UNP-MEDICINE 2021 Pathology

The lung
LECTURER: DR. GAIL DOMECQ TANAWIT, FPSP

APRIL 15, 2019

HEAD NOTES
 TITLE/EMPHASIZED Atelectasis (Collapse)
 AUDIO
 NOTES/RECALLS/ADD-ONS  refers to either to incomplete expansion of the lungs (neonatal
atelectasis) or to collapse of previously inflated lung, producing
The lungs are ingeniously constructed to carry out their cardinal function, areas of relatively airless pulmonary parenchyma.
the exchange of gases between insipired air and blood. Main types of Acquired Atelectasis
Resorption atelectasis
Respiratory Tree  Complete obstruction of an airway
 Mediastinum shifts toward the atelectatic lung
Trachea
Compression atelectasis
Bronchi  Pleural cavity as partially or completely filled exudates, tumor,
blood, or air
Bronchioles  Mediastinum shifts away from the atelectatic lung
Terminal Bronchioles Contraction atelectasis
 Fibrotic changes in the lung or pleura
Acinus (composed of respiratory bronchioles –> alveolar ducts -> alveolar  Focal or general preventing full expansion
sacs

Microscopic Structure of Alveolar Walls (Alveolar Septa)

Pulmonary Edema
 Capillary endothelium
 Basement membrane and surrounding interstitial tissue
 leakage of excessive interstial fluid which accumulates in
 Alveolar epithelium which contains two principal cell types
alveolar spaces. It can result from hemodynamic disturbances
o Type I pneumocytes (membranous pneumocytes)
(hemodynamic or cardiogenic pulmonary edema) or from direct
o Type II pneumocytes - surfactant
increases in capillary permeability, as a result of microvascular
 Alveolar macrophage
injury.
Causes:
1. Hemodynamic

Mechanisms:
Increased hydrostatic pressure
Decreased oncotic pressure
Lymphatic obstruction
Gross: heavy, wet lungs
Micro:
Engrorged alveolar capillaries
Intra alveolar granular pink precipitate
Michrohemorrhages
Few hemosiderophages

If long standing cases, such as in initial stenosis

Gross features:
 Lungs: brown induration

Microscopic features:
 Abundant hemosiderophages
 Fibrosis and thickening of alveolar walls

2. Microvascular (Alveolar) injury

LUNG: CONGENITAL ANOMALIES Mechanism:

Injury to the capillaries of the alveolar sept-primary
1. Agenesis or hypoplasia of both lungs, one lung, or single lobes. injury to vascular endothelium or damage to alveolar epithelial
2. Foregut cysts cells ( w/ 2’ microvascular injury) leakage of fluid and protein
o Bronchogenic cyst into interstitium and into the alveoli
o Esophageal
o Enteric cyst Acute Lung Injury and Acute Respiratory Distress Syndrome,
3. Pulmonary sequestration Diffuse Alveolar Damage (DAD)
4. Congenital pulmonary airway malformation  also called noncardiogenic pulmonary edema, characterized
5. Tracheal, and bronchial anomalies (atresia, stenosis, TEF) by abrupt onset of significant hypoxemia and bilateral
6. Vascular anomalies pulmonary infiltrates in the absence of cardiac failure. Acute
7. Congenital lobar overinflation (emphysema) Respiratory Distress Syndrome (ARDS) is a manifestation of
sever ALI.

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 Typically type I hypersensitivity reaction induced by
exposure to an intrinsic antigen
Clinical Course:
 Intrinsic Asthma
Profound dyspnea, tachypnea  Triggering mechanism non immune – ingestion of
CXR initially normal aspirin, pulmonary infections, cold, inhaled irritants,
stress, and exercise

Increasing cyanosis and hypoxemia, respiratory failure and diffuse

bilateral infiltrates on CXR

Unresponsive to oxygen therapy and respiratory acidosis develops

Acute Respiratory Distress Syndrome

 “shock lung”, “acute alveolar injury”, “acute lung injury”,
“diffuse alveolar damage”
Pathogenesis :
 Diffuse alveolar capillary
 Deficiency of pulmonary surfactant

Endothelial activation
Initial injury to capillary endothelium or alveolar epithelium either
infectious or noninfectious stimuli

Increase vascular permeability & alveolar flooding, loss of diffusion

capacity & widespread surfactant abnormalities
Adhesion & extravasation of neutrophils, Accumulation of intralaveolar
Fluid and formation of hyaline membranes

Synthesis of IL-8, IL-1, and TNF

Pulmonary microvascular sequestration
PMN activation releasing oxidants, proteases, PAF & leukotrienes
Active TISSUE DAMAGE & maintain inflammatory cascade

Morphology:
- Acute stage:
Gross: lungs are heavy, firm, red and boggy
Microscopic features
 Congestion
 Interstitial and intra-alveolar edema
 Inflammation
 Fibrin deposition II. Restrictive Lung Diseases
 Alveolar walls lined with waxy hyaline membranes  Reduced total lung capacity, while the expiratory flow rate is
normal or reduced proportionately
- Organizing stage:  Occurs in two general conditions
Microscopic features: o Chest wall disorders in the presence of normal lungs
 Type II epithelial cells undergo proliferation o Acute or chronic interstitial and infiltrative diseases
 Organization of exudates with resultant intra-alveolar
Fibrosis BRONCHIAL ASTHMA
 Marked thickening of the alveolar septa Bronchospasm
 Extrinsic Asthma
Categories of Patients with Diffuse Pulmonary Disease  Typically type I hypersensitivity reaction induced by
I. Obstructive Lung (Airway) Diseases exposure to an intrinsic antigen
 Increase in resistance to airflow  Intrinsic Asthma
 Partial or complete obstruction at any level  Triggering mechanism non immune – ingestion of
 Pulmonary function tests show limitation of maximal airflow aspirin, pulmonary infections, cold, inhaled irritants,
rates during forced expiration usually measured by FEV1 stress, and exercise
o Bronchial asthma Pathogenesis
o Emphysema TH2 – IL secretion
o Chronic bronchitis  Allergic inflammation
o Bronchiectasis  Stimulate B cells to produce IgE and other
Ab
Cause of death in COPD: TH1 – interferon-gamma and IL2
 Respiratory acidosis and coma  Initiate killing of viruses and
 Right sided heart failure intracellular organism
 Massive collapse of the lungs secondary to pneumothorax CYTOKINES from TH1 inhibit TH2 cells and vice versa
– any imbalance leads to ASTHMA.
Bronchial Asthma
Bronchospasm “Airway Remodeling” : hypertrophy of bronchial smooth muscle
 Extrinsic Asthma and deposition of subepithelial collagen
1. ADAM 33
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 Belong to MMPs collagenase
 Accelerate proliferation of bronchial smooth muscle
and fibroblasts – bronchial hyperactivity and
subepithelial fibrosis
2. Mast cells

ATOPIC Asthma
Pathogenesis
Microscopic:
EXPOSURE of Pre-sensitized IgE coated mast cells to ALLERGEN  Curshmann spirals
 Numerous eosinophils & Charcot-Layden crystals
Other characteristic histologic findings
CROSSLINKING of IgE and release of chemical mediators  Thickening of basement membrane of bronchial epithelium
 Edema and inflammation on bronchial walls predominantly
eosinophils
Direct stimulation of subepithelial vagal (parasympathetic) receptor  Increase in size of submucosal glands
promoting BRONCHOCONSTRICTION  Hypertrophy and hyperplasia of bronchial wall smooth muscle
 Overtime, features of “airway remodeling”
ACUTE or IMMEDIATE RESPONSE
Early phase mediators – (ETC4, D4, E4, Prostaglandin D2, E2, F2alpha,
Histamine, PAF, Mast cell tryptase)

Bronchoconstriction, Edema, Mucus secretion and hypotension

LATE PHASE REACTION

Starts 4-8 hours and persists for 12-24 hours or more
Mediators: Eosinophilic and neutrophilic chemotactic factors and
LTB4, IL4 and IL5, PAF, TNF
Mediators of Bronchospasm
 Leukotrienes C4, D4, E4 : bronchoconstriction, increased
vascular permeability and mucus secretion
 Acetylcholine : from intrapulmonary motor nerves causes airway
smooth muscle constriction directly by stimulating muscarinic
receptors
Mediators at the
“scene of the crime”
 Histamine : potent bronchoconstrictor
 PGD2 : bronchoconstrictor and vasodilator
 PAF : aggregation of platelets and release of histamine and
serotonin from their granules
“suspects”
 IL-1, TNF, IL-6, chemokines, neuropeptides, nitric oxide,
bradykinin and endothelin
EMPHYSEMA
- irreversible enlargement of the airspaces distal to the terminal
bronchiole, accompanied by destruction of their walls without
obvious
fibrosis
- The disease is strongly associated with cigarette smoking
Pathogenesis:
 Protease – Antiprotease imbalance aided and abetted by oxidant
– antioxidant imbalance
o Elastase – principally derived from neutrophils, also derived
from macrophages, mast cells, pancreas & bacteria
o Antielastase – alpha 1 antitrypsin (principal), leakoprotease
inhibitor & alpha 1 macroglobulin
 Destructive effect of high protease activity in subjects with low
antiprotease activity

NON ATOPIC Ashtma

 Most frequent trigger : respiratory tract infection (rhinovirus,
parainfluenza virus)
 Uncommon to find family history
 IgE levels are normal
 No associated allergies

Asthma
 Drug-Induced Asthma
o Aspirin : inhibiting the cyclooxygenase pathway of
arachidonic acid metabolism without affecting the
lipoxygenase route
 Occupational Asthma
o Fumes (epoxy resins, plastics)
o Organic and chemical dusts
o Gases
o Chemicals : formaldehyde, penicillin products

BRONCHIAL ASTHMA: Morphology

Gross:
 Overdistended lungs due to overinflation
 Small areas of atelectasis
 Most striking: mucous plugs

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 Airspace enlargement with fibrosis (irregular
emphysema)
- acinus is irregularly involved, is almost invariably associated
with scarring
- in most instances it occurs in small foci and is clinically
insignificant

Other Microscopic Types of Emphysema

Classical Clinical Features
 barrel-chested and dyspneic
 prolonged expiration
 sits forward in a hunched-over position
 breathes through pursed lips
 cough often slight
 “pink puffers”
Key to Diagnosis:
 Expiration airflow limitation
EMPHYSEMA: Anatomic Distribution
 Centriacinar (centrilobular) Emphysema
- the central or proximal parts of the acini are affected, whereas
distal alveoli are spared
- usually more severe in the upper lobes, particularly in the apical
segments
- inflammation around bronchi and bronchioles is common
- in severe cases, the distal acinus may also be involved, making
differentiation from panacinar emphysema difficult
- Occurs predominantly in heavy smokers, often in association
- with chronic bronchitis (COPD)
 Panacinar (panlobular) Emphysema
- the acini are uniformly enlarged from the level of the respiratory
bronchiole to the terminal blind alveoli
- the prefix “pan” refers to the entire acinus, not the entire lung
- occur more commonly in the lower zones and in the anterior
margins of the lung, and it is usually most severe at the bases
- associated with α1-antitrypsin deficiency
 Compensatory hyperinflation
- dilation of alveoli with no destruction of septal walls
- loss of lung substance
- best exemplified by the hyperexpansion of residual lung
parenchyma following surgical removal of a diseased lung or
lobe
 Obstructive overinflation
- the lung expands because air is trapped within it
- common cause is subtotal obstruction of the airways by a tumor
or foreign object
- another example is congenital lobar overinflation in infants,
probably resulting from hypoplasia of bronchial cartilage and
sometimes associated with other congenital cardiac and lung
abnormalities
- overinflation in obstructive lesions occurs either:
o obstructive agent acts as ball valve, allowing air to enter on
inspiration while preventing its exodus on expiration
o ventilation through collaterals
o pores of Kohn
o direct accessory bronchioalveolar connections (the canals of
Lambert)
- It can be a life-threatening emergency, because the affected
portion distends sufficiently to compress the remaining lung
 Bullous emphysema
- Large subpleural blebs or bullae (spaces >1 cm) that can occur
in any form of emphysema
- occur near the apex, sometimes near old tuberculous scarring
- on occasion, rupture of the bullae may give rise to
pneumothorax

 Distal Acinar (Paraseptal) Emphysema
- The proximal portion of the acinus is normal, and the distal part
is predominantly involved
- emphysema is more striking adjacent to the pleura, along the
lobular connective tissue septa, and at the margins of the
lobules
- occurs adjacent to areas of fibrosis, scarring, or atelectasis and Microscopic Features
is usually more severe in the upper half of the lungs
- characteristic findings are of multiple, continuous, enlarged
airspaces from less than 0.5 cm to more than 2.0 cm in
diameter, sometimes forming cyst-like structures
- this type of emphysema probably underlies many cases of
spontaneous pneumothorax in young adults
o
 Interstitial emphysema
- entrance of air into the connective tissue stroma of the lung,
mediastinum, or subcutaneous tissue produces interstitial
emphysema
- alveolar tears in pulmonary emphysema provide the avenue of
entrance of air into the stroma of the lung
- usually caused by rapid increases in pressure within alveolar
sacs, such as occurs when there is a combination of coughing
and bronchiolar obstruction
- premature children on positive pressure ventilation adults who
are being artificially ventilated are most at risk
- rarely, chest wounds that allow entry of air or fractured ribs
that puncture the lung substance underlie this disorder
 Large alveoli separated by
thin septa
 Destruction of alveolar walls
 Respiratory bronchioles &
vasculature is deformed &
compressed

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CHRONIC BRONCHITIS BRONCHIECTASIS
- Persistent cough with sputum production for at least 3 months in - disorder in which destruction of smooth muscle and elastic tissue
at least 2 consecutive years, in the absence of any other by chronic necrotizing infections leads to permanent dilation of
identifiable cause bronchi and bronchioles
- common in habitual smokers and inhabitants of smog-laden  Congenital or hereditary conditions, including cystic fbrosis,
cities, chronic bronchitis is one end of the spectrum of COPD, with intralobar sequestration of the lung, immunodefciency states, and
emphysema being the other primary ciliary dyskinesia and Kartagener syndromes
 Simple chronic bronchitis  Infections, including necrotizing pneumonia caused by bacteria,
 Chronic asthmatic bronchitis viruses, or fungi; this may be a single severe
 Obstructive chronic bronchitis episode or recurrent infections
 Bronchial obstruction, due to tumor, foreign bodies, or
Pathogenesis: mucus impaction; in each instance the bronchiectasis is
localized to the obstructed lung segment
 Other conditions, including rheumatoid arthritis,
systemic lupus erythematosus, inflammatory bowel
disease, COPD, and posttransplantation (chronic lung
rejection, and chronic graft-versus-host disease after
bone marrow transplantation)

Clinical Course:
 severe, persistent cough; expectoration of foul smelling,
sometimes bloody sputum
 dyspnea and orthopnea in severe cases
Morphology of Brochitis  on occasion, hemoptysis, which may be massive
Gross:  fever
 hyperemia, swelling, and edema of the mucous membranes,
frequently accompanied by excessive mucinous or Pathogenesis:
mucopurulent secretions  Bronchial Obstruction and infection
Microscopic: o Cystic Fibrosis
 the major change is the increase in size of mucous glands, which - the primary defect in ion transport leads to defective
can be assessed by the ratio of the thickness of the mucociliary action and airway obstruction by thick viscous
mucous gland layer to the thickness of the wall between secretions
the epithelium and the cartilage (Reid index)
 Reid index (normally 0.4) is increased in chronic bronchitis,
usually in proportion to the severity and duration of the
disease
 bronchial epithelium may exhibit squamous metaplasia and
dysplasia
 marked narrowing of bronchioles caused by mucus plugging,
inflammation, and fibrosis
 in the most severe cases, there may be obliteration of
lumen due to fbrosis (bronchiolitis obliterans)


o Primary Ciliary Dyskinesia
- ciliary dysfunction due to defects in ciliary motor proteins
such as absence or shortening od dynein arms
- associated with Kartagener syndrome (marked by situs
inversus or a partial lateralizing abnormality associated with
bronchiectasis and sinusitis)
o Allergic bronchopulmonary aspergillosis
- it is a condition that results from a hypersensitivity reaction
to the fungus Aspergillus fumigatus
- occurs in patients with asthma and cystic fibrosis who develop
periods of exacerbation and remission that may lead to
proximal bronchiectasis and fibrotic lung disease
- Sensitization to Aspergillus in the allergic host leads to
activation of TH2 helper T cells, which play a key role in
recruiting eosinophils and other leukocytes
- intense airway inflammation with eosinophils, and the
formation of mucus plugs, which play a primary role in its
pathogenesis

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Morphology:
DIFFUSE INTERSTITIAL (INFILTRATE RESTRICTIVE) DISEASE
- diffuse & chronic involvement of pulmonary CONNECTIVE TISSUE
– peripheral & interstitium of alveolar walls
 Restrictive lung disorders occur in two general conditions:
(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
Clinical Manifestation:
 Dyspnea
 Tachypnea
 end-inspiratory crackles
 eventual cyanosis, without wheezing or other evidence of airway
obstruction
Physiologic Features:
 reductions in CO diffusion capacity, lung volume, and lung
compliance
Chest radiographs:
 Diffuse infiltration by small nodules, irregular lines, or ground
glass shadows, all corresponding to areas of interstitial fibrosis
Gross Morphology:
 result in scarring and gross destruction of the lung, often referred
to as end-stage lung or honeycomb lung
FIBROSING DISEASES
Idiopathic Pulmonary fibrosis(IPF) Usual Interstitiial Pneumonia (UIP)
Pathogenesis:
repeated cycles of acute lung injury and wound healing with unidentified
agent leads to widespread fibrosis and loss of lung function.
Gross: cobblestone owing to retraction of scars; firm, rubbery white areas
with lower lobe predominance.
IDIOPATHIC PULMONARY FIBROSIS (UIP)
 Microscopic hallmark is patchy interstitial fibrosis.
 Grossly, pleural surface is cobblestoned as a result of scar retraction,
cut sections show firm, rubbery white areas of fibrosis primarily in
the lower lobes (subpleural region along the interlobular septa).
 Earliest lesion: fibroblastic foci
 Fibrosis cause collapse of alveolar walls and formation of cystic
spaces lined by hyperplastic type II pneumocytes or bronchial
epithelium (honeycomb fibrosis).
 Mild to moderate acute & chronic inflammation within fibrosis.
 Foci of squamous metaplasia and smooth muscle hyperplasia.
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Pathology
Clinical Course
 Begins insidiously w/ gradually increasing dyspnea on exertion
 Dry cough
 Most patients are 55-75 years old.
 Late cyanosis, clubbing, and hypoxemia.
NON-SPECIFIC INTERSTITIAL PNEUMONIA (NSIP)
 Diffuse interstitial disease of unknown etiology.
 These patients have much better prognosis than with usual.
 May be idiopathic or associated with connective tissue diseases.
Morphology:
 Divided into:
 Cellular Pattern- primarily of mild to moderate chronic interstitial
inflammation w/ lymphocytes and few plasma cells, in a uniform or
patchy distribution.
 Fibrosing Pattern – Diffuse or patchy interstitial fibrosis.
 Fibroblastic foci, honeycombing, hyaline membrane, granulomas are
all ABSENT.
Clinical Course:
 Dyspnea and cough of several months’ duration.
 More likely female, non-smokers in 6th decade of life.
 On CT, bilateral, symmetric, lower lobe reticular opacities.
 Patients w/ cellular pattern are younger & have better prognosis.
CYPTOGENIC ORGANIZING PNEUMONIA (COP)
 Synonymous with bronchiolitis obliterans organizing pneumonia
 Unknown etiology.
 Presents with cough and dyspnea with patchy subpleural or
peribronchial areas of airspace consolidation in CXR.
 Histologically, there are polypoid plugs of loose organizing
 tissues (Masson bodies) w/in alveolar ducts, alveoli, bronchioles.
 No interstitial fibrosis or honeycombing.
 “Bronchiolitis obliterans organizing pneumonia”
It is important to recognize that organizing pneumonia with intra- alveolar
fibrosis is most often seen as a response to infections or inflammation of
the lungs, including viral, bacterial pneumonia, inhaled toxins, connective
tissue diseases, GVHD.
PULMONARY INVOLVEMENT IN AUTOIMMUNE VASCULAR
DISEASES
Systemic lupus erythematosus (SLE)- Patchy transient parenchymal
infiltrates
Rheumatoid Arthritis – pulmonary involvement in 30-40% of px
 Chronic pleuritis w/ or w/o effusion
 Diffuse interstitial pneumonitis and fibrosis
 Intrapulmonary rheumatoid nodules
 Pulmonary Hypertension
 Follicular Bronchiolitis
Systemic Sclerosis
 Diffuse interstitial fibrosis (non-specific)
 Pleural Involvement
PNEUMOCONIOSES
 Non-neoplastic lung reaction to inhalation of mineral dusts, now
includes organic, inorganic particulate, fumes, and vapors.
Pathogenesis:
Development of pneumoconiosis depends on:
 Amount of dust retained in the lungs and airways
 Size, Shape, and Buoyancy of the particle
 Particle solubility and physicochemical reactivity
 Possible additional effects of other irritants (smokers)
Coal Worker’s Pneumoconiosis (CWP)
Inhalation of coal particles and other admixed forms of dust.
Spectrum of lung findings:
 Asymptomatic Anthracosis
 Single CWP with little or no pulmonary dysfunction
 Complicated CWP or progressive massive fibrosis (PMF)
 Contaminating silica can favor progressive disease.
 Carbon dust itself is the major culprit.
 May also develop emphysema and chronic bronchitis.
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Morphology:
Anthracosis- the most innocuous coal; induced pulmonary lesion.
Inhaled carbon pigment is engulfed by alveolar macrophages, which
accumulate in connective tissue along lymphatics.
Simple CWP-
 characterized by coal macules (1-2mm) which are carbon laden
macrophages and coal nodules which are delicate network of
collagen fibers.
 Upper lobes and upper zones of lower lobes are heavily
 involved, adjacent to respiratory bronchioles. Sometimes give rise to
centrilobular emphysema
Complicated CWP (progressive massive fibrosis)-
 characterized by intensely blackened scars 1 cm to 10 cm usually
multiple.
 Microscopically consist of dense collagen and pigment with necrotic
central portion most likely due to ischemia.
Clinical Course:
 Usually benign, little decrement in lung function.
 Less than 10% of cases leads to progressive massive fibrosis and
may manifest pulmonary dysfunction, pulmonary hypertension,
 and cor pulmonale.
Silicosis
 caused by inhalation of proinflammatory crystalline silicon
dioxide (silica), manifests after decades of exposure as slowly
progressing, nodular, fibrosing pneumoconiosis.
Pathogenesis:
 Crystalline forms (Quartz, Crystobalite, Tridymite) are more
 fibrogenic than the amorphous forms.
 Amorphous forms are biologically less active.
 The particles are phagocytosed and activate the inflammasome
leading to activation and release of following factors:
 IL-1,
 IL-18
 TNF
 Fibronectin
 Lipid Mediators
 O2-derived free radicals
 Fibrogenic cytokines
Morphology:
Gross:
 in early stages, tiny, barely palpable, discrete pale to blackened
nodule in the hilar lymph nodes and upper zones.
 The nodules coalesce into hard collagenous scars.
 central softening and cavitation due to superimposed tuberculosis or
ischemia.
 Fibrotic Lesions in the hilar nodes with “eggshell calcification” in CXR.
 Expansion and coalescence of lesions may produce progressive
massive fibrosis (PMF)
Microscopic:
there are concentric layers of hyalinized collagen surrounded by dense
capsule of more condensed ones.
On polarized microscopy, there are bifringent particles.
Clinical Course:
 Slow to kill, with impaired pulmonary function.
 Increased susceptibility to tuberculosis.
CXR show fine nodularity in upper zones of lungs.
Pulmonary functions are normal or moderately affected, most
do not develop shortness of breath until massive fibrosis
Asbestos
Asbestos- family of pro-inflammatory crystalline hydrated silicates
Occupational exposure is linked to:
 Localized fibrous plaques, or rarely, diffuse pleural fibrosis.
 Pleural effusions, recurrent
 Parenchymal Interstitial Fibrosis (Asbestosis)
 Lung Carcinoma
 Mesotheliomas
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Pathology
 Laryngeal, extrapulmonary neoplasms (colon carcinoma)
Pathogenesis:
 Occurs in two geometric forms: Serpentine and Amphibole.
 Amphiboles (includes crocidolite, amosite, tremolite, anthophyllite,
actinolyte) are more pathogenic w/ induction of mesothelioma.
 Greater pathogenicity of amphiboles is related to their aerodynamic
properties and solubility.
 Asbestos can act as a tumor initiator or tumor promoter, mediated by
free radicals.
 Same pathophysiology with silica upon macrophage ingestion.
Morphology:
 Diffuse pulmonary interstitial fibrosis with presence of Asbestos
Bodies, which are golden brown, fusiform or beaded rods, with a
translucent center and consists of asbestos fibers coated with an iron
coating proteinaceous material.
o Arise when phages phagocytose asbestos, iron is from the
phages’ own ferritin.
 Ferruginous bodies – other inorganic particulates that became
coated with similar iron-protein complex.
 Begins as fibrosis around respiratory bronchioles and alveolar ducts
and extends to adjacent alveolar sacs.
 Fibrous tissue distorts the architecture creating enlarged airspaces
enclosed with thick fibrous walls, eventually becomes honeycombed.
 Usually begins in the Lower lobes and subpleurally.
o The middle and upper lobes of the lungs become affected
as fibrosis progress
 Scarring may trap and narrow pulmonary arteries causing
pulmonary hypertension and cor pulmonale.
 Pleural Plaques, most common manifestation of asbestosis, are well-
circumscribed plaques of dense collagen often calcified.
o Most frequently on anterior and posterolateral aspects of
the parietal pleura and diaphragm.
 Risk of developing lung CA (5x risk), mesothelioma (1,000x)
Complications of Therapies
DRUG INDUCED LUNG DISEASES
Cytotoxic drugs:
 Bleomycin – pneumonitis and fibrosis
 Methotrexate – hypersensitivity pneumonitis
 Amiodarone – pneumonitis and fibrosis
 Nitrofurantoin – hypersensitivity pneumonitis
 Aspirin and beta-agonists - bronchospasm
RADIATION-INDUCED LUNG DISEASES
Acute Radiation Pneumonitis
 occurs 1-6 months after therapy, presents with fever, dyspnea,
pleural effusion, radiologic infiltrates.
Chronic Radiation Pneumonitis
 a progressed form of acute radiation pneumonitis manifested as
pulmonary fibrosis.
GRANULOMATOUS DISEASES
SARCOIDOSIS
 A systemic disease of unknown cause, may involve many organs.
 Produces non-caseating granuloma.
Clinical manifestations:
 bilateral hilar lymphadenopathy and lung involvement- Most common
 Eye and skin lesions
Pathogenesis:
Etiology remains unknown but evidences suggest a disease of
disordered immune regulation in genetically predisposed
individual.
Immunologic Factors
 Intra-alveolar and interstitial accumulation of CD4+ T cells resulting
in CD4:CD8 ratio from 5:1 to 15:1, suggesting there is oligoclonal
expansion of T cell subsets.
 Increased levels of TH1 cytokines (IL-2, IFN-Y).
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 UNP-MEDICINE 2021 Pathology
 Increased levels of cytokines in the local environment (IL-8, TNF,  BAL consistently with increased T cells, both CD4 and CD8.
MIP-1α) favors recruitment of T-cells & monocytes.  Presence of specific antibodies in serum (Type II
 Impaired in dendritic cell functions.  hypersensitivity).
Systemic Immunologic Abnormalities  Complement and Immunoglobulins are present in the vessel walls
 Anergy to common skin test antigens such as Candida or PPD. (Type III).
 Polyclonal hypergammaglobulinemia.  2/3 have non caseating granuloma (Type IV).
Genetic Factors
 Include familial and racial clustering cases. Morphology:
 Association with certain HLA genotypes (Class I HLA-A1 & B8). Characteristically centered on bronchioles.
Environmental Factors  Interstitial pneumonitis consisting primarily of lymphocytes, plasma
 Proposed putative microbes: Mycobacteria, Propionibacterium acnes, cells & macrophages.
Rickettsia sp.  Non-caseating granulomas in 2/3 patients.
 No unequivocal evidence to suggest that sarcoidosis is caused  Interstitial fibrosis & obliterative bronchiolitis
by infectious agent.  More then 1⁄2 of patients have (+) intra-alveolar infiltrates.

Morphology: Clinical Features:

 NON CASEATING granulomas  Acute attacks consist of recurring episodes of fever, dyspnea,
 Aggragate of tightly clustered epithelioid cells, often with Langhans  cough, and leukocytosis.
or foreign body type giant cells with unusual central necrosis
 Granulomas may become enclosed by fibrous rims or replaced by
hyaline fibrous scars.
 Giant cells are composed of Schaumann bodies that are laminated
concretions composed of calcium and proteins and stellate asteroid
inclusion bodies.
Lungs:
Gross:
o No demonstrable alteration.
o Small nodes, 1-2cm, non-caseating, non-cavitated granulomas
o Distributed along lymphatics around bronchi and vessels.
o Alveolar lesions may be seen.
o BLA: CD4/CD8 ratio of >2.5 and CD3/CD4 ratio <0.31
Lymph Nodes:
o Particularly the hilar and mediastinal nodes. Enlarged, discrete,
and calcified.
 Spleen is enlarged with granulomas
 Liver is slightly enlarged with scattered granulomas
 Bone marrow: the most common involvement are the phalangeal
bones of the feet and hand.
 Skin lesions include discrete subcutaneous nodules, focal slightly
elated, erythematous plaques or flat lesions.
 Eye involvement produces iritis and iridocyclitis
 Bilateral sarcoidosis of the salivary glands constitutes combined
uveoparotid involvement is designated as Mikulicz Syndrome.
 Muscle involvement is underdiagnosed, may be asymptomatic.

Clinical Course:
Have an unpredictable course:
 65%-70% recover with minimal or no residual manifestations.
 20% have permanent loss of lung function or some permanent visual
impairment.
 10-15% have cardiac or CNS damage, may succumb to
 progressive pulmonary fibrosis and cor pulmonale.

HYPERSENSITIVITY PNEUMONITIS
 Immunologically mediated, predominantly interstitial lung disorders
caused by intense, often prolonged exposure to inhaled organic
antigens.
 Immune complex & delayed type hypersensitivity (Type 2 and 4)
 Abnormal sensitivity or heightened reactivity to causative antigens
primarily involving the alveolar walls thus also called extrinsic allergic
alveolitis.
 Results from inhalation of organic dusts containing antigens made up
of spores of bacteria, fungi, etc.
 Involves primarily the alveoli, progressing to chronic fibrotic lung
diseases.
Types of hypersensitivity pneumonitis:
 Farmer’s Lung- dusts from hay with spores of Actinomyces.
 Pigeon Breeder’s Lung (Bird Francier’s)- provoked by
proteins from serum, excreta or feathers of birds.
 Humidifier / Airconditioner Lung- caused by thermophilic
bacteria in heated water reservoirs.
Immunologic basis:
 Bronchoalveolar lavage (BAL) shows increased pro-inflammatory
cytokines such as MIP-1 alpha and IL-8.
TRANSCRIBER: OBRERO, OCAMPO, PALADO
“I can do all this through HIM who gives me strength” Phil 4: 13 MED 2-C | 8