Pathology of respiratory system

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Pathology of respiratory system
Lecture on pathomorphology by Filonenko T.G.
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Patterns of Lung disorders

• Airway
• Bronchitis, Bronchiectasis, Bronchiolitis.
• Tumors / Cancer
• Parenchyma
• Pneumonia.
• Lung abscess, TB
• Hyaline membrane dis (HMD ARDS)
• Pneumoconiosis
• Tumors / Cancer
• Pleura
• Pleural effusion (TB)
• Tumors / Cancer

Infections
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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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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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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
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Pathogenesis
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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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Lobar Pneumonia

• 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 - ExudationRBC
• Gray Hepatizaiton 4d- neutro Macrophages
• Resolution 8d few macrophages, normal

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Pathogenesis of Pneumonia
Grey Hepatization Resolution
Congestion Red Hepatisation
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Lobar Pneumonia Congestion
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Lobar Pneumonia Red hepat.
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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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Lobar pneumonia
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Lobar Pneumonia Gray hep
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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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Bronchopneumonia
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Bronchopneumonia
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Broncho Pneumonia - Lobar

• Extremes of age.
• Secondary.
• Both genders.
• Staph, Strep, H.infl.
• Patchy consolidation
• Around Small airway
• Not limited by anatomic boundaries.
• Usually bilateral.

• 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
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Interstitial / atypical Pneumonia

• Primary atypical pneumonia in the 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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Interstitial Pneumonia
Lymphocyte Infiltrate in alveloar wall
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Complications of Pneumonia

• Abscesses
• 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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Abscess formation
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CHRONIC NONSPECIFIC DISEASES OF LUNGS(CNDL)

• CHRONIC OBSTRUCTIVE PULMONARY DISEASE
• (COPD)
• Chronic Bronchitis
• Bronchial Astma
• Chronic Obstructive Emphysema
• Bronchiectatic Disease
• Chronic abscess

• CHRONIC RESTRICTIVE PULMONARY DISEASE (CRPD)
• Restriction due to chest wall disorder
  (Kyphoscoliosis, Poliomyelitis, severe obesity,
  pleural diseases)
• Restriction due to interstitial and infiltrative
  diseases (Pneumoconiosis, Immunologic lung
  diseases, Idiopathic pulmonary fibrosis,
  Sarcoidosis)

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BRONCHITOGENIC(Chronic Obstructive Pulmonary
Diseases)1. Chronic Diffuse Bronchitis2.
Bronchial Astma3. Chronic Diffuse Obstructive
Emphysema4. Bronchiectatic Disease
Patho- and morphogenetic mechanisms of lungs
PNEUMONITOGENIC (Chronic Intersitial Pulmonary
Diseases) 1. Idiopathic pulmonary fibrosis
PNEUMONIOGENIC (Chronic Nonobstructive
Pulmonary Diseases) 1. Chronic pneumonia 2.
Chronic abscess
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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- Familial and genetic factors

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• Pathologic changes
• Hypersecretion of mucus in the large airways, and
  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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Chronic bronchitis increased numbers of chronic
inflammatory cells in the submucosa.
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- 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.
Outcomes and complications
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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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1.     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 Kartageners
syndromes.3.     Necrotizing pneumonias, most
often caused by tubercle bacillus, staphylococci
or mixed infections, measles may develop BE as
secondary complication.
Etiopathogenesis of BE
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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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Classification of BE

•  Cylindrical long, tube-like enlargements in 1
  to 4 type of bronchus.
• Fusiform having spindle-shaped bronchial
  dilatation.
• Saccular having rounded sac-like distention in
  6-10 types of bronchus.
• Varicous having irregular bronchial
  enlargements.

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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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Outcomes and complications1.    Obstructive
ventilatory insufficiency can lead to marked
dyspnea and cyanosis.2.    Pulmonary
hemorrhage3.    Pulmonary abscess4.    Empyema
of the pleura5.    Metastatic brain
abscess6.    Cor pulmonale and chronic
cardiac-pulmonary insufficiency7.    Amyloidosis
are less frequent complications of BE.
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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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Classification of Emphysema

• TRUE EMPHYSEMA
• Centriacinar (centrilobular)
• Panacinar (panlobular)
• Paraseptal (distal acinar)
• Irregular (para-cicatricial)
• Mixed (unclassified)
• 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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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.
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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 fingers pressure.  

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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.
Bullous emphysema
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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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Pathogenesis of emphysema       Disease is
accompanied with destruction of elastic and
collagen fibers of lungs due to action of
leukocytes proteases (in inflammation).      
Thus, emphysema is seen to result from the
destructive effect of the high protease activity
in subjects with low antiprotease
activity.       Main pathogenic mechanism is
genetically determined deficiency of
alpha-1-Antitripsin
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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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BRONCHIAL ASTHMA (BA)        A severe and
unremitting type of the disease termed status
asthmaticus may prove fatal.        BA has
traditionally been divided into two basis
types1.      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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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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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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Histologic findings of BA
1. Thickening of the basement membrane of the
bronchial epithelium2. Edema and inflammatory
infiltrate in the bronchial walls, with a
prominence of eosinophils3. An increase in size
of the submucosal glands4. Submucosa widened by
smooth muscle hypertrophy 5. Bronchitis and
Emphysematous changes.
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These lungs appear essentially normal, but are
normal-appearing because they are the
hyperinflated lungs of a patient who died with
status asthmaticus.
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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 collagen-vascular disease.
It is so called idiopathic pulmonary fibrosis
or cryptogenic fibrosing alveolitis or chronic
interstitial pneumonitis
Idiopathic pulmonary fibrosis
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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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Pathological changes are bilateral and
widespread.      Macroscopically the lungs are
dense, reduced volume.      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.
Morphology
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Hypersensitivity pneumonitis
Hypersensitivity pneumonitis occur when there is an inhaled organic dust that produces a localized for of type III hypersensitivity (Arthus) reaction from antigen-antibody complexes. Alveolar wall is enlarged with chronic inflammatory cells and giant cells
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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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"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 dense fibrous connective tissue.
                                 
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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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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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• 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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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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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 2-fold.
                                 
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Cor pulmonale