Lecture14  teratology
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Lecture14  teratology Lecture14 teratology Presentation Transcript

  • Lecture 14 ESS_2nd semester
    • Introduction into teratology. Congenital malformations caused by environmental factors. Critical periods
    • Overview of abormalities of the placenta and umbilical cord
    • Overview of c ongenital malformations of the heart and great blood vessels
    • Development of body cavities and diaphragm
    • Overview of development of the alimentary canal
    • INTRODUCTION INTO TERATOLOGY
    • t eratology is a branch of science that deals with study of congenital malformations or defects and their causes , mechanisms and patterns
    • c ongenital malformations (CM) = such defects of health that are secret in origin and occur before birth
    • t hey 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 genes c) 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 :
    • v ery small placenta - is found in women suffering from chronic hypertension
    • v ery 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
    • p lacenta membranous - extremely thin placenta, the chorionic villi persist on the smooth chorion , which takes part in formation of the placenta (together with villous chorion)
    • p lacenta 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
    • p lacenta duplex, triplex or multiplex - a placenta that is divided in two, three or more completely separate lobes
    • p lacenta succenturiata -
    • a placenta with one main lobe
    • and one or two small accessory lobes
    • b attledore placenta (marginal insertion - insertio marginalis) - the umbilical cord is attached to the margin of the placenta
    • v elamentous 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
    • p lacenta 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:
    • p lacenta praevia - placental attachment may partially or completely obturate the cervix
    • is hazardous to both mother and child because w ith 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 week
    • d ue to the position of the placenta, spontaneous vaginal delivery is a great risk
    • Abnormalities in the placenta attachment:
    • p lacenta 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
    • p lacenta increta - chorionic villi penetrate the myometrium! s pontaneous expulsion of the placenta is not possible ( such placenta must be removed by surgery ).
    • The umbilical cord
    • a t the end of the second month, the amniotic sac enlarges and sheathes the umbilical cord
    • core od the cord si form ed by the material of the connecting stalk
    • surface of the cord is covered with the amniotic ectoderm
    • t he 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 , b oth 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)
    • t he 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)
    • v ery short cord - 20-30 cm - it brings problems during delivery
    • v ery 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
    • c ord 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 frequent
    • they occur in 6 - 8 children from 1 000 at birth
    • t heir etiology is not clear and consists in rather complicated development of the heart and blood vessels
    • m ost of malformations are of multifactorial origin
    • Anatomic-functional classification of malformations
    • 1) 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 right
    • to the left side
    • clinically: 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 separated
    • blood volumes on the right and the left sides are equal
    • t he 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 diaphragm
    • body 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 transversum
    • is a thick plate of mesenchymal tissue occupying the space between the pericardial cavity and the stalk of the yolk sac
    • it grows off from the ventral wall dorsocranially and separates pericardial cavity from the peritoneal cavity
    • the partitioning of both cavities is not complete, as they communicate via paired pericardioperitoneal (pleural) canals
    • the canals lie lateral to the foregut and dorsal to the septum transversum
    • Pleuropericardial folds (membranes)
    • are frontal oriented paired membranes, which separate the pericardial cavity from the pleural (or pericardioperitoneal) canals
    • initially, they have form small ridges growing off from the lateral wall of the thorax medially
    • they finally fuse with each other and with the root of the lungs and definitively separate pleural canals (cavities) from the pericardial cavity
    • Pleuroperitoneal folds (membranes)
    • are transversally oriented paired membranes that gradually separate the pleural
    • cavities from the peritoneal cavity
    • the 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
    • directions and by 7th week fuse with mesentery of the esophagus and with
    • the septum transversum
    • they completely close the connection
    • between the pleural and peritoneal cavities
    • Development of the diaphragm
    • diaphragm 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 transversum
    • the 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
    • f ood 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
    • t he primitive gut forms during the fourth week, as the head, tail, and lateral folds incorporate the dorsal part of the yolk sac into embryo
    • t he 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
    • t he 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
  •  
    • Stomodeum
    • Oropharyngeal membrane
    • Primitive gut
    • foregut
    • midgut
    • hindgut
    • Cloacal membrane
    • Proctodeum
    • ventral mesenterium
    • dorsal mesenterium
  •  
  •  
  •  
  • DE RIVATIVES 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 m idgut :
          • 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
  •