Pathology - Chapter 10 - Diseases Of Infancy And Childhood

Front 1

Define: agenesis

Back 1

complete absence of an organ and its associated primordium

Front 2

Define: Aplasia

Back 2

absence of an organ due to failure of the developmental primordium

Front 3

Define: atresia

Back 3

Absence of an opening, usually of a hollow visceral organ (e.g., trachea or intestine)

Front 4

Define: dysplasia

Back 4

in the context of malformations, refers to abnormal organization of individual cells

Front 5

Define: hyperplasia

Back 5

overdevelopment of an organ associated with increased numbers of cells

Front 6

Define: hypoplasia

Back 6

incomplete development or underdevelopment of an organ, with decreased numbers of cells (less severe form of aplasia)

Front 7

Define: hypertrophy

Back 7

increase in organ size or function related to an increase in cell size

Front 8

Define: hypotrophy

Back 8

decrase in organ size or function related to a decrease in cell size

Front 9

Define: Deformations

Back 9

Result of mechanical factors. Usually manifest as abnormalities in shape, form, or position (e.g., clubfoot). Low risk of recurrence in subsequent siblings.

Front 10

Predisposing factors to deformations include

Back 10

1. First pregnancy
2. Uterine leiomyoma
3. Oligohydramnios
4. Multiple fetuses
5. Abnormal fetal presentation

Front 11

Define: Disruption

Back 11

Secondary destruction or interference with a previously developmentally normal organ or body region. May be due to either external or internal interferences (e.g., amniotic bands). They are not heritable

Front 12

Define: malformations

Back 12

1. Intrinsic abnormalities occurring relatively early during development.
2. May involve single or multiple organ systems.
3. Risk of recurrence varies

Front 13

Define: Sequence

Back 13

series of multiple congenital anomalies resulting from a single localized aberration in organogenesis with secondary effets on other organs.

Front 14

Good example of a sequence

Back 14

Oligohydramnios or Potter sequence:
1. Diverse factors, such as renal agenesis or amniotic leak
2. Results in decreased amniotic fluid, compression of the fetus, and a classic phenotype

Front 15

Define: syndrome

Back 15

several defects that cannot be readily explained on the basis of a single, localized initiating anomaly. Nevertheless, most often attributed to a specific etiologic agent (e.g., viral infection or chromosomal abnormality) that simultaneously affects several tissues

Front 16

The exact cause of a congenital anomaly is known in approximately __% of cases; common causes are grouped into three major categories. What are they?

Back 16

1a. Unknown causes (50%)
2a. Genetic causes (2-15%)
2b. Environmental causes (1-8%)
2c. Multifactorial causes (20-25%)

Front 17

List the most common karyotypic abnormalities in descending order of occurrence

Back 17

1. Trisomy 21
2. Klinefelter (47, XXY)
3. Turner syndrome (45, XO)
4. Trisomy 13

Most cytogenetic aberrations occur during gametogenesis, and thus are not inheritable

Front 18

Which factors are considered environmental causes of congenital anomalies in humans?

Back 18

1. Viruses (e.g., CMV, Rubella, Herpes simplex)
2. Drugs and chemicals (less than 1%, thalidomide, folate antagonists, androgenic hormones, alochol, anticonvulsants, and 13-cis-retinoic acid)
3. Radiation (during organogenesis)
4. Maternal diabetes

Front 19

What are the effects of CMV on the fetus?

Back 19

Results in
1. Mental retardation
2. Microcephaly
3. Deafness

Front 20

What are the effects of radiation on the fetus?

Back 20

1. Microcephaly
2. Blindness
3. Skull defects
4. Spina bifida

Front 21

What are the effects of maternal diabetes on the fetus?

Back 21

1. Increased body fat, muscle mass, organomegaly
2. Cardiac anomalies
3. NTDs
4. CNS malformations

Front 22

Examples of anomalies due to multifactorial causes

Back 22

1. Cleft lip and palate
2. NTDs
3. Congenital hip dislocation

Front 23

The pathogenesis of congenital anomalies is complex and frequently poorly understood, however, some general principles can be drawn from this:

Back 23

1. Timing - affects the occurrence and type of anomaly
2. Teratogens and genetic defects may act at several levels, including cellular proliferation, migration, or differentiation, or may damage already differentiated organs
3. Genetic defects may cause anomalies either directly or by influencing other genes.

Front 24

Based on birth weight, infants are

Back 24

1. appropriate for gestational weight - 10th-90th percentile
2. small for gestational age (below 10th percentile)
3. large for gestational age (above 90th percentile)

Front 25

What are the major risks of prematurity?

Back 25

1. Preterm premature rupture of placental membranes; most common cause of prematurity (30-40%)
2. Intrauterine membrane inflammation (chorioamnionitis), and umbilical cord inflammation (funisitis). Most common microorganisms are Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Trichomonas, gonorrhea, and Chlamydia
3. Uterine, cervical, and placental structural abnormalities
4. Multiple gestation (twin pregnancy)

Front 26

What are the three main factors that contribute to fetal growth restriction (FGR)?

Back 26

1. Fetal
2. Placental
3. Maternal (most common)

Front 27

The fetus contributes to FGR in which way?

Back 27

1. Chromosomal disorders (trisomy 13,18,21, monosomy X, triploidy)
2. Congenital anomalies
3. Congenital infections (TORCH)

Front 28

The placental contributions to FGR include

Back 28

1. abruptio placentae
2. placenta previa (low-lying placenta)
3. placental thrombosis and infarctions
4. placental infections
5. umbilical placental vascular anomalies
6. multiple gestations
7. confined placental mosaicism

Front 29

What are the maternal factors that contribute to FGR?

Back 29

The mechanism is decreased blood flow to the placenta, caused by:
1. Toxemia of pregnancy
2. HTN
3. Nutritional status
4. Narcotic or alcoholic intake
5. Heavy cigarette smoking
6. Certain drugs (may also be teratogens)

Front 30

Major cause of morbidity and death in preterm infants?

Back 30

Structural and functional organ system immaturity

Front 31

Morphologic findings in the lungs of preterm infants include?

Back 31

1. Thick-walled alveolar septa with increased connective tissue, physically separating vasculature from alveoli and hindering oxygenation
2. Alveolar spaces frequently contain eosinophilic proteinaceous precipitate and occasional squamous epithelial cells
3. Development of alveoli normally continues after birth, reaching the full complement of alveoli by age 8

Front 32

Morphologic findings in the kidneys of preterm infants include?

Back 32

1. Primitive glomeruli and tubules present in the subcapsular zone (nephrogenic zone)
2. However, deeper glomeruli and tubules are well formed and function is usually adequate

Front 33

Morphologic findings in the brain of preterm infants include?

Back 33

1. Smooth external surface, with markedly simplified to absent convolutions (sulci and gyri)
2. Incomplete cell migration and myelination
3. Soft and gelatinous brain, and there is poor demarcation of white and gray matter
4. Vital brain centers are sufficiently developed to sustain normal function even in severe prematurity, although homeostasis of some systems (e.g., temperature, respiration) is imperfect

Front 34

Morphologic findings in the liver of preterm infants include?

Back 34

1. Relatively large, partially as a result of extramedullary hematopoiesis
2. Liver enzymes are poorly synthesized, including those responsible for biliary excretion; when coupled with fetal erythrocyte breakdown, this causes physiologic jaundice in prematurity

Front 35

What are the parameters used to gauge the Apgar score?

Back 35

1. Heart rate
2. Respiratory effort
3. Muscle tone
4. Response to noxious stimulus
5. Skin colour

Each scored 0,1 or 2; the higher the score, the better the outlook. It is calculated at 1 and 5 minutes of life.

Front 36

Most common important birth injury

Back 36

intracranial hemorrhage

Front 37

Predisposing factors to intracranial hemorrhage

Back 37

1. Prolonged labour
2. Hypoxia
3. Hemorrhagic disorders
4. Intracranial vascular anomalies

Front 38

Consequences of intracranial hemorrhage include

Back 38

1. Increased intracranial pressure
2. Damage to brain substance
3. Herniation into the foramen magnum, with depression of medullary center function

Front 39

What is caput succedaneum?

Back 39

accumulation of interstitial fluid in the scalp soft tissue; it causes circular areas of edema, congestion, and swelling where the head enters the lower uterine canal. If hemorrhage occurs, it is called cephalohematoma. Both are of little clinical significance unless accompanied by skull fracture.

Front 40

Most common sequela of transcervical (ascending) infections

Back 40

1. pneumonia
2. sepsis
3. meningitis

Front 41

How do most parasites and viral infections enter the fetal bloodstream?

Back 41

Via chorionic villi

Front 42

Sequela of transplacental (hematologic) infections

Back 42

Highly variable, depending on the gestational timing and microorganism

Front 43

Define: sequela

Back 43

any abnormality following or resulting from a disease or injury or treatment

Front 44

Most common cause of respiratory distress in the newborn

Back 44

Most commonly respiratory distress syndrome (RDS), also known as hyaline membrane disease

Front 45

The many causes of respiratory distress in the newborn include

Back 45

1. Aspiration of blood or amniotic fluid during birth
2. Brain injury affecting respiratory centers
3. Umbilical cord around the neck
4. Excessive maternal sedation
5. RDS (hyaline membrane disease)

Front 46

When/where does RDS primarily occur?

Back 46

1. Primarily in the immature lung
2. It is caused by a lack of surfactant, produced by type II pneumocytes (most abundant after week 35)

Front 47

Decreased production of surfactant will result in

Back 47

1. Increased alveolar surface tension
2. Progressive alveolar atelactasis
3. Increasing inspiratory pressure required to expand alveoli
4. Hypoxemia; acidosis, pulmonary vasoconstriction, pulmonary hypoperfusion, capillary endothelial and alveolar epithelial damage, plasma leakage into alveoli; plasma proteins combine with fibrin and necrotic alveolar pneumocytes to form hyaline membranes.

Front 48

Drugs that help prevent RDS?

Back 48

Corticosteroids; induces formation of surfactant lipids and apoprotein in fetal lung

Front 49

The morphology of lungs in RDS

Back 49

1. Grossly, the lungs are solid, airless, and reddish purple
2. Microscopically, alveoli are poorly developed and frequently collapsed; proteinaceous "membranes" line respiratory bronchioles, alveolar ducts, and random alveoli

Front 50

Why is RDS associated with maternal diabetes?

Back 50

Surfactant synthesis is suppressed by high levels of insulin

Front 51

Method to assess fetal surfactant synthesis?

Back 51

Before delivery, amniotic fluid phospholipids (lecithin/sphingomyelin ratio) may be measured

Front 52

If delivery cannot be delayed until the fetus is capable of adequate surfactant synthesis, the therapy will be

Back 52

1. surfactant replacement
2. oxygen therapy

Front 53

In uncomplicated cases of preterm delivery, recovery begins in? However, they are at risk of developing what? Why?

Back 53

1. Recovery begins in 3-4 days
2. Retinopathy of prematurity and bronchopulmonary dysplasia (BPD).
3. Both due to high-concentration oxygen therapy

Front 54

What is the major hisopathologic abnormality in BPD?

Back 54

Decreased alveolar number (alveolar hypoplasia)

Front 55

Infants that recover from RDS may also have other complications of prematurity. Examples?

Back 55

1. Patent ductus arteriosus
2. Intraventricular hemorrhage
3. Necrotizing enterocolitis (NEC)

Front 56

Predisposing factors to necrotizing enterocolitis (NEC) include?

Back 56

1. Intestinal ischemia (prerequisite)
2. Bacterial colonization of the gut
3. Administration of formula feeds

The latter two aggravate mucosal injury in the immature bowel

Front 57

The clinical course of NEC?

Back 57

1. Bloody stools
2. Abdominal distention
3. Development of circulatory collapse

Front 58

NEC typically involves

Back 58

1. Terminal ileum
2. Cecum
3. Right colon

However, any part of the bowel may be involved

Front 59

Microscopic morphology of NEC

Back 59

1. mucosal or transmural coagulative necrosis
2. ulceration
3. bacterial colonization
4. submucosal gas bubbles

Front 60

Treatment of NEC?

Back 60

If caught early NEC may be treated conservatively, however, 20% to 60% require resection of necrotic bowel segments

Front 61

What is fetal hydrops?

Back 61

Fetal hydrops refers to fetal edema fluid accumulation during intrauterine growth

Front 62

Cause of immune hydrops?

Back 62

Consequence of blood group incompatibility between mother and fetus. The fetus inherits erythrocyte antigens from the father that the mother lacks. A small transplacental bleed allows fetal erythrocytes to enter the maternal circulation, where they induce antibody production.

Front 63

Which is more common, ABO or Rh incompatibility?

Back 63

ABO, but rarely results in disease severe enough to require treatment. Most anti-A and anti-B antibodies are IgM, and do not cross the placenta. In addition the neonatal RBCs poorly express A and B antigens, and many other cells express A and B antigens, thus diminishing the amount of RBCs being eliminated.

Front 64

What are the major causes of nonimmune hydrops?

Back 64

1. Cardiovascular defects
2. Chromosomal anomalies (Turner, trisomies 21 and 18)
3. Fetal anemia unrelated to immune hemolysis (e.g., homozygous α-thalassemia).
4. Parvovirus B19 infection (transplacental); it enters and replicates within erythroid precursors (normoblasts), leading to erythrocyte formation arrest and aplastic anemia.
5. Monozygous twin pregnancy (approximately 10%)

Front 65

Anatomic findings in fetuses with intrauterine fluid accumulation?

Back 65

1. Pale fetus and placenta in cases due to fetal anemia
2. Hepatosplenomegaly
3. Cardiac failure and congestion
4. Bone marrow hyperplasia
5. Large number of immature RBCs in the peripheral blood

Front 66

What is kernicterus?

Back 66

Central nervous system damage due to unconjugated bilirubin binding to lipids in the brain

Front 67

Which gene is mutated in PKU?

Back 67

Phenylalanine hydroxylase gene (PAH). The mutations have variable enzymatic deficiencies and consequently variably elevated phenylalanine. The most common form is common among people of Scandinavian descent and uncommon in blacks and Jews.

Front 68

What is the clinical picture of galactosemia?

Back 68

1. Variable, but overall, infants fail to thrive and present with vomiting and diarrhea after milk ingestion
2. Liver, eyes and brain are most severely affected; changes include hepatomegaly cirrhosis, cataracts, and nonspecific alterations in the CNS (including mental retardation)

Front 69

Incidence of cystic fibrosis?

Back 69

1 in 3,3200 live births in the US; it is the most common lethal genetic disease affecting whites

Front 70

Another name for CF?

Back 70

Mucoviscidosis

Front 71

Most common mutation in the CFTR gene?

Back 71

A triplet deletion normally coding for phenylalanine at position 508 (∆F508)

Front 72

Which areas are commonly affected by CF?

Back 72

1. Pancreas (85-90%)
2. Intestine (5-10%)
3. Liver (5%)
4. Salivary glands
5. Lungs (most cases)
6. Male genital tract (95% of males surviving to adulthood)

Front 73

Morphology of pancreas in patients suffering from cystic fibrosis?

Back 73

1. Mucus accumulation in small ducts with mild dilation to total atrophy of the exocrine pancreas
2. Avitaminosis A due to impaired fat absorption

Front 74

Morphology of intestines in patients suffering from cystic fibrosis?

Back 74

Thick viscous plugs of mucus (meconium ileus) may cause intestinal obstruction

Front 75

Morphology of liver in patients suffering from cystic fibrosis?

Back 75

Plugging of bile canaliculi by mucinous material results in diffuse hepatic cirrhosis

Front 76

Morphology of salivary glands in patients suffering from cystic fibrosis?

Back 76

1. Progressive duct dilation
2. Ductal squamous metaplasia
3. Glandular atrophy

Front 77

Morphology of lungs in patients suffering from cystic fibrosis?

Back 77

1. Dilated bronchioles (mucous secreting cells hyperplasia and viscous secretions block and dilate)
2. Superimposed infections and pulmonary abscesses

Front 78

Most common organisms affecting the lungs of CF patients?

Back 78

1. S. aureus
2. H. influenzae
3. P. aeruginosa
4. Burkholderia cepacia

Front 79

Clinical picture in classical CF?

Back 79

1. Pancreatic exocrine insufficiency
2. Cardiorespiratory complications; chronic cough, persistent lung infections, obstructive pulmonary disease, and cor pulmonale are the most common causes of death (80%)

Front 80

Malabsorption presents as

Back 80

1. Large, foul-smelling stools
2. Abdominal distention
3. Poor weight gain
4. Fat-soluble vitamin deficiencies

Front 81

SIDS is most common between

Back 81

2 and 4 months of life; the infant usually dies while asleep, without evidence of distress or struggle. It is the leading cause of death in children between 1 month and 1 year of age in the US.

Front 82

Which are more common, benign or malignant tumors?

Back 82

Benign tumors are most common, but cancer is the leading cause of death from disease in U.S. children aged 4 to 14

Front 83

What is heterotopia?

Back 83

Microscopically normal cells or tissue present in abnormal locations; these cells are usually of little significance but may be clinically confused with true neoplasms

Front 84

What are hamartomas?

Back 84

Excessive (but focal) overgrwoth of cells and tissues native to the organ or site in which they occur; may be considered a link between malformations and neoplasms

Front 85

Most common tumors of infancy?

Back 85

Hemangiomas; most are cutaneous, particularly on the face and palms. Hemangiomas may represent one facet of hereditary disorders such as von Hippel-Lindau (VHL) disease

Front 86

Where do lymphangiomas commonly occur?

Back 86

1. Skin
2. Deeper regions of the neck
3. Axilla
4. Mediastinum
5. Retroperitoneal tissue

Front 87

What are lymphangiomas composed of?

Back 87

cystic and cavernous lymphatic spaces, with variable numbers of associated lymphocytes

Front 88

Teratoma incidence peak at which age?

Back 88

1. Age 2
2. Late adolescence

Front 89

Where do teratomas most commonly occur?

Back 89

If early infancy and childhood, sacrococcygeal region

Front 90

Childhood malignancies differ biologically and histologically from their adult counterparts by three ways:

Back 90

1. a close relationship between abnormal development and tumor induction
2. a greater prevalence of underlying familial or genetic germline aberrations
3. a tendency for some malignanices in the fetal or neonatal period to regress spontaneously or cytodifferentiate

Front 91

The most frequent childhood malignancies arise where?

Back 91

1. Hematopoietic system (leukemia, some lymphomas)
2. Central nervous system (astrocytoma, medulloblastoma, ependymoma)
3. Adrenal medulla (neuroblastoma)
4. Retina (retinoblastoma)
5. Soft tissue (rhabdomyosarcoma)
6. Bone (Ewing sarcoma, osteogenic sarcoma)
7. Kidney (Wilm's tumor)

Front 92

What are 'small round blue cell tumors'?

Back 92

Some pediatric tumors with a primitive appearance are collectively referred to as this. These tumors include neuroblastoma, lymphoma, rhabdomyosarcoma, Ewing sarcoma/peripheral neuroectodermal tumor (PNET)