Normal lung histology and

COPD

Presented to
MBBS4-Year 2
Presented by
Dr Despina Moissidou (Histology)
Dr Demetrios Kanakis (Pathology) 14th of September 2016
Upper respiratory tract

Lower respiratory tract

The lungs are primarily responsible for the movement

of air and delivery of oxygen to and removal of carbon
dioxide from the circulation.

Respiratory mucosa:
Warm and humidify air (blood vessels / mucous glands)
Trap particulates (ciliated cells)
Barrier to infection (mucus is eventually swallowed)

Alveolar lining:
Gaseous exchange (blood-air barrier)
Surfactant production (pneumocytes II)
Elastic recoil (elastic fibres)
Location of lung tumours in
relation to carina is
important in lung cancer
staging.
Histology of upper airways

 Lining of upper airways = ciliated pseudostratified columnar

epithelium
– Ciliated cells -> mucociliary escalator
– Goblet cells -> mucus production
– Basal cells -> pluripotent reserve cell (close to the basal membrane)
– Neuroendocrine cells -> chemoreceptors, neuroactive substances
Histology of upper airways
NASAL CONCHA AND ITS MUCOSA ARE
SHOWN IN THE HISTOLOGICAL SLIDES
HERE.
- The top panel emphasizes the warming
function of the nasal mucosa. The large
number of dilated veins transfer heat from
the blood to the inspired air. This
appearance of thin-walled veins
immediately adjacent to the mucosa is
typical of the nasal walls and cavity.

-The lower panel is a close-up of the nasal

mucosa. Note the respiratory epithelium,
which is mainly composed of
pseudostratified, ciliated columnar
epithelium with goblet cells. The other
structures include mixed muco-serous
glands, nerves, normal arteries and veins,
and thin-walled dilated veins.
- The goblet cells and glands provide mucus
to humidify the inspired air and trap dust,
particles, and bacteria.
- The ciliated cells beat and help to clear the
nasal cavity of these foreign particles and
mucus and clean the inspired air.
- The olfactory mucosa is located at the
superior part of the nasal cavity. Respiratory
epithelium lines the remainder of the walls
of the nasal cavity.

- Olfactory epithelium:
- thicker than respiratory epithelium
- Bowman’s glands, which are pure
serous glands, below the epithelial
surface (production of odorant binding
protein)
- abundant nerve fibers originating
from olfactory receptor cells
converge and give rise to the olfactory
tract, providing the special sense of
smell
- absence of goblet cells

- Respiratory epithelium:
- thinner than olfactory epithelium
- many mucus-secreting glands
- no nerve fibers
- abundance of goblet cells
- After the nose and nasal cavity, the
air travels down the pharynx, which is
divided into the nasopharynx,
oropharynx, and laryngopharynx.

- In the side panel, the pharyngeal

mucosa is detailed – note the non-
keratinized stratified squamous
epithelium, connective tissue,
mucous glands, and underlying
elastic layer.
-The panel on the left shows the relative positions of the
true vocal cords (vocal fold) and false vocal folds
(ventricular or vestibular folds). The panel below
shows a magnified view
- The true vocal cords contain underlying skeletal muscle
called the vocalis muscles. Under the false vocal folds,
the connective tissue is filled with glands that secrete
mostly mucus.
- The vocal cord is covered by stratified squamous
non-keratinized epithelium.
- The false vocal cord is covered by respiratory
epithelium.
Histology of the Lower Respiratory tract

Trachea

Bronchi

Bronchioles

Alveoli
- As we continue down the respiratory tract, we enter
the trachea. Shown on the left panel is the trachea and
the major bronchi, which branch into segmental bronchi
and determine the bronchopulmonary segments.
- Histological slides of the trachea are shown below.
The bottom left panel exhibits the characteristic C-
shaped rings of hyaline cartilage (C). The rings are
joined posteriorly by bands of smooth muscle known as
trachealis muscle (T). Tracheal mucosa (M) and some
strands of longitudinal muscle (L) are also shown.
- The trachea is lined with respiratory epithelium
sitting on a thick basement membrane. The elastic layer
contains many longitudinally oriented elastic fibers. The
submucosa contains loose connective tissue and mixed
muco-serous glands.
-Continuing down the respiratory tract, the
trachea bifurcates into two main or primary
bronchi. Within the tracheal bifurcation is a
keel-shaped cartilage known as the carina.

- The main bronchi later divide into

segmental bronchi. A characteristic
component that allows us to identify bronchi
is the presence of cartilage that appear as
chips and not semi-circular as in the
trachea.
- Bronchi are lined with the
pseudostratified ciliated columnar
epithelium (respiratory epithelium) with
glands within the submucosa.
- The bronchi further separate into
bronchioles. The defining feature of a
bronchiole versus a bronchus is the
absence of cartilage.
- Notice the abundance of smooth muscle
within the bronchiole wall. The epithelium is
frequently folded due to contraction of the
smooth muscle.
- The epithelium goes through a transition
from the pseudostratified ciliated columnar
respiratory epithelium to cuboidal ciliated
epithelium, as shown magnified in the
lower panel.
- The lower panel also compares the
relative size of the bronchiole to a typical
pulmonary artery.
- There are progressively fewer goblet cells.
They are replaced by Clara cells.
Clara cells:
- cuboidal but do not have cilia.
- secrete a glycoprotein and lipid-rich
secretions into the airways – surfactant
- Detoxifying compound cytochrome
p450: regenerate the epithelium of small
airways when damaged
- Terminal bronchioles continue as respiratory bronchioles,
which then open into alveolar ducts and individual alveoli.
- This is the respiratory portion of the respiratory system, where
the actual gas exchange occurs.
- Note the walls are composed of squamous epithelium,
containing both type I and II pneumocytes.
-Type I pneumocytes or alveolar cells are very thin and provide
support to the alveoli .
-The type II pneumocytes synthesize and secrete surfactant –
reducing surface tension and allowing the alveoli to remain open.
-Can proliferate and replace type I pneumocytes.
- Pulmonary macrophages in the alveoli, but not within the
walls.
Design and structure of the human lung. In: Fishman AP, ed. Pulmonary Diseases and Disorders .
Vol 1. 2nd ed. New York: McGraw-Hill; 1988:14
-There are two different circulations within
the lung.
- The low pressure, high volume
circulation flows to the lungs from the right
heart in order to be oxygenated. The
pulmonary arteries and veins are both
thin-walled vessels in this circulation.
- The high pressure, small volume
circulation provides oxygenated blood
primarily from the left heart and aorta to the
conducting portion of the respiratory
system. It includes the bronchial arteries
that have thicker walls to carry the high
pressure blood flow.

- There are 4 layers that exist between the

blood and inspired air in the blood-air
barrier:
- 1) capillary endothelium (continuous, no
fenestrations)
- 2) fused basal lamina
- 3) alveolar epithelium (type I pneumocyte)
- 4) surfactant
- Note the proximity of the red blood cell to
the inhaled air within the alveoli.
Definitions of conditions associated with
airflow obstruction
 Chronic obstructive pulmonary disease (COPD): Airflow
obstruction that is usually progressive, not reversible,
and does not change markedly over several months. It
is predominantly caused by smoking
 Chronic bronchitis: Presence of chronic productive
cough on most days for 3 months, in each of 2
consecutive years, and other causes of productive
cough have been excluded
Definitions of conditions associated with
airflow obstruction
 Emphysema: Abnormal, permanent enlargement of the
distal airspaces, distal to the terminal bronchioles,
accompanied by destruction of their walls and without
obvious fibrosis
 Asthma: Widespread narrowing of the bronchial
airways which changes its severity over short periods
either spontaneously or after treatment
Chronic obstructive pulmonary disease (COPD)
Major obstructive lung disorders:
 Emphysema
 Chronic bronchitis
 Bronchiectasis
 Asthma
COPD is characterized by poorly reversible airflow obstruction
and an abnormal inflammatory response in the lungs
Patients characteristically show limitation of maximal airflow
rates during forced expiration (FEV1:FVC <0.7; FEV1 = 50-
80% of expected)
COPD – Aetiology and Epidemiology

 Common extrinsic trigger  Smoking

 Only about 10% of COPD patients are non-smokers
 Reversible airway reactivity (‘asthma’) may be a
component of COPD in some patients
 COPD affects about 3 million people in the UK
(prevalence of around 9%) and ranks 5th in the UK
as a cause of death and 4th worldwide (NICE
Guidelines 2010)
 About to become the 3rd leading cause of death
worldwide by 2020 (surpassed only by heart
disease and stroke)
Chronic obstructive pulmonary disease (COPD)
 Obstruction occurs due to:
 Anatomic airway narrowing (e.g. asthma, chronic
bronchitis)
 Loss of elastic recoil of lung (e.g. emphysema)
 Emphysema and chronic bronchitis are often grouped
together and referred to as Chronic Obstructive
Pulmonary Disease (COPD)
COPD - Pathogenesis
 Inflammation:
– ↑ numbers of neutrophils, macrophages and T
lymphocytes (CD8 > CD4)
– Extent of inflammation is related to the degree of airflow
limitation
 Imbalance between proteases and anti-proteases:
– Proteases include various matrix metalloproteases and
those produced by neutrophils and macrophages
 Imbalance between oxidants and antioxidants:
– Oxidative stress causes inactivation of anti-proteases,
stimulation of mucus production, and amplification of
inflammation by enhancing activation of transcription factor
COPD - Pathogenesis
 Main proteases are from neutrophils (elastase, cathepsin
G, and protease 3), macrophages (cysteine proteases and
cathepsins E, A, L and S) and matrix metalloproteases (e.g.
MMP-8, -9 and -12)
 Main anti-proteases involved in the pathogenesis of
emphysema include alpha-1 antitrypsin, secretory leuco-
protease inhibitor, and tissue inhibitors of metalloproteases
 Sources of oxidants include cigarette smoke and reactive
oxygen and nitrogen species
COPD - Pathogenesis COPD: Inflammatory mechanisms
 Cigarette smoke activates macro-
phages and epithelial cells to
release chemotactic factors
 The latter recruit neutrophils and
CD8 cells from the circulation
 These cells release factors that
activate fibroblasts, resulting in
abnormal repair processes and
bronchiolar fibrosis
 Imbalance between proteases
released from neutrophils and
macro-phages and anti-proteases
leads to alveolar wall destruction
(emphysema)
 Proteases also cause release of
mucus
 • Inflammation
• Oxidative stress
Pathogenic • Imbalance between proteases and anti-proteases
mechanisms

• Proximal cartilaginous airways (>2mm diameter)

• Peripheral non-cartilaginous airways (<2mm diameter)
Pathological • Lung parenchyma (respiratory bronchioles and alveoli)
changes • Pulmonary vasculature

• Mucus hypersecretion and ciliary dysfunction

• Airflow obstruction and hyperinflation
Physiological • Gas exchange abnormalities
abnormalities • Pulmonary hypertension
Emphysema

Lung condition characterized by:

 Abnormal permanent
enlargement of the airspaces
distal to the terminal bronchiole
 Accompanied by destruction of
their walls
 NO obvious fibrosis
Emphysema
Pathogenesis of emphysema
Emphysema - Classification

Sudhakar NJ. Pipavath, Rodney A. Schmidt, Julie E. Takasugi, J. David Godwin. Chronic Obstructive Pulmonary
Disease: Radiology-Pathology Correlation; Thoracic Imaging; Volume 24; Number 3; August 2009
Emphysema - Classification

www.pathologyoutlines.com
Emphysema - Classification
 Centriacinar (or centrilobular)
 Affects proximal parts of acini
(formed by respiratory bronchioles)
 Spares distal part of acinus
 Upper lobes (especially apical
segments) more severely affected
 Heavy smokers
Emphysema - Classification
 Panacinar (or panlobular)
 Uniform enlargement of acinus
(from level of respiratory bronchioles
to alveoli)
 Lower zones, usually most severe at
the bases
 α1-antitrypsin deficiency
Emphysema - Classification
Paraseptal
 Predominantly affects the distal
part of the acinus
 More strikingly located adjacent
to the pleura
 Propensity to cause pneumo-
thorax (‘bullous emphysema’)
 Adjacent to areas of scarring or
collapse

Sudhakar NJ. Pipavath, Rodney A. Schmidt, Julie E. Takasugi, J.

David Godwin. Chronic Obstructive Pulmonary Disease: Radiology-
Pathology Correlation; Thoracic Imaging; Volume 24; Number 3;
August 2009
Bullous emphysema

ww.library.med.utah.edu Sudhakar NJ. Pipavath, Rodney A. Schmidt, Julie E. Takasugi, J. David Godwin.
Chronic Obstructive Pulmonary Disease: Radiology-Pathology Correlation;
Thoracic Imaging; Volume 24; Number 3; August 2009
COPD - Complications
 Respiratory failure: Condition in which not enough oxygen
passes from lungs into the blood or lungs can't properly
remove carbon dioxide from the blood
 Pulmonary hypertension and Cor pulmonale
 Cor pulmonale is failure of the right side of the heart
brought on by long-term high blood pressure in the
pulmonary arteries and right ventricle of the heart
 Pulmonary arterial constriction (as a result of hypoxia),
endothelial dysfunction, remodeling of the pulmonary
arteries (smooth muscle hypertrophy and hyperplasia),
and destruction of the pulmonary capillary bed
COPD - Complications
 Pneumonia
 Pneumothorax
 Depression
 Muscle
wasting/cachexia
Thank you
for your attention!