(From Dr. Tomlinson’s path lecture, 9 Nov 2000, by Brian Buschman)
Return to Semester Three Goodies
Return to The Unofficial Ross Page
Malformations are morphological problems that come along from the beginning. These include things like congenital heart disease.
Deformations are defects arising later as problems from mechanical factors. These may be things like forces from leiomyomas or hydro- related factors.
Disruptions are a destruction of a body part that began proper formation but something went wrong. This may include amniotic bands.
Sequence refers to multiple congenital problems all secondary to a common cause. The most notable being oligohydraminos (Potter’s) sequence. Oligohydraminos causes fetal compression and problems with fancies, hands/feet and pulmonary hypoplasia.
Most congenital abnormalities do not have s ingle problem but are caused by:
1) Genetic causes
2) Environmental factors like radiation, viruses (rubella & CMV) and chemicals like thalidomide, EtOH, foliate and such.
3) Multifactoral causes
The timing of the insult is most serious with the critical period being around the 4th or 5th week of pregnancy. Before that the fetus is likely to either abort or repair itself. After that point it may be well enough developed to be able to take the insult and develop naturally.
Infections get at the fetus by either of two methods. One way is through the mother’s bloodstream (transplacentally) and the other is through her vagina (transcervically).
Transcervical (ascending) infections come from the mother’s vaginal area and are either inhaled through amniotic fluid or via acquisition during birth. It is usually bacterial (like b-hemolytic strep) but if it’s viral it’s probably HSV II.
Transplacental infections are mostly caused by viruses and parasites. The bacteria include Treponema palladium and Listeria monocytogenes. They can be remembered by the mnemonic TORCH.
T – toxoplasma
O – Others
R – Rubella
C – Cytomegalovirus
H – HSV
IUGR babies are usually small for gestational age as would be expected. Causes are either fetal, placental or maternal.
I) Fetal causes can be chromosomal disorders, abnormalities, trisomies as well as infections. Usually it’s systemic in that all systems are affected equally.
II) Placental causes include things messing with the umbilical supply line. This may be a single umbilical artery, abnormal cord insertion, placentitis, multiple gestations (compete for supply) or placental previa (low lying placenta).
III) Maternal factors are toxemia, hypertension, drug use, smoking and malnutrition.
Hyaline membrane disease is the most common cause of neonatal respiratory distress. It is related to premature lungs with insufficient surfactant.
Babies present in great respiratory distress and need support to live. Complications causing death are patient ductus arteriosus, interventricular hemorrhage and bronchial dysplasia.
Treatment is best if it’s possible to try to delay the delivery or give corticosteroid treatment to the mother pre-partum. Post-partum you can give surfactant and high frequency ventilations till the lungs develop sufficiently and enough surfactant is produced.
Erythroblastosis fetalis is caused by the mother and baby having different ABO/Rh blood types. It is mostly a problem when the mother develops Anti-D (Rh) antibodies or when the mother is type O and develops Anti-A or Anti-B antibodies. If mom is type O she may already have anti-A and anti-B antibodies. In either case the first exposure to blood (fetal or other) of another bloody type will produce IgM antibodies to the type. Then with the second exposure there will be IgG antibodies produced. That means with the second pregnancy they can cross the placenta.
There are two severe problems that are caused by erythroblastosis fetalis.
1) Hydrops details which is hypoxic injury to the heart and liver. You see general edema (anasarca) from hepatic and circulatory failure.
2) Kernicterus is the uptake of bilirubin into the brain. It is only a problem in little ones because their blood-brain barrier is not well developed yet.
It is treated pre-partum by administration of antibodies to block the maternal Abs. The kernicterus can be treated post-partum by photothearpy because sunlight causes conjugation of bilirubin to excretable products. This can be used to prevent the mental retardation.
Chromosome 7 can have a problem with the CFTR gene which causes problems with cAMP-dependent Cl- channels. Some Cl- channels work properly because they are Ca++ regulated. This leads to decreased reuptake of Cl- from sweat glands and decreases excretion of Cl- into the respiratory tract. This causes failure of Na+and H2O to follow in both cases which leads to “salty” bebies and thich respiratory mucus.
Morphologically you may see problems with a large number of organs because of thick mucus It can plug up the lungs, GI, pancrease and biliary tract. The obstructions can also lead to chronic bacterial infections.
Death is usually from respiratory failure from obstructive pulmonary disease due to inflammatory response to infection. The best treatment is to control infections. They also use organ transplants and are working to develop gene therapy.
SIDS is defined as sudden, unexplained death of an infant under age 1. 90% happen in the first 7 months. No one theory explains SIDS but some think some causes have to do with errors in acyl-CoA dehydrogenase (med-chain type) or sleep apnea from brain stem dysfunction.
Risk factors include:
I) Infant factors
a. Premature
b. Low birth weight
c. Male
d. Sleeping prone
e. Product of multiple births
f. Not the oldest
II) Maternal factors
a. Young mother
b. Unmarried
c. Low socioeconomic status
d. Smoking/drugs
e. Black
Hyperphenylalaninemia is caused by an enzyme deficiency. Hyperphenylalaninemia is young kids can lead to neural development problems by interfering with AA NT systems. It is treated by restricting the intake of phenylalanine. It most states it’s law that you screen newborns.
Malignant hyperphenylalaninemia does not respond to dietary restriction. It is caused by a different set of enzymes and blocks the metabolism of multiple AAs.
Adults do not need to be as strict at regulating their phenylalanine levels since their CNS has already developed but if they get pregnant they need to be restricting what they eat even before they get pregnant.
People with galactosemia have an error in galactose metabolism and hence need to regulate galactose intake. This is very tough since galactose is part of milk. They must be feed special formula.
These babies present with vomiting, diarrhea, failure to thrive and sometimes jaundice with hepatomegaly. If it is not regulated it will lead to mental retardation and cataracts.
Tumors are important in pediatrics because they are the number two killer of 4-14 year olds. Most are benign tumors.
Choristomas are normal microscopic cells that are just growing in the wrong place.
Hamartomas are extensive proliferations of cells in their proper location. The cells just grow wildly and do not represent a proper pattern of growth in the specific tissue.
Hemangiomas are proliferations of blood vessels at the surface of the skin. It has a “port-wine stain.” They will usually resolve on their own.
Lymphangiomas are proliferations of lymph channels often in the neck, axilla and mediastinum. They are only a problem when they bother important structures.
Sarcococcygeal tetratomas are tumors of the germ layers which cause a benign growth of a mass in the sacral/coccogeal region.
Malignancies in peds are similar to those in adults but:
1) Are different types. Tend to be of hemopoetic, neural and soft tissues.
2) Often they are tied to developmental abnormalities.
3) They may naturally regress or spread.
4) They are likely to be genetically caused.
Neuroblastomas are the most common cause of tumor in the first year. 1/3 of them are in the adrenal medulla and the rest are usually sympathetic. These tumors may progress to ganglioneuroma which is a proliferation looking like a ganglia. Others tend to regress naturally.
The staging system is similar to that of lymphoma but based on left/right rather then relation to the diaphragm. It appears in three types with set characteristics:
|
Type I |
Type II |
Type III |
|
Hyperdiploid DNA |
Near-diploid DNA |
Diploid DNA |
|
No N-myc amplification |
No N-myc amplification |
N-myc amplification |
Large Trk A expression |
Low Trk A expression |
Slight Trk A expression |
|
|
Older (not ped) patients |
|
|
High cure rate (>90%) |
Low cure rate (25-50%) |
Very low cure rate (<5%) |
The Wilm’s tumor is usually seen in age 2-5 and is the most common cause of solid abdominal tumors in peds. It shows a large abdominal mass with pain, hematouria, hypertension and intestinal obstruction. Often they have pulmonary metastasis.
There are three conditions associated with increased rates of Wilm’s tumor.
1) WAGR syndromes is related to 11p13- where a WT-1 anti-cancer gene is found. You see aniridia (no iris), GU problems and retardation.
2) Deny’s-Drash Syndrome has gonadal dysgenesis and renal abnormalities. The problem is usually found on 11p13.
3) Beckwith-Wiedmann Syndrome. These patients have large viscera and general gigantism. The problem is with 11p15.
Return to Semester Three Goodies
Return to The Unofficial Ross Page