Post on 08-May-2015
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