Lecture 13Lecture 13 ESS_2nd semesterESS_2nd semester

Microscopic structure of the respiratory

system

Nasal cavity, larynx, and tracheaHistology of the lung and blood-air barrier Outline of development of respiratory passagesand the lung

the respiratory system (RS) includes lungs and a system of tubes that links the sites of gas exchange with the external environment

Main functions of the RS are:oxygenation of blood by way of inspired airelimination of carbon dioxide (a toxic by-product of body metabolism) by way of expired airexcretion of water and volatile substances, such as alcohol etc,

besides mentioned functions, RS takes part in some specialized functions as

are phonationsmellfiltration of inspired air

Respiratory system consists of 2 principal parts:

1. conducting portion (respiratory passages) that involves

extrapulmonary one - nasal cavity,nasopharynx, larynx, trachea and primarybronchi

intrapulmonary one – bronchial tree (bronchi, bronchioles, and terminal bronchioles)2. respiration portion consisting of:

respiratory bronchiolesalveolar ducts and alveoli

A wall of respiratory passages

is rigid and prevents collapse lumen of the conducting portion

is composed of 3 layers mucosa - covers the luminal surface and consists of pseudostratified ciliated columnar epithelium with mucous goblet cells and thin lamina propria fibrocartilaginous layer - supports the walls, being composed of hyaline, and elastic cartilages and bundles of smooth muscle tissue (caudally and dorsally) adventitia - loosely connects both previous layers with surroundingsis composed of loose connective tissue with blood vessels and nerve bundles

Nasal cavity

- is divided by a midline nasal septum into right and left part - nasal fossae,

- both fossae communicates with the exterior through the nares (nostrils), with the nasopharynx through the posterior nares

each nasal cavity comprises

vestibule

respiratory portion (area) and

olfactory portion (area)

Vestibule

- narrow zone in which the epidermis from external surface of the nose is replaced by

nonkeratinized pseudostratified columnar epithelium

around the inner surface of the nares are large sebaceous and sweat glands bound to thick

and short hair called vibrissae

they filter out large particles from the inspired air

Respiratory area (portion)- is lined with pseudostratified ciliated columnar epithelium with goblet cells- a lamina propria containing seromucous glands

it grows deeply together with the periosteum or perichondrium of bone or cartilagethree bony shelf-like projections called conchae protrude into both nasal fossae from the lateral wall of

the nasal septumthe superior concha belongs to the olfactory portionthe middle and inferior conchae contain a rich vascular plexus (mainly in inferior conchae) that serves to

warm of inspired air (conditioning of the inspired air) – (They also produce turbulence of the air so that the

contact surface with mucosa becomes greater and thereby increasing the humidity!)

Olfactory area (portion)occupies the roof of each nasal fossa (regio olfactoria)it is lined with olfactory mucosa that contains

the receptors for the sense of smell (sensory cells-unipolar!)cells are modified bipolar neurons–they have dilated apex with nonmotile cilia and axon (BOWMANS

GLANDS)

Paranasal sinuses

are air-filled cavities within the bones of the skull (maxillary, frontal, ethmoid and sphenoid), which communicate through small openings with the nasal cavities they are lined with the same but thinner mucosa (periost + lamina propria + epithelium) as the respiratory portion of nasal fossae

The nasopharynx

is upper part of the pharynx which- anteriorly is open into the nasal cavity through posterior nares,choana!- posteriorly and laterally is surrounded by the muscular tissue- caudally is continued with the oropharynx and larynx

the epithelium of the pharynx is pseudostratified ciliated columnar with goblet cells

small glands (mucous, serous and mixed) and accumulations of lymphatic tissue (pharyngeal tonsil - posteriorly, tubal tonsils - laterally) are in the lamina propria

the middle layer of the pharynx is of muscular character being formed by bundles of

the striated muscles

Larynx C3-C6is an irregular tube connecting pharynx and trachea

the skeleton of the organ is formed large hyaline (thyroid, cricoid, and most of the arytaenoid) and small elastic (epiglottis, cuneiform and corniculate) cartilages that are bound together by ligaments + membranes.

striated skeletal muscles insert to the surface of cartilages and provide to move against each other

inner surface is covered by the mucosa consisting of dense connective tissue with seromucous glands and the islets of lymphatic tissue

except two sites, the entire larynx is lined with pseudostratified ciliated columnar epithelium with goblet cells

below the aditus, the mucosa forms 2 pairs of folds that extend into the lumen of the larynx

the upper pair constitutes the false vocal cords, covered by typical pseudostratified columnar epithelium;

the lower pair of folds constitutes true vocal cords that are covered by stratified squamous epithelium

bbetween folds the sinus and saccule of the larynx a small slit-like diverticulum of laryngeal cavity is located on each side

True vocal cords:

- stratified squamous epithelium,- lamina propria (loose fibroconnective tissue),- ligamentum vocale (elastic connective tissue),- musculus thyreoarytaenoideus (cross-striated muscle tissue lying in plica vocalis outer to ligamentum)

False vocal cords:

- pseudostratified ciliated columnar epithelium + goblet cells- lamina propria of mucosa with mixed glands

the shape of the opening between the vocal cords (the glottis) varies with

breathing and phonation

Tracheais a tube about 10-12 cm long, 2-2.5 cm in diameter

Mucosa: (inner side)- pseudostratified ciliated columnar epithelium + goblet cells- lamina propria mucosae (thin layer of

connective tissue (with elastic fibers, it contains islets of lymphatic tissue)

Submucosa: layer of loose connective tissue with

small mixed glands

Fibrocartilaginous layer: C-shaped hyalinecartilages (l6-20) + (annular lig.) , posteriorly

free ends are connected by ligaments (X, Y-shaped),

musculus trachealis is present in posterior part of the tracheal wall

Adventitia: loose connective tissue with blood vessels and nervesit connects the trachea with surrounding

structures

similar structure as trachea show the primary orextrapulmonary bronchi

Lungs (Lat. pulmo, Greek pneumón)

are located in the pleural cavity lined byparietal pleura, which is to come over thelungas the visceral pleura (mesothelium + thin layer of dense connective tissue) at the hilum of each lung the pleural cavity contains a small amountof watery, serous fluid

The bronchial tree

primary bronchi (extrapulmonary) enter the

right and left lungthey divide in secondary bronchi (3 in the right, 2 in the left that supply pulmonarylobessecondary or lobar bronchi divide into tertiary bronchi supplying broncho- pulmonary segments (anatomical units of the structure)

the tertiary bronchi repeatedly divide, at minimal 10 times, so that small bronchi of 12 orders arisethese are called bronchioles and conductair into pulmonary lobules

bronchioles are the last of intrapulmonary bronchi that contain cartilage in their wall

in general, the structure of primary bronchi is similar to the trachea

proceeding toward the respiratory portion, a simplification of histologic organization of both epithelium and underlying lamina propria is observedit must be emphasized that the simplification is gradual, and no abrupt transition can be observed between the bronchi and bronchioles

Pulmonary lobule

the unit of structure of the lung is called the pulmonary lobule

there is a part of the lung parenchyma of pyramidal shape (apex of the pyramid is

directed toward the hilum of the lung)at the apex; bronchiole and the branch of pulmonary artery enter the lobule

the branches of pulmonary vein (with oxygenate blood) run in the connective tissue

of interlobular septa, which delineate adjacent lobules

interlobular septa contain also lymphatic vessels

Pulmonary lobule

air is conducted to it by bronchiole

each bronchioles divides into

5 - 7 terminal bronchioles

each terminal bronchiolesubdivides into 2 or more respiratory bronchioles that are sites of transition

between the conducting and respiratory portions of RS

respiratory bronchioles pass

into alveolar ducts and sacsand these into alveoli

ALVEOLIALVEOLI (alveoli pulmonum)

- have diameter 100 – 300 m

- number of alveoli is cca 300 - 500 millions

- they occupy surface area of 80 - 120 m2

- are polyhedral or hexagonal and separated by a thin interalveolar septae

- the septum consists of interstitium (connective tissue with elastic andreticular fibers and different cell types (fibroblasts, mono- and lymphocytes, alveolar macrophages) and blood capillaries

- both sides of septae are covered withrespiratory epithelium on basal lamina

- interalveolar pores occur in the wallof alveoli and are important for collateral circulation

Respiratory epithelium

the type I alveolar cells or membranous pneumocytes - flattened, with micropino-cytotic vesicles near basal and apical surfaces and thin processes (20–25 nm), cells cover

cca 97 % of the alveolar surface the type II alveolar cells or granular pneumocytes - cuboidal cells with secretory granules in the cytoplasm; they contain phospholipid-protein and are secreted on the surface of epithelium as monomolecular film "lining complex" (surfactant) that is primarily composed of dipalmitoyl lecithinthe layer of surfactant (about 30 nm thick)prevents from atelectasis (alveolar collapse) lamina basalis

Alveolar macrophages: occur within the alveoli or in the septae cells are movable and able to phagocyte inspired particles of dust etc.

they form a part of phagocyte macrophages system

Blood-air barrier consists of:

1- respiratory epithelium with surfactant on the surface,

2- the basal laminae of closely apposed alveolar and endothelial cells,

3- endothelial cells of blood capillaries of continuous type

the total thickness of these layers varies from 0.1 to 1.5 m

insufficient surfactant production causes difficulty in expanding alveoli and injury of the respiratory epithelium in premature new-bornsthe disease - respiratory distress syndromeglucocorticoids stimulate the synthesis of surfactant and are used in treatment of the Respiratory Distress Syndrome (RDS).

TRACHEApseudostratified ciliated columnar ep.

with goblet cells^

right - PRIMARY BRONCHI - left(the same epithelium)

^3 - SECONDARY BRONCHI - 2

(LOBAR)LOBES

(the same epithelium)^

l0 - TERTIARY BRONCHI - 8(SEGMENTAL)

(the same epithelium)SEGMENTS

^ BRONCHIOLES (of 12 order) (ciliated columnar ep.) 1 mm in

diameterPULMONARY LOBULES

^

^̂

TERMINAL BRONCHIOLES

(simple ciliated columnar - cuboidal ep.) 0.5 mm in diameter

lamina propria is composed largely of smooth muscle and elastic fibers

^

RESPIRATORY BRONCHIOLES

(cuboidal- squamous ep.)<0.3 mm in diameter, wall is interrupted by more or

less numerous alveoli where gas exchange occurs

smooth muscle and elastic connective tissue lie beneath the epithelium

^

ALVEOLAR DUCTS

is a part of tree whose wall protrude in individual alveoli

A.d. open into atria that communicate with alveolar sacs (2 or more of which arise

from each atrium

^

ALVEOLAR SACS AND ALVEOLI

respiratory ep. with two cell types

The bronchial The bronchial treetree

Pleura

pleura parietalispleura visceralis

is composed of simple squamous epithelium (mesothelium) and thin layer of connective tussue ( 1 mm)

Blood supply of the lungstwo blood circulations are distinguished in the lungs: functional and nutritive ones

Functional circulation: truncus pulmonalis < into right and left pulmonary artery < their branches

(follow respir. tree) < capillary network around alveoli > venules (collect the blood rich in oxygen) > venules and veins in interlobular connective tissue (septa) > vv. pulmonales

Nutritive circulation: bronchial arteries (the branches of aorta or intercostal arteries) - follow the bronchi,

run in interlobular connective tissue and in pleura - return through vv. pulmonales into the heart

Outline of development of respiratory passages and the lung

the low part of respiratory system (from larynx downstairs) develops as an outgrowth of the ventral wall of the foregut

as the wall of entire gut is lined by the endoderm the epithelial lining of conducting as well as respiratory portions is of endodermal originthe cartilaginous and muscular components of the trachea and lungs derivefrom the mesenchyma (from the splanchnic mesoderm) initial stage of development is called as the respiratory diverticulumit occurs in the caudal end of the ventral wall of the pharynx when the embryo is aged 26 to 27 days

the diverticulum then expands in caudal direction and it becomes separated from the foregut by the development of two longitudinal esophagotracheal ridges (folds)the ridges subsequently fuse to form a septum–esophagotracheal septum

the foregut is divided in a dorsal portion, the esophagus, and a ventral portion, the trachea and lung bud

the site where the trachea communicates with the pharynx is called laryngealOrifice, between 5th and 6th pharyngeal arches.

4. The FOURTH – SIXTH.Cartilage – cartilages of larynx and trachea.

Mesenchyme – cricothyroid, levator veli palatini, constrictors of pharynx, intrisic muscle from larynx.

The 4th aortic arch – has the ultimate fate different on the left and right sides, On the left it forms a part of the arch of the aorta between the left common carotid artery and the left subclavian vein. On the right side the proximal segment of the right subclavian artery.

The 5th aortic arch - is transient and soon obliterates.

The 6th aortic arch – transform into pulmonary artery (their branches)

Branchial nerves – Superior laryngeal branch of the vagus, recurrent laryngeal branch of the vagus.

a lung bud soon divides into two knob-like bronchial budsearly in the fifth week, each bronchial bud enlarges to form a primitiveprimary bronchusconcurrently, the primary bronchi subdivide into secondary bronchi (on the right 3, on the left 2) that will supply future lobeseach secondary bronchus subsequently undergoes dichotomous branching;the branches are called the tertiary or segmental bronchi (supply bronchopulmonary segments) - 10 in the right, 8 or 9 in the left (7th week)

The 24 weeks, about 17 orders of branches have formed and the respiratory

bronchioles are present

with subsequent growth in caudal and lateral directions, the lung buds penetrate into primitive pleural cavities the mesoderm, which covers the outside of the lung, develops into the visceral pleurathe somatic mesoderm layer, covering the body wall from the inside, becomes the parietal pleurathe space between the parietal and visceral pleura is the pleural cavity

during development of the lungs, the endodermal lining thins so that the barrier

between the blood vessels in the mesenchyma and the air that will fill the lungs at birth is as slight as possible (BLOOD-AIR BARRIER)this continuous process is conventionally divided up into four general periods that overlap because differentiation is usually more advanced in the cranial part of the lungs than caudally

periods:

Pseudoglandular period - lungs somewhat resemble of a gland, at the end; all major elements of the organ have formed except those involved with gas exchange (respiratory bronchioles and alveoli)

endoderm cells are cuboidal

Canalicular period - vascularization begins and the respiratory bronchioles are developed, at the ends of some respiratory bronchioles thin-walled terminal sacs may be seensurvival of the fetus is unlikely at this time

Terminal sac period = primitive alveoli period - the development of terminal sacs continues, capillaries come into close contact with the epithelium of primitive alveoli, type I alveolar epithelial cells are already differentiate, production of pulmonary surfactant beginsafter 28 weeks survival of the fetus is possible

Alveolar period - is characterized by differentiation of terminal sacs into the future alveolar ducts

Malformations of the respiratory system

Lung agenesis - lung buds fail to form, unilateral or bilateral, survival is possible in unilateral form (compensation by the remaining lung)bilateral agenesis is fatal

Respiratory distress syndrome - inadequate production of surfactant in premature babiesthe lungs may therefore collapse and the endoderm cell surface may be damaged

Tracheo-esophageal fistula - situation when the trachea and gut were to come into contact - it is commonnly associated with esophageal atresia - blind ending of the gut - incidence is 1 per 3,000 - 4,500 births

clinical finds:the new-born baby will gag as its saliva enters its lungs and shows signs of respiratory distressmilk may be regurgitated on feedingwhen the child cries, its abdomen may become distended as air is drawn into the stomach