Recommended reading – Robbins Basic Pathology

10TH EDITION – pp 498- 505

Dr Rajani R
LECTURE OBJECTIVES

SLO# 1 :Define Chronic Obstructive Pulmonary Disease

SLO# 2 :List the major Chronic Obstructive Pulmonary Disease

SLO# 3 :Mention the risk factors for Chronic Obstructive Pulmonary Disease

SLO# 4 :Define Emphysema, Chronic bronchitis and Asthma

SLO# 5 :Mention types of Emphysema
SLO# 6 :Describe the pathogenessis, morphology, microscopic features,
clinical features and complications of emphysema,Chronic bronchitis and
Asthma
SLO# 7:Differentiate emphysema and chronic bronchitis
SLO#8:Differntiate atopic and non-atopic asthma
 DIFFUSE OBSTRUCTIVE DISEASES
▪ Lung diseases characterized by airflow limitation,
which is due to increase in resistance caused by
complete/partial obstruction at any level

Major obstructive diseases:

▪ Emphysema May co-exist - COPD
▪ Chronic bronchitis irreversible airway obstruction

▪ Bronchial asthma - reversible airway obstruction

▪ Bronchiectasis
Risk factors
 NOXIOUS AGENT
Tobacco smoke, Pollutants, Occupational
exposures
Genetic factors
Respiratory
Infection
Others l
exposures
COPD
 EMPHYSEMA
Definition:
Permanent and destructive enlargement of airspaces distal to
the terminal bronchioles without obvious fibrosis and with
loss of normal architecture.
▪ Types
▪ Centriacinar
▪ Panacinar
▪ Paraseptal
▪ Irregular

Advanced cases – mixed picture

 1. CENTRIACINAR EMPHYSEMA
 Centriacinar:

 Focal destruction limited to the

respiratory bronchioles and the
central portions of acinus

 associated with cigarette smoking

 most severe in the upper lobes

 Large amounts of black pigment and

dust-laden macrophages in walls of
acinus

 Peri-bronchial and bronchiolar

inflammation
 2. PANACINAR EMPHYSEMA
 Panacinar:

 Involves the entire alveolus

distal to the terminal
bronchiole

 develops in patients with

homozygous alpha1-
antitrypsin (AAT) deficiency

 most severe in the lower lung

zones

COTTON-CANDY
LUNG
Distal acinar: Emphysema
 Also called paraseptal
 involves distal airway structures, alveolar ducts, and sacs
 localized to fibrous septa or to the pleura and leads to
formation of bullae (can result in pneumothorax)
Irregular emphysema:

 Acinus is irregularly affected

 Lesions are associated with scars of healed
inflammatory processes
eg: old healed tuberculous scars at the apex of the
lung
 Clinically asymptomatic
 Most common of all types of emphysema
PATHOGENESIS OF EMPHYSEMA
PATHOGENESIS OF EMPHYSEMA
Smoking and emphysema

Excess neutrophils
in alveoli
 PROTEASE- ANTI PROTEASE
IMBALANCE

▪ Proteases – elastase – secreted by neutrophils

during inflammation
▪ α1-antitrypsin – serum, macrophages, tissue fluids
▪ α1 – antitrypsin - major inhibitor of elastase
▪ Patients with genetic deficiency of α1AT –
↑elastolytic activity - pulmonary emphysema
▪ Genetic deficiency of α1AT + smoking- ↑↑ risk
 EMPHYSEMA
GENES INVOLVED
▪ α1 – antitrypsin – coded by genes on proteinase
inhibitor (Pi) locus on chromosome 14
▪ Pi locus – polymorphic - many alleles
▪ Commonest allele – M – PiMM phenotype – normal
α1 – antitrypsin levels
▪ Z allele – PiZZ (homozygous) – severe
α1 – antitrypsin deficiency – EMPHYSEMA +
CIRRHOSIS
 MORPHOLOGY OF EMPHYSEMA
GROSS

▪ Diagnosis & classification of emphysema on

gross appearance
▪ Panacinar – pale, voluminous, obscure heart
▪ Centriacinar – deeper pink, less voluminous,
upper two –thirds of lungs
▪ Irregular emphysema - large apical blebs or
bullae
 MORPHOLOGY OF EMPHYSEMA
MICROSCOPY
▪ Thinning and destruction of alveolar walls –
confluent alveoli – large air spaces
▪ Loss of elastic tissue in alveolar septa – collapse of
small airways – chronic airflow obstruction
▪ Secondary involvement of the bronchioles
– bronchitis & bronchiolitis
 EMPHYSEMA
CLINICAL COURSE

▪ Symptoms appear when more than 1/3 rd of lung

function is lost
▪ Progressive dyspnea, cough/wheezing, weight loss
▪ Barrel chest – prolonged expiration
▪ PFT - FEV1 – decreased
FVC – normal FEV1 : FVC ↓ [<0.7]
▪ Hyperventilation – normal blood gas values even
late in disease – “PINK PUFFERS”
 EMPHYSEMA
COMPLICATIONS

▪ Respiratory acidosis/ Coma

▪ Secondary involvement of vessels – secondary pulmonary

hypertension - Right sided heart failure – Cor pulmonale

▪ Massive collapse of lungs secondary to pneumothorax

CHRONIC BRONCHITIS
 Definition:
Presence of a cough productive of sputum not attributable to
other causes on most days for at least 3 months over 2
consecutive years.

 Characterised by

 bronchial wall thickening

 Mucus gland enlargement
 goblet cell hyperplasia,
 variable amounts of airway smooth muscle hyperplasia,
 focal squamous metaplasia,
 ciliary abnormalities,
 inflammation,
 lumen occlusion by mucous plugging,
 distortion due to fibrosis
CHRONIC BRONCHITIS -
MORPHOLOGY
 CHRONIC BRONCHITIS
MICROSCOPY

Increase in size of mucous

glands

REID INDEX – b to c
a to d
N - < 0.4
Chronic bronchitis > 0.4
CHRONIC BRONCHITIS
ROLE OF INFECTION

▪ Secondary infections – lead to acute exacerbations

Why increased chances for infections ?

Cigarette smoke:
▪ Interferes with ciliary action of epithelium
▪ Damages the respiratory epithelium
▪ Inhibits the ability of bronchial and alveolar
leukocytes to clear debris
 CHRONIC BRONCHITIS
CLINICAL COURSE

▪ Productive cough
▪ Exertional dyspnea, mild cyanosis
▪ Severe COPD – hypercapnia, hypoxemia, cyanosis
▪ “BLUE BLOATERS”(blue + obese)
▪ Cor pulmonale, respiratory failure
 BRONCHIAL ASTHMA
▪ Increased irritability of bronchi causing
bronchoconstriction and airflow limitation
▪ Paroxysmal attacks
▪ Reversible – spontaneous, with treatment
▪ Various stimuli
respiratory failure that comes with the worst
▪ Status asthmaticus form of acute severe asthma, or an asthma
attack.
ASTHMA - TYPES
Atopic [70%] Non-atopic [30%]
▪ Family history of atopy+ ▪ No family history of atopy

▪ Caused by ▪ Caused by non-immune

environmental allergens stimuli -drugs (aspirin),

(immune stimuli) - pollen, LRI (viral), cold, exercise,

dusts, animal dander, food psychological stress,

occupational exposure to

▪ Type I hypersensitivity plastics, wood, cotton etc

reaction - ↑ IgE ▪ Normal serum IgE

PATHOGENESIS OF Environmental agent
dust, pollen, food etc
ATOPIC ASTHMA

Degranulation of mast cells

bearing IgE molecules

Release of
vasoactive substances

Histamine, ECF-A
SRS-A PAF
Bronchoconstriction, Platelet aggregation –
Attracts eosinophils
increased vascular release of more
to bronchial walls
permeability, mucus histamine, 5-HT
hypersecretion
 BRONCHIAL ASTHMA
MORPHOLOGY

▪ Over distended lungs

▪ Bronchial obstruction with distal atelectasis
▪ Hypertrophy of bronchial smooth muscle
▪ Hyperplasia of submucous glands
▪ Mucus plugging of bronchi
▪ Curschmann’s spirals – whorls of shed epithelium
within mucus plugs
▪ Charcot-Leyden crystals within eosinophil aggregates
Inspissated mucus – cast of Sputum with Charcot-Leyden
bronchial tree crystals - crystalloids of
eosinophilic
proteins

Curschmann’s spirals
 BRONCHIAL ASTHMA
CLINICAL COURSE
Classic asthmatic attack – one to several hours –
subsides with/without therapy.
▪ Persistent asthma (rarely) – status asthmaticus –
can be fatal.
▪ Diagnosis – clinical, eosinophilia, Curschmann’s
spirals, Charcot-Leyden crystals in sputum.
COMPLICATIONS -

Other COPD’s ,Cor-Pulmonale, Heart failure

Status asthmaticus -
post-mortem lungs
Tracheal mucus plug in
patient with status
asthmaticus