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HISTOLOGY OF RESPIRATORY BRONCHI, ALVEOLAR DUCT, ALVEOLI AND
BLOOD-AIR BARRIER
LEARNING OBJECTIVES:
At the end of the lecture, the student should be able to:
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Describe the microscopic anatomy of respiratory bronchiole.
Discuss the microscopic picture of alveolar ducts, alveolar sacs and alveoli.
Know the different types of cells found in respiratory tract like type 1 and type2 cells
found in alveoli
Discuss surfactant, alveolar septum, alveolar pores and alveolar macrophages
Describe blood-air barrier.
Discuss the clinical aspects related to the topic.
RESPIRATORY SYSTEM:
1) Conducting Zone:
(Air passages; air conditioning)
1. Nasal cavities
2. Nasopharynx and oropharynx
3. Larynx.
4. Trachea.
5. Paired primary bronchi.
6. Bronchiole tree.
A. internal bronchi.
B. bronchioles.
II). Respiratory Zone
A). Respiratory Bronchioles
B). Alveolar ducts
C). Alveolar Sacs
D). Alveoli
1). Type 1 cells
2). Pulmonary Capillaries
3). Respiratory Membrane
4). Type II cells
Surfactant
5). Alveolar Pores
6). Alveolar macrophages
BRONCHIOLES:
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Bronchioles, intralobular airways with diameters of 5 mm or less, have neither
cartilage nor glands in their
mucosa; there are only scattered
goblet cells within the epithelium
of the initial segments.
 In the larger bronchioles, the
epithelium is ciliated
pseudostratified columnar, which
decreases in height and complexity
to become ciliated simple columnar
or cuboidal epithelium in the
smaller terminal bronchioles.
 The epithelium of terminal
bronchioles also contains Clara
cells which are devoid of cilia, have
secretory granules in their apex,
and are known to secrete proteins
that protect the bronchiolar lining
against
oxidative
pollutants
and inflammation.
The bronchiolar epithelium, AND the
smooth muscle is clearly visible. There is
absence of cartilage and glands from the
bronchioli.
A lung section showing branching of bronchioles with
different sizes of bronchioles (1, 2, 3), large blood vessels,
and alveoli. PT stain. Low magnification.
Clara cells in the epithelium of a terminal bronchiole.
These cells show secretory granules and a bulging
apical cytoplasm. PT stain. High magnification.
Transition of a terminal bronchiole into an alveolar duct (arrow). Note the Clara cells
(arrowheads). PT stain. Medium magnification
RESPIRATORY COMPONENTS:
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The respiratory portions of the lungs are the structures that are directly involved in
the transfer of oxygen from the air into the
blood and carbon dioxide from the blood into
the air.
 The alveolus is the structural unit of gas
exchange:
 It is a spherical or polygonal air space about 250
micro m in diameter
 Its thin walls are
surrounded by a rich
network of pulmonary capillaries
All respiratory components are characterized by the presence of
alveoli.
RESPIRATORY BRONCHIOLES:
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Each terminal bronchiole (subdivides into two or more
respiratory bronchioles that serve as regions of transition
between the conducting and respiratory portions of the
respiratory system).
The respiratory bronchiolar mucosa is structurally identical to
that of the terminal bronchioles, except that their walls are
interrupted by numerous saclike alveoli where gas exchange occurs.
Portions of the respiratory bronchioles
are lined with ciliated cuboidal
epithelial cells and Clara cells, but at the
rim of the alveolar openings the
bronchiolar epithelium becomes
continuous with the squamous alveolar
lining cells (type I alveolar cells);
Proceeding distally along these
bronchioles, the alveoli increase greatly
in number, and the distance between
them is markedly reduced.
Between alveoli, the bronchiolar
epithelium consists of ciliated cuboidal
epithelium; however, the cilia may be
absent in more distal portions.
Smooth muscle and elastic connective
tissue lie beneath the epithelium of respiratory bronchioles.
Identify both type I and II alveolar cells and
capillaries in the alveolar walls, red blood cells
usually appear thicker than the entire wall of the
alveoli.
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Respiratory bronchioles are the smallest bronchioles and are considered to be
part of both the conducting and respiratory portions. They are characterized by
interspersed alveoli in their walls.
Are characterized by occasional alveoli in their walls
Arise from the branching of terminal bronchioles.
Are lined by mainly cuboidal ciliated epithelium and Clara cells.
Have smooth muscle in their walls
Undergo further branching (~3 orders) ultimately forming ill-defined alveolar
ducts (~3 orders) whose walls are mainly composed of alveoli and little smooth
muscle.
Alveolar ducts terminate in two or three alveolar sacs whose walls are
comprised completely of alveoli.
Reticular and elastic fibres form the bulk of the connective tissue present in the walls of
the alveoli. Collagenous fibres are sparse and fine in the alveolar walls. Recognize alveolar
ducts
LUNGS
Stained with haematoxylin and eosin:
1 - Middle diameter bronchus.
2 - Epithelium of the mucosa.
3 - Lamina propria of the mucosa.
4 - Lamina muscularis of the mucosa.
5 - Tunica submucosa.
6 - fibro-elastic layer.
7 - Tunica adventitia.
8 – Alveoli.
9 - Interstitial connective tissue of the lung.
10 - Glands in tunica submucosa.
LUNG Stained with haematoxylin and eosin:
1 - Small diameter bronchus.
2 – Alveoli.
3 - Epithelium of the mucosa.
4 - Lamina propria of the mucosa.
5 - Tunica muscularis.
6 - Tunica adventitia.
HISTOLOGICAL STRUCTURE OF ALVEOLI:
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The structure of the alveolar walls is specialized for enhancing diffusion between the
external and internal environments.
Generally, each wall lies between two neighboring alveoli and is therefore called an
interalveolar septum, or wall.
The wall of the alveoli is formed by a thin sheet (~2µm) of
tissue separating two neighbouring alveoli.
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This sheet is formed by epithelial cells and intervening connective tissue. Collagenous
(few and fine), reticular and elastic fibres are present.Between the connective tissue
fibres we find a dense, anastomosing network of pulmonary capillaries.
The capillaries and connective tissue constitute the interstitium.
Within the interstitium of the interalveolar septum is found the richest capillary
network in the body.
The walls of the capillaries are in direct contact with the epithelial lining of the
alveoli.
The basal laminae of the epithelium and endothelium may actually fuse.
Neighbouring alveoli may be connected to each other by small alveolar pores.
Three-dimensional
schematic diagram of
pulmonary alveoli showing
the structure of the
interalveolar septum. Note
the capillaries, connective
tissue, and macrophages.
These cells can also be
seen in—or passing into—
the alveolar lumen.
Alveolar pores are
numerous. Type II cells
are identified by their
abundant apical microvilli.
The alveoli are lined with
a continuous epithelial
layer of type I cells.
PULMONARY LOBULE:
Blood and lymph circulation in a
pulmonary lobule. Both vessels and
bronchi are enlarged out of proportion in
this drawing. In the interlobular septum,
only one vein (on the left) and one
lymphatic vessel (on the right) are shown,
although both actually coexist in both
regions. At the lower left, an enlargement
of the pleura shows its mesothelial lining.
ALVEOLAR TYPE I CELLS:
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The epithelium of the alveoli is formed by two cell types:
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(Small alveolar cells or
type I pneumocytes) are
extremely flattened (the
cell may be as thin as 0.05
µm) and form the bulk
(95%) of the surface of the
alveolar walls.
The shape of the cells is
very complex, and they
may actually form part of
the epithelium on both
faces of the alveolar wall.
Alveolar type II cells:
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(Large alveolar cells or type II pneumocytes) are irregularly
(sometimes cuboidal) shaped.
They form small bulges on the alveolar walls.
 Type II alveolar cells contain a large
number of granules called cytosomes
(or multilamellar bodies),
which consist of precursors to
pulmonary surfactant (the mixture of
phospholipids which keep surface
tension in the alveoli low.
ALVEOLI:
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Cilia are absent from the alveolar
epithelium and cannot help to
remove particulate matter
which continuously enters the
alveoli with the inspired air.
 Alveolar macrophages take
care of this job. They migrate
freely over the alveolar
epithelium and ingest
particulate matter.
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Towards the end of their life span, they migrate either towards the bronchioles,
where they enter the mucus lining the epithelium to be finally discharged into the
pharynx, or they enter the connective tissue septa of the lung.
BLOOD-AIR BARRIER:
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The blood-air barrier is formed by:
The Type I pneumocyte (alveolar epithelium
A single basement membrane*
Pulmonary capillary endothelium
* the single basement membrane is
formed by the fusion of the basement
membranes belonging to the
pneumocyte and the pulmonary
capillary endothelium.
RESPIRATORY (CONDITIONING) EPITHELIA:
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a) Ciliated cells:
i) columnar cells with 300 cilia/cell, 14 cycles/s, propel mucus at 2 cm/min
ii) cilia beat in one direction (towards oropharynx) propelling mucus and particulates
to be removed (spit it out or swallow it)
iii) loss of cilia activity results in respiratory infections
iv) microvilli also at apex of cell
b) Mucous goblet cells:
i) Secrete mucus that traps particulate matter
ii) have sparse microvilli.
c) Brush cells:
i) Columnar cell with short, blunt microvilli on
apical surface
ii) sensory receptor cell?
 d) Basal (short) cells:
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i) Located at the base of epith. And do not reach lumen
ii) stem cell function
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e) Small granule cells (bronchial Kulchitsky cells):
i) contain granules at base of cell
ii) thought to have neuroendocrine function (similar to
enteroendocrine cell of gut)
f) Clara cells [(distal elements of conducting portion (bronchioles
and terminal bronchioles)]
i) Secrete lipoprotein that is a surface active agent.
GAS EXCHANGE EPITHELIA
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a) Type I cells (pneumocytes):
i) very squamous (25 nm) epithelia
ii) organelles are very near nucleus so that the extranuclear
regions can be very thin
iii) have occluding junctions and intercellular linkages via
desmosomes
iv) cover 95% of the gas exchange surface-reduces surface
tension between alveolar wall and air.
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b) Type II cells (septal cells, great
alveolar cells):
i)
simple cuboidal cells typically
found at alveolar wall junctions
(septa)
ii) junctions like and with type I
cells
iii) cover 5% of the gas exchange
surface
iv) has lamellar bodies containing
phospholipids, GAGs, and proteins
that constitute pulmonary
surfactant-reduces surface
tension between alveolar wall and
air.
Secretion of surfactant by a type II cell. Surfactant is a protein–lipid complex synthesized in the rough
endoplasmic reticulum and Golgi complex and stored in the lamellar bodies. It is continuously secreted by
means of exocytosis (arrows) and forms an overlying monomolecular film of lipid covering an underlying
aqueous hypophase. Occluding junctions around the margins of the epithelial cells prevent leakage of
tissue fluid into the alveolar lumen.
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c) Brush cells (sparse and the same as those found in air conditioning epithelia
THE RESPIRATORY DISTRESS SYNDROME:
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The RDS of the newborn is a life-threatening disorder of the lungs caused by a
deficiency of surfactant.
It is principally associated with prematurity and is the leading cause of mortality
among premature infants.
The incidence of respiratory distress syndrome varies inversely with gestation age.
The immature lung is deficient in both the amount and composition of surfactant.
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In the normal newborn, the onset of breathing is associated with a massive release
of stored surfactant, which reduces the
surface tension of the alveolar cells.
This means that less inspiratory force is
needed to inflate the alveoli, and thus
the work of breathing is reduced.
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In the respiratory distress syndrome
the alveoli are collapsed, and the
respiratory bronchioles and alveolar
ducts are dilated and contain edema
fluid.
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A fibrin-rich eosinophilic material
called hyaline membrane lines the
alveolar ducts. This explains why
respiratory distress syndrome was
initially named hyaline membrane
disease.
Fortunately, synthesis of surfactant can be induced by administration of
glucocorticoids, a medication used in cases of respiratory distress syndrome.
Recently, surfactant has also been suggested to have a bactericidal effect, aiding in
the removal of potentially dangerous bacteria that reach the alveoli.
The surfactant layer is not static but is constantly being turned over. The lipoproteins
are gradually removed from the surface by the pinocytotic vesicles of the squamous
epithelial cells, by macrophages, and by type II alveolar cells.
Alveolar lining fluids are also removed via the conducting passages as a result of
ciliary activity. As the secretions pass up through the airways, they combine with
bronchial mucus, forming a bronchoalveolar fluid, which aids in the removal of
particulate and noxious components from the inspired air.
The bronchoalveolar fluid contains several lytic enzymes (eg, lysozyme, collagenase, glucuronidase) that are probably derived from the alveolar macrophages.
LUNG MACROPHAGES
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Alveolar macrophages, also called dust cells, are found in the interior of the
interalveolar septum and are often seen on the surface of the alveolus).
Numerous carbon- and dust-laden macrophages in the connective tissue around
major blood vessels or in the pleura probably are cells that have never passed
through the epithelial lining.
The phagocytosed debris within these cells was most likely passed from the alveolar
lumen into the interstitium by the pinocytotic activity of type I alveolar cells.
The alveolar macrophages that scavenge the outer surface of the epithelium within
the surfactant layer are carried to the pharynx, where they are swallowed.
Learning Resources:
1. Kieth L Moore.
2. June Queira LC. Carneiro J: Basic Histology.