Lecture 14Lecture 14 ESS_2nd semesterESS_2nd semester

Introduction into teratology. Introduction into teratology. Congenital malformations caused by environmental factors. Critical periods

Overview of abormalities of the placenta and Overview of abormalities of the placenta and umbilical cordumbilical cord

Overview of cOverview of congenital malformations of the heart ongenital malformations of the heart and great blood vesselsand great blood vessels

Development of body cavities and diaphragmDevelopment of body cavities and diaphragm

Overview of development of the alimentary canal

INTRODUCTION INTO TERATOLOGY

teratology is a branch of science that deals with study of congenital malformations or defects and their causes, mechanisms and patterns

congenital malformations (CM) = such defects of health that are secret in origin and occur before birth

they are found in all human populations and are characterized by generation continuity, i.e. may be passed from generation to generation in predictable ratios

major CM are observed in about 3% of new born infants, additional anomalies can be detected after birth

the incidence of CM approaches cca 6% in two-years and 8% in 5-years children

Etiologal factors inducing congenital malformations are usually classified as follows:

a) environmental -7-10 % , environmental factors inducing anomalies are called teratogens,

b) genetic - 10-15%, CM are caused by numerical chromosomal abnormalities or by mutant genesc) multifactorial - 20 25 %, CM are caused by action of both previous factors together

for cca 50% of CM, the causes are unknown

CM caused by environmental factors

a teratogen is any agent that can produce a congenital anomaly or raise the incidence of an anomaly in a population

the organs and parts of an embryo are very sensitive to teratogenes during periods of rapid differentiation factors cause 7 -10 percent of malformations

the exact mechanisms by which teratogenes disrupt embryonic development and induce anomalies are unclear

susceptibility of an embryo to a teratogen depends on stage of development when the teratogen is present

the most critical period in development is when cell differentiation and morphogenesis are at their peak

disruption of development of the embryo occurs most easily when the tissues and ogans are forming

each part, tissue, or organ of an embryo has a critical period during which its development may be disrupted

An overview of known human teratogenes

The most popular teratogens in humans are:

ionizing radiation - high levels may injure embryonic cells, resulting in cell death, chromosomal injury and retardation of mental development and physical growth

environmental chemicals:- pesticides and polychlorinated biphenyls (PCBs) - intrauterine growth

retardation (IUGR)- mercury (organic mercury) - fetal Minamata disease - cerebral atrophy,

mental retardation, spasticity- lead- crosses the placenta and accumulates in fetal tissues

alkaloids:- marihuana and cocaine - IUGR, microcephaly, urogenital anomalies

- nicotine - IUGR- LSD (lysergic acid diethylamide) - limb defects and increased incidence of

nervous system defects

drugs: - alcohol - fetal alcohol syndrom (FAS): IUGR,

mental retardation , microcephaly, ocualr anomalies, joint abnormalities

- anticonvulsants (phenytoin) - fetal hydantoin syndrom (FHS): IUGR, mental retardation , microcephaly, ridged metopic suture, eyelid ptosis etc.

- antibiotics - streptomycin - injury ot the 8th cranial merve; tetracycline - hypoplasia of enamel, stained teeth

- hormones - androgens and high doses of progesteron - masculinization of female fetuses, ambiguous external genitalia

infections:- cytomegalovirus - microcephaly, chorioretinitis, hydrocephaly,

delayed psychomotor development- herpes virus - hepatomegyly, trombocytopenia,hemolytic anemia,

hydranencephaly- rubella virus - IUGR, microcephaly, cardiac and great vessels abormalities,

mental retardation- varicella virus - cutaneous scars, limb paresis, cataract, microphthalmia,

microcephaly- Toxoplasma gondii - microcephaly or hydrocephaly, microphthalmia,

chorioretinitis- Treponema pallidum (syphilis) - hydrocephalus, congenital deafness,

mental retardation, abnormal teeat and bones - AIDS (HIV) - growth failure, microcephaly, triangular philtrum,

hypertelorism

Abnormalities of the placenta Abnomalities in the size and shape: very small placenta - is found in women suffering from chronic hypertension very large placenta – is found in fetal hydrops - a condition of the fetus with severe

hemolytic disease resulting from serological incompatibility between the mother and baby placenta membranous - extremely thin placenta, the chorionic villi persist on the smooth

chorion, which takes part in formation of the placenta (together with villous chorion)

placenta bipartita or tripartita - a placenta with two or three incomplete lobes (after delivery, one or two lobes may be retained in the uterus and may cause postpartum uterine hemorrhage or uterine infection

placenta duplex, triplex or multiplex - a placenta that is divided in two, three or more completely separate lobes

placenta succenturiata -a placenta with one main lobe and one or two small accessory lobes

battledore placenta (marginal insertion - insertio marginalis) - the umbilical cord is attached to the margin of the placenta

velamentous placenta (insertio velamentosa) - the umbical cord is not attached to the placenta but to the amniochorionic sac (such placenta is hazardous to the fetus because vessels may be compressed during pregnancy or ruptured during the course of labor

placenta fenestrata - a placenta with openings in the chorionic plate and absence of chorionic villi in sites of openings

Abnormalities in location of the placenta within the uterus: placenta praevia - placental attachment may partially or completely obturate the

cervixis hazardous to both mother and child because with the expansion of the lower part of

the uterus, the placenta is stretched and then bleeding may occur from the 20th week- most frequently in 28th weekdue to the position of the placenta, spontaneous vaginal delivery is a great risk

Abnormalities in the placenta attachment: placenta accreta - a basal decidua or plate is hypoplastic (poorly developed) and

chorionic villi are in direct contact with the myometrium of the uterus to which they are firmly attached

placenta increta - chorionic villi penetrate the myometrium! spontaneous expulsion of the placenta is not possible (such placenta must be removed by surgery).

The umbilical cordat the end of the second month, the amniotic sac enlarges and sheathes the umbilical cordcore od the cord si formed by the material of the connecting stalk surface of the cord is covered with the amniotic ectoderm the umbilical cord contains 2 umbilical arteries, one vein, rarely rests of the allantois

Due an enlargement of the amniotic sac, the extraembryonic coelom disappears and amnion lies to close vicinity of the chorionic sac, both membranes ultimately fuse in one common layer known as amniochorionic membrane

in the full term fetus, the umbilical cord measures 1-2 cm in diameter and 30-90 cm in length (average 55 cm) the cord is usually attached near the center of the placenta

(central insertion)

other ways of insertion are: marginal and velamentous one

Abnormalities of the umbilical cord (cord accidents)

very short cord - 20-30 cm - it brings problems during delivery very long cord - 80-90 cm - it tends to entwine around the neck or extremity of the fetus true knots - occur in about 1% of pregnancies, they form during labor as a result of the fetus passing through a loop of the cord - it causes of fetal anoxia cord with anomaly of umbilical vessels – number of umbilical arteries is reduced to one; the umbilical vein is developed normally

Congenital malformations of the heart and great blood vessels

are relatively frequentthey occur in 6 - 8 children from 1 000 at birththeir etiology is not clear and consists in rather complicated development of the heart and blood vesselsmost of malformations are of multifactorial origin

Anatomic-functional classification of malformations1) malformations with the left-right shunt (short circuit)oxygenated blood flows from the left to the right part of the heart, respectively from the aorta to the pulmonary trunk clinically: absence of cyanosis

- atrial septal defect (s)- ventricular septal defect- persistent ductus arteriosus

2) malformations with the right-left shunt (short circuit) – complicated malformations characterized by passage of venous blood

from the rightto the left sideclinically: permanent hypoxia, cyanosis of the central type, polyglobulia

and asthma- tetralogy of Fallot or morbus coerulleus (= a complex of

4 anomalies: stenosis of the pulmonary artery, ventricular septal defect, dextroposition of the aorta, hypertrophy of the right ventricle)

- transposition of the great vessels- tricuspid atresia

3) malformations without shunts (short circuits) - the pulmonary and systemic circulations are separatedblood volumes on the right and the left sides are equal

the group includes:- aortic valvular stenosis or atresia- coarctation of the aorta- double aortic arch- right aortic arch- valvular stenosis of the pulmonary artery

4) abnormalities in heart position: - dextrocardia - the heart lies on the right side- ectopia cordis - the heart is located on the surface of

the chest

Sequency of CM of the heart and great vessels:- persistent ductus arteriosus - ventricular septal defect- tetralogy of Fallot- atrial septal defect (s)- stenosis of pulmonary trunk

Development of body cavities and diaphragmDevelopment of body cavities and diaphragmbody cavities - initially one common cavity - are developed early during the fourth week of the embryonic life

anlage of them appear in the form of numerous small, isolated intercellular coelomic

spaces occured within the lateral mesoderm and the cardiogenic mesoderm

the intercellular spaces soon coalesce to form a horshoe-shaped cavity, the intraembryonic coelom

the cavity is lined by flattened epithelial cells called as the mesothelium

the curve, or bend, in this cavity indicates future pericardial cavity, and its limbs indicate future pleural and peritoneal cavities

the greater part of each limb of the cavity opens into extraembryonic coelom

at the lateral edges of the embryonic disc

during transverse folding of the embryo, the limbs or lateral parts of the intraembryonic coelom are brought together on the ventral aspect of the embryo

in the region of future peritoneal cavity, the ventral mesentery degenerates, thus resulting in a large embryonic peritoneal cavity extending from inferior of the heart to the pelvic region

at the beginning of the 2nd month, the common coelomic cavity include the following parts:

a large pericardial cavity

two relatively small pericardioperitoneal (pleural) canals connecting the pericardial and peritoneal cavities and

a large peritoneal cavity

the cavities posses

a parietal wall lined by mesothelium derived from the somatic mesoderm, and

a splanchnic (visceral) wall covered by mesothelium derived from the splanchnic mesoderm

the somatic mesoderm and overlying embryonic ectoderm form the body wall - somatopleura, whereas the splanchnic mesoderm and the embryonic endoderm form the splanchnopleura, or wall, of the primitive gut

during the 2nd month, the partitioning of the common coelomic cavity starts

three septae are developed

septum transversum

pleuropericardial folds

pleuroperitoneal folds(Membranes)

they divide the coelomic cavity into its definitive compartments as seen in adults:

the pericardial cavity

the pleural cavity (paired), and

the peritoneal cavity

Septum transversumSeptum transversum

is a thick plate of mesenchymal tissue occupying the space between the is a thick plate of mesenchymal tissue occupying the space between the pericardial cavity and the stalk of the yolk sacpericardial cavity and the stalk of the yolk sac

it grows off from the ventral wall dorsocranially and it grows off from the ventral wall dorsocranially and separates separates pericardial cavity from the peritoneal cavitypericardial cavity from the peritoneal cavitythe partitioning of both cavities is not complete, as they communicate via the partitioning of both cavities is not complete, as they communicate via paired pericardioperitoneal (pleural) canalspaired pericardioperitoneal (pleural) canalsthe canals lie lateral to the foregut and dorsal to the septum transversumthe canals lie lateral to the foregut and dorsal to the septum transversum

Pleuropericardial folds (membranes)Pleuropericardial folds (membranes)

are frontal oriented paired membranes, which are frontal oriented paired membranes, which separate the pericardial separate the pericardial cavity from the pleural (or pericardioperitoneal) canalscavity from the pleural (or pericardioperitoneal) canals

initially, they have form small ridges growing off from the lateral wall of initially, they have form small ridges growing off from the lateral wall of the thorax mediallythe thorax mediallythey finally fuse with each other and with the root of the lungs and they finally fuse with each other and with the root of the lungs and definitively separate pleural canals (cavities) from the pericardial cavitydefinitively separate pleural canals (cavities) from the pericardial cavity

Pleuroperitoneal folds (membranes)Pleuroperitoneal folds (membranes)

are transversally oriented paired membranes that gradually are transversally oriented paired membranes that gradually separate the pleural separate the pleural cavities from the peritoneal cavitycavities from the peritoneal cavity

the folds project into the caudal end of the pericardioperitoneal (pleural) canalsthe folds project into the caudal end of the pericardioperitoneal (pleural) canals

they grow off from the dorsolateral wall of the body, extend in medial and ventral they grow off from the dorsolateral wall of the body, extend in medial and ventral directions and by 7th week fuse with mesentery of the esophagus and with directions and by 7th week fuse with mesentery of the esophagus and with the septum transversumthe septum transversum

they completely close the connection they completely close the connection between the pleural and peritoneal cavitiesbetween the pleural and peritoneal cavities

Development of the diaphragmdiaphragm is dome-shaped, musculotendineous partition separating the pleural and abdominopelvic cavities it develops from 4 components:

the septum transversum - is mesenchymal septum, initially incompletely sepa-rating the pericardial and abdominopelvic cavities, it forms the central tendon of the diaphragm the pleuroperitoneal membranes - they fuse with the dorsal mesentery of the

esophagus and with dorsal portion of the septum transversumthe pleuroperitoneal membranes represent small intermediate portion of the definitive diaphragm the dorsal mesentery of the esophagus - gives rise to the median portion of

the diaphragm the body wall - contributes to peripheral portions of the diaphragm external

to the portions derived from the pleuroperitoneal membranes

The digestive system consists of

the alimentary canal - oral cavity, oropharynx, esophagus, stomach, small and large intestines, rectum and anus

associated glands - salivary glands, liver and pancreas

function is to obtain from ingested food the metabolites necessary for the growth and energy needs of the body

food is digested and transformed into small molecules that can be easily absorbed through the lining of alimentary canal

DEVELOPMENT OF THE DIGESTIVE SYSTEM: THE STOMODEUM, THE

PRIMITIVE GUT AND THE PROCTODEUM

Overview of development of the alimentary canal

the primitive gut forms during the fourth week, as the head, tail, and lateral folds incorporate the dorsal part of the yolk sac into embryo

the endoderm of the primitive gut give rise to most of the epithelium and glands of digestive tract

the epithelium at cranial and caudal extremities of the alimentary canal is derived from the ectoderm of the stomodeum (primitive mouth) and the proctodeum (anal pit), respectively

the muscular and fibrous elements of the alimentary canal, and the visceral peritoneum, are derived from the splanchnic mesenchyma surrounding the endodermal lining of the primitive gut

For descriptive purposes, the primitive gut is divided into three parts:• the foregut• the midgut• the hindgut

StomodeumOropharyngeal membrane

Primitive gutforegutmidguthindgut

Cloacal membrane

Proctodeum

ventral mesenteriumdorsal mesenterium

DERIVATIVES OF THE PRIMITIVE GUT

The hindgut:• the descending colon• the sigmoid colon• the rectum• the superior portion of the anal canal• the epithelium of the urinary bladder and most of the urethra

The foregut:• the pharynx and branchiogenic organs• the lower respiratory tract• the esophagus• the stomach• the duodenum proximal to the opening of the bile duct• the liver and pancreas- the biliary apparatus

The midgut: • the small intestines, including the part of the duodenum distal to the opening of the bile duct• the caecum and appendix• the ascending colon • the transverse colon