Restrictive lung diseases

Acute and Chronic

Restrictive lung diseases (Diffuse Interstitial Lung Disease)

• A heterogeneous group of disorders characterized predominantly by diffuse and usually chronic involvement of the pulmonary connective tissue

•Fibrosis•Stiff lung

Which level?principally the most peripheral and delicate interstitium in the alveolar walls

This result in reduced expansion of lung with reduction in total lung capacity

This result in reduced expansion of lung with reduction in total lung capacity

Restrictive lung diseases• Characterized by reduced compliance of the lung.• Caused by:

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2. parenchymal disease: Prominent changes in the interstitium (interstitial lung disease)

1. Chest wall abnormalities

Kyphoscoliosis sever obesity Guilian Barrre’ syndrome

Restrictive lung diseases (Interstitial lung disease)

• Important signs and symptoms:- Dyspnea.- Hypoxia (caused by damage to the alveolar epithelium and interstitial vasculature produces abnormalities in the ventilation-perfusion ratio)

- With progressive severe hypoxia, respiratory failure and cor pulmonale.

- Chest radiographs show diffuse infiltration by small nodules, irregular lines, or "ground-glass shadows

Restrictive lung diseases (Interstitial lung disease)

Acute edema in acute

respiratory distress syndrome

e.g. • Adult respiratory distress

syndrome• Neonatal respiratory distress

syndrome

Acute edema in acute

respiratory distress syndrome

e.g. • Adult respiratory distress

syndrome• Neonatal respiratory distress

syndrome

Chronic chronic inflammation &fibrosise.g.•Pneumoconiosis•Idiopathic pulmonary fibrosis•Sarcoidosis•Hypersensitivity pneumonitis•Immune mediated: SLE•Chemical related: berylliosis

Chronic chronic inflammation &fibrosise.g.•Pneumoconiosis•Idiopathic pulmonary fibrosis•Sarcoidosis•Hypersensitivity pneumonitis•Immune mediated: SLE•Chemical related: berylliosis

• Progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma, and diffuse pulmonary infections.

ACUTE LUNG INJURYAdult respiratory distress

syndrome(ARDS)

Causes of ARDS Direct Lung Injury Indirect Lung Injury

Common CausesPneumonia Sepsis

Aspiration of gastric contents Severe trauma with shock

Uncommon CausesPulmonary contusion Cardiopulmonary bypass

Fat embolism Acute pancreatitis

Near-drowning Drug: bleomycin overdose heroin

Inhalational injury Transfusion of blood products

Reperfusion injury after lung transplantation

Uremia

Causes of ARDS

• ARDS can be a manifestation of sever acute respiratory syndrome (SARS)

• SARS is a coronavirus that destroys the type II pneumocytes and causes diffuse alveolar damage

ACUTE LUNG INJURYAdult respiratory distress syndrome

(ARDS)• Diffuse alveolar damage with result in

increase in alveolar capillary permeability

leakage of protein-rich fluid into alveoli

formation of an intra-alveolar hyaline membrane composed of fibrin and cellular debri

ACUTE LUNG INJURY ARDS

• The pulmonary infiltrates in acute lung injury are usually caused by damage to the alveolar capillary membrane by neutrophils or by ROS •Result in noncardiogenic pulmonary edema.

Acute Respiratory Distress Syndrome Morphology

intra-alveolar hyaline membrane

There is marked proliferation of type II pneumocytes in an attempt to regenerate the alveolar lining.

Resolution is unusual

Acute Respiratory Distress Syndrome Morphology

organization of the fibrin exudates, with resultant intra-alveolar fibrosis.

Marked thickening of the alveolar septa ensues, caused by proliferation of interstitial cells and deposition of collagen.

Acute Respiratory Distress Syndrome

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ACUTE LUNG INJURY ARDS

Clinical Manifestations

1. acute onset of dyspnea

2. decreased arterial oxygen pressure (hypoxemia)

3. development of bilateral pulmonary infiltrates on radiographs

absence of clinical evidence of primary left-sided heart failureabsence of clinical evidence of primary left-sided heart failure

Manifestations appear within 72 hours of the initiating insultManifestations appear within 72 hours of the initiating insult

Acute Respiratory Distress Syndrome (ARDS)

Could progress to life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and that may progress to multisystem organ failure.

Clinical CourseHistorically, mortality rates approached

100%.

Despite improvements in supportive therapy the mortality is still about 60%.

Predictors of poor prognosis in ARDS include :advanced age,underlying bacteremia (sepsis) the development of multisystem (especially

cardiac, renal, or hepatic) failure.

RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN hyaline membrane diseasePathogenesis RDS

– is a disease of premature infants. – It occurs in about 60% of infants born at less than

28 weeks of gestation– Other causes:

• maternal diabetes• cesarean section before the onset of labor• twin gestation.

Hyaline membrane disease

Chronic restrictive lung disease(Chronic interstitial lung

disease)• Are a heterogenous group with little

uniformity regarding terminology and classification.

Chronic restrictive lung diseaseMajor Categories of Chronic Interstitial Lung Disease (CILD)

-Fibrosing: Pneumoconiosis

Usual interstitial pneumonia (idiopathic pulmonary fibrosis) Cryptogenic organizing pneumonia

Associated with collagen vascular diseases Drug and Radiation Reactions

-Granulomatous: Sarcoidosis

Hypersensitivity pneumonitis.Wegener’s granulomatosis

-Eosinophilic granuloma -Smoking related: Desquamative interstitial pneumonia

Respiratory bronchiolitis-associated interstitial lung disease

Chronic Interstitial Lung diseaseCILD

• Many entities are of unknown cause and pathogenesis

• Similar clinical signs, symptoms, radiographic alterations and pathophysiologic changes.– Patient have reduced forced vital capacity,

however the FEV1/ FVC is normal

• Account for about 15% of non-infectious lung diseases.

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)

(Usual interstitial pneumonia)UIP

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)

(Usual interstitial pneumonia)UIP

• A clinicopathologic syndrome with characteristic radiologic, pathologic and clinical features.– Radiology: Bilateral lung nodular infiltratre– Histology: diffuse interstitial fibrosis and inflammation.– Clinical features:

• Dyspnea, advanced cases result in sever hypoxemia and cyanosis.• Males are more affected than female• 2/3 of pt. older than 60 years

PathogenesisSome form of alveolar wall injury result in interstitial edema and alveolitis.

Type I pneumocyte is more susceptible to injury.

Type II pneumocyte hyperplasia (regenerate).

Fibroblast proliferation with progressive fibrosis of intra-alveolar exudate and interalveolar septa.

IgG deposits are seen in alveolar wall.

IL-8 leukotriens FGF, TGF-, PDGF

Morphology of IPF Gross -The lungs are firm.

-Pulmonary edema.

• The morphologic changes vary according to the stage of the disease.

• Early cases:-Intraalveolar exudate.-Hyaline membranes.-Infiltration of the alveolar septa with mononuclear cells.-Hyperplasia of type II pneumocytes

-

Morphology of IPF

Advancing disease:-Organization of the intraalveolar exudates by fibrous tissue.-Thickening of the alveolar septa owing to fibrosis and variable amounts of inflammation.-Alternating areas of fibrosis and normal tissue.

- Geographic variation - Temporal variation• In the end, the lung consists of spaces lined by cuboidal or

columnar epithelium separated by inflammatory fibrous tissue (honeycomb lung).

honeycomb lung

Prognosis of IPF

• Gradual onset of dyspnea with respiratory difficulty.

• Hypoxemia and cyanosis.• Cor pulmonale and cardiac failure may result.• The progression in individual cases is

unpredictable.• The median survival is about 2 to 4 years.

Smoking related CILDDesquamative interstitial pneumonia

• Smoking related

• Age : fourth decade

• Dyspnea and cough

• Complete recovery after

cessation of smoking

Hypersensitivity pneumonitis

• An immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis.

• Hypersensitivity to inhaled antigens in the form of organic substance: moldy hay, e.g. farmer’s lung, humidified lung or pigeon breeder’s lung.

Hypersensitivity pneumonitis

• May present either as an acute reaction with fever, cough, dypsnea and constitutional complains 4 to 8 hours after exposure

or

as a chronic disease with insidious onset of cough, dyspnea, malaise and weight loss.

Hypersensitivity pneumonitis

Acute form • result from the combination

of:

- A direct irritant effect.

- Activation of the complement pathway

- Immune complex

Acute form • result from the combination

of:

- A direct irritant effect.

- Activation of the complement pathway

- Immune complex

Chronic form of the disease is mediated by delayed hypersensitivity reactions.

Chronic form of the disease is mediated by delayed hypersensitivity reactions.

Selected cause of hypersensivity pneumonitis

Syndrome Exposure Antigens

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Plant product:

Farmer’s lung Moldy hay Micropolyspora faeni.

Bagassosis sugar cane Thermophilic Actinomycet

Maple bark disease Maple bark Cryptostroma Corticale

Animal products:

Pigeon breeder’s lung Pigeons Pigeon serum proteins

Chemicals:

Trimelitic anhydried Chemical industry Haptenated protein

pneumonia

Morphology of hypersensitivity pneumonitisMononuclear cell

infiltrates in the alveoli and alveolar walls and around terminal bronchioles.

Interstitial non-caseating granulomas reflecting type IV hypersensitivity reaction are present in more than two thirds of cases.

Diffuse interstitial fibrosis in chronic exposure.

Prognosis of hypersensitivity pneumonitis

• Clinical course is variable – Early, stop antigen exopsure pt. improve

– Late, Diffuse interstitial fibrosis in chronic exposure no improvement

Pneumoconiosis

• Non-neoplastic lung reaction to inhalation of mineral dusts.

• Most common dusts are coal dust, silica, asbestos and beryllium.

Pneumoconiosis

Pathogenesis• The development of pneumoconiosis is dependent on:

- The amount of dust retained in the lung and airways.

a. Concentration of the dust in the ambient air.

b. Duration of the exposure.

c. Effectiveness of the clearance mechanisms.

- The size (1-5) shape.

- Their solubility and physiochemical activity.

- The possible additional effects of other irritants, tobacco

smoking.

• The particles are impacted at alveolar duct macrophage, accumulate inflammatory response fibrosis.

Coal worker’s pneumoconiosis (CWP)

• Occurs in coal workers after many years of underground mine work.

• Two forms:

- The simple form:

- Focal aggregations of coal dust-laden macrophages

(coal macules, 1 to 2 mm) mainly in upper lobes.- Patients have slight cough and blackish sputum.- emphysema ( smoking related).

- The complicated form:With heavier pulmonary burdens of coal dust, fibrous scarring

appears (complicated CWP) also callled progressive massive fibrosis (PMF).

•Complicated CWP:-Black scars exceed 2

cm in diameter some times up to 10 cm

-It consists of dense collagen and carbon pigments.

-Cor pulmonale.-Miners who have

rheumatoid arthritis and PMF are called Caplan’s syndrome.

Coal worker pneumoconiosisMorphology:

• Clinical course:– CWP is usually benign disease with little

symptom– Minor cases progress to PMF– No increased risk to bronchogenic carcinoma

Coal worker pneumoconiosis

Silicosis• Long exposure to silica particles.• Nodular densely fibrosing pneumoconiosis.• Encountered in a diversity of industries: mining of gold,

tin, copper and coal, sandblasting, metal grinding, ceramic manufacturing, drilling and tunneling.

Pathogenesis:• Crystalline silica is highly fibrogenic.• Scattered lymphocytes and macrophages are drawn

rapidly with fibrosis.• Some particles are transported to lymph nodes.

Morphology of Silicosis

• Tiny collagenous nodules that enlarge forming stony-hard large fibrous scars usually in the upper lobes.

• The lung parenchyma between the scars may be compressed or emphysematous.

• Calcifications may appear (eggshell calcification) .

• Similar collagenous nodules within the lymph nodes.

• Fibrous pleural plaques may develop.

•Micro:

-Hyalinized collagen fiber surround an amorphous center (fibrous nodules).

- Scarring progress to PMF.

-Scarring extending and encroching the pulmonary arteries.

-Cor pulmonale.

Morphology of Silicosis

• depend on form of silicosis

Clinical features of Silicosis

Forms of Silicosis

• Acute silicosis:– results from exposure to high dose of silica. Fluid in alveoli.

– Pt. Have rapid onset of tachypnea, cough and repiratory failure.

• Chronic silicosis:– Inhalation of silica for long time with fibrotic nodules ( present in upper lobe of lung &

in subpleural spaces

• Complicated silicosis: – Progression of chronic silicosis with PMF with chronic hypoxia

• Other pulmonary disease:– Increased susceptibility to TB– Caplan syndrome ( uncommon)– Lung cancer

Silica and lung cancer

• The relationship between silica and lung cancer has been a contentious issue, but in 1997, based on evidence from several epidemiologic studies, the International Agency for Research on Cancer concluded that crystalline silica from occupational sources is carcinogenic in humans.

• However, this subject continues to be controversial.

Asbestosis

• Asbestos is a family of crystalline hydrated silicates with a fibrous geometry.

• Two forms: – Serpentine chrysotile (flexible fiber), more

common – Amphibole (straight and stiff fiber), more

pathogenic• Both forms are fibrogenic.

Asbestosis

• Inhalation of asbestos leads to:

- Asbestos pneumoconiosis.

- Pleural effusion.

- Pleural adhesions.

- Parietal pleural fibrocalcific plaques.

- Increased incidence of mesothelioma, bronchogenic carcinoma, laryngeal cancer.

• These consequences occurs decades after exposure has ended.

• An increased incidence of asbestos-related cancers in family members of asbestos workers has alerted the general public to the potential hazards of asbestos in the environment.

Morphology Of Asbestosis• diffuse pulmonary interstitial fibrosis• scarring containing asbestos bodies (ferrougenous bodies).

Pleural plaque in asbestos

Parietal pleura over dome of diaphragm

Asbestosis

• In asbestosis, pt. develop progressively worsened dyspnea with cough and sputum progressing to cor pulmonale and death.

• Both bronchogenic carcinoma and mesothelioma develop in workers exposed to asbestos.

• The risk of bronchogenic carcinoma is fivefold and for mesothelioma is 1000 fold greater.

• The risk of bronchogenic carcinoma in 50 X increased in smoking asbestos workers (but not that of mesothelioma)

Malignant Mesothelioma • Rare cancer of mesothelial cells

• Arise from parietal or visceral pleura

• Can arise from peritoneum and pericardium

• 50% of pt. have history of exposure to asbestos at work

• It also appeared in relatives of asbestos worker or in people living near asbestos factory

• The latent period between exposure and malignant mesothelioma is long (25 to 40 years)

• Nearly all cases are related to amphibole asbestos

• These minerals cannot be removed from the lung and the risk for malignant mesothelioma is life long

• Simian virus 40 (SV40) T antigen is found in 60 to 80% of malignant mesothelioma

• Characteristic E/M finding : numerous long microvilli on cell surface

SUMMARY ARDS is a clinical syndrome of progressive respiratory

insufficiency caused by diffuse alveolar damage

The setting are :• sepsis, severe trauma, and diffuse pulmonary

infections.

There is an imbalance of pro- and anti-inflammatory mediators causing acute inflammatory injury to the alveolar epithelium and capillary endothelium.

Neutrophils and their products have a crucial role in the pathogenesis of ARDS.

The characteristic histologic picture is that of alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence of hyaline membranes lining the alveolar ducts.