Mechanisms of Injury to Fetus and Newborn
Mechanism of Injury to Fetus and Newborn
1) anoxia, hypoperfusion, and ischemia
2) drugs and metabolites
3) Infection
- cause cell detah, malformation, Growth retardation, and inflammation
Anoxia, Hypoperfusion and Ischemia
Susceptibility
- early embryo (< 14 days) – resists most noxious stimuli
- later embryonic (14-56 days) – more susceptible; can lead to malformation or death
- The fetus has a greater toleration to anoxia from mid-gestation to shortly after birth
Ø vascular shunts preserve brain and heart
Ø circulatory by-pass of the lung because of increased resistance
Ø Hypoxia increases pulmonary arterial tone by inducing arterial constriction – further lung by-pass.
Respiratory Distress Syndrome
- Clinical
Ø shortly after birth the infant develops cyanosis and labored respiration
Ø retraction of the sternum and intercostal spaces is evident
Ø Anoxia, hypercarboxia, and exhaustion ensue
- Conditions that increase the risk
Ø premature birth (lack of surfactant)
Ø maternal diabetes
Ø twins
Ø C-section
- Morphology
1) lungs: solid, heavy, congested, moist
2) Atelectasis is most severe at the periphery
3) Hyaline Membrane disease where the terminal bronchioles and alveolar ducts are lined by a hyaline membrane
Ø does not appear until after 4 hours of life
Ø Results from lack of Surfactant
a. surfactants are lipoproteins which line the alveolar walls
b. surfactant usually appears at about 28 weeks gestation
c. surfactant disappears with pulmonary edema and atelectasis but reappears after a time.
Ø after 24 hours, the alveolar lining cells regenerate and macs proliferate along the membrane
Ø expansion of the ling with HMD may result in overdistension of proximal airway, which could lead to intestitial emphysema and pneumothorax.
- Bronchopulmonary Dysplasia (BPD)
Ø follows prolonged administration of O2 at high conc and high vent pressures
Ø necrosis of resp epithelium, proliferation and degeneration of alveolar epithelial cells and fibroblastic proliferation in the alveolar septa.
- Retrolental fibroplasia
Ø O2 at high conc also stimulates proliferation of retinal capillaries
Necrotizing Enterocolopathy
- Defined:
Ø diffuse or patchy necrosis of the mucosa or submucosa of the small or large bowel, initially localized, but with potential for longitudinal spread, infarction, and perforation
- Pathogenesis
Ø diminished perfusion due to the dive reflex results in decreased mucus production
Ø this exposes the gut mucosa to enzymatic digestion and bacterial invasion
- Pathologic Anatomy
Ø may affect any segment of the gut (usually spares the duodenum)
Ø Gross: (affects solitary segments of the gut)
1) two or more circumferential bands of congestion aroung gangrenous areas
2) multiple segments with varying lesions
3) perforations usually occur adjacent to the ileocecal valve
Ø MICRO
1) initial coagulation necrosis of the mucosa with ghosts of residual framework and little inflammation
2) DIC accompanies but does not precede necrosis
3) Fibrin covers the serosa adjacent to a perforation
4) Focal mucosal necrosis, bacterial proliferation
5) Transmural inflammation
- Healing processes
Ø epithelialization takes place by 3 days
Ø fibroblastic proliferation and gran tissue by 8-9 days
Ø submucosal fibrosis by 6 mths
- Natural Progression of Necrotizing Enterocolopathy (NEC)
1) mucosal ulcer
2) submucosal hemorrhage
3) Pseudomembrane on the surface
4) Perforation
5) Pneumatosis intestinalic
- Repair Mechanisms
1) May heal without sequalae – 65%
2) Gran tissue fills the mucosa
3) Scarring occurs throufh the walls, central> peripheral
Brain Perfusion
- Intraventricular hemorrhage (Germinal Matrix hemorrhage)
Ø unknown mechanism
Ø premies mostly (50% or more of those that die)
Ø the vessels of the subependymal germinal matrix are susceptible to anoxia and may rupture into ventricular space. May or may not be fatal
Ø Grades of Germinal Matrix Hemorrhage
1) Bleeding confined to the germinal matrix
2) Intraventricular hemorrhage w/o ventricular dilitation
3) Interventricular hemorrhage with ventricular dilitation
4) Hemorrhage into the cerebral parenchyma
Ø Association with RDS
- 28% of infants with RDS also have Germinal Matrix Hemorrhage
- 50% of infants with germinal matrix hemorrhage also have HMD
- Periventricular Leukomalacia
Ø Hypoxemic-ischemic effect on periventricular white matter produces coagulative necrosis followed by liquefactive necrosis
Ø Affects anoxic full term infants as well as premies.
DRUGS AND METABOLITES
- immature or latent enzyme systems fail to metabolize or detoxify
Hyperbilirubinemia in the newborn period
- physiologic jaundice peaks on the 3rd-4th day of life
- serum bilirubin levels reach 8-10 mg/dl on the 3-4th day of life
- Pathologic jaundice appears earlier (usu 1st day) than physiologic
Ø results from excessive blood destruction
a. Erythroblastosis (Rh, ABO,…)
b. Infection
- Kernicterus:bile staining of selected areas of CNS grey matter
- Glucoronide transferase activity
Ø usually adequate in neonate after a few days of life
Ø Pregnanediol in mother’s milk can inhibit conjugation
Infants of Diabetic Mothers
- Increased size for gestational age; all organs but CNS involved
Ø Large immature placenta
Ø Large baby: increased subQ fat
Ø Clinically reversible dilated of obstructive cardiomyopathy
Ø Adrenal: increased fetal cortex size
Ø Gonad: enlarged Leydig Cells, increased lutein in theca externa
Ø Hyperplastic islets
- Increased frequency of malformations
Ø incidence parallels severity of the maternal diabetes
- Increased susceptibility to HMD
- Fetal death 10-30%; also parallels the severity of the maternal diabetes
Tags: anoxia, Brain Perfusion, Bronchopulmonary Dysplasia, epithelialization, Germinal Matrix hemorrhage, Hyaline Membrane disease, hyperbilirubinemia, hypercarboxia, hypoperfusion, Hypoxia, ischemia, maternal diabetes, Necrotizing Enterocolopathy, Pneumatosis intestinalic, Respiratory Distress Syndrome, Retrolental fibroplasia, submucosal fibrosis, vascular shunts
