Respiratory system

DISEASES
OF
RESPIRATORY
SYSTEM

• Respiratory diseases, particularly lung infections,
cause most damage in developing countries where,
together with gastrointestinal infections, they
account for a heavy morbidity and mortality.

•Most respiratory illnesses are due to
environmental factors, especially smoking

Aetiological Factors in Respiratory Disease
___________________________________________________________________________
Aetiological Factors Disease
___________________________________________________________________________
Genetic Cystic Fibrosis
α 1 – Antitrypsin deficiency
Some types of Asthma
___________________________________________________________________________
Environmental
Smoking Lung cancer
Chronic Bronchitis and Emphysema
Susceptibility to infection

Air pollution Chronic Bronchitis
Susceptibility to infection

Occupation Pneumoconiosis
Asbestosis
Mesothelioma
Lung Cancer

Infection Influenza
Measles
Bacterial Pneumonias
Tuberculosis
___________________________________________________________________________

Normal Structure and Function

•The respiratory system extends from the nasal orifices to the periphery
of the lung and the surrounding pleural cavity.

• From the nose to the distal bronchi , the mucosa is lined by mainly
pseudo stratified ciliated columnar epithelium with mucus – secreting
goblet cells; this is Respiratory Mucosa .

• The co – ordinated rhythmic breathing of the cilia in the surface of the
respiratory mucosa wafts mucus containing dust particles from the
depths of the lung up to the larynx. From there the mucus can be either
expectorated or swallowed

Histology of the respiratory epithelium:
Anatomy of the respiratory system With the exception of pharynx, epiglottis
and vocal cards , the respiratory tract is lined by
specialized ciliated mucus-secreting epithelium

• The lungs are divided into lobes; the right lung has three lobes
( upper, middle, lower); the left lung has only two lobes ( upper and
lower) . Each lung is formed of ten anatomically defined Bronchopulomnary
Segments. Each segment is supplied by a segmental artery and a branch , but
the veins draining adjacent segments often anastomose before they reach the
hilum.

• The Lower Respiratory Tract consists of the trachea, bronchi, bronchioles,
alveolar duct and alveoli. The structure of each portion differs.

• The respiratory tree is designed to transport clean, humidified air into
distal airways and alveoli, where the waste product of metabolism (CO 2 ) is
exchanged for O2 .

Structure and nomenclature of lower respiratory tract

Structure of the Respiratory Tree
_________________________________________________
Part of Respiratory Tract Structure
_________________________________________________
Trachea Anterior C- shaped plates of
cartilage with posterior smooth
muscle . Mucous glands
_____________________________________________________________
Bronchi Discontinuous foci of cartilage with
smooth muscle . Mucous gland
_____________________________________________________________
Bronchioles No cartilage or submucosal mucous
glands. Clara cells secreting
proteinoaceous fluid . Ciliated
epithelium.
_____________________________________________________________
Alveolar Duct Flat epithelium. No glands. No cilia
_____________________________________________________________
Alveoli Type I and II pneumocytes
_____________________________________________________________

Obstructive
Vs
Restrictive
Lung
Diseases

Obstructive VS restrictive Lung Disease
Obstructive Lung Disease Restrictive Lung Disease

Characterized by limitation of Characterized by reduced
airflow usually resulting from expansion of lung parenchyma
partial or complete obstruction at accompanied by decreased total
any level lung capacity
Normal or increased total lung Decreased total lung capacity and
capacity and forced vital Forced Vital Capacity(FVC)
capacity(FVC)
Decreased Forced Expiratory Forced Expiratory Volume (FEV) is
Volume(FEV) is the hallmark normal
Ratio of FEV to FVC is Ratio of FEV to FVC is near normal
characteristically decreased

Obstructive VS restrictive Lung Disease

Examples of obstructive lung Examples of restrictive lung
diseases diseases
1. Emphysema a. Chest wall disorders in the
2. Chronic Bronchitis presence of normal lung:
Severe obesity; Diseases of
3. Bronchiactasis
pleura; Neuromuscular
4. Asthma disorders
b. Acute or Chronic restrictive
diseases
(i) Acute restrictive disease :
Acute Respiratory Distress
Syndrome (ARDS)
(ii) Chronic restrictive disease:
Pneumoconiosis; Interstitial
Fibrosis ; Sarcoidosis

CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
•The term Chronic Obstructive Pulmonary Disease (COPD) refers to
a group of conditions that share a major symptom - Dyspnoea -
and are accompanied by chronic or recurrent obstruction to airflow
within the lung.

• The diseases included in COPD are:
(i) Chronic Bronchitis
(ii) Bronchiactasis
(iii) Asthma
(iv) Emphysema
(v) Small Airway Disease ( Bronchiolotis)

DISORDERS ASSOCIATED WITH AIRFLOW OBSTRUCTION : THE SPECTRUM OF
CHRONIC OBSTRUCTIVE PULMONARY DISEASE

CLINICAL ANATOMIC MAJOR ETIOLOGY SIGNS/SYMPTO
TERM SITE PATHOLOGIC MS
CHANGES
Chronic Bronchus Mucous gland Tobacco Smoke; Cough; Sputum
Bronchitis hyperplasia, Air Pollutants production
hypersecretion
Bronchiactasis Bronchus Airway dilation Persistent or Cough; purulent
and scarring severe infections sputum; Fever

Asthma Bronchus Smooth Muscle Immunologic or Episodic
hyperplasia, undefined causes wheezing, Cough,
excess mucus, Dyspnoea
Inflammation
Emphysema Acinus Airspace Tobacco smoke Dyspnoea
enlargement;
Wall destruction
Small airway Bronchiole Inflammatory Tobacco smoke, Cough ;
disease scarring ; air pollutants, Dyspnoea
(Bronchiolotis) Obliteration miscellaneous

EMPHYSEMA
•Emphysema is a condition of lung characterized by
abnormal permanent enlargement of the airspaces distal to
the terminal bronchioles, accompanied by destruction of
their walls, and without obvious fibrosis
•Acinus: Acinus is the part of lung distal to terminal
bronchiole and includes respiratory bronchiole, alveolar
duct and alveoli; a cluster of three to five acini is referred to
as a lobule
•TYPES OF EMPHYSEMA: Emphysema is defined in terms of the
anatomic nature of the lesion, and it can be further classified according
to its anatomic distribution within lobule.
• Although the term emphysema is sometimes loosely applied to
diverse conditions, there are four major types:
(i) Centriacinar
(ii) Panacinar
(iii) Paraspetal
(iv) irregular

Classification of Emphysema: Emphysema is classified according to
the pattern of distribution of lesions. These can be correlated with
specific aetiological factors to some extent, e.g., centrilobular
emphysema and cigarette smoking

TYPES OF OCCURS LOCATION CAUSE
EMPHYSEMA

1. Centri - Acinar In central or In upper lobes Cigarette smoking
(Centri – Lobular) proximal part of the especially apical
acini, formed by segments
respiratory
bronchiole
2. Pan – Acinar In acini from In lower lung lobes Alpha1- Antitrypsin
(Pan – lobular) respiratory deficiency
bronchiole upto
terminal blind
alveoli
3. Distal – Acinar In distal part of the Severe in upper Adjacent to areas of
(Para – septal) acini, formed by half of the lung fibrosis, scarring or
alveolar ducts and usually adjacent to atelactasis
alveoli pleura
4. Irregular Acini are Adjacent to areas Healed
irregularly enlarged of scarring . inflammatory
and destroyed process e.g.,
Tuberculosis

Bullous Emphysema: This is not a separate category of emphysema.It
refers to the presence of balloon – like foci of emphysema over 10 mm in
diameter. Cases of emphysema with bullae should, where possible, be
classified into one of the four anatomical types. Bullae are prone to
rupture, causing Spontaneous Pneumothorax

PATHOGENESIS OF EMPHYSEMA

•Current hypothesis favours Emphysema arising as a
consequence of two critical imbalances:
(i) Protease- Antiprotease Imbalance
(ii) Oxidant – Antioxidant Imbalance
1. Protease – Antiprotease Mechanism
•The protease – Antiprotease theory holds that alveolar wall
destruction results from an imbalance between Proteases ( mainly
Elastase) and Antiprotease .So increased Protease and decreased
Antiprotease or antielastase like α 1 – Antitrypsin leads to Emphysema.
•The principal antielastase activity in serum and interstitial
tissue is α 1 – Antitrypsin.
• The principal cellular Elastase activity is derived from Neutrophils (
other Elastases are formed by macrophages, mast cells, pancreas, and
bacteria)

Protease – Antiprotease mechanism of Emphysema.
- Smoking inhibits Antielastase and favours the recruitment of
leucocytes and release of Elastase.

2. Oxidant – Antioxidant Imbalance:
Smoking leads to oxidant- antioxident imbalance
Normally lung contains a healthy complement of
Antioxidants:
- Superoxide dismutase
- Glutathione
These antioxidants protects lung from oxidative damage
Tobacco smoke contains abundant reactive oxygen species
(Free Radicals). ,which deplete antioxidant mechanisms,
thereby inciting tissue damage
Activated Neutriophils also add to the pool of reactive
oxygen species
As a result of oxidant injury there is “functional Alpha- 1 –
Antitrypsin deficiency”

Pathogenesis of Emphysema: The protease- Antiprotease imbalance and oxidant –
antioxidant imbalance are additive in their effects and contributes to tissue damage.
Alpha-1 Antitrypsin deficiency can be either congenital or “functional” as a
result of oxidative inactivation.

How smoking produces Emphysema?

Cigarette Smoking

(i) Nicotine is chemotactic for Neutrophils
(ii) Release of Cytokines ( IL -8)
(iii) Release of Free radicals from Cigarette smoke

(i) Increased Protease (Elastase) activity
(ii) Decreased α 1 Antitrypsin activity

Emphysema

Morphologic findings of Emphysema

Gross Examination:

1. In Centri- Acinar type: Lungs are pale , less voluminous with
rounded edges. Affects upper 2/3 of the lungs . May
demonstrate bullae.

2. In Pan – Acinar type: Lungs are pale , more voluminous with
rounded edges. Affects lower lung lobes . May obscure heart at
autopsy .

Emphysema: Gross Examination:
Cut section show dilated air spaces

Bullous Emphysema with large apical andsubpleural bullae

Centrilobular Emphysema: Central areas show marked emphysematous
damage

Panacinar Emphysema: involving the entire pulmonary architecture

Microscopic findings in Emphysema

• Microscopic examination is necessary to visualize the abnormal
fenestrations in the walls of the alveoli, the complete destruction of
septal walls, and the distribution of damage within the pulmonary
lobule.
• Histologically there is thinning and destruction of alveolar
walls.

• With advanced disease , adjacent alveoli become confluent,
creating large airspaces .

•With advance disease of the disease , adjacent alveoli fuse,
producing even larger abnormal airspaces and possibly blebs or
bullae.

•Often the respiratory bronchioles and vasculature of the lungs are
deformed and compressed by the emphysematous distortion of the
airspaces.

Emphysema : (Microscopic Examination): Loss of alveolar walls.
Remaining air spaces are dilated

CLINICAL COURSE OF EMPHYSEMA

• The clinical manifestations of Emphysema do not appear until at least one
third of the functioning pulmonary parenchyma is damaged.
• Mostly occurs in males and cigarette smokers.
• The common clinical features are:
- Dyspnoea
- Cough
- Wheezing
- Weight loss
• Classically the patient is barrel- chested and dyspneic, with
prolonged expiration , and sits forward in a hunched – over position,
attempting to squeeze the air out of the lungs with each expiratory effort.
•Patient have a pinched face and breathe through pursed lips
•Despite of dyspnea the oxygenation is adequate. So these patients are
sometimes called ‘pink puffers’
• The only reliable and consistently present finding on physical
examination is slowing of forced expiration.

CHRONIC BORNCHITIS
•Definition: Chronic Bronchitis is defined as persistent
cough with sputum production for at least 3 months in at
least 2 consecutive years.
• It is very common among habitual smokers and inhabitants
of smog- laden cities.
• When present for years it may lead to:
(i) Chronic Obstructive disease
(ii) Cor pulomanale and heart failure
(iii) Atypical Metaplasia and Dysplasia of the respiratory
epithelium.

Types of Chronic Bronchitis

1. Simple Chronic Bronchitis: The productive cough
raises mucoid sputum but airflow is not obstructed.

2. Chronic Mucopurulent Bronchitis: The sputum
contains pus because of secondary infection.

3. Chronic Asthmatic Bronchitis: Some with chronic
bronchitis may demonstrate hyper responsive
airways and intermittent episodes of asthma
4. Chronic Obstructive Bronchitis: A subpopulation of
bronchitis patients develops chronic outflow
obstruction

Pathogenesis of Chronic Bronchitis

Two sets of factors are important in the genesis
of chronic bronchitis:
(i) Chronic irritation by inhaled substances like
cigarette smoking
(ii) Microbiologic infections.

Role of Cigarette Smoking leads in Chronic Bronchitis

Cigarette smoking

Hypersecretion
and hypertrophy (i) Direct damage to respiratory
of Bronchial mucous epithelium
glands (ii) Decreased ciliary action of
airway epithelium
Metplastic formation of
mucin- secreting goblet Increased predisposition
cells in the surface epithelium to infections
of bronchi

Excessive mucus production

Air way obstruction

Morphologic Changes in Chronic Bronchitis

Gross Changes: There may be hyperemia, swelling and bogginess of
the mucous membranes, frequently accompanied by excessive
mucinous to mucopurulent secretions layering the epithelial
surfaces. Sometimes heavy casts of secretions and pus fill the
bronchi and bronchioles.
Microscopic Findings:
• The characteristic histologic feature of chronic bronchitis is
enlargement of the mucus – secreting glands of the trachea and
bronchi .
• Number of goblet cells also increase.
• Increased Reid index: Reid index is the ratio of the thickness of
the mucous gland layer to the thickness of the wall between the
epithelium and the cartilage.
• The bronchial epithelium may exhibit squamous metaplasia and
dysplasia. This can , eventually, lead to Carcinoma

•There is marked narrowing of bronchioles caused by goblet cell
metaplasia, mucous plugging, inflammation and fibrosis.

Chronic Bronchitis: the lumen of the bronchus is above. Note the marked
thickening of the mucus gland layer ( approximately twice normal) and
squamous metaplasia of lung epithelium

Clinical Course of Chronic Bronchitis

Mostly affected men in the 40 -65 years of age group.

Productive Cough: In patients with chronic bronchitis , a prominent cough
and the production of sputum may persist indefinitely without ventilatory
dysfunction

Some patients develop significant COPD with outflow obstruction .This is
accompanied by hypercapnia, hypoxemia and cyanosis

Differentiation of this form of COPD from that caused by emphysema can
be made in classic case, but many patients can have both conditions

With progression, chronic bronchitis is complicated by pulmonary
hyper secretion and cardiac failure

Recurrent infections and respiratory failure are common threats

Radiological findings in Chronic Bronchitis

Emphysema Vs Chronic Bronchitis

Chronic Emphysema
Bronchitis
AGE ((years) 40 -45 50 -75
DYSPNEA Mild; Late Severe; Early
COUGH Early; Copious sputum Late; Scanty sputum

INFECTIONS Common Occasional
RESPIRATORY Repeated Terminal
INSUFFICIENCY
COR PULOMNALE Common Rare ; Terminal
AIRWAY RESISTENCE Increased Normal or slightly
increased
ELASTIC RECOIL Normal Low
CHEST RADIOGRAPH Prominent vessels; Large Hyperinflation
heart
APPEARANCE BLUE BLOATERS(Due PINK PUFFERS
to hypercapnia and hypoxemia ) (Despite of dyspnea the
oxygenation is adequate)

●Patients of emphysema over ventilate and remain well
oxygenated and therefore are designated as Pink
Puffers.

● Patients with chronic bronchitis more often have
hypercapnia and severe hypoxemia , so are labeled as

Blue Bloaters

•Chronic bronchitis and Emphysema
almost always co –exist to some degree
• Causes of death in patients with
COPD:
1. Respiratory acidosis and coma
2. Right – sided heart failure
3. Massive collapse of lungs secondary to
Pneumothorax.

BRONCHIAL ASTHMA
Asthma is a chronic relapsing
DEFINITION:
inflammatory disorder characterized by
hyperactive airways, leading to episodic ,
reversible bronchoconstriction , due to
increased responsiveness of the
traceobnroncgial tree to various stimuli.

Normal bronchiole/
Asthmatic bronchiole

ETIOLOGY AND CLASSIFICATION OF ASTHMA
Two basic types:
A) Extrinsic
1. Atopic Or Allergic ( dust , pollen, etc)
2. Occupational (e.g., fumes, cotton, etc)
3. Allergic bronchopulmonary aspergilosos(bronchial
colonization with Aspergillus organisms, followed by
development of IgG antibodies)
B) Intrinsic ( Idiosyncratic)
1. Pharmacologic (e.g., aspirin)
2. Non – Reaginic ( respiratory tract infection)

•Both types can be precipitated by cold, stress and exercise

•Atopic Asthma is the most common
type of asthma , its onset is usually in
the first two decades of life, and it is
commonly associated with other
allergic manifestations in the patient
as well as in other family members.

ADAM33 Gene
A gene expressed by cell types
implicated in AIR WAY
REMODELING seen in Asthma

PATHOGENESIS OF EXTRINSIC ASTHMA
“Initiated by Type I Hypersensitivity”
Inhalation of allergen (antigen)

Simulation of Type 2 helper T cells

Production of Cytokines (IL – 2; IL-4; IL -13)

Sensitization of mast cells BY IL –2
Production of IgE BY IL -4
Activation of Eosinophils BY IL –5
Stimulation of mucus production BY IL -13

Second exposure

Degranulation of mast cells bearing specific IgE molecules

Release of vasoactive substances from the mast cell

Pathogenesis of extrinsic asthma – continued

Sensitization of CD 4 + T lymphocytes

Release of Cytokines (Interleukins; IL)
(IL-4;-IL- 5;IL-13)

Increased Synthesis of IgE

Mast cells degranulation

Release of mediators initiating Asthma
Leukotrines
Prostaglandins
Histamine
Platelet activating factor
Mast cell Tryptase
Eosinophilic & Neutrophilic chemo tactic Factor

Pathogenesis of Asthma: Inhalation of allergen (antigen) causes degranulation of
mast cells bearing specific IgE molecules . Release of vasoactive substances from
the mast cell causes bronchial constriction, oedema, and mucus hypresecretion

PATHOGENESIS OF INTRINSIC ASTHMA
Initiated by non- immune mechanisms to various stimuli

(1) Respiratory tract infections

(2) Cold, Stress, Exercise

(3) Aspirin (Decreased Prostaglandins and
increased Leukotrines)

All can trigger Bronchoconstriction

Extrinsic Asthma Intrinsic Asthma

Immune Mechanisms Non – immune
mechanisms
Family History + Family History – Negative

Eosinophilia No Eosinophilia

Serum IgE –elevated Serum IgE- Normal

MORPHOLOGY OF BRONCHIAL ASTHMA
GROSS FEATURES:
1. Lungs are over distended with small areas of atelactasis
2. There is occlusion of bronchi and bronchioles by thick , tenacious
mucus plugs.
MICROSCOPIC FEATURES:
1. Mucus plugs containing whorls of shed epithelium
(Cruschmann’s Spirals) , Eosinophils and Charcot- leyden
Crystels (Diamond shaped crystals composed of proteins)

2. Air Way Remodeling Characteristic findings of
asthma collectively called Air Way Remodeling include:
a. Thickening of basement membrane of bronchial epithelium
b. Edema and inflammatory infiltrate in bronchial walls with a
predominance of Eosinophils and mast cells
c. An increase in the size of submucosal glands
d. Hypertrophy of the bronchial muscle cells

Comparison of normal bronchiole with that in a patient with asthma .Note the
accumulation of mucus in the bronchial lumen resulting from an increase in the
Number of mucus – secreting goblet cells in the mucosa and hypertrophy of
submucosal glands .In addition, there is intense chronic inflammation due to
recruitment of eosinophils, macrophages and other inflammatory cells. Basement
membrane underlying the mucosal epithelium is thickened , and there is
hypertrophy and hyperplasia of smooth muscle cells.

CLINICAL FEATURES OF ASTHMA

1. Dyspnoea
2. Cough
3. Wheezing
4. Status Asthamticus: It is severe asthmatic paroxysm that does
not respond to bronchodilator or corticosteroid therapy and
persists for days and even weeks
5. Patient may ultimately develop chronic obstructive pulmonary
disease

COMPLICATIONS OF ASTHMA
1. Acute severe bronchial asthma
2. Acute respiratory failure
3. Pneumothorax
4. Side effects of medication e.g. long term corticosteroids, Beta –
agonists and Theophyline

BRONCHIACTASIS
“Bronchiactasis is the permanent
dilation of bronchi and bronchioles
caused by destruction of the muscle and
elastic supporting tissue, resulting form
or associated with chronic necrotizing
infections”

It is not a primary disease but rather
secondary to persisting infection a
obstruction caused by a variety of
condition .
s
It is manifested clinically by cough,
fever and expectoration of copious
amount of foul – smelling purulent
sputum .
To be considered Bronchiactasis the
dilation should be permanent

Etiology
1. Bronchial obstruction: Common causes of bronchial
obstruction which can lead to Bronchiactasis are
(i) Tumours
(ii) Foreign bodies
(iii) Impaction of mucus.
2. Congenital or Hereditary Conditions:
(i) Cystic Fibrosis: Widespread severe
bronchoconstriction caused by secretion of abnormally
viscid mucus.
(ii) Kartagner Syndrome: Structural abnormalities of
cilia impair meucocillary clearance in the airway leading to
persistent infections
(iii)Immundeficency states: Increased susceptibility to
repeated bacterial infections, that can eventually lead to
bronchiasctasis .
3. Necrotizing or suppurative pneumonias: Particularly due
to organisms like Staphylococcus and Klebsialla .

Pathogenesis of Bronchiactasis
Two processes are critical and intertwined in the Pathogenecitty of
Bronchiactasis:
1. Obstruction
2. Chronic persistent infection
Either infection can lead to obstruction or obstruction can lead to
infection . Both then can lead to bronchiactasis .
Bacteria involved in Bronchiactasis
1. Staphylococci
2. Streptococci
3. Pneumococci
4. Enteric organisms
5. Anaerobic and microaerophilic organisms
6. Haemophilus Influenzae
7. Pseudomonas Aeruguinosa

Bronchial Obstruction: The obstructing lesion causes a lipid or infective
pneumonia in the distal lung and, if unrelieved distal brochiactasis

MORPHOLOGY OF BRONCHIECTASIS

Gross Examination
*Usually lower lobes are involved ; Bilaterally
*There is dilatation of bronchi and bronchioles ,
with inflammatory infiltration especially of
neutrophils. The inflammation and associated fibrosis
extend into the adjacent lung tissue. The dilated
Bronchi and bronchioles can appear cylindrical,
saccular or fusiform..
Microscopic Findings:
- Acute and chronic inflammatory exudation
- Desquamation of lining epithelium
- Extensive areas of necrotizing ulceration
- Fibrosis Bronchiactasis: Permanent
dilatation of bronchi
- Necrosis destroys the bronchial or bronchiolar
wall and forms a lung abscess.

Bronchiasctasis: Cross section of lung demonstrating dilated bronchi
extending to the pleura

CLINICAL FEATURES OF BRONCHIACTESIS

1. Severe persistent cough
2. Expectoration of foul – smelling , sometimes bloody
sputum
3. Dyspnea and orthopnea in severe cases
4. A systemic febrile reaction may occur when powerful pathogens
are present
5. The symptoms are usually episodic
6. In the full blown cases the cough is usually paroxysmal in nature.
7. Such attacks are particularly
frequent when the
patient rises in the morning and the changes in
position lead to drainage into the bronchi of the collected pools
of pus.
8. Obstructive ventilatory insufficiency can lead to marked dyspnea
and cyanosis.
9. Patients may have clubbing of fingers

PULMONARY INFECTIONS
- Respiratory tract infections are more frequent than infections of
any other organ
- The account for the largest number of workdays lost in the general
population.
- The vast majority are upper respiratory tract infections caused by
viruses.
- Bacterial , viral , mycoplasmal and fungal infections of lungs also
account for an enormous amount of morbidity and rank among the
major immediate causes of deaths. The important lung infections
are:
- Pneumonias
- Tuberculosis
- Lung abscess

PNEUMONIA
-Infection of lung parenchyma
-It can be classified as:
1. On the basis of Aetiological agent involved:
(i) Bacterial: Streptococcus Pneumoniae ; Staph Aureus; etc
(ii) Viral: Influenza ; Measles
(iii) Fungal: Cryptococcus; Candida; Aspergillus.
(iv) Others: Pneumocystis carinii; Mycoplasma ;
2. On the basis of anatomical pattern: (Most widely used
classification)
(i) Bronchopneumonia
(ii) Lobar pneumonia
3. On the basis of clinical circumstances:
(i) Primary ( in an otherwise healthy person)
(ii) Secondary ( With local or systemic defects in defence)

Pneumonias in different clinical settings
(“ Pneumonia Syndromes”)
1. Community Acquired Acute Pneumonias

2. Community Acquired Atypical Pneumonias

3. Nosocomial Pneumonias

4. Aspiration Pneumonias

5. Chronic Pneumonias

6. Narcotizing Pneumonias and Lung Abscess

7. Pneumonias in immunocompromised

BRONCHOPNEUMONIA
- Patchy consolidation of the lung.
- Centered on bronchioles or bronchi
- Usually in extremes of ages (infancy or old age)
-Usually secondary to some pre- existing
disease like cancer, cardiac failure, chronic
renal failure or cerebrovasclar accidents
-Often Bilateral.
-Causative organisms may be low – virulence pathogens, especially
in an immunocomprised patient, and as such could not cause
similar disease in a young , healthy individual.
-Typical organisms include
- Staphylococci
- Streptococci
- Haemophilus influenzae
- Coliform
- Fungi

BRONCHPNEUMONIA: Patchi area of alveoli filled with
inflammatory cells

BRONCHOPNEUMONIA: Alveolar exudate mainly Neutrophils seen.
Surrounding capillaries are dilated and are filled with red blood cells

LOBAR PNEUMONIA
- Affect a large part, or the entire lobe
- Relatively uncommon in infancy and old age
- Affects males more than females
- 90% due to Streptococcus pneumoniae
- Affects otherwise healthy individuals
-

Lobar Pneumonia: Diffuse inflammation
affecting the entire lobe.

Morphologic Changes in Lobar Pneumonia
A classic example of acute inflammation.
It involves FOUR STAGES:
1st STAGE: STAGE OF CONGESTION: This stage lasts for about 24
hours and represents the outpouring of a protein rich exudate into
alveolar spaces, with venous congestion. The lung is heavy,
oedematous and red
2nd STAGE: STAGE OF RED HEPATIZATION: It last for a few days.
In the alveolar spaces there is massive accumulation of neutrophils
together with macrophages and lymphocytes. Numerous red blood
cells are also extravasated from the capillaries. The lung is red, solid
and airless, with a consistency resembling fresh liver.
3rd STAGE :GREY HEPATIZATION: It lasts a few days and
represents further accumulation of fibrin, with destruction of white
cells and red cells. The lung now is gray brown in colour and solid.
4th STAGE: RESOLUTION: It occurs at about 8 – 10 days in untreated
cases and represents the resorption of exudate and enzymatic
digestion of inflammatory debris, with preservation of underlying
alveolar wall architecture

Red Hepatization: The congested septal
capillaries and extensive neutrophil
exudation into alveoli corresponds to early
red Hepatization,. Fibrin not yet formed

Gray Hepatization: Advanced organizing
pneumonia featuring transformation of exudates
to Fibrinomyxoid masses richly infiltrated by
macrophages and fibroblasts

CLINICAL COURSE OF PNEUMONIA
-The major symptoms of pneumonia are malaise , fever, cough
productive of sputum and chest pain.

- The characteristic radiologic appearance of lobar pneumonia is that
of a radiopaque, usually well – circumscribed lobe, whereas
bronchopneumonia shows focal opacities.

Cough with greenish or yellow phlegm
Fever with shaking chills
Sharp chest pain
Rapid, shallow breathing
Shortness of breath
Headache

Excessive sweating
Clammy skin
Loss of appetite
Excessive fatigue
Confusion in elderly people

Radiological findings in Pneumonia

Lobar Pneumonia Broncho
Pneumonia
Usually Unilateral Usually Bilateral
Involvement of an entire Patchy involvement
lobe
Uncommon at extreme of More common in infancy
ages and old age
95% cases are due to Organisms of less
Strep Pnemococcus virulence are responsible

Microbiologic association of Pneumonia

1.Pneumonia due to Strep Pneumococcus:
Respond readily to Penicillin treatment but there are
increasing numbers of Penicillin – resistant strains
of Pneumococci

Commercial Pneumococal vaccines containing
capsular polysaccharides from the common serotypes
of Pneumococcus are available, and their proven
efficacy mandates their use in patients at risk for
the Pneumococal infections

2. Pneumonia due to Haemophilus Influenzae

Both unencapsualated and capsulated forms are important
causes of community - acquired pneumonias.

H. Influenzae is the most common cause of bacterial cause
of acute exacerbation of COPD

2. Pneumonia due to Moraxella Catarrhalis
 It is increasingly being recognized as a cause of pneumonia
especially in elderly.
3. Pneumonia due to Staph Aureus:
 It is an important cause of secondary bacterial pneumonia in
children and healthy adults following viral respiratory illness
(e.g., measles in children and influenza in both children and
adults).

 It is associated with a high incidence of complications , such
as lung abscess and empyema

Staphylococcal pneumonia is also an important cause of
nosocomial pneumonia

5. Pneumonia due to Klebsialla Pneumonia

It is the most common cause of gram – negative bacterial
pneumonia .

It frequently afflicts debilitated and malnourished persons
particularly chronic alcoholics.

Thick and gelatinous sputum is characteristic because
the organism produces an abundant viscid capsular
polysaccharide, which the patient may have difficulty
in coughing up.

6. Pneumonia due to Pseudomonas Aeruguinosa

It is most commonly seen in nosocomial settings

It is also common in patients who are neutropenic, usually
secondary to chemotherapy ; in patients with extensive burns;
and in those requiring mechanical ventilation

7. Pneumonia due to Legionella Pneumophilia:
It is the agent of Legionnaire’s Disease ,an eponym for the
epidemic and sporadic forms of pneumonia caused by this
organism.

It flourishes in artificial aquatic environments such as water –
cooling towers and within the tubing system of domestic
(portable) supplies.

The mode of transmission is thought to be either inhalation
of aerosolized organisms or aspiration of contaminated
drinking water
 Can be severe ; In immunocompromised the fatality rate is
30% to 50%
PONTIAC FEVER
Self limiting upper respiratory tract disease caused by
Legionella , without Pneumonic features

Special Types of Pneumonias

Community – Acquired Atypical Pneumonias

Nosocomial Pneumonias

Aspiration Pneumonias

Community Acquired Atypical Pneumonias

●Unlike “typical” acute pneumonias , atypical Pneumonia is
characterized by:
● Modest amount of sputum
● No Physical findings of consolidation of lung
● White cell counts normal or moderately increased
● May present as a severe upper respiratory tract infection
or “chest cold” that goes undiagnosed OR may present
as a fulminant life- threatining infection in
immunocompromised patients.
● Organisms responsible are:
(i) Mycoplasma Pnuemoniae (most common)
(ii) Viruses ( most importantly Influenza virus)
(iii) Chlamydia Pneumoniae
(iv) Rickettsiae

The term “ATYPICAL” denotes
the moderate amounts of
sputum, absence of physical
findings of consolidation, only
moderate elevation of white
cells count and lack of alveolar
exudates

Morphologic findings in Atypical Pneumonias
•The process may be patchy or it may involve whole lobes
bilaterally or unilaterally.

• Macroscopically the affected areas are red- blue , congested
and subcrepitant.

• Histologically the inflammatory reaction is largely
confined within the walls of alveoli. The septa are
widened and edematous ; they usually contain a mononuclear
inflammatory infiltrate of lymphocytes , histiocytes and
occasionally plasma cells.

• In contrast to bacterial pneumonias the alveolar spaces in
atypical pneumonias are remarkably free of cellular
exudate.

Viral Pneumonias; The thickened alveolar walls are heavily
infiltrated with mononuclear leucocytes

Clinical course of atypical pneumonia
•The clinical course of atypical pneumonia is extremely varied
• May present as a severe upper respiratory tract infection
or “chest cold” that goes undiagnosed OR may present as a
fulminant life- threatining infection in
immunocompromised patients.
• Most typically the onset is that of an acute, nonspecifically
febrile illness characterized by fever, headache, , malaise,
and later cough with minimal sputum.
• Chest radiographs usually reveal transient , ill – defined
patches , mainly on lower lobes.
• Physically findings are characteristically minimal.
• Prognosis for a uncomplicated is good; generally complete
recovery is the rule.

Typical Pnuemonia Atypical Pnuemonia
Consolidation of lung Consolidation is not evident

The major symptoms of pneumonia are May present as a severe upper
malaise , fever, cough productive of sputum respiratory tract infection or “chest cold”
and chest pain. that goes undiagnosed OR may present
as a fulminant life – threatining
infection in immunocompromised
patients

Copious amount of sputum Modest amount of sputum

White cell count is increased; with a White cell count is usually normal
predominance of Neutrophils

Histology: Inflammatory exudates in alveolar Histology: the inflammatory infiltrate is
spaces;Predominant cell is neutrophil largely confined within the walls of
alveoli; Predominant cell is Lymphocyte.

X-Ray: Findings of consolidation X- Ray: Transient ill – defined patches

Nosocomial Pneumonias OR Hospital Acquired Pneumonias

●Defined as the Pneumonias acquired in the course of a
hospital stay

● Common in patients with:
- severe underlying disease,
- immunosuppresson,
- prolonged antibiotic therapy,
- long standing intravascular catheters
- patients on mechanical ventilation.

● Organisms responsible are:
- Enterobactericeae
- Pseudomonas
- Staph Aureus.

Aspiration Pneumonias

●Occurs in markedly debilitated patients or in those who
aspirate gastric contents

● The resultant pneumonia is partly chemical , owing to the
extremely irritating effects of gastric acid , and partly
bacterial

● This type of pneumonia is often necrotizing , purses a
fulminant clinical course, and is a frequent cause of death in
patients predisposed to aspiration ; In those who survive ,
abscess is a common complication

PULMONARY TUBERCULOSIS
Communicable chronic Granulomatous disease
Lung is the commonest site for Tuberculosis
Pulmonary Tuberculosis is the leading cause of
death globally.
 It has been estimated that a third of world
population has been infected with tuberculosis.
Disease however only occurs in about 10% of
cases of infection, when the balance between
host resistance and the pathogenecity of the
bacteria tips in favours of the pathogenecity.

 airborne infection
 caused by bacillus Mycobacterium
tuberculosis
 spreads person to person or through air
 most are infected but do not develop the
disease
 form small black lesions in the lungs

Tuberculosis – Country Pro
•Tuberculosis causes a great deal of ill health and an
enormous burden on the populations of most low income
countries.

• According to prevalence and incidence of tuberculosis,
Pakistan is on 6th or 7th position in the list of 20 most
effected countries.

• InPakistan there are approximately more than 4 million
patients of tuberculosis.

• Accordingto a rough estimate, in Pakistan, more
than sixty thousands patients die every year due
to tuberculosis

• The economic factors, improper diagnostic facilities, non
affordability of treatment, problem of multidrug resistance
availability of substandard drugs and poor patients
compliance are heading us towards a state of failure in
tuberculosis control and treatment.

• Thisis regrettable since the disease can be easily
diagnosed and highly effective drugs for its treatment
are available

Mycobacterium – Bacterial characteristics

Strict Aerobe

Slender Rods

Are Acid Fast: Have a high complex lipid in their cell wall that readily binds
with Ziehl – Neelsen ( Carbol Fuchsin) stain BUT subsequently stubbornly
resists decolraization by Acid (Sulfuric Acid)

Mycobacterium Hominis is responsible for most cases
Other Mycobacterias:
- Mycobacterium Bovis
- Atypical Mycobacterias , i.e., Mycobacterium Avium Intracellularae.
Important in cases of AIDS and immunocompromised .

TUBERCULOSIS PATHOGENESIS
Typical example of Type –IV
Hypersensitivity
Transformation of Moncytes into
Epithelioid Cells and Multinucleated
Giant Cells under the influence of
TNF and IFN-γ:
Antigen presenting cells
secrete IL -12 which in turn acts on
CD-4 + T cells to stimulate the
secretion of IL-2, TNF and IFN-γ .
IL-2 acts on CD-4 cells (autocrine
effect), while TNF and IFN-γ acts on
macrophages, mobilize them and
modify them into epithelioid cells. A
few epithelioid cells get transformed
into multinucleated giant cells.

Types of Pulmonary Tuberculosis
1. Primary tuberculosis

2. Secondary Tuberculosis

3. Milliary Tuberculosis

Primary Tuberculosis
The lungs are usually the initial site of contact
between tubercle bacilli and humans. The focus
of primary infection which is usually
asymptomatic , is called GHON COMPLEX . The
pulmonary lesion is usually about 10 mm in Primary TB: produces a small mid –
diameter and consists of a central zone of zone lesion with involvement of
Hilar lymph nodes
caseous necrosis surrounded by palisaded
epithelioid histiocytes, the occasional
Langhan’s Giant Cells, and lymphocytes.
Similar granulomas are seen in lymph nodes that drain affected portion of the lung.
In almost all cases, a primary lesion will organize, leaving a fibrocalcific nodule in
the lung, and there will be no clinical sequalae. Hence the Ghon complex undergoes
fibrosis , often followed by radiologically detectable calcification ( Ranke
Complex).However, tubercle bacilli may persist as viable organism for years .
In a few cases , complications ,may occur, especially if the individual is
immunocomprised.

SECONDARY TUBERCULOSIS

-Secondary Tuberculosis represents reactivation
of old primary infection. These lesions are nearly
always located in the lung apices, sometimes Secondary TB: The lesions
are usually apical and often
bilaterally, and are about 30 mm in diameter bilateral
at clinical presentation. Histologically, typical
granulomas are seen, most having central zone of
caseous necrosis.Progressino of disease depends on the balance
between host sensitivity and organism virulence. Most lesions are
converted to fibrocalcific scars.

MILIARY TUBERCULOSIS

Milliary Tuberculosis may be a consequence of
either primary tuberculosis or secondary
tuberculosis in which there is severe Milliary Tuberculosis: lungs
impairment of host resistance. The disease and many other organs
contain numerous small
becomes widely disseminated, resulting in’ granulomas

numerous small granulomas in many
organs. Lesions are commonly found in the lungs, meninges,
kidneys, bone marrow and liver, but no organ is exempt.
The granulomas often contain numerous Mycobacteria , and the
Mantoux test is frequently negative.

Natural History and Spectrum of Tuberculosis

GROSS APPEARANCE

Primary pulmonary Tuberculosis: Ghon complex. The gray- white parenchymal focus
is under the pleura in the lower part of the upper lobe (topmost arrow) Hilar
lymph nodes with caseation are seen( lower most arrows)

Miliary Tuberculosis of the Spleen: The cut surface shows numerous
gray – white Granulomas

TUBERCULOSIS: (Gross Specimen)
Multiple areas of Caseaous necrosis
seen

TUBERCULOSIS LUNG: Multiple well
defined granulomas seen. Consisting
of aggregation of transformed
macrophages – the Epithelioid cells
(elongated cells with long pale nuclei and
pink cytoplasm. In addition Langhans type
of Giant cells, Lymphocytes and Fibroblasts
are also seen.

Acid Fast Bacilli (AFB) stain: Mycobacterium Tuberculosis seen as
red rods

Microscopic Findings in Tuberculosis:
At the active site of involvement, there
are both non- caseating and caseating
granulomas.
The important findings
in a case of Tuberculosis are:
1. Central caseation
2. Epithelioid cells derived from
macrophages
3. Surrounding collar of
lymphocytes .
4. Enclosing rim of fibroblasts
( in old lesions)
5. Langhan’s type of Giant
cells, with multiple nuclei
arranged in a horse – shoe
pattern.

LAB DIAGNOSIS OF TUBERCULOSIS
1.Blood Complete:
-Erythrocytes Sedimentation Rate (ESR) increased
- Total Leucocytes Count (TLC) increased in milliary
tuberculosis
2. Sputum Examination: Early morning sputum for at least three
consecutive days is examined. Z.N staning is done and Acid
Fast Bacilli (AFB) appear as red rods under microscope
3. Chest – X- ray:
i. Patchy consolidation in the post apical region
ii. Lung cavitation
iii. Areas of increased density suggesting caseation
iv. Scar tissue produce sharp margins and tends to contract
v. Hilar lymphadenopathy
vi. Unilateral pleural effusion
vii. Milliary spread may be evident

4. Sputum Culture: Done on L.J medium . After 4 – 6 weeks grey ,
rough and raised colonies of Mycobacteria appear
5. Bectec technique: Radioactive techniques are used to detect
Mycobacteria in a given sample in a shorter period as
compared to LJ medium
6. Fibrooptic Bronchoscopy: With bronchial washing from affected
lobe. Useful if no sputum is available
7. Biopsies of Pleura, Lymph nodes, Lung and other tissues:
It may be required
8. Mantoux Test: 0.1 ml of Purified Protein Derivative (PPD) is
injected intradermally on the flexor aspect of forearm
9. DNA detection by Polymerase Chain Reaction (PCR): By
amplification of mycobacterial DNA in clinical samples using
PCR .
10. Serodiagnosis: By Enzyme Linked Immunosorbent Assay
(ELISA), or Immunofluorescence or Column Chromatography

Colony Morphology – LJ Slant

CLINICAL FEATURES OF PULMONARY TUBERCULOSIS
1.Fever ( low grade, remittent and appear late each afternoon
and then subside)
2. Night sweats
3. Cough with sputum
4. Haemoptysis
3. Malaise
4. Anorexia
5. Cough, first mucoid, later purulent and bloody sputum
6. Pleuritic chest pain

Systemic manifestations are produced by
TNF- alpha and IL -1 released from
activated macrophages.

 ongoing cough
 constantly tired
 loss of weight
 loss of appetite
 fever
 night sweats
 coughing up blood

 has no symptoms  continuous bad cough

 does not feel sick  chest pain
 coughing up blood or sputum
 cannot spread TB
 weakness or fatigue
 Usually positive for
skin  loss of weight and appetite
 chills, fever, night sweats
test
 positive skin test
 has normal chest X-ray
 may have abnormal chest X-
and sputum test ray, or positive sputum smear or
culture

Lung Abscess
Lung Abscess refers to a localized area of

Suppurative necrosis within the pulmonary

parenchyma , resulting in the formation of one or

more large cavities .

Factors predisposing to Lung Abscess
1. Aspiration of infective material : from carious teeth or
infected sinuses or tonsils

2. Aspiration of gastric contents , usually accompanied by
infectious material.

3. As a complication of necrotizing bacterial pneumonia

4. Bronchial Obstruction particularly with Bronchogenic
Carcinoma

5. Septic Embolism from septic thrombophelibitis or from
infective endocarditis of the right side of heart

6. Hematogenous spread of bacteria in disseminated pyogenic
infections

Bacteria responsible for Lung Abscess

Anaerobic Bacteria
Present in almost all cases of lung abscesses.
The most frequently encountered anaerobes are
commensals normally found in oral cavity:
- Prevotella
- Fusobacterium
- Bacteriodes
- Peptostreptococcus
Aerobic Bacteria:
- Staph Aureus
- Beta hemolytic Streptococcus
- Nocardia
- Gram negative organisms

PNEUMOCONIOSES
 Lung disease caused by inhaled dusts
 Dusts may be inorganic ( mineral) of organic
 Reaction may be inert, fibrous , allergic or neoplastic
 Co- existing disease may aggravate the reaction

 When exposed to dust the lung can respond in several ways:
(i) Inert
-Simple Coal- Worker’s Pneumoconiosis
(ii) Fibrous:
-Progressive Massive Fibrosis
- Asbestosis
- Silicosis
(iii) Allergic:
- Extrinsic Allergic Alveoloitis
(iv) Neoplastic:
- Mesothelioma
- Lung Carcinoma

•For all Pneumoconioses, regulations limiting worker
exposure have resulted in a decreased incidence of dust-
associated diseases.

• Although the Pneumoconioses result from well –defined
occupational exposure to specific agents, there are also
deleterious effects of particulate air pollution for the
general population, especially in urban areas.

• Studies have found increased morbidity (e.g., asthma
incidence) and mortality rates in population exposed to
increased ambient air particulate levels, leading to calls for
greater efforts to reduce the levels of particulates in
urban air

COAL – WORKER’S PNEUMOCONIOSIS

Coal, a form of combustible carbon, has long been
mined for fuel. In Coal Worker’s Pneumoconiosis coal dust is
ingested by alveolar macrophages , which then aggregate around
bronchioles .The spectrum of lung findings in coal workers is wide.
Different lung lesions due to Coal can be grouped as:
1. Anthracosis: Asymptomatic Anthracosis in which pigment
accumulates without a perceptible cellular reaction.
2. Simple Coal – Worker’s Pneumoconiosis: In this condition
accumulation of macrophages occur with little or no pulmonary
dysfunction.
3. Complicated or Massive Lung Fibrosis: There is extensive lung
fibrosis and lung functions are impaired.

ANTHRACOSIS

Anthrocosis pigment in the macrophages . Anthracosis is accumulation
of carbon pigment from breathing dirty air. Smokers have the most
pronounced anthracosis

Pneumoconiosis; A possible scheme of the pathogenesis of idiopathic pulmonary
fibrosis

Pathogenesis of Pneumoconiosis: Inhaled particulates usually impact at the bifurcation of terminal
Respiratory bronchioles , where they are engulfed by alveolar macrophages, which are then stimulated
to secrete (1) various fibrogenic factors that recruit fibroblasts and induce collagen synthesis , (2) toxic
factors that initiate lung injury , and (3) proinflammatory factors that recruit additional inflammatory
cells
IGF – Insulin Like Growth Factor; IL- - Interleukins; LTB4 – Leukoterin B4; MIP – Macrophage Inflammatory Factor;
PDGF – Platelet Derived Growth Factor; TNF –Tumour Necrosis Factor s

It is known that in a group of miners
working at the same pit for the same length of time ,
some will develop massive lung fibrosis and die, while
others develop little respiratory impairment

Coal – worker’s Pneumoconiosis: This
transilluminated thin slice of lung shows
several large black fibrotic nodules

Gross Findings in
Pnuemoconiocossis

ASBESTOSIS

• Asbestos has been used for its fire-m resistant qualities
for many centuries. It is used for insulation and the
manufacture of brake lining and other friction materials.
• Based on epidemiological studies the occupational
exposure to asbestos is linked to:
(i) Localized fibrous plaques or, rarely diffuse pleural
fibrosis
(ii) Pleural effusions
(iii) Parenchymal interstitial fibrosis ( Asbestosis)
(iv) Bronchogenic Carcinoma
(v) Mesothelioma
(vi) Laryngeal and perhaps other extra pulmonary neoplasms,
including colon carcinoma

There are two distinct form of Asbestos:
- Serpentine Chrysotiles – flexible and curled structure
- Amphiboles – straight stiff form

Both these forms are fibrogenic

Asbestos acts as tumour initiator and promoter

Morphology:
- Diffuse pulmonary fibrosis
- Asbestos body: Golden brown, fusiform or beaded rods with a
translucent center. They consist of asbestos fibers coated with an iron –
containing proteinaceous material.
- Pleural Plaques: these are the most common manifestations of
asbestos exposure ad are well – circumscribed plaques of dense collagen ,
often containing calcium

Malignant Tumours due to Asbestos exposure:
- Bronchogenic Carcinoma
- Malignant Mesothelioma

Asbestosis: The fibrous reaction to inhaled asbestos has
resulted in a ‘honey – comb’ lung

Asbestosis: Markedly thickened visceral pleura covers the lateral and
diaphragmatic surface of lung .Note also severe interstitial fibrosis
diffusely affecting the lower lobe of lung

Asbestosis Body: Revealing the typical beading and knobbed ends (arrow)

Clinical Course of Asbestosis:
The clinical findings are Asbestosis are indistinguishable
from any other diffuse interstitial disease.

Typically, progressively worsening Dyspnea appears 10 to
20 years after exposure

The disease may remain static or progress to congestive
cardiac failure or cor pulmonale and death.

The lung or pleural cancer associated with asbestos has
a grim prognosis

SILICOSIS

Silicosis is lung disease caused by inhalation of crystalline silicon
dioxide (silica).
Currently Silicosis is the most prevalent chronic
occupational disease in the world.
Silicates are abundant in stone and sand. Consequently, any
industrial worker involved in the grinding of stone or sand will be at
risk from silicosis.
In contrast to pure coal dust, silicates are toxic to macrophages ,
leading to their death with release of proteolytic enzymes and the
undigested silica particles. The enzymes cause local tissue
destruction and subsequent fibrosis; the silica particles are ingested
by other particles and cycle repeats itself.
Nodules tend to form in the lungs after many years of exposure.
With progressive fibrosis and increasing numbers of nodules ,
respiratory impairment increases.

Several coalescent collagenous silicotic nodules:

SARCOIDOSIS
DEFINITION
A Granuloma characterized by tubercle- like lesions
without caseation
AETIOLOGY
Not settled, but may be an immnunologicaly
mediated disease caused by an unknown virus
PATHOLOGY
Site: Multiple lesions affect lungs, skin, lymph nodes, spleen, liver,
bones, eyes, salivary glands
Microscopic Picture: Small rounded nodules resembling milliary
tubercles , formed of epithelioid cells, giant cells and lymphocytes.
The giant cells are few in number, larger than those of tuberculosis
and contain inclusion bodies, Schaumann bodies and Asteroid
bodies. Schaumann bodies are laminated concretions composed of
calcium and proteins. Asteroid bodies are stellate inclusions.
Caseation is absent. Old lesions heal by fibrosis

Course: Spontaneous regression in most cases. Death may result
from pulmonary fibrosis, nephroclacinosis or intercurrent infection.
Diagnosis:
(i) Kvein test : Subcutaneous injection of sterile sarcoid tissue
homogenate is given , it produces granuloma in affected patients.
(i) Biopsy:
(iii) Serum levels of Angiotensin Converting Enzyme ACE):
Raised in 35 – 40% of patients.

Sarcoidosis: Characteristic Sarcoid noncseating Granuloma
in lung with many Giant cells

TUMOURS OF LUNG
- Lung tumours may be primary or secondary. Both are
common.
- In the primary lung tumours following are usually
included
(i) Bronchogenic Carcinoma (90 to 95% of tumours)
(ii) Bronchial carcinoids ( 5%)
(iii) Mesnchymal and other tumours ( 2 to 5%).

BRONCHOGENIC CARCINOMA
 Most common primary malignant tumour in the
world.
 Directly related to cigarette smoking.
 It accounts for approximately 95% of primary
lung tumours.
 Associated with occupational exposure to
carcinogens.
 Overall 5- year survival rate 4 – 7 %.
 It is a malignant tumour that arises in the lining
epithelium of major bronchi usually close to the
hilus of the lung

Morphologic Classification of Bronchogenic
Carcinoma

1. Squamous Cell Carcinoma
2. Small Cell Carcinoma ( including oat cell
carcinoma)
3. Adenocarcinomas
4. Large Cell Undifferentiated Carcinoma.

Lung Cancers- Bronchogenic carcinomas
Develops within the wall or epithelia of the
bronchial tree.
Epithelial cells that develop abnormal
chromosomal changes (dyplastic cells) turn
into cancer and invade deeper tissue.

AETIOLOGY & PATHOGENESIS OF
BRONCHOGENIC CARCINOMA

1.TOBACCO SMOKING
- Squamous cell and small cell lung carcinoma are more
common in males because of increased cigarette smoking
- There is 20 times increased risk of lung cancer with 40
cigarettes per day for several years
- About 80% of lung cancers occur in active smokers
- Cigarette smoke contains:
i. Initiators for carcinogenesis: Polycyclic aromatic
hydrocarbons like Benzopyrene
ii. Promoters for carcinogenesis: Phenol derivatives
iii. Radio – active elements: C – 14 , K - 40

In lung cancer it has been estimated
that 10 to 20 mutations have occurred by
the time the tumour is clinically apparent.

The dominant oncogenes in Bronchogenic
carcinoma:
- c- myc
- K –ras
- Mutation in tumuor suppressor
gene- p -53

Risk of Lung Cancer in Smokers

Risk of Lung Cancer in Smokers

70
Relative Risk for CA of lung
60

50

40

30

20

10

0
Non Smoker 1 to 10 11 to 20 21 to 30 31 to 40 > 41

No. of Cigarettes/day

Tobacco Smoke

Squamous Metaplasia of Respiratory Epithelium

Dysplasia

Carcinoma in situ

Lung Cancer

Adverse effects of smoking:
The more common on the left and the some
what less common on the right

Association between Cigarette smoking and
Carcinoma
 Bronchogenic Carcinoma
 Carcinoma Lip
 Carcinoma Tongue
 Carcinoma Floor of Mouth
 Carcinoma Pharynx
 Carcinoma Larynx
 Carcinoma Esophagus
 Carcinoma Urinary bladder
 Carcinoma Pancreas
 Carcinoma Kidney

2. Industrial Hazards
i. Radiations
ii. Minors of radioactive ores
iii. Asbestos
iv. Arsenic
v. Chromium
vi. Uranium
vii. Nickel
viii. Vinyl chloride
ix. Mustard gas

3. Air Pollution
It also contributes to lung cancer

. Molecular Genetics
- Ultimately different type of exposures thought to act by causing
genetic alterations in lung cells, which accumulate and ultimately
lead to neoplasia
- In lung cancers it is estimated that 10 to 20 genetic mutations have
occurred by the time the tumour is clinically apparent
- There is activation of Oncogenes and inactivation of Tumour
Suppressor Genes.
- The dominant Oncogenes involved are:
- c- myc
- K- ras
- The commonly inactivated or deleted gene is p-53

MORPHOLOGY OF BRONCHOGENIC CARCINOMA

1. SQUAMOUS CELL CARCINOMA
This is the type of lung cancer most commonly associated with
cigarette smoking. The tumours are almost always hilar and are
thought to arise from squamous metaplasia.
 Microscopically range from well – differentiated squamous cell
tumours showing keratin pearls and inter- cellular bridges to poorly
differentiated tumours having only minimal residual squamous cell
features

Squamous Cell Carcinoma (30%)
Obstructive manifestations (nonspecific)
Nonproductive cough or hemoptysis
Pneumonia
Atelectasis
Pain is a late symptom
Surgical intervention (in the absence of
mets)

SQUAMOUS CELL CARCINOMA
LUNG: (Gross Examination)
Arising centrally in the lung .

In almost all patterns the neoplastic
tissue is gray- white in colour and
firm to hard in consistency

Squamous cell carcinoma usually begin as central (hilar) masses and
grow contagiously into the peripheral parenchyma .

Well differentiated squamous cell carcinoma
showing keratinization

SQUAMOUS CELL CARCINOMA: (Microscopic Examination) At the
upper left a cell nest or keratin pearl is seen. At the right tumour
is less well differentiated and several mitotic figures are seen.

SQUAMOUS CELL CARCINOMA LUNG: (Microscopic Examination)
Pink cytoplasm with distinct cell borders and intracellular bridges
characteristic for squamous cell carcinoma seen. Such features are
seen in well differentiated tumour (those that more closely mimic
the cell of origin.

Squamous Cell Carcinoma – Evolution

A

The precursor lesions of squamous cell carcinoma may antedate the appearance of
invasive tumour by years. Some of the earliest (and “mild”) changes
in smoking - damaged respiratory epithelium include goblet – cell
hyperplasia


B

Basal Cell or (reserve cell) hyperplasia


C

Squamous Metaplasia


More ominous changes include the
appearance of squamous dysplasia
characterized by :
-The presence of disordered squamous
epithelium,
- Loss of nuclear polarity,
- Nuclear hyperchromasia,
- Pleomorphism, and
- Mitotic figures

D


E

Carcinoma – in situ (CIS): It is the stage that immediately precedes invasive
squamous cell carcinoma , and apart from the lack of basement membrane
disruption is CIS , the cytological features are similar to those frank carcinoma


F

Unless treated the CIS will eventually progress to invasive cancer

2. SMALL CELL CARCINOMA
 Also known as ‘OAT CELL CARCINOMA’
because the small nuclei are thought to resemble oat
grains. Usually arise in a hilar bronchus.
 Microscopically highly cellular tumour composed
of small cells with hyperchromatic nuclei and indistinct
nucleoli.
 The tumour cells are fragile and often show
fragmentation and “Crush Artifacts” in small biopsy
specimens
 Close apposition of tumour cells that have scant
cytoplasm show “Nuclear Molding”

Small Cell (Oat cell) Carcinoma (20-25%)
Ectopic Hormone Production
Paraneoplastic Syndromes
Worst prognosis
Chemotherapy & Radiation
Temporary remission

SMALL CELL (OAT CELL) CARCINOMA
Cut surface of the tumour has a soft,
lobulated, white or tan appearance.
The tumour has caused the
obstruction of main bronchus

SMALL CELL CARCINOMA: (Microscopic Examination) Small dark
blue cells with minimal cytoplasm are packed together in sheets

Small cell carcinoma lung with islands of small
deeply basophilic cells and areas of necrosis

3. ADENOCARCINOMAS
- These are usually peripheral
- Microscopic features are:
i. Neoplastic cells are cuboidal to columnar
ii. Secrete mucin in 80% of cases
iii. Form following structures:
- Papillary
- Solid and Scirrhous
- Acinar
iv. Considered as the most common lung cancer in women
and non- smokers.

Adenocarcinoma (35-40%)
Asymptomatic
Routine chest x-ray
Pleuritic chest pain
Shortness of breath
Unpredictable mets, usually early
Pulmonary arterial system
Mediastinal lymph nodes
Surgical intervention (in the absence of mets)

•The incidence of Adenocarcinoma is increasing and some
studies show it as the most common lung carcinoma in
women.
• The basis for this change is unclear. A possible factor is
the increase in women smoking, but this only highlights our
lack of knowledge about why women tend to develop
Adenocarcinoma.
• One interesting postulate is that changes in cigarette type
( filter tips, low tar and low nicotine) have caused smokers to
inhale more deeply and thereby expose more peripheral
airways and cells ( with a predilection to Adenocarcinoma) to
carcinogens.

ADENOCARCINOMA OF LUNG:
Adenocarcinomas and anaplastic
large cell carcinoma tend to occur
more peripherally.

Adenocarcinoma lung showing gland formation

Adenocarcinoma Lung – Evolution

A

The evolution of adenocarcinoma of the lung is thought to occur through a
sequence that begins with a small well – demarcated lesion known as Atypical
Adenomatous Hyperplasia , or AAH ( arrowheads)


B

Atypical Adenomatous Hyperplasia progresses toBronchoalveolar Carcinoma or
BAC (an insitu phase that grows along existing structures and does not demonstrate
stromal invasion)


C

In situ carcinoma ultimately culminates into Invasive Adenocarcinoma , with
stromal invasion and parenchymal destruction

4. LARGE CELL CARCINOMA
- Peripherally forming bulky masses
-Microscopic features:
i. Composed of Anaplastic cells with large vesicular
nuclei
ii. Cells may be:
- Multinucleated giant cells
- Clear cells
- Spindle cells

Large Cell Carcinoma (10-15%)
Undifferentiated, process of exclusion
High incidence of mets
Surgical intervention is palliative
Obstructive pneumonitis
Pleural effusions
Non responsive to radiation or chemo

Large cell carcinoma lung showing pleomorphic, anaplastic tumour
cells and absence of squamous or glandular differentiation

SPREAD OF BRONCHOGENIC CARCINOMA

1. DIRECT:
i. Into lung.
ii. Into pleura, pleural cavity and intrathrocic structures
2. LYMPHATIC
To scalene, clavicular, supraclavicular lymph nodes
3. HAEMATOLOGICAL:
To:
i. Bone
ii. Brain
iii. Liver
iv. Adrenals

NSCLC – metastases (M1)

M0 – No metastasis
M1 – Metastasis present

TNM STAGING OF BRONCHOGENIC CARCINOMA
OCCULT:
- TX N0 M0
- No clinical or radiographic evidence of primary tumour
or of spread , but bronchopulmoanry secretions contains malignant
cells
STAGE I:
- T1 N0 MO / T1 N1 MO
- Tumour of 3 cm or less
Stage II:
- T2 N1 M0
- Tumour greater than 3 cm in diameter invading the pleura with
involvement of ipsilateral hilar nodes but without distant metastasis.
Stage III:
- T3 N2 M1
- Any tumour that:
- invades pleura and adjacent structures(T3)
- involves contralateral Mediastinal nodes(N2)
- show distant metastasis (M1)

CLINICAL FEATURES OF
BRONCHOGENEIC CARCINOMA
1.Chronic cough
2. Expectoration
3. Dyspnea
4. Wheezing
5. Weight loss
6. Age incidence: 40 - 70 years ;
Male to female ratio = 2:1;
More in cigarette smokers

PARANEOLASTIC SYNDROMES SEEN IN BRONCHOGENIC
CARCINOMA

“Paraneoplastic syndromes are symptom complexes which can
not be readily explained by local or distant spread of the tumour
or by the elaboration of hormones indigenous to the tissue of
origin”
Bronchogenic Carcinoma is one of the tumours in which
Paraneoplastic syndromes are mostly seen.

Common Paraneoplastic Syndromes seen in
Bronchogenic Carcinoma
3 to 10% patients of Bronchogenic Carcinoma develop clinically overt
Paraneoplastic syndromes. These include:

(1) Hypercalcemia: caused by parathyroid hormone – related peptide

(2) Cushing Syndrome: From increased production of Adrenocorticotropic
hormone

(3) Syndrome of Inappropriate Production of Antidiuretic
Hormone (SIADH):

(4) Neuromuscular Syndromes: including Myasthenia syndrome, peripheral
neuropathy and polymyositis

(5) Clubbing of fingers and hypertrophic pulmonary osteoarthropathy

(6) Haematologic manifestations: including migratory thrombophelibitis
and disseminated intravascular coagulation

Adult Respiratory
Distress Syndrome(ARDS)
(Diffuse Alveolar Damage)
Descriptive terms for a syndrome caused by diffuse alveolar
capillary damage.
ARDS has many synonyms (including adult
respiratory failure, shock lung, diffuse alveolar damage,
acute alveolar injury and wet lungs) are
It is characterized clinically by the rapid onset of severe
life threatining respiratory insufficiency , cyanosis, and
severe arterial hypoxemia that is refractory to oxygen
therapy and that may progress to extra pulmonary
multisystem organ failure.
ARDS is a well – recognized complication of numerous and
diverse conditions ,including both direct injuries to the lung
and systemic disorders

Conditions associated with development of ARDS
Infections: Sepsis*; Diffuse pulmonary infections*;
Gastric aspiration*
Physical injury: Mechanical trauma including head
injuries* ; Pulmonary contusions; Near drawing;
Fractures with fat embolism; Burns; Ionizing
radiations
Inhaled Irritants: Oxygen toxicity; Smoke; Irritant
gases and chemicals
Chemical Injury: Heroin or methadone overdose; etc
Haematologic Conditions: Multiple transfusions;
Disseminated Intravascular Coagulation (DIC).
Pancreatitis
Uremia
Cardiopulmoanry Bypass
*More than 50% of cases are associated with these four conditions

Morphological changes in ARDS
- Lungs are heavy, edematous and boggy.
- Lungs exhibit congestion, interstitial and intra-alveolar
edema and inflammation.
- Fibrin deposition
- Alveolar walls become lined with waxy hyaline
membranes .These hyaline membranes are consist of fibrin-
rich edema fluid mixed with cytopaslmic and lipid remnants
of necrotic epithelial cells.
- Fatal cases often have superimposed bronchopneumonia

Diffuse alveolar damage in ARDS: Some of the alveoli are collapsed , others
distended. Many contain diffuse proteinaceous debris, desquamated cells,
and hyaline membranes.

Adult Respiratory Respiratory Distress
Distress Syndrome Syndrome in
in Adults Neonates
Caused by diffuse damage Due to deficiency in
to alveoli pulmonary surfactant

Pathogenesis of ARDS
-The capillary defect in ARDS is believed to be
produced by an interaction of leukocytes and
mediators , including cytokines, oxygen radicals,
complement and eicosanoids that damage the
endothelium and allows fluid and protein to leak
across it.

Clinical Course of ARDS

-Patients who develop ARDS are usually hospitalized for one of the
predisposing condition and initially they have no pulmonary
symptoms.

- X-ray: Diffuse bilateral infiltrates

- It is characterized clinically by the rapid onset of severe life
threatining respiratory insufficiency , cyanosis , and severe arterial
hypoxemia that is refractory to oxygen
therapy
- Therapy of ARDS is difficult and this disorder is frequently fatal

PULMONARY THROMBOEMBOLISM

Cause and Incidence: The most serious form of thrombembolism is
pulmonary embolism, which may cause sudden death. It has an
incidence of 20 to 25 per 100,000 hospitalized patients
Over 90% of Pulmonary Emboli originate in the deep veins
of the leg (phelebothrombosis). More rarely, thrombi in pelvic
venous plexus are the source.
Pulmonary embolism is common in the following conditions that
predispose to the development of phlebothrombosis:
(i) Immediate post operative period
(ii) Immediate post partum period
(iii) Lengthy immobilization in bed
(iv)Cardiac Failure
(v) use of Oral Contraceptives

CLINICAL EFFECTS OF PULMONARY EMBOLISM
The size of the embolus is the factor most influencing the
clinical effects of pulmonary embolism
1. Massive Emboli: Large emboli (several centimeter long)
may lodge in the outflow tract of the right ventricle or in the
main pulmonary artery, where they cause circulatory
obstruction and Sudden Death .

2. Medium Sized Emboli: obstruction of medium sized
arteries may cause Pulmonary Infarct

3. Small Emboli: Small emboli lodge in minor branches of
pulmonary artery with no immediate effects. In many
instances, the emboli either fragment soon after lodgment of
dissolve during fibrinolysis, in which case clinical effects are
minimal. If numerous small emboli occur over a long period,
however, the pulmonary microcirculation may be so severely
compromised that Pulmonary Hypertension

Pathogenesis of Pulmonary Thromboembolism: The thrombus usually originates from the
deep leg veins and after detachment becomes lodged in the pulmonary artery vasculature,
causing sudden death (if massive), pulmonary infarction ( if small), or Pulmonary
hypertension (if small and multiple)

PULMONARY HYPERTENSION AND
VASCULAR SCLEROSIS
• The pulmonary circulation is normally one of low resistance , and
pulmonary blood pressure is only about one eighth of systemic blood
pressure.
• Pulmonary hypertension takes place when mean pulmonary
pressure reaches one fourth of systemic level.
• Normal pulmonary arterial pressure averages 25/10 (mean 15 mm
Hg). If pressure exceeds 30/15 (mean 20 mm Hg) it is called pulmonary
hypertension.
• Pulmonary Hypertension takes place secondary to structural
cardiopulmonary conditions that increase :
- Pulmonary blood flow
- Pulmonary pressure
- Pulmonary blood flow and pressure, both.
- Increased Pulmonary vascular resistance
- Left heart resistance to blood flow.

Causes of Pulmonary Hypertension

1. Chronic Obstructive or Interstitial Lung Disease: Patients with
emphysema have hypoxia as well as destruction of lung parenchyma and
hence have fewer alveolar capillaries . This causes increased pulmonary
arterial resistance and secondarily , increased pressure.

2. Antecedent Congenital or Acquired Heart Disease: Pulmonary
hypertension occurs in patients with mitral stenosis . In mitral stenosis an
increase in left atrial pressure leads to an increase in pulmonary venous
pressure and, consequently , to an increase in pulmonary artery pressure

3. Recurrent Thromboemboli: Patients with recurrent pulmonary
emboli may have pulmonary hypertension owing to a reduction in the
functional cross sectional area of the pulmonary vascular bed brought
about by the obstructing emboli which in turn , leads to an increase in
pulmonary vascular resistance

Symptoms of Pulmonary Hypertension

• Symptoms of underlying disease and right
heart failure are usually prominent .

• Symptoms directly related to pulmonary
hypertension are:
-exertional syncope
- chest pain
- recurrent hemoptysis.

Diseases of Pleura
•The pleura is composed of connective tissue lined with mesothelial cells
forming two opposing surfaces, the visceral pleura covers the lungs and the
parietal pleura covers the thoracic cage.
1. Accumulation of Fluid in pleural cavity
• Proteinaceous fluid, blood, lymph or air may form collections.
2. Inflammation
• Inflammation is common, causing sharp localized chest pain
( pleurisy)

• Pleurisy seen with pneumonia, pulmonary tuberculosis, pulmonary
infarction, connective tissue diseases, etc.
3. Tumours
• Secondary tumours usually from lung or breast carcinomas .
• Mesothelioma

Disorders due to collection of fluid and air in the pleural cavities

Disorder Collection Causes
Haemothorax Blood Chest injury, ruptured
aortic aneurysm
Hydrothorax Low protein fluid Liver failure, cardiac
(transudate) ; High failure, renal failure,
protein fluid (Exudate) tumours, infection,
inflammation
Chylothorax Lymph Neoplastic obstruction
of thoracic lymphatics
Pneumothorax Air •Spontaneous
following rupture of
alveolus or bulla in
emphysema or
tuberculosis
• Traumatic, eg,
following penetrating
injuries of the chest
Pyothorax Pus Infection

Causes of Pleural Effusion

Exudate:( Protein more than 3 gram/dl)
1. Tuberculosis
2. Malignancy
3. Para pneumonic
4. Pulmonary infarction
5. Connective tissue disorders (SLE, Rheumatoid Arthritis)

Transudate: (Protein less than 3 grams/dl)
1. Congestive Cardiac Failure
2. Hypoproteinemia including Nephrotic Syndrome
3. Meig’s syndrome ( it can be exudate to)

Exudate VS Transudate

Transudate Exudate
Appearance Clear Usually cloudy or
turbid
Colour Watery Turbid to purulent or
bloody
Specific Gravity Less than 1.016 1.016 or more
Cell Count Less than 1 X 10 9/l More than 1 X109/l
DLC Lymphocytes and Neutriophils early but
mesothelial cells lymphocytes later
RBC Absent Often present
Clot formation None Usual
Glucose Same as serum Usually same as serum
or reduced.

Transudate Exudate
Total Protein Less than 3 gram/dl 3.0 g/dl or more
pH More than 7.5 Less than 7.5
Rivolta Test Negative or faint Positive
LDH Normal Increased
Pathogenesis Gradient of serum and Usually involves
pleural fluid inflammation which
maintained because of increases the
intact vascular permeability of
endothelium pulmonary and pleural
vasculature permitting
the passage of fluid
with high protein
content

Tumours of Pleura

Secondary Tumours of Pleura
-From Lungs
-From Breast
- From Ovaries
- Malignancies from any organ can metastasize to pleura

Primary Tumours of Pleura
- Benign Mesothelioma
-Malignant Mesothelioma

Benign Mesothelioma

•A localized growth that is often attached to the pleural surface
by a pedicle.
• Tumour may be a small or may reach enormous size.
• Usually do not produce pleural effusion
• Grossly consist of dense fibrous tissue with occasional cysts filled
with viscid fluid
• Microscopically the tumour show whorls of reticulin and
collagen fibers along with interspersed spindle cells resembling
fibroblasts.
• Benign Mesothelioma has no relationship with Asbestos

Malignant Mesothelioma

• Uncommon , but have assumed great importance because of
their association with Asbestos.
• In coastal areas with shipping industries and in South African
mine areas upto 90% of malignant Mesothelioma are associated
with Asbestos.
• A diffuse lesion that spreads widely in the pleural space.
Associated with extensive pleural effusion.
• The effected lung is ensheathed by a thick layer of soft gelatinous
grayish pink tumour tissue.

• Microscopically the malignant Mesothelioma has two
appearances:
1. Sarcomatoid Type:
Mesothelial cells tend to develop as a
mesenchymal mass.
Microscopically appear as a spindle cell sarcoma

2. Epithelial Type:
Microscopically cells appear like epithelium lining
cells. It consists of cuboidal, columnar or flattened cells forming
a tubular or papillary structure, resembling Adenocarcinoma

Pleural Mesothelioma: The tumour envelops
the lung

Malignant Mesothelioma, epithelial type: The tumor cells are immunoperoxidase
positive for keratin, as shown (brown), but would be carcinoembryonic antigen
negative

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