Respiratory system

Histology of
R E SPI R AT O R Y SYST E M /T R AC T
1

The Respiratory System
–Consists of the two lungs and a series of air passage ways
that lead to and from the air spaces (alveoli) in the lungs.
–is formed of two functional components:
– Conducting portion: consists of airways that deliver air
to and from the lungs.
– Respiratory portion: consists of structures within the
lungs where oxygen in inhaled air is exchanged for
carbon dioxide in the pulmonary blood.
–The conducting tubes possess lining epithelia, supporting
CTs (loose areolar tissue rich in collagen and elastic fibers and
cartilages), sero-mucous glands, smooth muscle tissue and
other features that are characteristics of each part.
–Each type of airway has its own characteristic structural
features but there is a gradual, rather than abrupt, transition
from one airway to the next along the whole length of the
tract.
2

The Conducting parts include:
– Nasal cavity & paranasal sinuses
– Pharynx
– Larynx
– Trachea
– Bronchi (10,
20
, 30
and so on)
– Bronchioles, and
– Terminal bronchioles
The Respiratory parts include:
– Respiratory bronchioles
– Alveolar ducts
– Alveolar sacs and
– Alveoli
4

Trachea

Main bronchi (1⁰)

Lobar bronchi (2⁰)

Segmental bronchi (3⁰)

---
Bronchioles

Terminal bronchioles

Respiratory bronchioles

Alveolar ducts

Alveolar sacs

Alveoli
Respiratory Tree
5

Conducting portion of the respiratory system
– links the sites of gas exchange within the lungs with the
external environment.
– includes the nose (nasal cavity), paranasal sinuses,
nasopharynx, larynx, trachea, bronchi, and bronchioles
down to and including the terminal bronchioles.
– has two main functions:
1. Provides a continuous conduit through which air can
travel to and from the lungs.
- ensure uninterrupted supply of air: a combination of
cartilage, elastic & collagen fibers and smooth muscle
provides the conducting portion with rigid, structural
support & the necessary flexibility & extensibility.
2. Conditions or modifies (filters, moistens, and warmth) the
inspired air = filtration, humidification and adjusting the
To
of inspired air. 6

Structural importance of the conducting respiratory tract
– The conducting part of respiratory system is essential to
ensure a continuous supply of air by the aid of three main
structural elements:
– Cartilage and Collagen fibers- prevent luminal collapse
– Elastic fibers- permit flexibility needed for expansion &
recoil
– Smooth muscle- to constrict/or dilate air passage during
respiration.
1- Cartilage: it is hyaline mainly but in larynx it is partly elastic
and partly hyaline. It is essential to support the conducting
wall and prevent its luminal collapse.
2-Elastic fibers: essential for flexibility of such part and spring
back after the distension.
– They are situated mainly in the lamina propria
especially of the bronchioles and lung stroma which
have the highest concentration of elastic fibers. 7

3-Smooth muscle fibers:
– completely surround the lower respiratory tubes.
– Their tone controls the luminal diameter of the
conducting tubes (when contract, reduce the diameter)
and thus render resistance to air flow within the
respiratory tree.
– Smooth muscle tone is under control of autonomic
nervous system, adrenal medullary hormones and local
factors such as histamine.
– Sympathetic stimulation causes smooth muscle relaxation and
thus dilatation of the air ways which is a desirable response in
the ‘flight or fight’ situation.
– Parasympathetic activity causes airway constriction; the
physiological significance of this may be to reduce ‘dead space’
on expiration.
8

– The other function of the conducting part is to clean,
moist and warm the air before it reaches the lung. This
function is called conditioning and performed by the
following tissue components:
1. The presence of very specialized respiratory epithelium
(ciliated pseudostratified columnar epithelium with
goblet cells) and lamina propria rich in mucous and serous
glands.
2. The presence of rich superficial vascular network in the
lamina propria.
3. The presence of special hairs (vibrissae) and cilia to
remove coarse particles of dust from the inspired air.
9

GENERAL STRUCTURE OF THE CONDUCTING PORTION OF
RESPIRATORY TRACT
– Conducting respiratory airways are pliable tubes lined by
respiratory mucosa and containing variable amounts of
muscle and/or cartilage in their walls.
– The principal structural features include:
1. The Respiratory Epithelium
– undergoes progressive transition from a tall, pseudo-
stratified columnar ciliated epithelium with goblet cells in
the nasal cavity, nasopharynx, larynx, trachea, bronchi
and bronchioles to a simple columnar in terminal
bronchioles.
– The goblet cells are numerous in the trachea but decrease
in number down the tree and are absent from the
terminal bronchioles and distally.
2. The lamina propria
– It is subepithelial loose fibroelastic CT rich in lymphoid
aggregations (BALT) of variable size as part of MALT. 10

– The lamina propria contains diffuse and nodular masses
of immune cells and lymphocytes (BALT), which produce
secretory immunoglobulin A, which kills the bacteria and
viruses and prevents them from penetrating the
epithelium.
3. Muscle Layer
– A layer of smooth muscle or skeletal muscle lying
deep to the mucosa (except in the trachea).
3. Submucosa (present in extrapulmonary airways only)
– contains sero-mucous glands whose secretion has moistening,
filtering, and detoxifying action on the soluble gases.
3. Adventitia: outermost layer
– loose fibroelastic CT continuous with the surrounding
tissue of lung parenchyma.
– In the smaller airways may contain glands and/or
cartilage plates.

Anatomically the respiratory system is divided into 2
parts:
– Upper respiratory tract
– Lower respiratory tract
1.The Upper Respiratory Tract:
– comprises a system of interconnected spaces of the nasal
cavities, paranasal sinuses and nasopharynx.
– principally involved conducting, filtering, humidifying and
adjusting the temperature of incoming air.
– The nasal cavity also contains special visceral sensory
organ of olfaction.
12

2.The Lower Respiratory Tract:
– Begins with the Larynx which then continues into the
thorax as the trachea, before dividing into numerous
orders (about 20 times in humans) of smaller airways to
reach the alveoli.
– At first, the trachea divides into two primary or main
bronchi.
– Each primary bronchus gives rise to three or two
secondary or lobar bronchi supplying the lobes of the
lungs.
– Each secondary bronchus again divided into tertiary or
segmental bronchi, which supply bronchopulmonary
segments of each lobe.
13

– The tertiary bronchi divide into numerous orders of
progressively smaller airways called bronchioles.
– The smallest of such divisions are called terminal
bronchioles.
– Terminal bronchioles mark the end of the purely
conducting portion of the respiratory tract.
– The terminal bronchioles branch further into a series of
transitional airways the respiratory bronchioles and
alveolar ducts, which become increasingly involved in
gaseous exchange.
– These passages finally terminate in dilated spaces called
alveolar sacs, which receives the openings of the alveoli.
14

Bronchopulmonary segment & its Intrapulmonary Bronchi
15

TB
AS
AD
RB
RB
AS
A
A
Pleura 16

Segmental
bronchus
Branch of
Segmental
bronchus
Segmental
BrofPA
17

TB
AS
AD
RB
RB
AS
A
A
Pleura 18

Bronchiole with BALT and its PA
20
PA
B

Respiratory mucosa
– Lines most parts of respiratory tract
– Refers to the lining epithelium and underlying lamina propria.
Typical Respiratory Epithelium: pseudostratified columnar ciliated
epithelium with goblet cells.
Lamina propria: loose areolar CT containing:
– Rich superficial blood vessels for warming of incoming air.
– Lymphocytes, plasma cells and mast cells for immune
response.
– Seromucous (branched tubuloacinar) glands for secretion of
mucus and absorption and detoxification of gases and
moistening of incoming air.
Note: In some regions of the nasal mucosa, there are veins
resembling erectile tissue termed swell or cavernous
bodies.
–These are specialized veins which engorge periodically and
alternatively close one side of the nasal cavity, thus giving it
time to recover from drying.
–This cyclic process is controlled by autonomic nerves.
21

Respiratory Epithelium
– The mucosa of the conducting respiratory tract is lined by
pseudostratified columnar ciliated epithelium with goblet cells.
– All the cells rest on the basement membrane but not all reach the
top (the luminal surface).
– By this way two rows of nuclei are visible which gives this epithelium
the name "pseudostratified". The columnar cells bear cilia on the
top, which beat to push the mucus and trapped particles towards
the pharynx. The goblet cells secrete mucous & appear hollow (white) in H & E.
24

The Respiratory Epithelium
– Most of the conducting portion of the respiratory system is
lined by pseudostratified columnar ciliated epithelium
with goblet cells.
– When bronchi divide to bronchioles, the epithelium
become shorter and is changed to simple columnar in the
terminal bronchioles then to simple cuboidal in the
respiratory bronchioles.
– Goblet cells are totally absent in the terminal bronchioles,
but cilia continue beyond the goblet cell disappearance to
prevent the accumulation of mucous in the respiratory
portion.
– In smokers, the epithelium undergoes metaplastic changes
to stratified squamous epithelium.
– There are five types of fixedcells in the respiratory
epithelium as seen by the EM:
25

1- Tall Ciliated Columnar Cells:
– are the most common cells with hundreds of long robust
cilia .
– In trachea, each cell carries about 250-300 cilia at its apical
surface.
– The apical localization of the mitochondria is of value in
ATP production which is important for energy needed for
ciliary movement.
– The ciliary movement depends on dynein, a motor protein
normally present in the cilia & helps in sliding of the ciliary
microtubules.
– If there is a decrease in dynein proteins, the ciliary movement is
affected as in Kartagener’s syndrome or Immotile cilia syndrome, a
disorder that causes infertility in men and chronic respiratory tract
infections in both sexes, is caused by immobility of cilia and flagella.26

2- Basal cells (stem cells):
– they are small & short cells located on the basement
membrane and never reach the luminal surface.
– they undergo mitotic divisions to be differentiated to the
other cell types in the respiratory epithelium.
– with their differentiating progeny account about 30% of
cell population in respiratory epithelium.
27

3. Goblet cells:
– are intraepithelial mucous cells interspersed between the
columnar cells and secrete mucus.
– are the third common cells in the respiratory epithelium.
– their apical cytoplasm is distended with abundant large
pale stained mucinogen secretory granules.
– the nucleus is flat and located in the basal part of the cell.
– they synthesize proteins from amino acids at the region of
RER, and carbohydrates are added in Golgi bodies to
release sulphated glycoproteins,
– the apical part of the cell is rich in polysaccharides and
mucous droplets.
– reveal short sparse microvilli 28

4. Brush cells:
– are a much more sparsely scattered and less easily found,
columnar cell type,
– have tapering apical cell surface characterized by a tuft of
numerous short, blunt microvilli for which they are named
brush cells.
– express some signal transduction components like those of
gustatory cells and have afferent nerve endings on their
basal surfaces and are considered to be chemosensory
receptors.
– they represent the rest of the columnar cells.
29

5. Small granule cells (Kulchitsky, K cells):
– they are similar to the basal Cells in their basal location.
– Like brush cells, they represent about 3% of the total cells
and are part of the diffuse neuroendocrine system or APUD
(amine precursor uptake and decarboxylation) cells which
have vital role in diffuse neuroendocrine system.
– they contain numerous dense basal cytoplasmic granules
(100-300 nm); serotonin, bombesin and calcitonin are
among the secretory products so far identified.
– They may regulate the mucous secretory processes.
 All the fixed cells in the respiratory epithelium touch the
basal lamina/basement membrane. 30

Types of Epithelial Cells in Typical Respiratory Epithelium:
- Three types of cells (more than 90% of cell population) are
seen by light microscope:
1. Ciliated columnar cells.
2. Goblet cells which produce mucous secretion.
3. Basal cells: these are undifferentiated cells which can
divide by mitosis and can give other types of cells.
- Two types of cells (less than 10% of cell population) seen
by electron microscope or by special staining technique:
4. Brush cells which contain cytoplasmic granules and carry
microvilli.
5. Granue cells which are of 2 types according to function of
granules:
– Catecholamine secreting cells (neurosecretory cells).
– Protein hormone secreting cells (enteroendocrine like cells).
31

Respiratory Epithelium: a classic
example of pseudostratified columnar
ciliated epithelium: rests on a thick
basement membrane (BM) and has
several cell types, most are columnar,
some basal and all contacting the
basal lamina. Ciliated columnar cells
are the most abundant, with
hundreds of long robust cilia (C) on
each of their bulging apical ends
which provide a lush cover of cilia on
the luminal surface. Most of the small
rounded cells at the basement
membrane are stem/basal cells and
their differentiating progeny.
Intraepithelial lymphocytes and
dendritic cells are also present in
respiratory epithelium as occasional
wondering cells. Mucus-secreting
goblet cells (G) are also present. The
lamina propria is well-vascularized
(V). X400. Mallory Azan trichrome.
32

As shown by SEM of some
region, goblet cells (G)
predominate in some areas,
with subsurface accumulations
of mucus evident in some
(arrows). The film of mucus
traps most airborne dust
particles and microorganisms
and the ciliary movements
continuously propel the sheet
of mucus toward the
esophagus for elimination.
Other columnar cells,
representing only about 3% of
the cells in respiratory
epithelium, are brush cells (B)
with small apical surfaces
bearing a tuft of short, blunt
microvilli. Brush cells have
features of chemosensory
receptors but their significance
is highly uncertain 34

Extrapulmonary conducting portion
– extends from nasal cavity to proximal portions of
secondary bronchi. It is characterized by:
– Lined by ciliated pseudostratified columnar
epithelium rich in goblet cells.
– Submucosa: loose CT rich in mixed seromucous
glands and blood vessels.
Function of the conducting passages:
– Trapping the inhaled particles and debris by the mucous
secretion which have suitable consistency to be expelled
out towards the nose or swallowed by the action of ciliated
epithelium.
– Individuals who suffer from immobile cilia have
chronic lung infections.
– The function of cilia is also lost in smokers thus 35

MEDICAL APPLICATION
– From the nasal cavities through the larynx, portions of the epithelial
lining are stratified squamous.
– This type of protective epithelium is evident in regions exposed to
direct airflow or physical abrasion (eg, oropharynx, epiglottis, vocal
folds); it provides more protection from wear and abrasion than
does respiratory epithelium.
– In smokers the proportion of ciliated cells to goblet cells is altered to
aid in clearing the increased particulate and gaseous pollutants (eg,
CO, SO2).
– Although the greater numbers of goblet cells in a smoker's
epithelium provide for a more rapid clearance of pollutants, the
reduction in ciliated cells caused by excessive intake of CO results in
decreased movement of the mucus layer and frequently leads to
congestion of the smaller airways. 36

Pulmonary Vasculature & Nerves
– Lungs are among the most vascular organs of the body.
– Circulation in the lungs includes both nutrient (systemic) and
functional (pulmonary) vessels.
– Pulmonary arteries and veins represent the functional circulation and
the arteries are relatively thin-walled as a result of the low pressures
(25 mmHg systolic, 5 mmHg diastolic) encountered in the pulmonary
circuit.
– Within the lung , the pulmonary artery branches and closely
accompanies the bronchial tree, with its branches surrounded by
adventitia of the bronchi and bronchioles.
– At the level of the alveolar duct, the branches of this artery form a
rich capillary network in the interalveolar septum and in close
contact with the alveoli.
– The lung has the best-developed capillary network of any organ, with
capillaries between all alveoli, including those in the respiratory
bronchioles. 37

Pulmonary Vasculature
– Diagram shows the
branching
relationship, as
well as the
pulmonary blood
vessels that travel
with the
bronchioles and the
dense layer of
branching
capillaries that
surrounds each
alveolus for gas
exchange between
blood and air. 38

Pulmonary arteries and its branches
– The Pulmonary arterial system is structurally unusual in
two respects:
1. they are thin-walled and of large caliber, their diameter
approximating that of the accompanying airway.
2. have the histological characteristics of elastic arteries
rather than of muscular/distributing arteries.
– elastic expansion and recoil of the vessels maintains
the pulmonary arterial pressure at a relatively
constant level through out the cardiac cycle.
40

Branch of pulmonary artery (PA) and bronchiolar arteriole in
the adventitia of a bronchiole
PA
41

– Venules that originate in the capillary network are found singly in the
parenchyma, somewhat removed from the airways, supported by a
thin covering of connective tissue.
– After veins leave lung acinus, they follow the bronchial tree toward
the hilum.
– Nutrient vessels follow the bronchial tree and distribute blood to
most of the lung up to the respiratory bronchioles, at which point
they anastomose with small branches of the pulmonary artery.
– The lymphatic vessels originate in the connective tissue of
bronchioles.
– They follow the bronchioles, bronchi, and pulmonary vessels and all
drain into lymph nodes in the region of the hilum.
– This lymphatic network is called the deep network to distinguish
it from the superficial network of lymphatic vessels in the visceral
pleura.
42

– Both deep and superficial lymphatic networks drain toward the
hilum, either following the entire length of the pleura or after
entering lung tissue via the interlobular septa.
– Lymphatic vessels are not found in the terminal portions of the
bronchial tree beyond the alveolar ducts.
– Both parasympathetic and sympathetic efferent fibers innervate the
lungs and general visceral afferent fibers, carrying poorly localized
pain sensations, are also present.
– Most of the nerves are found in the connective tissue surrounding
the larger airways.
43

LUNG BY HAEMATOXYLIN & EOSIN
PA
T
AD
AS
RB
AD
RB
44

LUNG INJECTED WITH GELATIN CARMINE TO SHOW VASCULATURE
45

PLEURAE
– Are double layered serous membranes associated the thoracic and
pleural cavities.
– The pleural layer lining the thoracic wall, called the parietal pleura, is
reflected at the lung hilum so as to invest the outer surface of the
lung, the visceral pleura.
– These two layers are directly applied to one another but separated
by a potential space (the pleural space) containing a minute amount
of serous fluid.
– Each pleura consists of a lining simple squamous epithelium
(mesothelium) and underlying fibrous supportive CT which consists
primarily of collagen and elastic fibers and occasional smooth muscle
fibers.
– This fibrous layer of the visceral pleura
– extends into the lung as fibrous septa which is continuous with
the fibro-elastic framework of lung stroma.
– contains superficial plexus of lymph vessels which drain into deep
plexuses surrounding the pulmonary blood vessels and airways.

THE NOSE
Anatomy of Nose
- It is the structure of the face region
- It is organ of respiration, olfaction (smelling) and
speech
- It has roof, floor, lateral wall, medial wall (nasal
septum), anterior opening (nostrils) and posterior
openings (posterior nares)
- It is divided into three main parts
1.Two Nasal vestibules- separated by a cartilaginous
septum
2.Two Nasal cavities-separated by a bony septum
3.Paranasal sinuses 48

The Nose Anterior,
lateral wall
and roof of
nasal cavity
49

- Most of the nose is lined with respiratory mucosa except
the vestibule, roof and upper part of the septum, and the
superior concha.
1- The Nasal Vestibule:
- is the anterior, external dilated part bounded anteriorly by
the two nasal orifices (Nostrils or the anterior Nares).
– consists of two cavities (Right and left) separated by a
cartilaginous nasal septum.
– Lined by thin hairy skin containing sebaceous & sweat
glands, and thick, short stiff hairs known as vibrissae, which
filter out coarse dust particles from the inspired air.
i.e. The vestibule contains sweat and sebaceous glands
– The nostrils are lined by stratified squamous keratinized
epithelium (thin hairy skin). 51

2- The Nasal Cavities Proper (fossae):
– These are two cavernous chambers of the nose separated
by the osseous nasal septum.
– Consists of two types of mucosae (olfactory & respiratory)
– Each lateral wall of the nasal cavity reveals three shelf-like
medial bony projections known as CONCHAE (Superior,
Middle and inferior).
– The inferior and the middle conchae are respiratory parts
and thus lined by respiratory mucosa and epithelium.
– The narrow passages between the conchae improve the
conditioning of the inspired air by increasing the surface
area of moist, warm respiratory epithelium and by slowing
and increasing turbulence in the airflow.
– The result is increased contact between air streams and the
mucous layer. 52

The Lamina Propria of Nasal Cavities
– is rich in large venous plexuses known as SWELL
(CAVERNOUS) BODIES which are very important in
warming the incoming air.
– Every 20–30 minutes, the swell bodies on one side become
temporarily engorged with blood, resulting in distension of
the conchal mucosa and a concomitant decrease in the
flow of air.
– During this time, most of the air is directed through the
other nasal fossa, allowing the engorged respiratory
mucosa to recover from dehydration.
– In nasal allergic diseases, swell bodies are dilated
decreasing the capacity of the nasal cavity leading to a
sense of nasal block. 53

3- Paranasal Sinuses:
– are bilateral air-filled cavities in the frontal, maxillary,
ethmoid, and sphenoid bones of the skull.
– communicate with the nasal cavities through small
openings that drain the mucus produced in the sinuses is
into the nasal cavities by activity of ciliated epithelium.
– lined with a thinner respiratory mucosa with a thinner
respiratory epithelium with fewer goblet cells and a thin
lamina propria.
– This lamina propria is continuous with the underlying
periosteum and contains only a few small mucous glands.
– Sinusitis is an inflammatory process of the sinuses that may
persist for long periods of time, mainly because of
obstruction of drainage orifices.
– Chronic sinusitis and bronchitis are components of immotile cilia
syndrome, characterized by defective ciliary action.
56

The Olfactory Mucosa (Receptor Organ of Smell)
– It is the mucous membrane lining the olfactory areas of
the nasal cavity, notably the roof of the nasal cavity, either
sides of the superior part of nasal septum, & the superior
nasal concha.
– In humans, it is about 10 cm2
area & thicker than the
respiratory mucosa but lacks the Goblet cells.
– Consists of olfactory epithelium [neuroepithelium] and
glandular lamina propria.
– The lamina propria is highly vascular (with many venous
plexuses) and consists of seromucous glands (Bowman’s
glands or olfactory glands) and unmyelinated nerve fibers
(axons of olfactory cells).
– These glands are purely serous and their thin watery
secretion dissolves the odoriferous substances and
also rapidly washes the olfactory hairs to clear the
receptors for new stimuli. 57

Section of the olfactory mucosa
61

The Olfactory Epithelium (Neuroepithelium)
– is tall (up to 100µm) pseudostratified columnar epithelium
without goblet cells, and consists of 3 types of cells:
1- Olfactory cells (bipolar nerve cells)- sensory cells1- Olfactory cells (bipolar nerve cells)- sensory cells
2- Sustentacular (supporting) cells2- Sustentacular (supporting) cells
3- Basal cells- stem cells3- Basal cells- stem cells
1.1. Olfactory cells:
– are modified bipolar neurons (receptors of smell),
characterized by a bulbous apical projection called
olfactory vesicle or knob, from which several (6-8 cilia
from each) long, non-motile, modified cilia extend.
– their peripheral part is simply modified dendrite of the
neuron 62

1.1. Olfactory cells:
– their basal part is the axon of these bipolar neurons, which
passes through the basement membrane, & joins other
axons to form small bundles of the olfactory nerve that
pass through the cribriform plate to reach the brain and
eventually synapse with 2nd
order neurons in the olfactory
bulb.
– distinguished from the supporting cells by the position of
their nuclei, which lie at the middle between those of the
supporting cells and the basal cells.
64

Olfactory Cilia (Olfactory hairs)
–are very long, nonmotile cilia (sterocilia), which extend over
the surface of olfactory epithelium.
–are receptors for odor
–they increase the receptors surface considerably.
–they respond to odoriferous substances by generating
receptor potential.
–their proximal third contains a typical 9+2 axoneme pattern,
but their distal two-third is composed of 9 peripheral single
microtubules surrounding a central pair of microtubules.
65

2. Sustentacular (Supporting) cells:
– are columnar cells with narrower tapering bases, and broad
cylindrical apexes that carry microvilli, forming a prominent
terminal web.
– possess nuclei more apically and superficially located than
those of the other two cell types.
– on their free surface are microvilli submerged in a fluid layer
– bound to adjacent olfactory cells with well developed
junctional complexes.
– their cytoplasm contains light yellow pigments that impart the
olfactory mucosa yellowish coloration.
3. Basal cells:
– rest on basal lamina, but do not extend to the surface.
– form an incomplete layer of cells.
– short pyramidal undifferentiated stem cells that can give rise to
the other two types of cells. 68

Bowman’s Glands (Olfactory Glands)
– found only in the olfactory region of nasal cavity situated
in the lamina propria of olfactory mucosa.
– are pure serous (branched tubulo-alveolar or tubulo-
acinar) glands located in lamina propria of olfactory
mucosa.
– produce thin watery secretion which released on to the
olfactory epithelial surface via narrow ducts.
– odorous substances dissolved in this watery secretion are
detected by the olfactory hairs.
– also wash the cilia and flushes the surface, preparing the
receptors to receive new odorous stimuli.
70

Olfactory neurons (First and Second order Neurons)
74

THE PHARYNX (THROAT)
– It is subdivided into three parts:
– Nasopharynx: is the first portion of the pharynx posterior to the
nasal cavities at its contact with soft palate, & continuing caudally
with the oropharynx. It is lined with respiratory epithelium [pseudo-
stratified columnar ciliated epithelium with goblet cells], and
contains a pharyngeal tonsil on the midline and the bilateral
openings of the auditory tubes to each middle ear.
– Oropharynx: lies posterior to
the oral cavity & lined by
nonkeratinized stratified
squamous epithelium and
contains palatine tonsils.
– A common passage for both
respiratory & digestive systems
– A muscular tube extending from the base of the skull to
the level of cricoid cartilage.
75

– Pharynx is divided into three anatomical
regions:
A. Nasopharynx
B. Oropharynx
C. Laryngopharynx
Interior of the Pharynx
A.A. NasopharynxNasopharynx
B.B. OropharynxOropharynx
C.C. LaryngopharynxLaryngopharynx
76

– lies posterior to the nasal cavity
– Contains tubal and pharyngeal tonsils
– Receives the openings the auditory tubes (Eustachian
tubes also called pharyngotympanic tubes) which connect
the nasopharynx to the middle ear cavities, an
arrangement which permits equilibration of air pressure in
the middle ear with that of the external environment.
– The Eustachian tubes
– are lined by typical respiratory epithelium and have
elastic cartilage support in their walls.
– Near its opening called tubal elevation contains tubal
tonsils.
A. Nasopharynx
77

– Lies posterior to
the oral cavity
– Extends from the
level of soft
palate to the
hyoid bone
– Has two pairs of
tonsils:
1. Palatine
tonsils
2. Lingual
tonsils
B. Oropharynx
78

– The wall of pharynx comprises three principal layers:
1. Mucosa: consists of
a. Lining Epithelium: ciliated pseudostratified columnar with
goblet cells in nasopharynx, nonkeratinized stratified
squamous epithelium in oropharynx and laryngopharynx.
b. Extensive Lamina Propria
– loose fibroelastic CT containing lymphoid organs (Tonsils)
& abundant numerous minor salivary glands, mucous type
– followed by a well-developed layer of elastic fibers called
elastic lamina that is continuous with the muscularis
mucosa of the esophagus.
2. The Muscularis: consists of skeletal muscles of the
pharyngeal constrictors (superior, middle & inferior)
externally and straight longitudinal muscles internally.
3. Adventitia: fibroelastic CT, covering the muscle layer.79

Numerous mucous glands in the lamina propria of pharynx
80

LARYNGOPHARYNX, BEHIND LARYNX
81

THE LARYNX (THE VOICE BOX)
– Below the oropharynx the respiratory & digestive tracts are separate.
– The larynx is an irregular, short tube that connects the oropharynx
with the trachea.
– The epiglottis (which contains elastic cartilage core) closes the
opening into the larynx called glottis during swallowing.
– The larynx is lined with respiratory epithelium except the vocal cords,
which are covered with nonkeratinized stratified squamous
epithelium.
Anterior
View

Posterior
View

82

LARYNX
– Its wall contains skeletal muscles and pieces of cartilages,
all of which make the larynx specialized for sound
production.
– Laryngeal cartilages include hyaline cartilages (thyroid,
cricoid, and the lower parts (base) of arytenoids) and
elastic cartilages (epiglottis, cuneiforms, corniculates, and
the tips of arytenoid cartilages).
– also possesses striated muscles, connective tissue, and
seromucous glands within its wall.
– The larynx & its cartilages and striated muscles perform
the following functions:
1. Acts as a valve that prevents the entrance of food or
fluid particles into the trachea (mainly by epiglottis).
2. Maintains an opened airway/ensures patency of airtube
3. Produces tones for phonation (thus, named voice box).83

The Larynx
– The larynx is the
organ for
vocalization
– located in the
anterior neck at
the level of the
bodies of C3 to C6
vertebrae
84

During swallowing,
– larynx is pulled superiorly
– Epiglottis tilts inferiorly to cover and seal laryngeal inlet &
Keeps food and fluid out of the lower respiratory tract.
Sound is produced by the vibration of vocal cords as air is
exhaled. Structures of Voice Production
vallecula
85

86
Three single & three paired cartilages of larynx

cuneiform
Laryngeal cartilages
corniculate
arytenoid
cricoid
90

– Two pairs of mucosal folding are found below the
epiglottis and extend through the cavity of larynx:
1- Upper paired Folds (vestibular folds or False vocal
cords), covered by respiratory epithelium.
2- Lower paired Folds (Vocal folds or True vocal
cords) covered by stratified squamous epithelium.
91

1. VESTIBULAR FOLDS (FALSE VOCAL CORDS)
– lie superior to the true vocal cords
– extend between the thyroid and the tip of arytenoid
cartilages, play little or no part in voice production; they
are protective in function.
– consist of two thick folds of mucous membrane enclosing
the vestibular ligaments.
– loose connective tissue core containing seromucous
glands, lymphoid aggregations (BALT), and fat/adipose
cells.
– are covered with typical respiratory epithelium beneath
which lie numerous seromucous glands
– The space between these folds is the rima vestibuli.
– Below each large vestibular fold is a narrow space or the ventricle
(V) of the larynx, below which is another pair of lateral folds, the
vocal folds or cords (VC). 92

Larynx: The low-power micrograph shows the upper laryngeal vestibule (LV), which is surrounded by
seromucous glands (G). The lateral walls of this region bulge as a pair of broad folds, the vestibular folds
(VF). These also contain seromucous glands and areolar tissue with MALT, often with lymphoid nodules (L)
and are largely covered by respiratory epithelium, with regions near the epiglottis having stratified
squamous epithelium. Below each large vestibular fold is a narrow space or ventricle (V), below which is
another pair of lateral folds, the vocal folds or cords (VC). These are covered by stratified squamous
epithelium and project more sharply into the lumen, defining the rim of the opening into the larynx itself.
Each contains a large striated vocalis muscle (VM) and nearer the surface a small ligament, which is cut
transversely and therefore difficult to see here.X15. H & E
94

V
LV- laryngeal vestibule
V- ventricle
VF- vestibular fold
CORONAL SECTION OF LARYNX
VF
95
LV

2. True Vocal Cords
– consists of skeletal muscle (the vocalis), the vocal
ligament (formed by a thick band of elastic fibers) covered
by a stratified squamous epithelium.
– contraction of the laryngeal muscles change the length
and tension of the vocal cords and the size and shape of
the opening between the vocal cords (rima glottidis),
which affects the pitch of the sounds caused by air passing
through the larynx.
– inferior to the vocal cords, the lining epithelium changes
to respiratory epithelium, which lines air passages down
through the trachea and primary bronchi.
– Contain the the vocal ligaments under stratified squamous
epithelium, vocalis muscles and the thyro-arytenoid muscle from
medial to lateral.
– The vocalis muscles produce minute adjustments of the vocal
ligaments, selectively tensing and relaxing the anterior and
posterior parts, respectively, of the vocal folds during
animated speech and singing. 96

Larynx, a vocal cord at the junction of nonkeratinized
stratified squamous & pseudostratified columnar
respiratory epithelium
100

Larynx, a vocal cord at the junction of nonkeratinized stratified
squamous & pseudostratified columnar respiratory epithelium
101

Vocal cord: covering epithelium and vocal ligament in
lamina propria
102

EPIGLOTTIS
– Consists of an elastic laryngeal cartilage core covered by
mucosa on both its lingual (anterior) and laryngeal
(posterior) surfaces.
– It has a tip which projects from the upper rim of the larynx
extending upward into oropharynx behind tongue.
– The entire lingual surface and the apical portion of its
laryngeal surface are covered with non-keratinized
stratified squamous epithelium.
– At a variable point on its laryngeal surface, the
epithelium undergoes a transition to the typical
respiratory epithelium.
– Mixed mucous and serous glands are seen in the lamina
propria beneath the epithelium.
– Its lingual surface may contain occasional taste buds.

Core of elastic cartilage
Lingual surface
Laryngeal surface
104

TRACHEA (THE WINDPIPE)
– 12 cm in length, 2.5 cm in diameter
– lined with typical respiratory mucosa.
– In the submucosa are numerous
seromucous glands which produce
watery mucus
– 16–20 C-shaped rings of hyaline
cartilage keep the tracheal lumen open
– The open ends of the cartilage rings are
on the posterior surface, against the
esophagus, and are bridged by a bundle
of smooth muscle (trachealis muscle)
and a sheet of fibroelastic CT attached
to the perichondrium.
– The entire organ is surrounded by
adventitia. 105

THE TRACHEA & MAIN BRONCHI
– The trachea is formed of
16-20 segments; each
containing a U- or a C-
shaped piece of hyaline
cartilage joined at the free
ends to one another by
bands of smooth muscle
called trachealis
posteriorly.
– The trachea and the
two main (primary)
bronchi are
histologically similar.
106

NORMAL TRACHEA, THYROID AND OESOPHAGUS
107

In cross section, the trachea and the extrapulmonary bronchi are
formed of 4 layers:
1. Mucosa:
– Epithelium: ciliated pseudostratified columnar epithelium with
goblet cells. All the cells rest on thick basal lamina.
– Lamina propria: loose CT, elastic & reticular fibers with lymphocytes.
2. Submucosa:
– Loose CT with seromucous glands.
– Their long ducts open directly to the lumen.
– Satellite shaped myoepithelial cells surround the acini and extend
to ducts (mainly in the trachea).
– The submucosa may contain aggregates of lymphoid tissue (BALT).
3- Supporting layer (musculo-cartilagenous coat):
– 16-20 C-shaped hyaline cartilages are seen in the tracheal wall.
– In the primary bronchi most cartilage rings completely encircle the
lumen
4- External fibrous layer (Adventitia):
– Made up of fibroelastic CT containing blood vessels and nerves.108

Trachea in T.S.Trachea in T.S.
Mucosa
Submucosa
Cartilage
109

Sero-mucous glands of trachea (submucosa)
111

NORMAL TRACHEA, LABELED ciliated pseudostratified columnar
epithelium with goblet cells.
118

Tracheal epithelium showing cilia in more detials by SEM
121

TRACHEAL EPITHELIUM, CILIATED & NON CILIATED CELLS, NOTE THE DIFFERENCE IN SIZE BETWEEN CILIA &
MICROVILLI ON THE SURFACE OF NON CILIATED CELLS,SEM
122

TRACHEAL EPITHELIUM, CILIATED & NON CILIATED CELLS, NOTE THE DIFFERENCE IN SIZE
BETWEEN CILIA & MICROVILLI ON THE SURFACE OF NON CILIATED CELLS, SEM
123

TRACHEAL EPITHELIUM, CILIATED & NON CILIATED CELLS, NOTE THE DIFFERENCE IN
SIZE BETWEEN CILIA & MICROVILLI ON THE SURFACE OF NON CILIATED CELLS, SEM
124

Types of cells in lining epithelium of trachea and bronchi:
- Three types of cells are seen by light microscope:
– Ciliated columnar cells.
– Goblet cells which produce mucous secretion.
– Basal cells: these are undifferentiated cells which can
divide by mitosis and can give other types of cells.
- Two types of cells seen by electron microscope:
– Brush cells which contain glycogen granules and carry microvilli.
They may be either immature columnar cells or degranuled
goblet cells.
– Granue cells which are of 2 types according to function of
granules:
• Catecholamine secreting cells (neurosecretory cells).
• Protein hormone secreting cells (enteroendocrine like cells).
They secrete amines and amine precursors. 125

Bronchial Tree & Lung
–The trachea divides into two primary bronchi that enter the lungs at
the hilum, along with arteries, veins, and lymphatic vessels.
–At the hilum, the primary bronchi course downward and outward,
giving rise to three secondary (lobar) bronchi in the right lung and two
in the left lung, each of which supplies a pulmonary lobe.
–These lobar bronchi again divide, forming tertiary (segmental)
bronchi.
–Each of the tertiary bronchi, together with the smaller branches it
supplies, constitutes a bronchopulmonary segment—approximately
10–12% of each lung with its own connective tissue capsule and blood
supply.
–The existence of such lung segments facilitates the specific surgical
resection of diseased lung tissue without affecting nearby healthy
tissue.
126

Trachea

Main bronchi

Lobar bronchi

Segmental bronchi

---
---
Bronchioles


Respiratory bronchioles

Alveolar ducts

Alveolar sacs

Alveoli Respiratory Tree
127

The main divisions of the respiratory tract. The natural proportions of
these structures have been altered for clarity; the respiratory
bronchiole, for example, is in reality a short transitional structure.
129

– The tertiary bronchi give rise to smaller and smaller bronchi, whose
terminal branches are called bronchioles.
– Each bronchiole enters a pulmonary lobule, where it branches to
form five to seven terminal bronchioles.
– The pulmonary lobules are pyramid-shaped, with the apex directed
toward the pulmonary hilum.
– Each lobule is delineated by a thin connective tissue septum, best
seen in the fetus.
– In adults, the pulmonary septa are frequently incomplete, resulting
in a poor delineation of the lobules.
– Moving through the smaller bronchi and bronchioles toward the
respiratory portion, the histologic organization of both the
epithelium and the underlying lamina propria gradually becomes130

Extrapulmonary Bronchi
– The basic structure of extrapulmonary bronchi is similar to
that of the trachea, but differs in several details as follows:
1. The respiratory epithelium is less tall and contains fewer
goblet cells.
2. The lamina propria is more dense with a large quantity of
elastin its most superficial layers.
3. The lamina propria is separated from the submucosa by a
discontinuous layer of smooth muscle which becomes
progressively more prominent in smaller airways.
4. The submucosa is less prominent and contains only fewer
sero-mucous glands.
5. The cartilage framework is arranged into fattened
interconnected plates rather than discrete c-shaped rings
as in the trachea.
131

EXTRAPULMONARY BRONCHUS, INTERCONNECTED CARTILAGENOUS
PLATES AND SPARSE SUBMUCOSA IN ITS WALL
132

Secondary Bronchi
– The intrapulmonary secondary bronchi differs from
extrapulmonary bronchi by the following, otherwise the
structure is the same:
– The mucosa is slightly folded.
– The presence of muscularis mucosa: a layer of
crisscrossing bundles of spirally arranged smooth muscle
beneath the lamina propria, which become more
prominent in the smaller bronchial branches.
– Contraction of this muscle layer is responsible for the
folded appearance of the bronchial mucosa observed in
histologic section.
– Adventitia (or the fibrocartilaginous layer) contains
interconnected cartilage plates and dense fibroelastic CT.133

Secondary Bronchi
Note:
– Smaller generations of secondary bronchi contain isolated
smaller discontinuous cartilage plates or patches of
cartilages in their adventitia.
– Numerous lymphocytes are found both within the lamina
propria and among the epithelial cells.
– Lymphatic nodules are present and are particularly
numerous at the branching points of the bronchial tree.
– Elastic fibers, smooth muscle, and BALT become relatively
more abundant as bronchi become smaller and cartilage
and other connective tissue are reduced.
134

INTRAPULMONARY BRONCHUS T.S.
137

Normal lung, small bronchus lined by pseudostratified columnar epithelium, smooth
muscle and hyaline cartilage are seen in the wall, section of pulmonary vessel lies
adjacent to one bronchus
139

Microscopic structure of the lung and the bronchial tree
• The main parenchymal lung tissue is formed of lobes, lobules, and
lung acini housing the different parts of the bronchial tree which are:
1- The intrapulmonary (secondary & tertiary) bronchi
2- Bronchioles
3- Terminal bronchioles
4- Respiratory bronchioles
5. Alveolar duct, sacs and alveoli
THE INTRAPULMONARY BRONCHI
- The wall of an intrapulmonary bronchus is formed of the following:
1- Mucosa which is folded and formed of:
– Epithelium, which is of the same typical respiratory type.
– Lamina propria formed of loose connective tissue rich in blood
vessels, lymphocytes, mast cells and elastic fibers.
2- Complete layer of smooth muscle fibers spirally arranged (criss-
crossing fibers) which encircle the whole lumen.
3- Layer of alternated hyaline cartilage plates with seromucous140

– The tertiary bronchi give rise to smaller and smaller bronchi, whose
terminal branches are called bronchioles.
– Each of these tertiary bronchi, together with all its smaller branches
it supplies, constitutes a bronchopulmonary segment—
approximately 10–12% of each lung with its own connective tissue
capsule and blood supply.
– Each bronchiole enters a pulmonary lobule, where it branches to
form five to seven terminal bronchioles.
– The pulmonary lobules are pyramid-shaped, with the apex directed
toward the pulmonary hilum.
– Each lobule is delineated by a thin connective tissue septum, best
seen in the fetus.
– In adults these septa are frequently incomplete, resulting in a poor
delineation of the lobules.
– Moving through smaller bronchi & bronchioles toward respiratory
portion, the histologic organization of both the epithelium &
underlying lamina propria gradually becomes more simplified.

Histology of Segmental Bronchus
145

BRONCHIOLES
– are intralobular air passage ways lacking cartilage support
and sero-mucous glands in their wall.
– are highly variable in size having outer diameter of 1mm
or less.
– the largest bronchioles, traditionally called primary
bronchioles are last divisions of bronchial tree which lacks
cartilage support and seromucous glands.
– bronchiolar wall is free of cartilages but consists of:
1. Mucosa: folded and contains:
a) Epithelium: shorter pseudostratified columnar ciliated
epithelium with fewer goblet cells (typical respiratory
epithelium but with fewer goblet cells) in the larger
(primary) bronchioles, but the epithelium decreases in
height and complexity to become ciliated simple columnar
or cuboidal epithelium in the terminal bronchioles and
respiratory bronchioles, respectively. 147

Bronchiolar Wall
b) The lamina propria: is composed largely of smooth
muscle, mast cells and elastic fibers.
1.Smooth muscle layer:
– relatively thick concentrically arranged smooth muscle
layer.
– Sympathetic stimulation relaxes these muscles, hence
epinephrine and sympathomimic drugs are used in asthma.
3.Adventitia:
– loose connective tissue without cartilage support
– blend with the surrounding lung parenchyma
No Submucosa and no seromucous glands.
– The primary bronchioles give rise to terminal bronchioles,
which give respiratory bronchioles, that receive the
alveoli. 148

– Absence of cartilage from the wall of bronchioles is a
potential hazard, since these airways can constrict to a
point of closing the lumen if the tone of their muscles is
increased.
– This is the problem of asthma which is an allergic condition
to non-specific lung irritant. Wheezing noises and difficulty
in breathing occurs during expiration rather than
inspiration.
– The musculature of both the bronchi and the bronchioles is
under the control of the vagus nerve and the sympathetic
nervous system, in addition to the influence of
neuroendocrine peptides and local factors.
– Stimulation of the vagus nerve decreases the diameter of
these structures; sympathetic stimulation produces the
opposite effect.
152

Normal lung labeled with bronchiole, 40x
153

Terminal Bronchioles
– are the smallest air tubes of purely conducting portion of
the respiratory system.
– give rise to further branches known as respiratory
bronchioles, which increasingly involve in gaseous
exchange.
1.Their mucosa is characterized by:
– ciliated simple columnar epithelium without goblet cells.
– only one or two layers of smooth muscle cells in LP.
– contain non ciliated, bronchiolar secretory cells known as
club cells (formerly called Clara cells).
– These non-ciliated, bronchiolar secretory cells secrete
surfactant-like product rich in phospholipids known as club
cell secretory protein that alters the surface tension of the
fluid layer covering the bronchiolar surface.

Cross-section of a terminal bronchiole showing: a lining columnar
epithelium containing both ciliated cells and non ciliated bronchiolar
secretory cells, and only one or two layers of smooth muscle cells. The
X300. PT. (b): The nonciliated Clara cells with bulging domes of apical
cytoplasm contain granules, as seen better in a plastic section.

Club (Clara) cells:
–are dome-shaped, non-ciliated, exocrine secretory cells
lining the bronchiolar mucosa.
–found interspersed in the ciliated epithelium of bronchioles
–originally described by their namesake of Dr. Max Clara, the
histologist who first described them in 1937 by using lung
tissue from executed victims of the Nazz’s Third Reich (1933-
1945)
–due to the ethical controversy surrounding the discovery of
these cells, new name known as Club cell was adopted on
January 1, 2013.
–Similarly, Clara cell secretory protein is also replaced by club
cell secretory protein.
–Ultrastructurally they reveal: Long cisternae of RER & SER, scattered
elongated mitochondria, small accumulation of glycogen.

Features & functions of Club (Clara) cells
–They have apical cytoplasm containing secretory granules
which act as a surfactant in protecting the bronchiolar
epithelium
–and also have other important functions including:
– producing enzymes that help break down mucus locally.
– contain high concentration of cytochrome (P450) enzyme
system which detoxifies potentially harmful compounds
in inspired air.
– In other defensive functions, club (Clara) cells also
produce:
– the secretory component for the transfer of IgA into the
bronchiolar lumen;
– lysozyme and other enzymes active against bacteria and
viruses; and
– several cytokines that regulate local inflammatory responses160

Bronchiolar epithelium, red & white blood cells on
the surface of the epithelium, SEM
162

Bronchiolar epithelium consisted of ciliated & non ciliated cells, note
the difference in size between cilia & microvilli on non ciliated cell
surface, SEM
163

RESPIRATORY BRONCHIOLES
– Named for the presence of individual alveoli attached to
them at irregular interval.
– Lined by ciliated simple cuboidal epithelium which is
interrupted by the openings of saclike individual alveoli
where gas exchange occur.
– Their wall is interrupted by the openings of many alveoli.
– are lined with simple cuboidal ciliated epithelium, some of
the cells are ciliated, and others are non-ciliated Clara cells.
– At the junction between the bronchiole and the alveoli the
cuboidal cells continue as simple squamous epithelium of
pneumocytes type l.
– Some smooth muscle fibers and elastic fibers are present in
the lamina propria under the bronchiolar epithelium. 164

High Magnification of the Lung Demonstrating a Respiratory Bronchiole
1. High
cuboidal
epithelium
2. Alveolus
3. Interalveolar
septum
4. Lumen
165

SEM shows in three dimensions the relationship of alveoli to
terminal and respiratory bronchioles
167

Alveolar Ducts and Alveolar sacs
– Respiratory bronchioles branch into wider and longer
tubes called alveolar ducts that receives the openings of
alveolar sacs.
– Alveoli and alveolar sacs are arranged alongside the
alveolar ducts and are continuous with them.
– Both the alveolar ducts and the alveoli are lined with
extremely attenuated squamous alveolar cells.
– The wall is deficient except in small areas lined by cuboidal
cells in between the alveolar sacs.
– In their lamina propria surrounding the rim of the alveoli &
alveolar sacs is a thin network of smooth muscle cells,
which disappears at the distal ends of alveolar ducts.
– A rich matrix of elastic and reticular fibers provides the
only support of the alveolar duct and its alveoli.
– It looks like a long corridor which opens into atria of two or
more alveolar sacs or antrum which in turn leads to the169

Terminal portion of the respiratory tree (Lung Acinus)
170

Green arrow - Alveolar Duct
Blue arrow - Alveolar Sac
Red arrow – Terminal
Bronchiole
Blue arrow – Respiratory
Bronchiole
171

TB
AS
AD
RB
RB
AS
A
A
Pleura 172

Alveolus and alveolar cells
173

– In the lamina propria surrounding the rim of the alveoli is a
thin network of smooth muscle cells, which disappears at
the distal ends of alveolar ducts.
– A rich matrix of elastic and collagen fibers provides the
only support of the duct and its alveoli.
– Alveolar ducts open into atria of two or more alveolar
sacs.
– Elastic and reticular fibers form a network encircling the
openings of atria, alveolar sacs, and alveoli.
– The elastic fibers enable the alveoli to expand with
inspiration and to recoil passively with quiet expiration.
– The reticular fibers serve as a support that prevents over
distention and damage to the delicate capillaries and thin
alveolar septa.
– Both fibers contribute to the connective tissue housing the
network of capillaries around each alveolus.
174

ALVEOLI
– cup-shaped/saclike blind-ended out pouching (up to
200μm in diameter) of the respiratory bronchioles,
alveolar ducts, and alveolar sacs.
– constitute the bulk of lung parenchyma
– lined by very thin simple squamous epithelium supported
by a thin elastic basement membrane
– This epithelium is known as alveolar epithelium and it is formed
entirely by type two alveolar cells (pneumocytes I cells).
– an alveolar sac consists of two or more alveoli that share a
common opening.
– alveolar sac and alveoli are responsible for the spongy
structure of the lungs.
– alveoli resemble small pockets that are open on one side,
similar to the honeycombs of a beehive.
175

ALVEOLI
– enveloped by a rich network of pulmonary capillaries
forming capillary basket around the alveolus.
– The structure of alveolar wall is also extremely thin due to
highly attenuated Type I pneumocytes.
– This arrangement provides a vast interface (which has been
calculated to be approximately 140 m2
) of minimal thickness
for gaseous (O2 and CO2)exchange between the air in the
alveoli and the blood in the surrounding capillary basket.
– Between two neighboring alveoli is thin CT called an
interalveolar septum (lung interstitium).
– These fibrous septa contain the cells and ECM of CT,
notably the elastic and reticular fibers, which is highly
vascularized with the richest capillary network in the body.
179

THE ALVEOLI AND THE INTERALVEOLAR SEPTUM
– The alveoli are lined by 2 types of cells: Alveolar cells Type I & II
Alveolar Cells Type I (also called Type I Pneumocytes)
– are flattened squamous, or extremely attenuated cells that line most
of the alveolar surfaces.
– cover about 95-97% of the alveolar surface (type II cells covering the
remainder), but account only about 40% of alveolar cell population.
– Form extremely thin epithelium about 25 nm thick
– Organelles such as the ER, Golgi apparatus, and mitochondria are
grouped around the nucleus, leaving large areas of their cytoplasm
virtually free of organelles and reducing the thickness of the blood-air
barrier.
– The cytoplasm in the thin portion contains pinocytotic vesicles, which
may play a role in the turnover of surfactant and the removal of small
particulate contaminants from the outer surface.
– In addition to desmosomes, all type I epithelial cells have occluding
junctions that prevent the leakage of tissue fluid into the alveolar air
space.
– The main role of these cells is to provide a barrier of minimal
thickness that is readily permeable to gases. 180

TYPE-1 PNEUMOCYTE (alveolar cell type 1)
181

– Air within the alveolus is separated from capillary blood by
three components collectively referred to as the
respiratory membrane or blood-air barrier/pulmonary
barrier.
The pulmonary barrier is formed of the following layers:
1. Cytoplasm of the alveolar epithelial cells
2. Fused Basal lamina of alveolar epithelial cells and
Basal lamina of the capillary endothelial cells
3. Cytoplasm of the endothelial cells.
182

Alveolar Cells Type II (Type II Pneumocytes)
–also called surfactant cells, alveolar secretory cells, or
septal cells, whose secretory product is pulmonary
surfactant which appears after week 25.
–are cuboidal or round cells that bulge into the alveolar
lumen and interspersed among the type I alveolar cells with
which they have occluding and desmosomal junctions.
–they often occur in groups of two or three along the alveolar
surface at points where the alveolar walls unite.
–they also rest on the basal lamina and are part of the
epithelium, with the same origin as the type I cells that line
the alveolar walls.
–they divide by mitosis to replace their own population and
also the type I population.
183

TYPE-2 PNEUMOCYTE (alveolar cell type II)
184

Alveolar Cells Type II (Type II Pneumocytes)
–In histologic sections, they exhibit a characteristic vesicular
or foamy peripheral cytoplasm, where membrane bound
secretory vesicles called lamellar bodies are located.
–Lamellar bodies, which average 1–2µm in diameter, contain
concentric or parallel lamellae limited by a unit membrane
(phospholipid monolayer).
185

TEM of a type II alveolar cell protruding into the alveolar lumen shows unusual
cytoplasmic features. Arrows indicate lamellar bodies which store newly synthesized
pulmonary surfactant after processing of its components in rough ER (RER) and the
Golgi apparatus (G). Smaller multivesicular bodies with intralumenal vesicles are
also often present. Short microvilli are present and the type II cell is attached via
junctional complexes (JC) with the adjacent, very thin type I epithelial cell. The ECM
contains prominent reticular fibers and elastic fibers (RF). X17,000.
187

– Histochemical studies show that lamellar bodies contain
phospholipids (dipalmitoyl phosphatidylcholine and
phosphatidylglycerol), glycosaminoglycans, and proteins,
which are continuously synthesized and released at the
apical surface of the cells.
– The lamellar bodies give rise to a material that spreads
over the alveolar surfaces as the pulmonary surfactant,
providing an extracellular coating that lowers surface
tension and prevents collapse of alveoli during expiration.
– The reduction of surface tension means that less
inspiratory force is needed to inflate the alveoli by
preventing adherence of alveolar walls together, easing
the work of breathing.
– Without surfactant, alveoli would tend to collapse and
stick together during expiration.

– Surfactant consists of an aqueous hypophase covered with
a monomolecular phospholipid film composed mainly of
dipalmitoyl phosphatidylcholine and
phosphatidylglycerol.
– Surfactant also contains several specific proteins.
Pulmonary surfactant serves several major functions in the
economy of the lung, but acts primarily to reduce the
surface tension on the alveoli.
– In fetal development, surfactant appears in the last weeks
of gestation as lamellar bodies develop in the type II cells.
– The surfactant layer is not static but is constantly being
turned over.
– The lipoproteins are gradually removed by pinocytosis in
both types of alveolar cells and by macrophages.

Respiratory distress syndrome (RDS)
– In premature delivery, type II cells are immature and to
produce the necessary pulmonary surfactant. This leads to
fatal respiratory difficulty in new born (respiratory distress
syndrome).
– 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. 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.190

Respiratory distress syndrome (RDS)
– Microscopically, the alveoli are collapsed and the
respiratory bronchioles and alveolar ducts are dilated and
contain edema fluid.
– RDS is treated by introducing synthetic or animal-derived
surfactant into the lungs through a tube.
– Surfactant also has bactericidal effects, aiding in the
removal of potentially dangerous bacteria that reach the
alveoli.
– Pulmonary Surfactant: Type II pneumocytes secrete
phospholipid surfactant that decreases the alveolar
surface tension forces to a minimal level thus preventing
the alveoli from collapse.
– The presence of this secretion is important for the
newborn to obtain their first breath of air.
191

– The distance between the two adjacent alveoli is called
the interalveolar septum, and is formed of the following:
1- Thin alveolar epithelium
2- Basal lamina of the alveolar epithelium
3- supporting connective tissue (lung interstitium) containing:
–Fibres: reticular and elastic.
–Septal cells (type II pneumocytes).
–Other Cells: Fibroblasts, fibrocytes, mast cells, leukocytes,
alveolar macrophages (dust cells).
–Other septal cells contain bundles of actin and myosin
filaments which contract in response to hypoxia (their role is
unknown).
–Blood capillaries (continuous, non-fenestrated);
4- Basal lamina of the alveolar epithelium.
5- Thin alveolar epithelium
• The air in the alveoli is separated from the blood inside the
capillaries by the blood air (pulmonary) barrier. 192

Alveolar macrophages (also called dust cells)
– are phagocytic cells which phagocytose erythrocytes lost from
damaged capillaries and air-borne particulate matter that has entered
alveoli.
– are found in lumina of the alveoli and in the interalveolar septum
– Some debris within these cells was most likely passed from the
alveolar lumen into the interstitium following the pinocytotic activity
of type I alveolar cells.
– Active macrophages in lung are often slightly darker due to their
content of dust and carbon from air and complexed iron
(hemosiderin) from erythrocytes.
– Filled macrophages have various fates: most migrate into bronchioles
where they move up the mucociliary escalator for removal in the
pharynx; others exit the lungs in the lymphatic drainage, while some
remain in the interalveolar connective tissue septa for years.
– Alveolar lining fluids are also removed via the conducting passages as
a result of ciliary activity.
193

DUST CELLS (Alveolar macrophages)
194

ALVEOLAR MACROPHAGE (Dust cell)
195

Cells of the interalveolar septum
1-Capillary endothelial cells (30%)
2-Pneumocytes type I (8%)
3-Pneumocytes type II (Septal cells) (16%)
4-Interstitial cells (Fibroblast, fibrocytes, leukocytes & mast cells)(36%)
5-Alveolar macrophages (DUST cells) (10%)
Alveolar Pores
Functions:
1- They can equalize the pressure inside the alveoli
2- They allow collateral air circulation if the bronchiole is
obstructed
Pleura
- It is a serous membrane covering the lungs.
- It is formed of two layers parietal and visceral which are
continuous at the hilum.
196

Portion of the interalveolar septum showing the blood air barrier. To
reach the erythrocyte, O2 traverses the surface lining, the alveolar
epithelium cytoplasm, and the plasma. In some locations, there is
loose interstitial tissue between the epithelium and the endothelium.

– The alveoli
inter-
communicate
through alveolar
pores, which
equilibrate air
pressure within
a lobule, but
may cause
spread of
infection.
Blood-Air barrier: (Alveolar Membrane, 0.1 to 1.5 µm thick):
consists of:
– Simple squamous epithelium of type I pneumocyte cells
of the alveolus.
– Common or fused basement membrane.
– Endothelial lining of capillaries.
198

Fused Basal laminae
Alveolar lumen
Capillary lumen
Alveolar Epithelium
Endothelium
Pulmonary membrane
199

Alveolar walls: The space between alveoli (A) contains several cell types. As seen
here the capillaries (C) contain erythrocytes and leukocytes. The alveoli are lined
mainly by squamous type I alveolar cells (I), which line almost the entire alveolus
surface and across which gas exchange occurs. Type II alveolar cells line a bit of each
alveolus and are large rounded cells, often bulging into the alveolus (II). Also present
are alveolar macrophages (M), sometimes called dust cells, which may be in the
alveoli or in the interalveolar septa.
200

1- Terminal bronchiole 2- Respiratory bronchiole 3- Alveolar duct
4- Atria 5-Alveolar sac 6- Alveolus or air cell m: smooth muscle
a: pulmonary artery branch v: pulmonary vein branch s: septum
between secondary lobules
201

LUNG BY HEMATOXYLIN & EOSIN (HIGH POWER)
T
R
202

Summary of structures of the Respiratory tree
– The structure of respiratory system changes according to the
functional need:
– The air is inhaled through nose or mouth where it is humidified,
warmed and the suspended particles trapped by the hair of nasal
vestibule and the mucus present on the mucosa. These particles are
ultimately expelled out by the cilia.
– As we go down the respiratory tree the cartilage decreases till it is
completely absent in the bronchioles. In trachea it is present as a
single semilunar plate while in secondary and tertiary bronchi, it is
present in few discontinuous patches.
– The height of the epithelium decreases down the tree till it becomes
interrupted simple cuboidal in the respiratory bronchioles.
– The cilia decrease in number as we go down till they are completely
absent in the alveolar ducts.
– The goblet cells disappear within the terminal bronchiole & beyond.
– The smooth muscle increase in quantity till it is maximum in the
bronchioles where it serves to act as a sphincter or control valve for
regulation of air. 207

REVISIONTrachea
– Pseudostratified columnar, ciliated
epithelium
– Goblet cells
– Sero-mucous glands
– Cartilage rings
Bronchi
– Pseudostratified columnar,
ciliated epithelium (shorter)
– Goblet cells (fewer)
– Sero-mucous glands
– Cartilage
– Smooth muscle
Bronchioles
– Pseudostratified columnar,
ciliated epithelium (shorter)
– Sparse goblet cells, no glands &
no cartilages
– Smooth muscle (relatively
abundant)
–Simple columnar ciliated epithelium
– Clara cells
Respiratory Bronchioles
– Simple cuboidal, ciliated
epithelium (shorter)
– Clara cells
– Receive alveolar openings
Alveoli
Type I Pneumocyte
–* flattened for gas exchange
–* covers 95% of alveolar
surface (but only accounts for
about 40% of pneumocyte
population)
Type II Pneumocyte
–* cuboidal
–* produces surfactant
–* constitutes about 60% of the
pneumocytes (but only 5% of
the surface area)

Regeneration in the Alveolar Lining
–Inhalation of toxic gases or similar materials can kill both
type I and type II pneumocytes lining pulmonary alveoli.
–Death of the first cells results in increased mitotic activity in
the remaining type II cells, the progeny of which become both
cell types.
–The normal turnover rate of type II cells is estimated to be
1% per day and results in a continuous renewal of both
alveolar cells.
–With increased toxic stress Clara cells can also divide and
give rise to alveolar cells.
210

Respiratory Movements
– During inhalation, contraction of the intercostal muscles elevates
the ribs and contraction of the diaphragm lowers the bottom of the
thoracic cavity, increasing its diameter and resulting in pulmonary
expansion.
– The bronchi and bronchioles increase in diameter and length during
inhalation.
– The respiratory portion also enlarges, mainly as a result of
expansion of the alveolar ducts.
– Individual alveoli enlarge only slightly.
– The elastic fibers of the pulmonary parenchyma are stretched by
this expansion.
– During exhalation, the lungs retract passively due to muscle
relaxation and the elastic fibers' return to the unstretched
condition.
211

Lung Development: Fetal Lung
1. Pseudoglandular period:
– 5th
to 15th
or 16th
weeks.
– duct system develops
– bronchi grow and branch to give rise to large
bronchioles
– alveoli are not present
2. Canalicular period:
– 15 or 16th
to 24th
weeks.
– bronchioles begin to form terminal bronchioles and
then respiratory bronchioles with developing primitive
alveoli.
– lung tissue is vascularized. 212

3. Terminal Saccular period:
– 25th
weeks to 32nd
weeks.
– development of terminal sacs which further differentiate
into alveolar sac and attached alveoli.
– differentiation of alveolar epithelium
– surfactant appears in this period and coincides with the
appearance of lamellar bodies in the type II
pneumocytes.
4. Alveolar period (postnatal):
– from 33rd
week to the first 8 or 10 years
– characterized by maturation and tremendous increase in
number of alveoli.
– at birth, only about 1/8th
of alveoli found in the adult are
present. i.e. more than 88% of alveoli develop
postnatally. 216

CLINICAL NOTES
A. Hyaline membrane disease (respiratory distress
syndrome)
– is frequently observed in premature infants who
lack adequate amounts of pulmonary surfactant.
– is characterized by labored breathing, which
results from difficulty in expanding the alveoli due
to high alveolar surface tension (caused by
inadequate levels of surfactant).
– is often be circumvented, if detected before birth,
by the administration of glucocorticoids, which
induce synthesis of surfactant. 217

B. Asthma
– is marked by excessive contraction of smooth muscles in the wall of
bronchioles, causing their constriction, a decrease in their diameter.
– is associated with extremely difficult expiration of air, accumulation
of mucus in the passageways, and infiltration of inflammatory cells
into the region.
– is often progressive and associated with allergic reactions during
which vasoconstrictive substances are periodically released within
the lungs.
– is treated by administering drugs such as epinephrine and
isoproterenol, & other sympathomimic drugs, which function to relax
the bronchiolar smooth muscles, thus dilating the passageways.
C. Emphysema
– a chronic lung disease characterized by enlargement of the air spaces
distal to the bronchioles into large cyst-like sacs, with destruction of
the interalveolar wall.
– usually develops gradually and results in respiratory insufficiency by
reducing the surface available for gas exchange.
218

– is marked by decreased elasticity of the lungs, which are
unable to recoil adequately during expiration.
– in time, the lungs become expanded and enlarge the
thoracic cavity (“barrel chest”).
– its major cause is cigarette smoking and exposure to other
substances that inhibit α1-antitrypsin secretion, a protein
that normally protects the lungs from the action of elastase
produced by alveolar macrophages.
– Irritation produced by cigarette smoking stimulates the
destruction, or impairs the synthesis of elastic fibers and
other components of the interalveolar septum.
– can be a hereditary condition resulting from a defective α1-
antitrypsin. In such cases, gene therapy with recombinant
α1-antitrypsin is being used. 219

D. Lung Tumor/Cancer
– Squamous cell carcinoma, the principal lung tumor
type, usually results from the effects of cigarette
smoking on the bronchial and bronchiolar epithelial
lining.
– Chronic smoking induces the transformation of the
respiratory epithelium into a stratified squamous
epithelium, an initial step in its eventual
differentiation into a lung tumor and/or cancer.
220

Respiratory system

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