RESPIRATORY PATHOLOGY Congenital abnormalitiesAtelectasisAcute Pulmonary Injury (eg:pulmonary oedema)

Pulmonary Infections

Obstructive Pulmonary Disease (COPD)

Restrictive (Infiltrative) Pulmonary Disease

Vascular Pulmonary Diseases

Tumors

Pathology of Common Respiratory Conditions Part [3]

OBJECTIVES

TO DISCUSS CAUSES, PATHOGENESIS, TYPES,

MORPHOLOGY,CLINICAL COURSE OF

ATELETASIS

BRONCHIETASIS

PNEUMOCONIOSIS

LEARNING OUTCOMESAt the end of this lecture student will be able to

• Define actelectasis

• Compare resorption actelectasis, compression actelectasis and

contraction actelectasis in regards predisposing factors,etiology

and morphology

• Define bronchiectasis

• Discuss the predisposing conditions ,pathogenesis,gross

&microscopic morphology ,clinical course and prognosis of

bronchiectasis

• Discuss the etiology, pathogenesis, basic morphology and

pulmonary reaction and complications of occupational lungs

diseases (pneumoconiosis- anthracosis, silicosis, asbetosis)

BRONCHIECTASISpermanent dilation of bronchi and bronchioles

and is secondary to cycles of obstruction and infection

Irreversible Dilation of Bronchi and

bronchioles

Caused by Destruction of Bronchial Wall

Muscle and Elastic Elements

BRONCHIECTASIS

BRONCHIECTASIS

Associated with chronic necrotizing infection

A characteristic symptom complex

dominated by

Cough

expectoration of copious amounts of

purulent sputum

ETIOLOGY & PATHOGENESIS

Predisposing conditions

Obstruction & infection are the major

influences

Obstruction is caused byTumorsInhaled foreign bodiesMucous plugs in asthma lymph node enlargementUnder these conditions, the bronchiectasis is localized to the obstructed lung

segment

Post infectious conditions including Necrotizing pneumonia

Caused by

Bacteria ( Mycobacterium tuberculosis,

Staphylococcus aureus, Haemophilus influenzae,

Pseudomonas ) viruses ( adenovirus, influenza virus, HIV )

fungi ( Aspergillus )

Congenital or hereditary conditions Cystic fibrosis (genetic defect, abnormal viscid mucus secretion → obstruction organ passages)

Intralobar pulmonary sequestrations presence of a discrete mass of lung tissue without normal connection to the airway system

Immunodeficiency states

Primary ciliary dyskinesia

Kartagener syndrome (bronchiectasis, sinusitis, and situs inversus or partial lateralizing abnormality )

Other conditions :

rheumatoid arthritis

SLE

inflammatory bowel disease

post transplantation ( chronic lung rejection & chronic graft-versus-host disease after bone marrow transplantation)

MORPHOLOGYGross

Site :Obstructive bronchiectasis is localized to a single

segment of the lungs

Nonobstructive bronchiectasis may be localized

or generalized

Size : Airways are dilated up to 4 times normal size → sufficiently dilated that they can be followed directly out to the pleural surfacesShape : cylindrical fusiform saccular Bronchial lumens : filled with thick mucopurulent secretion

Bronchiectasis

The resected upper lobe

shows widely dilated bronchi,

with thickening of the

bronchial walls and collapse

and fibrosis of the pulmonary

parenchyma

BronchiectasisCross-section of lung demonstrating dilated bronchi extending almost to the pleura

Histology vary with activity & chronicity of the disease

In the full blown active case, intense acute & chronic inflammatory exudatesdesquamation of lining epithelium & extensive areas of necrotizing ulcerationpseudostratification of columnar cellssquamous metaplasia of remaining epitheliumabscess formation chronic case – fibrosis of bronchial and

bronchiolar walls total or subtotal obliteration of

lumen

CLINICAL FEATURES Due to accumulation of pus in dilated bronchi &

bronchiolesChronic cough with production of copious

amount of purulent sputum severe, persistent, worse in morning, induced by change in

posture, may be paroxysmal

Purulent sputum (foul-smelling) – copious amount On standing → 3 layered sputum

1st – frothy layer2nd – clear mucous layer3rd – suppurated & necrotic debris, RBC

Chronic cough with production of copious amount of purulent sputum severe, persistent, worse in morning, induced by change in posture, may be paroxysmal

Purulent sputum (foul-smelling) – copious amount On standing → 3 layered sputum1st – frothy layer2nd – clear mucous layer3rd – suppurated & necrotic debris, RBC

CLINICAL FEATURES Due to accumulation of pus in dilated bronchi & bronchioles

CLINICAL FEATURES due to inflammatory response of the lung

parenchyma & pleura

Fever → febrile episodesChest pain due to pleuritisHaemoptysis or sometimes bloody sputum caused

by rupture of thin walled vessels situated in wall of

dilated bronchioles

Other respiratory symptomsDyspnoea, orthopnoea, cyanosis,

clubbing of fingers & toes.

COMPLICATIONSLung abscess- the necrosis destroys the bronchial or

bronchiolar walls

Pneumonia – infection spread to whole lung parenchyma

Bacteremia, septicemia with metastatic

abscess formation e.g. brain abscess, meningitis

Emphysema – secondary to obstruction

Secondary amyloidosisperibronchiolar fibrosis in chronic widespread

disease → increase pressure in pulmonary circulation → Cor

pulmonale and cardiac failure

COMPLICATIONS

COMPLICATIONS

COMPLICATIONS

Chronic Diffuse Interstitial (Restrictive) Diseases

Chronic interstitial diseases are

heterogeneous group of disorders

characterized predominantly by

inflammation and fibrosis of the

pulmonary connective tissue, principally

the most peripheral and delicate interstitium in

the alveolar walls

PNEUMOCONIOSIS

Pneumoconioses are

pulmonary diseases caused by mineral

dust inhalation in workplace

The specific types of pneumoconioses are

named by the substance inhaled

(e.g., silicosis, asbestosis, anthracosis)

PNEUMOCONIOSISMineral Dust-Induced Lung Disease

Coal dust Simple coal workers' pneumoconiosis:

macules and nodules

Complicated coal workers' pneumoconiosis:

PMF

Coal mining

Silica Silicosis Sandblasting,

quarrying, mining,

stone cutting,

foundry work,

ceramics

Asbestos Asbestosis pleural effusions, pleural plaques, or

diffuse fibrosis; mesothelioma; carcinoma of the

lung and larynx

Mining, milling,

and fabrication of

ores and

materials;

installation and

removal of

insulation

Pathogenesis

The reaction of the lung to mineral dusts

depends on

size, shape, solubility, and reactivity of the

particles

PNEUMOCONIOSIS

Pathogenesis

The development of a pneumoconiosis depends on

(1) the amount of dust retained in the lung and

airways

(2) the size, shape, and buoyancy of the particles

(3) solubility and physiochemical reactivity

(4) the possible additional effects of other irritants

(e.g., concomitant tobacco smoking)

PNEUMOCONIOSIS

Pathogenesis

(1)The amount of dust retained in the lungs

is determined by

dust concentration in surrounding air

duration of exposure

effectiveness of clearance mechanisms

PNEUMOCONIOSIS

Pathogenesis

(2) the size, shape, and buoyancy of the

particles

The most dangerous particles range from

1 to 5 μm in diameter because they may reach the

terminal small airways and air sacs and settle in

their linings

PNEUMOCONIOSIS

(3)The solubility and cytotoxicity of particles

modify the nature of the pulmonary response

Smaller particles tend to cause acute lung injury

Larger particles resist dissolution and so may

persist within the lung parenchyma for years -

tend to evoke fibrosing collagenous pneumoconioses

PNEUMOCONIOSIS

Pathogenesis

The key factor in the gene-sis of

symptomatic pneumoconioses is the

capacity of inhaled dusts to stimulate

fibrosis

The pulmonary alveolar macrophage is a

key cellular element in the initiation and

perpetuation of lung injury and fibrosis

PNEUMOCONIOSIS

The more reactive particles trigger the

macrophages

to release a number of products that

mediate an inflammatory response and

initiate fibroblast proliferation and

collagen deposition

PNEUMOCONIOSIS

Pathogenesis

(4) the possible additional effects of other

irritants (e.g., concomitant tobacco

smoking)

tobacco smoking worsens the effects of

all inhaled mineral dusts

PNEUMOCONIOSIS

In simple coal workers’ pneumoco-niosis

massive amounts of dust are inhaled and engulfed by macrophages

macrophages pass into the interstitium of the lung and aggregate around the respiratory bronchioles

Pathogenesis

Pathogenesis

In silicosisthe silica particles are toxic to macrophages, which die and release a fibrogenic factorIn turn, the released silica is again phagocytosed by other macrophagesThe result is a dense fibrotic nodulethe sili-cotic nodule

Pathogenesis

Asbestosis is characterized by

little dust and much interstitial fibrosis Asbestos bodies are the classic features

PNEUMOCONIOSISCoal Workers’ Pneumoconiosis Is Due to

Inhalation of Carbon Particles

The spectrum of lung findings in coal workers is wide,

varying from

(1)asymptomatic anthracosis

(2)simple CWP with little to no pulmonary

dysfunction

(3)complicated CWP

(4)progressive massive fibrosis (PMF),

PNEUMOCONIOSIS

Morphology

Anthracosis

Accumulation of carbon particles in the

lungs (in the connective tissue along the lymphatics,

including the pleural lymphatics, or in organized lymphoid

tissue along the bronchi or in the lung hilus)

Coal Workers’ Pneumoconiosis

Morphology

Simple CWP is characterized by

coal macules (1 to 2 mm in diameter, consists of

carbon-laden macrophages)

larger coal nodules (contains small amounts of a

delicate network of collagen

located primarily adjacent to respiratory

bronchioles

Complicated CWP (progressive massive fibrosis)

is characterized by multiple

intensely blackened scars larger than 2 cm,

sometimes up to 10 cm in greatest diameter

Occur on background of simple CWP by

coalescence of coal nodules and generally

requires many years to develop

Coal Workers’ Pneumoconiosis

Microscopically

The lesions consist of dense collagen and

pigment

The center of the lesion is often necrotic,

most likely due to local ischemia

Coal Workers’ Pneumoconiosis

Clinical Course

Simple CWP

-minor impairment of lung function

Complicated CWP

-cause significant respiratory impairment

Caplan syndrome was first described as rheumatoid nod-

ules (Caplan nodules) in the lungs of coal miners

with rheumatoid arthritis

Coal Workers’ Pneumoconiosis

Silicosis Is Caused by Inhalation of Silicon Dioxide (crystalline Silica)

Silica occurs in both

crystalline and amorphous forms

crystalline forms (including quartz,

crystobalite, and tridymite) are much more

fibrogenic

After inhalation, the particles interact with

epithelial cells and macrophages

Causing

activation and release of mediators

IL-1, TNF, fibronectin, lipid mediators, oxygen-

derived free radicals, and fibrogenic cytokines

Pathogenesis

Silicosis

SIMPLE NODULAR SILICOSIS

most common form of silicosis

occur in any worker with long-term

exposure to silica

silicotic nodules less than 1 cm in

diameter (usually 2 to 4 mm)

Morphology

slowly progressing, nodular, fibrosing

pneumoconiosis

Silicotic nodules are characterized grossly in their

early stages by

tiny, barely palpable, discrete, pale-to-blackened

(if coal dust is also present) nodules in the

upper zones of the lungs

Silicotic nodules

characteristic whorled appearance, with

concentrically arranged hyalinized collagen.At the

periphery are aggregates of mononuclear cells,mostly

lymphocytes and fibroblasts.

As the disease progresses, the individual

nodules may coalesce into

hard, collagenous scars, with eventual

progression to PMF

The intervening lung parenchyma may be

compressed or overexpanded, and a

honeycomb pattern may develop

Silicosis

Fibrotic lesions may also occur in the hilar

lymph nodes and pleura

Thin sheets of calcification occur in the

lymph nodes and are seen radiographically

as eggshell calcification

Advanced silicosis (transected lung). Scarring has contracted the upper lobe into a small dark mass (arrow). Note the dense pleural thickening

Clinical Course

Simple silico-sis

does not usually lead to significant

respiratory dysfunction

Pro-gressive massive fibrosis

dyspnea on exertion and later at rest

Silicosis is associated with an increased

susceptibility to tuberculosis

Asbestos-Related Diseases

Asbestos

(Greek, “unquenchable”)

includes a group of fibrous silicate

minerals that occur as thin fibers

Asbestos is a family of crystalline hydrated

silicates that form fibers

2 forms of asbestos2 forms of asbestos

a)serpentine (i.e., curly and flexible)

b) amphibole (i.e., straight, stiff and

brittle)

Asbestosis

Asbestosis

Asbestos

Causing fibrosis by interacting with lung

macrophages

also functions as both a tumor initiator

and a promoter

Morphology

Asbestosis is marked by diffuse pulmonary interstitial fibrosis

Characterized by

the presence of asbestos bodies

which are seen as golden brown, fusiform or beaded rods with a translucent center

coated with an iron-containing proteinaceous material

Asbestosis

Asbestos body

Asbestos bodiesThese ferruginous bodies are golden brown and beaded, with a central, colorless, nonbirefringent core fiber

Pleural plaque. The dome of the diaphragm is coveredby a smooth, pearly white, nodular plaque

Asbestos-related pleural plaquesLarge, discrete fibrocalcific plaques are seen on the pleural surface of the diaphragm

Which of the following inhaled pollutants is most likely to

produce extensive pulmonary fibrosis?

(A) Silica

(B) Tobacco smoke

(C) Ozone

(D) Wood dust

(E) Carbon monoxide

(A) Silica crystals incite a fibrogenic response after ingestion by macrophages. The greater the exposure and the longer the time of exposure, the greater is the lung injury.

• A 63-year-old male worked for 20 years in the sand-

blasting business, and he used no respiratory precautions

during that time. He now has increasing dyspnea without

fever, cough, or chest pain. Which of the following

inflammatory cell types is most crucial to the development

of his underlying disease?

•(A) Plasma cell

•(B) Mast cell

•(C) Eosinophil

•(D) Macrophage

•(E) Natural killer (NK) cell

The correct answer is (D)

Silica is a major component of sand, which contains the

mineral quartz. The small silica crystals are inhaled, and

their buoyancy allows them to be carried to alveoli. There

they are ingested by macrophages, which then secrete

cytokines that recruit other inflammatory cells and

promote fibrogenesis.

Plasma cells secrete immunoglobulins, which are not a major

component of this process.

Mast cells and eosinophils are prominent in type I hypersensitivity

response.

NK lymphocytes are more likely to be a prominent component of

inflammatory processes directed against infectious agents.

A 75-year-old male experienced increasing dyspnoea. The microscopic appearance of the lung is shown here. This is most characteristic for(A) Anthracosis(B) Berylliosis(C) Silicosis(D) Calcinosis(E) Asbestosis

The answer is (E)

The ferruginous bodies shown here are long, thin crystals of asbestos that have become encrusted with iron and calcium. The inflammatory reaction incited by these crystals promotes fibrogenesis and resultant pneumoconiosis.

Berylliosis is marked by noncaseating granulomas.

Anthracosis is a benign process seen in all city dwellers as a consequence of inhaled carbonaceous dust.

Silica crystals are not covered by iron and tend to result in formation of fibrous nodules (i.e., silicotic nodules).

Calcium deposition may occur along alveolar walls with a high serum calcium (i.e., metastatic calcification).

Which of the following morphologic changes can be

seen in advanced cases of both obstructive and restrictive

lung disease?

(A) Marked medial thickening of pulmonary arterioles

(B) Destruction of elastic tissue in the alveolar walls

(C) Fibrosis of the alveolar walls

(D) Hemorrhage in the alveolar lumen

(E) Hyaline membranes lining the airspaces

The correct answer is (A) Changes of pulmonary hypertension are characteristic for restrictive and obstructive lung diseases. This explains, for example, the occurrence of cor pulmonale and right-sided CHF in persons with chronic obstructive pulmonary disease or with pneumoconiosis

Atelectasis (Collapse)

Atelectasis

Neonatal atelectasis

incomplete expansion of the lungs

Acquired atelectasis

collapse of previously inflated lung

producing areas of relatively airless

pulmonary parenchyma

Acquired atelectasis may be divided

into

Resorption (or obstruction)

Compression

Contraction atelectasis

ATELETASIS (Collapse)

Resorption atelectasis

is the consequence of

complete obstruction of an airway leads to

resorption of the oxygen trapped in the

dependent alveoli

without impairment of blood flow through the

affected alveolar walls

lung volume is diminished

the mediastinum shifts toward the atelectatic lung

ATELETASIS (Collapse)

Airway obstruction is caused by

excessive secretions (e.g., mucus plugs) or

exudates within smaller bronchi (bronchial

asthma, chronic bronchitis, bronchiectasis)

postoperative states

aspiration of foreign bodies

bronchial neoplasms (rarely)

ATELETASIS (Collapse)

Compression atelectasis

results whenever

pleural cavity is partially or completely filled by fluid exudate, tumor, blood, or air (pneumothorax)

or with tension pneumothorax, when air pressure impinges on and threatens the function of the lung and mediastinum, especially the major vessels

mediastinum shifts away from the affected lung

ATELETASIS (Collapse)

Compression atelectasis

Contraction atelectasis

occurs when

local or generalized fibrotic changes in the

lung or pleura prevent full expansion

ATELETASIS (Collapse)

reduces oxygenation

predisposes to infection

collapsed lung parenchyma can be re-

expanded (reversible disorder)

except that caused by contraction

ATELETASIS (Collapse)

ANY QUESTIONS?