Pediatric Pathology Lectures 1 & 2

1. Disruption 2. Sequence 3. Deformation 4. Malformation sequence 5. Malformation

Are the following a description of a sequence, deformation, malformation, disruption, or a malformation sequence? 1. Structural defect caused by secondary destruction of or interference with a previously normally formed part 2. Multiple congenital anomalies that result from secondary effects of a single localized aberration in organogenesis 3. Localized or generalized compression of the growing fetus by abnormal biomechanical forces 4. The presence of 1 or more developmental anomalies of 2 or more systems due to a common etiology 5. Primary structural abnormality with poor formation of tissues due to a localized error that occurs during development

1. Malformation 2. Sequence 3. Malformation syndrome 4. Deformation Potter sequence is a sequence of problems that occurs as a result of oligohydraminos caused by renal agenesis, amniotic fluid leak, or uretroplacental insufficiency. This then leads to pulmonary hypoplasia (from lack of amniotic fluid expanding the lungs), altered facies (from the face compressing against the mother), feet and hand defects (same reason), and possible breach presentation as the neonate has difficulty getting into the right position for delivery.

Are the following examples of malformations, disruptions, deformations, sequence abnormalities, or malformation syndromes? 1. Cleft lip/palate 2. Potter sequence 3. Down syndrome 4. Compression of the fetus What is Potter sequence?

1. Malformation 2. Sequence 3. Malformation sydnrome 4. Disruption Polydactyly - additional fingers Syndactyly - fused fingers A condition in which there is entanglement of the fetus with amniotic bands that can lead to infarctions, amputations, necrosis, etc.

Are the following examples of malformations, disruptions, deformations, sequence abnormalities, or malformation syndromes? 1. Polydactyly & Syndactyly 2. Breech deformation sequence 3. XXY syndrome (Klinfelter syndrome) 4. Amniotic band syndrome What is polydactyly and syndactyly? Describe amniotic band syndrome?

Involves at least 2 gene that would normally have a small effect but when combined with certain environmental components lead to pathology. Sonic hedgehog and Homeobox genes. Holoproscencephaly and cyclopia. Limb, vertebral, and craniofacial abnormalities.

Multifactorial inherited abnormalities involve what? Cleft palate is one of the more common types of this condition. What genes are likely involved? Sonic hedgehog defects lead to what sort of condition? Homeobox defects lead to what abnormalities?

Retinoic acid (vitamin A) as it causes CNS, cardiac, and craniofacial abnormalities such as cleft lip and cleft palate. TGFβ

Pregnant women should not take what acne medication and why? What gene is thought to be associated with cleft lip?

Steroids Amniotic evaluation of fluid phospholipids can indicate if this condition may develop (because surfactant is made of phospholipids) and low phospholipid levels in the amniotic fluid could indicate poor surfactant production. Oxygen therapy given to infants with RDS can lead to suppression of VEGF and as they come off oxygen there may be a spike in the production of VEGF leading to endothelial and vessel growth into the vitreous humor of the eye.

What can we give to infants with RDS to induce the maturation of the type II pneumocytes? How can we evaluate a fetus to anticipate RDS? How does RDS lead to the development of retrolental fibroplasia?

Respiratory distress syndrome of the newborn (hyaline membrane disease) Hyaline membrane formation in the peripheral airspace. Lack of development of type II pneumocytes and decreased or absent production of surfactant.

What condition accounts for half of all neonate deaths in the USA? What occurs to the alveolar membrane in this condition? This condition is a result of what?

Preterm: <37 weeks Full-term: 37-42 weeks Postterm: >42 weeks AGA: Birthweight from 10th to 90th percentile SGA: Birthweight below the 10th percentile LGA: Birthweight above the 90th percentile

What gestational age is considered pre-term, full-term, and post-term? What birth weight is considered AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age)?

It is the result of decreased septation of alveoli during development leading to simplified and larger alveolar structures. Gentler ventilation, glucocorticoids, and prophylactic surfactant.

What is bronchopulmonary dysplasia? How can this be prevented?

Klinefleter's syndrome XXY (at least 2 X's and at least 1 Y) X0 - streak ovaries, horseshoe kidney, widely spaced nipples, infertility, short stature, amenorrhea, webbing of the neck, and broad chest (to name a few of the abnormalities associated with the condition).

You have a young male patient presenting with testicular atrophy, gynecomastia, and reduced facial, body, and pubic hair. What condition would you suspect? What chromosomal abnormality is associated with this condition? What are some signs of Turner syndrome and what is the chromosomal abnormality?

Chromosome 22 CATCH 22: Congenital heart defects, abnormal facies, thymic aplasia (hypoplasia also possible), cleft palate, and hypocalcemia (from parathyroid hypoplasia) 1. Di George Syndrome 2. Both 3. Velocardiofacial syndrome 4. Velocardiofacial syndrome 5. Di George Syndrome FISH

Di George Syndrome/Velocardiofacial syndrome is associated with what chromosome and leads to what characteristic conditions? Is Di George Syndrome of Velocardiofacial syndrome more associated with the following clinical presentation? 1. Thymic hypoplasia 2. Psychoses such as bipolar and schizophrenia 3. Congenital heart diseases (defects) 4. Palatal abnormalities/facial dysmorphism 5. Parathyroid hypoplasia How are these conditions diagnosed?

Those who live at least 12-24 hours develop hyaline membranes as those who die earlier do not have time to develop these membranes. Reparative changes including proliferation of type II pneumocytes and interstitial fibrosis. They are normal in size but are typically solid, airless, and resemble liver tissue.

Do hyaline membranes develop in RDS if the child dies within several hours of life or if they survive for at least 12-24 hours? If the infant dies after several days what changes would be expected? What do the lungs of these infants look like on autopsy?

Fetal cause: symmetric fetal growth restriction Placental & Maternal causes: asymmetric fetal growth restriction Symmetric fetal growth restriction means that the growth restriction affects all the organs including the brain whereas asymmetric growth restriction means that there is growth restriction that does not affect brain growth and development.

Fetal growth restriction has 3 main causes, fetal, placental, and maternal. Which are associated with asymmetric fetal growth restriction and which are associated with symmetric fetal growth restriction? What is the difference between symmetric and asymmetric fetal growth restriction?

1. From immaturity of the type II pneumocytes 2. High levels of insulin lead to suppression of surfactant production 3. Adrenaline, secreted by the fetus during the birthing process, usually helps to stimulate surfactant production 4. Likely the result of high chance of premature birth in twins Males Bell shaped with a ground glass appearance.

How can the following conditions lead to the development of RDS? 1. Prematurity 2. Maternal diabetes 3. Cesarean section before the onset of labor 4. Twin gestation Are males or females more prone to this condition? What is the typical appearance of these infants lungs on X-ray?

The fetal islets start to make up for the low level of insulin in the mother by making large amounts of insulin which leads to hyperplasia and increased growth of the child with poorly developed organs.

How does maternal diabetes lead to fetal complications?

A: Activity P: Pulse G: Grimace (in response to a catheter in the throat to clean out mucus) A: Appearance (color) R: Respiratory effort At 1 minute and 5 minutes after birth 10 1. ≥7 2. 4 3. 0-1

The APGAR score rates a newborn on various areas. What areas are rated? When should an APGAR score be conducted? What is the top score? Which score indicates the following risk of mortality in the first 28 days of life: 1. Mortality of 0% at 5 minutes 2. Mortality of 20% at 5 minutes 3. Mortality of 50% at 5 minutes

Downs syndrome Increased maternal age Epicanthic folds, simian crease, mental retardation, etc.

Trisomy 21 is also known as what? What is a risk factor for this condition? What are some common symptoms leading to a conclusion of this diagnosis?

Fracture of the clavicle Facial nerve palsy from forceps delivery compressing the facial nerve and Erb-Duchenne palsy from pulling on the arm during delivery. Not typically Caput succedaneum: mildest - Occurs when there is constriction of the venous return from the brain and surrounding tissue leading to a bump on the back of the head. Cephalohematoma: A lesion beneath the periosteum leading to bleeding in the space as well as anemia and jaundice from RBC breakdown. Skull fracture & intracerebral hemorrhage

What is the most common birth injury? What are two peripheral nerve birth injuries? Are these peripheral nerve birth injuries permanent? Two birthing cranial injuries are caput succedaneum and cephalohematoma. Which is milder and what is the difference between the two? Name two other cranial injuries that occur during the birthing process?

Congenital malformations, deformations, and chromosomal abnormalities. Accidents

What is the most common cause of death for infants (under 1 year of age)? What is the most common cause in children 1-14?

Uterine constraints 1. First pregnancy 2. Oligohydraminos 3. Breech presentation 4. Small uterus 5. Leiomyomas in the uterus 6. Multiple fetuses

What is the most common cause of deformations of a fetus? What about the following maternal and fetal factors leads to increased incidence of this condition? 1. Pregnancy number 2. Amount of amniotic fluid 3. Presentation 4. Size of uterus 5. Neoplasm 6. Number of fetuses

Chromosomal disorders, congenital malformations, and congenital infections. TORCH: Toxoplasmosis, others (SLAVE), rubella, CMV, and herpes simplex. It is the other intrauterine infections including syphilis, Listeria monocytogenes, adenovirus, varicella, and enterovirus.

What three fetal causes lead to fetal growth restriction? What are common congenital infections that lead to fetal growth restriction? What does SLAVE stand for?