PATHOLOGY - 12 - Pulmonary Diseases 2.pdf
OwenEliud
342 views
93 slides
Sep 21, 2024
Slide 1 of 93
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
About This Presentation
diseases of the respiratory system
Slide Content
Ephraim Imhotep Zulu, BSc BMS, MSc Path
University of ZambiaSchool of Health Sciences,Dept. of Biomedical Sciences,
Pathology
Lecture #12
Pulmonary Pathology
| Version 01 | April 2017
Procedural document:
Rare disease nomenclature in English
www.orpha.net www.orphadata.org
University of ZambiaSchool of Health Sciences,Dept. of Biomedical Sciences,
Pathology
Lecture #12
Pulmonary Pathology
| Version 01 | April 2017
Procedural document:
Rare disease nomenclature in English
www.orpha.net www.orphadata.org
Lecture Outline
•Congenital lung diseases
•Atelectasis
•Acute Respiratory Distress Syndrome
•Obstructive Pulmonary Diseases
•Diffuse Interstitial Lung Diseases
•Pulmonary Infections
•Lung Tumors
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY2
•Congenital lung diseases
•Atelectasis
•Acute Respiratory Distress Syndrome
•Obstructive Pulmonary Diseases
•Diffuse Interstitial Lung Diseases
•Pulmonary Infections
•Lung Tumors
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY2
Learning Objectives:
At the end of this lecture, the student is expected to
•Know and understand the aetiology, pathogenesis/pathophysiology and
complications of common Pulmonary diseases
•Know the general description of congenital lung disorders
•Know the general description of morphological types of emphysemas
•Differentiate/Compare and Contrast the following pairs of terms:
•Obstructive vs. Restrictive Lung diseases
•Lobar pneumonia vs. bronchopneumonia
•Bronchitis vs. Emphysema
•Primary Tuberculosis vs. Secondary Tuberculosis
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY3
At the end of this lecture, the student is expected to
•Know and understand the aetiology, pathogenesis/pathophysiology and
complications of common Pulmonary diseases
•Know the general description of congenital lung disorders
•Know the general description of morphological types of emphysemas
•Differentiate/Compare and Contrast the following pairs of terms:
•Obstructive vs. Restrictive Lung diseases
•Lobar pneumonia vs. bronchopneumonia
•Bronchitis vs. Emphysema
•Primary Tuberculosis vs. Secondary Tuberculosis
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY3
Synopsis
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY4
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY4
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY5
Congenital Lung Disorders
•Congenital means something is present “at birth.”
•Congenital lung disorders (also known as malformations
or cystic lung disease) are usually cysts or masses that
develop on the lungs in utero.
•Most congenital lung disorders are discovered during
prenatal ultrasounds.
•About 10% of congenital lung disorders are diagnosed at
birth, while another 14% show up by age 15.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY6
•Congenital means something is present “at birth.”
•Congenital lung disorders (also known as malformations
or cystic lung disease) are usually cysts or masses that
develop on the lungs in utero.
•Most congenital lung disorders are discovered during
prenatal ultrasounds.
•About 10% of congenital lung disorders are diagnosed at
birth, while another 14% show up by age 15.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY6
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY7
Pulmonary Agenesis
•Complete absence of the lung parenchyma, bronchus and pulmonary vasculature
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY8
A -Front view of the thoracic organs. Note a single pulmonary artery perfusing the left lung and lack
of the right lung.B -Posterior view characterized by the complete absence of the right main bronchus
and lung.
•Complete absence of the lung parenchyma, bronchus and pulmonary vasculature
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY8
A -Front view of the thoracic organs. Note a single pulmonary artery perfusing the left lung and lack
of the right lung.B -Posterior view characterized by the complete absence of the right main bronchus
and lung.
Pulmonary Aplasia
•Blind-ending rudimentary
bronchus is present,
without lung parenchyma
or pulmonary vasculature
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY9
Left-sided pulmonary
aplasia. The left chest cavity
contains only the heart which
is partly overlapped by the
anterior border of the right
lung.
•Blind-ending rudimentary
bronchus is present,
without lung parenchyma
or pulmonary vasculature
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY9
Left-sided pulmonary
aplasia. The left chest cavity
contains only the heart which
is partly overlapped by the
anterior border of the right
lung.
Pulmonary Hypoplasia
•Bronchus and rudimentary lungs are present; however, the airways, alveoli, and
pulmonary vessels are decreased in size and number
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY10
•Bronchus and rudimentary lungs are present; however, the airways, alveoli, and
pulmonary vessels are decreased in size and number
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY10
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY11
Congenital Cystic Adenomatoid Malformations (CCAMs)
•CCAMs are sometimes referred to as congenital pulmonary airway
malformations or CPAMs.
•Form when a baby's lung tissue grows more than normal.
•Babies may have just a single CCAM or several.
•They can cause cysts that fill with fluid or solid masses in the lungs.
•CCAMs can also prevent the alveoli (air sacs in the lungs) from
developing normally.
•CCAMs usually form in one lobe of the lung.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY12
•CCAMs are sometimes referred to as congenital pulmonary airway
malformations or CPAMs.
•Form when a baby's lung tissue grows more than normal.
•Babies may have just a single CCAM or several.
•They can cause cysts that fill with fluid or solid masses in the lungs.
•CCAMs can also prevent the alveoli (air sacs in the lungs) from
developing normally.
•CCAMs usually form in one lobe of the lung.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY12
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY13
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY14
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY15
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY16
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY17
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY18
CCAM – type 1 cystic variety. The right lung is enlarged, causing mediastinal shift to the left
and hypoplasia of the left lung.
CCAM – type 1 cystic variety. The right lung is enlarged, causing mediastinal shift to the left
and hypoplasia of the left lung.
Bronchogenic cysts
•Usually develop on the esophagus or trachea but can also sometimes be found on the
lower lobes of the lung. They can compromise airways if they become infected or grow
too large.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY19
•Usually develop on the esophagus or trachea but can also sometimes be found on the
lower lobes of the lung. They can compromise airways if they become infected or grow
too large.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY19
Pulmonary sequestrations
•Are solid masses of lung tissue that don't connect to any of the lungs'
airways or blood supply.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY20
In the picture, The left lung
has been reflected to the
right to reveal a separate
nodule of lung tissue lying
against the ribs. The
sequestration is completely
detached from the rest of
the lung but has a thin
pedicle containing systemic
blood vessels through
which it is supplied from
the aorta.
•Are solid masses of lung tissue that don't connect to any of the lungs'
airways or blood supply.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY20
In the picture, The left lung
has been reflected to the
right to reveal a separate
nodule of lung tissue lying
against the ribs. The
sequestration is completely
detached from the rest of
the lung but has a thin
pedicle containing systemic
blood vessels through
which it is supplied from
the aorta.
Congenital Lobaremphysema
•Is a rare, serious condition that can interfere with an infant’s airways by
trapping airflow during breathing.
•It can result in overinflation of the lobes of the lung.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY21
•Is a rare, serious condition that can interfere with an infant’s airways by
trapping airflow during breathing.
•It can result in overinflation of the lobes of the lung.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY21
Atelectasis (Collapse)
Monday, June 17, 202422Ephraim Zulu - PATHOLOGY
Monday, June 17, 202422Ephraim Zulu - PATHOLOGY
Atelectasis.,
•Atelectasis is loss of lung volume caused by inadequate
expansion of airspaces.
•It results in shunting of inadequately oxygenated blood from
pulmonary arteries into veins, thus giving rise to a ventilation-
perfusion imbalance and hypoxia.
•Atelectasis (except that caused by contraction) is potentially
reversible and should be treated promptly to prevent
hypoxemia and superimposed infection of the collapsed lung.
Monday, June 17, 202423Ephraim Zulu - PATHOLOGY
•Atelectasis is loss of lung volume caused by inadequate
expansion of airspaces.
•It results in shunting of inadequately oxygenated blood from
pulmonary arteries into veins, thus giving rise to a ventilation-
perfusion imbalance and hypoxia.
•Atelectasis (except that caused by contraction) is potentially
reversible and should be treated promptly to prevent
hypoxemia and superimposed infection of the collapsed lung.
Monday, June 17, 202423Ephraim Zulu - PATHOLOGY
Types of Atelectasis
•Resorption Atelectasis Occurs when an obstruction (eg mucous or
mucopurulent plug) prevents air from reaching distal airways.
•Compression Atelectasis AKA passive or relaxation atelectasis is usually
associated with accumulations of fluid, blood, or air within the pleural cavity,
which mechanically collapse the adjacent lung.
•Contraction Atelectasis AKA cicatrization occurs when either local or
generalized fibrotic changes in the lung or pleura hamper expansion and
increase elastic recoil during expiration
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY24
•Resorption Atelectasis Occurs when an obstruction (eg mucous or
mucopurulent plug) prevents air from reaching distal airways.
•Compression Atelectasis AKA passive or relaxation atelectasis is usually
associated with accumulations of fluid, blood, or air within the pleural cavity,
which mechanically collapse the adjacent lung.
•Contraction Atelectasis AKA cicatrization occurs when either local or
generalized fibrotic changes in the lung or pleura hamper expansion and
increase elastic recoil during expiration
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY24
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY25
On the basis of the underlying mechanism or the distribution of alveolar collapse,
atelectasis is classified into three forms.
On the basis of the underlying mechanism or the distribution of alveolar collapse,
atelectasis is classified into three forms.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY26
331Chapter 14 • Diseases of the Respiratory System
change gases properly and invites infection. There are
three types of atelectasis:
•Resorption atelectasisoccurs when a bronchial ob-
struction prevents air from reaching part of the lung,
and the air in the alveoli beyond the obstruction is
completely absorbed by blood circulating through
the alveoli. The most common cause of obstruction
is a mucous plug formed during general anesthesia.
Other causes include asthma, bronchitis, and ob-
structing tumors. A cause in children is aspiration of
foreign objects.
•Compression atelectasis(Fig. 14-4) occurs when ex-
ternal pressure is exerted on the lung from pleural
blood, fluid, or air or from abdominal upward pres-
sure on the diaphragm. Examples include pleural ef-
fusion of congestive heart failure, and compression
of the posterior lower lobes caused by upward pres-
sure on the diaphragm from patients who are bedrid-
den, who have ascites, or who have had chest or ab-
dominal surgery and are not breathing normally
because of pain associated with each breath.
•Contraction atelectasisoccurs when scars in the lung
or pleura constrict, collapsing the lung. Examples in-
clude tuberculous lung scars and pleural scars from
chronic pleural inflammation.
Compression and resorption atelectases are re-
versible; contraction atelectasis is not. Severe atelectasis
can cause hypoxia, and chronic or recurrent atelectasis
invites infection.
In right middle lobe syndrome, the right middle
lobe undergoes atelectasis because the bronchus is ob-
structed. Recall that the right lung has three lobes, the
smallest of them the right middle lobe, which is sand-
wiched anteriorly between the much larger upper and
lower lobes. The right middle lobe is served by an un-
usually long, thin bronchus that is particularly prone to
obstruction from bronchial mucus or inflammatory de-
bris. Recurrent episodes of atelectasis may evolve into
right middle lobe pneumonia or abscess.
Obstructive Lung Disease
In obstructive lung diseasethere is some general bar-
rier to the smooth flow of air through the bronchi. Lung
volume is not affected. The problem is getting air out,
not getting air in. The patient can draw a quick and
deep breath, but exhalation is difficult and slow because
small bronchioles are constricted, and the patient must
breathe in again before the previous breath has been
completely exhaled. The result is slow, labored breath-
ing with an audible expiratory wheeze as air whistles
through tight bronchi.
Recall from the discussion above and Figure 14-3 that
in obstructive disease the one-second forced expiratory
volume (FEV1) is low, and volume (forced vital capac-
ity, FVC) is normal. Therefore, the ratio FEV1/FVC is
low.
ASTHMA
Asthmais a chronic inflammatory disease of small
bronchi and bronchioles that is characterized by
episodes of bronchospasm and airtrapping. In normal
breathing, bronchioles expand slightly with inhalation
and constrict slightly on exhalation. In asthma the con-
striction on exhalation is exaggerated and obstructs air
outflow. The pathologic lesion is chronic inflammation,
sometimes associated with allergy, but in most cases
asthma is triggered by inhaled irritants, such as ciga-
rette smoke or polluted air. Regardless of the initial ir-
ritant, with repeated exposure bronchioles become pro-
gressively inflamed, irritated, and hyperreactive to
irritants.
Asthma can be classified according to the irritant in-
volved.
•Allergic asthma: In some patients the irritant is an al-
lergen that stimulates a type I hypersensitivity (ana-
Normal, aerated lung
SUPERIOR
INFERIOR
ANTERIOR
POSTERIOR
Airless, atelectatic
lung
Figure 14-4Compression atelectasis.Lateral view of right lung. In
this reclining patient pleural fluid compressed the lower and posterior
aspects of the right lung, which are dark and airless.
90981 ch 14.qxd 10/9/06 10:08 AM Page 331
enough, the function of the affected lung may be jeopardized
and the mediastinum may shift awayfrom the affected side.
In long-standing atelectasis, the area of collapsed lung
becomes fibrotic and bronchi dilate, in part due to infection
distal to the obstruction. Permanent bronchial dilation
(bronchiectasis) results.
Right middle lobe syndromerefers to atelectasis due to
obstruction of the bronchus to the right middle lobe, usually
from external compression by hilar lymph nodes. This
bronchus is particularly susceptible to external compres-
sion because it is long and slender and surrounded by
lymph nodes. Histologically, the lung shows bronchiectasis,
chronic bronchitis and bronchiolitis, lymphoid hyperplasia,
abscess formation and dense fibrosis. Acute and organizing
pneumonia may both be present. Tuberculous lymphadeni-
tis or metastatic lung cancer may cause the lymph node
enlargement, but the cause of the obstruction is often unde-
termined.
Bronchiectasis Is Irreversible Dilation of Bronchi
Caused by Destruction of Bronchial Wall Muscle
and Elastic Elements
ETIOLOGIC FACTORS: Bronchiectasis may be
obstructive or nonobstructive.
Obstructive bronchiectasisis localized and
occurs distal to a mechanical obstruction of a central bronchus
by, for example, tumors, inhaled foreign bodies, mucous
plugs in asthma or lymph node enlargement. Nonobstructive
bronchiectasisusually follows respiratory infections or
defects in airway defenses from infection. It may be localized
or generalized.
Localizednonobstructive bronchiectasis was once com-
mon, usually following childhood bronchopulmonary infec-
tions with measles, pertussis or other bacteria. Vaccines and
antibiotics have reduced the incidence of bronchiectasis, but
most cases still follow bronchopulmonary infection, usually
with adenovirus or RSV. Childhood respiratory infections
remain important causes of bronchiectasis in less developed
parts of the world.
Generalized bronchiectasisis, for the most part, second-
ary to inherited impairment in host defense mechanisms or
acquired conditions that permit introduction of infectious
organisms into the airways. Acquired disorders that predis-
pose to bronchiectasis include (1) neurologic diseases that
impair consciousness, swallowing, respiratory excursions and
the cough reflex; (2) incompetence of the lower esophageal
sphincter; (3) nasogastric intubation; and (4) chronic bronchi-
tis. The main inherited conditionsassociated with general-
ized bronchiectasis are cystic fibrosis, dyskinetic ciliary
syndromes, hypogammaglobulinemias and deficiencies of
specific immunoglobulin (Ig) G subclasses.
Kartagener syndromeis one of the immotile cilia syn-
dromes (ciliary dyskinesia) and consists of the triad of dex-
trocardia (with or without situs inversus), bronchiectasis and
sinusitis. It is caused by defects in the outer or inner dynein
arms of cilia, which generate or regulate cilia beats, respec-
tively. Other dyskinetic ciliary syndromes include radial
spoke deficiency (“Sturgess syndrome”) and absence of the
central doublet of cilia. In these diseases cilia are deficient
throughout the body. Both men and women are sterile,
because of impaired ciliary mobility in the vas deferens and
the fallopian tube. In the respiratory tract, ciliary defects lead
to repeated upper and lower respiratory tract infections and,
thus, to bronchiectasis.
Immunodeficiency may also predispose to repeated pul-
monary infection and bronchiectasis. In hypogammaglobu-
linemias the lack of IgAs or IgGs that protect against viruses
or bacteria can result in recurrent lung infections. Acquired
and inherited disorders of neutrophils also lead to a greater
risk of respiratory infections and bronchiectasis.
PATHOLOGY:On gross examination, bronchial dila-
tion is saccular, varicose or cylindrical.
!Saccular bronchiectasisaffects the proximal third to fourth
bronchial branches (Fig. 12-10). These bronchi are severely
dilated and end blindly in dilated sacs, with collapse and
fibrosis of the distal lung parenchyma.
!Cylindrical bronchiectasisinvolves the sixth to the eighth
bronchial branchings, which show uniform, moderate dila-
tion. It is a milder disease than saccular bronchiectasis and
leads to fewer clinical symptoms.
!Varicose bronchiectasisresults in bronchi that resemble
varicose veins when visualized by radiologic bronchogra-
phy, with irregular dilations and constrictions. Two to eight
branchings of bronchi are recognized grossly. Bronchiolar
obliteration is not as severe, and parenchymal abnormali-
ties are variable.
Generalized bronchiectasis is usually bilateral and is most
common in the lower lobes, the left more than the right. Local-
ized bronchiectasis may occur wherever there was obstruction
or infection. Bronchi are dilated, with white or yellow thick-
ened walls. Bronchial lumens often contain thick, mucopuru-
lent secretions. Microscopically, severe inflammation of
bronchi and bronchioles results in destruction of all compo-
nents of the bronchial wall. With the consequent collapse of
distal lung parenchyma, damaged bronchi dilate. Inflamma-
tion of central airways leads to mucus hypersecretion and
abnormalities of the surface epithelium, including squamous
544 RUBIN’S PATHOLOGY
RL
FIGURE 12-9.Atelectasis.The right lung of an infant is pale and
expanded by air; the left lung is collapsed.
331Chapter 14 • Diseases of the Respiratory System
change gases properly and invites infection. There are
three types of atelectasis:
•Resorption atelectasisoccurs when a bronchial ob-
struction prevents air from reaching part of the lung,
and the air in the alveoli beyond the obstruction is
completely absorbed by blood circulating through
the alveoli. The most common cause of obstruction
is a mucous plug formed during general anesthesia.
Other causes include asthma, bronchitis, and ob-
structing tumors. A cause in children is aspiration of
foreign objects.
•Compression atelectasis(Fig. 14-4) occurs when ex-
ternal pressure is exerted on the lung from pleural
blood, fluid, or air or from abdominal upward pres-
sure on the diaphragm. Examples include pleural ef-
fusion of congestive heart failure, and compression
of the posterior lower lobes caused by upward pres-
sure on the diaphragm from patients who are bedrid-
den, who have ascites, or who have had chest or ab-
dominal surgery and are not breathing normally
because of pain associated with each breath.
•Contraction atelectasisoccurs when scars in the lung
or pleura constrict, collapsing the lung. Examples in-
clude tuberculous lung scars and pleural scars from
chronic pleural inflammation.
Compression and resorption atelectases are re-
versible; contraction atelectasis is not. Severe atelectasis
can cause hypoxia, and chronic or recurrent atelectasis
invites infection.
In right middle lobe syndrome, the right middle
lobe undergoes atelectasis because the bronchus is ob-
structed. Recall that the right lung has three lobes, the
smallest of them the right middle lobe, which is sand-
wiched anteriorly between the much larger upper and
lower lobes. The right middle lobe is served by an un-
usually long, thin bronchus that is particularly prone to
obstruction from bronchial mucus or inflammatory de-
bris. Recurrent episodes of atelectasis may evolve into
right middle lobe pneumonia or abscess.
Obstructive Lung Disease
In obstructive lung diseasethere is some general bar-
rier to the smooth flow of air through the bronchi. Lung
volume is not affected. The problem is getting air out,
not getting air in. The patient can draw a quick and
deep breath, but exhalation is difficult and slow because
small bronchioles are constricted, and the patient must
breathe in again before the previous breath has been
completely exhaled. The result is slow, labored breath-
ing with an audible expiratory wheeze as air whistles
through tight bronchi.
Recall from the discussion above and Figure 14-3 that
in obstructive disease the one-second forced expiratory
volume (FEV1) is low, and volume (forced vital capac-
ity, FVC) is normal. Therefore, the ratio FEV1/FVC is
low.
ASTHMA
Asthmais a chronic inflammatory disease of small
bronchi and bronchioles that is characterized by
episodes of bronchospasm and airtrapping. In normal
breathing, bronchioles expand slightly with inhalation
and constrict slightly on exhalation. In asthma the con-
striction on exhalation is exaggerated and obstructs air
outflow. The pathologic lesion is chronic inflammation,
sometimes associated with allergy, but in most cases
asthma is triggered by inhaled irritants, such as ciga-
rette smoke or polluted air. Regardless of the initial ir-
ritant, with repeated exposure bronchioles become pro-
gressively inflamed, irritated, and hyperreactive to
irritants.
Asthma can be classified according to the irritant in-
volved.
•Allergic asthma: In some patients the irritant is an al-
lergen that stimulates a type I hypersensitivity (ana-
Normal, aerated lung
SUPERIOR
INFERIOR
ANTERIOR
POSTERIOR
Airless, atelectatic
lung
Figure 14-4Compression atelectasis.Lateral view of right lung. In
this reclining patient pleural fluid compressed the lower and posterior
aspects of the right lung, which are dark and airless.
90981 ch 14.qxd 10/9/06 10:08 AM Page 331
enough, the function of the affected lung may be jeopardized
and the mediastinum may shift awayfrom the affected side.
In long-standing atelectasis, the area of collapsed lung
becomes fibrotic and bronchi dilate, in part due to infection
distal to the obstruction. Permanent bronchial dilation
(bronchiectasis) results.
Right middle lobe syndromerefers to atelectasis due to
obstruction of the bronchus to the right middle lobe, usually
from external compression by hilar lymph nodes. This
bronchus is particularly susceptible to external compres-
sion because it is long and slender and surrounded by
lymph nodes. Histologically, the lung shows bronchiectasis,
chronic bronchitis and bronchiolitis, lymphoid hyperplasia,
abscess formation and dense fibrosis. Acute and organizing
pneumonia may both be present. Tuberculous lymphadeni-
tis or metastatic lung cancer may cause the lymph node
enlargement, but the cause of the obstruction is often unde-
termined.
Bronchiectasis Is Irreversible Dilation of Bronchi
Caused by Destruction of Bronchial Wall Muscle
and Elastic Elements
ETIOLOGIC FACTORS: Bronchiectasis may be
obstructive or nonobstructive.
Obstructive bronchiectasisis localized and
occurs distal to a mechanical obstruction of a central bronchus
by, for example, tumors, inhaled foreign bodies, mucous
plugs in asthma or lymph node enlargement. Nonobstructive
bronchiectasisusually follows respiratory infections or
defects in airway defenses from infection. It may be localized
or generalized.
Localizednonobstructive bronchiectasis was once com-
mon, usually following childhood bronchopulmonary infec-
tions with measles, pertussis or other bacteria. Vaccines and
antibiotics have reduced the incidence of bronchiectasis, but
most cases still follow bronchopulmonary infection, usually
with adenovirus or RSV. Childhood respiratory infections
remain important causes of bronchiectasis in less developed
parts of the world.
Generalized bronchiectasisis, for the most part, second-
ary to inherited impairment in host defense mechanisms or
acquired conditions that permit introduction of infectious
organisms into the airways. Acquired disorders that predis-
pose to bronchiectasis include (1) neurologic diseases that
impair consciousness, swallowing, respiratory excursions and
the cough reflex; (2) incompetence of the lower esophageal
sphincter; (3) nasogastric intubation; and (4) chronic bronchi-
tis. The main inherited conditionsassociated with general-
ized bronchiectasis are cystic fibrosis, dyskinetic ciliary
syndromes, hypogammaglobulinemias and deficiencies of
specific immunoglobulin (Ig) G subclasses.
Kartagener syndromeis one of the immotile cilia syn-
dromes (ciliary dyskinesia) and consists of the triad of dex-
trocardia (with or without situs inversus), bronchiectasis and
sinusitis. It is caused by defects in the outer or inner dynein
arms of cilia, which generate or regulate cilia beats, respec-
tively. Other dyskinetic ciliary syndromes include radial
spoke deficiency (“Sturgess syndrome”) and absence of the
central doublet of cilia. In these diseases cilia are deficient
throughout the body. Both men and women are sterile,
because of impaired ciliary mobility in the vas deferens and
the fallopian tube. In the respiratory tract, ciliary defects lead
to repeated upper and lower respiratory tract infections and,
thus, to bronchiectasis.
Immunodeficiency may also predispose to repeated pul-
monary infection and bronchiectasis. In hypogammaglobu-
linemias the lack of IgAs or IgGs that protect against viruses
or bacteria can result in recurrent lung infections. Acquired
and inherited disorders of neutrophils also lead to a greater
risk of respiratory infections and bronchiectasis.
PATHOLOGY:On gross examination, bronchial dila-
tion is saccular, varicose or cylindrical.
!Saccular bronchiectasisaffects the proximal third to fourth
bronchial branches (Fig. 12-10). These bronchi are severely
dilated and end blindly in dilated sacs, with collapse and
fibrosis of the distal lung parenchyma.
!Cylindrical bronchiectasisinvolves the sixth to the eighth
bronchial branchings, which show uniform, moderate dila-
tion. It is a milder disease than saccular bronchiectasis and
leads to fewer clinical symptoms.
!Varicose bronchiectasisresults in bronchi that resemble
varicose veins when visualized by radiologic bronchogra-
phy, with irregular dilations and constrictions. Two to eight
branchings of bronchi are recognized grossly. Bronchiolar
obliteration is not as severe, and parenchymal abnormali-
ties are variable.
Generalized bronchiectasis is usually bilateral and is most
common in the lower lobes, the left more than the right. Local-
ized bronchiectasis may occur wherever there was obstruction
or infection. Bronchi are dilated, with white or yellow thick-
ened walls. Bronchial lumens often contain thick, mucopuru-
lent secretions. Microscopically, severe inflammation of
bronchi and bronchioles results in destruction of all compo-
nents of the bronchial wall. With the consequent collapse of
distal lung parenchyma, damaged bronchi dilate. Inflamma-
tion of central airways leads to mucus hypersecretion and
abnormalities of the surface epithelium, including squamous
544 RUBIN’S PATHOLOGY
RL
FIGURE 12-9.Atelectasis.The right lung of an infant is pale and
expanded by air; the left lung is collapsed.
Acute Respiratory Distress Syndrome (ARDS)
Monday, June 17, 202427Ephraim Zulu - PATHOLOGY
ARDS is a clinical syndrome
caused by diffuse alveolar
capillary and epithelial damage.
Monday, June 17, 202427Ephraim Zulu - PATHOLOGY
ARDS is a clinical syndrome
caused by diffuse alveolar
capillary and epithelial damage.
Monday, June 17, 202428Ephraim Zulu - PATHOLOGY
ARDS - Pathogenesis.,
ARDS - Pathogenesis.,
Obstructive Vs Restrictive Pulmonary Diseases
Monday, June 17, 202429Ephraim Zulu - PATHOLOGY
Monday, June 17, 202429Ephraim Zulu - PATHOLOGY
Obstructive Pulmonary Diseases
Given their propensity to coexist, emphysema and chronic bronchitis are often clinically
grouped together under the rubric of chronic obstructive pulmonary disease (COPD).
Monday, June 17, 202430Ephraim Zulu - PATHOLOGY
The Respiratory System
CHAPTER 15
459
bronchitis. Cigarette smoke, however, pre dis poses to infection
responsible for acute exacerbation in chronic bronchitis.
5. Familial and genetic factors ! ere appears to be a poorly-
de" ned familial tendency and genetic pre dis position to develop
disabling chronic bronchitis. However, it is more likely that
nonsmoker family mem bers who remain in the air-pollution of
home are signi" cantly exposed to smoke (passive smoking) and
hence have increased blood levels of carbon monoxide.
MORPHOLOGIC FEATURES Grossly, the bronchial wall
is thickened, hyperaemic and oedematous. Lumina of the
bronchi and bronchioles may contain mucus plugs and
purulent exudate.
Microscopically, just as there is clinical de" nition, there
is histologic de" nition of chronic bronchitis by increased
Reid index. Reid index is the ratio between thickness
of the submucosal mucus glands (i.e. hypertrophy and
hyperplasia) in the cartilage-containing large airways to
that of the total bronchial wall (Fig. 15.17). ! e increase in
thickness can be quanti tatively assessed by micrometer lens
or by morphometry. ! e bronchial epithelium may show
squamous metaplasia and dysplasia. ! ere is little chronic
in# ammatory cell in" ltrate. ! e non-cartilage containing
small airways show goblet cell hyperplasia and intra luminal
and peri bronchial " brosis.
CLINICAL FEATURES ! ere is considerable overlap of
clinical features of chronic bronchitis and pulmonary emphy-
sema (discussed below) as quite often the two coexist. Some
important features of ‘predominant bronchitis’ are as under:
1. Persistent cough with copious expectoration of long
duration; initially beginning in a heavy smoker with ‘morning
catarrh’ or ‘throat clearing’ which worsens in winter.
2. Recurrent respiratory infections are common.
3. Dyspnoea is generally not prominent at rest but is more on
exertion.
4. Patients are called ‘blue bloaters’ due to cyanosis and
oedema.
5. Features of right heart failure (cor pulmonale) are common.
6. Chest X-ray shows enlarged heart with prominent vessels.
EMPHYSEMA
! e WHO has de" ned pulmonary emphysema as combination
of permanent dilatation of air spaces distal to the terminal
bronchioles and the destruction of the walls of dilated air
spaces. ! us, emphysema is de" ned morphologically, while
chronic bronchitis is de" ned clinically. Since the two conditions
coexist frequently and show considerable overlap in their
clinical features, it is usual to label patients as ‘predominant
emphysema’ and ‘predominant bronchitis’.
CLASSIFICATION As mentioned in the beginning of this
chapter, a lobule is composed of about 5 acini distal to a terminal
bronchiole and that an acinus consists of 3 to 5 generations
of respiratory bronchioles and a variable number of alveolar
ducts and alveolar sacs (page 442). As per WHO de" nition of
pulmonary emphysema, it is classi" ed according to the portion
of the acinus involved, into 5 types: centri acinar, panacinar
(panlobular), para-septal (distal acinar), irregular (para-
cicatricial) and mixed (unclassi " ed) emphysema. A number
Table 15.4Contrasting features of major forms of COPD.
FEATURE CHRONIC
BRONCHITIS
EMPHYSEMA ASTHMA BRONCHIECTASIS SMALL AIRWAYS
DISEASE
1. Location Bronchus Acinus Bronchus Bronchus Bronchiole
2. Age at diagnosisAdults Adults Extrinsic: children
Intrinsic: adults
Adults Children
3. Etiology Smoking,
air pollution
Smoking,
air pollution
Extrinsic: allergy
Intrinsic: viral
infection
Infection,
obstruction
Viral infection,
smoke
4. Pathogenesis Impaired ciliary
movement
De! ciency of D-1
antitrypsin
IgE-sensitised mast
cells
Damaged airways Damage to surfactant
5. Major gross
feature
Thickened bronchial
wall
Distended air sacs Overdistended lungs Dilated bronchi and
bronchioles
Occluded bronchioles
6. Main histologyHyperplasia of
mucous glands
Broken alveolar septa Mucus plugs in
bronchioles
In" ammed bronchi Fibrous plugs in
bronchioles
7. Major clinical
feature
Persistent cough with
expectoration
Exertional dyspnoea Bronchosplasm Copious foul-smelling
expectoration
Cough, dyspnoea
Figure 15.17 Diagrammatic representation of increased Reid’s index in
chronic bronchitis.
Given their propensity to coexist, emphysema and chronic bronchitis are often clinically
grouped together under the rubric of chronic obstructive pulmonary disease (COPD).
Monday, June 17, 202430Ephraim Zulu - PATHOLOGY
The Respiratory System
CHAPTER 15
459
bronchitis. Cigarette smoke, however, pre dis poses to infection
responsible for acute exacerbation in chronic bronchitis.
5. Familial and genetic factors ! ere appears to be a poorly-
de" ned familial tendency and genetic pre dis position to develop
disabling chronic bronchitis. However, it is more likely that
nonsmoker family mem bers who remain in the air-pollution of
home are signi" cantly exposed to smoke (passive smoking) and
hence have increased blood levels of carbon monoxide.
MORPHOLOGIC FEATURES Grossly, the bronchial wall
is thickened, hyperaemic and oedematous. Lumina of the
bronchi and bronchioles may contain mucus plugs and
purulent exudate.
Microscopically, just as there is clinical de" nition, there
is histologic de" nition of chronic bronchitis by increased
Reid index. Reid index is the ratio between thickness
of the submucosal mucus glands (i.e. hypertrophy and
hyperplasia) in the cartilage-containing large airways to
that of the total bronchial wall (Fig. 15.17). ! e increase in
thickness can be quanti tatively assessed by micrometer lens
or by morphometry. ! e bronchial epithelium may show
squamous metaplasia and dysplasia. ! ere is little chronic
in# ammatory cell in" ltrate. ! e non-cartilage containing
small airways show goblet cell hyperplasia and intra luminal
and peri bronchial " brosis.
CLINICAL FEATURES ! ere is considerable overlap of
clinical features of chronic bronchitis and pulmonary emphy-
sema (discussed below) as quite often the two coexist. Some
important features of ‘predominant bronchitis’ are as under:
1. Persistent cough with copious expectoration of long
duration; initially beginning in a heavy smoker with ‘morning
catarrh’ or ‘throat clearing’ which worsens in winter.
2. Recurrent respiratory infections are common.
3. Dyspnoea is generally not prominent at rest but is more on
exertion.
4. Patients are called ‘blue bloaters’ due to cyanosis and
oedema.
5. Features of right heart failure (cor pulmonale) are common.
6. Chest X-ray shows enlarged heart with prominent vessels.
EMPHYSEMA
! e WHO has de" ned pulmonary emphysema as combination
of permanent dilatation of air spaces distal to the terminal
bronchioles and the destruction of the walls of dilated air
spaces. ! us, emphysema is de" ned morphologically, while
chronic bronchitis is de" ned clinically. Since the two conditions
coexist frequently and show considerable overlap in their
clinical features, it is usual to label patients as ‘predominant
emphysema’ and ‘predominant bronchitis’.
CLASSIFICATION As mentioned in the beginning of this
chapter, a lobule is composed of about 5 acini distal to a terminal
bronchiole and that an acinus consists of 3 to 5 generations
of respiratory bronchioles and a variable number of alveolar
ducts and alveolar sacs (page 442). As per WHO de" nition of
pulmonary emphysema, it is classi" ed according to the portion
of the acinus involved, into 5 types: centri acinar, panacinar
(panlobular), para-septal (distal acinar), irregular (para-
cicatricial) and mixed (unclassi " ed) emphysema. A number
Table 15.4Contrasting features of major forms of COPD.
FEATURE CHRONIC
BRONCHITIS
EMPHYSEMA ASTHMA BRONCHIECTASIS SMALL AIRWAYS
DISEASE
1. Location Bronchus Acinus Bronchus Bronchus Bronchiole
2. Age at diagnosisAdults Adults Extrinsic: children
Intrinsic: adults
Adults Children
3. Etiology Smoking,
air pollution
Smoking,
air pollution
Extrinsic: allergy
Intrinsic: viral
infection
Infection,
obstruction
Viral infection,
smoke
4. Pathogenesis Impaired ciliary
movement
De! ciency of D-1
antitrypsin
IgE-sensitised mast
cells
Damaged airways Damage to surfactant
5. Major gross
feature
Thickened bronchial
wall
Distended air sacs Overdistended lungs Dilated bronchi and
bronchioles
Occluded bronchioles
6. Main histologyHyperplasia of
mucous glands
Broken alveolar septa Mucus plugs in
bronchioles
In" ammed bronchi Fibrous plugs in
bronchioles
7. Major clinical
feature
Persistent cough with
expectoration
Exertional dyspnoea Bronchosplasm Copious foul-smelling
expectoration
Cough, dyspnoea
Figure 15.17 Diagrammatic representation of increased Reid’s index in
chronic bronchitis.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY31
Monday, June 17, 202432Ephraim Zulu - PATHOLOGY
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY33
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY34
92 / CHAPTER 6
is much lower than in asthma. ! ere is signifi cant interindividual variability in
the response to the inhalants. First-degree relatives of COPD patients are more
likely to have airfl ow obstruction suggesting a genetic predisposition. Indeed,
polymorphisms in the tumor necrosis factor and heme oxygenase-1 genes have
been associated with an increased risk of COPD.
Generation of proteases, reactive oxygen species, and other toxic substances by
the infl ammatory cells may then degrade the connective tissue substratum of the
lung. In the peripheral airways, the response to injury includes collagen deposition
and scar formation. ! is is di" erent than in the alveolar space. Here destruction
of elastin fi bers along with epithelial and endothelial cell apoptosis leads to loss of
the alveolar walls without scar formation. ! us, abnormal repair mechanisms are
a likely component of COPD pathogenesis.
An imbalance between proteases and counterbalancing antiproteases has long
been thought to be central to the development of emphysema. ! is is supported by
the ability to produce emphysema in animal models by the instillation of elastase
and by the observation that individuals who are defi cient in D
1
-antitrypsin su" er
from premature-onset emphysema. D
1
-Antitrypsin is a serum protein produced by
the liver that is responsible for the inhibition of neutrophil elastase. ! e inability
to convincingly demonstrate an imbalance between proteases and antiproteases
in the lungs of most other patients with COPD has raised questions about this
hypothesis. However, quantum proteolysis may be occurring on a level that we are
currently unable to measure in these patients.
Injury to Respiratory Cells
Inhalation of Gas & Particles
Inflammation
Genetic
Susceptibility
Protective
Mechanisms
& Repair
Apoptosis Elastolysis
Emphysema
Chronic
Bronchitis
COPD
Peribronchial
Fibrosis
Figure 6–3. Schematic of pathogenesis of chronic obstructive pulmonary disease
(COPD).
92 / CHAPTER 6
is much lower than in asthma. ! ere is signifi cant interindividual variability in
the response to the inhalants. First-degree relatives of COPD patients are more
likely to have airfl ow obstruction suggesting a genetic predisposition. Indeed,
polymorphisms in the tumor necrosis factor and heme oxygenase-1 genes have
been associated with an increased risk of COPD.
Generation of proteases, reactive oxygen species, and other toxic substances by
the infl ammatory cells may then degrade the connective tissue substratum of the
lung. In the peripheral airways, the response to injury includes collagen deposition
and scar formation. ! is is di" erent than in the alveolar space. Here destruction
of elastin fi bers along with epithelial and endothelial cell apoptosis leads to loss of
the alveolar walls without scar formation. ! us, abnormal repair mechanisms are
a likely component of COPD pathogenesis.
An imbalance between proteases and counterbalancing antiproteases has long
been thought to be central to the development of emphysema. ! is is supported by
the ability to produce emphysema in animal models by the instillation of elastase
and by the observation that individuals who are defi cient in D
1
-antitrypsin su" er
from premature-onset emphysema. D
1
-Antitrypsin is a serum protein produced by
the liver that is responsible for the inhibition of neutrophil elastase. ! e inability
to convincingly demonstrate an imbalance between proteases and antiproteases
in the lungs of most other patients with COPD has raised questions about this
hypothesis. However, quantum proteolysis may be occurring on a level that we are
currently unable to measure in these patients.
Injury to Respiratory Cells
Inhalation of Gas & Particles
Inflammation
Genetic
Susceptibility
Protective
Mechanisms
& Repair
Apoptosis Elastolysis
Emphysema
Chronic
Bronchitis
COPD
Peribronchial
Fibrosis
Figure 6–3. Schematic of pathogenesis of chronic obstructive pulmonary disease
(COPD).
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY35
COPD – Clinical Features.,
COPD – Clinical Features.,
Emphysema
•Emphysema is characterized by abnormal permanent enlargement of the airspaces
distal to the terminal bronchioles, accompanied by destruction of their walls without
obvious fibrosis.
Monday, June 17, 202436Ephraim Zulu - PATHOLOGY
•Emphysema is characterized by abnormal permanent enlargement of the airspaces
distal to the terminal bronchioles, accompanied by destruction of their walls without
obvious fibrosis.
Monday, June 17, 202436Ephraim Zulu - PATHOLOGY
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY37
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY38
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY39
(perfusion with no ventilation) is unusual in chronic bronchitis.
B. Emphysema—The principal pathologic event in emphysema is thought to be
a continuing destructive process resulting from an imbalance between lung
oxidant insults and lung antioxidants and antielastases (particularly neutrophil
α1-anti-protease) (Figure 9–22). Oxidants, whether endogenous (superoxide
anion) or exogenous (eg, cigarette smoke), can inhibit the normal protective
function of protease inhibitors (antiproteases), allowing progressive tissue
destruction.
FIGURE 9–22 Schema of the elastase–antielastase hypothesis of emphysema. Activation is
represented by solid lines, inhibition by dashed lines. The lung is protected from elastolytic damage by α
1
-
protease inhibitor and α
2
-macroglobulin. Bronchial mucus inhibitor protects the airways. Elastase is derived
primarily from neutrophils, but macrophages secrete an elastase-like metalloprotease and may ingest and
later release neutrophil elastase. Oxidants derived from neutrophils and macrophages or from cigarette
smoke may inactivate α
1
-protease inhibitor and may interfere with lung matrix repair. Endogenous
antioxidants such as superoxide dismutase, glutathione, and catalase protect the lung against oxidant injury.
(MMPs, matrix metalloproteinases.)
In contrast to chronic bronchitis, a disease of the airways, emphysema is a
disease of the surrounding lung parenchyma. The physiologic consequences
result from three important changes: (1) destruction of terminal respiratory units;
(2) loss of alveolar–capillary bed; and (3) loss of the supporting structures of the
Pathogenesis of Emphysema
(perfusion with no ventilation) is unusual in chronic bronchitis.
B. Emphysema—The principal pathologic event in emphysema is thought to be
a continuing destructive process resulting from an imbalance between lung
oxidant insults and lung antioxidants and antielastases (particularly neutrophil
α1-anti-protease) (Figure 9–22). Oxidants, whether endogenous (superoxide
anion) or exogenous (eg, cigarette smoke), can inhibit the normal protective
function of protease inhibitors (antiproteases), allowing progressive tissue
destruction.
FIGURE 9–22 Schema of the elastase–antielastase hypothesis of emphysema. Activation is
represented by solid lines, inhibition by dashed lines. The lung is protected from elastolytic damage by α
1
-
protease inhibitor and α
2
-macroglobulin. Bronchial mucus inhibitor protects the airways. Elastase is derived
primarily from neutrophils, but macrophages secrete an elastase-like metalloprotease and may ingest and
later release neutrophil elastase. Oxidants derived from neutrophils and macrophages or from cigarette
smoke may inactivate α
1
-protease inhibitor and may interfere with lung matrix repair. Endogenous
antioxidants such as superoxide dismutase, glutathione, and catalase protect the lung against oxidant injury.
(MMPs, matrix metalloproteinases.)
In contrast to chronic bronchitis, a disease of the airways, emphysema is a
disease of the surrounding lung parenchyma. The physiologic consequences
result from three important changes: (1) destruction of terminal respiratory units;
(2) loss of alveolar–capillary bed; and (3) loss of the supporting structures of the
Pathogenesis of Emphysema
Monday, June 17, 202440Ephraim Zulu - PATHOLOGY
Lung Disorders 313
c. Epithelial injury and proteolysis of extracellular matrix (ECM): ! is in due to the
action of released products from in" ammatory cells. ! is in turn causes further
in" ammation.
Mechanism that checks the above cycle: ! ese include 1) antielastases (e.g. D
1-
antitrypsin) and 2) antioxidants. If these two mechanisms are defectiveresults in
1) protease-antiprotease imbalance (e.g. D
1-antitrypsin de# ciency) and 2) imbalance
between oxidants and antioxidants.
Unchecked in! ammation and proteolysis: Develops due to de# ciency of the above
protective mechanism.
B. Genetic factors:
De" ciency of D
1-antitrypsin: It is inherited as autosomal recessive, which exhibits
polymorphismtendency to develop emphysema. D
1-antitrypsin is a major inhibitor
of proteases (particularly elastase). It is normally present in serum, tissue " uids, and
macrophages and a balance is maintained between protease and antiproteases. During
in" ammation, protease is secreted by neutrophils.
Polymorphism of TGFB gene: It causes reduced response of mesenchymal cells to
TGF-E signalinginadequate synthesis of ECM.
Matrix metalloproteinases (MMPs) polymorphism: It is associated with increased
levels of MMP-9 and MMP-12increased susceptibility to emphysema.
Emphysema: Imbalance
between
• Protease and
antiprotease
• Oxidants and anti-
oxidants.
!
1-antitrypsin deficiency:
• Autosomal recessive
disorder
• Tendency to develop
emphysema.
Fig. 11.3:! Pathogenesis of emphysema. Exposure to environmental toxins (e.g. cigarette smoke) causes inflammatory
reaction, cell death and proteolysis of extracellular matrix (ECM). In genetically susceptible individuals mesenchymal
cell have decreased capacity to synthesis of ECM. "
1-antitrypsin ("
1-AT) deficiency also result in increased degradation
of ECM
Abbreviations: IL-8, interleukin 8; MMP, matrix metalloproteinases
Emphysema: Most
important etiologic agent
is smoking.
Lung Disorders 313
c. Epithelial injury and proteolysis of extracellular matrix (ECM): ! is in due to the
action of released products from in" ammatory cells. ! is in turn causes further
in" ammation.
Mechanism that checks the above cycle: ! ese include 1) antielastases (e.g. D
1-
antitrypsin) and 2) antioxidants. If these two mechanisms are defectiveresults in
1) protease-antiprotease imbalance (e.g. D
1-antitrypsin de# ciency) and 2) imbalance
between oxidants and antioxidants.
Unchecked in! ammation and proteolysis: Develops due to de# ciency of the above
protective mechanism.
B. Genetic factors:
De" ciency of D
1-antitrypsin: It is inherited as autosomal recessive, which exhibits
polymorphismtendency to develop emphysema. D
1-antitrypsin is a major inhibitor
of proteases (particularly elastase). It is normally present in serum, tissue " uids, and
macrophages and a balance is maintained between protease and antiproteases. During
in" ammation, protease is secreted by neutrophils.
Polymorphism of TGFB gene: It causes reduced response of mesenchymal cells to
TGF-E signalinginadequate synthesis of ECM.
Matrix metalloproteinases (MMPs) polymorphism: It is associated with increased
levels of MMP-9 and MMP-12increased susceptibility to emphysema.
Emphysema: Imbalance
between
• Protease and
antiprotease
• Oxidants and anti-
oxidants.
!
1-antitrypsin deficiency:
• Autosomal recessive
disorder
• Tendency to develop
emphysema.
Fig. 11.3:! Pathogenesis of emphysema. Exposure to environmental toxins (e.g. cigarette smoke) causes inflammatory
reaction, cell death and proteolysis of extracellular matrix (ECM). In genetically susceptible individuals mesenchymal
cell have decreased capacity to synthesis of ECM. "
1-antitrypsin ("
1-AT) deficiency also result in increased degradation
of ECM
Abbreviations: IL-8, interleukin 8; MMP, matrix metalloproteinases
Emphysema: Most
important etiologic agent
is smoking.
Emphysema.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY41
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY41
Chronic Bronchitis
•Chronic bronchitis is common among cigarette smokers and urban
dwellers in smog-ridden cities.
•The diagnosis of chronic bronchitis is made on clinical grounds: it is
defined as a persistent productive cough for at least 3 consecutive
months in at least 2 consecutive years.
•The distinctive feature of chronic bronchitis is hypersecretion of
mucus, beginning in the large airways.
•Although the single most important cause is cigarette smoking, other
air pollutants, such as sulfur dioxide and nitrogen dioxide, may
contribute.
Monday, June 17, 202442Ephraim Zulu - PATHOLOGY
•Chronic bronchitis is common among cigarette smokers and urban
dwellers in smog-ridden cities.
•The diagnosis of chronic bronchitis is made on clinical grounds: it is
defined as a persistent productive cough for at least 3 consecutive
months in at least 2 consecutive years.
•The distinctive feature of chronic bronchitis is hypersecretion of
mucus, beginning in the large airways.
•Although the single most important cause is cigarette smoking, other
air pollutants, such as sulfur dioxide and nitrogen dioxide, may
contribute.
Monday, June 17, 202442Ephraim Zulu - PATHOLOGY
Chronic Bronchitis.,
•These environmental irritants induce hypertrophy of mucous
glands in the trachea and main-stem bronchi and lead to a
marked increase in mucin-secreting goblet cells in the surface
epithelium of smaller bronchi and bronchioles (Histological
and diagnostic feature).
•In addition, these irritants cause inflammation with
infiltration of CD8+ T cells, macrophages, and neutrophils.
• In contrast to asthma, eosinophils are lacking in chronic
bronchitis unless the patient has asthmatic bronchitis.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY43
•These environmental irritants induce hypertrophy of mucous
glands in the trachea and main-stem bronchi and lead to a
marked increase in mucin-secreting goblet cells in the surface
epithelium of smaller bronchi and bronchioles (Histological
and diagnostic feature).
•In addition, these irritants cause inflammation with
infiltration of CD8+ T cells, macrophages, and neutrophils.
• In contrast to asthma, eosinophils are lacking in chronic
bronchitis unless the patient has asthmatic bronchitis.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY43
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY44
Chronic Bronchitis.,
Chronic Bronchitis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY45
Chronic Bronchitis.,
Chronic Bronchitis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY46
Chronic Bronchitis.,
Chronic Bronchitis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY47
Chronic Bronchitis.,
Chronic Bronchitis.,
•Asthma is a chronic inflammatory disorder of the
airways that causes recurrent episodes of wheezing,
breathlessness, chest tightness, and cough,
particularly at night and/or early in the morning.
•The victim labors to get air into the lungs and then
cannot get it out.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY48
Asthma
airways that causes recurrent episodes of wheezing,
breathlessness, chest tightness, and cough,
particularly at night and/or early in the morning.
•The victim labors to get air into the lungs and then
cannot get it out.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY48
Asthma
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY49
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY50
Asthma.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY51
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY51
Asthma.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY52
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY52
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY53
Asthma – Pathophysiology.,
Asthma – Pathophysiology.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY54
Asthma.,
Systemic Pathology
SECTION III
464
pattern in which the features do not ! t clearly into either of the
two main types. " e contrasting features of the two main types
are summed up in Table!15.6.
1. Extrinsic (atopic, allergic) asthma " is is the most
common type of asthma. It usually begins in childhood or
in early adult life. Most patients of this type of asthma have
personal and/or family history of preceding allergic diseases
such as rhinitis, urticaria or infantile eczema. Hyper sensitivity
to various extrinsic antigenic substances or ‘allergens’ is
usually present in these cases. Most of these allergens cause ill-
e# ects by inhalation e.g. house dust, pollens, animal danders,
moulds etc. Occupational asthma stimulated by fumes, gases
and organic and chemical dusts is a variant of extrinsic asthma.
" ere is increased level of IgE in the serum and positive skin
test with the speci! c o# ending inhaled antigen representing an
IgE-mediated type I hypersensi tivity reaction which includes
an ‘acute immediate response’ and a ‘late phase reaction’:
?Acute immediate response is initiated by IgE-sensitised
mast cells (tissue counterparts of circulating baso phils) on
the mucosal surface. Mast cells on degranu lation release
mediators like histamine, leukotrienes, prostaglandins, platelet
activating factor and chemotactic factors for eosinophils and
neutrophils. " e net e# ects of these mediators are broncho-
constriction, oedema, mucus hypersecretion and accumu-
lation of eosinophils and neutrophils.
?Late phase reaction follows the acute immediate response
and is responsible for the prolonged manifes tations of asthma.
It is caused by excessive mobilisation of blood leucocytes that
include basophils besides eosinophils and neutrophils. " ese
result in further release of mediators which accentuate the
above-mentioned e# ects. In addition, in$ ammatory injury is
caused by neutrophils and by major basic protein (MBP) of
eosinophils.
2. Intrinsic (idiosyncratic, non-atopic) asthma " is type
of asthma develops later in adult life with negative personal or
family history of allergy, negative skin test and normal serum
levels of IgE. Most of these patients develop typical symptom-
complex after an upper respiratory tract infection by viruses.
Associated nasal polypi and chronic bronchitis are commonly
present. " ere are no recognisable allergens but about 10% of
patients become hypersensitive to drugs, most notably to small
doses of aspirin (aspirin-sensitive asthma).
3. Mixed type Many patients do not clearly ! t into either of
the above two categories and have mixed features of both. " ose
patients who develop asthma in early life have strong allergic
component, while those who develop the disease late tend to
Table 15.6Contrasting features of the two major types of asthma.
FEATURE EXTRINSIC ASTHMA INTRINSIC ASTHMA
1. Age at onset In childhood In adult
2. Personal/family history Commonly present Absent
3. Preceding allergic illness (atopy) Present (e.g. rhinitis, urticaria, eczema) Absent
4. Allergens Present (dust, pollens, danders etc) None
5. Drug hypersensitivity None Present (usually to aspirin)
6. Serum IgE level Elevated Normal
7. Associated chronic bronchitis, nasal polypsAbsent Present
8. Emphysema Unusual Common
Figure 15.22 Diagrammatic appearance of Curschmann’s spiral and
Charcot-Leyden crystals found in mucus plugs in patients with bronchial
asthma.
be non-allergic. Either type of asthma can be precipitated by
cold, exercise and emotional stress.
MORPHOLOGIC FEATURES " e pathologic changes
are similar in both major types of asthma. " e patho logic
material examined is generally autopsy of lungs in patients
dying of status asthmaticus but the changes are expected to
be similar in non-fatal cases.
Grossly, the lungs are overdistended due to over-in$ ation.
" e cut surface shows characteristic occlusion of the
bronchi and bronchioles by viscid mucus plugs.
Microscopically, the following changes are observed
(Fig. 15.22):
1. " e mucus plugs contain normal or degenerated respira-
tory epithelium forming twisted strips called Curschmann’s
spirals.
2. " e sputum usually contains numerous eosino phils and
diamond-shaped crystals derived from eosino phils called
Charcot-Leyden crystals.
3. " e bronchial wall shows thickened basement membrane
of the bronchial epithelium, submucosal oedema and
in$ ammatory in! ltrate consisting of lymphocytes and
plasma cells with prominence of eosino phils. " ere is
hypertrophy of submucosal glands as well as of the bronchial
smooth muscle.
4. Changes of bronchitis and emphysema may super vene,
especially in intrinsic asthma.
Asthma.,
Systemic Pathology
SECTION III
464
pattern in which the features do not ! t clearly into either of the
two main types. " e contrasting features of the two main types
are summed up in Table!15.6.
1. Extrinsic (atopic, allergic) asthma " is is the most
common type of asthma. It usually begins in childhood or
in early adult life. Most patients of this type of asthma have
personal and/or family history of preceding allergic diseases
such as rhinitis, urticaria or infantile eczema. Hyper sensitivity
to various extrinsic antigenic substances or ‘allergens’ is
usually present in these cases. Most of these allergens cause ill-
e# ects by inhalation e.g. house dust, pollens, animal danders,
moulds etc. Occupational asthma stimulated by fumes, gases
and organic and chemical dusts is a variant of extrinsic asthma.
" ere is increased level of IgE in the serum and positive skin
test with the speci! c o# ending inhaled antigen representing an
IgE-mediated type I hypersensi tivity reaction which includes
an ‘acute immediate response’ and a ‘late phase reaction’:
?Acute immediate response is initiated by IgE-sensitised
mast cells (tissue counterparts of circulating baso phils) on
the mucosal surface. Mast cells on degranu lation release
mediators like histamine, leukotrienes, prostaglandins, platelet
activating factor and chemotactic factors for eosinophils and
neutrophils. " e net e# ects of these mediators are broncho-
constriction, oedema, mucus hypersecretion and accumu-
lation of eosinophils and neutrophils.
?Late phase reaction follows the acute immediate response
and is responsible for the prolonged manifes tations of asthma.
It is caused by excessive mobilisation of blood leucocytes that
include basophils besides eosinophils and neutrophils. " ese
result in further release of mediators which accentuate the
above-mentioned e# ects. In addition, in$ ammatory injury is
caused by neutrophils and by major basic protein (MBP) of
eosinophils.
2. Intrinsic (idiosyncratic, non-atopic) asthma " is type
of asthma develops later in adult life with negative personal or
family history of allergy, negative skin test and normal serum
levels of IgE. Most of these patients develop typical symptom-
complex after an upper respiratory tract infection by viruses.
Associated nasal polypi and chronic bronchitis are commonly
present. " ere are no recognisable allergens but about 10% of
patients become hypersensitive to drugs, most notably to small
doses of aspirin (aspirin-sensitive asthma).
3. Mixed type Many patients do not clearly ! t into either of
the above two categories and have mixed features of both. " ose
patients who develop asthma in early life have strong allergic
component, while those who develop the disease late tend to
Table 15.6Contrasting features of the two major types of asthma.
FEATURE EXTRINSIC ASTHMA INTRINSIC ASTHMA
1. Age at onset In childhood In adult
2. Personal/family history Commonly present Absent
3. Preceding allergic illness (atopy) Present (e.g. rhinitis, urticaria, eczema) Absent
4. Allergens Present (dust, pollens, danders etc) None
5. Drug hypersensitivity None Present (usually to aspirin)
6. Serum IgE level Elevated Normal
7. Associated chronic bronchitis, nasal polypsAbsent Present
8. Emphysema Unusual Common
Figure 15.22 Diagrammatic appearance of Curschmann’s spiral and
Charcot-Leyden crystals found in mucus plugs in patients with bronchial
asthma.
be non-allergic. Either type of asthma can be precipitated by
cold, exercise and emotional stress.
MORPHOLOGIC FEATURES " e pathologic changes
are similar in both major types of asthma. " e patho logic
material examined is generally autopsy of lungs in patients
dying of status asthmaticus but the changes are expected to
be similar in non-fatal cases.
Grossly, the lungs are overdistended due to over-in$ ation.
" e cut surface shows characteristic occlusion of the
bronchi and bronchioles by viscid mucus plugs.
Microscopically, the following changes are observed
(Fig. 15.22):
1. " e mucus plugs contain normal or degenerated respira-
tory epithelium forming twisted strips called Curschmann’s
spirals.
2. " e sputum usually contains numerous eosino phils and
diamond-shaped crystals derived from eosino phils called
Charcot-Leyden crystals.
3. " e bronchial wall shows thickened basement membrane
of the bronchial epithelium, submucosal oedema and
in$ ammatory in! ltrate consisting of lymphocytes and
plasma cells with prominence of eosino phils. " ere is
hypertrophy of submucosal glands as well as of the bronchial
smooth muscle.
4. Changes of bronchitis and emphysema may super vene,
especially in intrinsic asthma.
Bronchiectasis
•Bronchiectasis is the permanent dilation of bronchi and bronchioles caused
by destruction of the muscle and elastic supporting tissue, resulting from or
associated with chronic necrotizing infections.
Monday, June 17, 202455Ephraim Zulu - PATHOLOGY
•Bronchiectasis is the permanent dilation of bronchi and bronchioles caused
by destruction of the muscle and elastic supporting tissue, resulting from or
associated with chronic necrotizing infections.
Monday, June 17, 202455Ephraim Zulu - PATHOLOGY
Bronchiectasis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY56
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY56
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY57
Pathogenesis of bronchiectasis
Pathogenesis of bronchiectasis
Bronchiectasis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY58
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY58
Bronchiectasis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY59
Cross-section of lung demonstrating dilated bronchi extending almost to the pleura.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY59
Cross-section of lung demonstrating dilated bronchi extending almost to the pleura.
Bronchiectasis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY60
The resected upper lobe shows widely
dilated bronchi, with thickening of the
bronchial walls and collapse and
fibrosis of the pulmonary parenchyma.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY60
The resected upper lobe shows widely
dilated bronchi, with thickening of the
bronchial walls and collapse and
fibrosis of the pulmonary parenchyma.
Monday, June 17, 202461Ephraim Zulu - PATHOLOGY
Diffuse Interstitial (Restrictive, Infiltrative) Lung Diseases
The hallmark of these disorders is reduced compliance (i.e., more pressure is required to expand the lungs
because they are stiff), which in turn necessitates increased effort of breathing (dyspnea).
Diffuse Interstitial (Restrictive, Infiltrative) Lung Diseases
The hallmark of these disorders is reduced compliance (i.e., more pressure is required to expand the lungs
because they are stiff), which in turn necessitates increased effort of breathing (dyspnea).
Pneumoconioses
•Pneumoconiosis is the non-neoplastic lung reaction to inhalation of mineral dusts, particulates,
and chemical fume- and vapor. Tobacco smoking worsens the effects of all inhaled mineral dusts,
more so with asbestos than with any other particle.
Monday, June 17, 202462Ephraim Zulu - PATHOLOGY
•Pneumoconiosis is the non-neoplastic lung reaction to inhalation of mineral dusts, particulates,
and chemical fume- and vapor. Tobacco smoking worsens the effects of all inhaled mineral dusts,
more so with asbestos than with any other particle.
Monday, June 17, 202462Ephraim Zulu - PATHOLOGY
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY63
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY64
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY65
574 RUBIN’S PATHOLOGY
Macrophage
COAL
Type I
Type II
Interstitial
macrophage
Interstitial
space
Macrophage
Macrophage
SILICA
Type I
Type II
Interstitial
macrophage
Fibrogenic
factor(s)
Interstitial
space
Macrophage
ASBESTOS
FOCAL DUST EMPHYSEMA SILICOTIC NODULE ASBESTOSIS
Type I
Type II
Interstitial
macrophage
Interstitial
space
Collagen
Collagen
Fibroblast
Fibroblast
Fibroblasts
Asbestos
body
Distal
air space
Interstitial
fibrosis
Terminal
bronchiole
Lymphocytes
Dilated
respiratory
bronchioles
FIGURE 12-50.Pathogenesis of pneumoconioses.The three most important pneumoconioses are illustrated. In simple coal workers’ pneumoco-
niosis, massive amounts of dust are inhaled and engulfed by macrophages. The macrophages pass into the interstitium of the lung and aggregate
around the respiratory bronchioles. Subsequently, the bronchioles dilate. In silicosis, the silica particles are toxic to macrophages, which die and
release a fibrogenic factor. In turn, the released silica is again phagocytosed by other macrophages. The result is a dense fibrotic nodule, the sili-
cotic nodule. Asbestosis is characterized by little dust and much interstitial fibrosis. Asbestos bodies are the classic features.
574 RUBIN’S PATHOLOGY
Macrophage
COAL
Type I
Type II
Interstitial
macrophage
Interstitial
space
Macrophage
Macrophage
SILICA
Type I
Type II
Interstitial
macrophage
Fibrogenic
factor(s)
Interstitial
space
Macrophage
ASBESTOS
FOCAL DUST EMPHYSEMA SILICOTIC NODULE ASBESTOSIS
Type I
Type II
Interstitial
macrophage
Interstitial
space
Collagen
Collagen
Fibroblast
Fibroblast
Fibroblasts
Asbestos
body
Distal
air space
Interstitial
fibrosis
Terminal
bronchiole
Lymphocytes
Dilated
respiratory
bronchioles
FIGURE 12-50.Pathogenesis of pneumoconioses.The three most important pneumoconioses are illustrated. In simple coal workers’ pneumoco-
niosis, massive amounts of dust are inhaled and engulfed by macrophages. The macrophages pass into the interstitium of the lung and aggregate
around the respiratory bronchioles. Subsequently, the bronchioles dilate. In silicosis, the silica particles are toxic to macrophages, which die and
release a fibrogenic factor. In turn, the released silica is again phagocytosed by other macrophages. The result is a dense fibrotic nodule, the sili-
cotic nodule. Asbestosis is characterized by little dust and much interstitial fibrosis. Asbestos bodies are the classic features.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY66
574 RUBIN’S PATHOLOGY
Macrophage
COAL
Type I
Type II
Interstitial
macrophage
Interstitial
space
Macrophage
Macrophage
SILICA
Type I
Type II
Interstitial
macrophage
Fibrogenic
factor(s)
Interstitial
space
Macrophage
ASBESTOS
FOCAL DUST EMPHYSEMA SILICOTIC NODULE ASBESTOSIS
Type I
Type II
Interstitial
macrophage
Interstitial
space
Collagen
Collagen
Fibroblast
Fibroblast
Fibroblasts
Asbestos
body
Distal
air space
Interstitial
fibrosis
Terminal
bronchiole
Lymphocytes
Dilated
respiratory
bronchioles
FIGURE 12-50.Pathogenesis of pneumoconioses.The three most important pneumoconioses are illustrated. In simple coal workers’ pneumoco-
niosis, massive amounts of dust are inhaled and engulfed by macrophages. The macrophages pass into the interstitium of the lung and aggregate
around the respiratory bronchioles. Subsequently, the bronchioles dilate. In silicosis, the silica particles are toxic to macrophages, which die and
release a fibrogenic factor. In turn, the released silica is again phagocytosed by other macrophages. The result is a dense fibrotic nodule, the sili-
cotic nodule. Asbestosis is characterized by little dust and much interstitial fibrosis. Asbestos bodies are the classic features.
574 RUBIN’S PATHOLOGY
Macrophage
COAL
Type I
Type II
Interstitial
macrophage
Interstitial
space
Macrophage
Macrophage
SILICA
Type I
Type II
Interstitial
macrophage
Fibrogenic
factor(s)
Interstitial
space
Macrophage
ASBESTOS
FOCAL DUST EMPHYSEMA SILICOTIC NODULE ASBESTOSIS
Type I
Type II
Interstitial
macrophage
Interstitial
space
Collagen
Collagen
Fibroblast
Fibroblast
Fibroblasts
Asbestos
body
Distal
air space
Interstitial
fibrosis
Terminal
bronchiole
Lymphocytes
Dilated
respiratory
bronchioles
FIGURE 12-50.Pathogenesis of pneumoconioses.The three most important pneumoconioses are illustrated. In simple coal workers’ pneumoco-
niosis, massive amounts of dust are inhaled and engulfed by macrophages. The macrophages pass into the interstitium of the lung and aggregate
around the respiratory bronchioles. Subsequently, the bronchioles dilate. In silicosis, the silica particles are toxic to macrophages, which die and
release a fibrogenic factor. In turn, the released silica is again phagocytosed by other macrophages. The result is a dense fibrotic nodule, the sili-
cotic nodule. Asbestosis is characterized by little dust and much interstitial fibrosis. Asbestos bodies are the classic features.
Monday, June 17, 202467
Asbestosis. Markedly thickened visceral pleura covers the
lateral and diaphragmatic surface of lung. Note also severe
interstitial fibrosis diffusely affecting the lower lobe of the
lung.
Ephraim Zulu - PATHOLOGY
Advanced silicosis (transected lung). Scarring has
contracted the upper lobe into a small dark mass
(arrow). Note the dense pleural thickening.
Pneumoconioses
Asbestosis. Markedly thickened visceral pleura covers the
lateral and diaphragmatic surface of lung. Note also severe
interstitial fibrosis diffusely affecting the lower lobe of the
lung.
Ephraim Zulu - PATHOLOGY
Advanced silicosis (transected lung). Scarring has
contracted the upper lobe into a small dark mass
(arrow). Note the dense pleural thickening.
Pneumoconioses
Sarcoidosis
•Sarcoidosis is a multisystem disease of unknown etiology
characterized by noncaseating granulomas in many tissues and
organs.
•Sarcoidosis occurs throughout the world, affecting both sexes and all
races and ages.
•Sarcoidosis is one of the few pulmonary diseases with a higher
prevalence among nonsmokers.
•The histopathologic sine qua non of sarcoidosis is the noncaseating
epithelioid granuloma, irrespective of the organ involved.
Monday, June 17, 202468Ephraim Zulu - PATHOLOGY
•Sarcoidosis is a multisystem disease of unknown etiology
characterized by noncaseating granulomas in many tissues and
organs.
•Sarcoidosis occurs throughout the world, affecting both sexes and all
races and ages.
•Sarcoidosis is one of the few pulmonary diseases with a higher
prevalence among nonsmokers.
•The histopathologic sine qua non of sarcoidosis is the noncaseating
epithelioid granuloma, irrespective of the organ involved.
Monday, June 17, 202468Ephraim Zulu - PATHOLOGY
Sarcoidosis.,
•Rarely, foci of central necrosis may be present in sarcoid granulomas,
suggesting an infectious process. Caseation necrosis typical of tuberculosis is
absent.
•Although the etiology of sarcoidosis remains unknown, several lines of
evidence suggest that it is a disease of disordered immune regulation in
genetically predisposed individuals exposed to certain environmental
agents.
•Several putative "antigens" have been proposed as the inciting agent for
sarcoidosis (e.g., viruses, mycobacteria, Borrelia, pollen), but thus far there is
no unequivocal evidence to suggest that sarcoidosis is caused by an
infectious agent.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY69
•Rarely, foci of central necrosis may be present in sarcoid granulomas,
suggesting an infectious process. Caseation necrosis typical of tuberculosis is
absent.
•Although the etiology of sarcoidosis remains unknown, several lines of
evidence suggest that it is a disease of disordered immune regulation in
genetically predisposed individuals exposed to certain environmental
agents.
•Several putative "antigens" have been proposed as the inciting agent for
sarcoidosis (e.g., viruses, mycobacteria, Borrelia, pollen), but thus far there is
no unequivocal evidence to suggest that sarcoidosis is caused by an
infectious agent.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY69
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY70
Sarcoidosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY71
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY71
Pulmonary Infections
•Pneumonia can be very broadly defined as any infection in the lung.
Monday, June 17, 202472Ephraim Zulu - PATHOLOGY
•Pneumonia can be very broadly defined as any infection in the lung.
Monday, June 17, 202472Ephraim Zulu - PATHOLOGY
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY73
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY74
Monday, June 17, 202475Ephraim Zulu - PATHOLOGY
Monday, June 17, 202476
Bronchopneumonia. Gross section of lung
showing patches of consolidation (arrows).
Lobar pneumonia—gray hepatization, gross
photograph. The lower lobe is uniformly
consolidated.
Ephraim Zulu - PATHOLOGY
Bronchopneumonia. Gross section of lung
showing patches of consolidation (arrows).
Lobar pneumonia—gray hepatization, gross
photograph. The lower lobe is uniformly
consolidated.
Ephraim Zulu - PATHOLOGY
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY77
Tuberculosis
•Tuberculosis is by far the most important entity within the
spectrum of chronic pneumonias, and causes 6% of all deaths
worldwide, making it the most common cause of death resulting
from a single infectious agent.
•Tuberculosis is a communicable chronic granulomatous disease
caused by Mycobacterium tuberculosis.
•It usually involves the lungs but may affect any organ or tissue in the
body. Typically, the centers of tubercular granulomas undergo
caseous necrosis.
Monday, June 17, 202478Ephraim Zulu - PATHOLOGY
•Tuberculosis is by far the most important entity within the
spectrum of chronic pneumonias, and causes 6% of all deaths
worldwide, making it the most common cause of death resulting
from a single infectious agent.
•Tuberculosis is a communicable chronic granulomatous disease
caused by Mycobacterium tuberculosis.
•It usually involves the lungs but may affect any organ or tissue in the
body. Typically, the centers of tubercular granulomas undergo
caseous necrosis.
Monday, June 17, 202478Ephraim Zulu - PATHOLOGY
Tuberculosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY79
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY79
Tuberculosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY80
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY80
Tuberculosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY81
Exam Preparatory Manual for Undergraduates—General and Systemic Pathology342
TABLE 11.4: Main difference between primary and secondary tuberculosis of lung
Characteristics Primary TB Secondary TB
Type of infection Initial infection in an unsensitized
individual
Infection in a previously sensitized
individual
Source of infection
Exogenous Usually endogenous activation of
latent infection
Site of lung involved Lower part of upper lobe or upper
part of lower lobe and subpleural
Apex and posterior segments of the
upper lobe and superior segments
of lower lobe
Regional lymphnode involvement Significant and prominent Not prominent
Sputum for AFB Rarely positive Commonly positive
Cavity formation Rare Common
Healing Mainly by calcification By fibrosis
Extrapulmonary complicationsVery common Lesion usually localized to lung
Diagnosis: Pulmonary Disease
Based on the history, physical and radiographic ! ndings.
Identi! cation of acid-fast tubercle bacilli in the sputum.
Culture of the sputum: Conventional cultures require up to 10 weeks. Culture is the gold
standard.
PCR ampli! cation of M. tuberculosis: DNA is the rapid method of diagnosis. PCR can detect
as few as 10 organisms in clinical specimens.
Prognosis: Generally good if infections are localized to the lungs. All stages of HIV infection
are associated with an increased risk of tuberculosis.
SARCOIDOSIS
De! nition: Sarcoidosis is a multisystem disease of unknown cause characterized by the
presence of noncaseating granulomas in many tissues and organs.
Organs involved: Sarcoidosis can a" ect every organ of the body. It most commonly
a" ects the lung and the lymph nodes in the mediastinum and hilar regions. Other organs
commonly a" ected are the liver, skin, and eye.
Age and gender: Most patients are young (from 20 to 40 years of age) and more common in
women than in men.
Etiology
Exact cause of sarcoidosis is not known. Factors that play a role in its pathogenesis are: 1)
environmental, 2) genetic, and 3) immunological
Environmental factors: Environmental agents (infectious and noninfectious) have been
suggested as possible causes. Infectious inciting agent includes: mycobacteria (both
Mycobacterium tuberculosis and nontuberculous mycobacteria), Propionibacterium acnes,
Borrelia burgdorferi, viruses, fungi, spirochetes, and Rickettsia.
Genetic factors: Certain speci! c HLA genotypes (e.g. HLA-A1 and HLA-B8) are associated
with an increased risk for developing sarcoidosis.
Immunological factors: # ey are important in pathogenesis. # e most likely etiology is an
environmental agent (infectious or noninfectious) that triggers an cell-mediated immune
response to an unidenti! ed antigen in a genetically susceptible host.
Clinical features of
tuberculosis:
1. Drenching night sweats
2. Fever
3. Weight loss.
Most common cause of
drug resistant tuberculosis
is previous anti-
tuberculous treatment
(ATT).
Q. Write short note on diagnosis of
tuberculosis.
Lung: Granuloma with
necrosis is seen in:
1. Tuberculosis
2. Histoplasmosis
3. Wegener’s
granulomatosis
4. Crytococcosis.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY81
Exam Preparatory Manual for Undergraduates—General and Systemic Pathology342
TABLE 11.4: Main difference between primary and secondary tuberculosis of lung
Characteristics Primary TB Secondary TB
Type of infection Initial infection in an unsensitized
individual
Infection in a previously sensitized
individual
Source of infection
Exogenous Usually endogenous activation of
latent infection
Site of lung involved Lower part of upper lobe or upper
part of lower lobe and subpleural
Apex and posterior segments of the
upper lobe and superior segments
of lower lobe
Regional lymphnode involvement Significant and prominent Not prominent
Sputum for AFB Rarely positive Commonly positive
Cavity formation Rare Common
Healing Mainly by calcification By fibrosis
Extrapulmonary complicationsVery common Lesion usually localized to lung
Diagnosis: Pulmonary Disease
Based on the history, physical and radiographic ! ndings.
Identi! cation of acid-fast tubercle bacilli in the sputum.
Culture of the sputum: Conventional cultures require up to 10 weeks. Culture is the gold
standard.
PCR ampli! cation of M. tuberculosis: DNA is the rapid method of diagnosis. PCR can detect
as few as 10 organisms in clinical specimens.
Prognosis: Generally good if infections are localized to the lungs. All stages of HIV infection
are associated with an increased risk of tuberculosis.
SARCOIDOSIS
De! nition: Sarcoidosis is a multisystem disease of unknown cause characterized by the
presence of noncaseating granulomas in many tissues and organs.
Organs involved: Sarcoidosis can a" ect every organ of the body. It most commonly
a" ects the lung and the lymph nodes in the mediastinum and hilar regions. Other organs
commonly a" ected are the liver, skin, and eye.
Age and gender: Most patients are young (from 20 to 40 years of age) and more common in
women than in men.
Etiology
Exact cause of sarcoidosis is not known. Factors that play a role in its pathogenesis are: 1)
environmental, 2) genetic, and 3) immunological
Environmental factors: Environmental agents (infectious and noninfectious) have been
suggested as possible causes. Infectious inciting agent includes: mycobacteria (both
Mycobacterium tuberculosis and nontuberculous mycobacteria), Propionibacterium acnes,
Borrelia burgdorferi, viruses, fungi, spirochetes, and Rickettsia.
Genetic factors: Certain speci! c HLA genotypes (e.g. HLA-A1 and HLA-B8) are associated
with an increased risk for developing sarcoidosis.
Immunological factors: # ey are important in pathogenesis. # e most likely etiology is an
environmental agent (infectious or noninfectious) that triggers an cell-mediated immune
response to an unidenti! ed antigen in a genetically susceptible host.
Clinical features of
tuberculosis:
1. Drenching night sweats
2. Fever
3. Weight loss.
Most common cause of
drug resistant tuberculosis
is previous anti-
tuberculous treatment
(ATT).
Q. Write short note on diagnosis of
tuberculosis.
Lung: Granuloma with
necrosis is seen in:
1. Tuberculosis
2. Histoplasmosis
3. Wegener’s
granulomatosis
4. Crytococcosis.
Tuberculosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY82
Exam Preparatory Manual for Undergraduates—General and Systemic Pathology336
B. After 3 weeks of infection
Cell-mediated immunity: It develops about 3 weeks after exposure.
Presentation of antigen to CD4
+
T cells: Antigen-presenting cells (APCs which includes
macrophages, dendritic cells) process the mycobacterila antigen and present it to naïve
CD4
+
T cells. Processed antigen reaches regional lymph nodes.
Di! erentiation of CD4
+
T cells into T-helper 1 (T
H1) cell: It is due to the action of IL-12
secreted by macrophages. Role of T
H1 cells:
–T
H1 cells produce IFN-J which has several functions.
i. Activation of macrophages: ! ese macrophages become bactericidal and secrete
TNFwhich promotes recruitment of more monocytesdi! erentiation into
epithelioid (epithelium-like) cells.
ii. Stimulates formation of the phagolysosome in infected macrophagesexposes
the bacteria to acidic environment.
iii. Stimulates nitric oxide synthaseto produce nitric oxideantibactericidal.
iv. Generation of reactive oxygen species antibacterial.
–T
H1 is also responsible for the formation of granulomas and caseous necrosis.
i. Transformation of macrophages into epithelioid cells: Activated macrophages
are transformed into epithelioid cells. Some of these “epithelioid cells” may fuse
to form giant cells.
ii. Granuloma formation: A microscopic aggregates of epithelioid cells, surrounded
by a rim of lymphocytes, is referred as a granuloma and this pattern of in" a-
mmation, known as granulomatous in" ammation (refer page 75). Hypersensitivity
reaction results in tissue destruction caseation and cavitation.
Tuberculosis: T
H1 cells
produce IFN-! and
plays a crucial role in
the development of
granulomatous lesion.
Epithelioid granuloma is
caused by: Helper T-cells.
Figs 11.18A and B: Sequence of events in primary tuberculosis of lung
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY82
Exam Preparatory Manual for Undergraduates—General and Systemic Pathology336
B. After 3 weeks of infection
Cell-mediated immunity: It develops about 3 weeks after exposure.
Presentation of antigen to CD4
+
T cells: Antigen-presenting cells (APCs which includes
macrophages, dendritic cells) process the mycobacterila antigen and present it to naïve
CD4
+
T cells. Processed antigen reaches regional lymph nodes.
Di! erentiation of CD4
+
T cells into T-helper 1 (T
H1) cell: It is due to the action of IL-12
secreted by macrophages. Role of T
H1 cells:
–T
H1 cells produce IFN-J which has several functions.
i. Activation of macrophages: ! ese macrophages become bactericidal and secrete
TNFwhich promotes recruitment of more monocytesdi! erentiation into
epithelioid (epithelium-like) cells.
ii. Stimulates formation of the phagolysosome in infected macrophagesexposes
the bacteria to acidic environment.
iii. Stimulates nitric oxide synthaseto produce nitric oxideantibactericidal.
iv. Generation of reactive oxygen species antibacterial.
–T
H1 is also responsible for the formation of granulomas and caseous necrosis.
i. Transformation of macrophages into epithelioid cells: Activated macrophages
are transformed into epithelioid cells. Some of these “epithelioid cells” may fuse
to form giant cells.
ii. Granuloma formation: A microscopic aggregates of epithelioid cells, surrounded
by a rim of lymphocytes, is referred as a granuloma and this pattern of in" a-
mmation, known as granulomatous in" ammation (refer page 75). Hypersensitivity
reaction results in tissue destruction caseation and cavitation.
Tuberculosis: T
H1 cells
produce IFN-! and
plays a crucial role in
the development of
granulomatous lesion.
Epithelioid granuloma is
caused by: Helper T-cells.
Figs 11.18A and B: Sequence of events in primary tuberculosis of lung
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY83
Lung Disorders 339
Figs 11.21A and B:! Secondary pulmonary tuberculosis. A. (specimen); B. (diagrammatic). The lung shows gray-
white areas of caseation with a cavity in the upper lobe
Reactivated/Secondary TB
is most commonly located
near: Apex.
Assman focus:
Infraclavicular lesion of
tuberculosis.
Simon focus: Healed
calcified caseous nodule
of tuberculosis at the apex
of lung.
Rich focus: Tuberculous
granuloma occurring on
the cortex of the brain
that ruptures into the
subarachnoid space.
Ranke complex: Healed
primary complex
consisting of calcified
peripheral and calcified
hilar nodes.
Rasmussen aneurysm:
Aneurysm of pulmonary
artery within the
tuberculous cavity.
May rupture and cause
hemoptysis.
A B
Fig. 11.22: Natural history and various stages of tuberculosis
Simmond focus: Healed
foci of TB in the liver.
Weigart focus: Healed foci
of TB in the intima of blood
vessels.
Tuberculosis
Lung Disorders 339
Figs 11.21A and B:! Secondary pulmonary tuberculosis. A. (specimen); B. (diagrammatic). The lung shows gray-
white areas of caseation with a cavity in the upper lobe
Reactivated/Secondary TB
is most commonly located
near: Apex.
Assman focus:
Infraclavicular lesion of
tuberculosis.
Simon focus: Healed
calcified caseous nodule
of tuberculosis at the apex
of lung.
Rich focus: Tuberculous
granuloma occurring on
the cortex of the brain
that ruptures into the
subarachnoid space.
Ranke complex: Healed
primary complex
consisting of calcified
peripheral and calcified
hilar nodes.
Rasmussen aneurysm:
Aneurysm of pulmonary
artery within the
tuberculous cavity.
May rupture and cause
hemoptysis.
A B
Fig. 11.22: Natural history and various stages of tuberculosis
Simmond focus: Healed
foci of TB in the liver.
Weigart focus: Healed foci
of TB in the intima of blood
vessels.
Tuberculosis
Tuberculosis.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY84
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY84
Caseous Necrosis -Tuberculosis
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY85
Miliary Tuberculosis
Miliary tuberculosis of the spleen.
The cut surface shows numerous
gray-white granulomas.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY85
Miliary Tuberculosis
Miliary tuberculosis of the spleen.
The cut surface shows numerous
gray-white granulomas.
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY86
Lung Tumors
Lung Tumors
Lung Tumors.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY87
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY87
Lung Tumors.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY88
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY88
Lung Tumors.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY89
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY89
Lung Tumors.,
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY90
Metastatic Disease (Primary breast cancer)
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY90
Metastatic Disease (Primary breast cancer)
Monday, June 17, 202491Ephraim Zulu - PATHOLOGY
Numerous metastases to lung from a renal cell
carcinoma.
Numerous metastases to lung from a renal cell
carcinoma.
References & Credits
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY
•Barone J, Castro M.A. (2016), USMLE Step 1 Pathology Lecture Notes, Published by Kaplan
Medical, a division of Kaplan, Inc. 750 Third Avenue, New York, NY 10017: ISBN: 978-1-
5062-0772-8
•Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee brothers medical
publishers (p) ltd, India
•Levison D.A., Reid R, Burt A.D., Harrison D.J., Fleming S., (2008), Muir’s Textbook of
Pathology, 14th Edition, Edward Arnold (Publishers) Ltd
•Robbins SL and Kumar V (2013). Basic Pathology (9th Edition).WB Saunders Co. London.
•Rubin E, Rubin R, Strayer D.S. (2012) Rubin`s Pathology: Clinicopathologic Foundations
of Medicine (6th Edition), Lippincott Williams & Wilkins, a Wolters Kluwer business.
Philadelphia, PA.
92
References & Credits
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY
•Barone J, Castro M.A. (2016), USMLE Step 1 Pathology Lecture Notes, Published by Kaplan
Medical, a division of Kaplan, Inc. 750 Third Avenue, New York, NY 10017: ISBN: 978-1-
5062-0772-8
•Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee brothers medical
publishers (p) ltd, India
•Levison D.A., Reid R, Burt A.D., Harrison D.J., Fleming S., (2008), Muir’s Textbook of
Pathology, 14th Edition, Edward Arnold (Publishers) Ltd
•Robbins SL and Kumar V (2013). Basic Pathology (9th Edition).WB Saunders Co. London.
•Rubin E, Rubin R, Strayer D.S. (2012) Rubin`s Pathology: Clinicopathologic Foundations
of Medicine (6th Edition), Lippincott Williams & Wilkins, a Wolters Kluwer business.
Philadelphia, PA.
92
References & Credits
Monday, June 17, 2024Ephraim Zulu - PATHOLOGY
End of Lecture
Ephraim Imhotep Zulu
Pathology
93
End of Lecture
Ephraim Imhotep Zulu
Pathology
93
Tags
Categories
HealthcareDownload
Download Slideshow Get the original presentation fileQuick Actions
Statistics
- Views 342
- Slides 93
- Age 451 days
Related Slideshows
36
Clinical approach Dyspnoea A simple and practical approach.pptx
ShajahanPS
37 views
238
Cancer Awareness therapy for public by Dr Kanhu Charan Patro
kanhucpatro
36 views
41
Prof Satyadas Memorial oration Kozhikode.pptx
ShajahanPS
33 views
26
Viral Conjunctivitis and it;s managment.pptx
ZaidAzhar
43 views
30
Essential Thrombocythemia 15 Years of Experience at the Hematology Department, Algies, Algeria.pdf
sbelakehal
40 views
10
Hypertension sign symptoms cmdt style with regime
androiddabest
41 views