Normal lung histology and

COPD

Presented to
MBBS4-Year 2
Presented by
Dr Kyriacos N. Felekkis
Histopathology Lead 16th of September 2015
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
Trap particulates
Barrier to infection

Alveolar lining:
Gaseous exchange
Surfactant production
Elastic recoil
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
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
- Bowmans glands, which are pure
serous glands, are found below the
epithelial surface
- 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. Within
the magnified inset of the lower panel, the
Clara cells are cuboidal but do not have
cilia. They secrete a more watery substance
than mucus and the fluid continues to
moisten, warm, and clean the air.
-
- 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.
- The arrows in the lower right panel indicate 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.
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).
Obstruction occurs due to:

Anatomic airway narrowing (eg. asthma, chronic bronchitis)

Loss of elastic recoil of lung (eg. emphysema)
Emphysema and chronic bronchitis are often grouped together and
referred to as Chronic Obstructive Pulmonary Disease (COPD).
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 bronchitisPresence 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
EmphysemaAbnormal, permanent enlargement of the distal
airspaces, distal to the terminal bronchioles, accompanied by
destruction of their walls and without obvious fibrosis
AsthmaWidespread narrowing of the bronchial airways which
changes its severity over short periods either spontaneously or
after treatment
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)
set to become the 3rd leading COD worldwide by 2020
(surpassed only by heart disease and stroke)
COPD - pathogenesis
Inflammation:

numbers of neutrophils, macrophages and T lymphocytes

(CD8 > CD4).
generally, extent of inflammation is related to the degree of
airflow limitation.
pattern of inflammation is different to that seen in asthma.
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 inactivation of antiproteases, stimulation of

mucus production, and can amplify inflammation by enhancing
transcription factor activation
 Main proteases are from neutrophils (elastase, cathepsin
G, and protease 3), macrophages (cysteine proteases and
cathepsins E, A, L and S) and matrix metalloproteases (eg.
MMP8, 9 and 12).
Main anti-proteases involved in the pathogenesis of
emphysema include 1 antitrypsin,
secretory leucoprotease inhibitor, and tissue inhibitors of
metalloproteases.
Sources of oxidants include cigarette smoke and reactive
oxygen and nitrogen species
released from inflammatory cells.
COPD pathogenesis
Inflammatory mechanisms in COPD:
Cigarette smoke activates
macrophages and epithelial cells to
release
chemotactic factors that recruit
neutrophils and CD8 cells from the
circulation.
These cells release factors that activate
fibroblasts, resulting in abnormal repair
processes and bronchiolar fibrosis.

An imbalance between proteases

released from neutrophils and
macrophages
and antiproteases leads to alveolar wall
destruction (emphysema).
Proteases also cause the 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
without obvious fibrosis.
Emphysema classification 1
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.

sgupath.wikispaces
Emphysema classification 2

Panacinar (or panlobular)

Uniform enlargement of acinus (from level of RB to alveoli).
Lower zones, usually most severe at the bases.
1-AT deficiency.
Paraseptal

Predominantly affects the distal part of the acinus.

More strikingly located adjacent to the pleura.
Propensity to cause pneumothorax (bullous emphysema).
Adjacent to areas of scarring or collapse.
Irregular

Almost invariably associated with scarring.

What are the complications of COPD?
Respiratory failure
Pulmonary HT 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, remodelling of the pulmonary arteries
(smooth muscle hypertrophy and hyperplasia), and destruction
of the pulmonary capillary bed.
Pneumonia

Pneumothorax

Depression

Muscle wasting/cachexia
Thank you