Pediatric Disease Flashcards
What are congenital abnormalities?
- defects seen at birth
- range from mild to fatal
- mostly affect cardio. system
- associated with genetic abnormalities, environmental, maternal factors
What are the 2 common pediatric/prenatal diseases?
congenital abnormalities and prematurity
What are mutations?
- from alteration in DNA sequence
- point mutations cause common genetic diseases
What are the 5 types of mutations?
- silent (no effect)
- missense (code for different protein)
- nonsense (stop signal reading code)
- frameshift (alters reading frame)
- point ( substituting, adding, deleting a single nucleotide)
What are multifactorial disorders?
result from changes in many genes by chromosomal deletions, duplications, inversions, insertions, and translocations
What are epigenetic changes?
- modulate expression without altering DNA sequence
- post-translational modification and gene silencing by microRNAs
What are Mendelian Disorders?
- alterations in singles genes
- inherited through germline
- extent of disease depends on penetrance
- characterized by clustering of one unusual disease ina family
What can a family pedigree indicate a pattern of inheritance as?
- autosomal dominant
- autosomal recessive
- sex-linked dominant
- sex-linked recessive
What are autosomal dominant disorders?
- caused by point mutations in one allele
- produce abnormal receptor/structural protein
- equal susceptibility between male & female
- 50% risk among siblings
- expressed in heterozygous state
What is Marfan syndrome?
- autosomal dominant
- point mutations in glycoprotein fibrillin 1 gene (FBN1)
- deficient deposition of elastin fibers
- pts are tall with scaphoid chest, arachnodactyly (long digits), double jointed, subluxation (ocular dislocation)
- bone overgrowth related to TGF-beta
- risk for aortic dissection
What is familial hypercholesterolemia?
- autosomal dominant
- from mutations in low density lipoprotein (LDL) receptor gene
- heterozygotes 2-3 times increased plasma cholesterol (more common)
- homoxygotes > 5 times increased plasma cholesterol
What is anemia?
- diminished O2 capacity
- caused by inadequate RBC production
- inherited/acquired/infectious
What are the important numbers in anemia?
- RBC= 4.2-5.6 males; 3.8-5 females
- hematocrit= 38-48% males; 35-44% females
- MCV= 81-100 fl
- RDW= <15%
- Hgb= 13 males; 12 females
What is Hereditary spherocytosis?
- autosomal dominant
- results from mutations in ankyrins
- have aplastic crises (shut down of erythropoeisis)
- anisocytosis: unequal RBC size
- Howell-Jolly body: basophilic nuclear DNA remnants in circulating erythrocytes
What are autosomal recessive disorders?
- mutation by BOTH alleles
- homozygotic proband vs heterozygotic carrier
- largest group of Mendelian disirders
- 25% risk among siblings
- inherited equally in males & females
- can skip generations
- enzymatic effects in metabolism/storage
What is lysosomal storage disease (Tay-Sachs disease)?
- autosomal recessive
- accumulation of gangliosides due ot alpha-subunit of hexosaminidase A
- catastrophic infantile (usually kills infants)
What is Hurler’s disease?
- autosomal recessive
- MPS type 1: deficiency of alpha-L-iduronidase
- skin & musculoskeletal system affected
- growth retardation/coarse facial & skeletal features
What is Hunter’s disease?
- X-linked recessive
- MPS type 2: deficiency of L-iduronate sulfatase
- results in similar cellular accumulation of heparan sulfate and dematam sulfate as Hurler’s
What is sickle cell anemia?
- autosomal recessive
- affects 15.5:1000
- hemoglobin S: composed of 2 mutant beta-globin chains & 2 normal alpha-globin chains
- crescent/sickle shaped RBC
- ischemic microinfarcts and pain crisis
- chronic damage -> hemolytic anemia
- treatments: blood transfusions
- hydroxyurea
What is cycstic fibrosis?
- autosomal recessive
- mutations in CFTR
- loss of Cl- channel promotes excessive tissue Na+ absorption & water retention
- results in decreased surface water content in secreted mucin
What is the clinical course of cycstic fibrosis?
- meconium ileus: fecal congestion in the ileum
- pancreatic insuff, with recurrent pancreatitis
- mucus plugging contributes to cardiopulmonary complications
- predisposition to bacterial infection
- respiratory failure is most common cause of death
What is phenylketonuria?
- autosomal recessive
- lack of phenylalanine hydroxylase
- results in hyperphenylalanine, phenylketonuria, and phenylalanine secreted in sweat
- present in 6 months with severe mental retardation, failure to walk/talk, seizures
- controlled by dietary restriction of phenylalanine
What are X-chromosome linked disorders?
- transmitted by homozygous or heterozygous female carriers
- males (XY) can ONLY pass it on to their daughters
- can be recessive or dominant
- no known Y-chromosomal diseases
What are X-linked recessive diseases?
- abnormalities on X chromosome
- females are carriers who pass disease to sons
What is Duchenne’s Muscular Dystrophy?
- X-linked recessive
- identified by PCR
- alterations in dystrophin protein
- disrupts assembly of proteins into transmembrane complex
- results in microtrauma and plasma membrane tears that allow influx of extracellular Ca
What is the histology of Duchenne’s Muscular Dystrophy?
- hypercontraction of muscle fibers
- pseudohypertrophic appearance
- replacement of muscle fibers by fibroblasts/collagen & adipocytes
What is the clinical course of Duchenne’s Muscular Dystrophy?
- male patients usually have muscle weakness in early childhood
- pseudohypertrophy of calf muscles
- life expectancy: 30 years
What is hemophilia?
- X-linked recessive
- results from deficiency of clotting factors
- represented by group of bleeding disorders
- easily bleed; last for a long time
What is hemophilia A?
- caused by point mutations in factor 8 gene
- internal hemorrhage, hemarthrosis
What are X-linked dominant diseases?
- excess of affected females compared to X-linked recessive
- fathers -> pass to only to daughters
- mothers -> pass to daughters & sons
- one defected X chromosome
What is hypophosphatemia?
- X-linked dominant
- low phosphate in blood
- renal phosphate transport disorder
- osteomalacia (soft bones); rickets
- females suffer hypophosphatemia
- defective gene PHEX
- treatment: hydroxylated vitamin D
What are nonmendelian (chromosomal) disorders?
- result from quantitative alterations in gene or changes in chromatin structure
- NO family history
- arise de novo
What is trisomy 21 (down syndrome)?
- most common chromosomal disorder
- flat profile, oblique palprebral fissures, prominent epcanthic eye folds
- degree of mental retardation
- increased risk of myeloid leukemia
- onset of Alzheimer’s
What is trisomy 18 and 13?
- trisomy 18: Edward’s syndrome (affects 1:8,000)
- trisomy 13: Patau syndrome (1:15,000)
What is Turner syndrome?
- chromosomal disorder
- female hypogonadism
- webbing of neck, cubitus valgus
- accelerated oocyte loss
- coarctation/narrowing of aorta
- risk of getting autoimmune thyroiditis
What is Klinefelter Syndrome?
- chromosomal disorder
- male hypogandism
- ionizing radiation
- testicular atrophy (immatrue testes)
- reduced serum testosterone
- impaired spematogenesis
What is Fragile X syndrome?
- chromosomal disorder
- excessive number of copies of a trinucleotide repeat with FMR1 protein
- repeat copies cause epigenetic FMR1 gene DNA methylation/silencing
- second most common cause of mental retardation
- macroorchidism (large testicles)
- normal life expectancy
What are the causes of majority of infant deaths <1 year old?
- infection
- developmental anomalies
- complications of pregnancy
What is the cause of majority of infant deaths >1 year old?
accidents
What is hydrocephaly?
- congential anomaly
- dilation of the ventricular system
- atrophy of white and grey matter
- seizures, optic atrophy
What is anecephaly?
- congenital anomaly
- absence of cranial vault
What is fetal hydrops?
- congenital anomaly
- accumulation of edema in fetus
- immune hydrops -> from Rh incompatibility
- nonimmune hydrops -> from chromosomal/structural anomalies
- fetal D-antigen -> crosses into maternal circulation where hemolytic Abs cross placenta
What can cause massive intraventricular hemorrhage?
immaturity of fragile brain vasculature
What can’t immature lungs produce?
normal surfactant -> results in neonatal respiratory distress syndrome
What is respiratory distress syndrome?
- results from low surfactant & immature lung formation
- complications: retinopathy & bronchopulmonary dysplasia
- hyaline deposition in alveolar spaces
What is TORCH syndrome?
- maternal infection that can result in spontaneous abortion or cause malformations of fetus
- trans-cervically (ascending): bacterial, herpes
- transplacentally (hematologic): embryonic inhalation
- occurs 1-5% of births
- consists of toxoplasma, rubella virus, cytomegalovirus, herpes, other microbe
What is cat scratch lymphadenitis?
- caused by bartonella henselae
- enlarged axillary lymph node
- occurs in children or immunocomprised ppl
In asthma, airway remodeling contributes to what irreversible airway constriction?
- fibrosis
- hypertrophy
What can the use of tobacco lead to?
- chronic bronchitis
- emphasyma
- second hand smoke -> bronchitis & pneumonia
What can the exposure of lead cause?
- neuropathies
- intereferes with heme synthesis
- increased bone density -> “lead lines”
- usually ingested
What is fetal alcohol syndrome?
- alcohol exposure during pregnancy
- causes brain damage & growth problems
- decreased life expectancy
What is a first degree burn?
- only epidermis involved
- pain without necrosis
- healed by replacement regeneration
What is a second degree burn?
- epidermis, BM, & superficial dermal involvement
- healed by CT repair
What is marasmus?
- form of malnutrition
- deficiency of all dietary components
- weight falls to 60% normal
- retarded growth
What is kwashiorkor?
- form of malnutrition
- early weaning followed by a CHO diet
- protein deprivation
- edema
- large liver (hepatomegaly)
- skin patterns: desquamation & hyperpigmentation
What is Rickets?
- vitamin D deficiency
- aka osetomalacia in adults
What is the difference between type 1 and 2 diabetes?
- type 1: deficient secretion of insulin by beta cells
- type 2: resistance to action of insulin
What is severe hypoglycemia?
- complication of diabetes
- due to insufficient CHO intake
What is ketoacidosis?
- complication of diabetes
- hyperglyemia -> polyuria & dehydration/polidipsia
- ketonuria
What is hyperosmolar nonketotic coma?
- complication of diabetes
- hyperglyemia -> polyuria & dehydration/polidipsia
- occurs in elderly patients
