcus)
• Inhalation (ie Mtb and viral pathogens)
• Inoculation (contaminated equipment)
• Colonization (in patients with COPD)
• Hematogenous spread (patients with
sepsis)
• Direct spread (adjacent abscess)
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Pneumonia
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PATHOGENESIS
Step 2: Failure of t defense mechanisms
Decreased resistance - General/immune
Virulent infection
Defective Clearing mechanism
– Depressed cough and glottic reflexes– Coma,
paralysis, sick.
– Impaired mucociliary transport– smoking, toxin
aspiration
– Impaired alveolar macrophage function
– Leucocyte dysfunctions.
– Low Alveolar defense - Immunodeficiency
– Pulmonary edema – Cardiac failure, emboli.
– Endobronchial obstruction – foreign body, tumors
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Pathogenesis:
Pathogenesis:
Pneumonia
Pneumonia Types:
Etiologic Types:
• Infective
– Viral
– Bacterial
– Fungal
– Tuberculosis
• Non Infective
– Toxins
– chemical
– Aspiration
Morphologic types:
• Lobar
• Broncho
• Interstitial
Duration:
• Acute
• Chronic
Clinical:
• Primary / secondary.
• Typical / Atypical
• Community / hospital
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Pneumonia
Lobar Pneumonia:
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whole lobe, exudation - consolidation
95% - Strep pneum.(Klebsiella in aged, alcoholics)
High fever, rusty sputum, Pleuritic chest pain.
Four stages: (*also in bronchopneumonia)
– Congestion – 1d – vasodilatation congestion
– Red Hepatization 2d - Exudation+RBC
– Gray Hepatizaiton 4d- neutro & Macrophages
– Resolution – 8d few macrophages, normal
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Grey Hepatization
Resolution
Pathogenesis of Pneumonia
Congestion
Red Hepatisation
Pneumonia
Lobar Pneumonia: Congestion
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Pneumonia
Lobar Pneumonia: Red hepat.
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Pneumonia
Lobar Pneumonia: Grey hepat.
This is a high-power
view of the fibrinous
exudate covering the
pleural surface. A few
macrophages are
present.
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Pneumonia
Lobar pneumonia
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Pneumonia
Lobar Pneumonia – Gray hep…
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Pneumonia
Bronchopneumonia (patchy)
• Extremes of age. (infancy and old age)
• Staph, Strep, Pneumo & H. influenza
• Patchy consolidation – not limited to lobes.
• Suppurative inflammation
• Usually bilateral
• Lower lobes common
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Pneumonia
Bronchopneumonia
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Pneumonia
Bronchopneumonia:
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Pneumonia
Broncho – Pneumonia - Lobar
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Extremes of age.
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Secondary.
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Both genders.
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Staph, Strep, H.infl. •
Patchy consolidation •
Around Small airway •
Not limited by
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anatomic boundaries.
Usually bilateral.
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Middle age – 20-50
Primary in a healthy
males common.
95% pneumoc (Klebs.)
Entire lobe consolidation
Diffuse
Limited by anatomic
boundaries.
Usually unilateral
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Broncho – Pneumonia - Lobar
Pneumonia
Interstitial / atypical Pneumonia
• Primary atypical pneumonia in the
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immunocompetant host (Mycoplasma or
Chlamydia)
Interstitial pneumonitis
• immunocompromised host : Pneumocystic carinii; CMV
• Immunocompetant host: Influenza A
• Gross features:
– Lungs are heavy but not firmly consolidated
• Microscopic features:
– Septal mononuclear infiltrate
– Alveolar air spaces either ‘empty’ or filled with
proteinaceous fluid with few or no inflammatory cells
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Pneumonia
Interstitial Pneumonia:
Lymphocyte
Infiltrate in
alveloar wall
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Pneumonia
Complications of Pneumonia
• Abscesses
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– Localized suppurative necrosis, Right side often in
aspiration.
– Staphylococcus; Klebsiella; Pneudomonas
Pleuritis / Pleural effusion.
– Inflammation of the pleura ( Streptococcus
pneumoniae)
– Blood rich exudate (esp. rickettsial diseases)
Empyema
– Pus in the pleural space.
Septicemia
Organisation (carnification)
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Pneumonia
Abscess formation
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Pneumonia
CHRONIC NONSPECIFIC DISEASES
OF LUNGS
(CNDL)
CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
(COPD)
CHRONIC RESTRICTIVE
PULMONARY DISEASE (CRPD)
A. Restriction due to chest wall
disorder
(Kyphoscoliosis,
1. Chronic Bronchitis
2. Bronchial Astma
Poliomyelitis, severe obesity, pleural
diseases)
3. Chronic Obstructive
B. Restriction due to interstitial
Emphysema
4. Bronchiectatic Disease and infiltrative diseases
(Pneumoconiosis, Immunologic lung
5. Chronic abscess
diseases, Idiopathic pulmonary fibrosis,
Sarcoidosis)
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Pneumonia
Patho- and morphogenetic
mechanisms of lungs
BRONCHITOGENIC
PNEUMONIOGENIC
PNEUMONITOGENIC
(Chronic Obstructive
(Chronic Nonobstructive (Chronic Intersitial
Pulmonary Diseases)
Pulmonary Diseases)
Pulmonary Diseases)
1. Chronic Diffuse
1. Chronic pneumonia
Bronchitis
2. Chronic abscess
2. Bronchial Astma
3. Chronic Diffuse
Obstructive Emphysema
4. Bronchiectatic
Disease
1. Idiopathic pulmonary
fibrosis
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Pneumonia
CHRONIC BRONCHITIS
Chronic bronchitis is present in any
patient who has persistent cough with
sputum production for at least 3 months in
at least 2 consecutive years.
Etiopathogenesis
Smoking
- Atmospheric pollution
- Occupation
- Infection
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- Familial and genetic factors
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Pneumonia
Pathologic changes
• Hypersecretion of mucus in the large airways, and
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is associated with hypertrophy of the submucosal
glands in the trachea and bronchi.
Increase in goblet cells of small airways – small
bronchi and bronchioles – leading to excessive
mucus production that contributes to airway
obstruction.
Squamous metaplasia with mucus plugging of the
lumen.
Clustering of pigmented alveolar macrophages.
Iinflammatory infiltration.
Fibrosis of bronchiolar wall.
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Pneumonia
Chronic bronchitis: increased numbers of chronic
inflammatory cells in the submucosa.
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Pneumonia
Outcomes and complications
- Pulmonary emphysema;
- Right heart failure and formation
of “cor pulmonale”;
- Atypical metaplasia and dysplasia
of the respiratory epithelium,
providing a possible soil for
cancerous transformation;
- Amyloidosis of kidneys;
- Development of Bronchiectasis.
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Pneumonia
BRONCHIECTASIS (BE)
BE is defined as abnormal and
irreversible dilatation of the bronchi
and bronchioles developing
secondary to inflammatory
weakening of the bronchial wall.
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Pneumonia
Etiopathogenesis of BE
Endobronchial obstruction by tumor, foreign
bodies, and compression by enlarged hilar lymph
nodes and post-inflammatory scarring, lung
fibrosis.
2.
Congenital or hereditary factors, including
congenital BE, cystic fibrosis, intralobar
sequestration of the lung states, and immune cilia
and Kartagener’s syndromes.
3.
Necrotizing pneumonias, most often caused
by tubercle bacillus, staphylococci or mixed
infections, measles may develop BE as secondary
complication.
1.
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Pneumonia
BE usually
affects distal bronchi
and bronchioles
beyond the segmental
bonchi. The lungs may
be involved diffusely or
segmentally.
The pleura is
usually fibrotic and
thickened with
adhesions to the chest
wall. Cut surface has
honey-combed
appearance.
The walls of
bronchi are thickened
and the lumen are
filled with mucus.
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Pneumonia
Classification of BE
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Cylindrical: long, tube-like
enlargements in 1 to 4 type
of bronchus.
Fusiform: having spindleshaped bronchial dilatation.
Saccular: having rounded
sac-like distention in 6-10
types of bronchus.
Varicous: having irregular
bronchial enlargements.
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Pneumonia
The histologic findings of BE
• An intense acute and
chronic
inflammatory
exudation within the walls
of dilated bronchi and
bronchioles. The mucosa
and wall is not clearly seen
because of the necrotizing
inflammation
with
destruction.
• Desquamation
of
the
lining
epithelium
and
extensive
areas
of
necrotizing ulceration.
• Squamous metaplasia of
the remaining epithelium
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Pneumonia
Outcomes and complications
1. Obstructive ventilatory insufficiency can lead
to marked dyspnea and cyanosis.
2. Pulmonary hemorrhage
3. Pulmonary abscess
4. Empyema of the pleura
5. Metastatic brain abscess
6. “Cor pulmonale” and chronic cardiacpulmonary insufficiency
7. Amyloidosis are less frequent complications of
BE.
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Pneumonia
EMPHYSEMA
The WHO has defined pulmonary
emphysema as combination of
permanent dilatation of air
spaces distal to the terminal
bronchioles and the destruction
of the walls of dilated air spaces.
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Pneumonia
Classification of Emphysema
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A. TRUE EMPHYSEMA
Centriacinar (centrilobular)
Panacinar (panlobular)
Paraseptal (distal acinar)
Irregular (para-cicatricial)
Mixed (unclassified)
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B. OVERINFLATION
Compensatory overinflation
Senile hyperinflation (aging lung, senile emphysema)
Obstructive overinflation (infantile lobar emphysema)
Unilateral translucent lung (Unilateral emphysema)
Interstitial emphysema (surgical emphysema)
Bullous emphysema
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Pneumonia
Centriacinar
(cenrolobular) emphysema
The distinctive feature of
this type is the pattern of
involvement of the lobules; the
central or proximal parts of the
acini, formed by respiratory
bronchioles, are affected, whereas
distal alveoli are spared.
The walls of the
emphysematous spaces often
contain large amount of black
pigment.
Moderate-to-severe degrees
of emphysema occur predominantly
in heavy smokers and coal workers’
pneumoconiosis , often in
association with chronic bronchitis. 39
Pneumonia
Panacinar emphysema
•Panacinar emphysema occurs with
loss of all portions of the acinus
from the respiratory bronchiole to
the alveoli. This pattern is typical for
alpha-1-antitrypsin deficiency.
•Panacinar emphysema produces
voluminous lungs, often overlapping
the heart and hiding it when the
anterior chest wall is removed.
•Lungs is pale pink color.
•The crunch takes place when the
lungs are cuted; the pitish appears
after finger’s pressure.
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Pneumonia
Bullous emphysema
The chest cavity is
opened at autopsy to
reveal numerous large
bullae apparent on the
surface of the lungs in a
patient dying with
emphysema. Bullae are
large dilated airspaces
that bulge out from
beneath the pleura.
Emphysema is
characterized by a loss of
lung parenchyma by
destruction of alveoli so
that there is permanent
dilation of airspaces.
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Pneumonia
Microscopic examination
•The abnormal fenestrations in the
walls of the alveoli.
•The complete destruction of septal
walls.
•The distribution of damage within
the pulmonary lobule.
•Adjacent alveoli fuse, producing
even larger abnormal airspaces.
•The respiratory bronchioles and
vessels of the lung are deformed and
compressed by the emphysematous
distortion of the airspaces.
• Capillary's reducing may lead to the development of
the capillary-alveolar block and pulmonary
insufficiency.
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Pneumonia
Pathogenesis of emphysema
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Disease is accompanied with
destruction of elastic and collagen fibers of
lungs due to action of leukocytes proteases
(in inflammation).
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Thus, emphysema is seen to result
from the destructive effect of the high
protease activity in subjects with low
antiprotease activity.
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Main pathogenic mechanism is
genetically determined deficiency of alpha-1-
Antitripsin
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Pneumonia
BRONCHIAL ASTHMA (BA)
Asthma is a disease of airways that is
characterized by increased
responsiveness of the tracheobronchial
tree to a variety of stimuli resulting in
widespread spasmodic narrowing of the
air passages which may be relieved
spontaneously or by therapy.
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Pneumonia
BRONCHIAL ASTHMA (BA)
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A severe and unremitting type of the disease
termed status asthmaticus may prove fatal.
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BA has traditionally been divided into two basis
types:
1.
Extrinsic asthma: there is typically an association
with atopy (allergies) mediated by type 1
hypersensitivity, and asthmatic attacks are precipitated
by contact with inhaled allergens. This form occurs most
often in childhood.
2.
Intrinsic asthma: asthmatic attacks are precipitated
by respiratory infections, exposure to cold, exercise,
stress, inhaled irritants, and drugs such as aspirin. Adults
are most often affected.
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Pneumonia
The classic asthmatic attack lasts up to several
hours and is followed by prolonged coughing; the
raising of copious mucous secretions provides
considerable relief of the respiratory difficulty. In
some patients, these symptoms persist at a low
level all the time. In its most severe form, status
asthmaticus, the severe acute paroxysm persists
for days and even weeks, and, under these
circumstances, ventilatory function may be so
impaired as to cause severe cyanosis and even
death.
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Pneumonia
This cast of the bronchial tree is formed of inspissated mucus
and was coughed up by a patient during an asthmatic attack.
The outpouring of mucus from hypertrophied bronchial
submucosal glands, the bronchoconstriction, and dehydration
all contribute to the formation of mucus plugs that can block
airways in asthmatic patients.
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Pneumonia
Histologic findings
of BA
1. Thickening of the
basement membrane of the
bronchial epithelium;
2. Edema and inflammatory
infiltrate in the bronchial
walls, with a prominence of
eosinophils;
3. An increase in size of the
submucosal glands;
4. Submucosa widened by
smooth muscle hypertrophy;
5. Bronchitis and
Emphysematous changes.
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Pneumonia
These lungs appear essentially normal, but are normalappearing because they are the hyperinflated lungs of a
patient who died with status asthmaticus.
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Pneumonia
Idiopathic pulmonary
fibrosis
Diffuse interstitial fibrosis occurs as a result of
different pulmonary diseases such as pneumoconiosis,
hypersensitivity pneumonitis (“farmer's lung”, “bird
fancier's disease”, “silo filler's disease”) and collagenvascular disease. It is so called “idiopathic pulmonary
fibrosis” or “cryptogenic fibrosing alveolitis” or “chronic
interstitial pneumonitis”
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Pneumonia
PATHOGENESIS
The pathogenesis of idiopathic pulmonary
fibrosis is unknown and the condition is
diagnosed by excluding all known causes of
interstitial fibrosis:
- High levels of autoantibodies such as
rheumatoid factor and antinuclear antibodies.
- Elevated titres of circulating immune
complexes.
- Immunofluorescent demonstration of the
deposits of immunoglobulins and complement
on the alveolar walls in biopsy specimens.
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Pneumonia
Morphology
Pathological changes are bilateral and widespread.

Macroscopically the lungs are dense, reduced
volume.
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Honey-combing (i.e. enlarged, thick-walled air
spaces) develops in parts of lung. Microscopically,
changes vary according to the stage of the disease
with formation of hyaline membranes.

There is edema and cellular infiltrate in the
alveolar septa in early stage.

There is organization of the alveolar exudate
and replacement fibrosis in the alveoli and in the
interstitial septal wall with variable amount of
inflammation in advanced stage.
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Pneumonia
Hypersensitivity pneumonitis
Hypersensitivity
pneumonitis occur when
there is an inhaled organic
dust that produces a
localized for of type III
hypersensitivity (Arthus)
reaction from antigenantibody complexes.
Alveolar wall is enlarged
with chronic inflammatory
cells and giant cells
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Pneumonia
Idiopathic pulmonary fibrosis
This is an example of pulmonary fibrosis. The alveolitis
that produces fibroblast proliferation and collagen
deposition is progressive over time.
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Pneumonia
"honeycomb" lung
Regardless of the
etiology for restrictive
lung diseases, many
eventually lead to
extensive fibrosis. The
gross appearance, as
seen here in a patient
with organizing diffuse
alveolar damage, is
known as "honeycomb"
lung because of the
appearance of the
irregular air spaces
between bands of
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dense fibrous
Pneumonia
Diffuse alveolar damage (DAD) in the lung.
DAD is simply the final
common pathway for a
variety of severe lung
injuries.
In early DAD, there are
hyaline membranes, as
seen here, lining alveoli.
Later, type II pneumonocyte
proliferation and then
interstitial inflammation and
fibrosis are seen.
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Pneumonia
PNEUMOCONIOSES
The factors which determine the extent of damage
caused by inhaled dusts are:
• size and shape of the particles;
• their solubility and physico-chemical
composition;
• the amount of dust retained in the lungs;
• the additional effect of other irritants such as
tobacco smoke;
• host factors such as efficiency of clearance
mechanism and immune status of the host.
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Pneumonia
The tissue response to inhaled dust
may be one of the following three
types:
• Fibrous nodules e.g. in coal-workers'
pneumoconiosis and silicosis.
• Interstitial fibrosis e.g. in asbestosis.
• Hypersensitivity reaction e.g. in
berylliosis.
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Pneumonia
Anthracotic pigment ordinarily is not fibrogenic, but in
massive amounts (as in "black lung disease" in coal
miners) a fibrogenic response can be elicited to produce
the "coal worker's pneumoconiosis" seen here.
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Pneumonia
Silicosis
It is composed mainly of
bundles of interlacing
pink collagen. There is
a minimal inflammatory
reaction. The greater
the degree of exposure
to silica and increasing
length of exposure
determine the amount
of silicotic nodule
formation and the
degree of restrictive
lung disease. Silicosis
increases the risk for
lung carcinoma about 260
fold.
Pneumonia
Cor pulmonale
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