FLASHPATHH a z e m A l i

EMPHYSEMAH a z e m A l i

CLINICAL

Emphysema is one of the “obstructive lung diseases” that include:• Chronic bronchitis

• Bronchiectasis

• Small-airway disease “bronchiolitis”

• Asthma

CLINICALObstructive airway

diseaseRestrictive airway

diseaseGeneral features Increase in resistance to

airflow due to obstruction at any level

Reduced expansion of lung parenchyma

Total lung capacity (TLC)

Increased Reduced

Forced Expiratory Volume in one second (FEV1)

Reduced Normal

CLINICAL• Emphysema and chronic bronchitis are often clinically

grouped together and referred to as chronic obstructive pulmonary disease (COPD)

• COPD is the 3rd leading cause of global death

• Usually due to cigarette smoking and air pollution

• Usually present in adults (> 45 years old) and more common in males

• Main symptom are dyspnea and cough

CLINICALPredominant Chronic

BronchitisPredominant Emphysema

Age 40 – 45 years old 50 – 75 years oldAppearance Blue Bloater Pink Buffer

Dyspnea Mild, Late Early, SevereCough Early

Copious sputumLate

Scanty sputumInfections Common Occasional

Respiratory Insufficiency

Repeated Terminal

Cor pulmonale Common Rare, TerminalRadiology Prominent vessels

Large heartHyperinflation

Small heartAirway Resistance Increased Normal or slightly

increasedElastic Recoil Normal Low

CLINICAL• Emphysema is:

– Permanent enlargement of air spaces– Distal to the terminal bronchioles (= Acini)– Due to destruction of the alveolar septa– Without fibrosis

• Three main types:Centriacinar Panacinar Paraseptal

% 97% 1% 2%Affectedsegment

Proximal parts of acini“Respiratory bronchioles =

RB”

Entire acini“RB + alveolar duct +

alveoli”

Distal parts of acini“near septa/pleura”

Lobe Mainly upper lobes Mainly lower lobes Mainly sub-pleuraCause Smoking α1-antitrypsin

deficiencyFibrosis, atelectasis

CLINICAL• Centriacinar emphysema can be seen also in coal workers pneumoconiosis

• Panacinar emphysema can be seen also in talc IV drug abuse and in Ritalin use

CLINICALLines of treatment:• Smoking cessation• Medications (Bronchodilators, Steroids)• Oxygen therapy and Ventilatory support• Surgical (Lung volume reduction surgery, Lung transplant)• Replacement therapy (for alpha-1-antitrypsin deficiency)

Main causes of death:• Coronary artery disease• Respiratory failure• Right-sided heart failure• Massive lung collapse “secondary to pneumothorax”

PATHOGENESIS• Inflammatory mediators

– Smoking stimulate inflammation & inflammatory mediators• Protease / antiprotease imbalance ( = loss of elastin)

– Smoking increases elastase “protease”• released from neutrophils

– Smoking decrease of protective antiproteases– Alpha – 1 antitrypsin deficiency deficiency of antiproteases

• Oxidative stress– Oxidants are released by smoke substance, damaged tissue, and

inflammatory cells more tissue damage• Genetic predisposition

– Some people are genetically more susceptible to these factors than others

GROSS• Increased weight and size of lungs

– Overlap “hide” the heart in situ

• Outer surface– Blebs (< 1 cm) or bullae (> 1 cm)may be seen

• Cut section– Large, cystic alveoli– Anthracosis

• especially in centriacinar type

GROSS• Centriacinar type:Both emphysematous (E) and normal airspacesexist within the same acinus and lobule

• Panacinar type:All airspaces within acini are evenly enlarged

• Paraseptal type:Subpleural airspaces is mainly affected

MICROSCOPY

MICROSCOPYHistological landmarks of lung acinus:• Bronchovascular bundle “terminal bronchiole and arteriole”

– In the center of acinus• Connective tissue septa "secondary lobule of Millar"

– At the periphery of acinus– Often ambiguous in less inflamed lung

• Helpful to determine emphysema types– Upper pic Centriacinar– Lower pic Panacinar

MICROSCOPYEmphysema is characterized by:• Abnormal enlargement of airspaces

• “Floating” alveolar walls fragments within enlarged airspace

• No or little fibrosis

• Any degrees of chronic inflammationThe pores of Kohn are so large that septa appear to be floating or protrude blindly into alveolar spaces with a clubshaped end 

MICROSCOPY• Other Smoking-related conditions:

– Anthracosis– Desquamative interstitial pneumonia– Small airway disease

• Respiratory bronchiolitis• Respiratory bronchiolitis-associated interstitial lung disease

– Large airway disease• Chronic bronchitis

– Pulmonary eosinophilic granuloma• “Langerhans cell histiocytosis”

– Interstitial fibrosis

• Pulmonary hypertension

DIFFERENTIAL DIAGNOSISOther types of emphysema:• Combined pulmonary fibrosis and emphysema (CPFE)

– Coexistence of interstitial fibrosis and emphysema of unknown causes– Poor prognosis in comparison to pure emphysema or pure lung fibrosis

• Interstitial emphysema– Air gains access to the pulmonary interstitium to cause air leak and

pneumothorax– Common in premature infants

• Bullous emphysema– Formation of multiple bullae > 1 cm with thin wall to cause pneumothorax

DIFFERENTIAL DIAGNOSISOther types of emphysema:• Senile emphysema

– Due to age related alteration of acini

• Irregular emphysema– Occurs in relation to scars

• Congenital lobar emphysema– Hyperinflation of one or more lobes due to malformation of bronchioles– Causes respiratory distress

DIFFERENTIAL DIAGNOSIS

Chronic bronchitis

Bronchiectasis Asthma

Small-airway disease

“bronchiolitis”

Emphysema

Site B r o n c h u s Bronchioles AlveoliMajor

pathology

• Mucous gland hyperplasia

• Excess mucus

• Inflammation

• Airway dilation & scarring

• Smooth muscle hyperplasia

• Excess mucus

• Inflammation(eosinophils)

• Inflammatory scarring & obliteration

• Airspace enlargement

• Wall destruction

• No fibrosis

Other obstructive lung diseases:

DIFFERENTIAL DIAGNOSISO t h e r c o n g e n i t a l / c y s t i c l u n g d i s e a s e s :• Congenital:

– Bronchogenic cysts– Congenital pulmonary cysts– Congenital pulmonary airway malformation– Congenital lobar emphysema– Pulmonary sequestration

• Acquired:– Healed abscess– Honeycombing

• Mixed:– Cystic fibrosis

No destruction of alveoli

Fibrosis

DIFFERENTIAL DIAGNOSISAutolysis and inadequate fixation• Similar gross and microscopic appearance can be seen due to

inadequate inflation or fixation of the specimen with formalin– Clinical history– Other smoking-associated conditions

Favor emphysema

DIFFERENTIAL DIAGNOSISLymphangioleiomyomatosis Vs Emphysema?• Women of reproductive age• Multiple cysts and blebs of the lung

– Mural thickening around some cystic spaces– Chylous pleural effusion

• Interstitial proliferation of smooth muscle-like cells around airways and blood vessels

– Tumor cells are positive for HMB45• Other Tuberous Sclerosis-Associated lesions (e.g.

PEComas)

DIFFERENTIAL DIAGNOSISPlacental transmogrification of the lung• Very rare disease• Mainly seen in middle-aged males• Historically considered a microscopic variantof emphysema• Solitary giant bullous

– With/without solid nodules• Papillary/villous structures resembling chorionic villi within cystic

space– Villi cores contain fat cells and primitive mesenchymal clear cells

• Can be associated with pulmonary fibrochondromatous hamartomas

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