Diseases Of Infancy And Childhood - Dobson Flashcards
1
Q
Malformation
A
Intrinsic abnormal developmental process (gene or chr defect)
EX: polydactyl, syndactyly, cleft lip)
2
Q
disruptions
A
Destruction of an organ that was previously normal (extrinsic disturbance in morphogenesis), usually environmental
EX: amniotic bands
3
Q
Amniotic bands
A
Amnion ruptures forming bands that encircle + compress the fetus
(No known cause)
4
Q
Deformations
A
Extrinsic disturbance in development by abnormal biochemical forces (uterine constraint) = compresses fetus (small uterus or maternal problems, or fetal or placental , like low amounts, problems)
EX : potters sequence (from oligohydraminos)
5
Q
Sequence
A
1 defect causes many other congenital defects
Or one causes can make all malformation, disruption, and deformation happen in one place)
6
Q
Potters sequence causes
A
- Leakage of amniotic fluid (rupture)
- Uteriplacental insufficiency (maternal HTN, severe toxemia)
- Renal agenesis of fetus (urine unable to be excreted ——> amniotic fluid)
7
Q
Potters sequence SX:
A
- Flattened face, positional abnormalities in hand and feet (clubbed)
- Dislocated hips, breeches presentation
- Pulmonary hypoplasia
- Amnion nodosum
8
Q
Agenesis
A
Complete absence of an organ , no primordium of it either
9
Q
Aplasia
A
Absence of organ however the primordium is present
10
Q
Atresia
A
X opening in a hollow organ (trachea or esophagus usually)
11
Q
Dysplasia
A
Normal cells and size only wrong place or area (abnormal organization)
12
Q
2 genetically causes for congenital disease in fetus
A
- Chr aberration
2. Mendelian inheritance (gametogenesis)
13
Q
Holoproscencephaly
A
Forebrain and mid face defect most common due to no shh signaling (Mendelian inherited mutation)
14
Q
5 drugs that cause fetal malformation = tetragens
A
- Thalidomide = limb malformation
- 13-cis-retinoic acid (derm treatment, form of VIT A)
- Warfarin (HTN)
- Anti-convulsants
- Alcohol
15
Q
What does alcohol do
A
Microcephaly, maxillary hypoplasia, palpebral fissures, low growth
16
Q
Nicotine intake and fetus
A
Can cause spontaneous SIDS
17
Q
DM and fetus
A
Can cause
- fetal hyperinsulinemia = macrosomia (high body fat and muscle mass)
- cardiac, CNS problems
18
Q
What decreases the rates of neural tube defects in fetus
A
folic acid intake of mother
19
Q
Embryo is most susceptible to terogenesis when
A
Week 3- week 9
20
Q
Cyclopamine and fetus
A
Plant that ——I SHH (eaten usually by sheep) = causes face abnormalities, holoprosencephaly, cyclopia
21
Q
Valproic acid and fetus
A
———I HOX genes (limb, craniofacial, vertebrae structures)
22
Q
VIT A (RETINOL) and fetus
A
If excessive ——I TGF-B: CNS, cardiac, cleft plate, cleft lip
Needed in moderation for healthy lung, cardiac, GU, eyes, diaphragm health
23
Q
1st and 2nd most common neonatal death reasons
A
1st : congenital anomalies
2nd : prematurity
24
Q
Prematurity is defined as
A
Less then 37weeks
25
Reasons for prematurity
1. Preterm premature rupture of placental membrane (PPROM)
2. Intrauterine infection
3. Uterus, placental, cervical structural abnormalities (uterine fibroids, placenta Previn, abruptio placentae)
4. Multiple gestation (twins)
26
PROM
Spontaneous ROM AFTER 37 weeks, less fetal problems then PPROM
27
Intrauterine infection and fetus
Most common cause of preterm, (inflammation of placenta membranes = chorioamnionitis, inflammation of umbilical cord = funishitis)
28
Most common intrauterine infections
1. Ureaplasma urealyticum
2. Mycoplasma hominis
3. Gardnerella vaginalis
4. Trichomonas
5. Gonorrhea
6. Chlamydia
7. Malaria and HIV in developing countries
29
Risks of having PPROM
1. Neonatal RDS (hyaline membrane disease)
2. Necrotizing enterocolitis
3. Sepsis
4. Intraventricular + germinal matrix hemorrhage
30
Underground definition
Born at term only underweight , due to fetal growth restriction
1. Fetal issue (chr disorder, congenital anomalies, congenital infection)
2. Maternal issue (preeclampsia, chromic HTN, thrombophilias, malnutrition, drugs/alcohol)
3. Placental issue (uteroplacental insufficiency)
31
Ways there can be uteroplacental insufficiency
| 6
1. Umbilical-placental vascular anomalies——> 1 umbilical A, cord inserted not right, placental hemangioma
2. Placental abruption
3. Placental thrombosis/ infarction
4. Placenta previa
5. Many gestation said
6. Placental infection
32
What type of infection is usually involved in the fetal abnormalities causing undergrowth
TORCH group
| - (toxoplasmosis, rubella, cytomegalovirus, herpesvirus, syphilis)
33
Another name for RDS
Hyaline membrane disease
| = hyaline is deposited in the peripheral airspaces
34
Other ways newborn can have respiratory distress that is not RDS
1. Excessive sedation of mother
2. Fetal head injury
3. Aspiration of amniotic fluid or blood by fetus
4. Umbilical cord coiling around neck = intra-uterine hypoxia
35
Clinical signs for newborn with RDS
1. Preterm + normal weight for that gestational age
2. C-section, maternal DM, and male fetus has higher risk
3. Resuscitation causes normal breathing and color
4. After 30 min : hard breathing and cyanosis again + rales
5. X-ray : ground-glass picture
36
RDS % chance if norm at or below 28weeks
60%
37
Reason for RDS to happen
Low surfactant : SP-B (hydrophobic, is most important)
| = genes SFTPB and STFBC
38
What stimulates.acted the synthesis of surfactant
Glucocorticoids *
| TGF-B, thyroxine, prolactin, insulin, cortisol
39
Reason c-section increases RDS
Labour squeezes out fluid in lungs + labour increases surfactant synthesis
40
Reason DM increases RDS
High insulin inhibits steroids to activate type 2 cells to make surfactant
41
What does an RDS infants lung look like if they dont make it
Solid, purple, liver-like, sinking in water, necrotic tissue + Eosinophilic hyaline membrane *
42
What happens in RDS that leads to necrotic tissue and fibrin deposition = hyaline membrane
1. Prematurity
2. Low surfactant + high ST
3. Atelectasis (stiffening)
4. Hypoventilation, uneven perfusion
5. high CO2, and hypoxemia
6. Acidosis + pulmonary vasoconstriction
7. Pulmonary hypoperfusion
8. Endothelial damage , epithelial damage = plasma leaks to alveoli
9. Fibrin and necrotic cells make hyaline membrane
43
How to measure is a fetus has surfactant in synthesis
Level of phospholipids measured
44
What can happen if baby is on O2 ventilators for too long
1. Retrolental fibroplasia (VEGF decrease= apoptosis then increase = vascularization causing lesions)
2. Bronchopulmonary dysplasia (TNF, IL6, IL8, IL1B increased)
45
3 other complications besides RDS premature infants are at high risk of
1. Necrotizing enterocolitis
2. Intraventricular hemorrhage
3. Ductus arteriosus
46
What factor increases necrotizing enterocolitis
PAF , increasing mucosal permeability = enterocytes apoptosis = more holes in lumen = inflammation more damage
47
What is usually the cause of necrotizing enterocolitis
Introduction of some bacteria ——> inflammation and tissue destruction
48
Clinical signs of necrotizing enterocolitis
1. Bloody stools
2. ABD distention (gas in intestinal wall= pneumatosis intestinalis)
3. Circulatory collapse
49
What does necrotizing enterocolitis become after a while and also what part of GI does it usually involve
Terminal ileum, cecum, right colon
| Fibrosis
50
2 ways fetus can get an infection
1. Transcervially : ascending
| 2. Transplacentally : hematologic
51
Transcervical infection = ascending
```
From cervix and vagina (in utero or during delivery)= by inhaling infected amniotic fluid
Usually bacteria (some virus like herpes) = pneumonia, sepsis, meningitis
```
52
Reason transcervical infections happen more in preterm
Infection causes inflammation and also a lot of N ——> Prostaglandins released = contractions + amniotic sac rupture
53
Transplacental infections = Hematologic
```
Mostly parasitic (toxoplasma, malaria)+ viral + some bacterial (Listeria, Treponema)
= through chorionic villi into placenta , at any time in gestation
```
54
How does Parvovirus B19 infect the fetus
Transplacentally : erythema infectiosum “5th disease of childhood” during older ages of child, mother if non-immune can get this)
= viral infection or erythroid progenitor cells
55
TORCH infections infect fetus how
Transplacentally
56
SX: TORCH group infections
1. Fever
2. Encephalitis
3. Chorioretinitis
4. Hepatosplenomegaly
5. Pneumonitis
6. Myocarditis
7. Hemolytic anemia
8. Vesicular or hemorrhagic skin lesions
57
What are the TORCH infections
```
T : toxoplasmosis
O : other agents
R : rubella
C : cytomegalovirus
H : herpes
```
58
Early sepsis SX:
Pneumonia, sepsis, sometimes meningitis after birth (day 4,5)
59
EX of early onset sepsis
Group B streptococcus, early onset bacterial meningitis
60
EX: of late onset sepsis
Listeria and candida (latent period is long)
61
Fetal hydros are what
Accumulated fluid = edema during intrauterine growth
62
Immune hydrops
Rh incompatibility = hemolytic anemia
63
Non-immune fetal hydrops
| 2 types
1. Hydrops fetalis : progressive , generalized edema ——> usually fatal
2. Cystic hygroma: localized edema (pleural and peritoneal effusion)(postnuchal fluid accumulation)
64
TORCH infections cause what kind of hydrops
Non-immune
65
How to Rh incompatibility happen
Rh - MOM and Rh + DAD
66
Rh incompatibility 1 and 2nd pregnancy has what AB made
1st : IgM = cant cross placenta
| 2nd : IgG = can cross placenta
67
Rh incompatibility causes what to fetus
Anemia ——> cardiac decompensation ——> Hydrops
| RBC degradation ——> Jaundice an Kernicterus
68
What TX: Rh incompatibility
Rhesus Ig (RhIg) = anti-D ABs at 28 weeks and 72hr before delivery
69
ABO incompatibility happens when in fetus and mom
MOM = O
Fetus = A or B or AB
*both 1st and 2nd pregnancy can be effected ——> hemolytic anemia however usually not severe
70
Cardiac decompensation causes
Vasoconstriction
71
Kernicterus
Unconjugated bilirubin deposited in CNS brain
72
5 main causes of non immune fetal hydrops
1. Cardio defects
2. Chr anomalies (dysmorphic features****)
3. Fetal anemia (from a-thalassemia homozygous = all a-globins deleted)
4. Virus (parvovirus B)
5. Twins (anastomoses between circulations)
73
Hydrops due to anemia makes fetus and placenta look
Pale
| Large liver and spleen from cardiac failure + congestion
74
What does brain look like in Kernicterus
Large and edematous
| Yellow esp basal ganglia . Thalamus, cerebellum , grey matter and spinal cord
75
Erythroblastosis fetalis
Large amount of hematopoiesis = many immature reticulocytes, normoblasts, erythroblasts
= usually in liver during non immune hydrops
76
Clinical signs of hydrops
Pallor, hepatosplenomagaly, jaundice , edema , can cause CNS injury
77
How are inborn metabolic disease usually inherited
Autosomal recessive or X- linked
78
PKU what is it and demographics
Most common in Scandinavia
LEAST common in AA and Jews
X Phenylalanine Hydroxylase or X Dihydropteridine reductase
= Hyperphenylalaninemia
79
PKU Sx:
Mental problems, eczema, hair and skin low pigmented, seizures as early as 6mo
Some can never talk or walk if not TX in time
MUSTY URINE
80
Maternal PKU
If phenylalanine intake is not controlled in mothers with PKU, fetus is born with mental problems and congenital heart disease = Phenylalanine crosses placenta
81
Benign hyperphenylalaninemia
Partial defect on PAH = no CNS problems, only elevated Phe
82
Non-classic PKU
| What is and about TX
X DHPR = X BH4
| TX: dietary restrictions of Phe will NOT work
83
Galactosemia
Accumulation of galactose-1-phosphate
| X galactose-1-phosphate uridyl transferase (GALT) (some have X glucokinase, milder)
84
how is galactose formed and broken down beginning 2 steps
1. Lactose = galactose + glucose (lactase)
| 2. Galactose broken down by (Glucokinase and then GALT, then UDP-galactose-4-epimerase) ——> UDP-glucose
85
Where does galactose-1-phosphate accumulate in galactosemia
Liver (cirrhosis and hepatomegaly) , spleen, eye lens (cataract), kidney (aminoaciduria) , heart, cerebral cortex (edema, nerve loss, gliosis), RBCs
GALACTOSE-1-PHOSPHATE ———> GALACTITOL + GALACTONATE
86
What part of the brain is most effected in the galactosemia
```
Dentate nuclei (cerebellum)
Olivary nucleus (medulla)
```
87
Fetus with galactosemia SX:
D, V, jaundice (from milk ingestion), after 3 weeks you see cataracts, after 6mo you see mental problems
You can see Hemolysis and coagulopathy
88
Older pt with galactosemia are in higher risk of
Ataxia, speech problems, gonadal failure
89
CF is what and what locations
X CFTR in Respiratory, GI, Reproductive areas
| * most common in caucasians
90
What are the mutations in CF
Steatorrhea, chronic lung disease secondary to recurrent infections, pancreatic insufficiency, malnutrition, hepatic cirrhosis, SIO, male infertility
91
SX of heterozygous CF
Higher Respiratory + Pancreatic diseases
92
CFTR gene and function
7q31.2
| Cl- channel (usually out), in response to cAMP
93
How do K+ and NA+ move
Inward
| Na+ uses ENaC
94
ENaC inhibited by what
CFTR
95
CF what happens to ENaC, normally (in Resp and GI)
Activity increases and more Na+ goes into cell = dehydrated mucous on outside of RESP and GI cells (PLUS Cl- can’t leave cell)
96
One exception to CFTR action on ENaC
SWEAT GLANDS
= CFTR activates ENaC (so during CF, Na+ cant enter cells and Cl- cant ENTER cell)
= SALTY skin****
97
Reason a dehydrated mucus membrane can lead to complications
= makes a isotonic + low volume surface fluid layer
1. Defective mucociliary action
2. Accumulation and secretion of Viscid products = pulmonary infections
98
CFTR role in HCO-3
Activates SLC26 to secrete HCO-3
When CF (lumen becomes acid)
= pancreatic insufficiency*****
99
What other non- CF conditions can happen with X CFTR
1. Idiopathic chronic pancreatitis
2. Chronic pulmonary disease (late-onset)
3. Idiopathic bronchiectasis
4. Obstructive azoospermia (no vas deference)
100
Classic CF SX:
Mutated class 1,2,3
1. Pancreatic insufficiency
2. Sinopulmonary infections
3. GI symptoms
* ***atypic CF, or non-classical CF
101
Class involved in mild CF
Class 4 and 5
102
3 modifiers that play a role in preventing lung infection and GI good
TGF-B, MBL2, IFRD1
| = CF can be increased risk in low amounts of this
103
What causes chronic or acute lung infection
Colonization of (Peudomonas aeruginosa, Haemophilus influenzae, Staph)**** secreting Alginate (protect against ABs and immune system)
104
Meconium Ileus
SIO happening form viscid plugs of mucus form CF
105
What do most pt with later onset CF come in with
meconium ileus (palpable or pain in RLQ)
106
What is and happens in pancreatic insufficiency
Low protein and fat absorption
(Loss of fat and VIT A,D,K) ——> foul smelling feces
(Loss of protein)——> can lead to generalized edema
107
2 most common reasons for death in CF
Cardiopulmonary complications
| Liver failure or cirrhosis
108
CF that usually get resistance to anti bacteria to Pseudomonas
One mild allele and one severe allele
109
SIDS
Sudden death under 1yo, no reason even after autopsy, history, and death scene examination (if you can see in autopsy = SUDS)
* most common between 2mo-4mo
110
Most common SIDS
Death during sleep especially in prone or side position
111
SIDS more common in what fetus
Premature
112
SIDS usually happens due to what
1. Delayed arousal and cardiorespiratory control (medulla, and brain stem) : 5-HT activated this area
2. Or respiratory previous infection or male
113
Laryngeal chemoreceptors role in SIDE
Inhibits cardiorespiratory reflex = no swallowing and clearing airways during PRONE + respiratory infection
114
Reasons fro SUDS
Infections
Fatty acid oxidation disorders
And others
115
Heterotopia (choristoma)
Normal cells and tissue in wrong location
- can be confused as neoplasm
- rarely become neoplasm only if it does it will be confusing to find
116
Hamartoma
Overgrowth of a cell in a tissue (like a benign growth)
117
Hemangioma is what
Most common in infancy
Can happen in capillaries and veins if skin on face, scalp (red-blue masses + flat lesions = port-wine stains
= regresses on its own with cosmetics also
118
When do you mostly see hemangiomas
In the Hippel-Linda’s disease (mutation in CCM, cerebral cavernous malformation, genes)
119
Lymphangiomas
| Lymphangiectasis
1. Neoplasm or hamartoma of lymph nodes (neck, axilla, mediastinum, retroperitoneal tissue), travel and extend
2. Dilated lymph vessels (usually in any locations, extremities)
120
Fibrous tumors are what
Of the spindle-shaped cells= fibromatosis
| Many lesions = congenital infantile fribrosarcomas
121
congenital infantile fribrosarcomas happens due to
Translocation of t(12;15)(p13;q25) = ETV6-NTRK3 fusion transcript
122
Most common teratoma and when do they happen
First at around 2yo second at around early adult or late adolescence
Sacrococcygeal teratomas, more common in girls and 10% congenital form hindgut/cloaca formation
123
Where do teratomas usually occur
Genitals, ovaries
| Midline structures
124
What is a teratoma
Germ cell neoplasm, any cells type (hair, bone, muscle)
125
Most common areas for neoplasms in infants
CNS, adrenal medulla, retina, soft tissue, bone, kidney
126
Small round blue cell tumors
How cells of neoplasm in children look
127
Neuroblastoma
* adrenal gland nerves, some go away on own, DUE TO MYC amplification*
SX: ABD pain , can feel ABD mass, D or C, fever,
(Older children : bone pain, respiratory probs, GI probs)
(Neonates, many blue discolorations)
128
Wilms tumor
* in kidney
SX: ABD swelling, sometimes palpable mass, ABD pain
(Nephroblastoma)
129
Hepatoblatoma
* in liver
130
Rhabsomyosarcoma
* in skeletal muscles (sometimes bladder and uterus)
| SX: swelling of eyes, nose bleeds, headache , swollen leg or arm
131
Erwing sarcoma
* posterior fossa neoplasm
| Bones and soft tissue around bones (usually leg and pelvis)
132
Ependymoma
* cells that line CSF (ependymal cells) in brain and SC
133
Neuroblastic tumor
From sympathetic ganglia, adrenal medulla : FROM NCC
- spontaneous or therapy induced differentiation into mature cells
- DUE TO ALK GENE* (germline)
134
Blue berry muffin baby happens when
| And how to TX:
During neonate neuroblastoma , form high CATECHOLAMINES (shows as high VMA and HVA in urine)
TX: Florescent light : NO MYC AMPLIFICTION
135
What determines success of tx neuroblastoma
1. Age and stage (stage 1, 2A, 2B have best outcome)
2. X application of MYC
3. Schwann cells present
4. Hyper-diploid
136
When can neuroblastoma be TX
All stage can be before 1yo, or at most 18mo
| After that mild and intermediate usually can
137
Which type of neuroblastoma regresses on its own
```
4S class
In liver, BM, and skin
```
138
Near-diploid vs hyper-diploid
The hyper-diploid has high prognosis
Near-diploid: many chr are effected (chromothripsis : when random fragments combine)
(Part of neuroblastoma)
139
Wilms tumor involves what
```
Both kidneys
(Together = synchronous , one then the other = metachronous)
```
140
What type of mutation in wilms tumor
Germline deletion in gene 11p13 WT1 + PAX6 deleted
| 2-hit theory
141
WAGR syndrome
Increases risk to get Wilms tumor when both PAX6 and WT1 are deleted due to 11p13 deletion
142
If only PAX6 is deleted
Sporadic aniridia, no wilms tumors
143
Only WT1 deletion
Nothing if only 1st hit
144
Denys-Dash syndrome
X zinc finger of WT1 so cant bind to DNA(dominant)
1. Wilms tumor
2. Gonadoblastoma
3. Gonadal dysgenesis (male female features + renal failure)
4. Diffuse mesangial sclerosis (glomerular lesions)
145
Bench with-Wiedemann syndrome
Organomegaly, abnormal large cells in adrenal cortex
| X 11p15.5 (WT2)= over expressed IGF-2 + increased risk for Wilms tumor, liver, pancreas, adrenal, skeletal muscle tumors
146
B-cat in wilms tumor
Upregulated in 10%
147
Histology of wilms tumor
Anaplasia
| Lesions with blastema, stromal, epithelial cells
148
Histology of neuroblastoma
Eosinophilic fibrillation material (N), Homer-Wright peudorosettes, catecholamine containing granules, ganglion cells in many different differentiation stages = gangioneuroma
