repro week 5 Flashcards
1
Q
Topical or Percutaneous absorption in pediatric patients is
enhanced due to what 3 reasons?
A
- increased skin hydration
- thin stratum corneum
- The ratio of total body surface area-to-total body mass is highest in the youngest group, meaning the relative systemic exposure of topically applied drugs is higher in infants
2
Q
IV route from drug administration is commonly used in pediatric patients because intramuscular absorption is reduced from what reason?
A
Reduced blood flow to skeletal muscles and weak contraction in neonate
3
Q
pH of neonates stomach in the first 24 hours after birth
A
6-8 (basic)
4
Q
The pH of a neonates stomach 24-48 hours after birth
A
1-3 (acidic)
5
Q
In a pediatric patient, drugs that are weak bases in a basic environment (right after birth) exist in what form?
A
Non-ionized and can cross the plasma membrane
Easily absorbed
6
Q
Weakly acidic drugs in a basic environment (immediately after birth), will exist in what form?
A
Ionized form
Not Absorbed
7
Q
breast fed infants empty their stomach ________ as fast as formula fed infants
A
twice
Benefit: less drug absorption = less chance for toxicity
8
Q
Gastric motility is _________ in premeies. Important consideration in dosing due to _________ drug absorption
A
slower
increased
9
Q
Inhalation drugs in infants and older children through the pulmonary route has what major advantage?
A
Advantage – avoidance of systemic exposure
10
Q
At birth, what is immediately give via intramuscular route that takes advantage of the slow release and decreased clearance to allow for longer effects?
A
Vitamin K
11
Q
Infants have a __________ total body water and extracellular fluid than children or adolescents
A
higher
12
Q
Infants have a higher volume distribution on water soluble drugs, this means you have to do what to a neonates dose to achieve a therapeutic effect of a water soluble drug?
A
Increase the dose to achieve therapeutic serum concentration
e.i., Aminoglycosides (gentamicin and tobramycin)
13
Q
Lower amounts of adipose tissue in newborns (adipose peaks at 4-6 month) causes what effect to the volume distribution of fat soluble drugs?
The amount of body fat is SUBSTANTIALLY lower•Lower volume of distribution of fat-soluble drugs
A
The amount of body fat is SUBSTANTIALLY lower causes Lower volume of distribution of fat-soluble drugs
14
Q
Sulphonamides displaces bilirubin from its binding sites in infants and results in deposition in the brain causing what severe complication?
A
kernicterus - unconjugated (indirect) bilirubin accumulates in the brain
15
Q
Newborns and infants have ________ amounts of plasma proteins causing more free drugs available in the blood.
A
Lower
16
Q
In neonates, Vancomycin and phenobarbital may achieve higher concentration in CNS due to what main reason?
A
immature BBB.
17
Q
Phase I and II reactions are slower at birth in full-term infants
Preterm babies have _________ hepatic enzymes
Different timelines for different enzymes to mature
A
delayed
18
Q
What condition is associated with chloramphenicol administration in babies (used now as a “last resort” antibiotic b/c of various toxicities)
It is a rare but life-threatening condition in infant and premature babies where Uridine diphosphate-glycuronosyl transferase is not well developed. Due to the low GFR it cannot be eliminated causing an accumulation of toxic metabolite.
This syndrome usually begins 2–9 days (average of 4 days) after treatment is started.. Symptoms include vomiting, refusal to suck, irregular and rapid respiration, abdominal distention, periods of cyanosis, and passage of loose green stools occur within 24 hours. The children become severely ill by the end of the first day, and in the next 24 hours turn a color and become flaccid and hypothermic
A
Gray Baby Syndrome
19
Q
What drug causes mild inhibition of the cytochrome P450 CYP 2D6 enzyme?
Ultra rapid metabolizers (UMs) of this drug have at least three active copies of the CYP2D6 gene and present high metabolic capacity for CYP2D6 substrates (1% to 2% of the population in the US)
A
Diphenhydramine - Benadryl
20
Q
What rare condition arises in children and adolescents (2-16 years) and is a complication of influenza B, influenza A and herpesvirus varicella-zoster infections. It is thought to be caused by an acute noninflammatory brain swelling (encephalopathy) associated to the exposure of salicylates (aspirin) during a viral illness has been demonstrated
A
Reye Syndrome
21
Q
Newborns have a much lower capacity to excrete drugs due to what?
A
Newborns have much lower GFR
22
Q
Infants have a __________ half life of renal excreted drugs compared to adults?
A
Increased half life - need to administer in intervals to prevent drug accumulation
23
Q
What are the 3 components of pediatric dosing?
A
Age (mg/kg/day or mcg/kg/dose)
Weight
Surface area
Weight-based dosing in children with BMI> 31 may have suboptimal effects
24
Q
Scaling adult doses based on body weight or surface area does not account for what, that affects drug disposition or tissue/organ sensitivity.
A
developmental changes
25
Pediatric patients with what rare condition may require higher doses by weight and more frequent dosing interval due to the higher clearance of drugs such as gentamicin, tobramycin, etc..
**Cystic Fibrosis**
25
Pediatric patients with what rare condition may require higher doses by weight and more frequent dosing interval due to the higher clearance of drugs such as gentamicin, tobramycin, etc..
**Cystic Fibrosis**
26
Are over-the-counter cough and cold products effective and safe in young children?
“Not recommended for children below age 4 years”
Their efficacy and safety in children have not been documented
27
What do all of these drugs have in common when ingested by a pediatric patient?
Calcium channel blockers **(Nifedipine)**
**Tricyclic antidepressants (TCAs)**- have anticholinergic side effects, potent NE reuptake inhibitor (**Amitriptyline)**
**Clonidine**, guanfacine, Guanabenz
**Opiates (Fentanyl)**
Antifreeze
Alcohols
**Sulfonylureas** (Glipizide, **glyburide**)
Hydrocarbons
1 dose is enough to cause a toxic effect = emergency
28
A pediatric patient ingested a centrally acting α2-adrenergic agonist (clonidine, imidazolines) and is experiencing CNS depression, respiratory depression, bradycardia and hypotension. What is the antidote to clinically intervene?
**Naloxone - opiod antagonoist (binds and blocks opiod receptors)**
IV fluid resuscitation or **atropine** (bradycardia)
IV fluid resuscitation (hypotension)
Vasopressors (if needed)
29
A pediatric patient has ingested tricyclic antidepressants (amitriptyline, imipramine) and is experiencing a sudden onset of coma, convulsions, hypotension and dysrhythmias. What is the antidote to clinically intervene?
**Benzodiazepine - lorazepam (seizures)**
**Sodium bicarbonate** (alkalinization of urine)
30
A pediatric patient has ingested opioids and is experiencing respiratory depression, coma, urinary retention, ↑oropharyngeal secretions. What antidote is used clinically to treat this condition?
Naloxone - treats the respiratory depression
31
A pediatric patient has ingested a calcium channel blocker (Nifedipine), causing bradycardia and severe hypotension. What is used clinically as the antidote?
**IV fluid resuscitation**- treats hypotension
**atropine** - treats bradycardia
32
A pediatric patient is admitted for ingesting sulfonylureas (glyburide), and is suffering from severe hypoglycemic symptoms – altered mental status, seizure or coma. What is the clinical antidote used to treat this patient?
**IV dextrose**, monitor blood sugar
33
Acetaminophen is metabolized in the liver. A small percentage goes through the pathway that leads to the toxic metabolite. In overdose the supply of **glutathione reduced**, and this metabolite binds covalently to liver cells to induce necrosis. A pediatric patient has ingested this drug, what is the clinical intervention?
**Acetyl cysteine**
* replenishes glutathione stores
can be given orally or IV. Acetyl cysteine is most effective when given within 8 hours after ingestion. It is also effective when given more than 24 hours after ingestion.
34
Would an infant have any hepatic side effects from taking acetaminophen?
No, infants do not have mature Cyp enzymes, thus only having the sulfate pathway to break down acetaminophen. There is no production of toxic metabolite or depletions of glutathione stores, rendering it less toxic to infants
35
What is the reactive metabolite produced by the Cyp2E1 enzyme breaking down acetaminophen?
N-acetyl-p-benzoquinoneimine (NAPQI)
takes electrons from gllutathione
36
A pediatric patient has ingested antifreeze (ethylene glycol), and is experiencing •nausea, vomiting, convulsions, stupor (decreased level of alertness), and metabolic acidosis. What is used to treat this condition?
Fomepizole
MOA: competitive inhibitor of alcohol dehydrogenase
The slower rate of metabolite production (Acetaldehyde) allows the liver to process and excrete the metabolites as they are produced, limiting the accumulation in tissues.
Primary treatment is to block the enzyme alcohol dehydrogenase which converts ethylene glycol to toxic metabolites
**Ethanol** can be given but can lead to CNS depression and hypoglycemia in children
Hemodialysis is indicated for higher concentrations and persistent metabolic acidosis or end organ toxicity
37
What is Fomepizole MOA and when is it used clinically?
competitive inhibitor of alcohol dehydrogenase
used to prevent toxic metabolite formation if ethylene glycol is ingested
38
**kernicterus** is caused by the entry of bilirubin into the brain, causing yellow discoloration of brain tissue, seizures, and death.
Kernicterus is a condition only seen in young children that results from high concentrations of free bilirubin in the plasma.
It occurs because infants have a l**ack of what critical hepatic enzyme**, and therefore, less ability to glucuronidate bilirubin?
Infants also have immature blood-brain barriers, which allow more of the free bilirubin to cross into and damage the brain.
**glucuronosyl transferase**
39
Patient presents with foamy white patches on eyes causing irreversible blindness (keratomalacia xerophthalmia), growth deficiency and dry scaly patches on skin from follicular hyperkeratosis. What is this patient deficient in?
Vitamin A
40
To prevent rickets and tenany, what supplement can be added to infants diet at 1 month?
Vitamin D
41
What is the term for antibodies produced in breast milk in late pregnancy and the first few days post birth, that work to protect the newborn?
Colostrum
42
A deficiency in what could cause RBC hemolysis, muscle weakness, hyporeflexia and ataxia?
Vitamin E deficiency
43
A deficiency in what vitamin could impose a significant risk of hemorrhage and is responsible for the synthesis of coagulation factors II, VII, IX, and X
Vitamin K
44
Patient presents with hypoglycemia, high uric acid levels, high amount of fat in the blood and a significant amount of lactic acid build up. What inborn error of metabolism could cause this presentation?
Vonn Gierkes Disease
45
in Von Gierkes Disease, what enzyme is deficient?
*Glucose-6-phosphatase*
46
Pompe glycogen storage deceases results in the deficiency in what enzyme causing the accumulation of glycogen in lysosomes?
*Lysosomal a1 -→ 4 & a1 -→ 6 glucosidase* deficiency
47
What inborn error of metabolism presents with fasting hypoglycemia, hepatomegaly in infants, accumulation of characteristic branched polysaccharide (limit dextrin); muscle weakness?
Cori's - defect in glycogen deb ranching enzyme
48
what inborn error of metabolism causes poor exercise tolerance, muscle glycogen is abnormally high, blood lactate very low after exercise?
**McArdle (Type V) glycogen storage disease**
_Enzyme:_ *muscle phosphorylase* deficiency
49
What enzyme is deficient in Phenylketonuria?
*phenylalanine hydroxylase* deficiency
50
A mutation in what gene can also be a cause of PKU due to a cofactor deficiency?
BH4
51
A patient with a BH4 deficiency with PKU will have low what levels in their urine?
Pterin
52
What would be the least effective treatment of a cofactor deficiency induced PKU?
Avoidance of dietary phenylalaine
53
A mother does NOT have PKU, but her fetus does. Does the mother need to adhere to a special diet until delivery? What about can she breast feed?
No special diet in pregnancy
Absolutely NO breast feeding
54
A mother has PKU, what kind of diet does she need to maintain during pregnancy and after birth?
Low phenylalanine
55
What is the classical form of malnutrition with inadequate intake of BOTH proteins and calories
Marasmus
56
A malnourished child who will have a deceptively plump appearance from adequate caloric intake but inadequate protein in their diet has what condition?
Kwashiorkor
57
The main difference from marasmus is that the high carbohydrate intake in kwashiorkor **stimulates ________ secretion**, which interferes with the adaptation to starvation.
insulin
58
Patient presents with increased orotic acid in blood and urine, Decreased BUN, Hyperammonemia, Vomiting, lethargy, cerebral edema, slurred speech, blurred vision, flapping hand tremor. What is a urea cycle deficient enzyme that could cause this?
**Ornithine Transcarbamylase Deficiency**
* X-linked recessive deficiency in I
* Enzyme that converts ornithine to citrulline in the urea cycle
* More common in males
* Evident in the first few days of life
59
What given to people with urea cycle disorders?
alpha - keto acids
60
Patient presents with vomiting, lethargy, jaundice, and hepatosplenomegaly upon eating fructose or sucrose. Children display self-correcting behaviors like only eating the apple peel but not the apple. What enzyme is deficient?
**Fructose intolerance**
_Enzyme:_ *Aldolase B* deficiency
_Reaction:_ fructose-1- phosphate DHAP + glyceraldehyde
61
Patient presents with no clinical symptoms, but has extremely high fructose level in urine. What enzyme is deficient in this disease?
**Essential fructosuria**
_Enzyme:_ *fructokinase* deficiency
_Reaction:_ Fructose + ATP fructose-1- phosphate
62
Patient presents with cupping, fraying joints, rachitic rosary and widen wrists. Increased alkaline phosphatase and PTH with a decrease in calcium and phosphate. What is the diagnosis?
Vitamin D deficiency
63
What nutrient plays a role in collagen synthesis, NE synthesis and when deficient can cause bleeding gums, skin lesions, periodontal decease and corkscrew hairs?
Vitamin C deficiency - scurvy
64
Breast milk is high in IgA, vitamin A, C, & E, and what type of protein?
Whey
65
In familial hypercholesterolemia, the over production of what molecule causes decreased recycling of the LDL receptor and increases blood plasma levels of LDL?
PCSK9
66
What autosomal dominant inborn error of metabolism can cause xanthomas on the elbows, ankles, knees and eyelids and increase risk for CVD?
Famililai hypercholesterolemia
67
What is used to treated familial hypercholesterolemia?
Statins - HMG Co-A reductase inhibitor
68
What inborn error of metabolism is a glycogen debrachning enzyme defect, causing large hepatic glycogen stores causing hepatomegaly, hypotonia (floppy baby), HYPOglycemia and cardiomyopathy?
Cori's Disease - treat with frequent high protein meals
69
What inborn error of metabolism is caused by a defect in phosphorylase (no glucose 1 phosphate produced) and only affecting muscle tissue?
McArdles (Hers) disease
70
A defect in cystathionine B-synthase is a disorder of trans-sulfuration and causes what disease?
Homocystinuria - homocysteine builds up
71
Patient presents with displacement of the lens, intellectual disabilities, marfanoid habits and osteoporosis. What is the inborn error of metabolism?
Homocystinuria
72
What are the two classes of lysosomal storage diseases?
Sphingolipidoses and mucopolysaccharidoses
73
What is a common symptom seen in the eyes from all sphingolipidoses?
Cherry red spots in eyes due to accumulation of gylcolipids in lysosome
74
What disease has the enzyme deficiency in hexosaminidase A, converting GM2 to GM3 and causes cognitive impairment, blindness, muscular weakness and cherry red spots in eyes?
Tay-sachs disease - shipngolipidosis
75
What disease has a defect in B-glucosidase (converting glucocerebroside to ceramide) and causes enlarged liver and spleen, erosion of long bones, cognitive impairment, cherry red spots in eyes and is the most common shipngolipidosis?
Gaucher's disease - shipngolipidosis
76
What disease has a defect in a-galactosidase, is X-linked mainly affecting males and causes a skin rash, kidney failure and cherry red spots in eyes?
Fabry's - shipngolipidosis
77
What disease is fatal in early life from a defect in sphinomyelinase causing a build up of glycolipids in the brain, enlarged liver and spleen and has potential for replacement therapy? Type A most severe and seen with cherry red spots in eyes
Niemann-pick disease - shipngolipidosis
78
What two glycosaminoglycans accumulate in the lysosome and present in the urine when their is a defect in their breakdown from a mucopolysaccharidoses lysosomal storage disorder?
Dermatan Sulfate and Heparin sulfate
79
What is the structure between the left and right frontal bones, that can remain unfused into adulthood, but is normally obliterated by one year old?
Metopic suture
80
What is the term for premature closing of sutures in infants head?
craniosynostosis
81
What is the most common craniosynostosis in infants where the sagittal suture fuses too early and the head becomes narrow extending anteroposteriorly?
scaphocephaly
82
What is the term for the craniosynostosis where there is early fusion of the coronal sutures on both sides and the head widens growing transversely?
Brachycephaly
83
What is the term for the craniosynostosis where there is early fusion of the coronal sutures on ONE side and the head widens growing transversely causing asymmetry?
anterior plagiocephaly
84
What is the term for the craniosynostosis where there is early fusion of the metric suture which results in a prominent ridge (triangular bump) on the infants head? This can effect the orbit shape disrupting vision.
Trigonocephaly - (Tri = triangle shaped head)
85
Teeth erupt in a standard sequence, a delay in tooth development can be seen in what genetic condition?
Down syndrome
86
What condition of preterm infants is caused by multifactorial array of pathogens invading the intestinal wall leading to inflammation and necrosis? This only occurs postnatally, thus not seen in still births and is the 2nd most common cause of morbidity in preterm infants.
Necrotizing Enterocolitis
87
What developmental problem in premature infants is caused by a lack of surfactant in the lungs causing alveoli to collapse and is the MOST common cause of death in the first month of life?
Infant Respiratory Distress Syndrome
88
What is seen in premature infants where the capillaries around the ventricles rupture and the blood enters the CSF system?
Intraventricular hemorrhage
89
What can be seen in premature infants causing leukocoria from the mature blood vessels unable to supply the retina? (can resolve on own)
Retinopathy of prematurity
90
What is the most common anomaly of the alimentary tract (congenital problem of the ilium), more common in men and can mimic appendicitis if becomes inflamed?
Meckel's Diverticulum
91
What affects infants and is the absence of autonomic ganglion cells in the myenteric plexus due to failure of neural crest cell migration in the 5th to 7th week of development?
Hirschsprung Disease (Congenital Megacolon)
92
What class of congenital abnormalities of the heart are more severe, less common, are right to left shunts and include the 5 T's?
Cyanotic - less blood to the lungs
93
What congenital cyanotic abnormality of the heart causes four abnormalities that arise from the displacement of the ventricular septum at the infundibulum (where the right ventricle leads into the pulmonary artery)?
Tetralogy of Fallot
94
What is the most common cyanosis of the neonatal period where the aorta originates from the right ventricle and the pulmonary artery form the left ventricle? What therapy can be used to help keep child alive until surgical intervention?
Transposition of the great arteries
* keep ductus arterosus open with prostaglandins
95
What disease causes a decrease in Galactokinase, mild form and can cause early cataract formation from build up of galactitol?
Type II galactosemia
96
Galactose 1-phosphate uridyl transferase enzyme helps convert Galactose - phosphate to glucose -1-phosphate using what type of intermediate?
UDP-glucose intermediate
97
What does the defect in Galactose -1-phosphate uridyl transferase cause?
Type I galactosemia \*most severe due to the buildup of galactose-1-p
98
A defect in what enzyme would cause hepatoegaly, jaundice, early cataract formation, lethargy, nausea, vomitting, diarrhea and poor feeding? Would also see and increase in creatine, urea and galactose levels in the blood.
Galactose -1-phosphate uridyl transferase (galactosemia type I)
99
Type III galactosemia is caused by a defect in what enzyme causing a phenotypically similar disease to type I?
UDP-galactose epimerase
100
Lead inhibits what two enzymes in heme synthesis?
delta-ALA dehydratase & ferrochelatase
101
Lead poisoning inhibits rRNA degradation inside RBCs causing what presentation on a peripheral blood smear showing purple spots in RBC?
basophilic stippling of erythrocytes
102
A patient has an elevated reticulocyte count (immature RBCs), Hypochromatic, microcytic RBCs and nucleated RBCs. Symptoms include anemia, constipation, demylimnation, encephalopathy, foot drop, growth retardation and hypertension. What is the most likely diagnosis?
Lead poisoning
103
Children exposed to high levels of lead are at risk for what?
Stunted growth, neurotoxicity and ADHD
104
What is a classic presentation of lead poisoning found on the gums of the teeth?
Burton lines - blue lines on gums
105
What treatment is used for children with lead toxicity blood lead levels over 70?
intravenous loading dose of **dimercaprol**.
After 4 hours, intravenous treatment with dimercaprol plus **CaNa2 EDTA** is begun.
106
What treatment is used for adults with lead poisoning BLL between 45-69?
Oral Succimer
107
What drug is more toxic and is less potent and selective for chelation of heavy metals (lead)relative to other available chelation drugs. It is therefore not a first-line treatment for acute intoxication with lead, mercury, or arsenic.
[Penicillamine](https://accessmedicine-mhmedical-com.cmich.idm.oclc.org/drugs.aspx?GbosID=423134)
108
What two chelating agents can cross the BBB and what one cannot?
Succimer and Dimercaprol can cross BBB
EDTA cannot cross BBB
109
When giving a chelating agent, what needs to be monitored closely and why?
GFR - high BLL can cause proximal tubular nephopathy and glomerulosclerosis, decreasing GFR, raising BP
110
What substance in monitored when assessing a patients with lead poisonings GFR undergoing chelation therapy?
Creatine
111
Milestones are important in assessing the development of the neuromuscular system and the meylienation process. When does myelination occur?
36th week gestation to 3 years old
112
What process beings at the 20th week gestation and remains until puberty (peaks at 6 months) and is involved in pruning (very critical for language development)
synaptogenesis
113
what anatomical terms are used to describe the direction of myelination in the CNS\>
cephalocaudal and proximodistal
114
Primitive reflexes are mediated by what area of the brain and an abnormality would indicate what?
brainstem and abnormality in neuromuscular system if absent or asymmetric
115
A child who has recurrence of primitive reflexes post 6 months is indicative of what condition?
Brain damage
116
What primitive reflex is triggered by the passive turning of the infants head to one side and the extension of arm and leg on same side and flexion of arm and leg on the opposite side?
Asymmetric tonic neck reflex
117
What primitive reflex is also known as the startle reflex where an infants head is gently lifted off the table and when released the infants arms raising into the air (abducts arms) and should disappear at 4 months
Moro reflex
118
What substance is produced by fat cells and needed to induce the pulsatile release of GnRH for the onset of puberty?
Leptin
119
A patient presents with a webbed neck, hashimotos, horse shoe kidney and a heart defect in the bicuspid aortic valve, what is the likely diagnosis?
Turners 45 X0
120
Why is a karyotype preferred when testing for Turners syndrome over a bar body test?
Turners patients do NOT have Barr body because they only have 1 X chromosome
A karyotype would test many cells types and Turner syndrome can be mosaic
121
A 17 year old female comes to her doctor with primary amenorrhea. Upon examination she has a vagina that ends in a blind pouch, has no uterus, little body hair and elevated levels of testosterone and DHT. What is the likely cause of these symptoms?
Complete Androgen Insensitivity Syndrome - this patient is actually XY male with undecsendend testes
122
A phenotypical female at puberty age begins to notice rapid onset of masculaization, increase in testosterone levels, growth of male external genitalia that was once ambiguous. What is the likely diagnosis
5-a-reductase deficiency
* cannot convert testosterone to DHT (caused not external male genitalia at birth) - common in Dominican Republic called Guevedoces
123
Males with 5-a-reductase deficiency have an increased risk of what type of cancer due to what complication?
Increased risk of testicular germ cell tumors from chryporchadism
124
What drug is used to treat anxiety but can cause light headed, dizziness, headache and tiredness?
Alprazo - Benzodiazepine (Xanax)
125
What SSRI can be used in pediatric patients to treat depression and has anxiety as a side effect by inhibiting the Cyp2D6 enzyme and 5HT metabolism?
Fluoxetine (prozac)
126
Escritalopram (Lexapro) is considered to be what class of drug and what medication is preferred to treat pediatric depression due to its longer half life?
SSRI and Fluoxetine has a longer ½ life
127
What is a potential therapy for androgen receptor driven cancers that prevents receptor from being degraded and can prevent unregulated cell growth?
HSP90 inhibitor
128
HSP90 is what type of protein that provides cell cycles control, cell survival and a role in other signaling pathways
ubiquitous molecular chaperone
129
What is the most common tumor of the adrenal medulla in **children,** usually \< 4 years old. Originates from **n**eural crest cells an occurs anywhere along the sympathetic chain?
Neuroblastoma
130
What endocrine tumor has the most common presentation of abdominal distension and a firm, irregular mass that can cross the midline (vs Wilms tumor, which is smooth and unilateral). Less likely to develop hypertension than with pheochromocytoma (**n**euroblastoma is **n**ormotensive). Can also present with opsoclonus-myoclonus syndrome (“dancing eyes-dancing feet”).
increased HVA and VMA (catecholamine metabolites) in urine. Homer-Wright rosettes (neuroblasts surrounding a central lumen) characteristic of this tumor is Bombesin and **N**SE ⊕. Associated with amplification of **N**-*myc* oncogene.
Neuroblastoma
131
What is another name for a nephroblastoma?
Wilms tumor
132
What is the most common renal malignancy of early childhood (ages 2–4)? Contains embryonic glomerular structures. Most often present with large, palpable, unilateral flank mass and/or hematuria and possible HTN.
## Footnote
Can be associated with loss-of-function mutations of tumor suppressor genes *WT1* or *WT2* on chromosome 11.
May also be a part of several syndromes - but more commonly sporadic.
Wilms tumor (nephroblastoma)
133
What syndrome is associated with **W**ilms tumor, **A**niridia (absence of iris from *PAX6* deletion), **G**enitourinary malformations, **R**ange of developmental delays (*WT1* deletion)
WAGR Complex
134
What syndrome is associated with 90% of Wilms tumor, **D**iffuse mesangial sclerosis (early-onset nephrotic syndrome), **D**ysgenesis of gonads (male pseudohermaphroditism), *WT1* mutation?
**D**enys-**D**rash syndrome
135
What syndrome is associated with **W**ilms tumor, macroglossia, organomegaly, hemihyperplasia, adrenal cytomegaly (***W****T2* mutation), omphalocele (abdominal wall defect) and is caused by a loss of imprinting control
Beckwith-**W**iedemann syndrome
136
What is the term for a group of blastema cells (undifferentiated cells) resting outside of the kidneys on the periphery? these are immature cells - not actual tumor cells, but if seen on both sides of kidneys can be indicative of early Wilms defect in WT1
Nephrogenic rests
137
What disease is associated …
**H**emangioblastomas (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum, spin; **A**ngiomatosis; bilateral **R**enal cell carcinomas; **P**heochromocytomas.
Numerous tumors, benign and malignant. **HARP**.
**VHL** = **3** letters = chromosome **3**; associated with RCC (also 3 letters).
**Von Hippel-Lindau disease**
**AD. Deletion of** ***VHL*** **gene on chromosome 3p. pVHL ubiquitinates hypoxia- inducible factor 1a.**
138
What disease is most often cerebellar **G**. Associated with von Hippel-Lindau syndrome when found with retinal angiomas. Can produce erythropoietin 2° polycythemia. Characteristic **bundle of grape**s appearance and **foamy stromal** cells histologically
**Hemangioblastoma**
139
What is the likely diagnosis for a tumor of the adrenal gland that secretes BOTH NE and E that arise from neuroendocrine chromaffin cells (paraganglionic neural crest cells)? Can cause systemic symptoms like sweating, hypertension and an increased HR?
Pheochromocytoma
* not to be confused with neuroblastoma that can only produce NE and raised from sympathetic ganglia anywhere on the sympathetic chain
