4. Disease of Infancy and Childhood (Ch 10) Flashcards
What are the four time spans to group disorders?
the neonatal period- first 4 weeks life
infancy- first year of life
Toddler/preschool- age 1-4
School age- age 5-15
The US is ranked 31st in infant mortility rates among the developed nations in the western hemisphere. About 5.3 in every 1000 americans die during pregancy, what about among african americans?
12.4 / 1000
What is any deviation from or interruption of the normal structure or function of a part, organ, or system of the body as manifested by characteristic symptoms and sign; the etiology pathology and prognosis may be knonw or unknown?
Disease
What is a derangement or abnormality of function; a morbid physical or mental state / condition?
Disorder
What is any new and abnormal growth; specifically a new growth of tissue in which the growth is uncontrolled and progressive?
Neoplasm
What is a set of symptoms that occur together; a symptom complex; the sum of signs of any morbid state?
Syndrome
Under what two situations can apoptosis occur? Give an example for each
Physiologic situations such as destruction during embryogenesis, withdrawl of hormons, cell loss, cells that are no longer useful
Pathologic Situations: DNA damage, accum of misfolded proteins, cell death by infection, duct obstruction
What are anatomic defects that are present at birth but some such as cardiac defects and renal anomalies may not become clinically apparent until years later?
Congenital abnormalities
Determine which age group the following causes of death (most common to least) fall under... Accidents Malignant neoplasms congenital malformations influenza / pneumonia
Age 5-9 yrs
Determine which age group the following causes of death (most common to least) fall under... Accidents Congenital malformations Assault Malignant Neoplasms Disease of heart
Age 1-4
Determine which age group the following causes of death (most common to least) fall under…
Congenital malformations
DOs related to short gestation and low birth weight
Sudden Infant death syndrome SIDS
—–Respiratory Distress of newborn
Younger than 1 year
Determine which age group the following causes of death (most common to least) fall under... Accidents Malignant Neoplasms Suicide Assault Congenital malformations
Age 10-14 years
What represents primary errors of morphogenesis in which there is an *intrinsically abnormal developmental process due to a single gene or chormosomal defect and are commonly multifactorial in origin?
Malformation
What are some examples of malformations? 4
Polydactyly
Syndactyly
Congenital heart defects/anencephaly
Holoprosencephaly (penis nose)
What is a result from secondary destruction of an organ or body region that was previously normal in development, thus arising from EXTERNAL disturbance in morphogenesis?
Disruption
What is an example of disruption which denotes rupture of amnion with resultant formation of bands that encircle or attach to parts of the fetus? NOT heritable, NOT associated with increase risk in future pregs (unlike malformations)
Amniotic Bands
What also represent an extrinsic disturbance of development rather than intrinsic, due to localized or generalized compression of the growing fetus by ABNORMAL biochemical forces, leading to structural abnormalities?
Deformations
What is the most common cause of deformation?
between 35-38 weeks fetus is growing and uterus is not- can cause compression, due to maternal factors like first pregnancy, small uterus, leiomyomas, Fetal/placental factors like oligohydramnios, multiple fetuses.
Uterine constraint
what is a cascade of anomalies triggered by one initiating abberation, half of the time due to congenital anomalies singly, the remaining d/t multiple congenital anomilies.
Sequence
A good example of sequence caused by one initiating abberation is potter sequence. Explain the cause of the sequence and what it causes (5)…?
Renal agenesis/amniotic leak cause OLIGOhydramnios causes fetal compression resulting in..
- pulmonary hypoplasia
- Compressed/altered facies
- Clubfeet / abnormalities of hands
- Breech positioning
- Amnion Nodosum
What is amnion nodosum and what can be assumed if it is seem upon autopsy?
They are nodules in the amnion due to oligohydramnios = potter sequence
What is a constellation of congenital anomalies that cannot be explained on the basis of a single, localized, initiating defect?
Malformation syndrome
What refers to the complete absence of an organ and its associated primordium?
Agenesis
What closely related term to agenesis, referes to the absence of an organ, but one that occurs due to failure of growth of the existing primordium?
Aplasia
What describes the absence of an opening, usually of a hollow visceral organ such as the trachea or intestine?
Atresia
The common known causes of congenital anomolies can be grouped into 3 categories: genetic, environmental and multifactoral. What falls under each category?
genetic: chromosomal aberration 10-15% / mendalian 2-10%
environmental: Maternal infection 2-3%, maternal disease state 6-8%, teratogen 1%
multifactoral - 20-25%
***40-60 of abnormalities remain unknown
Thalidomide used in the past as a tranquilzer showed 50-80% fetus with limb abnormalities. Alcohol consumption is a teratogen which can lead to growth retardation, facial anomalies (microcephaly, short palpebral fissures, maxillary hypoplasia), and psychomotor disturbances, together known as?
Fetal alcohol syndrome
***No philtrum between lip and nose!
Low IQ
There are two general principles of developmental pathology which are releveant regardless of the etiologic agent. The first is?
The timing of the prenatal teratogenic insult has an important impact on the occurence and type of anomaly produced
The intrauterine development of humans is divided into two phases 1- embyonic period during first 9 weeks, 2- fetal period for remainder. In the early embryonic period (first 3 weeks after fert) injurious agents cause damage and death. Between the third and ninth weeks, what can occur?
the embryo is extremely susceptible to teratogenesis, with PEAK sensitivity occuring during 4th-5th week**!
After 9 weeks, during fetal period the child is not as susceptible to teratogenic agents but instead the fetus is susceptible to?
growth retardation/injury to alreadu formed organs
List during which weeks is the critical periods of development for the fetus... CNS Heart Arms Eyes Legs Teeth Palate External genetalia Ears
CNS 3-6 Heart 3-6 Arms 4-7 Eyes 4-8 Legs 4-7 Teeth 6-8 Palate 6-9 External genetalia 7-9 Ears 4-9
The second general principle of developmental pathology: The interplay between environmental teratoens and intrinsic genetic defects is examplified by the fact that features of dysmorphogenesis caused by environmental insults can often be recapitulated by genetic defects in the pathways targeted by these teratogens. What are three general examples?
Cyclopamine
Valproic Acid
Retinoic acid (Vitamin A-retinol)
Valproic acid is an antiepileptic drugs that can lead to valproic acid embryopathy, which is due to a mutation where?
homeobox proteins (HOX)
A vitamin A derivative that is require for normal development and differentiation is retinoic acid. When there is excess it can lead to?
it is teratogenic and causes CNS, cardiac, cleft lipi/palata and limb abnormalities
What is defined by a gestational age less than 37 weeks, and is the second most common cause of neonatal mortality, behind congeital abnormalities?
Prematurity (premature infant is considered under 37months)
*12% of all live births are premature
What are the 3 subcategories of preterm/ premature births which are base on gestational age?
extremely preterm less than 28weeks
Very preterm between 28 and 32 weeks
Moderate to late preterm 32 to 37 weeks
There are major risk factors for prematurity, including preterm premature rupture of placental membranes PPROM. PPROM is responsible for 1/3 of preterm deliveries. What is the major difference between PPROM and PROM?
PPROM occurs before 37 weeks with higher risk
PROM occurs after 37 weeks and involves decreased risk
Another risk factor for prematurity is intrauterine infection which causes about 25% of preterm births. this is a major cause of?
preterm labor with and without itnact membranes
The third risk factor for prematurity is uterus/cervix/placental abnormalities which include uterine distortion, compromised structural cerivcal support, placenta previa, and abruptio placentae. What is the 4th risk factor that increases incidence of premature birth?
Having Multiple gestations (twin pregnancy)
Infants that are undergrown from where they should be for their gestational age (small for gestation age SGA) in which they are below 10th percentile for gestation age suffer from?
fetal growth restriction which may result from fetal, maternal or placental abnormalities
Some of the fetal causes of fetal growth restriction include chromosomal disease, congenital anomalies, congenital infections. Most common infections responsible for FGR are the TORCH group of infections which are?
ToxOplasmosis
Rubella
Cytomegalovirus
Herpesvirus
*will see proportional FGR meaning all organs are similarly effected
Some placental abnormalities can lead to fetal growth restriction such as uteroplacental insufficiency resulting from umbilical-placental vascular anomalies, placental abruptions, placenta previa, placental thrombosis, and placental infection— causing what type of FGR?
Placental causes FGR to result in asymetic/ disproportionate growth retardation of the fetus, sparing the brain
Maternal abnormalities also can lead to FGR, most commonly conditions that result in decreased placental blood flow. This includes preeclampsia, hypertension. Also thrombphilias. What are 3 avoidable maternal factors?
smoking, alcohol intake, narcotic abuse
What are two major hazards/ diseases that comes along with prematurity?
neonatal respiratory distress syndrome (RDS)
Necrotizing entercolitis
There are many causes of respiratory distress in the newborn the most common cause is _____ which is also known as _________ because of the deposition of a layer of hyaline proteinaceous material in the peripheral airspaces of infants who succumb to this condition.
RDS
hyaline membrane disease
In untreated infants (no surfactant) there is characteristic presentation; preterm with appropriate weight for age, resusitation at birth but normal breathing after few minutes, thne problems in 30 minutes leading to? 5
cyanosis respiratory distress fine rales hypoxemia *ground glass picture upon CXR
Immature lungs is what RDS develops from. The younger the gestation age (28weeks) the more likely of having RDS. The fundamental defect in RDS is a deficiency in?
pulmonary surfactant
Surfactant consists of two groups of surfactant associated proteins; defesnse and surfactant proteins. What are in each category?
Defense proteins: SP-A, SP-D
Surfactant proteins: SP-B, SP-C, surfactant lipids (can measure these in amniocentesis*)
Surfactant decreases surface tension and allows alveoli to stay open with less pressure. Surfactant production is produced by _____ and is accelerated after the 35th week of gestation.
Type II pneumocytes (alveolar cells)
Without surfactant, the lungs collapse with each breath, working just as hard as they did for their first breath. What mutations cause congenital deficiency of surfactant?
SFTPB and SFTBC gene mutations
The lecithin-sphingomyelin L/S ratio can be measure in the amniotic fluid. If the ratio is greater than 2 it indicates the fetal lungs are mature. If it is lower than that it can lead to immature lungs, why do we care?
we can easily fix the lack of surfactant by providing glucocorticoids to the mother which can increase surfactant production (diabetic mothers have high insulin which counteracts steroids = dec. surfactant production)
Along with glucocorticoids, prolactin, thyroxine and what other agent modulates surfactant production?
TGFB
*Note: labor increases surfactant production so if the mother is planned C section make sure to give steroid before hand for adequate surfactant production
Upon gross examination of the lungs they are red purple, solid airless like the liver. Microscopically alveoli are poorly developed. When the infant passes necrotic material is incorporated with what?
eosinophilic hyaline membranes (fibrin+necrotic cells) lining the respiratory bronchioles, alveolar ducts and alveoli
In RDS after exogenous surfactant administration after birth, recovery begins in 3-4 days. OXygen is required, but high concentration for prolong times leads to what two complications?
Retrolental fibroplasia ROP-retinopathy of prematurity
Bronchopulmonary dysplasia
* not as frequent anymore
There are two phases of retrolental fibroplasia, 1 is during hyperoxia in which VEGF is decreased and the second phase is hypoxia when bb goes back to room O2, causing?
VEGF to increase, resulting in increased blood vessel formation
The major abnormality with bronchopulmonary dysplasia is striking decrease in alveolar septation (large alveoli), caused by reversible impairment in the development of alveolar septation. Possibly due to proinflammatory cytokines released by the dysplasia, including?
TNF, IL1, IL6, IL8 which arrest alveolar development
What is most common in premature infants with the incidence of disease increasing with very low birth weight infants (<1500gm)? 2500 cases occur annually…
Necrotizing enterocolitis NEC
NEC is multifactorial, along with prematurity ist is postulated that there is a postnatal insult such as bacteria, leading to tissue destruction. What mediatory has been implicated in increasing mucosal permeability by promoting enterocyte apoptosis and compromising intercellular tight junctions— fuel to the fire?
Platelet activating factor PAF
The clinical course of NEC is fairly typical, with the onset of bloody stools, abdominal distention, and development of circulatory collapse. Radiographs demostrate gas within the intestinal wall known as?
pneumatosis intestinalis Most common diagnostic sign
GOLF BALLS IN INTESTINE
Necrotizing enterocolitis typically involves the terminal ileum, cecum, and right colon although any part may be involved. The segment is distended, friable and congested- gangrenous with perforation and peritonitis. What is the treatment?
60% require resection of necrotic segments but post surgery delevop necrosis and strictures from fibrosis
Fetal and perinatal infections are acquired through one of two primary routes- transcervically (ascending) or?
transplacentally (hematologic)
Most parasitic and viral infections and a few bacterial infections gain access to the fetal bloodstream transplacentally via the?
chorionic villi
What are the two primary routes that perinatal infections are acquired?
parvovirus B19
TORCH
Parvovirus 19 which causes erythema infectiosum or ‘fifth disease of childhood’ in immunocompetent older children, can infect 1-5% of seronegative pregnant women- most are normal. In the abnormal response to parvovirus 19 what is seen?
it can induce spontaneous abortion, stillbirth, hydrops fetalis and congenital anemia
What has a particular tropism for erythroid cells, and diagnostic viral inclusions can be seen in early erythroid progenitors in infected infants?
Parvovirus B19
What is another group of infections that leads to perinatal infection, which provoke fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, and vesicular or hemorrhagic skin lesions?
TORCH (Toxoplasmosis, Other, Rubella, CMV, Herpes/HIV) - early in gestation
- can lead to mental retard, cataracts, cardiac anomalies and bone defects as well
What refers to accumulation of edema fluid in the fetus during intrauterine growth? Can be immune due to hemolytic anemia of the newborn (d/t Rh- in mom) or nonimmune which is more common now, with many causes.
Fetal hydrops
The intrauterine fluid accumulation can be variable, from progressive generalized edema of the fetus to more localized degrees of edema such as isolated pleural and peritoneal effusions or postnuchal fluid accum… what are examples for both?
generalized edema = hydrops fetalis
localized like in postnuchal fluid accum = cystic hygroma
What is a hemolytic disease caused by blood group antigen incompatibility between mother and fetus? This reaction occurs in second and subsequent pregnancies in a Rh negative mom and Rh+ father.
Immune hydrops
The major antigens known to induce clinically significant immunologic reactions in immune hydrops is?
Rh antigens and th ABO blood groups
Initial exposure to to Rh antigen evokes the formation of IgM Abs that unlike IgG, dont cross placenta; so Rh disease is uncommon with the first pregnancy. Only which antigen is the major cause of Rh incompatibility?
D antigen
The incidence of maternal Rh isoimmunization has decreased significantly since the use of what immune globulin which contains anti-D antibodies?
Rhesus immune globulin (RhIg)
