Chapter 10--Diseases of Infancy and Childhood Flashcards
(187 cards)
1
Q
A morphologic defect present at birth
A
Congenital anomaly
2
Q
What % of fertilization are so anomalous that they never develop into a viable conceptus?
A
20%
3
Q
Complete absence of an organ and its associated primordium
A
Agenesis
4
Q
Absence of an organ due to failure of the developmental anlage
A
Aplasia
5
Q
Absence of an opening usually of a hollow visceral organ
A
Atresia
6
Q
In the context of malformation, refers to abnormal cellular organization
A
Dysplasia
7
Q
Enlargement of an organ associated with increased number in cells
A
Hyperplasia
8
Q
Underdevelopment of an organ with decreased number of cells
A
Hypoplasia
9
Q
Decreased organ size due to decreased cell size
A
Hypotrophy
10
Q
Intrinsic disturbances in morphogenesis; typically multifactorial and not caused by single genetic defect
A
Malformation
11
Q
Extrinsic disturbances in morphogenesis causing a secondary destruction of a previously developmentally normal tissue; NOT heritable!
A
Disruptions
12
Q
Example of disruption
A
Amniotic band resulting from an amniotic rupture that causes fibrous stranding that encircles, compresses or attaches to a developing body part
13
Q
Result from an external disturbance in morphogenesis. Caused by localized or generalized compression by abnomal mechanical forces and they manifest as abnormalities in shape, form or position (club feet)
A
Deformations
14
Q
Most common underlying factor in deformations
A
Uterine constraint; first pregnancy, small uterus, leiomyomas
15
Q
Constellation of anomalies resulting from one initiating aberration that leads to multiple secondary effects
A
Sequence
16
Q
Classical example of a sequence
A
Potter sequence
17
Q
What happens in potter sequence?
A
Oligohydramnios–decreased amniotic fluid–causes fetal compression with facial flattening, hand and foot malpositioning, hip dislocation, and chest compression with Hypoplasia
18
Q
Combination of anomalies that cannot be explained on the basis of one initiating aberration and a subsequent cascade.
A
Syndrome
Most syndromes are caused by a single pathology that simultaneously affects several tissues (viral infection or chromosomal abnormality)
19
Q
3 causes of developmental anomalies
A
Genetic causes
Environmental causes
Multifactorial causes
20
Q
2 genetic causes of developmental anomalies
A
Chromosomal abnormalities
Single gene mutations
21
Q
5 examples of chromosomal abnormalities that cause developmental anomalies?
A
Trisomy 21 (Down Syndrome) Klinefelter Syndrome (47 XXY) Turner Syndrome (XO) Trisomy 13 (Patau syndrome) Trisomy 18 (Edwards syndrome)
22
Q
How do single gene mutations cause developmental anomalies?
A
Loss of function genes that drive organogenesis or development; hedgehog genes
23
Q
5 examples of environmental causes of developmental anomalies
A
Viruses Drugs and chemicals Alcohol Radiation Maternal diabetes
24
Q
Most common fetal viral infection? What does it result in?
A
Cytomegalovirus–mental retardation, microcephalic, deafness
25
What trimester is the highest risk period for cytomegalovirus infection?
Second trimester
26
What is congenital rubella syndrome?
A rubella infection (German measles/3 day measles) occurring before 16 weeks of gestation that can result in tetras of defects: cataracts heart defects deafness mental retardation
27
An agent or factor that causes a malformation in an embryo?
Teratogen
28
Examples of drugs and chemicals that act as environmental causes of developmental anomalies (5 examples)
```
Thalidomide
Folate antagonists
Androgenic hormones
Anticonvulsants
13-CIS-retinoic acid
```
29
Most widely used Teratogen?
Alcohol
30
Structural anomalies, cognitive and behavioral deficits related to alcohol use in mother
Fetal alcohol spectrum disorders
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Classic teratogenic phenotype that describes infants most severe affected by fetal alcohol spectrum disorders
Fetal alcohol syndrome
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Teratogenic phenotype of fetal alcohol syndrome
```
Growth retardation
Microcephaly
Atrial septal defects
Short palpebral fissures (elliptic space bw medial and lateral can't hi of the two open eye lids)
Maxillary Hypoplasia
```
33
Large fetus caused by maternal diabetes is called?
Fetal macrosomia
34
Series of malformations occurring with maternal diabetes; hyperinsulinemia resulting in increased body fat, muscle mass and organometallic, cardiac anomalies neural tube defects and other CNS malformations
Fetal macrosomia
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Interaction of environmental factors with mutated genes; independently they may have no or minimal effect
Multifactorial causes of developmental anomalies
36
Two examples of multifactorial causes of developmental anomalies
Congenital hip dislocation--shallow Acetabular socket (genetics) and a breech delivery (environment)
Neural tube defects--genetic predisposition (genetic) and low maternal folate (environmental)
37
Importance of timing and teratogenic insult
Timing of any teratogenic insult influences the nature and incidence of the anomaly produced--a given agent can have a significantly different outcome depending on when it is encountered
38
Embryonic period of development
First 8 weeks after fertilization
39
Teratogenic influence of the early (first 3 weeks) of the embryonic period
Either kills, so many cells die causing spontaneous abortion or limited numbers of cells are affected such that the fetus can recover without consequence
40
Fetal period of development
Weeks 9-36
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Sensitivity to teratogens during the fetal period
Greatly reduced to teratogenic agents; the fetus is still susceptible to growth retardation
42
Do teratogens and genetic defects typically act on the same developmental pathways?
They can/do and will result in similar anomalies. Example: valproate embropathy--valproic acid (an anti-seizure medication) is teratogenic and disrupts the homeobox transcription factors. Homeobox gene mutations give rise to the same congenital anomalies
43
Most common cause of neonatal mortality
Congenital anomalies
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Second most common cause of neonatal mortality
Prematurity
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When does the greatest mortality of childhood occur?
In the first year and then declines progressively
46
When is a baby considered preterm?
Birth before 37
47
Birth before 42 weeks
POST-term
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What are appropriate age and weight for gestation?
Between 10th and 90th percentile; below 10=small and above 90 is large
49
What are the major risk factors for prematurity? (4)
Preterm premature rupture of the placental membranes (PPROM)
Intrauterine infection
Uterine, cervical and placental structural abnormalities
Multiple gestational
50
What is PPROM?
Preterm premature rupture of the placental membrane
51
What is the most common cause of prematurity?
Preterm premature rupture of the placental membranes
52
What is the pathophysiology of PPROM?
Placental inflammation and matrix metalloproteinase activation
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What is choroioamnionitis?
Inflammation of the placental membrane
54
What is funisitis?
Inflammation of the umbilical cord
55
Organisms associated with intrauterine infection and prematurity
```
Urea plasma urealyticum
Mycoplasma hominids
Gardnerella vaginalis
Trichomonas
Gonorrhoea
Chlamydia
```
56
What are the 3 categories of causes for fetal growth restriction/intrauterine growth retardation?
Fetal
Placental
Maternal
57
Fetal causes of fetal growth restriction/intrauterine growth retardation
Despite adequate maternal nutritional supply, there is compromised fetal growth potential; typically there is symmetric growth restriction--all organ systems are proportionally affected
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What are 3 fetal causes of fetal growth restriction/intrauterine growth retardation?
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Chromosomal abnormalities (trisomies)
Congenital anomalies
Congenital infections (TORCH)
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59
What does TORCH stand for?
```
Toxoplasmosis
Other
Rubella
Cytomegalovirus
Herpes virus
```
60
Placental causes of fetal growth restriction/intrauterine growth retardation
Vigorous fetal growth in the 3rd trimester demands adequate placental growth and development; defects in placental supply typically cause asymmetric growth retardation, with relative sparing of the brain
61
What are 7 placental causes of fetal growth restriction/intrauterine growth retardation?
1. Umbilical-placental vascular anomalies
2. Placental abrupt ion-placenta separates from uterus
3. Placenta Previn (low lying placenta)
4. Placental thrombosis and infarction
5. Placental infections
6. Multiple gestations
7. Placental mosaicism
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What is placental mosaicism?
Genetic mutations arising after zygote formation lead to two genetic populations of cells within the placenta and/or fetus
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What kind of fetal growth restriction/intrauterine growth retardation causes is the most common?
Maternal
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What do maternal causes of fetal growth restriction/intrauterine growth retardation result in?
Decreased placental blood supply
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What are the 7 maternal causes of fetal growth restriction/intrauterine growth retardation?
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Preeclampsia--high blood pressure and protein in urine
Hypertension
Inherited thrombophilias
Malnutrition
Narcotic or alcohol
Intake
Cigarette smoking
Certain drugs (teratogens)
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66
5 risks associated with prematurity? What complications are associated with prematurity?
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Hyaline membrane disease (neonatal respiratory distress syndrome)
Necrotizing enterocolitis
Sepsis
Intravenricular hemorrhage
Long term complications
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67
Causes of neonatal respiratory distress?
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Respiratory distress syndrome
Maternal sedation
Blood or fluid aspiration
Fetal head injury
Umbilical cord around neck
```
68
Most common cause of neonatal respiratory distress?
Respiratory distress syndrome (also known as hyaline membrane disease)
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Incidence of neonatal RDS is 60% in infants born before 28 weeks of gestation and less than 5% of infants born after how many weeks gestation?
37 weeks
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Key feature of respiratory distress syndrome
Inadequate pulmonary surfactant
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Cell type that makes surfactant
Type II pneumocytes
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Surfactant production by type II pneumocytes is highest at what week of gestation?
30? 35??
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What is surfactant made of?
Phospholipids and glycoproteins
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Decreased surfactant results in ___ alveolar surface tension, progressive alveolar _____ and increasing inspiratory pressures required to expand the ____
Increased
Atelectasis
Lung alveoli
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RDS is associated with what damaging effects?
```
Acidosis
Pulmonary vasoconstriction
Pulmonary hypoperfusion
Capillary endothelial and Alvolar epithelial damage
Plasma leakage into alveoli
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76
In neonatal RDS plasma proteins leak into the alveoli and combine with fibrin and necrotic Alvolar pneumocytes to form ____ that further impede gas exchange
Hyaline membrane
77
How do corticosteroids reduce neonatal respiratory distress syndrome?
Induce surfactant lipid and apoprotein production
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Grossly what is seen in lungs of a neonatal RDS patient?
Lungs are solid, airless and reddish purple
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What can you see microscopically in patients with neonatal RDS?
Alveoli poorly developed and frequently collapsed; protein acess membranes line respiratory bronchioles, alveolar ducts and random alveoli
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Lung maturity in neonatal respiratory distress syndrome directly reflects the synthesis of what?
Surfactant synthesis
81
What aspect of the amniotic fluid is measurable and reflects lung maturity in neonatal respiratory distress syndrome (surfactant synthesis?)
Lecithin/sphingomyelin ratio
82
Necrotizing enterocolitis occurs most commonly in?
Premature infants; it is inversely proportional to gestational age
83
What predisposing conditions can lead to necrotizing enterocolitis?
Bacterial colonization
| Enteral feeding
84
Etiology and perinatal mortality rate of NEC
Induction of inflammatory mediators in bowel (platelet activating factor production) promotes enerocyte apoptosis and increased intercellular permeability. This augments trans mural bacterial migration with a viscous cycle of inflammation and mucosal necrosis. Perinatal mortality is high
85
NEC typically involves what areas of the bowel?
Terminal ileum, cecum, and right colon
86
Microscopically what is seen in NEC
Mucosal to trans mural coagulative necrosis, ulceration, bacterial colonization and submucosal gas bubbles
87
How are perinatal infections usually acquired?
Transcervically or transplacentally
88
Transcervical route of perinatal infection
Ascending infection up and through the cervix
89
Transplacentally route of perinatal infection
Transferred to fetus from mother through placenta; hematologic
90
Most bacterial and a few viral perinatal infections occur via the ____ route
Cervicovaginal; transcervical (ascending route)
91
How does the fetus usually become infected in a transcervical (ascending) infection?
Inhaling infected amniotic fluid into lungs during parturition, it passes through an infected birth canal
92
If there is a transcervical (ascending) infection, what diseases will also be present? What often is the result of a transcervical ascending infection
Choroioamnitis and funisitis
| Preterm birth
93
Most common sequelae of a transcervical (ascending) infection
Preterm birth
94
What are the most common sequelae of a transcervical (ascending) infection
Pneumonia, sepsis, and meningitis
95
How do most transplacental (hematologic) infections enter the fetal bloodstream?
Via the chorionic villi
96
Sequelae of transplacental (hematologic) infection are commonly the same regardless of when it occurs. T/F?
False--depends highly on the timing and the organism
97
Do all TORCH infections have similar manifestations?
Yes
98
Manifestations of TORCH infections
```
Fever
Encephalitis
Chorioetnitis
Hepatosplenomegaly
Pneumonitis
Myocarditis
Hemolytic anemia
Skin lesions (vesicular hemorrhagic)
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99
Long term sequela of TORCH infection
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Growth retardation
Mental retardation
Cataracts
Congenital cardiac anomalies
Bone defects
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100
Early-onset (during the first 7 days of life) sepsis is most commonly due to _______, acquired at or shortly before birth
Group B streptococcus
101
Late-onset (up to 3 months) sepsis is often due to _____ or _____
Listeria, candida
102
What is fetal hydrops?
Fetal edema fluid collection during intrauterine growth
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Severe and generalized fluid collection in fetus is referred to as what?
Hydrops fetalis
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Postnuchal fluid accumulation in fetus
Cystic hyngroma
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Hemolytic disorder caused by blood group incompatibility between mother and fetus
Immune hydrops
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Underlying basis of disease in immune hydrops
Immunizations of the mother by antigens present on fetal erythrocytes, followed by free passage of maternal antibodies across the placenta and into fetus; these abs bind to erythrocytes and mediate complement dependent lysis and/or phagocytosis by Fc receptor bearing cells; results in fetal red cell hemolysis
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What are the most important molecules on erythrocytes that are associated with immune hydrops?
RhD and ABO blood group antigens
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What is the major sequela of immune hydrops?
Anemia
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In immune hydrops, _____ develops because hemolysis of RBCs and produces unconjugated bilirubin; this passes across the poorly developed fetal blood-brain barrier and causes CNS injury (_____)
Jaundice, kernicterus
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Major causes of non-immune hydrops
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Cardiovascular defects
Chromosomal anomalies (Turner syndrome, trisomies 18 & 21)
Fetal anemia unrelated to immune hemolysis
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111
In fetal anemia, what two things are pale?
Fetus and placenta
112
What is erythroblastosis fetalis?
Bone marrow exhibits compensatory erythroid hyperplasia and (could be in the setting--immune hydrops fetalis/anemia) multiple organs exhibit extra medullary hematopoiesis; increased hematopoiesis deposits large numbers of immature RBCs in peripheral. Blood (erythroblastosis fetalis)
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3 inborn errors of metabolism and genetic disorders
PKU
Galacotemia
Cystic fibrosis
114
Role of phenylalanine hydroxylase (PAH) in phenylketonuria
PAH is an enzyme that irreversibly converts phenylalanine to tyrosine; in this autosomal recessive disease, most commonly there is a bi allelic mutation of the gene encoding PAH resulting in the accumulation of phenylalanine and brain damage
115
What is the enzyme that undergoes biallelic mutations in phenylketonuria?
Phenylalanine hydroxylase
116
Intestinal mucosal lactase converts lactose into glucose and ____
Galactose
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One Name the disorder: one of the enzymes that metabolizes galactose undergoes a genetic mutation and results in the accumulation of varying toxic metabolites of galactose
Galactosemia
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In the most common and clinically significant form of Galactosemia there is an autosomal recessive mutation in what enzyme?
Galactose-1-phosphate accumulated levels of galatitol and galactonate
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Most common lethal genetic disease affecting Caucasian populations in the US
Cystic fibrosis
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Autosomal recessive disorder that affects epithelial cell ion transport and causes abnormal fluid secretion in exocrine glands, respiratory GI and reproductive mucosa
Cystic fibrosis
121
Gene mutated in cystic fibrosis encodes what protein?
Cystic fibrosis transmembrane conductance regulator (CFTR) protein
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CFTR protein in cystic fibrosis only effects the sodium channel. T/F
False it regulates many ion channels and cellular process
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What epithelial sodium channel is most greatly effected in CF by the CFTR protein?
ENaC channel
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Role of the ENaC
ENaC is an apical membrane protein in exocrine epithelium that is responsible for sodium transport
125
Describe the role of CFTR in eccrine glands, and the disease state in CF
In eccrine sweat duct epithelium, normal CFTR augments ENAc activity. In CF, augmented activity is lost, resulting in hypertonic sweat
126
Role of CFTR in respiratory and intestinal epithelium and in the disease state of CF
Normal CFTR inhibits ENaC activity. In CF, augmented (increased) ENaC activity increases sodium movement into cells; coupled with reduced luminal chloride, there is increased osmotic water resorption from the lumen, leading to dehydration of mucus secretions. Defective mucociliary action and the accumulation of hyper concentrated viscous secretions ultimately obstruct ductascending outflow from the organs=mucoviscidosis
127
CFTR mediates bicarbonate transport; CFTR is co-expressed with a family of anion exchangers called what?
SLC26
128
In the setting of some CFTR mutations associated with bicarbonate transport, ___ fluids are secreted leading to an ___ environment that causes mucin precipitation and duct obstruction
Acidic
129
What is the most common CFTR gene mutation (70% worldwide)?
A three nucleotide deletion for phenylalanine at position 508 (F508)
130
How does CF affect the pancreas?
Mucus accumulation in small ducts with mild dilation to total atrophy of exocrine pancreas; impairment of fat absorption and avitaminosis A and duct all squamous metaplasia
131
How does CF affect the intestines?
Thick viscous plugs of mucus (meconium ileum) can cause small bowel obstruction
132
Thick viscous plugs of mucous can cause small bowel obstruction in CF. What are these called?
Meconium ileus
133
How can CF affect the liver and what it results in
Bile canalicular plugging by mucinous material that results in diffuse hepatic cirrhosis
134
How CF affects salivary glands
Similar to pancreas--progressive dilation of ducts, duct all squamous metaplasia and glandular atrophy
135
Which organ results in the most serious complications in CF? How?
Lungs--mucus cell hyperplasia and viscous secretions block and dilate bronchioles. Superimposed infections and pulmonary abscesses are common
136
Which microbes are most commonly associated with lung infections in CF?
Staphylococcus aureus
Haemophilus influenzae
Pseudomonas aeruginosa
137
Which microbe is associated with fulminant (coming on suddenly with great severity including death) onset in CF?
Burkholderia cepacia
138
How does CF affect the male genital tract?
Azoospermia and infertility occur in 95% of male patients surviving into adulthood, frequently with congenital absence of the vas deferens
139
What are the most common causes of death in CF?
Cardiorespiratory complications: chronic cough, persistent lung infections, obstructive pulmonary disease, cor pulmunale
140
Definition of SIDS
Sudden death of infant less than 1 yr of age that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of death scene, and a review of clinical history
141
SIDS is a diagnosis of ____ and a disease of unknown cause
Exclusion
142
When and in what position do infants usually die in SIDS?
Infants usually die while asleep, mostly in the prone or side position. Most SIDS deaths occur bw 2 and 4 months of life; 90% occur within 6 months of birth
143
Leading cause of death in children between 1 month and 1 year of age and the 3rd leading cause of infant death overall
SIDS
144
Hypothesis of SIDS
Developmental immaturity of critical brain stem regions (arcuate nucleus) involved in arousal and cardio respiratory control and that environmental influences (infection) further fatally impair these regulatory mechanisms
145
Parental risk factors for SIDS
```
Young maternal age
Short gestational interval
Inadequate prenatal care
Low socioeconomic status
Maternal smoking or drug abuse
```
146
Infant risk factors in SIDS?
Low birth weight
SIDS in a prior sibling (suggests a genetic component)
Male gender
147
What are some environmental risk factors in SIDS?
Sleeping prone
Hyperthermia
Sleeping on soft surface
148
Leading cause of death (after accidents) in US children bw ages 4 and 14
Cancers
149
What % of all cancers occur in infancy and childhood?
2%
150
What is more common in infancy and childhood? Benign or malignant tumors?
Benign
151
Another name for heterotopia/choristoma?
Microscopically normal cells or tissue present in abnormal locations; are usually of little clinical significance but can be the origin of true neoplasms
152
Example of heterotopia/choristoma
pancreatic tissue in the wall of the stomach
153
Excessive but focal overgrowth of mature cells or tissue native to organ or site in which they occur that do not recapitulate normal architecture. Are histologically benign but can be clinically signficant
Hemartomas
154
4 benign tumors and tumors like lesions of infancy and childhood
Hemangiomas
Lymphatic tumors
Fibrous tumors
Teratomas
155
Most common tumors of infancy
Hemangiomas
156
Where do Hemangiomas occur?
Face and scalp
157
Hemangioma may represent one facet of hereditary disorders such as _____
Von Hippel-Lindau disease
158
_____ are composed of cystic and cavernous lymphatic spaces, with variable numbers of associated lymphocytes
Lymphatic tumors
159
____ range from sparsely cellular proliferation a to richly cellular lesions indistinguishable from adult fibrosarcomas
Fibrous tumors
160
Congenital infantile fibrosarcomas has an ____ prognosis
Excellent
161
When are two peaks for Teratoma incidence?
At age 2 and in late adolescence
162
40% of teratomas occurring in infancy and childhood occur where?
Sacrococcygeal region
163
What % of teratomas are benign and mature?
75%
164
What is the most frequent childhood cancer of the hematopoietic system?
Acute lymphoblastic leukemia (ALL)
165
Most frequent childhood cancers of the CNS
Astrocytoma
Medulloblastoma
Ependymoma
166
Most frequent childhood cancer of the adrenal medulla
Neuroblastoma
167
Most frequent childhood cancer of the retina
Retinoblastoma
168
Most frequent childhood cancer of soft tissue
Rhabdomyosarcoma
169
Most frequent childhood cancers of the bone
Ewing sarcoma
| Osteogenic sarcoma
170
Most frequent childhood cancer of the kidney
Wilms tumor
171
What accounts for more deaths in children younger than 15 years than all other tumors?
Leukemia
172
Many pediatric cancers tend to have a more primitive ____ rather than a frankly anaplastic histology, with features of organogenesis consistent with the site of origin
Embryonal
173
Tumors with a more primitive embryo all rather than a frankly anaplastic histology with features of organogenesis consistent with site of origin are collectively labeled as?
Small round blue cell tumors
174
7 tumors that fall under the category of small round blue cell tumors
```
Lymphoma
Wilms tumor
Rhabdomyosarcoma
Ewing sarcoma/ peripheral neuroectodermal tumor (PNET)
Neuroblastoma
Medulloblastoma
Retinoblastoma
```
175
Where do Neuroblastoma tumors arise?
Adrenal medulla or sympathetic ganglia
176
What is the most common Neuroblastic tumor?
Neuroblastoma
177
1-2% of Neuroblastic tumors are familial associated with what enzyme mutations?
Anaplastic lymphoma kinase (ALK)
178
40% of Neuroblastoma occur where?
Adrenal medulla
179
Tumor characterized by sheets of small round blue Neuroblastoma within a neurofibrillay background and characteristic Homer-wright pseudo rosettes
Neuroblastoma
180
Wilms tumors are presumed to be related with Germaine mutations and are associated with malformation syndromes all involving what chromosome?
11p
181
When is Wilms tumor usually diagnosed? Is it malignant? Survival rate?
Usually diagnoses between ages 2 and 5, is malignant but has overall survival rate of more than 90%
182
Syndrome associated with a associated deletion on chromosome 11p band 13 and patients have aniridia (absence of Iris), genital anomolies, mental retardation and a 33% chance of developing a Wilms tumor
WAGR syndrome: Wilms tumor, Aniridia, Genital anomolies, Retardation (mental)
183
Syndrome in which patients have gonadal dysgenesis and nephropathy leading to renal failure; 90% develop Wilms tumors
Denys-Drash syndrome
184
Syndrome in which patients have enlarged body organs, hemilhypertrophy, adrenal cytomegaly, and a predisposition to developing Wilms and other primitive tumors
Beckwith-Wiedermann syndrome
185
Wilms tumors are soft, large, well circumscribed renal masses characterized by what triphasic features?
Blastema
Immature stroma
Tubules
(Trying to recapitulate nephrogenesis)
186
Identifying rests on a unilateral Wilms tumor resection mandates watchful waiting for a malignancy on the ____ side; nephrogenic rests are putative precursor lesions to Wilms tumors are are seen in renal parenchyma adjacent to 40% of unilateral lesions; the frequency rises to nearly 100% in bilateral Wilms tumors
Contralateral
187
Patient presentation of Wilms tumor:
Large abdominal masses; hematuria, pain, hypertension, bowel obstruction
