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Lecture 7

Prepared and presented by

Marc Imhotep Cray, M.D.

Photo: Colorized scanning electron micrograph of the lung, showing alveoli. Seeley’s Anatomy & Physiology. 10th ed. New York, NY: McGraw-Hill 2010
Respiratory Pathology
Lecture 7

Learning Objective
To provide the basic description, pathogenesis, types,
morphology (gross and microscopic), clinical presentation
(signs & symptoms) and complications of asthma.

Marc Imhotep Cray, M.D. 2

Respiratory Pathology
Schematic representation of Lecture 7

overlap between chronic

obstructive lung diseases:

Marc Imhotep Cray, M.D. Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. 2014 3
Respiratory Pathology
Lecture 7

Asthma: Overview
 Bronchial asthma is a chronic relapsing inflammatory disorder
presenting with hyperreactive airways that cause episodic,
reversible bronchoconstriction
 an enhanced bronchoconstrictor response to type I (allergic) immune
reaction to extrinsic or intrinsic stimuli

 Etiology and pathogenesis is multifactorial and includes genetic

conditions, psychologic stress, and allergic and infectious stimuli

 Severe coughing with expectoration of a characteristic mucoid

sputum with masses of eosinophils and their breakdown products
(Charcot-Leyden crystals), gyrate mucus clumps (Curschmann
spirals), and clusters of epithelial cells (Creola bodies) follows acute
phase of the attack
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Lecture 7

Asthma: Overview (2)

 Histologically, asthmatic bronchitis appears as a mucoid
metaplasia of bronchial epithelium, eosinophilic infiltration,
hyaline thickening of basement membrane, and muscular and
glandular hypertrophy

 Bronchial lumina are often occluded by mucous plugs

 Status asthmaticus is a severe persistent bronchoconstriction

that does not respond to treatment
 It leads to severe hypoxia, acidosis, and hypercapnia and may
be fatal

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Anatomic site Bronchus

Pathology Smooth muscle hyperplasia,

Excess mucus, inflammation

Etiology Immunologic or undefined

Main symptoms Episodic wheezing,
cough, dyspnea

Respiratory Pathology
Lecture 7

Asthma Types: extrinsic and intrinsic

Extrinsic type (atopic) is induced by exposure to an extrinsic antigen
(type I hypersensitivity reaction)
It comprises:
 Atopic (allergic) asthma (the most common type)
 Occupational asthma (fumes, organic and chemical dusts, gases, and other
 Allergic bronchopulmonary aspergillosis
Intrinsic (idiosyncratic/nonatopic) type is initiated by diverse,
nonimmune mechanisms, including:
 Ingestion of aspirin (drug-induced asthma)
 Pulmonary infection, especially viral (most frequent cause of nonatopic asthma)
 Cold
 Inhaled irritants
 Stress
 Exercise
 drugs such as aspirin
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Respiratory Pathology
Lecture 7

Pathogenesis of atopic asthma

 Atopic asthma usually begins in childhood, when it is triggered by
environmental antigens, such as dusts, pollens, animal dander, and
 Patients usually have a positive family history of atopy, and
asthmatic attacks are often preceded by allergic rhinitis, urticaria, or
 It is a classic example of type I immunoglobulin E (IgE)-mediated
hypersensitivity reaction

 In airways, inhaled antigens (allergens) initiate reactions, which

eventually promote IgE production by B cells, growth of mast cells,
and growth and activation of eosinophils

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Respiratory Pathology
Lecture 7

Asthma: acute and late-phase reactions

 Acute (immediate) response is caused by exposure of
presensitized IgE-coated mast cells to same or cross-reacting
antigen and occurs within minutes after stimulation
 Either directly or via neuronal reflexes, mediators induce
bronchoconstriction and increase vascular permeability (edema), mucus
production, and, in extreme instances, hypotension
 Mast cells also release cytokines cause influx of other
leukocytes (particularly eosinophils)

 Late-phase response is mediated by mediators released from

leukocytes (neutrophils, monocytes, lymphocytes, basophils, and
eosinophils), endothelium, and epithelial cells
 Occurs 4 to 8 hours after exposure and may persist for 12 to 24
hour or more
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Respiratory Pathology
Lecture 7

Asthma mediators of bronchospasm

 Mediators responsible for bronchospasm in pts. with bronchial
asthma, include:
 Leukotrienes C4, D4, and E4 cause prolonged
bronchoconstriction, increased vascular permeability, and
increased mucus secretion
 Acetylcholine causes smooth muscle constriction in walls of
 Histamine is a potent bronchoconstrictive agent
 Prostaglandin D2 causes bronchoconstriction and
 Platelet-activating factor causes aggregation of platelets and
release of histamine and serotonin from their granules

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Respiratory Pathology
Lecture 7

Asthma: Pathology
Pathologic characteristics:
 Grossly, lungs are overdistended because of overinflation,
although small areas of atelectasis are sometimes evident as well
 Most striking macroscopic finding is bronchial and bronchiolar
occlusion by thick, tenacious mucous plugs
 Histologically, mucous plugs contain whorls of shed respiratory
epithelium, forming the well-known Curschmann spirals
 Numerous eosinophils and Charcot–Leyden crystals (collections of
crystalloids) are present
 Basement membrane of bronchial epithelium is thickened,
bronchial walls show edema, and an inflammatory infiltrate is
 Submucosal glands are increased in size, whereas bronchial wall
muscle is hypertrophic because of prolonged bronchoconstriction
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Respiratory Pathology
Lecture 7

Bronchial asthma, gross

 Hyperinflated lungs of a
patient who died with
status asthmaticus

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

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Lecture 7

Bronchial asthma, gross

 This cast of the bronchial tree

is formed from inspissated
mucus secretions and was
coughed up during an acute
asthmatic attack

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

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Respiratory Pathology
Lecture 7

Bronchial asthma, microscopic

 Between bronchial cartilage on

right and bronchial lumen filled
with mucus on left is a
submucosa widened by smooth
muscle hypertrophy (*), edema,
and an inflammatory infiltrate
with many eosinophils

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

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Respiratory Pathology
Lecture 7

Bronchial asthma, microscopic

 At high magnification,
numerous eosinophils are
prominent from their bright-
red cytoplasmic granules in
this case of bronchial asthma

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

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Respiratory Pathology
Lecture 7

Bronchial asthma, microscopic

 Sputum analysis with an
acute asthmatic episode
reveals Charcot-Leiden
crystals derived from
breakdown of eosinophil

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

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Lecture 7

Asthma: Clinical features and prognosis

Clinical findings:
 Classic asthmatic attack can last up to several hours it is followed
by prolonged coughing, and raising of copious mucous secretions
provides considerable relief
 Clinical diagnosis is confirmed by demonstration of an elevated
peripheral eosinophil count and presence of eosinophils,
Curschmann spirals, and Charcot–Leyden crystals in sputum
 Emphysema sometimes occurs predisposing to chronic bacterial
infections and sometimes chronic bronchitis, bronchiectasis, or
 In some patients, cor pulmonale and heart failure eventually

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Respiratory Pathology
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Asthma: Treatment
 Pharmacologic therapies used emergently to treat asthma
 short-acting β-adrenergic agonists, such as albuterol, and
 longer-acting agents such as salmeterol
 Theophylline, a methylxanthine, promotes bronchodilation by
increasing cyclic adenosine monophosphate (cAMP), whereas
 anticholinergics, such as tiotropium, also produce
 Long-term asthma control includes:
 use of glucocorticoids,
 leukotriene inhibitors such as zileuton,
 receptor antagonists such as montelukast, and
 mast cell–stabilizing agents such as cromolyn sodium
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Respiratory Pathology
Lecture 7

Sources and further study:

 Damjanov I, Pathology secrets 3rd ed. Philadelphia: Mosby, 2009
 Kemp WL, Burns DK and Brown TG. The Big Picture: Pathology. New York: McGraw-Hill,
 Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015
 L. Maximilian Buja LM and Krueger GR. Netter’s Illustrated Human Pathology Updated Ed.
Philadelphia: Saunders, 2014
 IVMS General and Systemic Pathology Cloud Folder
 Internet Pathology Laboratory for Medical Education: Pulmonary Pathology

 Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed.
Philadelphia: Saunders, 2014
 Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine,
6th Ed. Baltimore: Lippincott Williams & Wilkins, 2012
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Respiratory Pathology
Lecture 7

e-Medicine Articles (Clinical)

Obstructive Airway Diseases
• Alpha1-Antitrypsin Deficiency
• Asthma
• Bronchiectasis
• Bronchiolitis
• Bronchitis
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease
• Emphysema
• Status Asthmaticus

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