Diseases of Infancy and Childhood Past Paper PDF

CM 109: INTEGRATED BASIC SCIENCES II (PATHOLOGY) DISEASES OF INFANCY AND CHILDHOOD DR. DIANA DOMASIAN-DIMAYA | 09 NOVEMBER 2024 TABLE OF CONTENTS II. CO...

CM 109: INTEGRATED BASIC SCIENCES II (PATHOLOGY) DISEASES OF INFANCY AND CHILDHOOD DR. DIANA DOMASIAN-DIMAYA | 09 NOVEMBER 2024 TABLE OF CONTENTS II. CONGENITAL ANOMALIES A. MALFORMATIONS I. LEADING CAUSES OF DEATH 1 Represent primary errors of morphogenesis, in which there is an II. CONGENITAL ANOMALIES 1 intrinsically abnormal developmental process A. MALFORMATIONS 1 Malformation syndrome B. DISRUPTIONS 1 PRECEPTOR NOTES C. DEFORMATIONS 1 Can be a single gene or chromosomal defect but most of the time, E. SEQUENCE 2 multifactorial Single body affected F. AGENESIS 2 → Anencephaly G. ATRESIA 2 ▪ A part of the brain is exposed due to incomplete closure of H. HYPOPLASIA OR HYPERPLASIA 2 the skull → Congenital heart defects I. HYPOTROPHY OR HYPERTROPHY 2 Multiorgan affected J. DYSPLASIA 2 → Malformation syndromes III. CAUSES OF CONGENITAL ANOMALIES 3 A. CYCLOPAMINE 3 B. VALPROIC ACID 3 C. VITAMIN A OR RETINOL 3 IV. PREMATURITY & FETAL GROWTH RESTRICTION 3 A. FETAL GROWTH RESTRICTION 3 B. NEONATAL RESPIRATORY DISTRESS SYNDROME 4 (HYALINE MEMBRANE DISEASE) 4 C.NECROTIZING ENTEROCOLITIS (NEC) 5 V. PERINATAL INFECTIONS 5 A. TRANSCERVICAL (ASCENDING) INFECTIONS 5 B. TRANSPLACENTAL (HEMATOLOGIC) INFECTIONS 5 C. SEPSIS 5 VI. FETAL HYDROPS 5 A. FETAL HYDROPS (IMMUNE HYDROPS) 5 B. NON-IMMUNE HYDROPS 6 VII. INBORN ERRORS OF METABOLISM & OTHER GENETIC DISORDERS 7 A. PHENYLKETONURIA 7 Figure 1. Anencephaly B. GALACTOSEMIA 8 Retrieved from Dr. Dimaya’s PPT (2024). C. CYSTIC FIBROSIS (MUCOVISCIDOSIS) 8 B. DISRUPTIONS Result from secondary destruction of an organ or body region that VIII. SUDDEN INFANT DEATH SYNDROME 11 was previously normal in development IX. TUMORS AND TUMORLIKE LESIONS OF INFANCY AND CHILDHOOD 12 PRECEPTOR NOTES A. HEMANGIOMA 12 Extrinsic disturbance Example: Amniotic Bands B. FIBROUS TUMOR 12 → There is a rupture of amnion resulting in the formation of bands C. TERATOMA 12 that encircle, compress, or attach to parts of the developing D. NEUROBLASTIC TUMORS 13 fetus E. WILMS TUMOR 14 X. REFERENCE 15 I. LEADING CAUSES OF DEATH Infancy → Congenital anomalies → Prematurity and low birth weight → Sudden infant death syndrome → Maternal complications and injuries >1 year old → Accidents → Congenital anomalies → Malignant neoplasms 10-14 years old → Accidents → Malignancies → Suicide → Homicide → Congenital malformations Figure 2. Amniotic Band Syndrome Retrieved from Dr. Dimaya’s PPT (2024). PRECEPTOR NOTES C. DEFORMATIONS Infancy or first 12 months of life Like disruptions, represent an extrinsic disturbance of development Ages 1-4 and 5-9 rather than an intrinsic error of morphogenesis → Unintentional injuries resulting from accidents are the leading cause of death PRECEPTOR NOTES Congenital anomalies and malignant neoplasms Extrinsic disturbance → Assumed major significance among the natural diseases in Fundamental to the pathogenesis of deformations is localized or order of importance generalized compression of the growing fetus by abnormal biomechanical forces leading eventually to a variety of structural abnormalities Trans # 14 B6: Lareza, Marchan, Martinez, Moral, Napoles, Pecson, Rico, Salvo, Sernias, Tadiosa, Villar, Yaneza TH: Saysay 1 of 18  Table 1. Causes of Congenital Anomalies in Live-Born Infants → Example: Clubfeet ▪ Deformed feet that is may be due to a small uterus or an Cause Frequency (%) insufficient amount of amniotic fluid that affects the baby’s cushioning Genetic ▪ There could be many causes that could lead to the formation of clubfoot especially from the maternal side such as the Chromosomal aberrations 10-15 presence of mass which takes up space and hinders the baby’s growth Other possible causes of deformations: Mendelian inheritance 2-10 → Small uterus like in the cases of bicornuate uterus → Triplets - not enough space Environmental → Fetal position Maternal/Placental infections Rubella Toxoplasmosis 2-3 Syphilis Cytomegalovirus Human immunodeficiency virus Figure 3. Club Feet Maternal disease states Retrieved from Dr. Dimaya’s PPT (2024). Diabetes E. SEQUENCE Cascade of anomalies triggered by one initiating aberration Phenylketonuria 6-8 PRECEPTOR NOTES Example: Potter Sequence Endocrinopathies, → Due to oligohydramnios or decreased amniotic fluid including severe → The fetal compression associated with significant obesity oligohydramnios results in a classic phenotype in the newborn infant: Drugs and Chemicals ▪ Flattened facies ▪ Positional abnormalities of hands Alcohol, smoking ▪ Deformed leg ▪ Clubfeet Folic acid antagonists ▪ Hips could be dislocated ▪ The chest wall is compressed so the lungs are compromised − Hypoplastic lungs that could lead to fetal demise Androgens ▪ Nodules on amnion or Amnion Nodosum − Can be seen in the placenta as big visible yellow plaques Phenytoin 1 Thalidomide Warfarin 13-cis-retinoic acid Others Irradiation 1 Multifactorial 20-25 Unknown 40-60 Figure 4. Potter Sequence PRECEPTOR NOTES Retrieved from Dr. Dimaya’s PPT (2024). The most common cause of congenital anomalies is unknown F. AGENESIS cause (40-60%) but if it is a known cause, its multifactorial cause is Complete absence of an organ and its associate primordium (20-25%) (aplasia*) Common known causes of congenital anomalies are grouped into Doesn’t develop or missing 3 major categories: Genetic, Environmental, and Multifactorial G. ATRESIA Genetic → Chromosomal aberrations Absence of an opening ▪ Virtually all chromosomal syndromes are associated with Example: Trachea congenital malformations H. HYPOPLASIA OR HYPERPLASIA ▪ Down syndrome, Turner syndrome, Klinefelter syndrome Incomplete development or decreased size of an organ with → Mendelian inheritance decreased number of cells/enlargement of an organ due to ▪ Characterized by single gene mutations increased number of cells − Example: Holoprosencephaly Related to the number of cells involved o Brain did not divide into the right and left sphere Environmental I. HYPOTROPHY OR HYPERTROPHY → Maternal diseases Increase or decrease in size of individual cell ▪ Diabetes Mellitus (mother) Related to the size of cells involved − Baby could develop cardiac anomalies and neural tube J. DYSPLASIA defects Abnormal organization of cells − Difficulty in delivery → Viral infections ▪ Rubella during pregnancy - baby may develop congenital deafness → Drugs ▪ Many drugs can cause congenital anomalies, so before prescribing or administering certain medications, we ask patients if they are pregnant. CM 109 Diseases of Infancy and Childhood 2 of 18  → Alcohol B. VALPROIC ACID ▪ Most of the time, the effect is growth restriction Valproic acid embryopathy ▪ Facial anomalies such as small head or facial features PRECEPTOR NOTES → Smoking Anti-epileptic ▪ does not usually cause deformations Disrupts the expression of a family of highly concerned ▪ highly associated with spontaneous abortion, premature developmentally critical transcription factors known as homeobox labor, and placental abnormalities → Hox proteins ▪ prone to develop Sudden Infant Death (SID) → Invertebrates hox proteins → Irradiation ▪ Which have been implicated in the patterning of limbs vertebrae and craniofacial structures Figure 5. Congenital Anomalies Retrieved from PPT of Dr. Domasian-Dimaya (2024). PRECEPTOR NOTES Two principles Figure 7. Fetal Valproate Syndrome → Timing of the prenatal teratogenic insult has an important impact Retrieved from PPT of Dr. Domasian-Dimaya (2024). on the occurrence in the type of anomaly produced C. VITAMIN A OR RETINOL → Early embryonic period (First three weeks after fertilization) ▪ Cells are small, therefore when injured, may affect all other Retinoic acid embryopathy cells PRECEPTOR NOTES − Embryo may die and be aborted during this stage Infants born to mothers treated with retinoic acid for severe acne ▪ With minimal damage, the embryo may be able to survive but have a predictable phenotype a.k.a. Retinoic Acid Embryopathy with the presence of an anomaly which includes CNS, cardiac, and craniofacial defects such as → 3rd to 9th week of life → Cleft lip ▪ Most susceptible to teratogenesis → Cleft palate → Fetal period Vitamin A is needed for embryogenesis but in excessive amounts ▪ Growth restriction is the main concern can be teratogenic First 2 weeks of life: Prenatal death Embryonic period: Major morphologic abnormalities Fetal period: Minor morphologic abnormalities III. CAUSES OF CONGENITAL ANOMALIES A. CYCLOPAMINE Severe craniofacial abnormalities including holoprosencephaly and “cyclopia” PRECEPTOR NOTES This compound is an inhibitor of the Hedgehog signaling in the embryo and mutations of the Hedgehog genes are present in subsets of patients with → Holoprosencephaly → Cyclopia (craniofacial abnormalities) Figure 8. Cleft Palate Retrieved from PPT of Dr. Domasian-Dimaya (2024). IV. PREMATURITY & FETAL GROWTH RESTRICTION Risk factors → Preterm premature rupture of membranes (PPROM) → Intrauterine infection → Uterine, cervical, and placental structural abnormalities → Multiple gestations Conditions associated with prematurity → Neonatal respiratory distress syndrome → Necrotizing enterocolitis → Sepsis → Intraventricular and germinal matrix hemorrhage PRECEPTOR NOTES Preterm premature rupture of membranes (PPROM) → The reason it's considered a risk factor is that when the water breaks, it can induce labor, which might lead to the baby being born prematurely Intrauterine infection is a major cause of preterm labor with and without intact membranes → Histological findings: ▪ Chorioamnionitis or inflammation of the placental membranes ▪ Funisitis or inflammation of the fetal umbilical cord ▪ Most common microorganisms: − Ureaplasma urealyticum − Mycoplasma hominis Figure 6. Cyclopia − Gardnerella vaginalis Retrieved from PPT of Dr. Domasian-Dimaya (2024). − Trichomonas, Chlamydia, and Gonorrhea → For low income countries like PH, common causes include Malaria and HIV CM 109 Diseases of Infancy and Childhood 3 of 18