Chapter 10 - Childhood/infancy diseases Flashcards
Term for primary errors of morphogenesis in which there is an intrinsically abnormal developmental process
Malformation
Result from secondary destruction of an organ or body region that was previously normal in development
Disruption
Localised or generalised compression of the growing fetus by abnormal biochemical forces, leading to structural abnormalities e.g. uterine constraint
Deformations
Cascade of anomalies triggered by one initiating aberration e.g. oligohydramnios
Sequence
Constellation of congenital anomalies believed to be pathologically related and cannot be explained by a single, localising, initiating event
Malformation syndrome
complete absence of an organ and its associated primordium
Agenesis
Incomplete development or decreased size of an organ
Hypoplasia
Time in pregnancy when the embryo is extremely susceptible to teratogenesis
3rd - 9th weeks
Refers to the first 9 weeks of pregnancy
Early embryonic period
Fetal period
Period of pregnancy from 9 weeks to birth
Refers to the accumulation fo oedema fluid in the fetus during intrauterine growth
Fetal hydrops
Haemolytic disease caused by blood group antigen incompatibility between mother and fetus
Immune hydrops
3 major causes of nonimmune hydrops?
- cardiovascular defects
- chromosomal anomalies
- fetal anaemia
Autosomal recessive disorder caused by a severe deficiency of the enzyme phenylalanine hydroxylase (PAH) leading to hyperphenylalaninaemia
Phenylketonuria (PKU)
Autosomal recessive disorder of galactose metabolism resulting from accumulation of galactose-1-phosphate in tissues
Galactosaemia
Most common enzyme to be affected in galactosaemia
Galactose-1-phosphate uridyl transferase (GALT)
Most affected organs in galactosaemia
Liver, brain and eyes
Most common lethal genetic disease that affects Caucasian populations
Cystic fibrosis
Primary defect in cystic fibrosis
Abnormal transport of chloride and bicarbonate ions mediated by an anion channel encoded by the CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7q31.2
Microscopically normal cells or tissues that are present in abnormal locations
Heterotopia
Excessive, focal overgrowth of cells and tissues native to the organ in which it occurs
Hamartoma
3 groups of congenital malformations associated with increased risk of Wilms tumour
- WAGR syndrome
- Denys-Drash syndrome
- Beckwith-Wiedemann syndrome
Tumours of the sympathetic ganglia and adrenal medulla that are derived from primordial neural crest cells populating these sites
Neuroblastic tumours
Enzyme that is deficient in PKU
Phenylalanine hydroxylase
Management of infants identified as having PKU
Dietary restriction of phenylalanine early in life
Biochemical abnormality in PKU?
Inability to convert phenylalanine into tyrosine
Germline mutations in this gene are a major cause of familial predisposition to neuroblastoma
ALK gene (Anaplastic lymphoma kinase)
About 90% of neuroblastomas regardless of location produce…
Catecholamines
Amplification status of this gene is significant in the prognosis of neuroblastomas
MYCN
Amniotic bands are an example of what type of error of morphogenesis
Disruption
What is a malformation?
Primary error of morphogenesis, in which there is an intrinsically abnormal developmental process
What is a common cause of deformations?
Uterine constraint
What is the difference between agenesis and aplasia?
Agenesis - complete absence of an organ and its associated primordium
Aplasia - also absence of an organ but one that occurs due to failure of growth of existing primordium
What is atresia?
Absence of an opening, usually of a hollow visceral organ e.g. trachea or intestine
What are the sequelae of maternal hyperglycaemia
Fetal hyperinsulinaemia ->
- fetal macrosomia
- cardiac anomalies
- neural tube defects
- CNS malformations
Which gene does valproate disrupt to cause teratogenesis
Homeobox (HOX)
What are 4 major risk factors for prematurity?
- PPROM
- Intrauterine infections
- Uterine, cervical and placental structural abnormalities
- Multiple gestation
Is caesarean birth associated with higher or lower rates of RDS and why?
Labour is known to increase surfactant synthesis
C-section before the onset of labour may increase the risk of RDS
What are the two major consequences of high dose oxygen therapy in neonates
- Retinopathy of prematurity (Retrolental hyperplasia)
- Bronchopulmonary dysplasia
Who is susceptible to necrotising enterocolitis?
Premature infants
Which part of the gut does NEC affect?
Typically involves the ileum, caecum and Right colon (although any part of the small or large intestine may be affected)
How does NEC present?
Typical course is onset of bloody stools, abdominal distention, development of circulatory collapse
What is often demonstrated on abdo X-ray for cases of NEC?
Gas within the intestinal wall (pneumatosis intestinalis)
An inflammatory mediator that has been implicated in NEC in increasing mucosal permeability by promoting enterocyte apoptosis and compromising intercellular tight junctions
Platelet activating factor (PAF)
Describe the pathogenesis of retrolental fibroplasia (retinopathy of prematuritiy). What happens when the offending agent is removed?
Phase 1 - hyperoxic phase. VEGF is markedly decreased causing endothelial cell apoptosis
Phase 2 - VEGF levels rebound after return to relatively hypoxic room air including retinal vessel proliferation characteristic of the lesions in the retina
What are the two chronological types of neonatal sepsis? What usually causes the earlier one?
Early onset (within the first 7 days of life). Group B Strep is most common cause. Late onset (7 days to 3 months)
Does ABO incompatibility increase or decrease the risk of rhesus-related hydrops and why?
Concurrent ABO incompatibility protects the mother against Rh immunisation because the fetal RBCs are promptly coated and removed from the maternal circulation by anti-A or anti-B IgM antibodies that do not cross the placenta
In hydrops associated with fetal anaemia, what does the bone marrow usually demonstrate, and what is the exception to this in terms of cause?
Bone marrow demonstrates compensatory hyperplasia of erythroid precursors
Parvovirus-associated red cell aplasia is the notable exception
What is erythroblastosis fetalis?
Increased haematopoeitic activity -> presence in the peripheral circulation of numbers of immature red cells, including reticulocytes and erythroblasts
Most serious threat in fetal hydrops?
CNS damage known as kernicterus
Is there a form of PKU in which dietary restriction of phenylalanine is ineffective? What is the incidence of this?
Approx 2% of PKU is due to abnormalities in synthesis or recycling of the cofactor BH4. These cannot be treated by dietary restriction.
What deposits in the tissues in galactosaemia?
Galactose-1-phosphate
Common causes of oligohydramnios?
Amniotic fluid leak
uteroplacental insufficiency
bilateral renal agenesis
cystic renal dysplasia
Most common cause of death associated with the oligohydramnios sequence?
Respiratory insufficiency resulting from pulmonary hypoplasia
