Pediatric Pathology Flashcards
1
Q
What is the fetal period and its two subsections?
A
9 weeks until birth - where differentiation and maturation of the organ systems occurs
9-20 weeks: Previable period
20-38 weeks: Viable period
2
Q
What is a neonate vs infant?
A
Neonate = first 4 weeks, as in psychiatry the time when perinatal depression occurs.
Infant = 4 weeks - 1 year of life
3
Q
What is meant by AGA, SGA, and LGA birth weights?
A
SGA = small for gestational age, <10th percentile
AGA = appropriate for gestational age, 10-90th percentile
LGA = large for gestational age, >90th percentile
4
Q
What are the categories of things which can cause small birth weights?
A
- Appropriate for gestational age, but low birth weight -> due to prematurity
- Small for gestational age, but low birth weight -> normal small (low percentile)
- Small for gestational age, but low birth weight -> pathologically small fetus
5
Q
Why are babies typically very low birthweight (less than 1500g)?
A
Due to extreme prematurity -> accounts for half of all neonatal deaths
6
Q
What is meant by intrauterine growth retardation?
A
Being born small for gestational age, i.e. fetal growth retardation. Includes weight, height, and head circumference <10th percentile
-> Infnants are born at <2500gm and are simply small despite making it to full gestation based on number of weeks
7
Q
What are the two types of intrauterine growth retardation? When in the pregnancy do these onset?
A
Type 1: Symmetric Growth Retardation - early onset in pregnancy. Body and organs, including the brain, are proportionate.
Type 2: Asymmetric Growth Retardation - late onset in pregnancy. Body and organs are disproportionately small relative to the brain.
8
Q
What causes symmetric growth retardation?
A
Chromosomal disorders, congenital anomalies / malformation syndrome, early intrauterine infections (i.e. TORCH infections)
-> fetal causes, early onset
9
Q
What causes asymmetric growth retardation?
A
> uteroplacental causes, later onset
Due to maternal conditions, i.e. vascular insufficiency, nutrition, toxin / drug, infection
10
Q
Is Large for Gestation Age (LGA) a problem? What causes it?
A
Yes, it is associated with increased morbidity and mortality
Caused by maternal diabetes mellitus, or a postmaturity syndrome (baby is born late)
11
Q
What are the three categories of factors which influence fetal growth, and which one is most commonly aberrant?
A
- Fetal - intrinsic fetal conditions (genetic or infection), reducing growth potential of fetus despite an adequate supply of nutrients
- Maternal - most common cause of IUGR - decreased placental blood flow, due to maternal CVD, preeclampsia, renal disease, smoking, infections, narcotics, alcohol, etc.
- Placental - Inadequate uteroplacental function
12
Q
What are things that can cause uteroplacental insufficiency?
A
Vascular anomalies (i.e. single umbilical artery), placental abruption (tearing of placenta from uterine wall), infarction, infection, multiple gestations
13
Q
What is the clinical definition of abortion? What is early vs late?
A
Abortion: spontaneous or induced termination of pregnancy prior to fetal viability (~22 weeks)
Early - embryonic period, up to 8 weeks
Late - fetal period, 9-22 weeks (viability)
14
Q
What are the leading causes of death in children under 1 year?
A
- Congenital anomalies
- Prematurity, low birth weight
- SIDS
15
Q
What are the leading causes of death in children 1-4 years?
A
- Accidents
- Cancer
- Congenital anomalies
16
Q
Define the following clinical categories of abortion: threatened, inevitable, incomplete, missed, recurrrent.
A
Threatened: Blood discharge without cervical dilation
Inevitable: Prolonged bleeding with cervical dilation
Incomplete: Retention in the uterus of portions of conceptus (fetus or placenta)
Missed: Retention of dead fetus in uterus for >4 weeks
Recurrent: 3 or more consecutive spontaneous abortions
17
Q
Is spontaneous abortion common?
A
Yes, up to 15-25% of recognized pregnancies abort in the first two trimsters
18
Q
What is the definition of stillbirth and its two types?
A
Death prior to delivery of a potentially viable fetus (>22 weeks)
- Intrauterine death - occurring more than 24 hours prior to delivery
- Intrapartum death - occurring within 24 hours before or during or 24 hours after delivery
19
Q
How are intrauterine vs intrapartum stillbirths told apart?
A
Intrauterine= macerated stillborn = baby will be macerated due to autolytic change in utero. Will also have been decreased body movements and stoppage of maternal weight gain
Intrapartum = fresh stillborn = baby will not be macerated, but will instead have meconium passed. Baby dies within 24 hours prior, during, or after delivery. If dead during delivery, will exhibit deceleration of heartbeat, acidosis, and cessation of movements
20
Q
What is meconium? Why is it associated with intrapartum death?
A
Dark greenish material accumulating in bowel during fetal life which is normally discharged shortly after birth.
Distress in utero may cause fetus to defecate meconium prior to delivery -> meconium will be present as they come out.
21
Q
How do you calculate gestational age?
A
Weeks since last menstrual period - 2 = GA
LMP - 2 = GA, since ovulation + fertilization happens 2 weeks after LMP
22
Q
How are the causes of spontaneous abortion / stillbirth similar to those causing intrauterine growth retardation (IUGR)
A
- Fetal / placental causes like chromosomal abnormalities, malformations no associated with genetics (i.e. NTD, limb development), and placental factors like abruption, multiple births and umbilical cord accidents can cause death.
- Maternal causes also cause this.
- Obstetrical difficulties -> unique to abortion / stillbirth
23
Q
What are the maternal causes of spontaneous abortion / stillbirth? Specify:
- Maternal age
- Infections
- Uterine abnormalities
- Maternal diseases
- Nutrition status
- Exposure to toxins / drugs
A
- Maternal age - increased risk in young or old mothers
- Infections - Commonly ascending genital infections like Mycoplasma hominis, Chlamydia, TORCH
- Uterine abnormalities - IUD, uterine alformations
- Maternal diseases - HTN, diabetes vascular insufficiency, antibodies from previous pregnancy
- Nutrition status - decreased folate, zinc
- Exposure to toxins / drugs - cigarettes, teratogens
24
Q
Why might a congenital malformation leading to an abortion / stillbirth not become apparent until after fetal death?
A
Heart, lungs, kidneys, and other internal organs may not have their faulty functioning exposed util after birth, when the placental unit is no longer there.
This is why we count babies that die within 24 hours as fresh stillborns
25
What are the three primary changes that occur during maceration and how do they allow us to identify the intrauterine time of death of the baby?
1. Skin changes - skin slippage / bulla formation within 24 hours
2. Color change - from normal to purple to yellow to gray over a 1-2 week period
3. Fluid - fluid accumulates in body cavities
26
What happens in the placenta during maceration?
Fibrin deposition and fibrosis with calcification, due to long-lived fibroblasts even after the death of the placental unit.
27
What do necrosis / inflammation of the fetus or placenta indicate?
A non-autolytic tissue change (not maceration) which is likely a pathologic process which may have contributed to fetal death
28
What is the defining characteristic of hydrops fetalis?
Generalized edema - interstitial, subcutaneous, body cavities
29
What is immune hydrops fetalis called and what are its two causes?
Erythroblastosis fetalis -> hemolytic disease of the fetus or newborn via passage across placenta of maternal antibodies against fetal erythrocytes
1. Rh incompatability - maternal antibodies to D antigen
2. ABO incompatibility - most common in type A infants. Significant disease is uncommon.
30
Why does erythoblastosis fetalis lead to edema / hydrops?
Resultant anemia from binding of Rh antigens or ABO antigens will lead to decreased O2 carrying capacity of the blood, making the baby's heart work harder.
-> eventual cardiac decompensation and heart failure leads to systemic congestion / edema
31
What are the three basic mechanisms by which hydrops fetalis can be caused?
1. Increased capillary / venous pressure
2. Decreased oncotic pressure
3. Decreased capillary integrity
(basically all the causes of transudative / exudative edema)
32
What types of things can lead to increased capillary / venous pressure -> hydrops fetalis?
High cardiac output state (i.e. AV malformation)
Vascular obstruction
Cardiac failure
33
What types of things can lead to decreased oncotic pressure in the fetus?
Decreased albumin synthesis (hepatic disease) or increased loss of albumin (renal disease)
34
What types of things can damage capillary integrity?
Sepsis
Drugs or toxins
Hypoxia of tissues
35
How will the bone marrow, liver, and spleen respond to hydrops fetalis?
Bone marrow - hyperplasia of erythroid precursors to make more RBCs
Liver - extramedullary hematopoiesis + hepatomegaly
Spleen - extramedullary hematopoiesis + splenomegaly
36
What is the most serious long-term threat of sequelae in hydrops fetalis?
Permanent CNS damage due to hyperbilirubinemia -> easily cross BBB in fetus -> kernicterus, causing selective necrosis of neurons
37
Where does unconjugated bilirubin tend to accumulate in kernicterus?
Basal ganglia and thalamus
38
What are the two categories of intrapartum birth injury and some major risk factors?
1. Traumatic birth injury
2. Perinatal asphyxia
Risk factors: Maternal poor health, placental abnormalities, fetal conditions (especially LGA), and obstetrical problems like forceps delivery
39
What is caput succedaneum and what does it cause?
A type of traumatic birth injury -> cranial trauma
Interstitial fluid in soft tissues of the scalp - not clinically significant
40
What do you call a hemorrhage under the periosteum of the skull which can lead to the thickening of the skull in traumatic birth injury?
Cephalhematoma
41
What is the most common important birth injury?
Intracranial hemorrhage
42
When does a skull fracture typically happen?
Occurs in deliveries with inappropriate use of forceps, with large fetal head size in comparison to birth control
43
What is osteodiathesis? Where does it commonly occur?
Separation of cranial bone sutures, happens especially with occipital sutures.
44
What other traumatic injuries can occur in birth?
Laceration of brain, other soft tissue
Bone fractures / dislocations (shoulder is tough), peripheral nerve injures (especially brachial plexus), cervical spinal cord injuries
Organ injuries
45
What is some nonspecific evidence of fetal distress / birth asphyxia?
Skin / placental staining with meconium
Aspiration of meconium in lungs
Vascular congestion
Hemorrhages on organ surfaces like thymus and lungs
46
What are some specific patterns of acute organ injury due to asphyxia?
1. Hypoxic-ischemic brain damage -> especially in Purkinje cells
2. Neonatal respiratory distress syndrome
3. Acute tubular necrosis in kidneys
4. Lymphocyte depletion in thymus (starry sky appearance)
5. Adrenal hemorrhages
47
What is being assessed on APGAR score and what is the highest score possible? List the best possible state in each category
APGAR
Appearance - Completely pink (vs blue body, or blue extremities)
Pulse - >100 bpm
Grimace - Cough / Sneeze to nasal catheter
Activity - Active motion (vs just some flexion)
Respirations - Good / crying is best
All scores are 0, 1, or 2
Highest score is 10, >7 is normal, <3 = poor prognosis
48
What is static encephalopathy?
Cerebral palsy - permanent, nonprogressive brain dysfunction due to intrauterine or perinatal brain damage
49
How is prematurity defined? What is the lowest weight which can survive typically?
Spontaneous or induced birth prior to 37 weeks gestation
500g+ can survive with extensive care
50
What are the anatomical stages of lung development?
Lung bud = 4-6 weeks
Pseudoglandular period = 6-16 weeks
Canalicular period = 16-26 weeks
Alveolar period = 26 weeks to term
End of canalicular period you start having some respiratory epithelium and can potentially survive (around 22 weeks)
51
How is maturity of the lungs measured in utero?
Lecithin:sphingomyelin ratio in amniotic fluid. If >2, very low chance of neonatal respiratory distress syndrome. (Lecithin is produced more later, and sphingomyelin gets filtered out)
52
When do Type 2 pneumocytes first appear and then produce adequate surfactant?
First appear around 22 weeks gestation -> beginning of viability
Produce adequate surfactant (lecithins, DPPC) by around 36 weeks
53
What happens to connective tissue in the lung during development?
It decreases, as the alveolar septae get thinner and thinner
54
How does nervous system immaturity affect premature infants?
Poor respiratory, vasomotor control, regulation of temperature, and feeding (lack of moro reflex)
55
What are premature infants at increased risk of kernicterus?
Liver may be physiologically immature and unable to conjugate bilirubin -> hyperbilirubinemia
Very bad because they have immature BBB
56
What is the leading cause of morbidity and mortality in premature infants, and what is it also called?
Respiratory distress syndrome, also called hyaline membrane disease (HMD)
57
What is the pathogenesis of hyaline membrane formation in premature fetal lungs (respiratory distress syndrome)?
1. Deficiency of pulmonary surfactant and underdevelopment of lungs -> increased surface tension and atelectasis of airways.
2. Decreased ventilation + hypoxia leads to pulmonary vasoconstriction and hypoperfusion.
3. Pulmonary capillaries and pneumocytes become damaged, with some hemorrhaging into septae
4. Plasma leaks into alveoli, forming fibrin clots and causing necrosis of pneumocytes -> hyaline membrane formation
58
How does oxygen therapy contribute to pathology in RDS?
Oxygen free radicals also damage the endothelium, leading to formation of clotting / hyaline clots.
59
What is bronchopulmonary dysplasia? What pathologically characterizes it?
The condition which develops if the infant (<32 weeks) survives RDS with >28 days of oxygen.
Characterized by alveolar interstitial fibrosis (lots of scarring), and obliteration of airspaces with hyperplasia and squamous metaplasia of the bronchiolar epithelium (in the bronchi / bronchioles). Often, the alveoli will be lined by Type 2 pneumocytes which are cuboidal since they can divide and Type 1 can't.
60
How will the lungs appear in early stage RDS via chest X-ray? How are they treated?
They have opacification with a "ground glass" appearance -> infants require intubation and mechanical ventilation
-> lungs are airless, red, and firm and sink in water
61
Where does intracerebral hemorrhage usually arise in the newborns? What is its function?
Germinal matrix - embryonic structure on wall of lateral ventricle which persists until 30 weeks.
It functions to populate neurons / glial cells and will be susceptible to hypoxic damage
62
What is associated with the development of intracerebral hemorrhage, and how are these graded?
RDS -> small vessels will supply this embryonic area and hemorrhage when there is hypoxia (due to damage).
Graded 1-4 based on where hemorrhage spreads
```
1 = confined to germinal matrix
2 = extension into lateral ventricle without dilation
3 = Intraventricular hematoma with dilatation
4 = Extension back into parenchyma of brain
```
63
What are the long-term sequelae of intracerebral hemorrhage?
Hydrocephalus and permanent neurological defects
64
What is the most common gastrointestinal emergency of newborns and who does it tend to occur in?
Necrotizing enterocolitis, tends to occur in infants recovering from RDS in prematurity, after introduction of oral feedings.
65
What is the pathogenesis of necrotizing enterocolitis?
Ischemic damage due to generalized hypoperfusion of gut when shuttling blood towards more vital organs during RDS.
Injury allows to transluminal migration of gut bacteria, followed by inflammation and necrosis of gut wall, with perforation, peritonitis, sepsis, and shock
66
What does necrotizing entercolitis look like pathologically (where does it happen)? What is the special name for one of these features?
Typically in terminal ileum or right side of colon, intestine shows dilatation / segmental necrosis, air bubbles in wall (pneumatosis intestinalis) -> due to bacteria and poor integrity of luminal epithelium which was never perfused in the past due to feeding via central line, and often perforation.
67
What are the secondary complications of necrotizing enterocolitis?
1. Short gut syndrome - if a significant length of small intestine had to be removed surgically
2. Strictures due to fibrosis
3. Complete obstruction due to fibrosis
68
What is the medical definition of SIDS? Is it common?
Sudden death of an infant between week 3 and 8 months, apparently during sleep, not preceded by signs and symptoms of a lethal disease
Still the leading cause of death in infants age 1 month to 1 year in USA (most will happen by 6 months)
69
What is the legal definition of SIDS?
Sudden death of an infant under one year of age remaining unexplained after investigation / autopsy
70
What are a couple important risk factors for SIDS?
Drug abuse in either parent, prone sleep position
71
What are the internal pathologic findings of SIDS?
Congested lungs
2. Petechiae on pleura, thymus, and epicardium
3. Thymic involution (like in asphyxia of abortion / stillbirth)
4. URI evidence not sufficient enough for death
5. Gliosis (glial scarring) and CNS changes
72
What are the external findings in SIDS?
Well developed and nourished, healthy looking, some cyanosis of lips and nailbeds, with postmortem lividity
73
What are some conditions mimicking SIDS which should be on the differential? (once you diagnose one of these, it is by definition not SIDS)
Viral myocarditis, bronchopneumonia
Drugs / toxins intoxication
74
What is the most likely pathogenesis of SIDS?
Delayed development in brain arousal / cardiorespiratory centers, involving serotonin pathways in medulla.
-> spontaneously stop breathing
75
How long does it take for the fetal immune system to develop?
Immune function begins at around 12 weeks gestation, but is not fully developed until 1 year of age
76
Why are neonates so susceptible to infection?
Immature liver, bone marrow, and spleen disallows speedy compensatory WBC and RBC synthesis
Brain is also immature, leading to poor hemodynamic and thermal control
-> shock and hypothermia if stressed
77
How is the fetus kept well protected from infection prior to birth?
Maternal and fetal barriers are strong, placenta provides a physical barrier through the amnion, and even the amniotic fluid is bacteriostatic
78
When are micro-organisms transferred to the fetus via the transplacental (hematogenous) rout?
At any time during gestation, or occasionally at time of delivery (a maternal to fetal transfusion across placenta)
79
What are common transplacental infections?
TORCH + Listeria, HIV, and Zika
```
T = Toxoplasma
O = Other, i.e. syphillis, parvovirus
R = Rubella
C = Cytomegalovirus
H = Herpes Simplex Virus
```
80
How does Parvovirus B19 or "fifth disease" / erythema infectiosum appear in a bone marrow smear? What will this cause clinically?
With intranuclear viral inclusions in the bone marrow of erythroid cells -> leads to congenital anemia / hemolysis.
-> Hemolysis leads to hydrops fetalis from anemia. May lead to abortion / stillbirth
81
What is the ascending, amniotic route of infection? When does this occur?
Transcervical, occurs in utero or around time of birth -> organisms penetrate ruptured membranes and invade amniotic fluid, which fetus may inhale before birth or during delivery
82
How does postnatal examination of placenta help identify infection?
Chorioamnionitis - inflammation of chorion and amnion of placenta
Funisitis - inflammation of umbilical cord
-> often candida or HSV
83
How can you have intrauterine transmission of infection?
Via fetal instrumentation -> i.e. contaminated amniocentesis or chorionic villus sampling
84
What is it called when you transmit infection during passage through the birth canal? What are a few common culprits?
Intrapartum route
Commonly:
Neisseria, Chlamydia, HSV, Group B strep, E. coli K1, Listeria, VZV, S. aureus
85
What would be considered early vs late onset perinatal infection? Most common organism?
Early - within first 7 days
Late - 7 days to 3 months
Most common organism is Group B Streptococcus
86
While it is clear that children are most susceptible for hematopoietic, CNS and embryonic neoplasms as well as soft tissue sarcomas, which two tumor types are fairly well associated only infancy and early childhood?
Wilms tumor (kidney malignancy) and retinoblastoma
87
What are some of the unique congenital neoplasms?
Hemangiomas, lymphangiomas, nevi, sacrococcygeal teratoma
88
What is a heterotopia?
Another name for a choristoma (as seen with pancreatic tissue in the esophagus)
-> masses of microscopically normal cells or tissues in abnormal locations
89
Other than heterotopias, give one other common non-neoplastic mass that appears due to errors in development. Are these more common or rarer than malignant neoplasms in pediatric populations?
Hamartomas - excessive focal overgrowths of cells / tissue NATIVE to that organ, but lacking normal arrangement.
Benign tumors / tumor-like conditions are more common
90
What is the most common congenital tumor?
Hemangioma - a tumor of mature blood vessels
91
Why can large hemangiomas be problematic?
May lead to coagulopathies because of the heart trying to perfuse the vessels, or high-output cardiac failure
92
What syndrome is associated with the development of multiple hemangiomas in the retina, brain, and other organs? Mode of inheritance?
von Hippel-Lindau -> think of the lady with cysts all over her
Autosomal dominant
93
What is the other name for a cystic hygroma and where do they usually arise? Why is this a problem?
Lymphangioma
- > usually arise in axillary or neck region
- > can compress neck structures or the respiratory system
94
What are "birth marks" and their pathogenesis, what do they predispose you to?
Congenital melanocytic nevi -> benign proliferations of melanocytes into the DE junction / dermis
->increased risk of malignant transformation to melanoma
95
What is the definition of a fibroma / fibromatosis? Is it benign or malignant? Are they homogenous?
Proliferation of fibroblastic cells in soft tissues
-> looks like sarcomas in adults, but it is benign
They are not homogenous -> their cellularity is highly variable depending on what tissue they infiltrate
96
Are fibromastoses dangerous? Where do they tend to develop?
Tend to develop in the skin, fingers, and neck (especially near sternocleidomastoid muscle)
They can enlarge and impede on vital organs like heart and lung, but generally benign.
97
What is the most common malignant neoplasm of children? Its most common form?
Leukemia
-> Acute lymphoblastic leukemia
98
What is leukemia vs lymphoma?
Leukemia - malignant cells start in bone marrow (especially hematopoetic stem cells / myeloid line)
Lymphoma - malignant cells start in lymph nodes, shows differentiation towards lymphocytic cells (multipotent lymphoid line)
99
What is a Langerhans cell histiocytosis?
A malignant neoplasma of children, with tumor-like proliferation of Langerhans cells in the skin and bones
100
What is Letterer-Siwe disease? Prognosis?
The most severe form of Langerhans cell histiocytosis
- > Acute disseminated
- > Skin / systemic involvement, onset in infancy with rapid progression
101
What is Hand-Schuller-Christian disease? When is the onset / prognosis
Langerhans cell histiocytosis with multifocal lesions
- > typically involves bones / organs
- > onset is childhood
- > many patients develop diabetes insipidus due to involvement of posterior pituitary
- > controllable by chemotherapy
102
What is the solitary lesion form of langerhans cell histiocytosis called, and where and when is it identified?
Eosinophilic granuloma
- > lytic lesion within bones appearing in late childhood / early adulthood
- > excellent prognosis, heals spontaneously or by local incision
103
How is Langerhans cell histiocytosis identified histologically?
Langerhans cells with grooved, irregular nuclei and cytoplasmic inclusions called "Birbeck granules" -> an endosomal inclusion.
Langerhans cells are associated with EOSINOPHILS, plasma cells, and lymphocytes
104
What is the definition of germ cell tumor?
Neoplasms whose cell components resemble components of the gonadal cells (germ cells include oogonia / spermatogonia), embryo, or placenta
105
Where do extragonadal germ cell tumors tend to arise?
Midline structures such as sacrococcygeal region (esp. infants), mediastinum, retroperitoneum, and pineal gland
106
What is the most common place for germ cell neoplasms to arise?
Gonadal tumors -> in the ovary or testis
107
What is the most common type of germ cell tumor in children, and its most common type? What malformation is associated with that?
Teratoma
- > sacrococcygeal teratoma
- > associated with spinal defects like spina bifida / meningocele
108
What is the most common type of MALIGNANT germ cell tumor in children
Yolk sac tumor
109
What is the difference between mature and immature teratomas, what germ layers do they express, and are they ever malignant?
Mature - express adult somatic tissues
Immature - exist as differentiating embryonal / fetal tissues
- > both types will express all three germ layers
- > only immature teratomas in adults will be malignant
110
Identify the name for the germ cell neoplasms of the following structures, and say whether they are benign or malignant.
Germ cells of ovary
Germ cells of sperm
Primitive embryonic epithelium (i.e. outer cell mass)
yolk sac
placental tissue
```
Germ cells of ovary - dysgerminoma
Germ cells of sperm - seminoma
Primitive embryonic epithelium (i.e. outer cell mass) - embryonal carcinoma ("carcinoma" in children, but embryonic)
yolk sac - yolk sac tumor
placental tissue - choriocarcinoma
```
111
How can yolk sac tumor and choriocarcinoma be diagnosed via CSF or blood hormone secretion?
Yolk sac tumor - alpha-fetoprotein (produced by yolk sac / liver in early development, the fetal form of albumin)
Choriocarcinoma - human chorionic gonadotropin
112
What type of malignant tumors are referred to as small round blue cell tumors? What happens to your chances of getting them as you age?
Embryomas / Blastomas - comprised of primitive-appearing cells which resemble embryonic or fetal somatic tissues
As you age, progressively lower chance of getting them. (rare in adults)
113
What is the most common site for neuroblastoma and how is it diagnosed?
Adrenal medulla, diagnosed by urinary catecholamine breakdown products (VMA)
114
What type of tumor is Wilms tumor and where is it found? What tumor is associated with it?
It is an embryoma, found in kidney -> associated with Beckwith-Wiedemann syndrome, an 11p15 problem of overgrowth associated near Wilms tumor's 11p13
115
What is the most common site for medulloblastoma?
Cerebellum
116
What is the most common extracranial solid tumor in children and what is derived from?
Neuroblastoma (as previously described, a tumor of adrenal medulla identified by urinary VMA)
-> Derived from neural crest cells (sympathetic ganglia)
117
What is the definition of malformation?
Morphological defect of an organ or structure arising from an INTRINSICALLY abnormal developmental process
i.e. genetic abnormality, or single system-nongenetic malformation
118
What is the definition of deformation?
Morphological defect of an organ or structure arising from an EXTRINSICALLY abnormal developmental process
-> i.e. physical stress caused by mechanical forces, like oligohydramnios leading to the potter sequence
119
What is the definition of a disruption?
Breakdown or destruction of a tissue with was developmentally NORMAL, and then was disrupted
-> i.e. teratogens, radiation, infection, amniotic band formation which takes off your fingers
120
What is a major vs minor malformation?
Major - adverse effect on organ function / social function or acceptability, like congenital heart disease
Minor - configurational or consmetic, like clinodactyly (curved finger)
Normal variant - frequent malformation, without effect on function (like mongolian spot - birth mark)
121
How do amniotic bands cause a disruption?
Early rupture of amnion -> formation of fibrous connective tissue -> constriction / distortion of fetus
122
What is a sequence?
A cascade of events in development which may be explained by a single known primary malformation, disruption, or deformation (pathophysiological mechanism)
123
Give a brief description of the Potter sequence?
Oligohydramnios due to renal agenesis, amniotic leak, or other causes starts a sequence
- > fetal compression leads to flattened face, positioning defects of hand / feet, and breech position (unable to turn in utero)
- > pulmonary hypoplasia due to lack of amniotic fluid to drink for developing lung
124
What is a syndrome (in development)?
Multiple anomalies thought to be pathophysiologically related but cannot be explained on the basis of a single initating defect -> includes viral infection (i.e. rubella) or chromosomal abnormality (i.e. NF-1, with neurofibromas, cafe au lait spots, and lisch nodules)
125
How does an association differ from a syndrome?
Association - multiple anomalies which are STATISTICALLY related, but not known to share the same timing in embryology, or origin
126
Give an example of an association?
```
VATER
Vertebral anomalies
Anal atresia
Tracheo-
Esophageal fistula
Radial dysplasia / Renal abnormalities
```
127
What is a developmental field defect?
Multiple anomalies resulting from a single disturbed development of a morphogenic region of the embryo
-> i.e. caudal regression syndrome (agenesis of caudal axis, including bladder, anus, genitalia, and lower extremities)
128
What is agenesis vs aplasia?
Agenesis - complete absence of an organ AND its associated primordial precursor
Aplasia - failure of primordial precursor to develop into organ (with complete absence of that organ)
129
What does dysplasia mean in the context of a malformation?
A type of malformation - describes an abnormal organization of cells within a tissue
-> i.e. renal dysplasia, or achondroplasia
130
What causes the majority of congenital anomalies?
Unknown causes, followed by multifactorial.
Only about 5-10% are due to teratogens.
131
Define holoprosencephaly.
Lack of separation of cerebral hemispheres, a single ventricle, and fused basal ganglia.
132
What are the features of congenital rubella syndrome? When is the greatest hazard?
Triad of patent ductus arteriosis (congenital heart defects), cataracts, and deafness
- > think of roman aqueduct being open
- > babies with cataracts for eyes, and holding their ears
Like all congenital infections, earlier = worse, especially before 8 weeks
133
What is the most common fetal viral infection and its effects?
Intrauterine CMV
-> think of boy covering his ears with the brain helmet, as well as the cow in the corner with a liver. Milk is spilling on the ventricles of his helmet.
Causes Microcephaly, periventricular calcifications, sensorineural deafness, and hepatosplenomegaly
134
What major anomalies are caused by thalidomide?
Limb abnormalities
135
What are the features of fetal alcohol syndrome?
Growth retardation, microcephaly, atrial septal defect, and abnormal facial features (short palpebral fissues, smooth philtrum, micrognathia, maxillary hypoplasia)
136
Can radiation be teratogenic?
Yes, was often incurred when radiation was used to treat cervical cancer.
-> microcephaly, blindness, spina bifida, skull defects
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What explains the multifactorial pathogenesis of congenital dislocation of the hip?
Genetic: Shallow acetabular socket + laxity of ligaments
Environmental: Delivery in breech position with flexed hips
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When is the peak sensitivity for teratogenic insult?
4-5 weeks development (before this point, an insult is likely to cause spontaneous abortion, or cells will be totipotent enough to fully recover)
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What will teratogens tend to do in the fetal period?
More likely to cause growth retardation / injury to already formed organs
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What congenital anomalies are associated with uncontrolled maternal diabetes?
CNS - Holoprosencephaly, occipital encephalocele (bulging NTD in occipital region)
Heart - Transposition of great vessels, tetralogy of fallot, VSD/ASD
Other - Omphalocele, CAUDAL REGRESSION SYNDROME - very specific, renal anomalies
