RESPIRATORY DISEASE PART 2

FRED MAATE MD
2019
NORMAL CXR PNEUMONIA

PNEUMONIA
PNEUMONIA HISTOLOGY
OBSTRUCTIVE AND RESTRICTIVE
LUNG DISEASES
• Obstructive conditions:
– an increase in resistance to airflow due to partial or
complete obstruction at any level from the trachea
and larger bronchi to the terminal and respiratory
bronchioles.
– An FEV /FVC ratio of less than 0.7
1

• Restrictive diseases:
– characterized by reduced expansion of lung
parenchyma and decreased total lung capacity.
– Normal FEV /FVC ratio
1
 Obstructive lung diseases
• COPD- Emphysema and chronic bronchitis
• Asthma
• Bronchiectasis
• Small airway disease, bronchiolitis
• Emphysema is characterized by
– irreversible enlargement of the airspaces distal to
the terminal bronchiole,
– accompanied by destruction of their walls
– without obvious fibrosis
• centriacinar, panacinar, paraseptal, and
irregular.
• Centriacinar (centrilobular) emphysema
– Most common 95%
– the central or proximal parts of the acini, formed
by respiratory bronchioles, are affected, whereas
distal alveoli are spared
– in heavy smokers, often in association with
chronic bronchitis (COPD).
 Pan- acinar emphysema
• acini are uniformly enlarged from the level of
the respiratory bronchiole to the terminal
blind alveoli
• Associated with alpha-1 antitrypsin deficiency
Centri- acinar and pan- acinar
Emphysema
 Distal/ septal emphysema
• proximal portion of the acinus is normal, and
the distal part is predominantly involved
• Spontaneous pneumothorax
Airspace enlargement with fibrosis
(irregular emphysema).
•Usually insignificant
Pathogenesis
 MORPHOLOGY
• abnormally large alveoli are separated by
thin septa with only focal centriacinar fibrosis
 CLINICAL FEATURES
• Dyspnea
• Cough or wheezing
• Weight loss
• barrel-chested and dyspneic, with obviously
prolonged expiration, sits forward in a
hunched-over position, and breathes through
pursed lip
Pink puffer vs blue bloater
 CHRONIC BRONCHITIS
• defined clinically as persistent cough with
sputum production for at least 3 months in at
least 2 consecutive years, in the absence of
any other identifiable cause.
• It is one end of the spectrum, emphysema is
the other
 Pathogenesis
• Mucous hypersecretion
– associated with hypertrophy of the submucosal
glands in the trachea and bronchi
– increase in goblet cells in small airways
• Inflammation- acute & chronic
• Infection- may maintain chronic bronchitis
 MORPHOLOGY
• Numbers of goblet cells increase slightly,
• Major change is in the size of mucous glands
(hyperplasia).
• Reid index: ratio of the thickness of the mucous gland
layer to the thickness of the wall between the
epithelium and the cartilage
• Squamous metaplasia & dysplasia
• bronchiolitis obliterans
ASTHMA
• a chronic disorder of the conducting airways
• usually caused by an immunological reaction
• Characterised by
– episodic bronchoconstriction due to increased
airway sensitivity to a variety of stimuli;
– inflammation of the bronchial walls; and
– Increased mucus secretion
• Recurrent episodes of
– wheezing,
– breathlessness,
– chest tightness, & cough,
particularly at night and/or in the early morning
• Acute Severe Asthma (formerly known as
status asthmaticus)- a state of unremitting
attacks
 Classification
• Atopic vs non-atopic
– Atopic- evidence of allergen sensitization &
immune activation(Eczema, allergic rhinitis)
• IgE mediated type 1 hypersensitivity; allergens
– Non- atopic: No evidence of allergen sensitization
• Usually due to respiratory infections (RSV,
parainfluenza)
• Clinical features- early onset
• Etiology- cold, smoking, drugs (Aspirin),
occupational
 Pathogenesis- atopic asthma
• Atopic asthma is caused by a TH2 and IgE
response to environmental allergens in
genetically predisposed individuals
– Genetic susceptibility- multigenic
– Environmental factors- Asthma is a disease of
industrialized societies where the majority of
people live in cities
• Hygiene hypothesis
Immediate
response:
•Bronchospasm
•Increased vascular
permeability
• Mucus production
•recruitment of
leukocytes

Late response:
Effects of recruited
Inflammatory cell
effects- epithelial
damage
 MORPHOLOGY
• Distended overinflated lungs
• Eosinophils
• Curschman spirals
• Charcot-Leyden crystals
• Airway remodeling
– Thickening of airway wall
– Subbasement membrane fibrosis (due to deposition of type I
and III collagen)
– Increased vascularity
– An increase in the size of the submucosal glands and number of
airway goblet cells
– Hypertrophy and/or hyperplasia of the bronchial wall muscle
Charcot-Leyden crystals &
Curschmann spirals
“airway remodeling”
 Treatment
• Bronchial dilators
• Steroid
 Bronchiectasis
• a disorder in which destruction of smooth
muscle and elastic tissue by chronic
necrotizing infections leads to permanent
dilation of bronchi and bronchioles
 Predispositions
• Congenital or hereditary conditions-
– Cystic fibrosis,
– intralobar sequestration of the lung,
– immunodeficiency states,
– primary ciliary dyskinesia and
– Kartagener syndrome
• Infections- bacterial, viral or fungal
• Bronchial obstruction- tumour, foreign bodies, mucus
impaction
• Other conditions- RA, SLE, IBD, COPD, Post transplantation,
graft versus host disease
• Idiopathic
 MORPHOLOGY
• See picture above
 CLINICAL FEATURES
• severe, persistent cough;
• expectoration of foul smelling, sometimes
bloody sputum;
• dyspnea and orthopnea in severe cases
• hemoptysis, which may be massive
Chronic Diffuse Interstitial (Restrictive)
Diseases
Two types
1. chronic interstitial and infiltrative diseases, such as
pneumoconioses and interstitial fibrosis of unknown
etiology;
2. chest wall disorders (e.g., neuromuscular diseases
such as poliomyelitis, severe obesity, pleural diseases,
and kyphoscoliosis)

• Chronic interstitial pulmonary diseases are a

heterogeneous group of disorders characterized
predominantly by inflammation and fibrosis of the
pulmonary interstitium
Major Categories of Chronic Interstitial
Lung Disease
 PNEUMOCONIOSIS
• Originally described the nonneoplastic lung
reaction to inhalation of mineral dusts
encountered in the workplace,
• now also includes diseases induced by organic
as well as inorganic particulates and chemical
fumes and vapors.
 Pathogenesis
• Factors:
1. the amount of dust retained in the lung & Airways
2. the size, shape, and buoyancy of the particles
3. particle solubility and physiochemical reactivity; and
4. the possible additional effects of other irritants (e.g.,
concomitant tobacco smoking)
• Small particles are more likely to cause ALI
• Larger particles are more likely to resist
dissolution and may persist within the lung
parenchyma for years.(e.g. Silicon)
 Coal Workers’ Pneumoconiosis
Simple coal worker’s
pneumoconiosis:
•Coal macules
•Coal nodules

Complicated coal
workers’
pneumoconiosis
•progressive massive
fibrosis
•occurs on a
background of
simple disease &
requires many years
to develope

Anthracosis
 Caplan syndrome
• Rheumatoid nodules with pneumoconiosis
 SILICOSIS
• Silicosis is a common lung disease caused by
inhalation of proinflammatory crystalline
silicon dioxide (silica)
• Presents after decades of exposure as slowly
progressing, nodular, fibrosing
pneumoconiosis
• Silicosis is the most prevalent chronic
occupational disease in the world
 Pathogenesis
• Both crystalline and amorphous forms occur
• Crystalline (e.g. Quartz) forms are more
fibrogenic
• After inhalation, particles phagocytosed by
mθs
• Phagocytosed silica activates the
inflammasome→ IL1, IL18 release
• Silicosis is slow to kill, but impaired pulmonary
function may severely limit activity
• It is associated with an increased susceptibility
to tuberculosis
• Patients with silicosis have double the risk for
developing lung cancer.
• The onset of silicosis may be
– slow and insidious (10 to 30 years after exposure;
most common),
– accelerated (within 10 years of exposure) or
– rapid (in weeks or months after intense exposure
to fine dust high in silica; rare
 Asbestos-Related Diseases
• Asbestos is a family of proinflammatory
crystalline hydrated silicates that are
associated with pulmonary fibrosis,
carcinoma, mesothelioma, and other cancers
 Asbestos related diseases
• Localized fibrous plaques or, rarely, diffuse pleural
fibrosis
• Pleural effusions, recurrent
• Parenchymal interstitial fibrosis (asbestosis)
• Lung carcinoma
• Mesotheliomas
• Laryngeal, ovarian and perhaps other
extrapulmonary neoplasms, including colon
carcinomas;
Asbestos related pleural plaques
 Pathogenesis
• The disease-causing capabilities of the
different forms of asbestos depend on
concentration, size, shape, and solubility
• serpentine and amphibole- both fibrogenic
• Some of its oncogenic effects are mediated by
reactive free radicals generated by asbestos
fibers, which preferentially localize in the
distal lung, close to the mesothelial layers
• As with silica crystals, once phagocytosed by
macrophages asbestos fibers activate the
inflammasome and stimulate the release of
proinflammatory factors and fibrogenic
mediators
 MORPHOLOGY
• Diffuse pulmonary interstitial fibrosis
• Asbestos bodies- Iron coated asbestos
• Ferruginous bodies- iron coated inorganic
particulates
• Pleural plaques
Asbestos bodies
 Paraneoplastic syndromes
• Example is syndrome of inappropriate secretion of ADH
• Cushing’s syndrome- ACTH
• Parathormone, parathyroid hormone-related peptide,
prostaglandin E, and some cytokines, all implicated in
the hypercalcemia often seen with lung cancer
• Calcitonin, causing hypocalcemia
• Gonadotropins, causing gynecomastia
• Serotonin and bradykinin, associated with the carcinoid
syndrome
 PLEURAL LESIONS
• PLEURAL EFFUSIONS
– Inflammatory vs non-inflammatory
• PNEUMOTHORAX
• PLEURAL TUMOURS
– Solitary fibrous tumour
• Benign
• No relationship with asbestos exposure
– Mesothelioma
SFT
MALIGNANT MESOTHELIOMA

HISTOLOGIC TYPES
•Epithelioid
•Sarcomatoid
•Mixed

•Needs to be differentiated
from Adenocarcinoma