MiniLecture EMBRYOLOGY(Respi ML)16Sept'06(Dr.soeherman)

8/10/2019 MiniLecture EMBRYOLOGY(Respi ML)16Sept'06(Dr.soeherman)

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EMBRYOLOGY

Embryonic disc begins to fold entoderm lined cavityprimitive gut

- the anterior end: fore gut,- the posterior end: hind gut

- mid gutconnected to yolk-sac

The opening between fore gut and mid gut: anterior intestinal portalBetween hind gut and mid gut: posterior intestinal portal

RB.SoehermanH, dr.,MKes

of The Respiratory System


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Primitive gut or tubular gutmouth, pharynx, digestive tube

The epithelial lining of digestive and respiratorytracts: entoderm

Fore gut specializes into: mouth, pharyn, partof digestive tube

!ind gutrest of small, intestine, colon, rectum

"id gut will: disappear

#erivatives of the entodermal digestive tube:- respiratory system- thyroid, parathyroid, thymus- liver, vesica felea and pancreas


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Accessory coats: muscle and connective tissue

from splanchnic mesodermtunica mucosa

PHAR!"

-# pairs of pharyngeal pouches

-Pharyngeal pouches:

$ Auditory tube and tympanic cavity

$$ Palatine tonsil

$$$Thymus and parathyroid

$%Rudimentary thymus and parathyroid

%Rudimentary the thyroid glands&


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THE NOSE.

-%entrolateral of the headthic'enedolfactory placodeolfactory pit&

-Peripheral of the pitmedian and lateral nasal processnasal septum&

-(axillary and nasal processnostril

- )lfactory epitheliumolfactory nerve

THE RESPIRATORY SYSTEM&


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-The primordia : out gro*th of the fore gutlaryngotracheal grooveslarynx, trachea,

bronchi and lungs&-+iverticulum is in open comunication *ith the fore gut&

-The caudal endlung bud

Larynx.-The internal lining is entoderm origin&

-(esenchymal cells become cartilage and the muscle&

-The opening : glottis - epiglottis

The trachea and Primary bronchi.

-The tracheal tube elongates-The epithelial pseudostratified ciliated type

(esenchymal cells become smooth muscle and cartilagenous rings and plates

- The glands : from ingro*th of epithelium

The Ln!&

-The endsprimary bronchi

-The right bronchus lateral bronchus

-The left bronchusone lateral bronchus

-The end of main tube becomes stem bronchus

The right bronchusupper, midle and

lo*er lobe

-The left bronchusupper and lo*er lobe

-The development of the lungs: branching of the tubules: bronchibronchiolesalveo


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lar ducts alveoli&


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Terminal Respiratory nit .gas-exchange unit/acinus0

-the basic functional unit of the lung-consist:-the structures distal to the terminal bronchiole&

-the respiratory bronchiale

- alveolar ducts -alveoli

-in the adult lung:- total gas volume:#11ml -surface area 21 m

-*ithin the terminal respiratory units: type of intercommunicating channels provide

collateral ventilation for the gas-exchanging units : 3&the alveolar pores of 4ohn

& the canals of 5ambertAdd 3" the a#$eo#ar %ore& o' (ohn

-are holes in the alveolar *all of 6-36 um in diameter that provide channels for gas movement bet*een contiguous alveoli&

-are not present in ne*born lungs&


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Add : the cana#& o' Lambert-are accessory channels that connect a small air*ay to an air space normally supplied by

a different air*ay&7ollateral ventilation

$n the adult collateral ventilation 8 the movement of gas from one acinus to another-

occurs through holes in the alveoli, the pores of 4ohn 9 epithelium-lined channelsbet*een terminal bronchioles 9 adacent alveoli called the canals of 5ambert&

These structures may be present in the infant lung, but they are probably not of sufficientsi;e to allo* for air drift&

Although collateral path*ay in the adult are probably not of great significance for

ventilation they do prevent absorbtion of gas in regions distal to air*ay obstruction&

The relative absence of collateral path*ays probably contribute to the pathcy atelectasis

so common in air*ay disease of infants 9 young children&

The product of resistance 9 compliance the time constants, of these collateral path*ays

have been investigated in maturing sheep 9 in young adults

The alveoli are lined by types of epithelial cells: of the alveolar surface&

-is mar'edly differentiated cell possessing fe* organelles& of the alveolar surface area.table 6-30&

-characteri;ed histologically by microvilli and osmophilic inclusion bodies&

-the type $$ epithelial cell:maintains homeostasis *ithin the alveolar space in several

*ays: 3&it is the source of pulmonary surfactant and as such indicates maturity of the

lung?it decreases the surface tension at the alveolar air-li@uid interface&

&it cell is li'ely the precursor of the alveolar type $ cell and thus plays a 'ey

role in the repair process follo*ing lung inury

6&it is capable of actively transporting ions against an electrochemical gradient andli'ely is involved in both fetal lung li@uid secretion and, post natally, the reabsorption of

fluid from the air space follo*ing the development of alveolar pulmonary edema&


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T*o pediatric disorders associated *ith the type $$ epithelial cell:3&hya#ine membrane di&ea&e:its lac' of maturity and surfactant secretion

&a#$eo#ar %roteino&i&:its excessive and disordered secretion of surfactant

The cell unctions bet*een alveolar type $ and $$ cells are very tight and restrict the

movement of both macromolecules and small ions such as sodium and chloride&

This tightness is an essential characteristic of the cells lining the alveolar space? its

enables the active transport of ions&Tight unctions provide a margin of safety for patients susceptible to pulmonary

edema:significant interstitial pulmonary edema can be present *ithout alveolar flooding

occurring, thus preserving gas exchange&

The time constants of path*ays in the young lung 9 in the right middle lobe are longer

than those in the older lung 9 in regions other than the right middle lobe suggesting thatatelectasis of the right middle lobe so common *ith generali;ed air*ay diseases in

infants 9 young children, may in part be related to comparatively little collateral

ventilation 9 air drift into regions obstructed by secretion 9 cellular debris&


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I Smooth muscle and cartilage are no* observed adacent to the conducting air

*ays&

I The pulmonary vascular system develops in close relationship to the bronchialand bronchiolar tubules bet*een the = th and 3 th *ee's of gestation

I Cronchial arteries arise from the aorta and form along the epithelial tubules&

I A variety congenital defect may arise during

the pseudoglandular stage :

I Tracheobronchomalacia

I Pulmonary se@uestration

I 7ystadenomatoid malformation

I Dctopic lobesI 7yst formation

I 7ongenital pulmonary lymphangiectasia

I The pleuroperitoneal cavity closes early in

pseudoglandular period& 'ai#re to com%#ete#y %artition thi& &%a&e into a %eritonea#and %#era# ca$ity i& o'ten accom%anied by dia%hra!matic hernia and #ead& to #n!

hy%o%#a&ia

III.*ANALI*0LAR Period ,1 to 6 2ee3&4

I 7haracteri;ed by:-luminal expansion - the formation of acinarstructures in the distal tubules,-thining of the mesenchyme,and formation of the

capilary bed,*hich come into close apposition to the dilating aciner tubules

.Bigs&3-3CI Cy the end of this period,the terminal bronchioles have devided to form or more

respiratory bronchioles and each of these have devided into multiple acinar

tubules,forming the primitive alveolar ducts and pulmonary acini&I Dpithelial cell differentiation becomes increasingly complex and is especiallyapparent in the distal region of the lung parenchyma&

I Cronchiolar cells express differentiated features and synthe;ed *#ara *e##

Secretory Protein,77SP45and Sr'actan Protein .SP-A,SP-C,and SP-70inincreasing abundance&

I 7ells lining the distal tubules assume cuboidal shapes and express increasingamounts of surfactant proteins and lipids&

I 5amellar bodies,composed of surfactant phospholipids and protein,are seen in

association *ith rich glycogen stores in these cuboidal pre-type $$ cells &

Some cells of the acinus become s@uamos, ac@uiring features of typical type $ alveolar

epithelial cells& Thinning of the pulmonary mesenchyme continues? the basal lamina of

the epithelium and mesenchyme fuse& 7apillaries surround the distal acinar tubules that*ill ultimately form the gas exchange area& Cy the end of the canalicular period in the

human infant .E to 2 *ee's0, gas exchange can be supported after birth, especially

ogenous surfactants&


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+e$e#o%menta# o' the re&%iratory &y&tem

The respiratory system continues to develop from birth to young adulthood& Some of the

steps in the development of the lung that bear particularly on lung function duringchildhood and on the pattern of respiratory disease follo*&

The air*ay are derived from an outpouching of the ventral groove of the embryo&

+uring the embryonal periodethe proximal branches are formed&Burther branching ofthe air*ay,*hich is dichotomous,occurs during the pseudo glandular period&

Cy the 3 *ee' of gestation the full number of generation of conducting air*ays has

been establishedthere after no ne* conducting air*ays develop,but there is continuing

gro*th. increase in length and diameter0 of the existing air *ays,and thinning of the

respiratory epithelium&

The air*ay *all and the respiratory epithelium change during gestation and postnatallife&+uring fetal life the thic' columnar glycogen 8rich epithelium develops cilia and

thins,particularly in the periphery of the air*ay&

The thinning of the epithelium may continue postnatally in the human &Although the epithelium of the infantKs air*ay,li'e the adultKs,is a ciliated

pseudostratified columnar type in the trachea and gradually thins to a columnar type in

the bronchioles&,there are substantial differencesThe infantKs air*ay epithelium contains a higher ratio of mucous glands than the adultKs

9 the constituents of the secretions may change throughout childhood

The rate of tracheal mucociliary clearance, studied in animal, is greater in the young adultthan in the infant

Smooth muscle is present in the air*ays of the fetus early in development 9 extend from

the trachea to the alveolar ducts in both ne*borns 9 adults

The contractile response of young compared to adult air*ay smooth muscle depends onthe species studied 9 the methodes of normali;ation

Ho*ever smooth muscle contents appears to remain relatively constant in air*ays of agiven generation 9 mechanisms controlling air*ay tone in the neonate are comparable to

the adult

7artilage is present in bronchi at about # *ee's of gestation and its distribution is

similar to that of the adult& $ncreased cartilage develops in the first year of life probably

contributing to the stiffening of the air*ays observed in the first months of postnatal life&

Postnatal gro*th of the air*ay has been investigated in only a limited number ofanatomic studies in humans&

The data are conflicting& The limited anatomic 9 more extensive physiologic studies onexcised human lung performed by Hogg 9 co *or'ers suggest that peripheral air*aysthose distal to the tenth or t*elfth generation, increase in si;e relative to the central

air*ay after the fifth year&


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A#$eo#i and Ln! Parenchyma

Jhereas the air*ays are estabilished in early gestational life and gro* by

enlargement, the alveoli develop in late gestational life and early childhood by foormingne* structures .i&e&, alveolar ducts and alveol0&

The development of alveoli is preceded by the formation of saccules at the end of the

budding air*ay&These structures, larger, thic'er *alled, and more irregular than alveoli, are probably

capable of sustaining gas exchange&

Brom 2 to 6 *ee's of gestation, some of the subdivisions of the saccules have the

cupped shape and single capillary layer characteristic of alveoli, but prematurely born

infants may have virtually no alveoli&

Approximately #1 million alveoli are present at birth in the term infant& His datasuggest that most of the 611 million alveoli present in the adult lung are formed by the

age of years&

Thereafter, gro*th of alveoli ta'es place for the most part by enlargement& Although bothcollagen and elastin are important in air*ay morphogenesis and branching, the

interestitium of the lung contains little collagen and elastin during late gestation and atbirth&

This near absence of collagen and elastin may contribute to the relative ease of rupture of

air spaces in the premature lung&

GRO/TH AN+ +E)ELOPMENT O: THE L0NG

Prenatal 5ung Fro*th

The five stages of lung development are .30 embryonic .day E to day #0, .0pseudoglandular .day # to *ee' 3E0,.60 canalicular .*ee' 3E to 20, .0 saccular .*ee'

2 to 6E0, and .#0 alveolar .*ee' 6E to term0&

This slight change in classification largely result from the observation that there are truealveoli present in the human lung before birth, *ith the first being seen at = to 6 *ee's

of gestation&

The lung first appears in the embryonic period as a ventral outpouching of the primitive

gut& The primary bronchi elongate into the mesenchyme and divide into the t*o main

bronchi&

$n the pseudoglandular period, the branching continues by means of a higher mitotic ratein the epithelium relative to the mesenchyme&

The mesenchyme differentiates into cartilage, smooth muscle, and connective tissue

around the epithelial tubes& Cy the end of the pseudoglandular period .3E *ee's0 all themaor conducting air*ays including the terminal bronchioles have formed&

The canalicular period is characteri;ed by the development of respiratory bronchioles,each of *hich ends in t*o or three thin-*alled dilations called terminal sacs or primitive

alveoli&


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The maturation of surfactant production has been studied intesively since Avery and

(eadLs discovery that prematurely born infants *ith hyaline membrane disease had

abnormal surface tension at the air-li@uid interface& $t is no* 'no*n that the source ofpulmonary surfactant is the mature type $$ epithelial cell&

Jhen the type $$ epithelial cell first appears *ithin the lung during the saccular stage,ho*ever, it is immature and contains much intracellular glycogen&

(any drugs and hormones, including steroids, thyroid and peptide hormones, can

influence surfactant biosynthesis and accelerate lung maturation& )ne intriguingobservation is the interaction of the pulmonary fibroblast *ith the type $$ epithelial cell&

The fibroblast can secrete a factor that induces the type $$ cell to rapidly synthesi;e and

secrete surfactant .see subse@uent discussion0&

Surfactant it self is a mixture of phospholipids .predominantly dipalmityl

phosphatidylcholine but also contains lesser amounts of other phospholipids, such as

phosphatidylinositol and phosphatidylgycerol0 and lipophilic proteins&

These surfactant-associated proteins .Sps0 are important for normal surfactant function,because their exclusion from surfactant preparations prevents normal in vivo

performance&There are at least three families of SP-A has a molecular *eight of approximately 6#,111

daltons? this family, along *ith SP-C, *ith molecular *eight of approximatelly 3#,111

daltons&

, does not appear to be necessary for in vivo surfactant performance&

$nstead SP-A and SP-C may play a role in the recycling of surfactant *ithin the distal

lung unit& $n contrast, SP-7, *hich has a molecular *eight of approximately 6#11daltons, is essential for in vivo performance of surfactant&

$dentification of the genes responsible for the synthesis of these SPs *ill shortly enable

their large-scale production, *hich, *hen combined *ith synthetic phospholipids, can beused in the treatment of respiratory distress syndromes&

(esenchymal and epithelial interactions may, in some circumstances, depend on directcell-to-cell communication& (orphlogic studies have demonstrated that during the later

stages of lung development the epithelial cells extend foot processes through the

basement membrane and contact interstitial cells& $n other circumstances, secreted factors

might influnce cellular differentiation& )ne example of this last process is fibroblastpneumonocyte factor .BPB0&

$f type $$ cells are exposed in vitro to corticosteroids, there is no induction of surfactantsynthesis& $n contrast, if fibroblasts are exposed to steroids, they release BPB, *hich in

turn causes type $$ cell maturation and surfactant release.Big&6-0&


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(olecular determinants of lung development)rganogenesis of the lung:

Dvents critical to organogenesis of the lungbegin *ith formation of anterioposterior

and proximodistal axes in the early embryo

The body plant is determined by genes that control cellular proliferation anddifferentiation and depends upon complex interactions among many cell types&

Segmentation and organ formation in the embryo are profoundly influenced by sets ofmaster control genes 'no*n as homeotic,or Hox,genes&Hox genes are arrayed in clearly

defined spatial patterns *ithin clusters on several chromosomes&

Hox gene expression in the developing embryo is determined, in part , by the position ofthe individual genes *ithin these gene clusters, *hich are aligned along the

chromosome in the same order as they are expressed along the anteroposterior axis&

Hox genes encode nuclear proteins that bind to +!A via a conserved homeodomainmotif and thereby modulate the transcription of specific sets of target genes

Dxpression of Hox genes influences many do*nstream genes for example, transcriptionfactors, gro*th factors and cell adhesion mollecules, that are critical to the formation of

the primitive endoderm from *hich the respiratory epithelium is derived

Documents

MiniLecture EMBRYOLOGY(Respi ML)16Sept'06(Dr.soeherman)