Diseases of infancy and childhood Flashcards
(157 cards)
1
Q
Why are diseases that originate in the perinatal period of importance?
A
They have significant morbidity and mortality
2
Q
What ethnicity has infant mortality rates more than twice that of caucasian americans?
A
African americans
3
Q
What are the leading causes of death in infants within the first 12 months of life?
A
Congenital anomalies
Disorders releating to prematurity and low birth weight
Sudden infant death syndrome (SIDS)
4
Q
Common causes of death in children between the ages of 1 and 4 y/o
A
Unintentional accidents
COngenital malformation, deformations, chromosomal abnormalities
Assault (homicide)
Malignant neoplasms
Diseases of the heart
5
Q
Common causes of death in children between 5 and 9 y/o
A
Accidents
Malignant neoplasms
congenital malformations, deformations, chromosomal abnl
Assault (homicide)
Influenza and PNA
6
Q
Common causes of death in children between 10 and 14 y/o
A
Accidents
Malignant neoplasms
Intentional self-harm (suicide)
Assault (homicide)
Congenital malformations, deformations, chromosomal abnormalities
7
Q
What is the most common cause of mortality in the first year of life?
A
Congenital anomalies
8
Q
Malformations represent primary errors of morphogenesis, what is the cause of most malformations?
A
They can be a result of a single gene or chromosome defect, but are more commonly multifactorial
9
Q
Disruptions are extrinsic disturbances in morphogenesis resulting from
A
secondary destruction of an organ or body region that was previously normal in development
10
Q
Define morphogenesis
A
Organ and tissue development
11
Q
Deformations are another example of extrinsic disruption of morphogenesis, what is fundamental to the pathogenesis of deformations?
A
localized or general compression of the growing fetus by abnormal mechanical forces, leading to a variety of structural abnormalities
12
Q
A sequence is a cascade of abnormalities triggered by what?
A
One initiating abberation
13
Q
How does a malformation syndrome differ from a sequence?
A
Malformation syndromes are a constellation of congenital anomalies, but unlike a sequence, it cannot be explained by the basis of a single initiating defect/aberration
14
Q
define agenesis
A
the complete absence of an organ and its associated primordium
15
Q
Define aplasia
A
Absence of an organ d/t the failure of existing primordium growth
16
Q
Define atresia
A
the absence of an opening, usually of a hollow organ (trachea, intestine)
17
Q
Define dysplasia
A
Abnormal organization of cells
18
Q
What are the three major categories of causes of congenital anomalies?
A
Genetic
Environmental
Multifactorial
19
Q
What are the common genetic causes of congenital anomalies and what are their frequencies?
A
Chromosomal aberrations (10-15%)
Mendelian inheritance (2-10%)
20
Q
What are the common environmental causes of congenital anomalies and what are their frequencies?
A
Maternal/placental infections (rubella, toxoplamosis, syphilis): 2-3%
Maternal disease states (DM, PKU, endocrinopathies): 6-8%
Drugs and chemicals (thalidomide, alcohol, folic acid antagonists): 1%
Multifactorial: 20-25%
21
Q
What are the two general principles affecting the pathogenesis of congenital anomalies?
A
Timing of the prenatal teratogenic insult
Interplay between environmental teratogens and intrinsic genetic defects
22
Q
Define prematurity
A
Gestational age less than 37 weeks
23
Q
What is the second most common cause of infant mortality, behind congenital anomalies?
A
Prematurity
24
Q
Major risk factors for prematurity
A
Preterm premature rupture of placental membranes
Intrauterine infection
Uterine, cervical, placental structural abnormalities
Multiple gestation
25
What is the major cause of preterm labor?
Intrauterine infection
26
Histologically, what is seen with intrauterine infection?
inflammation of placental membranes (chorioamnionitis)
Inflammation of the umbilical cord (funisitis)
27
What are the common microorganisms implicated in intrauterine infection?
Ureaplasma urealyticum
Mycoplasma hominis
Gardnerella vaginalis
Trichomonas
Chlamydia
28
What is the concept behind fetal growth restriction?
infants born at term that weight less than 2500g are considered to be undergrown, rather than immature and are small-for-gestational-age (SGA) infants
29
What should be considered in all infants with fetal growth restriction?
Fetal infection, commonly caused by the TORCH group of infections (toxoplasmosis, rubella, cytomegalovirus, herpesvirus)
30
Placental causes of fetal growth restritction result in
asymmetric growth retardation of the fetus
31
What are the most common maternal abnormalities leading to FGR?
Preeclampsia
HTN
Thrombophilias
Hypercoagulability
32
SGA infants have a significant risk for morbidity in what forms?
Major handicap
cerebral dysfunction
learning disability
hearing or visual impairment
33
What is the most common cause of respiratory distress in infants?
Respiratory distress syndrome aka hyaline membrane disease
34
What is the most important cause of the development of RDS?
Immaturity of the lungs
35
What is the fundamental defect in RDS?
Deficiency in surfactant
36
What cell type produces surfactant?
Type II pneumocytes
37
What is the role of surfactant in a normal lung?
Lines alveoli, reducing surface tension; thus, less pressure is required to keep the alveoli open for aeration
38
The lack of surfactant in infants with RDS results in?
Progressive lung atelectasis resulting in deposition of protein and fibrin-rich exudation in the alveolar spaces, causing a deficiency in gas exchange and difficulty breathing
39
The role of what is important in the synthesis of surfactant?
Glucocorticoids
40
What morphologic changes are seen in RDS/hyaline membrane disease?
Lungs are solid, airless and reddish purple; they sink in water
Microscopically, alveoli are poorly developed, necrotic cellular debris is seen in terminal bronchioles and alveolar ducts, eosinophilic hyaline membranes
41
Clinical findings in untreated infants with RDS
Preterm though appropriate weight for gestational age
Dyspnea
Cyanosis
Rales over both lung fields
Ground glass picture on CXR
42
In neonates affected by RDS, oxygen is often required. What are the complications of high concentration oxygen delivery by ventillation?
Retrolental fibroplasia
Bronchoplumonary dysplasia
43
Infants who recover from RDS are at an increased risk for developing what conditions?
PDA
Intraventricular hemorrhage
Necrotizing enterocolitis
44
Premature infants with necrotizing enterocolitis have stool and serum samples with higher levels of what mediator?
Platelet activating factor
45
Clinical course of necrotizing enterocolitis?
Bloody stools
Abd distension
Development of circulatory collapse
Abd radiography shows gas within intestinal walls
46
Morphological changes seen in necrotizing enterocolitis
Involved segment, usually the terminal ileum, cecum or right colon, is distended, friable and congested.
Mucosal coagulative necrosis is seen microscopically
Granulation tissue and fibrosis can be seen after an acute episode
47
Necrotizing enterocolitis is associated with high mortality, those that survive often develop
Strictures from fibrosis during the healing process
48
Fetal and perinatal infetcions are acquired through two routes, what are they?
Transcervical (ascending)
Transplacental (hematologic)
49
How does a fetus acquire an infection transcervically?
By inhaling infected amniotic fluid into the lungs or by passing through an infected birth canal
50
Most common sequelae of fetus' infected by inhaled amniotic fluid
PNA
Sepsis
Meningitis
51
The TORCH group of infections (Toxoplasmosis, Other, Rubella, CMV, Herpes/HIV) are grouped together because they evoke similar clinical and pathological manifestations, what are they?
Fever
Encephalitis
Chorioretinitis
HSM
Pneumonitis
Myocarditis
hemolytic anemia
hemorrhagic skin lesions
52
Define fetal hydrops
accumulation of fluid in the fetus during intrauterine growth
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What causes immune hydrops?
Blood group Ag incompatibility between mother and fetus
54
What major Ags are known to induce an immunologic rxn between mother and fetus?
Rh factor
ABO blood groups
55
What is the underlying pathogenic basis of immune hydrops?
Immunization of the mother by blood group ags on fetal RBCs and the free passage of Abs from the mother to the fetus through the placenta
56
What Ag is responsible for Rh incompatibility?
D Antigen
57
What are the consequences of excessive destruction of RBCs in the neonate?
Anemia
Jaundice (can lead to kernicterus)
58
What are the 3 major causes of nonimmune hyrdops?
CV defects
Chromosomal anomalies
**Fetal anemia 2/2 α-thalassemia**
59
What chromosomal abnormalities are associated with fetal hydrops?
Turner Syndrome (45, X)
Trisomy 18
Trisomy 21
60
What is the most serious threat in fetal hydrops?
Kernicterus
61
What occurs in kernicterus?
Unconjugated bilirubin from the break down of RBCs can pass through the BBB.
It is unsoluble and binds lipids in the brain, damaging the CNS, causing edema and a yellow tinge to the tissue
62
What are the clinical manifestations of fetal hydrops?
Minimally affected infants: pallor, HSM
Gravely ill infants: intense jaundice, edema, neurologic injury
63
Most inborn errors of metabolism are rare diseases that are inherited through what patterns?
Autosomal recessive
OR
X-linked
64
What is the cause of phenylketonuria (PKU)
Autosomal recessive disorder arising from a severe deficiency in the enzyme phenylalanine hydroxylase (PAH) leading to a toxic build up of phenylalanine in the blood
65
Clinical manifestations of PKU
Normal at birth
Phenylalanine levels rise in the blood over the first few weeks
At 6 months severe mental retardation is seen along with hypopigmentation of skin and hair, along with eczema, mousy or musty odor to sweat and urine
66
Tx for PKU
Restrict phenylalanine in the diet
67
What is the mechanism behind maternal PKU?
Females affected by PKU who live to child bearing age stop phenylalanine restriction once they hit adulthood; levels of Phe in the blood are high
During pregnancy, phenylalanine or its metabolites can cross the placenta, inducing teratogenic effects on the fetus
Child born to PKU mothers are usually mentally disabled and microencephalic, some have congenital heart disease
68
What is the biochemical abnormality in PKU?
Without PKU, phenylalanine cannot be converted into tyrosine
(why you get secondary albinism, tyrosine is converted into melanin)
69
What variant form of PKU cannot be treated by dietary restriction of phenylalanine?
The form caused by abnormal synthesis or recycling of tetrahydrobiopterin BH4
70
What are the general clinical abnormalities that suggets an inborn error of metabolism?
Dysmorphic features
Deafness
Self-mutilation
Abnormal hair
Abnormal body or urine odor
HSM or cardiomegaly
Hydrops
71
What are the neurologic clinical abnormalities that suggets an inborn error of metabolism?
Hypotonia or hypertonia
Coma
Persistent lethargy
Seizures
72
What are the GI clinical abnormalities that suggets an inborn error of metabolism?
Poor feeding
Recurrent vomiting
Jaundice
73
What are the clinical abnormalities seen in the eyes that suggets an inborn error of metabolism?
Cataracts
Cherry red macula
Dislocated lens (ectopia lentis)
Glaucoma
74
Galactosemia is an autosomal recessive disorder of galactose metabolism resulting from
Accumulation of galactose-1-phosphate in tissues including: liver, spleen, lens of the eye, kidneys, cardiac muscle, brainm and RBCs
2/2 deficiency in galactose-1-phosphate uridyl transferase
75
What are the clinical manifestations of galactosemia
Infants fail to thrive
Vomiting and diarrhea appear within a few days of milk ingestion
Jaundice and hepatomegaly evident the first week of life
Cataracts and mental retardation develop within 6-12 months
76
What is the cause of cystic fibrosis?
Autosomal recessive disorder
Mutation in the CFTR gene on chromosome 7q31.2 leading to a defect in the transport of chloride
77
Clinical manifestations of patients with CF
Chronic lung disease (bronchiectasis)
Pancreatic insufficiency
Steatorrhea
Hepatic cirrhosis
Intestinal obstruction (meconium ileus)
Male infertility
78
What is the most common lethal genetic disease that affects caucasian populations?
Cystic fibrosis
79
What is the incidence of CF?
1/2,500 live births
80
What is the major function of CFTR in sweat gland ducts?
Resorb luminal chloride ions and augment sodium reabsorption via ENaC
81
Pathogenesis of respiratory and intestinal complications in CF arise from?
Isotonic but low volume surface fluid layer
82
Pancreatic insufficiency is almost always present when there are CFTR mutations that result in
Abnormal bicarbonate conductance
83
What are the 6 classes of mutations based on their effect on the CFTR protein
I. Defective protein synthesis
II. Abnormal protein folding, processing, trafficking
III. Defective regulation
IV. Decreased conductance
V. Reduced abundance
VI. Altered function in regulation of channels
84
What common class II mutation is found in 70% of CF patients and is associated with a complete lack of CFTR protein at the apical surface of epithelial cells?
A deletion of 3 nucleoties coding for phenylalanine at AA position 508 (ΔF508)
85
What are possible explanations for the significant phenotypic differences in individuals with similar CFTR mutations?
Genetic and environmental modifiers
86
In all variants of CF, sweat glands are morphologically
unaffected
87
Morphologic changes in the pancreas of patients with CF
Accumulation of mucus in ducts, atrophy of exocrine glands, progressive fibrosis
88
Viscid plugs of mucus in the small intestines of infants with CF can cause a bowel obstruction known as
Meconium ileus
89
Morphologic changes in the liver of patients with CF
Bile canaliculi full of mucus
Steatosis
Focal biliary cirrhosis
90
Morphologic changes in the salivary glands of patients with CF
Dilation of ducts
Squamous metaplasia of epithelial lining
Glandular atrophy followed by fibrosis
91
Morphologic changes in the lungs of patients with CF
Bronchioles distended with thick mucus associated with marked hyperplasia and hypertrophy of the mucus-secreting cells
Bronchiectasis 2/2 infection
Lung abscesses
92
Infertility is common in 95% of males with CF, what is also found relating to the infertility?
Bilateral absence of the vas deferens
93
What are the common organisms that lead to the bronchiectasis seen in patients with CF?
Staph aureus
Haemophilus influenzae
Pseudomonas aeruginosa
Burkholderia cepacia (B. cenocepacia)
94
After cardiopulmonary and transplant-relataed complications, what is the most common cause of death of patients with CF?
Liver disease
95
What is the gold standard in diagnosing CF?
Sequencing the CFTR gene
96
How does the National Institute of Child Health and Human Development define SIDS?
The sudden death of an infant under 1 yr of age which remains unexplained after thorough case investigation, including performance of autopsy, examination of death scene and review of clinical hx
97
Why does SIDS have the pseudonym of crib death?
infant usually dies in their sleep, lying prone or on their side
98
What is the leading cause of death in children between 1 mo and 1 y/o
SIDS
99
Common morphological findings on postmortem examination of an SIDS infant
Multiple petechiae on the thymus, pleura, epicardium
Lung congestion
Vascular engorgement with pulmonary edema
Astrogliosis in CNS
100
What is the triple-risk model of SIDS
Vulnerable infant
Critical developmental period in homeostatic control
Exogenous stressor
101
What is the most common cause of sudden "unexpected" death
infections
102
What are some parental risk factors of SIDS
Young maternal age
Maternal smoking during pregnancy
Drug abuse
Late or no prenatal care
Low socioeconomic group
AA or American indian ethnicity
103
What are some infant risk factors for SIDS
Brain stem abnormalities
Prematurity
Low birth weight
SIDS in a prior sibling
Antecedent respiratory infections
Germline polymorphisms in ANS genes
104
What are some environmental risk factors for SIDS
Prone or side sleep position
Sleeping on soft surfaces
Hyperthermia
Co-sleeping in the first 3 months
105
What are two categories of tumor-like lesions that should be distinguished from true tumors (neoplasia)
Heterotopia (choristoma)
Hamartoma
106
Define heterotopia
Microscopically normal cells or tissues that are present in abnormal places
107
Define hamartoma
Excessive, focal overgrowth of cells and tissues native to the organ in which it occurs
108
The most common neoplasms of childhood are
Soft-tissue tumors of mesenchymal derivation
109
List the common benign tumors of childhood
hemangioma, lymphatic tumors, fibrous tumors, teratomas
110
What are the most common tumors of infancy?
Hemangiomas
111
What is a common location for a hemangioma?
The skin, specifically the face and scalp
112
Lymphangiomas are characterized by
cystic or cavernous spaces
113
Common locations of lymphangiomas
Deep in the neck, axilla, mediastinum, retroperitoneal tissues
114
Fibrous tumors occuring in infants and children occur across a range, what types of tumors occur?
Fibromatosis to congenital-infantile fibrosarcomas
115
What characteristic chromosomal translocation has been identified in congenital-infantile fibrosarcoma?
What does it result in?
t(12;15)(p13;q25)
ETV6-NTRK3 fusion transcript
116
What is unique to infantile fibrosarcomas, making it a useful diagnostic marker?
ETV6-NTRK3 fusion transcript
117
Most common teratoma of childhood?
Sacrococcygeal teratoma
118
Sacrococcygeal teratomas affect females 4 times more than males and are associated with what?
Congenital anomalies, primarily defects in the hindgut and cloacal region and other midline defects (spina bifida, etc)
119
The differences between cancers of infancy/childhood and those that occur later in life are attributed to:
Incidence and tumor type
Relatively frequent demonstration of a close relationship between abnl development and tumor induction
Underlying familial or genetic aberrations
Tendency of fetal and neonatal malignancies to regress or differentiate spontaneously
120
The most frequent childhood cancers arise where?
Hematopoietic system
Nervous tissue
Soft tissues
Bone
Kidney
121
What type of cancer causes more deaths in children under 15 y/o than all other cancers combined?
Leukemia
122
Because of their primitive histologic appearance, many childhood tumors are referred to as
Small round blue cell tumors
123
Malignant non-hematopoietic neoplasmas show features of organogenesis specific to the site of tumor origin, because of this, they are distinguished from other tumors by the suffix
-blastoma
124
Neuroblastic tumors include tumors of the sympathetic ganglia and adrenal medulla, derived from what cell type that populates these sites?
Neural crest cells
125
What is the most common extracranial solid tumor of childhood and what is its prevalence?
Neuroblastoma
1/7,000 live births (700 cases per year)
126
Germline mutations in what gene has been determined to be a major cause of familial predisposition to neuroblastoma?
Anaplastic lymphoma kinase
127
40% of neuroblastomas arise where?
Adrenal medulla
128
What are classic histologic findings in neuroblastomas
small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets
Background often with eosinophilic neuropil
Rosettes (homer-wright pseudorosetters) often found as well
129
Morphologic features of a ganglioneuroblastoma
Organized fascicles of neurotic processes
Schwann cells
Fibroblasts
130
What is the typical presentation of a child, under 2 y/o, with a neuroblastoma
Abd masses
Fever
Weight loss
131
Locations of common metastases from neuroblastoma?
Liver
Lungs
Bone marrow
132
An important diagnostic feature of neuroblastomas is?
production of catecholamines, which occurs in 90% of cases
133
The most pertinent prognostic factors of neuroblastoma include:
1. age and stage (most important!!)
2. Morphology
3. Amplification of the MYCN oncogene (most profound impact)
4. Ploidy
134
What stages of neuroblastoma have the best prognosis, irrespective of age of the child?
1, 2A and 2B
135
What is the age that has become the critical point of dichotomy in terms of prognosis?
18 months
(younger than 18 mo have better prognosis than those over 18 mo)
136
Morphologic evidence of schwannian stroma and gangliocytic differentation have what type of prognosis for a child with neuroblastoma?
Favorable
137
What has the most profound impact on prognosis of neuroblastoma?
Amplification of the MYCN oncogene
(presence of amplification puts tumor into high risk category with poor prognosis)
138
What category of ploidy is associated with a better prognosis of neuroblastoma?
Hyper-diploid
139
High expression of what neurotrophin receptor is associated with a favorable prognostic factor in neuroblastoma?
TrkA (tyrosine kinase receptor A)
140
What is the most common primary renal tumor in children and what is its prevalence?
Wilms tumor
1/10,000 children
141
Tumors that involve both kidneys simultaneously is referred to as?
Synchronous
142
Tumors that involve one kidney after the other is referred to as?
Metachronous
143
The risk of wilms tumor increases with three recognizable groups of congenital malformations associated with distinct chromosomal loci, what are they?
Children with WAGR syndrome
Children who have Denys-Drash syndrome
Children with Beckwith-Wiedemann syndrome
144
WAGR syndrome is characterized by
**W**ilms tumor
**A**niridia
**G**enital anomalies
mental **R**etardation
145
What is the chromosomal deletion associated with WAGR syndrome?
What genes on this chromosome are deleted, leading to the sxs associated with WAGR syndrome
11p13
WT1 (wilms tumor-associated gene)
PAX6 (gene for aniridia)
146
Denys-drash syndrome is characterized by
gonadal dysgenesis
early-onset nephropathy leading to renal failure
147
What is the genetic abnormality in Denys-Drash syndrome
Dominant-negative missense mutation in the zinc-finger region of WT1 protein, affecting DNA binding properties
148
Beckwith-Wiedemann syndrome is characterized by
Organomegaly
Macroglossia
hemihypertrophy
Omphalocele
Abnormal large cells in the adrenal cortex
149
What chromosomal region is implicated in Beckwith-Weidemann syndrome?
11p15.5
150
The predisposition to tumorigenesis in beckwith-weidemann syndrome is influenced by what?
The specific WT2 imprinting abnormalities present
151
What are nephrogenic rests
Precursor lesions of Wilms tumors, seen in the renal parenchyma adjacent to approx 25-40% of unilateral tumors and 100% of bilateral tumors
152
Gross morphologic features associated with wilms tumor
large, solitary, well-circumscribed mass
When cut, tumor is soft, homogenous and often tan/gray in color with occassional hemorrhage, cyst or necrosis
153
Histologic features associated with wilms tumor
sheets of small blue cells with few distinctive features characterize the bastemal feature
Epithelial differentiation of abortive tubules or glomeruli
stromal cells are fibrocytic or myxoid in nature
154
Clinical presentation of a child with wilms tumor
large abd mass
hematuria
intestinal obstruction
HTN
155
What histologic finding is a critical determinant of adverse prognosis of wilms tumor?
Anaplasia
156
Those with a history of wilms tumor are at an increased risk of developing what secondary tumors?
Bone sarcoma
Soft-tissue sarcoma
Leukemia
Lymphoma
Breast CA
157
Loss of material on chromosomes 11q and 16q as well as gain of chromosome 1q in Wilms tumor cells indicates what prognosis?
poor
