Topics A39-44 Pediatric Diseases: Congenital anomalies, prematurity, SIDS, hydrops, CF, Childhood Tumors Flashcards
What does “congenital” mean?
Structural defects present at birth. May be cosmetic or functional. Many may not be apparent until later in life.
Incidence is as high as 1 in 33.
Definitions of:
- Malformation
- Disruption
- Deformation
[Note that these definitions are really bitchy and I hope no one cares about this]
Malformation: primary errors of morphogenesis, intrinsically abnormal developmental process. Not usually one gene or chromosomal defect, but many factors.
Disruption: secondary destruction of organ/region, so by contrast to malformation they arise from an extrinsic disturbance. Classic example is “amniotic bands” that encircle and compress developing fetus. Not heritable. In contrast to deformation, a previously-formed organ is destroyed, not just malformed.
Deformation: also extrinsic disturbance of development, but via abnormal biomechanical forces such as uterine constraint.
Definitions:
- Sequence
- Malformation Syndrome
Sequence: a single aberration that snowballs and leads to many secondary effects. Example is oligohydramnios sequence (decreased amniotic fluid). Many things can cause decreased amniotic fluid, but the low fluid leads to fetal compression, which makes a fetus with a flattened face, positional abnormalities of the limbs, poor growth of chest, etc.
Malformation Syndrome: several defects that cannot be explained by a single localizing error in morphogenesis. May be chromosomal abnormality or viral infection that affects several tissues
Definitions:
- Agenesis
- Aplasia/Hydroplasia
- Atresia
Agenesis: complete absence of organ
Aplasia/Hypoplasia: incomplete development or under-development
Atresia: absence of an opening, usually a hollow visceral organ or duct like the intestine or bile duct
3 major categories of causes for human malformations
- Genetic
- Environmental
- Multifactorial
Genetic causes of malformation:
-Which ones are inheritable?
Chromosomal disorders (Down syndrome, Klinefelters) are not usually inheritable because they arise during gametogenesis, not spread. But single gene mutations undergo Mendelian inheritance.
Can you give 3 examples of specific environmental factors that cause fetal disruptions of development? (listing more than 3 on the answers but at least try to get 3)
- Infections like Rubella (rare due to vaccine)
- Medications like thalidomide (tranquilizer and cancer treatment)
- Alcohol
Others: radiation, cigarettes, 13-cis-retinoic acid (acne treatment), warfarin, anticonvulsants, maternal hyperglycemia
During which weeks of development is the embryo most susceptible to teratogens?
Weeks 3-9, and the peak sensitivity is between weeks 4 and 5.
What is multifactorial inheritance?
What are 3 common defects that occur?
Multifactorial inheritance: interaction of environmental influences with 2 or more genes, commonly causing congenital defects
Examples:
- Cleft Lip
- Cleft Palate
- Neural tube closure defects
What are the two ways that perinatal infections can occur?
- Transcervical (Ascending) infections: spread of infection from vaginal canal upwards. The fetus may “inhale” infected amniotic fluid, or contract it while passing thru birth canal. Some viruses but mostly bacteria like S. agalactiae
- Transplacental: crosses placenta via chorionic villi. Mostly viruses and parasites, some bacteria
What is the common acronym for the most important transplacental infections?
TORCH
T: Toxoplasma O: Other (Listeria, Trepenoma, Malaria) R: Rubella virus C: Cytomegalovirus H: Herpes virus
If an embryo/fetus gets a TORCH infection, what is the difference if they get it early in pregnancy vs late?
Early: growth restriction, mental retardation, cardiac abnormalities
Late: Inflammatory tissue injury (pneuomonia, myocarditis, encephalitis…)
A baby is considered premature if it is born at a gestational age of how many weeks?
How much do they normally weigh?
Less than 37 weeks.
Usually weigh less than 2500 g
What is the pathogenesis of the respiratory disease associated with premature birth?
Infant Respiratory Distress Syndrome (IRDS) aka Hyaline Membrane Disease
Fundamental problem is that type II pneumocytes have not matured and cannot produce surfactant. Without surfactant, the surface tension is too high and the alveoli collapse on expiration. The neonate has to exert more effort to inhale again, gets tired, and generalized atelactasis sets in (airlessness, “collapsed lung”).
If the baby was able to live for a short time after birth but then died, it may show eosinophilic “hyaline membrane” lining inner surface of alveoli. It’s fibrin preciptate and necrotic epithelial cells. Worsens effectiveness of oxygen exchange.
What are the major treatments for the respiratory problems of prematurely born babies? What are 2 complications that can occur as a result?
Respiratory Treatments
1. Surfactant supplemented (has greatly improved prognosis since it’s been implemented)
- High-frequency oscillatory ventilator (HFOV) gives small jet streams of air that open up alveoli. Provides high oxygenation (80-100%)
Complications of High Oxygenation:
- Bronchoplulmonary dysplasia: decrease in alveolar separation
- ROS from oxygen may damage retina, causing blindness
Why do premature babies often have intraventricular hemorrhage?
Brain reacts to hypoxia by dilating its vessels. However, the vessels are not fully mature in the neonate and so hemorrhage can occur.
What is the syndrome that commonly affects the colon of very low birth weight premature babies?
Necrotizing Enterocolitis (NEC) - 1 in 10 VLBW infants
May be related to premature introduction of GI bacteria, but nothing specific has been identified. Inflammatory mediators like PAF may be related by increasing mucosal permeability, causing enterocyte apoptosis.
Can develop gangrenous intestinal perforations and peritonitis. May require bowel resection. If these babies survive, they may have post-NEC structures and fibrosis.
What must be done before a diagnosis of SIDS?
The infant <1 year of age must have a full autospy, death scene examined, and clinical history reviewed, and then the cause of death must still be unexplainable. Multiple petechiae is the most common finding in SIDS autopsies.
When and at what age are babies most at risk for SIDS?
What region of the brain may be related to SIDS deaths?
In what position should babies lay to prevent SIDS?
Babies are most at risk when they are sleeping, also between the 2nd and 4th month.
The arcuate nucleus may be related to SIDS as it has a critical role in arousal and response to noxious stimuli. SIDS babies may have delayed development of arousal reflexes and cardiorespiratory control.
Babies should lay on their back; babies who died of SIDS were often found laying prone. There is also some correlation between laying on soft surfaces and being too warm. Also a correlation between mothers who smoke or parents who use drugs.
What does “hydrops foetalis” mean?
What are the two major categories of fetal hydrops?
Fetal hydrops: accumulation of edema in fetus during intrauterine growth.
- Immune Hydrops: usually results from hemolysis as a result of Rh or ABO incompatability. Less common nowadays with good prophylaxis.
- Non-immune Hydrops: associated with cardiovascular defects, chromosomal abnormalities, and fetal anemia.
When can Rh- mothers have antibodies that attack an Rh+ fetus?
When is ABO incompatibility most likely a problem during pregnancy?
Rh- mothers may get large dose of Rh+ fetal blood with one pregnancy, providing enough antigens to lead to formation of IgG antibodies that can later cross the placenta in the next pregnancy.
ABO incompatibility is rarely a problem because most people just form IgM antibodies against other blood groups, and they can’t cross the placenta. However, type O mothers can sometimes have IgG antibodies against A and B antigens. Even then, the effects are more mild than Rh incompatibility.
What are some chromosomal abnormalities that can cause fetal hydrops (non-immune kind)?
45X (Turner), Trisomies 21 and 18.
The basis is usually cardiac anomalies. Turner syndrome may have impaired lymph drainage from the neck, causing nuchal fluid accumulation and “cystic hygroma” (an isolated effusion that can be compatible with life)
What are 2 non-immune causes of fetal anemia that may lead to fetal hydrops?
[may not be too important, just feel I should put more as fetal hydrops is an entire topic. The main thing to know for this topic is Rh incompatibility, which I didn’t want to fully explain because you probably know it]
- α-thalassemia: genetic defect causing impaired production of hemoglobin. More common in Southeast Asia
- Parvovirus transplacental infection
What is the prevalence of Cystic Fibrosis?
What type of inheritance does it follow?
What is the most common gene mutation?
1 in 3200 births in the U.S., commonly affecting Caucasian people. It’s the most common lethal genetic disease in white people
Follows autosomal recessive inheritance
CFTR gene change F508 (CFTRΔF508) is the most common mutation (70%), located on chromosome 7
