Download Diseases of Infancy and Childhood

Pathology
11.05.08
Diseases of Infancy and Childhood
Transcriber: Sheila Karst Morris
Slide 1
The reason we have a separate lecture on childhood and infancy is because there are unique things that
happen to children and not adults. You need to understand some of the things that we’ll be talking
about that occur in infancy and childhood.
Slide 2
One of the first things is some terminology you need to be familiar with. A neonate is someone from the
first 4 weeks or 28 days of post natal life. Infancy includes neonatal period and extends to the first 12
months. Childhood is the period beyond infancy up until puberty, which varies according to when it
starts, around 11 or 12 depending on gender. Adolescence is puberty until growth cessation. Immature
infant refers to a pre term infant less than 1000g or less than 28 weeks of gestation. We’re seeing more
of these; they tend to have more medical problems. We use the general term pre-term infant to include
all infants of less than 37 weeks and 2500g, so an immature infant is a subcategory. Not all pre-term
infants are immature, greater than 1000g less than 2500g, which are pre-term but not immature. The
post term infants, that hang around in the womb too long, over 42 weeks, are post term, they have
problems too.
Slide 3
What makes babies come before they should? A lot of things, the single most important is infection, in
the mother and in the amniotic fluid. A lot of things that happen, if you have an infection in the
amniotic cavity from the lower genital tract in the mother, this can cause cytokine release and
inflammation, phospholipases and things that trigger labor. Many bacteria have been implicated in this.
Prolonged rupture of the fetal membranes stimulates labor as well. If you have more than one fetus,
they grow bigger and quicker so your body thinks it’s time to get rid of them sooner. This is why almost
all multiple gestation births, especially beyond two, tend to occur prematurely. These women often
have to go to bed rest in the latter part of pregnancy. The multiple gestations are becoming more
common due to fertility treatments. Cervical incompetence is where the cervix opens before it should.
This causes many miscarriages and premature deliveries. Placental abnormalities, such as improper
implantation or implanted in the wrong place, can cause the pregnancy to culminate sooner than it
should.
Slide 4
A baby that’s born prior to term is beset with a great many problems because it’s not ready to be out
there doing things on its own, it should have more time in the uterus having things done for it. For
example, the developing fetus makes much of it’s hematopoeisis in the liver before it shifts over to the
bone marrow in later gestation and after birth. The liver is also important in the breakdown of RBC into
bilirubin and bile pigments. If you have a baby that’s born before term, the liver’s not ready to take on
all those responsibilities, that’s why you have physiologic jaundice of the newborn. The liver’s not quite
doing as much as it should, breaking down RBC and making bilirubin, and processing and conjugating the
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 2
bilirubin and excreting it in the bile. The bilirubin in the circulation of the baby is higher than it should
be, so the baby may be jaundiced. This is usually something transient, after the baby’s born the liver
begins to work, if it’s born preterm it may be several days before this happens.
In the cases that aren’t terribly severe, putting the baby under UV light or a sunny window, because UV
breaks down bilirubin in the cutaneous vessels under the skin, breaking it down until the liver can take
over.
Slide 5
One of the more important things that has occurred in children is immaturity of the lungs with
respiratory distress syndrome. This is the pathogenesis: the lungs develop a lot in the late stages and
weeks of gestation. The two types of cells lining the alveoli and terminal bronchioles is the type 1, which
are involved in gaseous exchange, and type 2, the cuboidal cells, which come in later gestation and
produce surfactant. Surfactant is necessary to reduce the oxygen tension in the lungs and help diffuse
oxygen and allow gaseous exchange to take place more readily. If you don’t have enough type 2
surfactant secreting cells, you don’t have enough surfactant and the lungs tend to collapse. Surfactant
keeps them open, you have negative pressure in your thoracic cavity, inhale they expand, exhale they
contract but don’t collapse. In a preterm baby that’s not making enough surfactant, the lungs will
collapse when it exhales.
Slide 6
You then have uneven perfusion and hypoventilation. The oxygen concentration in the circulation goes
down because you have impaired gaseous exchange. CO then is retained in the tissues, ultimately a
respiratory acidosis occurs. Due to the acidosis you get vasoconstriction in the lung, which further
aggravates the hypo-perfusion. You get damage to the endothelia of the capillaries; ultimately you get
plasma leaking into the alveoli. Fibrin and necrotic cells enter the alveoli, mixed in with the plasma,
which further aggravates ending in hyaline membrane disease. In a newborn infant, especially one born
preterm, the lungs are much more cellular, the interstitial spaces have more cells than mature lungs, but
you see pink fibrin/hyaline membranes. The baby manifests this by grunting, it’s trying to produce
pressure in the lungs to open the alveoli. In many cases you can just give them end expiratory pressure,
positive pressure like CPAP that help expand the lungs. In more severe cases, they have to be put on a
ventilator because they get too tired to breathe. We now have exogenous surfactant, bovine, that can
be given through an endotracheal tube to the infant until their lungs produce surfactant on their own.
In the case of the respiratory distress syndrome, if you have to put a baby on positive pressure oxygen
and a ventilator and give them high concentration of oxygen to oxygenate their brains, this runs the risk
of doing two things. It will cause them to develop bronchopulmonary dysplasia; you get the effects of
the oxygen on the lung, ultimately a fibrosis of the lung or chronic lung disease. The baby may have
chronic dependence on a ventilator. The other is changes in the eye that can occur. High
concentrations of oxygen can cause toxicity in the retina. This is why it’s a standard of care for all
newborn infants who have received oxygen and ventilation to be given a careful ophthalmologic
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Sheila Karst Morris
pg. 3
examination to make sure there are no abnormalities in the eye. They have to have routine eye care
thereafter; there can be significant visual problems.
Slide 7
Another problem that newborn infants can have is immaturity of the brain. When babies come out too
soon things aren’t ready. An infant born at about 7 months has a smaller brain, without a temporal
lobe, they don’t have as many sulci and gyri. The brain is very delicate at this time; if a preterm baby
passes through the mother’s birth canal the head is squeezed (that’s why the bones haven’t fused in the
baby’s skull, so it can compress to get out). In a newborn infant there is a rich plexus of vessels lining
the ventricles of the brain, especially an immature infant. Squeezing through the cervix can cause them
to bleed. Other things such as temperature instability or fluctuating blood glucose, they can’t regulate
as well, when they go up and down you’re at risk for developing a hemorrhage. In cross section you can
see a hemorrhage in the ventricle. Because of the bleeding into the ventricles as a result of trauma at
birth, the blood can stop up the flow of CSF through the aquaduct, causing hydrocephalus. The baby’s
head starts getting larger because the bones have not fused. In some cases you have to draw off the
CSF or put a shunt in to get it into the peritoneal cavity.
Slide 8
Another complication that preterm infants can get is called necrotizing enterocolitis. What happens in
many cases where infants are delivered prematurely, if there is a strangulation of the umbilical cord or
premature separation of the placenta, anything that causes asphyxia or decreased oxygenation can
cause ischemia in the intestinal epithelium. When the baby becomes colonized with bacteria after birth,
especially with formula feeding, the bacteria invade the bowel because of the damaged epithelium. You
get gas production; it’s manifested by a distended abdomen and bloody diarrhea. In some cases the
infection and inflammation in the bowel becomes so severe you get gangrene and they have to remove
a portion of the bowel. You see the black colored area of the small bowel due to gangrene. It’s almost
always in preterm infants asphyxiated during delivery. In many cases there’s a low threshold towards
doing a cesarean section to get the baby out of the womb so you can get it oxygenated.
Slide 9
There are a lot of things that can affect the growth of a fetus while it’s in the mother’s womb.
Intrauterine growth retardation is children born less than the 10th percentile of the gestational age for
birth. A lot of things can cause this and affect up to 1/3 of all live births. Any type of abnormality of the
placenta, it’s the vehicle though which nutrients get to the baby. Any anomalies of genetics that can
affect the developing fetus can cause growth to be slowed. Congenital infections such as CMV that can
cross the placenta can certainly affect growth. Things like hypertension, drug abuse and smoking in the
mother also have smaller babies.
Slide 10
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 4
One of the things commonly done in the delivery room when a baby is born to get an idea of the
prognosis during the neonatal period is the Apgar score. It’s what the obstetrician measures at 1 min
and 5 min after birth. The parameters they look at, a score of 2 each, heart rate greater than 100,
spontaneous respiratory effort, pink rather than blue color, muscle tone when pulling the babies toe or
scratching its foot, and response to noxious stimuli (they should cry). Two points each, the higher the
score the more likely it’s a normal neonate. Lower means look out for problems.
Slide 11
If you survived your gestation and come into the world there’s all kinds of things that can happen. The
things that cause infants and children to die are much different that cause older people to die. Last
month I gave you examples of the common causes for death in developed/undeveloped countries.
Children die for different reasons than adults, in some cases the adults aren’t watching after them, and
some are unique to children. Infants less than one year, the things that cause them to die are often
things that happened at the time they were born or before. Congenital abnormalities, SIDS, and
infections.
At one to four years, it’s still some of the congenital anomalies, and others. Injuries: less than one year
they stay where you put them, after one year they start running around. Drowning, neoplasias,
homicide, and heart disease, in some cases congenital. You see some of the same things repeated in
different age groups, but when you get to the teenage period you begin to see suicide. Adolescents
tend to get depressed and try to kill themselves.
Slide 12
What causes children to get injured? They get burned, drowned, suffocated, shot, fall down or get
poisoned.
Slide 13
Some of the other things: malformations and deformations. The things that are intrinsic defects in
morphogenesis: congenital malformations. Up to 3% of births have them, but in most cases you have a
child with something wrong and don’t know what caused it, the mother, the father, or no one. In many
cases you have no idea. Some of them may be inherited; some may be a spontaneous mutation. The
important thing is whenever a parent gives birth to a child with a malformation both parents should
have a genetic evaluation to see if there’s something in their genetic background that could attribute to
it. It can make a difference if they choose to have subsequent children.
Some of the causes of congenital malformations are many of the chromosomal or multi-factorial
conditions. Single gene mutations, maternal disease, exposure to drugs and chemicals and of course
exposure to radiation.
Slide 14
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 5
One example of malformations is a common heart condition, a septal defect. The septum between the
ventricles has a cardiac malformation.
Slide 15
This is anencephaly, a failure of the brain to develop. The neural tub on the back of the embryo must
fuse, the brain develops from the telencephalon and diencephalon, etc…if none of that develops you get
anencephaly. You can diagnose this prenatally with choriocentesis or do an ultrasound and see the
head’s not there. The babies may die in utero or carry to term but die soon thereafter.
Slide 16
There are a number of other CNS malformations. Be familiar with these terms. Encephalocele is a
herniation of the brain through an opening of the skull. Meningocele is the meninges through the skull
or spinal column, not the brain tissue. Meningomyelocele is the herniation of the meningeal tissue
through the spinal column. Some babies are born with this, it must be operated on right way because
their nervous system is exposed to the environment and can get infected. The common name for these
conditions is spina bifida, it’s a failure of the neural tube to close in embryogenesis. You may have a lack
of control of the bladder and paralysis of the lower limbs because all the nerves to the lower limbs may
not function properly.
Slide 17
In the GI tract some of the terminology you should be familiar with is omphalocele, a protrusion of the
intestine through a defect in the abdominal wall at the umbilicus. A gastroschisis you have extrophy of
abdominal contents but it doesn’t involve the umbilicus. The baby can be born with the viscera
protruding; it must be poked back in and sewn up.
Slide 18
Congenital CMV is one congenital infection you should be familiar with. I mention it because it’s the
most common type of congenital viral infection and it has some important things you need to know.
The baby with CMV is called the “blueberry muffin” syndrome because with the little spots,
thrombocytopenia where the virus goes throughout the body during the pregnancy, infects the bone
marrow and causes problems with the megakaryoctyes that make platelets. You don’t have enough
platelets and get hemorrhage. Also microencephaly, MR, a receding chin, importantly you can get
blindness or vision problems because the virus infects the optic nerves. It can also affect the 8th nerve,
the auditory nerve; this is why deafness can occur as well. Remember we showed earlier the different
inclusions you can see with DNA viruses, here’s a thyroid from a baby that died with congenital CMV.
You can diagnose the CMV cells in the tissues; you can also detect them from the body fluids by
culturing secretions. You can also find an antibody response to CMV. Most women that have CMV
don’t have a problem, many babies with CMV don’t have a problem, but if a pregnant woman gets a
CMV infection, there is the risk that it will cross the placenta and cause a problem. It can cause it to be
born preterm, cause intrauterine growth problems and congenital problems.
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 6
Slide 19
I mention rubella for historical interest mainly. This is the German measles. Everyone gets vaccinated
as an infant now. Before the vaccine if a woman got pregnant and got the rubella virus while pregnant,
there was a high likelihood that the baby would be born with a congenital septal defect, cataracts and
deafness, the rubella triad. You’re not going to see this because of the vaccine.
Slide 20
Disruptions and deformations are developmental anomalies due to mechanical factors that are extrinsic
disturbances. Not something genetically wrong with the baby but something that happened during
pregnancy to cause the problems. This usually doesn’t occur during the first trimester when
organogenesis occurs; it usually develops at a later part of pregnancy and occurs in up to 2% of birth.
Uterine constraint, like if a mother has leiomyoma tumors in the uterus. If you have oligohydramnios,
not enough amniotic fluid it can affect the development of the lungs and kidneys.
Slide 21 – skip
Slide 22
If you have renal agenesis, this is called “Potter’s syndrome”, if the baby doesn’t make kidneys it doesn’t
make urine. Much of the amniotic fluid and amniotic cavity comes from the baby’s urine. Without it the
lungs don’t develop properly. The characteristics in addition to the lack of kidneys are low set ears,
deformed hands and feet and flattened facial features and micronathia, receding chin. These babies
usually die soon after birth.
Slide 23
This is a child at autopsy born with pulmonary hypoplasia due to oligohydramnios. This is the abdominal
cavity; the lungs and chest cavity are very small, the lungs never developed.
Slide 24
Another condition, always questions on the optometry boards about this, fetal alcohol syndrome. It has
a number of important aspects you need to be familiar with. This is why you shouldn’t drink while
you’re pregnant, just 2-6oz a day can put the fetus at risk. The baby can be growth retarded, MR, will
have microcephaly, and these children are often quite a burden on society.
Slide 25
Sudden infant death syndrome also appears on the optometry boards. It’s by definition of the death of
an infant less than one year of age that there’s no obvious explanation for, after a thorough explanation.
Usually within the first 6 months, usually at home in their sleep. They often have a preceding
respiratory infection; there are a lot of things related to it, a lot of studies going on.
Slide 26
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 7
It’s more common in younger women who are unmarried that have a lot of babies, and that are poor,
smoke and abuse drugs. These are all associations, it’s hard to say if there’s cause and effect this way.
There’s some suggestion it may be an arrhythmia, a congenital heart condition and the heart stopped
beating. This is why they have heart rate monitors, especially if you’ve had a child with this and have
another child, the heart rate monitor goes off and the mother can hear it.
Slide 27
We need to mention cystic fibrosis; we have a lab case with it. CF is very common, 2-4% in the
Caucasian race is carriers of the gene, it’s autosomal recessive so if two parents carry the gene one out
of four children may be homozygous recessive and have CF. it is a disease that has variable penetrance.
Many children may be affected to a greater degree than others, depending on a lot of things, a lot of
different genes involved. It’s a disorder of epithelial transport of chloride. What it amounts to is that in
the respiratory and GI and reproductive tract you get very thick secretions that clog everything up. In
the respiratory tract these secretions cause infections with pseudomonas, respiratory infections are a
big problem. You can get chronic lung disease from this.
The pancreas, cysts develop because the pancreatic ducts are plugged up. You can’t secrete the
enzymes, you don’t secrete lipases and proteases, and as a result you get malabsorption, get
steatorrhea, and can’t digest fat. You can’t digest proteins very well. This is why the infants have failure
to thrive; they don’t get the benefits of the things they eat. They get infections, they grow poorly and
there’s a high rate of death in childhood. It’s certainly a shortened life span, and they’re infertile due to
the plugging in the reproductive system, they can’t produce sperm.
Now, because of better treatment of the infections, giving exogenous enzymes and vitamins to replace
the things they can’t produce themselves and better overall care, and in the adults they’re doing lung
transplants to give them healthy lungs. More people are living longer than ever; there are a lot of adults
leading fairly normal lives with CF.
One of the ways to diagnose cystic fibrosis is through a sweat test; the chloride content will be elevated
because of the lack of the chloride system. Stimulate sweating by administrating pilocarpine and then
collecting the sweat and measuring chlorine content. Elevated chlorine is diagnostic.
Slide 28, 29, and 30, already covered.
It is caused by a gene mutation on chromosome 7, a lot of different mutations have been described and
that’s why you see a difference in severity.
Slide 31
Here’s the pancreas showing the cysts and the secretions that result in pancreatic cystic fibrosis/
Slide 32
Here’s the lungs, the have chronic obstructive lung disease due to the CF.
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
pg. 8
Slide 33
The last thing I’d like to mention is some tumors of childhood. The tumors that children get are very
different from the tumors adult get in most cases. The most common in infancy are benign tumors like
hemangiomas, they’re often called birthmarks. These are like capillary plexus; you see it in cross
section. They’re not a problem except for cosmetic purposes, and sometimes they regress.
Slide 34
Sacrococcygeal teratoma, we talked about teratomas already, these can occur in adults.
Slide 35
Leukemias bear mentioning because they are the most common cause of neoplastic death in childhood.
They represent more than half of all childhood neoplasias. Children with downs syndrome are at higher
risk for developing leukemias. This is one of the great success stories in cancer treatment. The majority
of children diagnosed with leukemia, especially acute lymphocytic leukemias can go into remission and
be cured. With aggressive chemotherapy they can go into long term, perhaps permanent remission.
Slide 36
Neuroblastoma is the most common solid tumor of childhood. These are actually a tumor that grows in
the adrenal cortex or somewhere else in the sympathetic nervous system. These will secrete
catacholamines, epinephrine and norepinephrine. That’s one of the ways you can diagnose them.
Often found early, here’s a large one on the kidney in the adrenal. Sometimes they can evolve into a
ganglioneuroma, and this (neuroblastoma) can spontaneously regress.
Slide 37
The one that the optometrists should be familiar with is retinoblastoma. This is the most common
intraocular tumor in childhood, arises in the retina, usually 16mo-2 yrs, sometimes bilaterally, and
associated with deletion of the long arm of chromosome 13. You see the globe is filled with the
retinoblastoma.
Slide 38
Finally we have Wilm’s tumor, one of our lab cases, nephroblastoma. It arises in the kidney, the most
common renal tumor in children, usually occurs in infants to 2 yrs. You see the kidney; the tumor’s
actually bigger than the kidney. The nice thing about this is that it’s associated with a good prognosis.
Take the kidney out, give chemotherapy; many times you actually cure it. There’s also an optometric
association with this one, aniridia, an abnormality of the iris is one of the things associated with it. If
you see this palpate the abdomen and alert the child’s parent that there’s a risk for wilm’s tumor and
have an appropriate exam. This is associated with a deletion of the short arm of chromosome 11.
Pathology: Diseases of Infancy and Childhood
Sheila Karst Morris
**Aniridia
pg. 9