Developmental Diseases and Pathology: Vast summary for review
Esophageal Anomalies
Atresia – failure to recanalize lumen
- associated w/ tracheoesophageal fistula
- results in polyhydramnios due to inability to swallow (embryo)
- * VACTERL Association
- Type C most common: distal tracheoesophageal fistula and proximal atresia
- Inability to pass feeding tube into stomach
- Early surgical repair
Stenosis – narrowing of lumen
- Incomplete recanalization
Short Esophagus – failure to lengthen
- results in congenital hiatal hernia
Stomach Anomalies
Pyloris stenosis – most common
- hypertrophy of muscularis externa muscle of pyloric sphincter
- more common in males
- projectile vomiting after eating
- mass at right subcostal margin
- easily corrected surgically
- treatment: pyloromyotomy either open or laproscopic
Duodenal Anomalies
Atresia – failure to recanalize
- or associated w/ annular pancreas
- polyhydramnios present during pregnancy
- vomiting w/ bile present after birth
- “double-bubble”: 2 fluid filled bags in 2 dilated bags of intestines
- common in down’s children
- presents in a couple of hours
Stenosis – incomplete recanalization
Liver Anomalies
- rare and minor
Gall Bladder and biliary Duct Anomalies
Variations in duct system
- duplications common
- keep in mind during surgery
Atresia
- failure of duct to recanalize
- occurs near but outside liver
- jaundice at birth
Pancreatic Anomalies
Annular Pancreas
- most common
- caused by bifurcation of ventral bud
- one rotates ant and the other posterior
- fuse w/ each other and distal bud
- dudodenal obstruction can occur
- pancreas surrounds duodenum
- double bubble
Accessory Pancreatic Tissue
- occurs in wall of stomach, duodenum or ileal (Meckel’s) diverticulum
Midgut Anomalies
Stenosis – incomplete recanalization
Atresia – failure to recanalize
Omphalocele
- failed retraction of midgut
- intestinal loops in proximal portion of umbilical cord
- small abdominal cavity
Gastroschsis
- large midline defect in ant body wall
- faulty lateral folding and ant wall formation
- common in males
- abdominal contents extruded into environment
Umbilical Herniation
- imperfect closure of umbilical opening
- herniation of omentum or small intestines with crying
Ileal or Meckel’s diverticulum
- remnant of vitelline duct
- Disease of 2′s
- 2 feet upstream from ileocolic junction
- 2 inches long
- occurs in 2% of population
- 2 epithelial types present (gastric and pancreatic)
Rotational anomalies
- nonrotation, incomplete or reversed rotation
Jejunal and ileal Atresia
Type I
- intraluminal diaphragm
- continuous w/ muscular coats of proximal and distal segment
Type II
- atresia w/ cordlike segment b/t blind ends of bowel
Type IIIA
- atresia w/ complete separation of blind ends
- V-shaped mesenteric defect
Type IIIB
- atresia w/ mesenteric defect
- disal ileum acquire blood from single ileocolic artery
- “apple peel” deformity – distal intestine coils around vessel
- extreme prematurity
- unusually small distal bowel
- significant shortening of overall bowel length
Type IV
- multiple atresia of small intestine
Diagnosis:
- abdominal distention
- bilious vomiting
Treatment
- exploratory laparotomy w/ tapering jeunoplasty
- resection of proximal dilated intestine
Hindgut Anomalies
Congenital megacolon (colonic aganglionosis, Hirschprung’s Disease)
- failure of neural crest cells to migrate to form Auerbach’s & Meissner’s plexuses (parasympathetic ganglia)
- results in paralysed segment of colon w/ massive dilatation of colon proximal to segment
Imperforate anus or membranous anal atresia
- retention of anal membrane
Anal stenosis
- slight dorsal deviation of urorectal septum
Anal Agenesis
- incomplete separation of anorectal canal from urogenital sinus by urorectal septum
- fistular openings into vagina (female) or urethra (male
- or anal canal can end blindly
Anorectaal agenesis
- similar to anal agenesis
- higher in region
- fistula may or may not be present
- if present, fistula opens into bladder and meconium in urine is diagnostic
VACTERL Association
- Vertebral Anomalies
- Anal malformations
- Cardiac malformations
- Tracheoesophageal fistula
- Renal deformities
- Limb deformities
Malrotation and Volvulus
Diagnosis
- bilious vomiting
- usually presents in 1st month of life, but can be any time
Treatment
- immediate operation
- fluid and electrolytes
- Ladd procedure:
o Reduce volvulus via counterclockwise reduction
o Place small bowel in right abdomen
o Exciss Ladd’s bands
o Large bowel in left abdomen
o Appendectomy
Meconium Ileus
- intraluminal obstruction seen during newborn period
- inspissated meconium blocking intestine
- assoc w/ cystic fibrosis
- degree of obstruction varies
- cured in mild cases by rectal irrigations
- severe cases: failure to pass meconium, abdominal distention and vomiting
- use gastrograffin (hyperosmolar aq solution) 1st to try and soften and loosen meconium
- operation required only if no relief found by gastrograffin
Hirschsprung’s Disease
- absence of parasympathetic innervation to distal intestine
- proximal colon becomes distended and walls thicken due to muscle hypertrophy
- no Auerbach’s or Meissner’s Plexuses
- symptoms: delayed passage of meconium
Imperforate Anus
- no division of urinary and rectal tracts
- assoc. anomalies: GI (esophageal or intestinal atresia, or malrotation); cardiovascular; skeletal (spina bifida or sacrum agenesis); genitourinary
- Diagnosis: meconium “pearls,” bucket handle, fistula, meconium at meatus
- Therapy:
o Low lesions – perineal anoplasty
o High lesions – diverting colostomy w/ pullthrough later
Kidney Abnormalities
- 3-4% of population
- failure of ureteric bud to develop
- early degeneration of ureteric bud
- ectopic, malrotated, or fail to descend
Unilateral Renal Ageneis
- unilateral absence of renal tissues
- absence/abnormality of mesonephric duct can lead to absence of kidney or vas deferens
- associated w/ ipsilateral absence of ureter, bladder hemitrigone
- remaining kidney can be in abnormal position/rotation or can be normal
Bilateral Renal Agenesis
- incompatible w/ life
- absence of intrauterine urine production
- assoc hypoplastic lungs – responsible for death
- Potter Facies: inc. width b/t eyes, flattened nose, large low-set ears
Supernumerary kidney
- rare
- splitting of nephrogenic blastema (possible explanation)
Malrotation
- occurs around vertical axis
- most common: persistent ant position of renal pelvis
Pelvic Kidney
- often assoc w/ cryptorchidism, hypospadias, absent vagina, dysplastic vertebrae, congenital heart disease and GI anomalies
Intrathoracic Kidney
- usually on left
- very rare
Fusion
- prevents normal rotation
- some malrotation
- pelvis pointing anteriorly
- abnormal blood supply
Crossed renal ectopia w/ fusion
- incomplete ascent
- one kidney migrates to opp side
- crossed kidney lies below normal one
- ureteral orifices in normal position
Horseshoe Kidney
- most common type of fusion
- 90% fused at level of lower pole
- situated at lower level than normal
- isthmus at level of lower lumbar vertebrae
- 1/3 associated w/ urogenital anomalies
Renal Pelvis and Ureter Anomalies
Complete Ureteral Duplication
- occurs when 2 ureteral buds arise from one Wolffian duct
- most frequently found anomaly of urinary tract
- Weigert-Meyer Law – upper ureteral orifice is inferomedial to lower one
Partial Ureteral Duplication
- bifurcation may be at any level (bladder wall-renal pelvis)
Ectopic Ureter
- faulty devo of terminal Wolffian duct
- associated w/ ureteral duplication
- more common in females
- 70% associated w/ complete duplication of upper urinary tract
- ectopic orifice in female can open into vestibule, urethra, vagina, uterus
- in males can open into prostatic urethra, seminal vesicle, ejaculatory duct, vas deferens
Retrocaval ureter
- ureter passes behind vena cava, b/t VC and aorta, courses laterally to reach normal position
- devo error is in formation of VC, not ureter
- persistence of ventral subcardinal vein
- only significant when hydronephrosis results from obstruction of ureter
- only exists on the right
Bladder and Urachus
Exstrophy of Bladder
- abnormal position in cloacal membrane prevents mesodermal invasion
- common: acute and chronic inflammatory changes in mucosa, adenocarinoma
- associated w/; bifid clitoris
- corpus spongiosum absent
- treated by either primary closure of bladder or by proximal diversion of urine
Patent urachus
- failure of luminal closure of urachus
- presents when urine drains from umbilicus
Urachal Cyst
- epithelial lining of urachal remnant fails to completely obliterate
- presents as abdominal mass
Urachal Sinus
- sequelae of infected small urachal cyst
Congenital Adrenal Hyperplasia
- autosomal recessive trait
- abnormal increase in cells of cortex leads to increase cortical function and androgen production
Sex Chromosome Abnormalities
XXX – Triple X
XXY – Klinefelter Syndrome
XO – Turner syndrome
Congenital Anomalies of Repro System
True Hermaphroditism
- extremely rare
- reared as females
- have nonfunctional testicular and ovarian tissue
- error in sex determination
Female Pseudohermaphroditism
- usu caused by congenital adrenal hyperplasia
- excessive production of androgens
Hypospadias
- most common anomaly of penis
- external urethral orifice on ventral body of penis
Epispadias
- urethra opens on dorsal penis
- assoc w/ exstrophy of bladder
Cryptorchidism
- unilateral or bilateral
- testes descend by end of 1st year
- may be in abdomen or anywhere along usual path of descent
- deficiency of androgen is impt factor
- increased risk of testicular cancer
Congenital inguinal hernia
- more common in males
Hydrocele
- peritoneal fluid passes into patent processus vaginalis
Double Uterus, bicornuate uterus
Teratology – science dealing w/ causes, mechanisms, & manifestations of devo deviations, either structural, or functional
- this science involves recognizing the patterns of abnormalities and keeping track of pregnancy exposures
Teratogen-acts on somatic cells of developing organism
Mutagen-acts of the germ cells, altering genetic material-it’s the one that’s inherited…
- If you take out an environmental agent out of the environment, such that a 2nd pregnancy isn’t exposed, recurrence <0%
ALL-or-NOTHING period: 1st two weeks of pregnancy when mitosis is going on like crazy-exposure to a teratogen during this time either causes significant birth problems so that pregnancy’s lost, or it causes no problems
- USUALLY, this is NOT a susceptible time for teratogens
Weeks 3-12-very susceptible time………..
CNS, EYES, & EXT. GENITALS-susceptible during entirety of pregnancy
Other organ systems, heart, arms…etc..susceptible until about the 8th week
Palate is susceptible from 6-12 weeks
CNS, brain mostly, is actually susceptible until 5th year of life
TIME and DOSAGE of exposure as well as GENOTYPES of mom and baby are important factors
- Mechanisms of fetal damage are varied-could be placental, related to thrombosis & vasculititis, viral, etc….
TERATOGENS: infectious, chemical, maternal, radiation……. know mechanisms
THALIDOMIDE-results in phocomelia, defective dev. of arms and/or legs
- 21-35 days-bad time to be affected b/c that’s when you get arm and leg buds
- shows specificity of time-baby’s arms can be affected, and legs unaffected, if exposure is time-confined
- was thought to be specific for limbs, but also affects other systems
- marked originally for morning sickness and was just re-marketed (Celgen) as a tranquilizer and for leprosy
ALCOHOL-concomitant w/ stillbirths, spontaneous abortions, and Fetal Alcohol Syndrome(FAS)
FAS-1/1000 live births, 1/100-750 in Native Amer.
- costs $320mil/yr for recognized cases-think of Health Care and schooling
- babies born small, and remain small, can have microcephaly (small head), extra epicantric folds(side eye-skin fold), small palpebral fissures, small mouth, micrognanthia, congenital heart disease, and mental retardation/hyperactivity
- Again: depressed nasal bridge, extra epicantic folds, short nose, upturned nose, smooth philtrum, thin upper lip
- Brain anomalies: thought to be b/c aberrant neural & glial tissue migration so there’s cerebellar dysplasia and heterotopic cell cluster abnormalities- brain exposure to alcohol causes abnormal development
- Problem is thought to be related to breakdown products of alcohol-acetaldehyde levels
- Higher acetaldehyde levels are high in mothers of FAS babes- not always seen w/ chronic alcoholics causes they the genes required to metabolize alcohol differently
- How much alcohol during pregnancy is safe? NONE-even <2 per day shows FAS symptoms; increasing your intake increases chances of FAS babe
COCAINE-most commonly crack-relatively common, approx. 15%
- causes prematurity, or placental abruption, then prematurity; prematurity = underdeveloped lungs, eyes, brain
- can see microcephaly, and thus small brain, and thus learning disabilities
- can see intestinal atresias, cardiac anomalies, limb reduction defects, and the MOST COMMON ANOMALY, urinary tract abnormalities
- Long Term Effects: CNS abnormalities leading to neuro-behavioral abnormalities
DIETHYLSTILBESTEROL(DES)-synthetic hormone given in 40s/50s for women w/ bleeding & threatening miscarriage
- originally seen as problem causing adenocarcinoma of the vagina in female offspring at a earlier-than-normal age…19
- DES is seen to cause vaginal adenosis-abnormal cells present at birth, but not present ‘til approx 21 yrs later
- Males can get genital tract problems: decrease sperm # and motility, increased # of abnormal sperm
RUBELLA syndrome-triad composed of cataracts, congenital heart defects, & microcephaly
- Rubella virus attack back of eye and inner ear specifically, causing retinopathy and hearing loss respectively
- almost no time during pregnancy is safe from this virus
HERPES I & II-both affected by stress-II lives on neural ganglia, can traverse out & cause it’s problems, then unnoticed
- baby severely affected during birth via birth canal-is less of a problem for babes w/ only transplacental infection
- babe’s affected via birth canal can have CNS abnormalities because the virus likes to attack the brain-can lead to convulsions, encephalitis, hepatosplenomegaly, and often, these children die
- Herpes II: older are more likely to get it; smarter and richer more likely-so the lady says-what a drag eh?
TOXOPLAMOSIS-protozoan-50-80% US woman are susceptible to primary infection; secondary infection usually not a problem
- approx. 1/1000 births
- infection from eating raw meat, contaminated soil, unwashed veggies-lettuce, and cysts in undercooked meat-pregnant women should not eat pork, or uncooked or undercooked steak
TORCH Screen: Toxoplasmosis, Other, Rubella, Cytomegalo, Herpes
Ampetamines, bendictine, clomid, LSD, and tofranil are not known teratogens
PKU, thyroid diseases, increased androgens-can cause masculinization in female fetus
- mom w/ untreated PKU can have mentally retarded, underdeveloped, children
- mom w/ bicornate uterus-baby can have deformations and positional abnormalities
RADIATION-high doses, over 100R can cause skeletal malformations, microcephaly, congenital heart defects
- fetus’s chance of leukemia can increase 2 fold when exposed in utero
Tags: annular pancreas, auerbach's plexus, cocaine, colonic aganglionosis, cryptorchidism, d.e.s., diethylstilbesterol, duodenal atresia, ectopic ureter, epispadias, esophageal atresia, exstrophy of bladder, female pseudohermaphroditism, gastroschisis, hirschprung's disease, hydrocele, hypospadias, imperforate anus, malrotation, Meckel's diverticulum, meconium ileus, meissner's plexus, omphalocele, patent urachus, potter facies, potter's syndrome, pyloric stenosis, rebuella syndrome, teratogens, teratology, thalidomide, true hermaphroditism, urachal cyst, urachal sinus, vacterl syndrome, volvulus, weigert-meyer law, wolffian duct
